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

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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.

The significance of the psychosocial factors influence in pathogenesis of cardiovascular disease.

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Masic, Izet; Alajbegovic, Jasmin

2013-11-01

Cardiovascular diseases (CVD) are the leading cause of death in the world today. Risk factors are those factors that influence the development of CVD. Risk factors can be divided into materialistic (genetic predisposition, smoking, alcohol) and non-materialistic (psychosocial factors). Our goal is to note the role of the health system, to emphasize the importance of psychosocial factors in the pathogenesis of CVD, explain the relationship between psychosocial factors and other risk factors, stress the importance of prevention through the provision of management of the cardiovascular system (CVS) diseases. A DESCRIPTIVE ANALYSIS WAS PERFORMED ON SCIENTIFIC STUDIES IN SEVERAL PUBLISHED ARTICLES IN JOURNALS ON CVS: Public Health Reviews, CVD, European Heart Journal, Materia Socio Medica and other indexed journals that publish articles on CVS. THE IMPORTANCE AND ROLE OF THE HEALTH SYSTEM IN THE EARLY DETECTION, DIAGNOSIS, THERAPY AND CVS DISEASE PREVENTION IS PRESENTED THROUGH THREE THEMATIC AREAS: (a) The incidence and prevalence of CVS diseases; (b) treatment of CVS diseases and (c) promotion of health in patients with CVS disease and those the risk of their occurrence. Health promotion is the most important aspect of the health system monitoring. Health promotion is adequately implemented ifthe management ofCVD is proper. The main objectives of CVD management are: Preventing or delaying the occurrence of CVD, reducing the number and severity of worsening and complications of CVD. Management Includes: Individual and family, the health system and the community. Materialistic and non-materialistic risk factors together contribute to the development of CVD.

Pilonidal sinus disease - Etiological factors, pathogenesis and clinical features

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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

The pathogenesis of foot-and-mouth disease in pigs

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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

Extrahepatic manifestations of cholestatic liver diseases: pathogenesis and therapy

NARCIS (Netherlands)

Pusl, Thomas; Beuers, Ulrich

2005-01-01

Pruritus, fatigue, and metabolic bone disease are frequent complications of cholestatic liver diseases, which can be quite distressing for the patient and can considerably reduce the quality of life. The molecular pathogenesis of these extrahepatic manifestations of cholestasis is poorly understood,

Pathogenesis of diverticulosis and diverticular disease.

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Walker, Marjorie M; Harris, Angela K

2017-06-01

Diverticulosis is defined by the presence of diverticula due to herniation of mucosa and muscularis mucosa through the muscularis propria at sites of vascular penetration in the colon and is asymptomatic in the vast majority affected. There are global differences of distribution, in Western industrialized societies, the most common site is in the left colon, but in Asia right sided diverticulosis predominates. Whilst present in 17.5% of a general population and 42% of all comers at endoscopy it is seen in 71% of those aged ≥80 years. Diverticular disease is defined as clinically significant and symptomatic diverticulosis, which may have an absence of macroscopically overt colitis and in true diverticulitis there is macroscopic inflammation of diverticula with related acute or chronic complications. Whilst overall, diverticulitis affects only 4% of those with diverticulosis, in younger patients (aged 40-49 years) this peaks at 11%. Diverticulosis is one of the most common chronic diseases, yet research in this field on pathogenesis has lagged behind other common conditions such as diabetes mellitus. However, in the last decade there have been major advances in taxonomy that can be used to relate to patients' outcome and treatment in both medicine and surgery. It has been shown there is an association with age, diet, drugs and smoking. Genetic studies have shown a familial association and a specific gene, TNFSF 15 may predict severity of disease. The role of the microbiome has been explored and microbial and metabolomic signatures are also important in predicting disease severity. That diverticulosis is a chronic disease is shown by mucosal pathology with subtle chronic inflammation present in those with asymptomatic diverticulosis and inflammation may lead to muscular hypertrophy, enteric nerve remodeling with disordered motility. The diverticulitis quality of life instrument shows that this condition impacts markedly on patients' well-being and prevention and

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

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Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

Directory of Open Access Journals (Sweden)

Duraisamy Kempuraj

2017-12-01

Full Text Available Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases

Polycystic Kidney Disease: Pathogenesis and Potential Therapies

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Takiar, Vinita; Caplan, Michael J.

2011-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. PMID:21146605

Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control.

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Tang, Ze-Li; Huang, Yan; Yu, Xin-Bing

2016-07-06

Clonorchiasis, caused by Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease and one of the most common zoonoses. Currently, it is estimated that more than 200 million people are at risk of C. sinensis infection, and over 15 million are infected worldwide. C. sinensis infection is closely related to cholangiocarcinoma (CCA), fibrosis and other human hepatobiliary diseases; thus, clonorchiasis is a serious public health problem in endemic areas. This article reviews the current knowledge regarding the epidemiology, disease burden and treatment of clonorchiasis as well as summarizes the techniques for detecting C. sinensis infection in humans and intermediate hosts and vaccine development against clonorchiasis. Newer data regarding the pathogenesis of clonorchiasis and the genome, transcriptome and secretome of C. sinensis are collected, thus providing perspectives for future studies. These advances in research will aid the development of innovative strategies for the prevention and control of clonorchiasis.

Physiology and pathogenesis of gastroesophageal reflux disease.

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Mikami, Dean J; Murayama, Kenric M

2015-06-01

Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

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Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

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 non-HLA 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 trans- 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 anti-endomysial 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. PMID:23155333

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

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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.

MicroRNAs in the pathogenesis of cystic kidney disease.

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Phua, Yu Leng; Ho, Jacqueline

2015-04-01

Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cysts replace existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is increasing evidence that microRNA (miRNA) dysregulation is associated with the pathogenesis of cystic kidney disease. In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific miRNAs, such as the miR-17∼92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers.

Gene knockout of tau expression does not contribute to the pathogenesis of prion disease.

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Lawson, Victoria A; Klemm, Helen M; Welton, Jeremy M; Masters, Colin L; Crouch, Peter; Cappai, Roberto; Ciccotosto, Giuseppe D

2011-11-01

Prion diseases or transmissible spongiform encephalopathies are a group of fatal and transmissible disorders affecting the central nervous system of humans and animals. The principal agent of prion disease transmission and pathogenesis is proposed to be an abnormal protease-resistant isoform of the normal cellular prion protein. The microtubule-associated protein tau is elevated in patients with Creutzfeldt-Jakob disease. To determine whether tau expression contributes to prion disease pathogenesis, tau knockout and control wild-type mice were infected with the M1000 strain of mouse-adapted human prions. Immunohistochemical analysis for total tau expression in prion-infected wild-type mice indicated tau aggregation in the cytoplasm of a subpopulation of neurons in regions associated with spongiform change. Western immunoblot analysis of brain homogenates revealed a decrease in total tau immunoreactivity and epitope-specific changes in tau phosphorylation. No significant difference in incubation period or other disease features were observed between tau knockout and wild-type mice with clinical prion disease. These results demonstrate that, in this model of prion disease, tau does not contribute to the pathogenesis of prion disease and that changes in the tau protein profile observed in mice with clinical prion disease occurs as a consequence of the prion-induced pathogenesis.

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

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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.

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.

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

HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

Science.gov (United States)

Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

2013-01-01

Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

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.

The role of clusterin in Alzheimer's disease: pathways, pathogenesis, and therapy.

Science.gov (United States)

Yu, Jin-Tai; Tan, Lan

2012-04-01

Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associated with brain atrophy, baseline prevalence and severity, and rapid clinical progression in patients with AD, highlighting the importance of clusterin in AD pathogenesis. Emerging data suggest that clusterin contributes to AD through various pathways, including amyloid-β aggregation and clearance, lipid metabolism, neuroinflammation, and neuronal cell cycle control and apoptosis. Moreover, epigenetic regulation of the clusterin expression also seems to play an important role in the pathogenesis of AD. Emerging knowledge of the contribution of clusterin to the pathogenesis of AD presents new opportunities for AD therapy.

[Current concepts in pathogenesis of age-related macular degeneration].

Science.gov (United States)

Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

2014-01-01

Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

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

Although epidemic jaundice was well known to physicians of antiquity, it is only in recent years that medical science has begun to unravel the origins of hepatitis A virus (HAV) and the unique pathobiology underlying acute hepatitis A in humans. Improvements in sanitation and the successful development of highly efficacious vaccines have markedly reduced the worldwide prevalence and incidence of this enterically-transmitted infection over the past quarter century, yet the virus persists in vulnerable populations and remains a common cause of food-borne disease outbreaks in economically-advantaged societies. Reductions in the prevalence of HAV have led to increases in the median age at which infection occurs, often resulting in more severe disease in affected persons and paradoxical increases in disease burden in some developing nations. Here, we summarize recent advances in the molecular virology of HAV, an atypical member of the Picornaviridae family, survey what is known of the pathogenesis of hepatitis A in humans and the host-pathogen interactions that typify the infection, and review medical and public health aspects of immunisation and disease prevention. Copyright © 2017. Published by Elsevier B.V.

Pathogenesis of Graves' disease and therapeutic implications

International Nuclear Information System (INIS)

Seif, F.J.

1997-01-01

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.) [de

Genes, autoimmunity and pathogenesis of rheumatic heart disease

International Nuclear Information System (INIS)

Guilherme, L; Köhler, K F; Postol, E; Kalil, J

2011-01-01

Pathogenesis of rheumatic heart disease (RHD) remains incompletely understood. Several genes associated with RHD have been described; most of these are involved with immune responses. Single nucleotide polymorphisms in a number of genes affect patients with RHD compared to controls. Molecular mimicry between streptococcal antigens and human proteins, including cardiac myosin epitopes, vimentin and other intracellular proteins is central to the pathogenesis of RHD. Autoreactive T cells migrate from the peripheral blood to the heart and proliferate in the valves in response to stimulation with specific cytokines. The types of cells involved in the inflammation as well as different cytokine profiles in these patients are being investigated. High TNF alpha, interferon gamma, and low IL4 are found in the rheumatic valve suggesting an imbalance between Th1 and Th2 cytokines and probably contributing to the progressive and permanent valve damage. Animal model of ARF in the Lewis rat may further contribute towards understanding the ARF

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

SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

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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.

A potential role of Chlamydia pneumoniae in the pathogenesis of periodontal disease in adolescents and adults.

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Ajonuma, Louis Chukwuemeka

2010-01-01

Periodontal diseases are among the most common human infections that not only impact oral health but also are associated with adverse systemic diseases such as cardiovascular diseases, stroke, diabetes, and respiratory diseases. Periodontal diseases is a chronic severe inflammatory process of the gingiva leading to the destruction of tooth-supporting structures, alveolar bone, and subsequently tooth loss due to bacteria infection. While it has been reported that several oral biofilm-forming bacteria might be involved, the role of C. pneumoniae infection in the pathogenesis of periodontal disease remains unknown. The present hypothesis proposes that C. pneumoniae is involved in the pathogenesis of periodontal diseases. This will lead to a better understanding of the etiopathogenesis of periodontal disease, better treatment strategy and savings on total health care costs.

Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases.

Science.gov (United States)

Dolan, Kyle T; Chang, Eugene B

2017-01-01

The rising incidence of inflammatory bowel diseases in recent decades has notably paralleled changing lifestyle habits in Western nations, which are now making their way into more traditional societies. Diet plays a key role in IBD pathogenesis, and there is a growing appreciation that the interaction between diet and microbes in a susceptible person contributes significantly to the onset of disease. In this review, we examine what is known about dietary and microbial factors that promote IBD. We summarize recent findings regarding the effects of diet in IBD epidemiology from prospective population cohort studies, as well as new insights into IBD-associated dysbiosis. Microbial metabolism of dietary components can influence the epithelial barrier and the mucosal immune system, and understanding how these interactions generate or suppress inflammation will be a significant focus of IBD research. Our knowledge of dietary and microbial risk factors for IBD provides important considerations for developing therapeutic approaches through dietary modification or re-shaping the microbiota. We conclude by calling for increased sophistication in designing studies on the role of diet and microbes in IBD pathogenesis and disease resolution in order to accelerate progress in response to the growing challenge posed by these complex disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

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Mitchell, Emily P; Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the

Online testable concept maps: benefits for learning about the pathogenesis of disease.

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Ho, Veronica; Kumar, Rakesh K; Velan, Gary

2014-07-01

Concept maps have been used to promote meaningful learning and critical thinking. Although these are crucially important in all disciplines, evidence for the benefits of concept mapping for learning in medicine is limited. We performed a randomised crossover study to assess the benefits of online testable concept maps for learning in pathology by volunteer junior medical students. Participants (n = 65) were randomly allocated to either of two groups with equivalent mean prior academic performance, in which they were given access to either online maps or existing online resources for a 2-week block on renal disease. Groups then crossed over for a 2-week block on hepatic disease. Outcomes were assessed using timed online quizzes, which included questions unrelated to topics in the pathogenesis maps as an internal control. Questionnaires were administered to evaluate students' acceptance of the maps. In both blocks, the group with access to pathogenesis maps achieved significantly higher average scores than the control group on quiz questions related to topics covered by the maps (Block 1: p online testable pathogenesis maps are well accepted and can improve learning of concepts in pathology by medical students. © 2014 John Wiley & Sons Ltd.

Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan.

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Sullivan, Mitchell A; Nitschke, Silvia; Steup, Martin; Minassian, Berge A; Nitschke, Felix

2017-08-11

Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen. Recent data clearly show that an abnormal glycogen chain length distribution, but neither hyperphosphorylation nor impairment of general autophagy, strictly correlates with glycogen accumulation and the presence of LBs. This review summarizes results obtained with patients, mouse models, and cell lines and consolidates apparent paradoxes in the LD literature. Based on the growing body of evidence, it proposes that LD is predominantly caused by an impairment in chain-length regulation affecting only a small proportion of the cellular glycogen. A better grasp of LD pathogenesis will further develop our understanding of glycogen metabolism and structure. It will also facilitate the development of clinical interventions that appropriately target the underlying cause of LD.

Selected Aspects in the Pathogenesis of Autoimmune Diseases

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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.

Prevention of infectious diseases in patients with Good syndrome.

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Multani, Ashrit; Gomez, Carlos A; Montoya, José G

2018-08-01

Good syndrome is a profoundly immunocompromising condition with heterogeneous immune deficits characterized by the presence of thymoma, low-to-absent B-lymphocyte counts, hypogammaglobulinemia, and impaired cell-mediated immunity. Opportunistic infectious diseases associated with Good syndrome represent a diagnostic and therapeutic challenge, given their protean clinical manifestations. Although these infectious complications have been reviewed in prior publications, recommendations regarding their prevention have been lacking. Good syndrome usually occurs in adult patients between the ages of 40 and 70 years. Immunologically, it is characterized by low or absent peripheral blood B lymphocytes, hypogammaglobulinemia, and variable defects in cell-mediated immunity including low CD4 T counts, inverted CD4:CD8 T-lymphocyte ratio, and reduced T-lymphocyte mitogen proliferative responses. Patients with Good syndrome are susceptible to a variety of infectious diseases, of which the most common are recurrent bacterial sinopulmonary infections, mucocutaneous candidiasis, and CMV tissue-invasive disease. Preventive guidelines including targeted antimicrobial prophylaxis and vaccination strategies can mitigate infectious complications in patients with Good syndrome. Immunological deficits and infectious complications in Good syndrome have been described for over 60 years. Further research is needed to elucidate its exact pathogenesis and define the mechanistic relationship between thymoma and hypogammaglobulinemia. However, tailored prophylactic strategies can be recommended for patients with Good syndrome.

Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis.

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Taymans, Jean-Marc; Nkiliza, Aurore; Chartier-Harlin, Marie-Christine

2015-08-01

Protein translation is one of the most fundamental and exquisitely controlled processes in biology, and is energetically demanding. The deregulation of this process is deleterious to cells, as demonstrated by several diseases caused by mutations in protein translation machinery. Emerging evidence now points to a role for protein translation in the pathogenesis of Parkinson's disease (PD); a debilitating neurodegenerative movement disorder. In this paper, we propose a hypothesis that protein translation machinery, PD-associated proteins and PD pathology are connected in a functional network linking cell survival to protein translation control. This hypothesis is a potential game changer in the field of the molecular pathogenesis of PD, with implications for the development of PD diagnostics and disease-modifying therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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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.

Alzheimer's Disease: Genes, pathogenesis and risk prediction

NARCIS (Netherlands)

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

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

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

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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.

Inflammatory bowel diseases (IBD) - critical discussion of etiology, pathogenesis, diagnostics, and therapy

International Nuclear Information System (INIS)

Ochsenkuehn, T.; Sackmann, M.; Goeke, B.

2003-01-01

Aims Crohn's disease and ulcerative colitis are the most frequent inflammatory bowel diseases (IBD) with a prevalence of approximately one out of 500.Cytokine research opened new and potent treatment options and thus stimulated clinical and basic research.However, the IBD still remain a challenge for patients and physicians,demanding close cooperation between gastroenterologists,radiologists and surgeons.The basic understanding of IBD,which is necessary for efficient diagnostic and therapeutic concepts is reviewed. Based upon recent publications and our clinical experience we discuss aspects of etiology,pathogenesis,diagnostics,and therapy of Crohn's disease and ulcerative colitis. A genetically influenced, exaggerated and sustained immune response against the own gut flora seems to be one of the most important factors in the pathogenesis of IBD.Not less important are environmental influences.For instance, cigarette smoking had been judged to have some negative influence on the natural course of Crohn's disease.Now,however, recent studies show that smoking is even a significant independent risk factor in the pathogenesis of IBD. Since IBD and especially Crohn's disease can effect the whole body, detailed analysis of inflammatory organ involvement is necessary before therapy.For instance, the MRIenteroclysis technique adds a necessary diagnostic tool for the exploration of those parts of the small bowel that cannot been reached by routine endoscopy like the upper ileum and the lower jejunum. In terms of therapy, a change of paradigms can be observed: patients will no longer be treated only when symptoms arise, but will early be integrated into a therapeutic concept, which is determined by site and extent of the disease and adapted to the abilities and needs of the patient.Furthermore,immunosuppressive agents like azathioprine and 6-mercaptopurine will establish as central concept in the medical treatment of IBD.Discussion IBD-therapy should rather be adapted to the

Understanding rare disease pathogenesis: a grand challenge for model organisms.

Science.gov (United States)

Hieter, Philip; Boycott, Kym M

2014-10-01

In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.

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Retta, Saverio Francesco; Glading, Angela J

2016-12-01

factors related to differences in vascular sensitivity to oxidative stress and inflammation contribute to inter-individual differences in CCM disease susceptibility and severity. This review discusses recent progress into the understanding of the molecular basis and mechanisms of CCM disease pathogenesis, with specific emphasis on the potential contribution of altered cell responses to oxidative stress and inflammatory events occurring locally in the microvascular environment, and consequent implications for the development of novel, safe, and effective preventive and therapeutic strategies. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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

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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. Copyright © 2014, American Association for the Advancement of Science.

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

Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment.

Science.gov (United States)

Iweala, Onyinye I; Burks, A Wesley

2016-05-01

Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.

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

NARCIS (Netherlands)

Wiersinga, Wilmar M.

2016-01-01

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

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

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Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

2014-07-01

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

New Insights into the Pathogenesis of Celiac Disease

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Valli De Re

2017-08-01

Full Text Available Celiac disease (CD is an autoimmune and multisystem gluten-related disorder that causes symptoms involving the gastrointestinal tract and other organs. Pathogenesis of CD is only partially known. It had been established that ingestion of gluten proteins present in wheat and other cereals are necessary for the disease and develops in individuals genetically predisposed carrying the DQ2 or DQ8 human leukocyte antigen haplotypes. In this review, we had pay specific attention on the last discoveries regarding the three cellular components mainly involved in the development and maintenance of CD: T-cells, B-cells, and microbioma. All of them had been showed critical for the interaction between inflammatory immune response and gluten peptides. Although the mechanisms of interaction among overall these components are not yet fully understood, recent proteomics and molecular studies had shed some lights in the pathogenic role of tissue transglutaminase 2 in CD and in the alteration of the intestinal barrier function induced by host microbiota.

New Insights into the Pathogenesis of Celiac Disease.

Science.gov (United States)

De Re, Valli; Magris, Raffaella; Cannizzaro, Renato

2017-01-01

Celiac disease (CD) is an autoimmune and multisystem gluten-related disorder that causes symptoms involving the gastrointestinal tract and other organs. Pathogenesis of CD is only partially known. It had been established that ingestion of gluten proteins present in wheat and other cereals are necessary for the disease and develops in individuals genetically predisposed carrying the DQ2 or DQ8 human leukocyte antigen haplotypes. In this review, we had pay specific attention on the last discoveries regarding the three cellular components mainly involved in the development and maintenance of CD: T-cells, B-cells, and microbioma. All of them had been showed critical for the interaction between inflammatory immune response and gluten peptides. Although the mechanisms of interaction among overall these components are not yet fully understood, recent proteomics and molecular studies had shed some lights in the pathogenic role of tissue transglutaminase 2 in CD and in the alteration of the intestinal barrier function induced by host microbiota.

The pathogenesis, detection and prevention of Vibrio parahaemolyticus

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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.

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

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Aneal Gadgil

2008-11-01

Full Text Available Aneal Gadgil, Steven R DuncanDivision of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death in the US and a major worldwide healthcare problem. The pathophysiologic mechanisms that drive development and progression of this disease are complex and only poorly understood. While tobacco smoking is the primary risk factor, other disease processes also appear to play a role. Components of the innate immune system (eg, macrophages and neutrophils have long been believed to be important in the development of COPD. More recent evidence also suggests involvement of the adaptive immune system in pathogenesis of this disease. Here we will review the literature supporting the participation of T-cells in the development of COPD, and comment on the potential antigenic stimuli that may account for these responses. We will further explore the prospective contributions of T-cell derived mediators that could contribute to the inflammation, alveolar wall destruction, and small airway fibrosis of advanced COPD. A better understanding of these complex immune processes will lead to new insights that could result in improved preventative and/or treatment strategies.Keywords: COPD, T-lymphocytes, adaptive immunity, cytokines

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

Pathogenesis of salivary gland disease and xerostomia. The conception of Mikulicz's disease based on new knowledge

International Nuclear Information System (INIS)

Himi, Tetsuo; Kanaizumi, Etsuko; Ogasawara, Noriko; Yamamoto, Motohisa; Takahashi, Hiroki

2007-01-01

This review focuses on two topics of salivary gland diseases regarding xerostomia. First, the pathogenesis and treatment of xerostomia after radiotherapy against head and neck cancer is discussed. It is well known that the extent of radiation-induced salivary dysfunction and mucositis depends on the radiation dose and field. Moreover, the balance in the defense system of oropharyngeal cavity alters after radiotherapy. This altered balance may impair the ability to maintain the stable immunological control mechanism. Second, the newly established concept about Mikulicz's disease is discussed. Recently, elevated IgG4 concentration in serum and prominent infiltrating by plasmacytes expressing IgG4 in the salivary glands in Mikulicz's disease were revealed. Mikulicz's disease is different from Sjoegren's syndrome, and may be a systemic IgG4-related plasmacytic disease. (author)

Contribution of pertussis toxin to the pathogenesis of pertussis disease

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Carbonetti, Nicholas H.

2015-01-01

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. PMID:26394801

The role of bile acids in the pathogenesis of bowel diseases

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Magdalena Panek-Jeziorna

2017-08-01

Full Text Available Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19, as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.

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.

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

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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.

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

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Eisfeld, Amie J.; Halfmann, Peter J.; Wendler, Jason P.; Kyle, Jennifer E.; Burnum-Johnson, Kristin E.; Peralta, Zuleyma; Maemura, Tadashi; Walters, Kevin B.; Watanabe, Tokiko; Fukuyama, Satoshi; Yamashita, Makoto; Jacobs, Jon M.; Kim, Young-Mo; Casey, Cameron P.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gritsenko, Marina A.; Monroe, Matthew E.; Weitz, Karl K.; Shukla, Anil K.; Tian, Mingyuan; Neumann, Gabriele; Reed, Jennifer L.; van Bakel, Harm; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; N' jai, Alhaji; Sahr, Foday; Kawaoka, Yoshihiro

2017-12-01

The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies.

Science.gov (United States)

Wallace, John L

2012-01-01

The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Roles of T Cells in the Pathogenesis of Autoimmune Diseases

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Dinglei Su

2013-01-01

Full Text Available γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy.

The pathogenesis of amyloidosis in periodic disease: Some aspects

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Z. T. Djndoyan

2014-07-01

Full Text Available Sufficient information indicating the implication of dysfunction of interleukins (IL-6 and IL-1 in particular in the pathogenesis of amyloidosis in a number of autoinflammatory, rheumatic, and autoimmune diseases, including those in periodic disease (PD, has been recently accumulated. Its genetic defect – pirin mutation – gives rise to an alternative innate immune response (phagocytic cell activation to secrete IL-1 by macrophages and to activate T-helper cells. This causes imbalance in the synthesis of proinflammatory (IL-6, IL-8, and TNF-α and anti-inflammatory (IL-4, IL-10, and IL-1 receptor antagonist cytokines. Moreover, the uncontrolled macrophage (monocyte secretion of a great deal of IL-6 that together with IL-1 is a mediator of the synthesis of the serum amyloid fibril protein precursor SAA by hepatocytes, neutrophils, and fibroblasts plays one of the key roles in the pathogenesis of PD through amyloidosis. With this, IL-6 stimulates the inflammatory process, by enhancing the release of lysosomal enzymes, reactive oxygen species, and eicosanoids (prostaglandins, leukotrienes, thromboxane from the polymorphic nuclear leukocytes, macrophages, endotheliocytes, and fibroblasts and by augmenting the chemotaxis of macrophages and neutrophils, and the degranulation of the latter, i.e. through its action on the effector cells of inflammation, and prepares the tissue basis for amyloid deposits in this fashion. Thus, the analysis of literary and own materials gives grounds to suggest that pirin mutation is a trigger of the synthesis of IL-1 and IL-6 in PD and their hypersecretion is an initial link of the synthesis of SAA.

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

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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

Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

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Barage, Sagar H; Sonawane, Kailas D

2015-08-01

Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pertussis: Microbiology, Disease, Treatment, and Prevention

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Salim, Abdulbaset M.; Zervos, Marcus J.; Schmitt, Heinz-Josef

2016-01-01

SUMMARY Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. PMID:27029594

[Advances in the pathogenesis of non alcoholic fatty liver disease].

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Pár, Alajos; Pár, Gabriella

2017-06-01

Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

T cell-dependence of Lassa fever pathogenesis.

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Lukas Flatz

2010-03-01

Full Text Available Lassa virus (LASV, the causative agent of Lassa fever (LF, is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.

Dental caries: Strategies to control this preventable disease

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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.

Microbial Endocrinology in the Pathogenesis of Infectious Disease.

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Lyte, Mark

2016-04-01

Microbial endocrinology represents the intersection of two seemingly disparate fields, microbiology and neurobiology, and is based on the shared presence of neurochemicals that are exactly the same in host as well as in the microorganism. The ability of microorganisms to not only respond to, but also produce, many of the same neurochemicals that are produced by the host, such as during periods of stress, has led to the introduction of this evolutionary-based mechanism which has a role in the pathogenesis of infectious disease. The consideration of microbial endocrinology-based mechanisms has demonstrated, for example, that the prevalent use of catecholamine-based synthetic drugs in the clinical setting contributes to the formation of biofilms in indwelling medical devices. Production of neurochemicals by microorganisms most often employs the same biosynthetic pathways as those utilized by the host, indicating that acquisition of host neurochemical-based signaling system in the host may have been acquired due to lateral gene transfer from microorganisms. That both host and microorganism produce and respond to the very same neurochemicals means that there is bidirectionality contained with the theoretical underpinnings of microbial endocrinology. This can be seen in the role of microbial endocrinology in the microbiota-gut-brain axis and its relevance to infectious disease. Such shared pathways argue for a role of microorganism-neurochemical interactions in infectious disease.

Pathogenesis and Prevention of Hepatic Steatosis

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Nassir, Fatiha; Rector, R. Scott; Hammoud, Ghassan M.

2015-01-01

Hepatic steatosis is defined as intrahepatic fat of at least 5% of liver weight. Simple accumulation of triacylglycerols in the liver could be hepatoprotective; however, prolonged hepatic lipid storage may lead to liver metabolic dysfunction, inflammation, and advanced forms of nonalcoholic fatty liver disease. Nonalcoholic hepatic steatosis is associated with obesity, type 2 diabetes, and dyslipidemia. Several mechanisms are involved in the accumulation of intrahepatic fat, including increased flux of fatty acids to the liver, increased de novo lipogenesis, and/or reduced clearance through β-oxidation or very-low-density lipoprotein secretion. This article summarizes the mechanisms involved in the accumulation of triacylglycerols in the liver, the clinical implications, and the prevention of hepatic steatosis, with a focus on the role of mitochondrial function and lifestyle modifications. PMID:27099587

Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease.

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Mattoo, Hamid; Stone, John H; Pillai, Shiv

2017-02-01

IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4 + T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated. Among the CD4 + T-cell subsets, Th2 cells were initially thought to contribute to IgG4-RD pathogenesis, but many previous studies were confounded by the concomitant history of allergic diseases in the patients studied and the failure to use multi-color staining to definitively identify T-cell subsets in tissue samples. More recently, using an unbiased approach to characterize CD4 + T-cell subsets in patients with IgG4-RD - based on their clonal expansion and ability to infiltrate affected tissue sites - CD4 + CTLs have been identified as the major CD4 + T-cell subset in disease lesions as well as in the circulation. CD4 + CTLs in affected tissues secrete pro-fibrotic cytokines including IL-1β, TGF-β1, and IFN-γ as well as cytolytic molecules such as perforin and granzymes A and B. In this review, we examine possible mechanisms by which activated B cells and plasmablasts may collaborate with the expanded CD4 + CTLs in driving the fibrotic pathology of the disease and describe the lacunae in the field and in our understanding of IgG4-RD pathogenesis.

Sugary drinks in the pathogenesis of obesity and cardiovascular diseases.

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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.

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

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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.

Evaluation of circulating zonulin as a potential marker in the pathogenesis of nonalcoholic fatty liver disease.

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Hendy, Olfat M; Elsabaawy, Maha M; Aref, Mona M; Khalaf, Fatma M; Oda, Abdel Moaty A; El Shazly, Helmy M

2017-07-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested. Liver function tests, serum glucose, fasting insulin, C peptide, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), IL-6, and circulating zonulin were performed to all subjects. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), triglycerides, HDL-c, fasting insulin, C peptide, HOMA-IR, IL-6, and serum zonulin were higher in NAFLD group than in controls (p Zonulin was positively correlated with body mass index (BMI), ALT, triglycerides, fasting insulin, HOMA-IR, liver histopathology, and serum IL-6 (p zonulin was found to be of diagnostic value of NASH occurrence with 100% sensitivity and specificity (AUR = 1.000, p-value = zonulin levels in NAFLD patients with steep rise in NASH group denotes a possible role in pathogenesis of NAFLD occurrence and progression. This could open a new avenue of implicating zonulin antagonists as targeted therapies in NAFLD prevention. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Amyloid-β and chronic cerebral hypoperfusion in the early pathogenesis of Alzheimer’s disease

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Salvadores Bersezio, Natalia

2016-01-01

Alzheimer’s disease (AD) is a severe age-related neurodegenerative disorder and is the most common form of dementia. Although the pathogenesis of AD remains unknown, the deterioration of the cerebrovascular system constitutes a risk factor associated with the development of the disease. Notably, brain hypoperfusion, a feature of healthy ageing brain and AD, occurs prior to the onset of cognitive decline in AD and correlates with the severity of dementia. Although there is a cle...

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.

The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases.

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Brodziak, Andrzej; Ziółko, Ewa; Muc-Wierzgoń, Małgorzata; Nowakowska-Zajdel, Ewa; Kokot, Teresa; Klakla, Katarzyna

2012-06-01

This paper presents a new, recently formulated theory, which concerns the etiopathological process of autoimmune diseases. This theory takes into account the existence in the human genome, since approximately 40 million years, of so-called human endogenous retroviruses (HERVs), which are transmitted to descendants "vertically" by the germ cells. It was recently established that these generally silent sequences perform some physiological roles, but occasionally become active and influence the development of some chronic diseases like diabetes, some neoplasms, chronic diseases of the nervous system (eg, sclerosis multiplex), schizophrenia and autoimmune diseases. We present a short synopsis of immunological processes involved in the pathogenesis of autoimmune diseases, such as molecular mimicry, epitope spreading and activation of the superantigen. We then focus on experimental findings related to systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and some diseases of hepar and otorhinal tissues. We conclude the outline of this new model of the development of chronic diseases and indicate the conclusions important for the teaching of the basis of pathology.

Recent advances in recurrent urinary tract infection from pathogenesis and biomarkers to prevention

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Jia-Fong Jhang

2017-01-01

Full Text Available Recurrent urinary tract infection (UTI might be one of the most common problems in urological clinics. Recent research has revealed novel evidence about recurrent UTI and it should be considered a different disease from the first infection. The pathogenesis of recurrent UTI might include two mechanisms, bacterial factors and deficiencies in host defense. Bacterial survival in the urinary bladder after antibiotic treatment and progression to form intracellular bacterial communities might be the most important bacterial factors. In host defense deficiency, a defect in pathogen recognition and urothelial barrier function impairment play the most important roles. Immunodeficiency and urogenital tract anatomical abnormalities have been considered the essential risk factors for recurrent UTI. In healthy women, voiding dysfunction and behavioral factors also increase the risk of recurrent UTI. Sexual intercourse and estrogen deficiency in postmenopausal women might have the strongest association with recurrent UTI. Traditional lifestyle factors such as fluid intake and diet are not considered independent risk factors now. Serum and urine biomarkers to predict recurrent UTI from the first infection have also attracted a wide attention recently. Current clinical evidence suggests that serum macrophage colony-stimulating factor and urinary nerve growth factor have potential predictive value for recurrent UTI. Clinical trials have proven the efficacy of the oral immunoactive agent OM-89 for the prevention of UTI. Vaccines for recurrent UTI are recommended by the latest guidelines and are available on the market.

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

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Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John W.; Metz, Thomas O.

2009-01-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the ...

The Mechanisms of Traditional Chinese Medicine Underlying the Prevention and Treatment of Parkinson's Disease

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Xiaoliang Li

2017-09-01

Full Text Available Parkinson's disease (PD, characterized with bradykinesia, static tremor, rigidity and disturbances in balance, is the second most common neurodegenerative disorder. Along with the largely aging population in the world, the incidence is increasing year by year, which imposes the negative impacts on patients, their families and the whole society. Traditional Chinese medicine (TCM has a positive prospect for the prevention and cure of PD due to its advantages of less side effects and multi-target effects. At present, the pathogenesis of PD is not yet fully discovered. This paper elaborates the mechanisms of TCM underlying the prevention and treatment of PD with regards to the inhibition of oxidative stress, the regulation of mitochondrial dysfunction, the reduction of toxic excitatory amino acids (EAA, the inhibition of neuroinflammation, the inhibition of neuronal apoptosis, and the inhibition of abnormal protein aggregation.

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

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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.

Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

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Marilita M. Moschos

2014-01-01

Full Text Available Age-related macular degeneration (ARMD is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

Role of Nutritional Factors at the Early Life Stages in the Pathogenesis and Clinical Course of Type 1 Diabetes

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Yukiko Kagohashi

2015-01-01

Full Text Available Nutrition has been suggested as an important environmental factor other than viruses and chemicals in the pathogenesis of type 1 diabetes (T1D. Whereas various maternal dietary nutritional elements have been suggested and examined in T1D of both humans and experimental animals, the results largely remain controversial. In a series of studies using T1D model nonobese diabetic (NOD mice, maternal dietary n-6/n-3 essential fatty acid ratio during pregnancy and lactation period, that is, early life stages of the offspring, has been shown to affect pathogenesis of insulitis and strongly prevent overt T1D of the offspring, which is consistent with its preventive effects on other allergic diseases.

Advances in the microbial etiology and pathogenesis of early childhood caries

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Hajishengallis, Evlambia; Parsaei, Yassmin; Klein, Marlise I.; Koo, Hyun

2016-01-01

Early childhood caries (ECC) is one of the most prevalent infectious diseases affecting children worldwide. ECC is an aggressive form of dental caries, which left untreated, can result in rapid and extensive cavitation in teeth (rampant caries) that is painful and costly to treat. Furthermore, it affects mostly children from impoverished background, and thus constitutes a major challenge in public health. The disease is a prime example of the consequences arising from complex, dynamic interactions between microorganisms, host and diet, leading to the establishment of highly pathogenic (cariogenic) biofilms. To date, there are no effective methods to identify those at risk of developing ECC or control the disease in affected children. Recent advances in deep-sequencing technologies, novel imaging methods and (meta)proteomics-metabolomics approaches provide an unparalleled potential to reveal new insights to illuminate our current understanding about the etiology and pathogenesis of the disease. In this concise review, we provide a broader perspective about the etiology and pathogenesis of ECC based on previous and current knowledge on biofilm matrix, microbial diversity and host-microbe interactions which could have direct implications for developing new approaches for improved risk assessment and prevention of this devastating and costly childhood health condition. PMID:26714612

Intestinal Epithelial Cell Endoplasmic Reticulum Stress and Inflammatory Bowel Disease Pathogenesis: An Update Review

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Xiaoshi Ma

2017-10-01

Full Text Available The intestinal epithelial cells serve essential roles in maintaining intestinal homeostasis, which relies on appropriate endoplasmic reticulum (ER function for proper protein folding, modification, and secretion. Exogenous or endogenous risk factors with an ability to disturb the ER function can impair the intestinal barrier function and activate inflammatory responses in the host. The last decade has witnessed considerable progress in the understanding of the functional role of ER stress and unfolded protein response (UPR in the gut homeostasis and its significant contribution to the pathogenesis of inflammatory bowel disease (IBD. Herein, we review recent evidence supporting the viewpoint that deregulation of ER stress and UPR signaling in the intestinal epithelium, including the absorptive cells, Paneth cells, goblet cells, and enteroendocrine cells, mediates the action of genetic or environmental factors driving colitis in experimental animals and IBD patients. In addition, we highlight pharmacologic application of chaperones or small molecules that enhance protein folding and modification capacity or improve the function of the ER. These molecules represent potential therapeutic strategies in the prevention or treatment of IBD through restoring ER homeostasis in intestinal epithelial cells.

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis

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Donaldson, David S.; Else, Kathryn J.

2015-01-01

ABSTRACT Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis.

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Donaldson, David S; Else, Kathryn J; Mabbott, Neil A

2015-09-01

Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal

Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I.

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Heppner, Jonathan M; Zaucke, Frank; Clarke, Lorne A

2015-02-01

Progressive skeletal and connective tissue disease represents a significant clinical burden in all of the mucopolysaccharidoses. Despite the introduction of enzyme replacement strategies for many of the mucopolysaccharidoses, symptomatology related to bone and joint disease appears to be recalcitrant to current therapies. In order to address these unmet medical needs a clearer understanding of skeletal and connective tissue disease pathogenesis is required. Historically the pathogenesis of the mucopolysaccharidoses has been assumed to directly relate to progressive storage of glycosaminoglycans. It is now apparent for many lysosomal storage disorders that more complex pathogenic mechanisms underlie patients' clinical symptoms. We have used proteomic and genome wide expression studies in the murine mucopolysaccharidosis I model to identify early pathogenic events occurring in micro-dissected growth plate tissue. Studies were conducted using 3 and 5-week-old mice thus representing a time at which no obvious morphological changes of bone or joints have taken place. An unbiased iTRAQ differential proteomic approach was used to identify candidates followed by validation with multiple reaction monitoring mass spectrometry and immunohistochemistry. These studies reveal significant decreases in six key structural and signaling extracellular matrix proteins; biglycan, fibromodulin, PRELP, type I collagen, lactotransferrin, and SERPINF1. Genome-wide expression studies in embryonic day 13.5 limb cartilage and 5 week growth plate cartilage followed by specific gene candidate qPCR studies in the 5week growth plate identified fourteen significantly deregulated mRNAs (Adamts12, Aspn, Chad, Col2a1, Col9a1, Hapln4, Lum, Matn1, Mmp3, Ogn, Omd, P4ha2, Prelp, and Rab32). The involvement of biglycan, PRELP and fibromodulin; all members of the small leucine repeat proteoglycan family is intriguing, as this protein family is implicated in the pathogenesis of late onset osteoarthritis

THE ROLE OF EPIDERMAL BARRIER IMPAIRMENTS IN ATOPIC DERMATITIS: MODERN CONCEPTS OF DISEASE PATHOGENESIS

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Nikolay N. Murashkin

2018-01-01

Full Text Available Atopic dermatitis is a common chronic inflammatory skin disease characterized by a recurring course and progressive decrease in the quality of life. Recent studies in this area demonstrate the multifaceted pathogenesis of atopic dermatitis. Interaction of such factors as epidermal dysfunction, immune system disorders, and the consequences of genetic mutations contributes not only to the development of the disease but also to its progression and chronic course. The article presents various components of the etiopathogenesis of atopic dermatitis, describes the role of lipids, thereby the new therapeutic targets are revealed to specialists.

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

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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.

RISC in PD: The Impact of MicroRNAs in Parkinson’s Disease Cellular and Molecular Pathogenesis

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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.

A Perspective on the Maillard Reaction and the Analysis of Protein Glycation by Mass Spectrometry: Probing the Pathogenesis of Chronic Disease

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Zhang, Qibin; Ames, Jennifer M.; Smith, Richard D.; Baynes, John; Metz, Thomas O.

2008-12-18

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide on overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease.

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Zhang, Qibin; Ames, Jennifer M; Smith, Richard D; Baynes, John W; Metz, Thomas O

2009-02-01

The Maillard reaction, starting from the glycation of protein and progressing to the formation of advanced glycation end-products (AGEs), is implicated in the development of complications of diabetes mellitus, as well as in the pathogenesis of cardiovascular, renal, and neurodegenerative diseases. In this perspective review, we provide an overview on the relevance of the Maillard reaction in the pathogenesis of chronic disease and discuss traditional approaches and recent developments in the analysis of glycated proteins by mass spectrometry. We propose that proteomics approaches, particularly bottom-up proteomics, will play a significant role in analyses of clinical samples leading to the identification of new markers of disease development and progression.

Advances in canine distemper virus pathogenesis research: a wildlife perspective.

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Loots, Angelika K; Mitchell, Emily; Dalton, Desiré L; Kotzé, Antoinette; Venter, Estelle H

2017-03-01

Canine distemper virus (CDV) has emerged as a significant disease of wildlife, which is highly contagious and readily transmitted between susceptible hosts. Initially described as an infectious disease of domestic dogs, it is now recognized as a global multi-host pathogen, infecting and causing mass mortalities in a wide range of carnivore species. The last decade has seen the effect of numerous CDV outbreaks in various wildlife populations. Prevention of CDV requires a clear understanding of the potential hosts in danger of infection as well as the dynamic pathways CDV uses to gain entry to its host cells and its ability to initiate viral shedding and disease transmission. We review recent research conducted on CDV infections in wildlife, including the latest findings on the causes of host specificity and cellular receptors involved in distemper pathogenesis.

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

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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.

Dysregulated microRNAs in neural system: Implication in pathogenesis and biomarker development in Parkinson's disease.

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Lu, Jiangkun; Xu, Yan; Quan, Zhenzhen; Chen, Zixuan; Sun, Zhenzhen; Qing, Hong

2017-12-04

Parkinson's disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. However, despite years of investigation, still little is known about early events in the molecular pathogenesis. MicroRNAs are small non-coding RNAs that can regulate post-transcriptional expression of mRNAs. Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA's mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

The pathogenesis of Newcastle disease: A comparison of selected Newcastle disease virus wild-type strains and their infectious clones

International Nuclear Information System (INIS)

Wakamatsu, Nobuko; King, Daniel J.; Seal, Bruce S.; Samal, Siba K.; Brown, Corrie C.

2006-01-01

The effect of mutations of Newcastle disease virus (NDV) fusion (F) gene, hemagglutinin-neuraminidase (HN) gene, and phosphoprotein (P) gene and HN chimeras between the virulent Beaudette C and low virulence LaSota strains on pathogenesis and pathogenicity was examined in fully susceptible chickens. A virulent F cleavage site motif within a LaSota backbone increased pathogenicity and severity of clinical disease. A LaSota HN within a Beaudette C backbone decreased pathogenicity indices and disease severity. A Beaudette C HN within a LaSota backbone did not change either pathogenicity indices or severity of disease in chickens. Loss of glycosylation at site 4 of the HN or modified P gene of Beaudette C decreased pathogenicity indices and caused no overt clinicopathologic disease in chickens. Both pathogenicity indices and clinicopathologic examination demonstrated that the F, HN, and P genes of NDV collectively or individually can contribute to viral virulence

Modern concepts of pathogenesis of ichthyosis

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Світлана Володимирівна Дмитренко

2015-06-01

Full Text Available The modern concepts of ichthyosis are rather ambiguous and need more precise definition. The modern conception of pathogenesis of ichthysosis is offered and considered in this article.Aim. An aim is to analyze received data of our researches about molecular disturbances of keratin on the background of ichthyosis and the current data on the pathogenesis of disease.Materials and methods. An analysis of the results of research in 70 patients with ichthyosis by the methods of the flow cytometry, immunohistochemistry and by immunologic methods is presented in an article.Results. Authors revealed molecular, immunologic and immunohistochemical changes that realizes the disturbance of keratinization on the background of this disease. The model of pathogenesis of the various manifestations of gene mutations that causes ichthyosis is proposed and it can be taken into account when elaborating the new directions of therapy.Conclusions. Gene mutations that cause ichthyosis realizes on the background of disturbance of the cell cycle causing cornification and disturb the local and general immune reactions that summarily lead to the clinical presentations of disease. 

Parkinson's disease--the debate on the clinical phenomenology, aetiology, pathology and pathogenesis.

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Jenner, Peter; Morris, Huw R; Robbins, Trevor W; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V; Brooks, David

2013-01-01

The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article--widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include--Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).

Mobile Health, a Key Factor Enhancing Disease Prevention Campaigns: Looking for Evidences in Kidney Disease Prevention

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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

Mid-Atlantic Microbial Pathogenesis Meeting

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2005-12-01

rheumatic fever, yet little is understood about the regulation of streptococcal genes involved in disease processes and survival in the host. Genome...of brucellosis, a disease that is characterized by abortion and infertility in ruminant animals and undulant fever in humans. In the natural hosts...were presented at this session. 15. SUBJECT TERMS bacteria, pathogenesis, microbiology, virulence, disease 16. SECURITY CLASSIFICATION OF: 17

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

Extranodal Rosai-Dorfman disease of bone, subcutaneous tissue and paranasal sinus mucosa with a review of its pathogenesis

International Nuclear Information System (INIS)

Yoon, Angela J.; Parisien, May; Feldman, Frieda; Young-In Lee, Francis

2005-01-01

We report an unusual case of extranodal Rosai-Dorfman disease presenting in a 36-year-old man with lesions of bone, subcutaneous tissue of the arm and maxillary sinus mucosa unassociated with lymphadenopathy or systemic symptoms. These lesions appeared metachronously within a 6-month period. The diagnostic light microscopic and immunohistochemical findings and pathogenesis of this interesting disease are discussed. (orig.)

The role of the apelinergic and vasopressinergic systems in the regulation of the cardiovascular system and the pathogenesis of cardiovascular disease.

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Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka

2014-01-01

Research studies indicate a role of the apelinergic and vasopressinergic systems both in the regulation of the cardiovascular system and the pathogenesis of CVD, including in such settings as obesity and stress. Based on these data, it may be suggested that interactions between these systems underlie numerous physiological and pathophysiological processes, some of them related to the cardiovascular system. Better understanding of the role of these systems and their interactions, both physiological and related to the pathogenesis of CVD, will allow further advances in prevention and drug therapy.

Action of mechanism of traditional Chinese medicine in prevention and treatment of nonalcoholic fatty liver disease

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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.

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

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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.

[Prevention of Chronic Kidney Disease and strategies to counteract chronic diseases in Italy].

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Mastrilli, Valeria; D'Elia, Roberto; Galeone, Daniela

2016-01-01

The Prevention of Chronic Kidney Disease (CKD) is placed in the more general context of prevention of major chronic Non Communicable Diseases (NCDs): cardiovascular diseases, diabetes, chronic lung diseases and tumors that are the main problem for public health worldwide. Any health policy strategy aimed to the prevention of NCDs has to provide knowledge of health and socioeconomic status of the population, to reduce the level of exposure to risk factors and to adapt health services to the request for assistance. To this purpose, population monitoring systems have been implemented in the last years. The NCDs share some risk factors that are related, in large part, to unhealthy individual behaviours: smoking, alcohol abuse, unhealthy diet and physical inactivity. NCDs prevention has to be understood as the set of all actions, sanitary and not, aiming to prevent or delay the onset of diseases or their complications. Preventive measures should, therefore, involve not only the health sector but also all the actors that can help to prevent that disease. As for the Prevention of CKD, the Ministry of Health has established a working table, which handled the Drafting of the "Position paper for the CKD", approved in the State-Regions Conference on august 8th 2014. The document draws a national strategy to combat this disease through primary prevention, early diagnosis and the establishment of diagnostic - therapeutic pathways (DTP).

Helicobacter pylori virulence and cancer pathogenesis.

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Yamaoka, Yoshio; Graham, David Y

2014-06-01

Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

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Françoise Stoll-Keller

2012-10-01

Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

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Hai-yang JIANG

2017-10-01

Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

Office of Disease Prevention and Health Promotion

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... Health Literacy Health Care Quality Healthy People healthfinder Office of Disease Prevention and Health Promotion Spotlight: This ... 16/2017 This site is coordinated by the Office of Disease Prevention and Health Promotion, Office of ...

[Prevention of systemic lupus erythematosus in children born to mothers treated for this disease].

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Kardaszewicz, E; Machalski, M; Woszczyk, D; Woszczyk, M; Harbut-Gryłka, A

Genetic predisposition and environmental factors (physical, chemical, hormonal and drugs inducing collagen-like syndrome) play an important role in the pathogenesis of the systemic lupus erythematosus. Elimination of these factors from the environment of the genetically predisposed individuals may prevent part of them against the disease. Basing on the above assumption, a chart of prophylaxis has been constructed and distributed among the mothers with the systemic lupus erythematosus, recommending prophylactic measures in both mothers and children. Within 1977-1987, 50 children were examined from time to time. Basic laboratory tests, phenomenon LE, antinuclear antibodies and antibodies anti-DNA have been determined. Transient presence of antinuclear antibodies was seen in 23 children. A tendency to an increase in the antibody titre was observed in girls of this group whereas a decrease in the titre was noted in the boys with the time lapse. Systemic lupus erythematosus prophylaxis in both mothers and children is uncomplicated and favourable for children. Regular determination of antibodies enables early diagnosis of the disease.

Does prevention for Alzheimer's disease exist?

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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.

Primary Prevention of Congenital Anomalies: Special Focus on Environmental Chemicals and other Toxicants, Maternal Health and Health Services and Infectious Diseases.

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Taruscio, Domenica; Baldi, Francesca; Carbone, Pietro; Neville, Amanda J; Rezza, Giovanni; Rizzo, Caterina; Mantovani, Alberto

2017-01-01

Congenital anomalies (CA) represent an important fraction of rare diseases, due to the critical role of non-genetic factors in their pathogenesis. CA are the main group of rare diseases in which primary prevention measures will have a beneficial impact. Indeed, since 2013 the European Union has endorsed a body of evidence-based recommendations for CA primary prevention; the recommendations aim at facilitating the inclusion of primary prevention actions the National Rare Disease Plans of EU Member States and encompass different public health fields, from environment through to maternal diseases and lifestyles.The chapter overviews and discusses the assessment of main risk factors for CA, such as environmental toxicants, maternal health and lifestyles and infections, with a special attention to issues that are emerging or need more knowledge.Overall, the availability of CA registries is important for estimating the health burden of CA, identifying possible hotspots, assessing the impact of interventions and addressing further, fit-to-purpose research.The integration of relevant public health actions that are already in place (e.g., control of noxious chemicals, vaccination programmes, public health services addressing chronic maternal conditions) can increase the affordability and sustainability of CA primary prevention. In developing countries with less primary prevention in place and limited overall resources, a first recognition phase may be pivotal in order to identify priority targets. In the meanwhile, policy makers should be made aware that primary prevention of RD supports publicly endorsed societal values like the knowledge-based promotion of health, empowerment, equity and social inclusiveness.

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

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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

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.

Heart Disease Prevention: Does Oral Health Matter?

Science.gov (United States)

... Will taking care of my teeth help prevent heart disease? Answers from Thomas J. Salinas, D.D.S. Taking ... teeth isn't a proven way to prevent heart disease. While there appears to be some connection between ...

[Condom effectiveness to prevent sexually transmitted diseases].

Science.gov (United States)

Vera, Eduardo Gayón; Orozco, Hilda Hernández; Soto, Selene Sam; Aburto, Esther Lombardo

2008-02-01

Sexual transmitted diseases (included HIV/AIDS) are a common and preventable cause of perinatal morbidity and mortality. When used consistently and correctly, condoms are effective to prevent these diseases, however, its protection does not account for 100%. To know the effectiveness of male condom, through bibliographic evidence, to prevent sexual transmitted infections in heterosexual serodiscordant partners. A bibliographical review of Medline/Pubmed, LILACS and Cochrane databases, and publications of the National Health Institutes, Centers for Disease Control and Prevention, World Health Organization, and WHO AIDS Global Program was done to analyze male condom effectiveness to prevent sexual transmitted diseases. Reports demonstrated that male condom protection against HIV/AIDS in heterosexual serodiscordant partners goes from 60 to 95%. Most recent information (2006) showed 80%. Two studies demonstrated no HPV protection with male condom, and another one 70% of protection. Male condom demonstrated no HPV-1 protection, but decrease of risk in HVS-2 transmission in women (0.85 of protection). Male condom protection against sexual transmitted diseases is not 100%. There must be used additional measures that have demonstrated its utility to decrease transmission risk.

Pathogenesis of Hepatic Encephalopathy

Directory of Open Access Journals (Sweden)

Irena Ciećko-Michalska

2012-01-01

Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

Pathogenesis of Hepatic Encephalopathy

Science.gov (United States)

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

Strengthening the prevention of periodontal disease

DEFF Research Database (Denmark)

Petersen, Poul Erik; Ogawa, Hiroshi

2005-01-01

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....... Updated information concerning WHO standard age groups was used to describe the prevalence rates of signs of periodontal disease, i.e., gingival bleeding, periodontal pocketing, and loss of attachment. RESULTS: Gingival bleeding is highly prevalent among adult populations in all regions of the world...

Genes contributing to prion pathogenesis

DEFF Research Database (Denmark)

Tamgüney, Gültekin; Giles, Kurt; Glidden, David V

2008-01-01

incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

The peculiarities of pathogenesis of NSAID-induced gastrointestinal injuries and current prevention strategies

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Anatol Święcicki

2014-07-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are among the most widely used medications. However, NSAID intake is accompanied by an increased risk of gastroduodenal side effects. These adverse events are largely attributed to the ability of these drugs to suppress prostaglandin synthesis, penetrate the mucosal layer in the acid media of the stomach and damage epithelial cells. However, it is becoming clear that such mediators as prostaglandins, NO and lipoxins can protect the stomach from injury. This injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors. In contrast, the pathogenesis of intestinal injury induced by NSAIDs is less well understood. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. In this review the results of recent studies are described, which will help to clarify some mechanisms of development of NSAID gastropathies and NSAID enteropathies and to improve the treatment of these patients.

Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

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Staci D. Bilbo

2012-01-01

Full Text Available Several lines of evidence support the view that autism is a typical member of a large family of immune-related, noninfectious, chronic diseases associated with postindustrial society. This family of diseases includes a wide range of inflammatory, allergic, and autoimmune diseases and results from consequences of genetic/culture mismatches which profoundly destabilize the immune system. Principle among these consequences is depletion of important components, particularly helminths, from the ecosystem of the human body, the human biome. Autism shares a wide range of features in common with this family of diseases, including the contribution of genetics/epigenetics, the identification of disease-inducing triggers, the apparent role of immunity in pathogenesis, high prevalence, complex etiologies and manifestations, and potentially some aspects of epidemiology. Fortunately, using available resources and technology, modern medicine has the potential to effectively reconstitute the human biome, thus treating or even avoiding altogether the consequences of genetic/cultural mismatches which underpin this entire family of disease. Thus, if indeed autism is an epidemic of postindustrial society associated with immune hypersensitivity, we can expect that the disease is readily preventable.

Endothelin type B (ETB) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk?

Science.gov (United States)

Mirabito Colafella, Katrina M

2018-01-16

In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ET B ) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ET B receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. Currently, there is great interest in the role of the endothelin system in pre-eclampsia. Targetting the endothelin system, potentially by modulating upstream pathways to prevent ET B receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Kaposi sarcoma herpesvirus pathogenesis

Science.gov (United States)

Koch, Sandra; Schulz, Thomas F.

2017-01-01

Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

Demonstrating concepts of pathogenesis using effectors of Phytophthora infestans

Science.gov (United States)

Pathogenesis, or how pathogens cause disease, is an important concept in plant pathology. The study of pathogenesis in plant pathology has rapidly expanded and is now a significant portion of plant pathology research (especially research at the molecular level of host-pathogen interaction). With the...

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

Science.gov (United States)

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

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Lianjun Yang

2016-12-01

Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one’s susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated.

Biology and pathogenesis of Acanthamoeba

OpenAIRE

Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

2012-01-01

Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and ev...

Neuroinflammation in Alzheimer's disease

DEFF Research Database (Denmark)

Heneka, Michael T; Carson, Monica J; Khoury, Joseph El

2015-01-01

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia......, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded...... therapeutic or preventive strategies for Alzheimer's disease....

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

Science.gov (United States)

Lee, Kyung-Yil

2017-06-01

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

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. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Introduction to the Centers for Disease Control and Prevention and Healthcare Infection Control Practices Advisory Committee Guideline for Prevention of Surgical Site Infection: Prosthetic Joint Arthroplasty Section.

Science.gov (United States)

Segreti, John; Parvizi, Javad; Berbari, Elie; Ricks, Philip; Berríos-Torres, Sandra I

Peri-prosthetic joint infection (PJI) is a severe complication of total joint arthroplasty that appears to be increasing as more of these procedures are performed. Numerous risk factors for incisional (superficial and deep) and organ/space (e.g., PJI) surgical site infections (SSIs) have been identified. A better understanding and reversal of modifiable risk factors may lead to a reduction in the incidence of incisional SSI and PJI. The Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recently updated the national Guideline for Prevention of Surgical Site Infection. The updated guideline applies evidence-based methodology, presents recommendations for potential strategies to reduce the risk of SSI, and includes an arthroplasty-specific section. This article serves to introduce the guideline development process and to complement the Prosthetic Joint Arthroplasty section with background information on PJI-specific economic burden, epidemiology, pathogenesis and microbiology, and risk factor information.

When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy.

Science.gov (United States)

Tang, Jun; Pei, Yijin; Zhou, Guangji

2013-08-01

Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations. Copyright © 2013 Elsevier Inc. All rights reserved.

Theories on the Pathogenesis of Endometriosis

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Samer Sourial

2014-01-01

Full Text Available Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

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.

Pathogenesis and immunobiology of brucellosis: review of Brucella-host interactions.

Science.gov (United States)

de Figueiredo, Paul; Ficht, Thomas A; Rice-Ficht, Allison; Rossetti, Carlos A; Adams, L Garry

2015-06-01

This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Novel lipid signaling pathways in Alzheimer's disease pathogenesis.

Science.gov (United States)

Giannopoulos, Phillip F; Joshi, Yash B; Praticò, Domenico

2014-04-15

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. With an increasing longevity and the absence of a cure, AD has become not only a major health problem but also a heavy social and economic burden worldwide. In addition to the presence of abundant intra- and extra-cellular neurotoxic amyloid β (Aβ) peptides, which form the amyloid plaques, and intracellular hyperphosphorylated tau protein, the main component of neurofibrillary tangles, consistent evidence indicates that the AD brain is characterized by extensive neuroinflammatory processes. The 5-lipoxygenase (5LO) is a pro-inflammatory enzymatic pathway widely distributed within the central nervous system and is up-regulated in AD. In the last five years our group has been involved in unraveling the neurobiology of this protein and investigating its relationship with cellular and molecular events of functional importance in AD pathogenesis. By using a combination of in vitro and in vivo experimental tools and implementing genetic as well as pharmacological approaches today we know that 5LO is likely an endogenous regulator of Aβ formation via the modulation of the γ-secretase complex, and tau metabolism by modulating its phosphorylation state at specific epitopes via the cyclin-dependent kinase-5 (cdk-5). In addition, 5LO influences synaptic function and integrity and by doing so significantly affects learning and memory in the Tg2576 and 3xTg AD transgenic mouse models. Taken together our data establish this protein as a pleiotropic contributor to the development of the full spectrum of the AD-like phenotype in these mouse models of the disease, making it a viable therapeutic target for the treatment of AD in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

Trichomonas vaginalis Pathogenesis: a Narrative Review

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Zahra Arab-Mazar

2015-07-01

Full Text Available In the latest articles which were published during 2013-2014, Trichomonas vaginalis (T. vaginalis was mentioned as a neglected sexual transmission disease (STD, while the exact mechanism of its pathogenesis has not been cleared yet. Although trichomonasiasis is easy curable, there is concern that resistance to drug are increasing. This common infection as concerning the important public health implications needs more research to be done for understanding the diagnosis, treatment, immunology and pathogenesis. In this review we searched all valuable and relevant information considering the pathogenesis of T. vaginalis. We referred to the information databases of Medline, PubMed, Scopus and Google scholar. The used keywords were the combinations of T. vaginalis and words associated with pathogenicity. This review discusses the host-parasite interaction and pathogenicity of this parasite.

Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

Science.gov (United States)

Saad, Leonide; Washington, Ilyas

2016-01-01

We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

TOWARDS THE ELIMINATION OF PREVENTABLE DISEASES

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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. 

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.

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

DEFF Research Database (Denmark)

Nielsen, Liza Rosenbaum

Mycoplasma bovis introduction to and spread within cattle herds is difficult to predict, and no vaccines provide efficient prevention today despite the fact that this infection severely affects animal welfare and leads to economic losses in cattle farms worldwide. The most common transmission...... from infected bulls and perhaps long-distance airborne pathogens being spread between outbreaks and susceptible farms. Prevention and control methods have to focus on management and biosecurity measures that maximise resilience of the farm system and the animals’ resistance against the disease in case...

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.

Pathogenesis of peptic ulcer disease and current trends in therapy.

Science.gov (United States)

Desai, J K; Goyal, R K; Parmar, N S

1997-01-01

Traditionally drugs used in peptic ulcer have been directed mainly against a single luminal damaging agent i.e. hydrochloric acid and a plethora of drugs like antacids, anticholinergics, histamine H2-antagonists etc. have flooded the market. An increase in 'aggressive' factors like acid and pepsin is found only in a minority of peptic ulcer patients. These factors do not alter during or after spontaneous healing. It is well-known that the gastric mucosa can resist auto-digestion though it is exposed to numerous 'insults' like high concentration of hydrochloric acid, pepsin, reflux of bile, spicy food, microorganisms and at times alcohol and irritant drugs. It is thus evident that the integrity of the gastric mucosa is maintained by defense mechanisms against these 'aggressive' damaging factors. Recently, attention has been focused more on gastroduodenal defense mechanisms leading to the concept of 'Cytoprotection'. The old dictum "no acid--no ulcer" now extends to "if acid--why ulcer"? as a fundamental question. During last decade more information has poured in about the prevalence and changing pattern of the disease, the influence of environmental factors and speculation on the role of a recently characterized bacterial organism, Helicobacter pylori which colonizes in the gastric mucosa, particularly the antral region. This review briefly describes current knowledge about the pathogenesis of peptic ulcer disease and discusses strategies for its treatment.

Primary prevention of chronic obstructive pulmonary disease in primary care.

Science.gov (United States)

van der Molen, Thys; Schokker, Siebrig

2009-12-01

Chronic obstructive pulmonary disease (COPD) is a prevalent disease, with cigarette smoking being the main risk factor. Prevention is crucial in the fight against COPD. Whereas primary prevention is targeted on whole populations, patient populations are the focus of primary care; therefore, prevention in this setting is mainly aimed at preventing further deterioration of the disease in patients who present with the first signs of disease (secondary prevention). Prevention of COPD in primary care requires detection of COPD at an early stage. An accurate definition of COPD is crucial in this identification process. The benefits of detecting new patients with COPD should be determined before recommending screening and case-finding programs in primary care. No evidence is available that screening by spirometry results in significant health gains. Effective treatment options in patients with mild disease are lacking. Smoking cessation is the cornerstone of COPD prevention. Because cigarette smoking is not only a major cause of COPD but is also a major cause of many other diseases, a decline in tobacco smoking would result in substantial health benefits.

Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer's disease model mouse.

Science.gov (United States)

Oue, Hiroshi; Miyamoto, Yasunari; Koretake, Katsunori; Okada, Shinsuke; Doi, Kazuya; Jung, Cha-Gyun; Michikawa, Makoto; Akagawa, Yasumasa

2016-09-01

Previous studies have reported that tooth loss is a risk factor of Alzheimer's disease (AD). However, the association between tooth loss and cognition and the impact of tooth loss on the molecular pathogenesis of AD remain elusive. In this study, we tested the effect of tooth loss on learning and memory and on the molecular pathogenesis of AD in an aged AD model mice. We divided 14-month-old amyloid precursor protein (APP) transgenic mice, an AD model mouse line, into upper molar extracted group (experimental) and molar intact group (control). At 18 months old, we analysed not only the changes of amyloid-beta (Aβ), pyramidal cells in the brain but also the learning and memory ability with step-through passive avoidance test. The amount of Aβ and the number of pyramidal cells in the hippocampus were not significantly different between the experimental and control group. Similarly, the difference of learning and memory ability could not be distinguished between the groups. Neither molecular pathogenesis of AD nor associated learning and memory were aggravated by tooth loss in these mice. The limited results of this study which used the aged mice may help the dental profession to plan and explain treatments to patients with AD, which must be designed while taking into account the severity of the AD symptoms. © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Prevention of Suicidal Behavior..., discussion, and evaluation of applications received in response to ``Prevention of Suicidal Behavior through...

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

Foot-and-mouth disease virus infection in young lambs: pathogenesis and tissue tropism

DEFF Research Database (Denmark)

Ryan, Eoin; Horsington, Jacquelyn; Durand, Stephanie

2008-01-01

Foot-and-mouth disease (FMD) in adult sheep usually causes milder clinical signs than in cattle or pigs, and is often subtle enough to go undiagnosed. In contrast, FMD in lambs has been reported to cause high mortality during field outbreaks. In order to investigate the pathogenesis of FMD in lambs......, two groups, aged 10–14 days, were infected with foot-and-mouth disease virus (FMDV) type O UKG. One group of lambs (n = 8) was inoculated with FMDV in the coronary band, while the other (n = 4) was infected by direct contact with FMDV-inoculated ewes. Daily serum samples and temperature measurements...... were taken. Lambs were killed sequentially and tissue samples taken for analysis. Using real-time RT-PCR, viral RNA levels in tissue samples and serum were measured, and a novel strand-specific real-time RT-PCR assay was used to quantify viral replication levels in tissues. Tissue sections were...

Measures to prevent nosocomial infections during mechanical ventilation.

Science.gov (United States)

Ramirez, Paula; Bassi, Gianluigi L; Torres, Antonio

2012-02-01

Endotracheal intubation and mechanical ventilation are lifesaving measures in critically ill patients. However, these interventions increase the risk of respiratory infections, particularly ventilator-associated pneumonia (VAP). VAP constitutes a serious burden for the healthcare system and worsens the patient's outcomes; thus, several preventive strategies have been implemented. This communication reviews the current knowledge on VAP pathogenesis and the latest preventive measures. Pathogen-laden oropharyngeal secretions leak across the endotracheal tube (ETT) cuff; thus, a continuous control of the internal cuff pressure and cuffs made of polyurethane improve sealing effectiveness and associated risks of infections. Subglottic secretions aspiration prevents VAP, and the latest evidence demonstrated a reduction in the incidence of late-onset VAP. The role of ETT biofilm in the pathogenesis of VAP is not fully elucidated. Nevertheless, antimicrobial-coated ETTs have showed beneficial effects in VAP incidence. Recent experimental evidence has challenged the benefits associated with the use of the semirecumbent position; yet, these findings need to be corroborated in clinical trials. The latest results from trials testing the effects of selective digestive decontamination (SDD) showed beneficial effects on patients' outcomes, but concerns remain regarding the emergence of bacterial resistance, specifically upon digestive tract re-colonization. The use of oropharyngeal decontamination with antiseptics and the use of probiotics are potential alternatives to SDD. There is consistent evidence that strategies affecting the primary mechanisms of VAP pathogenesis efficiently reduce the occurrence of the disease. Preventive measures should be implemented grouped into bundles to improve overall efficacy.

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus.

Science.gov (United States)

da Fontoura Budaszewski, Renata; von Messling, Veronika

2016-10-11

Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

[Strategies for cardiovascular disease prevention].

Science.gov (United States)

Gabus, Vincent; Wuerzner, Grégoire; Saubade, Mathieu; Favre, Lucie; Jacot Sadowski, Isabelle; Nanchen, David

2018-02-28

Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

Potential of tocotrienols in the prevention and therapy of Alzheimer's disease.

Science.gov (United States)

Xia, Weiming; Mo, Huanbiao

2016-05-01

Currently there is no cure for Alzheimer's disease (AD); clinical trials are underway to reduce amyloid generation and deposition, a neuropathological hallmark in brains of AD patients. While genetic factors and neuroinflammation contribute significantly to AD pathogenesis, whether increased cholesterol level is a causative factor or a result of AD is equivocal. Prenylation of proteins regulating neuronal functions requires mevalonate-derived farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The observation that the levels of FPP and GGPP, but not that of cholesterol, are elevated in AD patients is consistent with the finding that statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, reduce FPP and GGPP levels and amyloid β protein production in preclinical studies. Retrospective studies show inverse correlations between incidence of AD and the intake and serum levels of the HMG CoA reductase-suppressive tocotrienols; tocopherols show mixed results. Tocotrienols, but not tocopherols, block the processing and nuclear localization of sterol regulatory element binding protein-2, the transcriptional factor for HMG CoA reductase and FPP synthase, and enhance the degradation of HMG CoA reductase. Consequently, tocotrienols deplete the pool of FPP and GGPP and potentially blunt prenylation-dependent AD pathogenesis. The antiinflammatory activity of tocotrienols further contributes to their protection against AD. The mevalonate- and inflammation-suppressive activities of tocotrienols may represent those of an estimated 23,000 mevalonate-derived plant secondary metabolites called isoprenoids, many of which are neuroprotective. Tocotrienol-containing plant foods and tocotrienol derivatives and formulations with enhanced bioavailability may offer a novel approach in AD prevention and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

New discoveries in the pathogenesis and classification of vitiligo.

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Rodrigues, Michelle; Ezzedine, Khaled; Hamzavi, Iltefat; Pandya, Amit G; Harris, John E

2017-07-01

Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these patterns provides both diagnostic and prognostic clues. Recent insights into disease pathogenesis offer a better understanding of the natural history of the disease, its associations, and potential for future treatments. The first article in this continuing medical education series outlines typical and atypical presentations of vitiligo, how they reflect disease activity, prognosis, and response to treatment. Finally, we discuss disease associations, risk factors, and our current understanding of disease pathogenesis. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle.

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Arzt, Jonathan; Pacheco, Juan M; Stenfeldt, Carolina; Rodriguez, Luis L

2017-05-02

Understanding the mechanisms of attenuation and virulence of foot-and-mouth disease virus (FMDV) in the natural host species is critical for development of next-generation countermeasures such as live-attenuated vaccines. Functional genomics analyses of FMDV have identified few virulence factors of which the leader proteinase (L pro ) is the most thoroughly investigated. Previous work from our laboratory has characterized host factors in cattle inoculated with virulent FMDV and attenuated mutant strains with transposon insertions within L pro . In the current study, the characteristics defining virulence of FMDV in cattle were further investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). The only difference between the two viruses was an insertion mutation in the inter-AUG region of the leader proteinase of FMDV-Mut. All cattle were infected by simulated-natural, aerosol inoculation. Both viruses were demonstrated to establish primary infection in the nasopharyngeal mucosa with subsequent dissemination to the lungs. Immunomicroscopic localization of FMDV antigens indicated that both viruses infected superficial epithelial cells of the nasopharynx and lungs. The critical differences between the two viruses were a more rapid establishment of infection by FMDV-WT and quantitatively greater virus loads in secretions and infected tissues compared to FMDV-Mut. The slower replicating FMDV-Mut established a subclinical infection that was limited to respiratory epithelial sites, whereas the faster replication of FMDV-WT facilitated establishment of viremia, systemic dissemination of infection, and clinical disease. The mutant FMDV was capable of achieving all the same early pathogenesis landmarks as FMDV-WT, but was unable to establish systemic infection. The precise mechanism of attenuation remains undetermined; but current data suggests that the impaired replication

Distinct Roles of Wnt/β-Catenin Signaling in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

Science.gov (United States)

Shi, Juan; Li, Feng; Luo, Meihui; Wei, Jun

2017-01-01

Wnt signaling pathways are tightly controlled under a physiological condition, under which they play key roles in many biological functions, including cell fate specification and tissue regeneration. Increasing lines of evidence recently demonstrated that a dysregulated activation of Wnt signaling, particularly the Wnt/β-catenin signaling, was involved in the pathogenesis of chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In this respect, Wnt signaling interacts with other cellular signaling pathways to regulate the initiation and pathogenic procedures of airway inflammation and remodeling, pulmonary myofibroblast proliferation, epithelial-to-mesenchymal transition (EMT), and development of emphysema. Intriguingly, Wnt/β-catenin signaling is activated in IPF; an inhibition of this signaling leads to an alleviation of pulmonary inflammation and fibrosis in experimental models. Conversely, Wnt/β-catenin signaling is inactivated in COPD tissues, and its reactivation results in an amelioration of airspace enlargement with a restored alveolar epithelial structure and function in emphysema models. These studies thus imply distinct mechanisms of Wnt/β-catenin signaling in the pathogenesis of these two chronic pulmonary diseases, indicating potential targets for COPD and IPF treatments. This review article aims to summarize the involvement and pathogenic roles of Wnt signaling pathways in the COPD and IPF, with a focus on the implication of Wnt/β-catenin signaling as underlying mechanisms and therapeutic targets in these two incurable diseases. PMID:28588349

Obesity Revised. Chapter at "Periodontal Disease: Symptoms, Treatment and Prevention"

DEFF Research Database (Denmark)

Cinar, Ayse Basak

2011-01-01

Abstract: Obesity, diabetes and oral diseases (dental cariesand periodontal diseases), largely preventable chronic diseases, are described as global pandemic due their distribution and severe consequences. WHO has called for a global action for prevention and promotion of these diseases as a vital...... the likelihood of periodontitis which is one of the most common chronic diseases worldwide, described as pandemic, and closely related to DM2. Promoting good oral health is significantly essential for prevention and reducing the negative consequences of periodontal diseases, DM2 and obesity, and to maintain good...

Aetiology and pathogenesis of alcoholic liver disease.

Science.gov (United States)

Lieber, C S

1993-09-01

carcinogens and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation and decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes glutathione depletion, free-radical mediated toxicity and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis: both in vivo and in vitro (in cultured myofibroblasts and lipocytes), ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding of the pathogenesis of alcoholic liver disease may eventually improve therapy with drugs and nutrients.

The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention.

Science.gov (United States)

Safdar, Nasia; Crnich, Christopher J; Maki, Dennis G

2005-06-01

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the intensive care unit and is associated with major morbidity and attributable mortality. Strategies to prevent VAP are likely to be successful only if based upon a sound understanding of pathogenesis and epidemiology. The major route for acquiring endemic VAP is oropharyngeal colonization by the endogenous flora or by pathogens acquired exogenously from the intensive care unit environment, especially the hands or apparel of health-care workers, contaminated respiratory equipment, hospital water, or air. The stomach represents a potential site of secondary colonization and reservoir of nosocomial Gram-negative bacilli. Endotracheal-tube biofilm formation may play a contributory role in sustaining tracheal colonization and also have an important role in late-onset VAP caused by resistant organisms. Aspiration of microbe-laden oropharyngeal, gastric, or tracheal secretions around the cuffed endotracheal tube into the normally sterile lower respiratory tract results in most cases of endemic VAP. In contrast, epidemic VAP is most often caused by contamination of respiratory therapy equipment, bronchoscopes, medical aerosols, water (eg, Legionella) or air (eg, Aspergillus or the severe acute respiratory syndrome virus). Strategies to eradicate oropharyngeal and/or intestinal microbial colonization, such as with chlorhexidine oral care, prophylactic aerosolization of antimicrobials, selective aerodigestive mucosal antimicrobial decontamination, or the use of sucralfate rather than H(2) antagonists for stress ulcer prophylaxis, and measures to prevent aspiration, such as semirecumbent positioning or continuous subglottic suctioning, have all been shown to reduce the risk of VAP. Measures to prevent epidemic VAP include rigorous disinfection of respiratory equipment and bronchoscopes, and infection-control measures to prevent contamination of medical aerosols. Hospital water should be

A point of view: quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model.

Science.gov (United States)

Floros, J; Wang, G

2001-05-01

The high degree of similarity at the molecular level, between humans and other species, has provided the rationale for the use of a variety of species as model systems in research, resulting in enormous advances in biological sciences and medicine. In contrast, the individual variability observed among humans, for example, in external physique, organ functionality and others, is accounted for, by only a fraction of 1% of differences at the DNA level. These small differences, which are essential for understanding disease pathogenesis, have posed enormous challenges in medicine, as we try to understand why patients may respond differently to drugs or why one patient has complications and another does not. Differences in outcome are most likely the result of interactions among genetic components themselves and/or the environment at the molecular, cellular, organ, or organismal level, or the macroenvironment. In this paper: (1) we consider some issues for multifactorial disease pathogenesis; (2) we provide a review of human SP-A and how the knowledge gained and the characteristics of the hSP-A system may serve as a model in the study of disease with multifactorial etiology; and (3) we describe examples where hSP-A has been used in the study of disease.

The role of O-GlcNAc signaling in the pathogenesis of diabetic retinopathy.

Science.gov (United States)

Semba, Richard D; Huang, Hu; Lutty, Gerard A; Van Eyk, Jennifer E; Hart, Gerald W

2014-04-01

Diabetic retinopathy is a leading cause of blindness worldwide. Despite laser and surgical treatments, antiangiogenic and other therapies, and strict metabolic control, many patients progress to visual impairment and blindness. New insights are needed into the pathophysiology of diabetic retinopathy in order to develop new methods to improve the detection and treatment of disease and the prevention of blindness. Hyperglycemia and diabetes result in increased flux through the hexosamine biosynthetic pathway, which, in turn, results in increased PTM of Ser/Thr residues of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation is involved in regulation of many nuclear and cytoplasmic proteins in a manner similar to protein phosphorylation. Altered O-GlcNAc signaling has been implicated in the pathogenesis of diabetes and may play an important role in the pathogenesis of diabetic retinopathy. The goal of this review is to summarize the biology of the hexosamine biosynthesis pathway and O-GlcNAc signaling, to present the current evidence for the role of O-GlcNAc signaling in diabetes and diabetic retinopathy, and to discuss future directions for research on O-GlcNAc in the pathogenesis of diabetic retinopathy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive genetic study of fatty acids helps explain the role of noncoding inflammatory bowel disease associated SNPs and fatty acid metabolism in disease pathogenesis.

Science.gov (United States)

Jezernik, Gregor; Potočnik, Uroš

2018-03-01

Fatty acids and their derivatives play an important role in inflammation. Diet and genetics influence fatty acid profiles. Abnormalities of fatty acid profiles have been observed in inflammatory bowel diseases (IBD), a group of complex diseases defined by chronic gastrointestinal inflammation. IBD associated fatty acid profile abnormalities were observed independently of nutritional status or disease activity, suggesting a common genetic background. However, no study so far has attempted to look for overlap between IBD loci and fatty acid associated loci or investigate the genetics of fatty acid profiles in IBD. To this end, we conducted a comprehensive genetic study of fatty acid profiles in IBD using iCHIP, a custom microarray platform designed for deep sequencing of immune-mediated disease associated loci. This study identifies 10 loci associated with fatty acid profiles in IBD. The most significant associations were a locus near CBS (p = 7.62 × 10 -8 ) and a locus in LRRK2 (p = 1.4 × 10 -7 ). Of note, this study replicates the FADS gene cluster locus, previously associated with both fatty acid profiles and IBD pathogenesis. Furthermore, we identify 18 carbon chain trans-fatty acids (p = 1.12 × 10 -3 ), total trans-fatty acids (p = 4.49 × 10 -3 ), palmitic acid (p = 5.85 × 10 -3 ) and arachidonic acid (p = 8.58 × 10 -3 ) as significantly associated with IBD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Medico-social aspects of the prevention of noncommunicable diseases

Directory of Open Access Journals (Sweden)

T.V. Peresypkina

2017-03-01

Full Text Available Background. The noncommunicable disease (NCDs are very common among population around the world. They are the main cause of preventable mortality, cause temporary and permanent disability. NCDs are the major reason for attending for medical care and lead to economic losses. The implementations of preventive strategy, increasing the role of preventive measures are general tasks for all health care system. The analysis of trends of preventive measure for NCD nowadays is the aim of this research. Materials and methods. The study included the result of analysis of science publication and WHO database about NCD and preventive measure used as well as the results of the analysis of data of the Center for Statistics in Medicine of MoH of Ukraine. Results. Diabetes, cardiovascular diseases, cancer, chronic respiratory diseases are the major NCDs. The base factors which lead to NCD are behavioral risk factors, namely tobacco use, unhealthy diet, physical inactivity, and alcohol abuse. The WHO prepared a lot of documents, among which the most significant are the strategies on noncommunicable diseases prevention, convention against smoking, strategy on diet and physical activity, global strategy on reducing alcohol abusing and so on. Nowadays the world population follows Global Action Plan for Prevention of Noncommunicable Diseases for 2013–2020. The documents emphasize the importance of state support, the use of scientific potential and intersectoral interaction to effectively combat noncommunicable diseases. The major of scientific direction are NCD monitoring, detection of the determinant of NCD development and making strategy for usage it in conditions of limited resources. The role of Digital marketing today increases that leads to the acquisition and consolidation of the habits and behavior of modern youth. Internet marketing is very effective to form unhealthy food behavior in children and adolescents that requires adequate and urgent actions. The

Global strategies to prevent chronic diseases1

African Journals Online (AJOL)

Nicky

leading global causes of death and disability, are ... global strategies for the prevention and control of chronic ... Preventing Chronic Diseases: A Vital Investment, will ..... Millennium Development Goals for Health In Europe and Central Asia.

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.

A systematic review of high-fibre dietary therapy in diverticular disease

NARCIS (Netherlands)

Ünlü, Cagdas; Daniels, Lidewine; Vrouenraets, Bart C.; Boermeester, Marja A.

2012-01-01

The exact pathogenesis of diverticular disease of the sigmoid colon is not well established. However, the hypothesis that a low-fibre diet may result in diverticulosis and a high-fibre diet will prevent symptoms or complications of diverticular disease is widely accepted. The aim of this review is

Parkinson’s Disease – the Debate on the Clinical Phenomenology, Aetiology, Pathology and Pathogenesis

Science.gov (United States)

Jenner, Peter; Morris, Huw R.; Robbins, Trevor W.; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V.; Brooks, David

2014-01-01

The definition of Parkinson’s disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article - widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic per-spective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include - Parkinson’s syndrome, Parkinson’s syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA). PMID:23938306

The role of platelets in the pathogenesis of systemic sclerosis

Directory of Open Access Journals (Sweden)

Giuseppe A. eRamirez

2012-06-01

Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

[Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

Science.gov (United States)

Hagymási, Krisztina; Tulassay, Zsolt

2008-03-23

Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

Pathogenesis and treatment modalities of localized scleroderma.

Science.gov (United States)

Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

2010-01-01

Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

Systematic approach to understanding the pathogenesis of systemic sclerosis.

Science.gov (United States)

Zuo, Xiaoxia; Zhang, Lihua; Luo, Hui; Li, Yisha; Zhu, Honglin

2017-10-01

Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

2016-01-01

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 (SMN1) 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. These contribution of non-motor neuronal cells to disease pathogenesis has important therapeutic implications: in fact, 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 will be crucial to take this evidence into account before clinical translation of the novel therapeutic approaches that are currently under development. PMID:26681261

ROLE OF MAGNESIUM IN HEADACHE PATHOGENESIS IN CHILDREN AND ADOLESCENTS

Directory of Open Access Journals (Sweden)

E. S. Akarachkova

2013-01-01

Full Text Available Article is dedicated to the problem of headache in children. This pathology is being found more frequently in pediatric and children’s neurologic practice. The authors examine headache pathogenesis from the position of magnesium deficiency. Analysis of results of the modern studies on magnesium deficiency and its correction in patients with headache indicates that magnesium metabolism may play an important role both in pathogenesis of different headache types and in its treatment and prevention.

Will Culling White-Tailed Deer Prevent Lyme Disease?

Science.gov (United States)

Kugeler, K J; Jordan, R A; Schulze, T L; Griffith, K S; Mead, P S

2016-08-01

White-tailed deer play an important role in the ecology of Lyme disease. In the United States, where the incidence and geographic range of Lyme disease continue to increase, reduction of white-tailed deer populations has been proposed as a means of preventing human illness. The effectiveness of this politically sensitive prevention method is poorly understood. We summarize and evaluate available evidence regarding the effect of deer reduction on vector tick abundance and human disease incidence. Elimination of deer from islands and other isolated settings can have a substantial impact on the reproduction of blacklegged ticks, while reduction short of complete elimination has yielded mixed results. To date, most studies have been conducted in ecologic situations that are not representative to the vast majority of areas with high human Lyme disease risk. Robust evidence linking deer control to reduced human Lyme disease risk is lacking. Currently, there is insufficient evidence to recommend deer population reduction as a Lyme disease prevention measure, except in specific ecologic circumstances. © 2015 Blackwell Verlag GmbH.

Hidradenitis suppurativa : From pathogenesis to emerging treatment options

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Dickinson-Blok, Janine Louise

2015-01-01

Hidradenitis suppurativa (HS) is a chronic skin disease that is characterized by inflammation of the hair follicles. The cause of HS is largely unknown and the disease remains difficult to treat. Mrs. Janine Dickinson-Blok studied the pathogenesis of HS and the efficacy of existing and emerging

Type 1 diabetes: New horizons in prediction and prevention.

Science.gov (United States)

Razack, Natasha N; Wherrett, Diane K

2005-01-01

Significant advances have been made in our understanding of the pathogenesis of type 1 diabetes and our ability to predict risk for the condition. This knowledge is being used to develop new and innovative strategies to prevent type 1 diabetes or to prevent further destruction of beta cells in those who are newly diagnosed. Several multicentre studies are underway investigating the natural history of the disease, the genetics behind the disease and ways to stop the autoimmune reaction against beta cells (Type 1 Diabetes TrialNet, Type 1 Diabetes Genetics Consortium and the Trial to Reduce Diabetes in the Genetically at Risk [TRIGR] Study Group). The stage is set to find an agent or strategy to prevent type 1 diabetes or to preserve the residual beta cell mass in new-onset patients.

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.

Understanding Anaplasmataceae pathogenesis using ‘Omics’ approaches

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Ludovic ePruneau

2014-07-01

Full Text Available This paper examines how Omics approaches improve our understanding of Anaplasmataceae pathogenesis, through a global and integrative strategy to identify genes and proteins involved in biochemical pathways key for pathogen-host-vector interactions.The Anaplasmataceae family comprises obligate intracellular bacteria mainly transmitted by arthropods. These bacteria are responsible for major human and animal endemic and emerging infectious diseases with important economic and public health impacts. In order to improve disease control strategies, it is essential to better understand their pathogenesis. Our work focused on four Anaplasmataceae, which cause important animal, human and zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia chaffeensis and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was also included in this review as a model of a non-pathogenic Anaplasmataceae.A gap analysis on Omics approaches on Anaplasmataceae was performed, which highlighted a lack of studies on the genes and proteins involved in the infection of hosts and vectors. Furthermore, most of the studies have been done on the pathogen itself, mainly on infectious free-living forms and rarely on intracellular forms. In order to perform a transcriptomic analysis of the intracellular stage of development, researchers developed methods to enrich bacterial transcripts from infected cells. These methods are described in this paper. Bacterial genes encoding outer membrane proteins, post-translational modifications, eukaryotic repeated motif proteins, proteins involved in osmotic and oxidative stress and hypothetical proteins have been identified to play a key role in Anaplasmataceae pathogenesis. Further investigations on the function of these outer membrane proteins and hypothetical proteins will be essential to confirm their role in the pathogenesis. Our work underlines the need for further studies in this domain and on host and vector responses

Alzheimer's disease prevention: A way forward.

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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.

View and practices of dermatologists regarding preventable skin diseases

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Raza, N.; Seir, F.; Qadir, S.N.R.

2014-01-01

To find out views and practice of dermatologists regarding prevention of preventable skin diseases. Study Design: Cross-sectional study. Place and Duration of Study: The study was set up in Apr-May 2010 at PAF Hospital Faisal, Karachi, Pakistan. Material and Methods: A close-ended questionnaire was sent to 100 dermatologists through resource persons at different places throughout the country. It included basic information about them, their views and practice regarding prevention of these diseases. Data was managed and analyzed using SPSS-17. Results: Fifty dermatologists thought that frequency of preventable skin diseases in their clinical practice is 26-50%. Fifty-six observed educated community as the most important link for prevention, 46 held governments responsible and 42 consider busy schedule as barrier to educate community. Thirty dermatologists delivered talk to general public, 11 at schools, colleges and factories, 07 appeared on mass media and 08 prepared leaflets, pamphlets and brochures regarding preventive aspects of skin diseases at least once during last one year. Conclusion: Dermatologists in Pakistan are aware of magnitude of the problem and understand importance of public education; however only a few dermatologists have endeavored to take up this task. (author)

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.

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Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie; Jim, Belinda

2016-06-06

Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. Copyright © 2016 by the American Society of Nephrology.

Burden of four vaccine preventable diseases in older adults

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Kristensen, Maartje; van Lier, Alies; Eilers, Renske; McDonald, Scott A.; Opstelten, Wim; van der Maas, Nicoline; van der Hoek, Wim; Kretzschmar, Mirjam E.; Nielen, Mark M.; de Melker, Hester E.

2016-01-01

Background: Implementation of additional targeted vaccinations to prevent infectious diseases in the older adults is under discussion in different countries. When considering the added value of such preventive measures, insight into the current disease burden will assist in prioritization. The aim

Bordetella pertussis pathogenesis: current and future challenges

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Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

2014-01-01

Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

Work-related rhinitis – Is it always an occupational disease?

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Witold Salski

2016-12-01

Full Text Available Rhinitis is a chronic inflammatory disease of the upper respiratory tract, characterized by a high prevalence and a complex pathogenesis. Work-related rhinitis (WRR can be divided into occupational rhinitis (OR and work-exacerbated rhinitis (WER. It is not only considered as a disease entity but also in the context of medical certification as the allergic disease associated with occupational exposure. Epidemiology of work-related rhinitis has been found to vary depending on the occupation and specific exposure, on the other hand the prevalence data may be underestimated due to the lack of uniform diagnostic criteria. This paper reviews the issues comprising the pathogenesis, epidemiology, diagnosis and treatment of patients with work-related rhinitis. It also discusses the significance of the disease in occupational medicine, particularly in terms of preventive worker care, general principles of good practice in primary and secondary WRR prevention and the necessary directions of changes in medical certification in the cases of occupational rhinitis. Med Pr 2016;67(6:801–815

The role of free kappa and lambda light chains in the pathogenesis and treatment of inflammatory diseases.

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Esparvarinha, Mojgan; Nickho, Hamid; Mohammadi, Hamed; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Majidi, Jafar

2017-07-01

Kappa (κ) or lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. FLCs have been shown to participate in several key processes of immune responses. They are necessary to adjust PMN functions and assist PMN pre-stimulation. Moreover, they cause mast cell degranulation which releases pro-inflammatory mediators and stimulates local inflammatory responses in some conditions such as inflammatory bowel disease (IBD). Having low molecular weights which may straightly be toxic to proximal tubule cells (PTCs), FLCs can also have an important role in renal diseases. In this review we have highlighted the involvement of light chains in the pathogenesis of some inflammatory diseases and discussed their potential to be the targets of therapeutic purposes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

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Yan Cao

2017-01-01

Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

Eosinophils in vasculitis: characteristics and roles in pathogenesis

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Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

2016-01-01

Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

New approaches to the implementation of cardiovascular disease prevention

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Jørstad, H.T.

2016-01-01

Cardiovascular disease is one of the biggest contemporary health problems worldwide. To aid preventive measures, risk calculators have been developed to estimate the risk of dying of cardiovascular disease within 10 years, for use in healthy individuals. Decisions to initiate preventive measures are

A novel pathogenesis of inflammatory bowel disease from the perspective of glyco-immunology.

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Shinzaki, Shinichiro; Iijima, Hideki; Fujii, Hironobu; Kamada, Yoshihiro; Naka, Tetsuji; Takehara, Tetsuo; Miyoshi, Eiji

2017-05-01

Oligosaccharide modifications play an essential role in various inflammatory diseases and cancers, but their pathophysiologic roles, especially in inflammation, are not clear. Inflammatory bowel disease (IBD) is an intractable chronic inflammatory disorder with an unknown aetiology, and the number of patients with IBD is increasing throughout the world. Certain types of immunosuppressant drugs, such as corticosteroids, are effective for IBD, suggesting that immune function is closely associated with the pathophysiology of IBD. Recent progress in the analysis of oligosaccharides revealed a role for oligosaccharides in intestinal inflammation based on both experimental models and human samples from IBD patients. Moreover, changes in the oligosaccharide structures on glycoproteins in the sera and tissue samples may serve as biomarkers of IBD. Here, we present current studies of IBD with regard to the immunologic aspects of glycobiology, suggesting a novel concept for IBD pathogenesis and the function of oligosaccharides on immune cells, termed "glyco-immunology". © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Prevention of cancer and non-communicable diseases.

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Cannon, Geoffrey; Gupta, Prakash; Gomes, Fabio; Kerner, Jon; Parra, William; Weiderpass, Elisabete; Kim, Jeongseon; Moore, Malcolm; Sutcliffe, Catherine; Sutcliffe, Simon

2012-01-01

Cancer is a leading cause of death worldwide, accounting for approximately 7.6 million deaths (13% of all deaths) in 2008. Cancer mortality is projected to increase to 11 million deaths in 2030, with the majority occurring in regions of the world with the least capacity to respond. However, cancer is not only a personal, societal and economic burden but also a potential societal opportunity in the context of functional life - the years gained through effective prevention and treatment, and strategies to enhance survivorship. The United Nations General Assembly Special Session in 2011 has served to focus attention on key aspects of cancer prevention and control. Firstly, cancer is largely preventable, by feasible means. Secondly, cancer is one of a number of chronic, non- communicable diseases that share common risk factors whose prevention and control would benefit a majority of the world's population. Thirdly, a proportion of cancers can be attributed to infectious, communicable causal factors (e.g., HPV, HBV, H.pylori, parasites, flukes) and that strategies to control the burden of infectious diseases have relevance to the control of cancer. Fourthly, that the natural history of non-communicable diseases, including cancer, from primary prevention through diagnosis, treatment and care, is underwritten by the impact of social, economic and environmental determinants of health (e.g., poverty, illiteracy, gender inequality, social isolation, stigma, socio-economic status). Session 1 of the 4th International Cancer Control Congress (ICCC-4) focused on the social, economic and environmental, as well as biological and behavioural, modifiers of the risk of cancer through one plenary presentation and four interactive workshop discussions. The workshop sessions concerned 1) the Global Adult Tobacco Survey and social determinants of tobacco use in high burden low- and middle-income countries; 2) the role of diet, including alcohol, and physical activity in modifying the

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

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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.

Pathogenesis and pharmacologic treatment of obesity: the role of energy regulatory mechanism.

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Manulu, Mangatas S M; Sutanegara, I N Dwi

2006-01-01

Obesity has become a worldwide public health problem affecting millions of people. This is a chronic, stigmatized, and costly disease, rarely curable and is increasing in prevalence to a point today where we define obesity as an epidemic disease that not only in developed but also on developing countries. The pathogenesis of obesity is largely unknown, especially about energy regulatory mechanism that involved wide area of neuroendocrinology that is very interesting but very complex and makes internists "refuse" to learn. Obesity occurs through a longstanding imbalance between energy intake and energy expenditure, influenced by a complex biologic system that regulates appetite and adiposity. Obesity influences the pathogenesis of hypertension, type 2 diabetes, dyslipidemia, kidney, heart, and cerebrovascular disease. It is very wise for every internist to learn the pathogenesis and treatment of this worldwide diseases. Until now, the available treatments, including drugs, are palliative and are effective only while the treatment is being actively used; and besides so many side effects reported.

ALLERGIC EYE DISEASES IN CHILDREN. MODERN VIEW ON PATHOGENESIS AND TREATMENT

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E. Y. Markova

2017-01-01

Full Text Available The prevalence off allergic diseases has  been  significantly increased among  adults  and children during last 30-40 years. International study has  shown  that  the  frequency  of atopy  in developed  countries, including Russia,   is higher  than  in developing.  Often atopic dermatitis, started in infancy, can develop into an “allergic march”  — food allergy, followed by the formation of allergic rhinitis, allergic conjunctivitis and  other  allergic diseases. The problem  of prophylaxis and  treatment of allergic pathology  becomes actual  for these reasons. An opinion according some  preventive  measures has  changed in recent. It was  noted  that  in families  with many children, where  children  were  often  sick  with respiratory infections,  the  incidence  of allergic  diseases was  lower  than  among  rarely sick children.  It is explained by the  “hygienic theory” — insufficient “training” of the  Th1 response in rarely sick children.  Allergic diseases, which are  based on IgE-mediated inflammation,  have a common  pathogenetic nature and,  consequently, general  principles of therapy, in which, as  is well known,  antihistamines take  a significant  place.  This is cased by the  mandatory involvement of histamine  in the mechanism of development of the main symptoms of allergic diseases. Current  capabilities  of local ophthalmologic  antiallergic therapy includes medicines  with multiple action mechanisms, such as mast cell stabilizers, antihistamines, combined  agents, steroids and nonsteroidal anti-inflammatory effects. The latest generation antihistamine drug — olopatadine hydrochloride  0.2% is a new form of the molecule of olopatadine, which is intended  to increase the duration  of the action.  The article considers the main modern directions in prevention  and treatment of allergic diseases, including allergic eye diseases, which are  a

Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

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McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

2017-10-23

The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Prevalence of periodontal disease, its association with systemic diseases and prevention.

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Nazir, Muhammad Ashraf

2017-01-01

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.

Complications of HIV Disease and Antiretroviral Therapy

OpenAIRE

Luetkemeyer, Anne F.; Havlir, Diane V.; Currier, Judith S.

2010-01-01

There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to refl...

New concept of the pathogenesis and therapeutic orientation of acquired communicating hydrocephalus.

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Xu, Hao

2016-09-01

Hydrocephalus is a common medical condition characterized by abnormalities in the secretion, circulation and absorption of cerebrospinal fluid (CSF), resulting in ventricle dilatation. For the communicating hydrocephalus, without etiological treatment, its pathogenesis has been considered as a research emphasis. Many factors can damage the CSF system and trigger communicating hydrocephalus, including tumor surgery and hydrocephalus neurological diseases, such as brain trauma, infection, ICH and SAH. But according to our clinical experience, a big proportion of patients do not develop hydrocephalus. That is because the absorbing ability of CSF can compensate within a certain range. If the damage exceeds that range, hydrocephalus will occur. Once it occurs, it is not likely to be reversed, so a shunt surgery is always needed. Therefore, we believe that our orientation could transform the treatment of patient who has already showed hydrocephalus symptoms to the prevention of the occurrence in the patient with high risk of hydrocephalus. Based on the hypothesis above, we first divide the process of hydrocephalus into three stages and we believe that hydrocephalus are possible be reversed or halted in stage 1 and 2. The new concept of the pathogenesis in hydrocephalus will enrich our understanding and provide new insights to the therapeutic orientation. In conclusion, the future research direction should be the prevention of hydrocephalus, which should take a long period from the immediate occurrence of brain injury to several months or even years after the injury.

Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

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Licitra, Beth N.; Millet, Jean K.; Regan, Andrew D.; Hamilton, Brian S.; Rinaldi, Vera D.; Duhamel, Gerald E.

2013-01-01

Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses. PMID:23763835

Chronic obstructive pulmonary disease with lung cancer: Prevalence, severity, and common pathogenesis

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Griffin JP

2016-01-01

Full Text Available Objectives: To develop a clinical prediction model of contribution of chronic obstructive pulmonary disease (COPD to the pathogenesis of lung cancer, by reporting the estimated prevalence and severity by GOLD criteria in a single-institution cohort of patients with newly diagnosed lung cancer. Primary objective was investigating the effects of impaired lung function with various histological cell types on crude survival, while considering the initial staging of disease extent. Materials & methods: A total of 441 patients, in this historical cohort from electronic medical records, completed spirometry prior to invasive diagnostic procedures and initial treatment of their lung cancer. All statistical analyses, including ANOVA and survival analysis, were performed using SAS version 9.1 software. Results: Estimated prevalence of COPD was 79.1% (95% confidence interval: 71.3%-82.9%. Lung function as measured by spirometry was a significant predictor of survival time in months (p<0.0001 both with and without adjusting for tumor-cell-type, age, and stage of disease. Median survival was similar (p=0.32 and longer among those patients with normal pulmonary function, those with restrictive disease patterns, and those with COPD–GOLD-1 defects. Median survival was shortest among patients with COPD–GOLD-4 impairment (p=0.001. Those patients with COPD–GOLD-2 and COPD-GOLD-3 impairment levels had intermediate survival times (p=0.003. Conclusions: This investigation suggests that strategies for early detection and slowing the progression of COPD before the development of lung cancer might increase patient survival. As demonstrated in this study, the presence and severity of COPD in lung cancer patients is an independent predictor of survival time, different from the established staging of initial extent of disease.

The pathogenesis of progressive multifocal leukoencephalopathy.

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Berger, Joseph R; Khalili, Kamel

2011-12-01

Interest in pathogenesis of progressive multifocal leukoencephalopathy (PML) followed the observation of the high risk for the disease in HIV infection and the recent observation of an association with a variety of newer therapeutic modalities, e.g., natalizumab, an α4β1 integrin inhibitor, and efalizumab, an anti-CD11a monoclonal antibody. Any hypothesis of PML pathogenesis must account for a number of facts. Firstly, the causative agent JC virus is ubiquitously present, yet only a vanishingly small number of infected persons develop the disease. Secondly, disorders of cell-mediated immunity increase the risk of the disease, particularly HIV infection. Impaired innate immunity is not a risk for PML, and antibodies against JC virus are not protective. Thirdly, a latent period of several months appears necessary following the administration of natalizumab and efalizumab before PML develops. Fourthly, restoration of the immune system can arrest the PML. It is possible that infection with JC virus occurs with a form of the virus shed in the urine of as many as 40% of all adults and present in sewage worldwide. Once acquired, perhaps through an oropharyngeal route, it may replicate and disseminate. A neurotropic form of JC virus that replicates in glial tissues causes PML when immunosurveillance is impaired. There are many unanswered questions with respect to PML pathogenesis. How is virus acquired? What tissues are infected? What is the origin of the neurotropic form? When does virus enter brain? What is the role of central nervous system immunosurveillance? The lack of an animal model has made answering these questions challenging. © Discovery Medicine

Garlic for Cardiovascular Disease: Prevention or Treatment?

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Alali, Feras Q; El-Elimat, Tamam; Khalid, Lila; Hudaib, Reema; Al-Shehabi, Tuqa Saleh; Eid, Ali H

2017-01-01

Cardiovascular disease (CVD) is the leading cause of global mortality with a substantial economic impact. The annual deaths are expected to increase in the next decade. An array of dietary supplements is being used by people worldwide to ameliorate cardiovascular risk factors. Garlic (Allium sativum L.), a top-selling herbal dietary supplement, is renowned for its wide range beneficial effects, particularly in the treatment and prevention of CVD. This review aims to present a thorough discussion of the available evidence-based data which support the use of garlic in the treatment or prevention of cardiovascular diseases, including atherosclerosis, hypertension, and hyperlipidemia. The molecular mechanisms underlying these effects are dissected as well. This review supports the notion that garlic has the potential to treat mild hypertension, to decrease hypercholesterolemia, and to prevent atherosclerosis. More clinical studies are essential to unequivocally understand the mechanisms underlying treatment or prevention of these cardiovascular conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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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

Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

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Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

2017-02-15

Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

Centers for Disease Control and Prevention

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[Disease prevention in the elderly: misconceptions in current models].

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Veras, Renato Peixoto

2012-10-01

The Brazilian population is aging significantly within a context of gradual improvement in the country's social and economic indicators. Increased longevity leads to increased use of health services, pressuring the public and social welfare health services, generating higher costs, and jeopardizing the system's sustainability. The alternative to avoid overburdening the system is to invest in policies for disease prevention, stabilization of chronic diseases, and maintenance of functional capacity. The current article aims to analyze the difficulties in implementing preventive programs and the reasons for the failure of various programs in health promotion, prevention, and management of chronic diseases in the elderly. There can be no solution to the crisis in financing and restructuring the health sector without implementing a preventive logic. Scientific research has already correctly identified the risk factors for the elderly population, but this is not enough. We must use such knowledge to promote the necessary transition from a healthcare-centered model to a preventive one.

High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

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Elizabeth M. Gordon

2016-09-01

Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

Role of TGFβ signaling in the pathogenesis of Alzheimer’s disease

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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.

Rotator Cuff Disease and Injury--Evaluation and Management.

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Williams, Randy

This presentation considers the incidence, evaluation, and management of rotator cuff disease and injury. Pathogenesis, symptoms, physical findings, treatment (therapeutic and surgical), and prevention are discussed. It is noted that rotator cuff problems, common in athletes, are usually related to an error in training or lack of training. They…

[Expert consensus for the prevention of cardiovascular disease in Chinese women].

Science.gov (United States)

2017-06-01

Cardiovascular disease is the leading cause of death for Chinese women, which has not been paid enough attention at present. Chinese women account for 20 percent of 3.5 billion women all over the world. Health promotion and prevention are facing the rigorous challenge. The pathophysiological characteristics, clinical manifestations, disease diagnosis, drug metabolism and prevention strategies of woman cardiovascular diseases are different from those of men in some respects and require special attention. "Consensus for the prevention of cardiovascular diseases in Chinese women" is developed by Women Physician Committee of Chinese College Cardiovascular Physicians and Women's Health Work Group of Chinese Society of Cardiology, which is aimed at strengthening and promoting prevention of cardiovascular diseases in Chinese women.

The role of high mobility group box 1(HMGB1)in the pathogenesis of kidney diseases

Institute of Scientific and Technical Information of China (English)

Qingjie Chen; Xiaofeng Guan; Xiaocong Zuo; Jianglin Wang; Wenjun Yin

2016-01-01

High mobility group box 1(HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule(DAMP)(also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products(RAGE) and toll-like receptors(TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases.

Diet, Gut Microbiome and Epigenetics: Emerging Links with Inflammatory Bowel Diseases and Prospects for Management and Prevention.

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Aleksandrova, Krasimira; Romero-Mosquera, Beatriz; Hernandez, Vicent

2017-08-30

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated with IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes, and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and have weak evidence. This review summarises the current knowledge on the complex interactions between diet, microbiome and epigenetics in IBD. Whereas an overabundance of calories and some macronutrients increase gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, and D, folic acid, beta carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, an anti-inflammatory dietary pattern as a complex intervention approach has become popular in recent years. Hence, exclusive enteral nutrition in paediatric Crohn's disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet (SCD), the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet and, most recently, the Mediterranean diet have shown strong anti-inflammatory properties and show promise for improving disease symptoms. More work is required to evaluate the role of individual food compounds and complex nutritional interventions with the

[Work-related rhinitis - Is it always an occupational disease?

Science.gov (United States)

Salski, Witold; Wiszniewska, Marta; Salska, Agata; Tymoszuk, Diana; Walusiak-Skorupa, Jolanta

2016-12-22

Rhinitis is a chronic inflammatory disease of the upper respiratory tract, characterized by a high prevalence and a complex pathogenesis. Work-related rhinitis (WRR) can be divided into occupational rhinitis (OR) and work-exacerbated rhinitis (WER). It is not only considered as a disease entity but also in the context of medical certification as the allergic disease associated with occupational exposure. Epidemiology of work-related rhinitis has been found to vary depending on the occupation and specific exposure, on the other hand the prevalence data may be underestimated due to the lack of uniform diagnostic criteria. This paper reviews the issues comprising the pathogenesis, epidemiology, diagnosis and treatment of patients with work-related rhinitis. It also discusses the significance of the disease in occupational medicine, particularly in terms of preventive worker care, general principles of good practice in primary and secondary WRR prevention and the necessary directions of changes in medical certification in the cases of occupational rhinitis. Med Pr 2016;67(6):801-815. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Molecular Pathogenesis of NASH

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Alessandra Caligiuri

2016-09-01

Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

Genetic determinants of pathogenesis by feline infectious peritonitis virus.

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Brown, Meredith A

2011-10-15

Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive viral disease of cats associated with feline coronavirus (FCoV). Viral genetic determinants specifically associated with FIPV pathogenesis have not yet been discovered. Viral gene signatures in the spike, non-structural protein 3c, and membrane of the coronavirus genome have been shown to often correlate with disease manifestation. An "in vivo mutation transition hypothesis" is widely accepted and postulates that de novo virus mutation occurs in vivo giving rise to virulence. The existence of "distinct circulating avirulent and virulent strains" is an alternative hypothesis of viral pathogenesis. It may be possible that viral dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic data suggests that the genetic background of the cat contributes to the manifestation of FIP. Further studies exploring both viral and host genetic determinants of disease in FIP offer specific opportunities for the management of this disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Pathogenesis of varicelloviruses in primates.

Science.gov (United States)

Ouwendijk, Werner J D; Verjans, Georges M G M

2015-01-01

Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Primary Prevention of Cardiovascular Disease

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Danny J. Eapen, MD

2016-09-01

Full Text Available Cardiovascular disease (CVD is the leading cause of death worldwide. This article focuses on current guidelines for the primary prevention of CVD and addresses management of key risk factors. Dietary modification, weight loss, exercise, and tobacco use cessation are specific areas where focused efforts can successfully reduce CVD risk on both an individual and a societal level. Specific areas requiring management include dyslipidemia, hypertension, physical activity, diabetes, aspirin use, and alcohol intake. These preventive efforts have major public health implications. As the global population continues to grow, health care expenditures will also rise, with the potential to eventually overwhelm the health care system. Therefore it is imperative to apply our collective efforts on CVD prevention to improve the cardiovascular health of individuals, communities, and nations.

Update on mucormycosis pathogenesis.

Science.gov (United States)

Ibrahim, Ashraf S; Kontoyiannis, Dimitrios P

2013-12-01

Mucormycosis is an increasingly common fungal infection with unacceptably high mortality. The recent sequencing genome projects of Mucorales and the development of gene manipulation have enabled significant advances in understanding the pathogenesis of mucormycosis. Therefore, we review the pathogenesis of mucormycosis and highlight potential development of novel diagnostic and therapeutic modalities against this lethal disease. Much of the work has been focused on the role of iron uptake in the virulence of Mucorales. Additionally, host receptors and fungal ligands involved in the process of tissue invasion as well as sporangiospore size and sex loci and their contribution to virulence of Mucorales are discussed. Finally, the role of innate and adaptive immunity in protection against Mucorales and new evidence about drug-induced apoptosis in these fungi are discussed. Recent discoveries introduce several potentially novel diagnostic and therapeutic modalities, which are likely to improve management and outcome for mucormycosis. Future preclinical and clinical research is warranted to develop these diagnostic and therapeutic strategies.

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

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.

Food and nutrition in the prevention of atherosclerosis

Directory of Open Access Journals (Sweden)

Izabela Kamila Wojarska

2018-05-01

Full Text Available Cardiovascular disease is the most frequent cause of hospitalization (15% and death (46% in Poland, as well as worldwide (31%, by reason of strenuous activity in the field of preventative healthcare in all age groups has to be taken. Preventative nutrition of atherosclerosis predicts mostly intake restriction of food containing: fatty acids, cholesterol, salt, monosaccharides and animal protein, while increasing intake of vitamins, minerals, fiber and antioxidant substances. Eating habits and nutritional status of women who are planning pregnancy have a crucial impact on its course, development of the fetus and children’s health in later years of their life. For all of cardiac patients well balanced diet is advised. In preventative care of Cardiovascular Disease it is advised to apply the diet given by a certified dietician and adjusted to fit patient’s needs. It is to remember, that besides a good diet, an important therapeutic factor of the patients with atherosclerosis is physical activity. Cardiovascular disease is a serious concern in Poland, as well as worldwide. Eating habits are playing a big role in pathogenesis and prevention of atherosclerosis.

The prevention of oral complications in bone-marrow transplantations by means of oral hygiene and dental intervention

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Abraham-Inpijn, L.; van Leeuwen, E. F.; Lustig, K. H.; van Winkelhoff, A. J.

1989-01-01

Oral complications cause morbidity and mortality in patients, undergoing allogeneic or autologous bone-marrow transplantation. The clinical features and the pathogenesis of the oral sequelae of bone marrow ablative therapy and graft-versus-host disease are discussed. In addition, a preventive oral

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Yao Hongwei; Rahman, Irfan

2011-01-01

Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.

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.

Modern views on the epidemiology, etiology and pathogenesis of gynecomastia

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Yu. N. Yashina

2014-01-01

Full Text Available The review deals with one of the pressing andrological issues – gynecomastia, its etiology and pathogenesis. Based on the current epidemiological and experimental data, most common etiological factors of gynecomastia were investigated. A multiple-valued role of various causes of gynecomastia in several age-groups was revealed. Literature data show that gynecomastia may be a manifestation of various diseases: endocrine, genetic, systematic. As well as that, gynecomastia may occur in patients with oncological diseases. However, gynecomastia can be an iatrogenic complication. Currently, we continue to make insights to the problem of gynecomastia in order to be able to classify its etiological factors and determine its basic pathogenesis pathways.

Hyperthyroidism in cats: what's causing this epidemic of thyroid disease and can we prevent it?

Science.gov (United States)

Peterson, Mark

2012-11-01

Since first being reported in the late 1970s, there has been a dramatic increase in the prevalence of hyperthyroidism in cats. It is now recognized worldwide as the most common feline endocrine disorder. Hyperthyroidism is an important cause of morbidity in cats older than 10 years of age. It is estimated that over 10% of all senior cats will develop the disorder. Despite its frequency, the underlying cause(s) of this common disease is/are not known, and no one has suggested a means to prevent the disorder. Because of the multiple risk factors that have been described for feline hyperthyroidism, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid disruptor chemicals or goitrogens in food or water, acting together in an additive or synergistic manner, may first lead to euthyroid goiter and then to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism. This review draws on published research studies to summarize the available evidence about the risk factors for feline hyperthyroidism. Based on the known goitrogens that may be present in the cat's food, drinking water or environment, it proposes measures that cat owners can implement that might prevent, or reduce the prevalence of, thyroid tumors and hyperthyroidism in their cats.

Preeclampsia: A review of the pathogenesis and possible management strategies based on its pathophysiological derangements.

Science.gov (United States)

El-Sayed, Amel A F

2017-10-01

This review is divided into three parts. The first part briefly describes the pathogenesis of preeclampsia. This is followed by reviewing previously reported management strategies of the disease based on its pathophysiological derangements. Finally, the author defines the safe and acceptable methods/medications that may be used to 'prevent' preeclampsia (in high risk patients) and those that may be used to 'treat' preeclampsia (meant to prolong the pregnancy in patients with established preeclampsia). The review concludes that multi-center trials are required to include multiple drugs in the same management protocol. Copyright © 2017. Published by Elsevier B.V.

Prevention and Treatment of Cardiovascular Disease in Adolescents and Adults through the Transcendental Meditation® Program: A Research Review Update

Science.gov (United States)

Barnes, Vernon A.; Orme-Johnson, David W.

2012-01-01

The pathogenesis and progression of cardiovascular diseases are thought to be exacerbated by stress. Basic research indicates that the Transcendental Meditation® technique produces acute and longitudinal reductions in sympathetic tone and stress reactivity. In adolescents at risk for hypertension, the technique has been found to reduce resting and ambulatory blood pressure, left ventricular mass, cardiovascular reactivity, and to improve school behavior. Research on adults with mild or moderate essential hypertension has reported decreased blood pressure and reduced use of anti-hypertensive medication. The technique has also been reported to decrease symptoms of angina pectoris and carotid atherosclerosis, to reduce cardiovascular risk factors, including alcohol and tobacco use, to markedly reduce medical care utilization for cardiovascular diseases, and to significantly decrease cardiovascular and all-cause morbidity and mortality. These findings have important implications for inclusion of the Transcendental Meditation program in efforts to prevent and treat cardiovascular diseases and their clinical consequences. ®Transcendental Meditation and TM are trademarks registered in the US. Patent and Trademark Office, licensed to Maharishi Vedic Education Development Corporation and are used with permission. PMID:23204989

Prevention and Treatment of Cardiovascular Disease in Adolescents and Adults through the Transcendental Meditation(®) Program: A Research Review Update.

Science.gov (United States)

Barnes, Vernon A; Orme-Johnson, David W

2012-08-01

The pathogenesis and progression of cardiovascular diseases are thought to be exacerbated by stress. Basic research indicates that the Transcendental Meditation(®) technique produces acute and longitudinal reductions in sympathetic tone and stress reactivity. In adolescents at risk for hypertension, the technique has been found to reduce resting and ambulatory blood pressure, left ventricular mass, cardiovascular reactivity, and to improve school behavior. Research on adults with mild or moderate essential hypertension has reported decreased blood pressure and reduced use of anti-hypertensive medication. The technique has also been reported to decrease symptoms of angina pectoris and carotid atherosclerosis, to reduce cardiovascular risk factors, including alcohol and tobacco use, to markedly reduce medical care utilization for cardiovascular diseases, and to significantly decrease cardiovascular and all-cause morbidity and mortality. These findings have important implications for inclusion of the Transcendental Meditation program in efforts to prevent and treat cardiovascular diseases and their clinical consequences.(®)Transcendental Meditation and TM are trademarks registered in the US. Patent and Trademark Office, licensed to Maharishi Vedic Education Development Corporation and are used with permission.

Biology and pathogenesis of Acanthamoeba

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Siddiqui Ruqaiyyah

2012-01-01

Full Text Available Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

The Possibilities of Drug Prevention of Diabetes Mellitus Type 2

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V.I. Pankiv

2013-08-01

Full Text Available Over the past few years there have been several randomized controlled trials that examine the effect of lifestyle modification and pharmacological interventions on the likelihood of developing diabetes mellitus (DM type 2 in people at high risk. These studies demonstrated that the number of people newly diagnosed with diabetes within 3–6-year period may be considerably reduced. Therefore focus of discussing the tactics to control DM type 2 is shifted from the relatively narrow topic of treatment of the disease at a wide range of issues of its prophylaxis: prevention of development and early treatment of DM, aimed to stabilization or reverse progression of the disease and prevention of its progression. This review discusses the general concept and the evidence base on preventing DM type 2 in the context of the pathogenesis of the disease. In addition, the attention is paid to the possibilities of the use of the discussed approaches to clinical practice, taking into account pathogenetic features of the disease and and clinical findings.

Role of CXCL10 in pathogenesis of hepatitis C and antiviral therapy

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LI Mi

2015-11-01

Full Text Available Hepatitis C virus (HCV infection represents an important public health problem worldwide. Eradicating HCV can finally delay or prevent the progression of HCV infection to end-stage liver diseases such as liver cirrhosis and liver cancer. Chemokine (C-X-C motif ligand 10 (CXCL10 is a chemokine belonging to the CXC chemokine family, and it exerts its function through binding to chemokine (C-X-C motif receptor 3 (CXCR3, playing a critical role in eradication of HCV. This article reviews the relationship of CXCL10 with the pathogenesis of HCV and the effectiveness of antiviral treatment, as well as the CXCL10 measurements. Meanwhile, this article introduces the clinical value of CXCL10 in assessing the risk of liver fibrosis and liver cancer. Further studies are needed to investigate the association between CXCL10 and liver diseases, and CXCL10 may provide a new therapeutic strategy for HCV infection.

Individualized Vascular Disease Prevention in High-Risk Patients

NARCIS (Netherlands)

Kaasenbrood, L

2016-01-01

In the pharmacologic prevention of vascular events, clinicians need to translate average effects from a clinical trial to the individual patient. Prediction models can contribute to individualized vascular disease prevention by selecting patients for treatment based on estimated risk or expected

Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

Directory of Open Access Journals (Sweden)

Guanliang Chen

2016-08-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin.

The Roles of Environmental Pollutants in the Pathogenesis and ...

African Journals Online (AJOL)

ADOWIE PERE

Toxic chemicals in pollutants may destroy or cause mutation ... Keywords: Diabetes, Pathogenesis, Pancreas, Mutation, Insulin, Blood vessel. INTRODUCTION. Diabetes is a chronic disease that occurs either when .... alter insulin metabolism.

Association between Alzheimer’s disease pathogenesis and early demyelination and oligodendrocyte dysfunction

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Yu-Xia Dong

2018-01-01

Full Text Available The APPSwe/PSEN1dE9 (APP/PS1 transgenic mouse model is an Alzheimer’s disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer’s disease. Previous clinical autopsy and imaging studies suggest that Alzheimer’s disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction (qRT-PCR for myelin basic protein (MBP mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1 (MCT1 mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer’s disease pathogenesis.

Coronary artery disease - strategies for primary prevention in Pakistan

International Nuclear Information System (INIS)

Khan, M.H.

2000-01-01

Coronary artery disease is the leading cause of death among middle aged and elderly population. The increase in prevalence of coronary artery disease in Pakistan, has also involved the younger population and about 30% of the patients of coronary artery disease are below the age of 40 years. It seems that with this high prevalence of coronary artery disease, we will be entering in the new millennium with coronary artery disease as number one killer in young adults in Pakistan. This is the time, though belated, we must embark on strategies for primary prevention of this disease so that we are able to reduce the incidence of the disease and the economic burden it entails on the national exchequer. Before suggesting the strategies for the prevention of coronary artery disease in Pakistan, let us briefly review the significance of modifiable risk factors for coronary artery disease. Several studies have been found a significant relationship between physical inactivity and coronary artery disease. (A.B./orig.)

Allergen immunotherapy for the prevention of allergic disease

DEFF Research Database (Denmark)

Dhami, Sangeeta; Nurmatov, Ulugbek; Halken, Susanne

2016-01-01

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the pre......BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT...

Alzheimer's disease prevention: from risk factors to early intervention.

Science.gov (United States)

Crous-Bou, Marta; Minguillón, Carolina; Gramunt, Nina; Molinuevo, José Luis

2017-09-12

Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public-private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer's dementia for only a few years, would have a huge impact on public health.

Influenza vaccines for preventing cardiovascular disease.

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Clar, Christine; Oseni, Zainab; Flowers, Nadine; Keshtkar-Jahromi, Maryam; Rees, Karen

2015-05-05

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. To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease. 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. 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. 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. 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 and reported cardiovascular outcomes among their safety analyses; four trials (n = 1682) focused on prevention of

Evolution in obesity and chronic disease prevention practice in California public health departments, 2010.

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Schwarte, Liz; Ngo, Samantha; Banthia, Rajni; Flores, George; Prentice, Bob; Boyle, Maria; Samuels, Sarah E

2014-11-13

Local health departments (LHDs) are dedicating resources and attention to preventing obesity and associated chronic diseases, thus expanding their work beyond traditional public health activities such as surveillance. This study investigated practices of local health departments in California to prevent obesity and chronic disease. We conducted a web-based survey in 2010 with leaders in California's LHDs to obtain diverse perspectives on LHDs' practices to prevent obesity and chronic disease. The departmental response rate for the 2010 survey was 87% (53 of California's 61 LHDs). Although staff for preventing obesity and chronic disease decreased at 59% of LHDs and stayed the same at 26% of LHDs since 2006, LHDs still contributed the same (12%) or a higher (62%) level of effort in these areas. Factors contributing to internal changes to address obesity and chronic disease prevention included momentum in the field of obesity prevention, opportunities to learn from other health departments, participation in obesity and chronic disease prevention initiatives, and flexible funding streams for chronic disease prevention. LHDs that received foundation funding or had a lead person or organizational unit coordinating or taking the lead on activities related to obesity and chronic disease prevention were more likely than other LHDs to engage in some activities related to obesity prevention. California LHDs are increasing the intensity and breadth of obesity and chronic disease prevention. Findings provide a benchmark from which further changes in the activities and funding sources of LHD chronic disease prevention practice may be measured.

Is Oxidative Stress Associated with Activation and Pathogenesis of Inflammatory Bowel Disease?

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Yuksel Mahmut

2017-08-01

Full Text Available Background: We aimed to determine the levels of total antioxidant status (TAS, total oxidant status (TOS, oxidative stress index (OSI and paraoxonase1/arylesterase levels in inflammatory bowel disease (IBD, and the relation be - tween these molecules and the activity index of the disease. Methods: Eighty IBD patients (ulcerative colitis (UC/Crohn disease (CD 40/40 and 80 control group participants were included in the study. Oxidative stress parameters were measured using the colorimetric method. As disease activity indexes, the endoscopic activity index (EAI was used for UC and the CD activity index (CDAI was used for CD. Results: In IBD patients, mean TAS (1.3±0.2 vs 1.9±0.2, respectively; p<0.001 and arylesterase (963.9±232.2 vs 1252.9±275, respectively; p<0.001 levels were found to be lower and TOS level (5.6±1.6 vs 4.0±1.0, respectively; p<0.001 and OSI rate (4.5±1.6 vs 2.2±0.8, respectively; p<0.001 were found to be higher compared to the control group. A strong positive correlation was found between EAI and TOS levels (r=0.948, p<0.001 and OSI rate (r=0.894, p<0.001 for UC patients. A very strong positive correlation was found between EAI and TOS levels (r=0.964, p<0.001 and OSI rate (r=0.917, p<0.001 for CD patients. It was found in a stepwise regression model that C-reactive protein, OSI and arylesterase risk factors were predictors of IBD compared to the control group. Conclusion: Increased oxidative stress level in IBD patients and the detection of OSI rate as an independent predictor for disease activity indexes lead to the idea that oxidative stress might be related to the pathogenesis of IBD.

Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD).

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Tokarz, Paulina; Kaarniranta, Kai; Blasiak, Janusz

2013-10-01

Cells in aerobic condition are constantly exposed to reactive oxygen species (ROS), which may induce damage to biomolecules, including proteins, nucleic acids and lipids. In normal circumstances, the amount of ROS is counterbalanced by cellular antioxidant defence, with its main components-antioxidant enzymes, DNA repair and small molecular weight antioxidants. An imbalance between the production and neutralization of ROS by antioxidant defence is associated with oxidative stress, which plays an important role in the pathogenesis of many age-related and degenerative diseases, including age-related macular degeneration (AMD), affecting the macula-the central part of the retina. The retina is especially prone to oxidative stress due to high oxygen pressure and exposure to UV and blue light promoting ROS generation. Because oxidative stress has an established role in AMD pathogenesis, proper functioning of antioxidant defence may be crucial for the occurrence and progression of this disease. Antioxidant enzymes play a major role in ROS scavenging and changes of their expression or/and activity are reported to be associated with AMD. Therefore, the enzymes in the retina along with their genes may constitute a perspective target in AMD prevention and therapy.

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis.

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Tejera, Eduardo; Cruz-Monteagudo, Maykel; Burgos, Germán; Sánchez, María-Eugenia; Sánchez-Rodríguez, Aminael; Pérez-Castillo, Yunierkis; Borges, Fernanda; Cordeiro, Maria Natália Dias Soeiro; Paz-Y-Miño, César; Rebelo, Irene

2017-08-08

Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further

Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

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Cheng-Yen Kao

2016-02-01

Full Text Available Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1 Survival in the acidic stomach; (2 movement toward epithelium cells by flagella-mediated motility; (3 attachment to host cells by adhesins/receptors interaction; (4 causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

[The evolution of related names of Bi syndrome and the theory of etiology and pathogenesis].

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Dai, Jian-hua; Shi, Ying-jie; Yin, Hai-bo; Du, Hui

2009-07-01

In the Traditional Chinese medical literature of ancient times, Bi referred to the pathogenesis, or the symptoms as well as the name of the disease. As the name of a disease, Bi has the different meanings of broad and narrow., joint-running, joint-running wind, white tiger joint-running, gout etc. referring to the narrow meaning of Bi disease. The theory of etiology and pathogenesis of the narrow meaning of Bi disease developed from damp-impediment, wind-cold-damp impediment to damp-hot impediment, stasis-hot impediment, which reflected the constant deepening of cognition.

Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers.

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Sharma, Susmeeta T; Nestler, John E

2006-06-01

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in United States, affecting 6-10% of females in the reproductive age group. Recent studies have shown that insulin resistance plays an important role in the pathogenesis of PCOS. Traditionally, management of PCOS consisted mainly of ovulation induction, treatment of acne and hirsutism, and prevention of endometrial cancer. However, with mounting evidence showing that PCOS is associated with dysmetabolic syndrome and an increased risk for developing diabetes and heart disease, this can no longer be our sole focus. Current data support a strong recommendation that women with PCOS should undergo comprehensive evaluation for diabetes and recognized cardiovascular risk factors and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many obese women with PCOS find weight loss difficult to achieve and maintain, and this is not an option for lean women with PCOS. For these reasons, insulin-sensitizing drugs are proving to be a promising and unique therapeutic option for chronic treatment of PCOS.

Molecular Pathogenesis of Neuromyelitis Optica

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Bukhari, Wajih; Barnett, Michael H; Prain, Kerri; Broadley, Simon A

2012-01-01

Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies. PMID:23202933

The Paradox of Feline Coronavirus Pathogenesis: A Review

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Luciana Wanderley Myrrha

2011-01-01

Full Text Available Feline coronavirus (FCoV is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP. Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.

Magnesium in Disease Prevention and Overall Health12

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Volpe, Stella Lucia

2013-01-01

Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to, protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes. Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure, and glucose and insulin metabolism. Because of magnesium’s many functions within the body, it plays a major role in disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including migraine headaches, Alzheimer’s disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers). This review presents recent research in the areas of magnesium and chronic disease, with the goal of emphasizing magnesium’s role in disease prevention and overall health. PMID:23674807

Metabolomic Quantitative Trait Loci (mQTL Mapping Implicates the Ubiquitin Proteasome System in Cardiovascular Disease Pathogenesis.

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William E Kraus

2015-11-01

Full Text Available Levels of certain circulating short-chain dicarboxylacylcarnitine (SCDA, long-chain dicarboxylacylcarnitine (LCDA and medium chain acylcarnitine (MCA metabolites are heritable and predict cardiovascular disease (CVD events. Little is known about the biological pathways that influence levels of most of these metabolites. Here, we analyzed genetics, epigenetics, and transcriptomics with metabolomics in samples from a large CVD cohort to identify novel genetic markers for CVD and to better understand the role of metabolites in CVD pathogenesis. Using genomewide association in the CATHGEN cohort (N = 1490, we observed associations of several metabolites with genetic loci. Our strongest findings were for SCDA metabolite levels with variants in genes that regulate components of endoplasmic reticulum (ER stress (USP3, HERC1, STIM1, SEL1L, FBXO25, SUGT1 These findings were validated in a second cohort of CATHGEN subjects (N = 2022, combined p = 8.4x10-6-2.3x10-10. Importantly, variants in these genes independently predicted CVD events. Association of genomewide methylation profiles with SCDA metabolites identified two ER stress genes as differentially methylated (BRSK2 and HOOK2. Expression quantitative trait loci (eQTL pathway analyses driven by gene variants and SCDA metabolites corroborated perturbations in ER stress and highlighted the ubiquitin proteasome system (UPS arm. Moreover, culture of human kidney cells in the presence of levels of fatty acids found in individuals with cardiometabolic disease, induced accumulation of SCDA metabolites in parallel with increases in the ER stress marker BiP. Thus, our integrative strategy implicates the UPS arm of the ER stress pathway in CVD pathogenesis, and identifies novel genetic loci associated with CVD event risk.

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

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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.

The emerging role of interleukin (IL)-1 in the pathogenesis and treatment of inflammatory and degenerative eye diseases.

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Fabiani, Claudia; Sota, Jurgen; Tosi, Gian Marco; Franceschini, Rossella; Frediani, Bruno; Galeazzi, Mauro; Rigante, Donato; Cantarini, Luca

2017-10-01

Interleukin (IL)-1 plays a key role in the pathogenesis and thereafter in the search for specific treatments of different inflammatory and degenerative eye diseases. Indeed, an overactivity of IL-1 might be an initiating factor for many immunopathologic sceneries in the eye, as proven by the efficacy of the specific IL-1 blockade in different ocular diseases. For instance, the uveitis in monogenic autoinflammatory disorders, such as Blau syndrome and cryopyrin-associated periodic syndrome, or in complex polygenic autoinflammatory disorders, such as Behçet's disease, has been successfully treated with IL-1 blockers. Similarly, therapy with the IL-1 receptor antagonist anakinra has proven successful also in scleritis and episcleritis in the context of different rheumatic conditions. Moreover, interesting findings deriving from animal models of ocular disease have set a rational basis from a therapeutic viewpoint to manage patients also with dry eye disease and a broadening number of ocular inflammatory and degenerative conditions, which start from an imbalance between IL-1 and its receptor antagonist.

Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

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Tugizov, Sharof

2016-01-01

Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

Pathogenesis of helicobacter pylori infection involves interaction ...

African Journals Online (AJOL)

It is now clear that both bacterial virulence factors and host susceptibility play key roles in disease pathogenesis. The nature and levels of these interactions between these major factors has been found to determine the spectrum of clinical outcomes of the infection with this important bacterium. Virulence factors include the ...

Long Non-Coding RNA Profiling in a Non-Alcoholic Fatty Liver Disease Rodent Model: New Insight into Pathogenesis

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Yi Chen

2017-01-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis were then performed to explore their function. In the current analysis, 89 upregulated and 177 downregulated mRNAs were identified, together with 291 deregulated lncRNAs. Bioinformatic analysis of these RNAs has categorized these RNAs into pathways including arachidonic acid metabolism, circadian rhythm, linoleic acid metabolism, peroxisome proliferator-activated receptor (PPAR signaling pathway, sphingolipid metabolism, steroid biosynthesis, tryptophan metabolism and tyrosine metabolism were compromised. Quantitative polymerase chain reaction (qPCR of representative nine mRNAs and eight lncRNAs (named fatty liver-related lncRNA, FLRL was conducted and this verified previous microarray results. Several lncRNAs, such as FLRL1, FLRL6 and FLRL2 demonstrated to be involved in circadian rhythm targeting period circadian clock 3 (Per3, Per2 and aryl hydrocarbon receptor nuclear translocator-like (Arntl, respectively. While FLRL8, FLRL3 and FLRL7 showed a potential role in PPAR signaling pathway through interaction with fatty acid binding protein 5 (Fabp5, lipoprotein lipase (Lpl and fatty acid desaturase 2 (Fads2. Functional experiments showed that interfering of lncRNA FLRL2 expression affected the expression of predicted target, circadian rhythm gene Arntl. Moreover, both FLRL2 and Arntl were downregulated in the NAFLD cellular model. The current study identified lncRNA and corresponding mRNA in NAFLD

Pathogenesis and Laboratory Diagnosis of Childhood Urinary Tract Infection

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Jharna Mandal

2016-04-01

Full Text Available Urinary tract infection (UTI is one of the most common infections of childhood. The clinical presentations are mostly non-specific or mild. As any episode of UTI can potentially damage the kidneys, timely diagnosis and treatment are necessary to prevent renal damage. Incidence of UTI varies depending on the age, gender, and race of the child. UTIs in children are commonly caused by bacteria, though viruses, fungi, and parasites are also occasionally involved. The pathogenesis of UTI is complex where several host and pathogen factors influence the course of the disease and its outcome. Urine culture is still considered the gold standard method for the diagnosis of UTI. The means of obtaining urine samples from children for culture involves urethral catheterisation and suprapubic aspiration. The conventional methods of antibiotic susceptibility testing are labour intensive and time exhaustive. With the advent of technology, many automated platforms are available which are rapid, involve less volume of the culture or the sample, and have high accuracy.

Persistent perineal sinus. Incidence, pathogenesis, risk factors, and management

International Nuclear Information System (INIS)

Lohsiriwat, V.

2009-01-01

This review discusses the incidence, pathogenesis, risk factors, diagnosis, and therapeutic options for persistent perineal sinus (PPS), defined as a perineal wound that remains unhealed more than 6 months after surgery. The incidence of PPS after surgery for inflammatory bowel disease (IBD) ranges from 3% to 70% and after abdominoperineal resection (APR) for Low rectal cancer, it can be up to 30%. These unhealed wounds are frequently related to perioperative pelvic or perineal sepsis. Crohn's disease (CD) and neoadjuvant radiation therapy are also important risk factors. The management of PPS is based on an understanding of pathogenesis and clinical grounds. The advantages and disadvantages of the current therapeutic approaches, including the topical administration of various drugs, vacuum-assisted closure, and perineal reconstruction with a muscle flap or a myocutaneous flap are also discussed. (author)

Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.

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Bukhari, Hassan; Glotzbach, Annika; Kolbe, Katharina; Leonhardt, Gregor; Loosse, Christina; Müller, Thorsten

2017-09-01

Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD". Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of pelvic inflammatory disease by primary care physicians. A comparison with Centers for Disease Control and Prevention guidelines.

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Hessol, N A; Priddy, F H; Bolan, G; Baumrind, N; Vittinghoff, E; Reingold, A L; Padian, N S

1996-01-01

The Centers for Disease Control and Prevention published recommendations for clinicians on the management of pelvic inflammatory disease, but it is unknown if providers are aware of the guidelines or follow them. To compare pelvic inflammatory disease screening, diagnosis, treatment, and reporting practices among primary care physicians with the Centers for Disease Control and Prevention guidelines for pelvic inflammatory disease. A weighted random sample of California primary care physicians surveyed in November 1992 and January 1993. Of the 1,165 physicians surveyed, 553 (48%) returned completed questionnaires. Among respondents, 302 (55%) reported having treated a case of pelvic inflammatory disease during the last 12 months, and of these, 52% answered that they were unsure of or do not follow the Centers for Disease Control and Prevention guidelines for pelvic inflammatory disease. Pediatricians and those with more years since residency were less likely to deviate from the Centers for Disease Control and Prevention guidelines for pelvic inflammatory disease, and family practitioners were more likely to deviate from the guidelines. Pelvic inflammatory disease is commonly encountered by primary care physicians in California. Training and experience were important predictors of compliance with the Centers for Disease Control and Prevention recommendations; however, substantial divergence from the guidelines occurs.

Legionella (Legionnaires' Disease and Pontiac Fever): Prevention

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... and Trends Fast Facts For Clinicians Disease Specifics Clinical Features Diagnosis, Treatment, & Prevention For Health Departments Surveillance & Reporting Resources Case Definitions CDC Surveillance Classifications How to Report Cases Case ...

Involvement of immune cells in the pathogenesis of endometriosis.

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Izumi, Gentaro; Koga, Kaori; Takamura, Masashi; Makabe, Tomoko; Satake, Erina; Takeuchi, Arisa; Taguchi, Ayumi; Urata, Yoko; Fujii, Tomoyuki; Osuga, Yutaka

2018-02-01

Endometriosis is characterized by the implantation and growth of endometriotic tissues outside the uterus. It is widely accepted the theory that endometriosis is caused by the implantation of endometrial tissue from retrograde menstruation; however, retrograde menstruation occurs in almost all women and other factors are required for the establishment of endometriosis, such as cell survival, cell invasion, angiogenesis, and cell growth. Immune factors in the local environment may, therefore, contribute to the formation and progression of endometriosis. Current evidence supports the involvement of immune cells in the pathogenesis of endometriosis. Peritoneal neutrophils and macrophages secrete biochemical factors that help endometriotic cell growth and invasion, and angiogenesis. Peritoneal macrophages and NK cells in endometriosis have limited capability of eliminating endometrial cells in the peritoneal cavity. An imbalance of T cell subsets leads to aberrant cytokine secretions and inflammation that results in the growth of endometriosis lesions. It is still uncertain whether these immune cells have a role in the initial cause and/or stimulate actions that enhance disease; however, in either case, modulating the actions of these cells may prevent initiation or disease progression. Further studies are needed to deepen the understanding of the pathology of endometriosis and to develop novel management approaches of benefit to women suffering from this disease. © 2018 Japan Society of Obstetrics and Gynecology.

Basic webliography on health promotion and disease prevention

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Mario Ferreira Junior

2009-12-01

Full Text Available Objectives: To introduce a basic webliography to access highly qualified evidence-based material on health promotion and disease prevention, aiming at the continuing education of health professionals. Methods: By means of Google® browser, applying the descriptors in sequence to progressively refine the search on Internet and key concepts to be learned, all previously defined by the authors themselves, we proceeded a qualitative analyses of the 20 first listed links for each searched issue and the final selection of the most scientifically relevant ones. Results: The 34 selected links are presented in 4 groups: 23 portals, 5 guides and recommendations, 4 scientific journals and 3 blogs that allow free access to health promotion and disease prevention related subjects, such as: concepts; national and international public policies; epidemiology, statistics and health indicators; diseases screening and prophylaxis; counseling for behavior change of health related habits; and interdisciplinary work. Among the selected links 10 (29% are written in English while the others are in Portuguese. Conclusions: The identification of reading materials on health promotion and disease prevention available on Internet, many in Portuguese, allowed us toselect relevant scientifically qualified literature and turn it accessible to health professionals, enabling the acquisition of new knowledge or quick update.

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes.

Science.gov (United States)

Hooper, Philip L; Balogh, Gabor; Rivas, Eric; Kavanagh, Kylie; Vigh, Laszlo

2014-07-01

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease.

Public-Private Partnerships in Chronic Disease Prevention-Part 3

Centers for Disease Control (CDC) Podcasts

2009-04-06

This podcast is the third of a seven part series discussing public health partnerships with the private sector. In this segment, CDC's Elizabeth Majestic and University of North Carolina's Gene Matthews talk about how building credibility on preparedness issues can help develop support for initiatives around chronic disease prevention.  Created: 4/6/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2009.

Prevention of allergic disease in childhood

DEFF Research Database (Denmark)

Halken, Susanne

2004-01-01

rhinoconjunctivitis. In one prospective observational study of a birth cohort of unselected infants we evaluated possible predictive/risk factors. In two prospective intervention studies including 1 yr birth cohorts of high-risk(HR) infants we investigated the effect of feeding HR infants exclusively breast milk (BM......The development and phenotypic expression of atopic diseases depends on a complex interaction between genetic factors, environmental exposure to allergens,and non-specific adjuvant factors, such as tobacco smoke, air pollution and infections. Preventive measures may include both exposure...... to allergens and adjuvant risk/protective factors and pharmacological treatment. These measures may address the general population, children at risk for development of atopic disease (high-risk infants), children with early symptoms of allergic disease or children with chronic disease. The objective...

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

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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.

Modern vitiligo genetics sheds new light on an ancient disease

Science.gov (United States)

SPRITZ, Richard A.

2013-01-01

Vitiligo is a complex disorder in which autoimmune destruction of melanocytes results in white patches of skin and overlying hair. Over the past several years, extensive genetic studies have outlined a biological framework of vitiligo pathobiology that underscores its relationship to other autoimmune diseases. This biological framework offers insight into both vitiligo pathogenesis and perhaps avenues towards more effective approaches to treatment and even disease prevention. PMID:23668538

Influenza vaccines for preventing cardiovascular disease

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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

Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages

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Bryan J. Neth

2017-10-01

Full Text Available Metabolic dysfunction is a well-established feature of Alzheimer’s disease (AD, evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D, hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. This association may in part be due to the systemic mitochondrial dysfunction that is common to these pathologies. Accumulating evidence suggests that mitochondrial dysfunction is a significant feature of AD and may play a fundamental role in its pathogenesis. In fact, aging itself presents a unique challenge due to inherent mitochondrial dysfunction and prevalence of chronic metabolic disease. Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.

Research progress in early diagnosis of Alzheimer's disease

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Meng-sha SUN

2018-04-01

Full Text Available Alzheimer's disease (AD is a kind of central nervous system degenerative disease with higher incidence, which has been paid increasing attention. The pathogenesis is not yet clear though it has been studied a lot. The existing theories focused on amyloid β-protein (Aβ deposit, hyperphosphorylation of tau and cholinergic neuronal loss. There is mainly symptomatic treatment which cannot reverse disease course. So early diagnosis is particularly important for prevention and treatment of AD. The article will review recent advances in the studies of early diagnosis of AD. It may help accurately diagnose the process from mild cognitive impairment (MCI to early AD and give advice on prevention and treatment. DOI: 10.3969/j.issn.1672-6731.2018.03.011

Epidemiology, Pathogenesis, and Control of a Tick-Borne Disease- Kyasanur Forest Disease: Current Status and Future Directions

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Syed Z. Shah

2018-05-01

Full Text Available In South Asia, Haemaphysalis spinigera tick transmits Kyasanur Forest Disease Virus (KFDV, a flavivirus that causes severe hemorrhagic fever with neurological manifestations such as mental disturbances, severe headache, tremors, and vision deficits in infected human beings with a fatality rate of 3–10%. The disease was first reported in March 1957 from Kyasanur forest of Karnataka (India from sick and dying monkeys. Since then, between 400 and 500 humans cases per year have been recorded; monkeys and small mammals are common hosts of this virus. KFDV can cause epizootics with high fatality in primates and is a level-4 virus according to the international biosafety rules. The density of tick vectors in a given year correlates with the incidence of human disease. The virus is a positive strand RNA virus and its genome was discovered to code for one polyprotein that is cleaved post-translationally into 3 structural proteins (Capsid protein, Envelope Glycoprotein M and Envelope Glycoprotein E and 7 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. KFDV has a high degree of sequence homology with most members of the TBEV serocomplex. Alkhurma virus is a KFDV variant sharing a sequence similarity of 97%. KFDV is classified as a NIAID Category C priority pathogen due to its extreme pathogenicity and lack of US FDA approved vaccines and therapeutics; also, the infectious dose is currently unknown for KFD. In India, formalin-inactivated KFDV vaccine produced in chick embryo fibroblast is being used. Nevertheless, further efforts are required to enhance its long-term efficacy. KFDV remains an understudied virus and there remains a lack of insight into its pathogenesis; moreover, specific treatment to the disease is not available to date. Environmental and climatic factors involved in disseminating Kyasanur Forest Disease are required to be fully explored. There should be a mapping of endemic areas and cross-border veterinary

Hepatitis E: Molecular Virology and Pathogenesis

Science.gov (United States)

Panda, Subrat K.; Varma, Satya P.K.

2013-01-01

Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5′ distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3′ distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV. PMID:25755485

The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

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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.

Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris.

Science.gov (United States)

Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching; Two, Aimee; Shu, Chih-Wen; Huang, Chun-Ming

2015-01-01

Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus

Energy Technology Data Exchange (ETDEWEB)

Messaoudi, Ilhem; Amarasinghe, Gaya K.; Basler, Christopher F.

2015-10-06

Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirus pathogenesis.

Potential of the Antibody Against cis-Phosphorylated Tau in the Early Diagnosis, Treatment, and Prevention of Alzheimer Disease and Brain Injury.

Science.gov (United States)

Lu, Kun Ping; Kondo, Asami; Albayram, Onder; Herbert, Megan K; Liu, Hekun; Zhou, Xiao Zhen

2016-11-01

Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) share a common neuropathologic signature-neurofibrillary tangles made of phosphorylated tau-but do not have the same pathogenesis or symptoms. Although whether traumatic brain injury (TBI) could cause AD has not been established, CTE is shown to be associated with TBI. Until recently, whether and how TBI leads to tau-mediated neurodegeneration was unknown. The unique prolyl isomerase Pin1 protects against the development of tau-mediated neurodegeneration in AD by converting the phosphorylated Thr231-Pro motif in tau (ptau) from the pathogenic cis conformation to the physiologic trans conformation, thereby restoring ptau function. The recent development of antibodies able to distinguish and eliminate both conformations specifically has led to the discovery of cis-ptau as a precursor of tau-induced pathologic change and an early driver of neurodegeneration that directly links TBI to CTE and possibly to AD. Within hours of TBI in mice or neuronal stress in vitro, neurons prominently produce cis-ptau, which causes and spreads cis-ptau pathologic changes, termed cistauosis. Cistauosis eventually leads to widespread tau-mediated neurodegeneration and brain atrophy. Cistauosis is effectively blocked by the cis-ptau antibody, which targets intracellular cis-ptau for proteasome-mediated degradation and prevents extracellular cis-ptau from spreading to other neurons. Treating TBI mice with cis-ptau antibody not only blocks early cistauosis but also prevents development and spreading of tau-mediated neurodegeneration and brain atrophy and restores brain histopathologic features and functional outcomes. Thus, cistauosis is a common early disease mechanism for AD, TBI, and CTE, and cis-ptau and its antibody may be useful for early diagnosis, treatment, and prevention of these devastating diseases.

Estrogen signalling in the pathogenesis of age-related macular degeneration.

Science.gov (United States)

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Metabolic and mineral conditions of retained placenta in highly productive dairy cows: pathogenesis, diagnostics and prevention – a review

Directory of Open Access Journals (Sweden)

Ryszard Mordak

2017-01-01

Full Text Available The time around calving in highly productive dairy cows is a critical period in terms of their metabolism, which is connected with high demands of the foetus as well as with the onset of lactation. Retained placenta in cows may have multifactorial aetiology, but in herds which are free from infectious diseases, the most important reasons are; periparturient metabolic changes and disturbances to the internal balance and stress. During the periparturient period, the most important factor causing immune suppression and hypotony of uterus in cows is metabolic stress due to hormonal and nutritional factors, including metabolic fluctuations, negative energy balance, as well as shortage of proteins, minerals, vitamins and antioxidants. This metabolic stress as a result of an imbalance in the internal metabolic homeostasis activates the hypothalamic-pituitary-adrenocortical axis (HPA and increases serum corticosterid (cortisol concentration, especially on the day of calving. Cortisol is a powerful immune suppressive factor that causes depression of leukocyte proliferation and their functions. The periparturient metabolic stress may also stimulate the production of catecholamines, especially adrenalin. Elevated levels of adrenalin activate adrenoreceptors of the myometrium, which in turn cause hypotony or atony of the uterus at calving in cows. Elevated levels of cortisol and adrenalin may significantly inhibit the rejection and expulsion of foetal membranes in cows, resulting in an increased incidence of their retention. These important mechanisms for placental retention in highly productive dairy cows often have primary nutritional metabolic aetiology, but they also occur during secondary metabolic disturbances and metabolic stress during calving. This metabolic and immunological aetiology and pathogenesis of retained placenta usually occur in highly productive periparturient cows on dairy farms in the absence of bovine infectious diseases, which can

Seven challenges in modeling vaccine preventable diseases

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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.

Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice.

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Hiroaki J Kimura

2009-11-01

Full Text Available Oncocytes of the thyroid gland (Hürthle cells are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors.In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.

Transposon mutagenesis reveals differential pathogenesis of Ralstonia solanacearum on tomato and Arabidopsis.

Science.gov (United States)

Lin, Yu-Mei; Chou, I-Chun; Wang, Jaw-Fen; Ho, Fang-I; Chu, Yu-Ju; Huang, Pei-Cheng; Lu, Der-Kang; Shen, Hwei-Ling; Elbaz, Mounira; Huang, Shu-Mei; Cheng, Chiu-Ping

2008-09-01

Ralstonia solanacearum causes a deadly wilting disease on a wide range of crops. To elucidate pathogenesis of this bacterium in different host plants, we set out to identify R. solanacearum genes involved in pathogenesis by screening random transposon insertion mutants of a highly virulent strain, Pss190, on tomato and Arabidopsis thaliana. Mutants exhibiting various decreased virulence levels on these two hosts were identified. Sequence analysis showed that most, but not all, of the identified pathogenesis genes are conserved among distinct R. solanacearum strains. A few of the disrupted loci were not reported previously as being involved in R. solanacearum pathogenesis. Notably, a group of mutants exhibited differential pathogenesis on tomato and Arabidopsis. These results were confirmed by characterizing allelic mutants in one other R. solanacearum strain of the same phylotype. The significantly decreased mutants' colonization in Arabidopsis was found to be correlated with differential pathogenesis on these two plants. Differential requirement of virulence genes suggests adaptation of this bacterium in different host environments. Together, this study reveals commonalities and differences of R. solanacearum pathogenesis on single solanaceous and nonsolanaceous hosts, and provides important new insights into interactions between R. solanacearum and different host plants.

Urinary Tract Infection: Pathogenesis and Outlook

Science.gov (United States)

McLellan, Lisa K.; Hunstad, David A.

2016-01-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. PMID:27692880

'Omics investigations of HIV and SIV pathogenesis and innate immunity.

Science.gov (United States)

Palermo, Robert E; Fuller, Deborah H

2013-01-01

In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

Early chronic obstructive pulmonary disease: definition, assessment, and prevention.

Science.gov (United States)

Rennard, Stephen I; Drummond, M Bradley

2015-05-02

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD, however, is a heterogeneous collection of diseases with differing causes, pathogenic mechanisms, and physiological effects. Therefore a comprehensive approach to COPD prevention will need to address the complexity of COPD. Advances in the understanding of the natural history of COPD and the development of strategies to assess COPD in its early stages make prevention a reasonable, if ambitious, goal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

Science.gov (United States)

Harris, Steven A.; Harris, Elizabeth A.

2018-01-01

This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer’s disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis. The AD susceptibility genes apolipoprotein E (APOE), phosphatidylinositol binding clathrin assembly protein (PICALM), complement receptor 1 (CR1) and clusterin (CLU) are involved in the HSV lifecycle. Polymorphisms in these genes may affect brain susceptibility to HSV-1 infection. APOE, for example, influences susceptibility to certain viral infections, HSV-1 viral load in the brain, and the innate immune response. The AD susceptibility gene cholesterol 25-hydroxylase (CH25H) is upregulated in the AD brain and is involved in the antiviral immune response. HSV-1 interacts with additional genes to affect cognition-related pathways and key enzymes involved in Aβ production, Aβ clearance, and hyperphosphorylation of tau proteins. Aβ itself functions as an antimicrobial peptide (AMP) against various pathogens including HSV-1. Evidence is presented supporting the hypothesis that Aβ is produced as an AMP in response to HSV-1 and other brain infections, leading to Aβ deposition and plaque formation in AD. Epidemiologic studies associating HSV-1 infection with AD and cognitive impairment are discussed. Studies are reviewed supporting subclinical chronic reactivation of latent HSV-1 in the brain as significant in the pathogenesis of AD. Finally, the rationale for and importance of clinical

Mitochondrial Drugs for Alzheimer Disease

Directory of Open Access Journals (Sweden)

Xiongwei Zhu

2009-12-01

Full Text Available Therapeutic strategies for Alzheimer disease (AD have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus far are limited to agents that slow disease progression without halting it, and although much work towards a cure is underway, a greater understanding of disease etiology is certainly necessary for any such achievement. Mitochondria, as the centers of cellular metabolic activity and the primary generators of reactive oxidative species in the cell, received particular attention especially given that mitochondrial defects are known to contribute to cellular damage. Furthermore, as oxidative stress has come to the forefront of AD as a causal theory, and as mitochondrial damage is known to precede much of the hallmark pathologies of AD, it seems increasingly apparent that this metabolic organelle is ultimately responsible for much, if not all of disease pathogenesis. In this review, we review the role of neuronal mitochondria in the pathogenesis of AD and critically assess treatment strategies that utilize this upstream access point as a method for disease prevention. We suspect that, with a revived focus on mitochondrial repair and protection, an effective and realistic therapeutic agent can be successfully developed.

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

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Yogy Simanjuntak

2018-02-01

Full Text Available Despite the low case fatality, Zika virus (ZIKV infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

Science.gov (United States)

Simanjuntak, Yogy; Liang, Jian-Jong; Chen, Si-Yu; Li, Jin-Kun; Lee, Yi-Ling; Wu, Han-Chung; Lin, Yi-Ling

2018-02-01

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

Vaccine-preventable diseases and vaccination rates in South Dakota.

Science.gov (United States)

Kightlinger, Lon

2013-01-01

Vaccine-preventable diseases have historically caused much illness and death in South Dakota. Sixty-seven diphtheria deaths were reported in 1892 and 1,017 polio cases were reported at the peak of the polio epidemic in 1952. As vaccines have been developed, licensed and put into wide use, the rates of diphtheria, polio, measles, smallpox and other diseases have successfully decreased leading to control, statewide elimination or eradication. Other diseases, such as pertussis, have been more difficult to control by vaccination alone. Although current vaccination coverage rates for South Dakota's kindergarten children surpass the Healthy People 2020 targets of 95 percent, the coverage rates for 2-year-old children and teenagers are below the target rates. Until vaccine-preventable diseases are eradicated globally, we must vigilantly maintain high vaccination coverage rates and aggressively apply control measures to limit transmission when diseases do occur in South Dakota.

Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

Science.gov (United States)

Ghazaei, Ciamak

2018-01-01

Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies.

Science.gov (United States)

Fett, Nicole

2013-01-01

Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc.

Preventing Zika disease with novel vector control approaches ...

International Development Research Centre (IDRC) Digital Library (Canada)

Preventing Zika disease with novel vector control approaches. The highest numbers of dengue cases in Latin America in the last few years have occurred in Brazil, Colombia, and Mexico. These countries have also faced outbreaks of chikungunya (2014-2015) and Zika (2015-2016). All three diseases are transmitted by the ...

[Project summarize of "reestablishing disease prevention and control system of China"].

Science.gov (United States)

Hao, Mo; Yu, Jingjin; Yu, Mingzhu; Duan, Yong

2005-01-01

This paper introduced the project of "reestablishing the disease control and prevention system of China" in brief, including background, objectives, funding resources, researching objects and sampling methods. This project which funded by National Outstanding Younger Fund and the research fund of MOH aimed at nailing down the key problem existed in disease control and prevention system of China, demonstrating the reasons and mechanism of key problem, developing feasible policy idea and strategy. This paper also introduced some issues concerning the reestablishing of the disease control and prevention system of China: the definition of public function, the standard of human resource allocation and the standard of financing. The Centers for Disease Control and Prevention in 8 provinces, 80 cities and 80 counties have been sampled to provide information that project needed. In addition, this project also cited some data which come from the early study, in which 3 provinces, 12 counties, 49 towns, 179 villages and 9781 rural families have been sampled and investigated.

75 FR 76987 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP...

Science.gov (United States)

2010-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Epidemiologic and Ecologic...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and...

[AETIOLOGY AND PATHOGENESIS GASTRO-DUODENALES ULCERATIVE LESIONS IN ELDERLY].

Science.gov (United States)

Chernekhovskaya, N E; Povalayev, A V; Layshenko, G A

2015-01-01

In review today conceptions of view to aetiology and pathogenesis gastro-duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of the heart and hypertension are reasons of acute ulcers and erosions in elderly. The breaking of microcirculation are very importance.

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

Science.gov (United States)

Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

2015-01-01

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

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

Science.gov (United States)

2016-05-20

ANDV strain Chile -9717869 (27) was propagated in Vero E6 cells 122 (Vero C1008, ATCC CRL 1586). Preparation of twice-plaque-purified ANDV stock has...Research and Material Command, Military 537 Infectious Disease Research Program , Program Area T. Research reported in this publication 538 was also...prior to kidney, involvement, and diagnosed by viral 684 inclusions in lung macrophages. European journal of clinical microbiology & infectious

Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research.

Science.gov (United States)

Paraskevaidi, Maria; Martin-Hirsch, Pierre L; Kyrgiou, Maria; Martin, Francis L

2017-05-01

Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell's functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Perceptions about Sickle Cell Disease and its Prevention among ...

African Journals Online (AJOL)

Perceptions about Sickle Cell Disease and its Prevention among ... Methods Three hundred undergraduate students from Bayero University Kano and Federal ... about SCD prevention to youths in schools and through other media; as well as strengthen prenatal screening and premarital counseling and testing services.

Prevention and management of noncommunicable disease: the IOC Consensus Statement, Lausanne 2013.

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Matheson, Gordon O; Klügl, Martin; Engebretsen, Lars; Bendiksen, Fredrik; Blair, Steven N; Börjesson, Mats; Budgett, Richard; Derman, Wayne; Erdener, Uğur; Ioannidis, John P A; Khan, Karim M; Martinez, Rodrigo; van Mechelen, Willem; Mountjoy, Margo; Sallis, Robert E; Schwellnus, Martin; Shultz, Rebecca; Soligard, Torbjørn; Steffen, Kathrin; Sundberg, Carl Johan; Weiler, Richard; Ljungqvist, Arne

2013-11-01

Morbidity and mortality from preventable, noncommunicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: 1. Focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease. 2. Establish actual centers to design, implement, study, and improve preventive programs for chronic disease. 3. Use human-centered design (HCD) in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet, and lifestyle. 5. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this

Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.

Directory of Open Access Journals (Sweden)

S Rochelle Mikkelsen

2011-02-01

Full Text Available Feline immunodeficiency virus (FIV infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+CD25(hiFoxP3(+ immunosuppressive regulatory T (Treg cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+ T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.

Partial regulatory T cell depletion prior to acute feline immunodeficiency virus infection does not alter disease pathogenesis.

Science.gov (United States)

Mikkelsen, S Rochelle; Long, Julie M; Zhang, Lin; Galemore, Erin R; VandeWoude, Sue; Dean, Gregg A

2011-02-25

Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4(+)CD25(hi)FoxP3(+) immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4(+) T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection.

75 FR 4406 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational...

Science.gov (United States)

2010-01-27

... recommendations to the Disease, Disability, and Injury Prevention and Control SEP: Occupational Safety and Health... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational Safety and Health Training...

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

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.

Science.gov (United States)

Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen

2017-01-01

Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extremely low-frequency magnetic exposure appears to have no effect on pathogenesis of Alzheimer's disease in aluminum-overloaded rat.

Directory of Open Access Journals (Sweden)

Cheng Zhang

Full Text Available OBJECTIVE: Extremely low-frequency magnetic field (ELF-MF has been reported to be of potential pathogenetic relevance to Alzheimer's disease (AD for years. However, evidence confirming this function remains inconclusive. Chronic Al treatment has been identified as a contributing factor to cognitive function impairment in AD. This study aims to examine whether or not ELF-MF and Al have synergistic effects toward AD pathogenesis by investigating the effects of ELF-MF with or without chronic Al treatment on SD rats. METHODS: Sprague-Dawley (SD rats were subjected one of the following treatments: sham (control group, oral Al (Al group, ELF-MF (100 µT at 50 Hz with oral Al (MF+Al group, or ELF-MF (100 µT at 50 Hz without oral Al (MF group. RESULTS: After 12 wk of treatment, oral Al treatment groups (Al and MF+Al groups showed learning and memory impairment as well as morphological hallmarks, including neuronal cell loss and high density of amyloid-β (Aβ in the hippocampus and cerebral cortex. ELF-MF without Al treatment showed no significant effect on AD pathogenesis. ELF-MF+Al treatment induced no more damage than Al treatment did. CONCLUSIONS: Our results showed no evidence of any association between ELF-MF exposure (100 µT at 50 Hz and AD, and ELF-MF exposure does not influence the pathogenesis of AD induced by Al overload.

Hypoxia and GABA shunt activation in the pathogenesis of Alzheimer's disease.

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Salminen, Antero; Jouhten, Paula; Sarajärvi, Timo; Haapasalo, Annakaisa; Hiltunen, Mikko

2016-01-01

We have previously observed that the conversion of mild cognitive impairment to definitive Alzheimer's disease (AD) is associated with a significant increase in the serum level of 2,4-dihydroxybutyrate (2,4-DHBA). The metabolic generation of 2,4-DHBA is linked to the activation of the γ-aminobutyric acid (GABA) shunt, an alternative energy production pathway activated during cellular stress, when the function of Krebs cycle is compromised. The GABA shunt can be triggered by local hypoperfusion and subsequent hypoxia in AD brains caused by cerebral amyloid angiopathy. Succinic semialdehyde dehydrogenase (SSADH) is a key enzyme in the GABA shunt, converting succinic semialdehyde (SSA) into succinate, a Krebs cycle intermediate. A deficiency of SSADH activity stimulates the conversion of SSA into γ-hydroxybutyrate (GHB), an alternative route from the GABA shunt. GHB can exert not only acute neuroprotective activities but unfortunately also chronic detrimental effects which may lead to cognitive impairment. Subsequently, GHB can be metabolized to 2,4-DHBA and secreted from the brain. Thus, the activation of the GABA shunt and the generation of GHB and 2,4-DHBA can have an important role in the early phase of AD pathogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Theory in Chronic Disease Prevention and Health Promotion

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Hall, Michael; Elise, Eifert

2016-01-01

Morbidity and mortality related to chronic diseases are a primary concern of health professionals, including Health Educators. According to the Centers for Disease Control and Prevention, over one half of the adult population in the United States suffer from one or more chronic conditions. Understanding the health risk behaviors that contribute to…

Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis.

Science.gov (United States)

Riancho, J; Gonzalo, I; Ruiz-Soto, M; Berciano, J

2016-02-04

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Insights into mechanisms of transmission and pathogenesis from transgenic mouse models of prion diseases

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Moreno, Julie A.; Telling, Glenn C.

2018-01-01

Prions represent a new paradigm of protein-mediated information transfer. In the case of mammals, prions are the cause of fatal, transmissible neurodegenerative diseases, sometimes referred to as transmissible spongiform encephalopathies (TSE’s), which frequently occur as epidemics. An increasing body of evidence indicates that the canonical mechanism of conformational corruption of cellular prion protein (PrPC) by the pathogenic isoform (PrPSc) that is the basis of prion formation in TSE’s, is common to a spectrum of proteins associated with various additional human neurodegenerative disorders, including the more common Alzheimer’s and Parkinson’s diseases. The peerless infectious properties of TSE prions, and the unparalleled tools for their study, therefore enable elucidation of mechanisms of template-mediated conformational propagation that are generally applicable to these related disease states. Many unresolved issues remain including the exact molecular nature of the prion, the detailed cellular and molecular mechanisms of prion propagation, and the means by which prion diseases can be both genetic and infectious. In addition, we know little about the mechanism by which neurons degenerate during prion diseases. Tied to this, the physiological role of the normal form of the prion protein remains unclear and it is uncertain whether or not loss of this function contributes to prion pathogenesis. The factors governing the transmission of prions between species remain unclear, in particular the means by which prion strains and PrP primary structure interact to affect inter-species prion transmission. Despite all these unknowns, advances in our understanding of prions have occurred because of their transmissibility to experimental animals and the development of transgenic (Tg) mouse models has done much to further our understanding about various aspects of prion biology. In this review we will focus on advances in our understanding of prion biology that

Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

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Rao, P. S. S.; Kumar, Santosh

2015-01-01

High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of CYP1A1 and CYP1B1, which are the major PAH-activating CYP enzymes. Our results have shown that treatment with cigarette smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers. PMID:26082767

75 FR 32190 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs...

Science.gov (United States)

2010-06-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Examining the Impact of... Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the...

Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease

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... Patient Page Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease Mariana Mirabel , Kumar Narayanan , Xavier Jouven , Eloi Marijon ... regurgitant ) valves. Over time, there is progressive damage (rheumatic heart disease, RHD) that may lead to heart failure, stroke, ...

Raman Spectroscopy: An Emerging Tool in Neurodegenerative Disease Research and Diagnosis.

Science.gov (United States)

Devitt, George; Howard, Kelly; Mudher, Amrit; Mahajan, Sumeet

2018-03-21

The pathogenesis underlining many neurodegenerative diseases remains incompletely understood. The lack of effective biomarkers and disease preventative medicine demands the development of new techniques to efficiently probe the mechanisms of disease and to detect early biomarkers predictive of disease onset. Raman spectroscopy is an established technique that allows the label-free fingerprinting and imaging of molecules based on their chemical constitution and structure. While analysis of isolated biological molecules has been widespread in the chemical community, applications of Raman spectroscopy to study clinically relevant biological species, disease pathogenesis, and diagnosis have been rapidly increasing since the past decade. The growing number of biomedical applications has shown the potential of Raman spectroscopy for detection of novel biomarkers that could enable the rapid and accurate screening of disease susceptibility and onset. Here we provide an overview of Raman spectroscopy and related techniques and their application to neurodegenerative diseases. We further discuss their potential utility in research, biomarker detection, and diagnosis. Challenges to routine use of Raman spectroscopy in the context of neuroscience research are also presented.

The Role of Pest Control Advisers in Preventative Management of Grapevine Trunk Diseases.

Science.gov (United States)

Hillis, Vicken; Lubell, Mark; Kaplan, Jonathan; Doll, David; Baumgartner, Kendra

2016-04-01

Vineyards with trunk diseases (Botryosphaeria dieback, Esca, Eutypa dieback, and Phomopsis dieback) can have negative returns in the long run. Minimizing economic impacts depends on effective management, but adopting a preventative practice after infection occurs may not improve yields. Pest control advisers may reduce grower uncertainty about the efficacy of and need for prevention, which often entails future and unobservable benefits. Here, we surveyed advisers in California to examine their influence over grower decision-making, in the context of trunk diseases, which significantly limit grape production and for which curative practices are unavailable. Our online survey revealed adviser awareness of high disease incidence, and reduced yields and vineyard lifespan. Advisers rated both preventative and postinfection practices positively. Despite higher cost estimates given to postinfection practices, advisers did not recommend preventative practices at higher rates. High recommendation rates were instead correlated with high disease incidence for both preventative and postinfection practices. Recommendation rates declined with increasing cost for preventative, but not for postinfection, practices. Our findings suggest that even when advisers acknowledge the risks of trunk diseases, they may not recommend preventative practices before infection occurs. This underscores the importance of clear outreach, emphasizing both the need for prevention and its long-term cost efficacy.

Fifty communities putting prevention to work: accelerating chronic disease prevention through policy, systems and environmental change.

Science.gov (United States)

Bunnell, Rebecca; O'Neil, Dara; Soler, Robin; Payne, Rebecca; Giles, Wayne H; Collins, Janet; Bauer, Ursula

2012-10-01

The burden of preventable chronic diseases is straining our nation's health and economy. Diseases caused by obesity and tobacco use account for the largest portions of this preventable burden. CDC funded 50 communities in 2010 to implement policy, systems, and environmental (PSE) interventions in a 2-year initiative. Funded communities developed PSE plans to reduce obesity, tobacco use, and second-hand smoke exposure for their combined 55 million residents. Community outcome objectives and milestones were categorized by PSE interventions as they related to media, access, promotion, pricing, and social support. Communities estimated population reach based on their jurisdiction's census data and target populations. The average proportion of each community's population that was reached was calculated for each intervention category. Outcome objectives that were achieved within 12 months of program initiation were identified from routine program records. The average proportion of a community's jurisdictional population reached by a specific intervention varied across interventions. Mean population reach for obesity-prevention interventions was estimated at 35%, with 14 (26%) interventions covering over 50% of the jurisdictional populations. For tobacco prevention, mean population reach was estimated at 67%, with 16 (84%) interventions covering more than 50% of the jurisdictional populations. Within 12 months, communities advanced over one-third of their obesity and tobacco-use prevention strategies. Tobacco interventions appeared to have higher potential population reach than obesity interventions within this initiative. Findings on the progress and potential reach of this major initiative may help inform future chronic disease prevention efforts.

A tale of two maladies? Pathogenesis of depression with and without the Huntington’s disease gene mutation

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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.

The pathogenesis of Ebola hemorrhagic fever.

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Takada, A; Kawaoka, Y

2001-10-01

Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenicity of this virus. There are also indications that genetically engineered vaccines, including plasmid DNA and viral vectors expressing Ebola virus proteins, and passive transfer of neutralizing antibodies could be feasible options for the control of Ebola virus-associated disease.

Pathogenesis of Idiopathic Pulmonary Fibrosis

Science.gov (United States)

Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

The Role of the spv Genes in Salmonella Pathogenesis

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Donald G. Guiney

2011-06-01

Full Text Available Salmonella strains cause three main types of diseases in people: gastroenteritis, enteric (typhoid fever, and non-typhoid extra-intestinal disease with bacteremia. Genetic analysis indicates that each clinical syndrome requires distinct sets of virulence genes, and Salmonella isolates differ in their constellation of virulence traits. The spv locus is strongly associated with strains that cause non-typhoid bacteremia, but are not present in typhoid strains. The spv region contains three genes required for the virulence phenotype in mice: the positive transcriptional regulator spvR and two structural genes spvB and spvC. SpvB and SpvC are translocated into the host cell by the SPI-2 type-three secretion system. SpvB prevents actin polymerization by ADP-ribosylation of actin monomers, while SpvC has phosphothreonine lyase activity and has been shown to inhibit MAP kinase signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection. Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive. This association is not seen with typhoid fever, indicating that the pathogenesis and immunology of typhoid have fundamental differences from the syndrome of non-typhoid bacteremia.

Melioidosis: An emerging infectious disease

Directory of Open Access Journals (Sweden)

Raja N

2005-01-01

Full Text Available Infectious diseases account for a third of all the deaths in the developing world. Achievements in understanding the basic microbiology, pathogenesis, host defenses and expanded epidemiology of infectious diseases have resulted in better management and reduced mortality. However, an emerging infectious disease, melioidosis, is becoming endemic in the tropical regions of the world and is spreading to non-endemic areas. This article highlights the current understanding of melioidosis including advances in diagnosis, treatment and prevention. Better understanding of melioidosis is essential, as it is life-threatening and if untreated, patients can succumb to it. Our sources include a literature review, information from international consensus meetings on melioidosis and ongoing discussions within the medical and scientific community.

Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore.

Science.gov (United States)

Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita

2014-01-01

The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults.

Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.

Science.gov (United States)

Scott, Lesley J

2016-09-01

Tetravalent, live-attenuated, dengue vaccine (Dengvaxia(®); CYD-TDV) is the first vaccine approved for the prevention of dengue disease caused by dengue virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high dengue endemic areas. This narrative review discusses the immunogenicity, protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of dengue disease. In Latin American and Asian phase 3 trials in children and adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was efficacious in preventing virologically-confirmed dengue (VCD) during the period from 28 days after the last dose (month 13) to month 25, meeting the primary endpoint criteria. Protective efficacy against VCD in the respective individual trials was 60.8 and 56.5 % (primary analysis). During the 25-month active surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in children aged 9 years and older. CYD-TDV was generally well tolerated, with no safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1) in ongoing long-term studies. Based on evidence from the dengue clinical trial program, the WHO SAGE recommended that countries with high dengue endemicity consider introducing CYD-TDV as part of an integrated disease prevention strategy to lower disease burden. Pharmacoeconomic considerations will be pivotal to implementing dengue vaccination prevention strategies in these countries. The availability of a dengue vaccine is considered essential if the 2012 WHO global strategy targets for reducing the burden of dengue disease by 2020 are to be attained. Hence, CYD-TDV represents a major advance for the prevention of dengue disease in high dengue endemic regions.

Prevention, screening and therapy of thyroid diseases and their cost-effectiveness

International Nuclear Information System (INIS)

Dietlein, M.; Moka, D.; Schmidt, M.; Theissen, P.; Schicha, H.

2003-01-01

Cost-effectivness analyses focused on benign thyroid diseases are under-represented in the literature. The calculation of costs per additionally gained life year is difficult: The benefit of prevention is shifted into the distant future. The influence of an untreated subclinical thyroid disease on life expectancy can only be demonstrated by a long-term follow-up and by epidemiological databases. Iodine supplementation and programs for the prevention of tobacco smoking (primary prevention) are very cost-effective. Smoking increases the risk both of multinodular goiter and of Graves' disease. Screening programs (secondary prevention) are discussed for the laboratory parameters thyrotropin (TSH), calcium and calcitonin. TSH testing seems to be very cost-effective for epidemiological considerations in a certain lifespan (newborn, pregnancy, postpartal), older persons, hospitalisation due to acute diseases and in persons with previously elevated TPO-antibodies for TSH-values >2 mU/l, but dedicated cost-effectiveness analyses are lacking. On the other hand, the cost-effectiveness of a routine TSH testing beyond the age of 35 years has been shown by a high-quality decision analysis. Therapeutic strategies (tertiary prevention) aim at the avoidance of complications (atrial fibrillation, myocardial infarction, death for cardiac reasons) and of iatrogenic complications. Examples of a tertiary prevention are: firstly the definitive therapy of Graves' disease in patients who have on increased risk of relapse after antithyroid drugs (ATD), secondly the radioiodine therapy for subclinical hyperthyroidism and the radioiodine therapy of large goiters in older patients or in patients suffering from a relevant comorbidity. Cost-effectiveness analyses for different therapeutic strategies of Graves' disease were published using a lifelong time-horizon. The ablative radioiodine dose-regime is cost-effective as a fist line therapy if the risk of relapse after ATD exceeds 60%. (orig

Role of antioxidants in disease and cancer prevention: a literature review

International Nuclear Information System (INIS)

Ahmed, I.; Ishtiaq, S.

2015-01-01

This review was written on data collected from, review articles, cross-sectional studies, randomized control trials, open-label studies, critical reviews, Cochrane data base system reviews, meta-analysis, population based trials, different phase-I and phase-II trials reported in literature between 1993 to 2014. Web sites and other online resources of Medline, NCBI, Pub med, Medscape resource centers, American college of surgeons were used to extract the data. The debate about the role of antioxidant therapy in disease or cancer prevention has long-loomed. Oxidative damage induced by free radicals has been implicated in most inflammatory and degenerative diseases. Scientific research has reported that the antioxidants may have a role in carcinogenesis, while antioxidant-containing fruits, vegetables may protect against some of these diseases while the role of supplements containing antioxidants in the prevention of chronic diseases remains unproven. This review provides basic information about antioxidants and summarizes different studies reported in literature about the role antioxidants in disease or cancer prevention. (author)

The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

Science.gov (United States)

Marsh, Sharon; Hu, Junbo; Feng, Wenke

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

Nutrition in the prevention and treatment of disease

National Research Council Canada - National Science Library

Coulston, Ann M; Boushey, Carol; Ferruzzi, Mario G

2013-01-01

.... Given its unique focus and extensive coverage of clinical applications and disease prevention, this edition is organized for easy integration into advanced upper-division or graduate nutrition curriculums...

Studies on the pathogenesis and management of prostate carcinoma in dogs

NARCIS (Netherlands)

L'Eplattenier, H.F.

2009-01-01

The dog is one of the few species to develop spontaneous prostate carcinoma (PCA) and is thus an attractive model for the study of the disease in humans. Many of the features of the disease in the dog are similar to its human counterpart, however a number of aspects of the pathogenesis, diagnosis

The Role of Aspirin in the Prevention of Cardiovascular Disease

Science.gov (United States)

Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

2014-01-01

Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

High-throughput screening for novel anti-infectives using a C. elegans pathogenesis model.

Science.gov (United States)

Conery, Annie L; Larkins-Ford, Jonah; Ausubel, Frederick M; Kirienko, Natalia V

2014-03-14

In recent history, the nematode Caenorhabditis elegans has provided a compelling platform for the discovery of novel antimicrobial drugs. In this protocol, we present an automated, high-throughput C. elegans pathogenesis assay, which can be used to screen for anti-infective compounds that prevent nematodes from dying due to Pseudomonas aeruginosa. New antibiotics identified from such screens would be promising candidates for treatment of human infections, and also can be used as probe compounds to identify novel targets in microbial pathogenesis or host immunity. Copyright © 2014 John Wiley & Sons, Inc.

The normal bacterial flora prevents GI disease

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. The normal bacterial flora prevents GI disease. Inhibits pathogenic enteric bacteria. Decrease luminal pH; Secrete bacteriocidal proteins; Colonization resistance; Block epithelial binding – induce MUC2. Improves epithelial and mucosal barrier integrity. Produce ...

Study of the participation of MMP-7, EMMPRIN and cyclophilin A in the pathogenesis of periodontal disease.

Science.gov (United States)

de Oliveira Nóbrega, Fernando José; de Oliveira, Denise Hélen Imaculada Pereira; Vasconcelos, Rodrigo Gadelha; Nonaka, Cassiano Francisco Weege; Queiroz, Lélia Maria Guedes

2016-12-01

Periodontal disease is an infectious disease resulting from the immunoinflammatory response of the host to microorganisms present in the dental biofilm which causes tissue destruction. The objective of this study was to evaluate the immunohistochemical expression of matrix metalloproteinase 7 (MMP-7), extracellular matrix metalloproteinase inducer (EMMPRIN) and cyclophilin A (CypA) in periodontal disease. Gingival tissue samples were divided as follows: clinically healthy gingiva (n=32), biofilm-induced gingivitis (n=28), and chronic periodontitis (n=30). Histological sections of 3μm were submitted to immunoperoxidase method and undergone quantitative analysis. The results were analyzed statistically by the Mann-Whitney and Spearman correlation tests, with the level of significance set at 0.05 (α=0.05). Immunopositivity for MMP-7, EMMPRIN and CypA differed significantly between the three groups, with higher percentages of staining in chronic periodontitis specimens, followed by chronic gingivitis and healthy gingiva specimens (pEMMPRIN (r=0.289; p=0.006). In addition, there was a significant positive correlation between probing depth and expression of MMP-7 (r=0.726; pEMMPRIN (r=0.345; p=0.001), and CypA (r=0.803; pEMMPRIN and CypA are associated with the pathogenesis and progression of periodontal disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of selected mediators of inflammation in the pathogenesis of cancer

Directory of Open Access Journals (Sweden)

Zofia Marchewka

2018-03-01

Full Text Available The role of the immune system, consisting of many different types of cells and proteins, is to recognize and/or reaction to “foreign material”. Disorders of the immune system, among others may lead to inflammatory diseases and cancers. The cytokines, such as IL-1, -2, -4, -6, -8, -10, -13, -15, -17 i IL-18, play an important, and often divergence role in the cancer progression. They can exhibit a different activity, often opposite, depending on their source as well as its activity in environmental. The article focuses in particular on three interleukins: IL-6, IL-8 and IL-18, discussing in detail their contribution to the pathogenesis of cancer. Current views on the role of these interleukins in the cancer pathogenesis in different aspects of this process are presented. Both their pro- and anti-tumor activity, their role in the proliferation, migration, growth and differentiation of cancer cells as well as in the promotion of tumor metastases to organs was described. We discussed their impact on the regulation of angiogenesis, the most important stage of tumor progression, and their role in the weakening of the process of apoptotic cell death. Presented data can be used to create practical guidelines in the cancer fighting (prevention and treatment by modulating the activity of these cytokines.

Urinary Tract Infection: Pathogenesis and Outlook.

Science.gov (United States)

McLellan, Lisa K; Hunstad, David A

2016-11-01

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

The modern features of pathogenesis-induced prevention of preeclampsia

Directory of Open Access Journals (Sweden)

Konkov D.G.

2016-03-01

Full Text Available Purpose — the assessment of clinical effectiveness of preventive therapy in pregnant women with high risk of preeclampsia. Patients and methods. In the comparative study on the effectiveness of preventive therapy were participated 110 pregnant women with decidual vasculopathy and endothelial dysfunction, which had high risk of preeclampsia. We investigated the clinical efficacy for medications that containing 75 mg of acetylsalicylic acid and L-arginine. Results. The results of the study have shown that use of preventive treatment (L-arginine and acetylsalicylic acid from 12 weeks, among pregnant women with high risk of preeclampsia, led to a significant decrease of perinatal loss, reduction of clinical manifestations of preeclampsia, preterm delivery, malformations and malpresentation of the placenta, cases of asphyxia of the newborns, perinatal CNS lesions and intra-ventricular hemorrhage. Conclusions. Clinical effectiveness of preventive treatment (L-arginine and ASA among pregnant women with high risk of preeclampsia was proven. Furthermore it was recognized clinically effective use of 75 mg of ASA from 12 weeks of pregnancy. No side effects of drugs in the study were noted.

Peroxisomal β-oxidation regulates whole body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease

Science.gov (United States)

Moreno-Fernandez, Maria E.; Giles, Daniel A.; Stankiewicz, Traci E.; Sheridan, Rachel; Karns, Rebekah; Cappelletti, Monica; Lampe, Kristin; Mukherjee, Rajib; Sina, Christian; Sallese, Anthony; Bridges, James P.; Hogan, Simon P.; Aronow, Bruce J.; Hoebe, Kasper

2018-01-01

Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression. Here, we show that mice with a point mutation in Acox1 (Acox1Lampe1) exhibited altered cellular metabolism, modified T cell polarization, and exacerbated immune cell inflammatory potential. Further, in context of a brief obesogenic diet stress, NAFLD progression associated with Acox1 mutation resulted in significantly accelerated and exacerbated hepatocellular damage via induction of profound histological changes in hepatocytes, hepatic inflammation, and robust upregulation of gene expression associated with HCC development. Collectively, these data demonstrate that β-oxidation links metabolism and immune responsiveness and that a better understanding of peroxisomal β-oxidation may allow for discovery of mechanisms central for NAFLD progression. PMID:29563328

Challenges and opportunities for primary, secondary, and tertiary prevention of Chagas' disease.

Science.gov (United States)

Rassi, A; Dias, J C P; Marin-Neto, J A; Rassi, A

2009-04-01

A century after its discovery, Chagas' disease still represents a major public health challenge in Latin America. Moreover, because of growing population movements, an increasing number of cases of imported Chagas' disease have now been detected in non-endemic areas, such as North America and some European countries. This parasitic zoonosis, caused by Trypanosoma cruzi, is transmitted to humans by infected Triatominae insects, or occasionally by non-vectorial mechanisms, such as blood transfusion, mother to fetus, or oral ingestion of materials contaminated with parasites. Following the acute phase of the infection, untreated individuals enter a chronic phase that is initially asymptomatic or clinically unapparent. Usually, a few decades later, 40-50% of patients develop progressive cardiomyopathy and/or motility disturbances of the oesophagus and colon. In the last decades several interventions targeting primary, secondary and tertiary prevention of Chagas' disease have been attempted. While control of both vectorial and blood transfusion transmission of T cruzi (primary prevention) has been successful in many regions of Latin America, early detection and aetiological treatment of asymptomatic subjects with Chagas' disease (secondary prevention) have been largely underutilised. At the same time, in patients with established chronic disease, several pharmacological and non-pharmacological interventions are currently available and have been increasingly used with the intention of preventing or delaying complications of the disease (tertiary prevention). In this review we discuss in detail each of these issues.

Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease

Directory of Open Access Journals (Sweden)

Priscilla Azambuja Lopes de Souza

2017-09-01

Full Text Available Coronary artery disease (CAD is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B, inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce.

Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive services Task Force recommendation statement.

Science.gov (United States)

Moyer, Virginia A

2014-04-15

Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on vitamin supplementation to prevent cardiovascular disease and cancer. The USPSTF reviewed the evidence on the efficacy of multivitamin or mineral supplements in the general adult population for the prevention of cardiovascular disease and cancer. This recommendation applies to healthy adults without special nutritional needs (typically aged 50 years or older). It does not apply to children, women who are pregnant or may become pregnant, or persons who are chronically ill or hospitalized or have a known nutritional deficiency. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of multivitamins for the prevention of cardiovascular disease or cancer. (I statement). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of single- or paired-nutrient supplements (except β-carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement). The USPSTF recommends against β-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation).

Diabetic kidney disease.

Science.gov (United States)

Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

2015-07-30

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

Molecular pathogenesis of intrahepatic cholangiocarcinoma

DEFF Research Database (Denmark)

Andersen, Jesper Bøje

2014-01-01

Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next-generation sequencing has begun to underline the persistent alterations, which may...

Preventing invasive Group B Streptococcus (GBS) disease in South ...

African Journals Online (AJOL)

9 No. 3 has been successfully used for the prevention of tetanus, influenza and pertussis in infants.[11] A trivalent GBS polysaccharide-protein conjugate vaccine (against serotypes Ia, Ib and III) has completed phase-II evaluation among pregnant women and has the potential to prevent 70 - 80% of all invasive GBS disease.

Routine Immunization of Adults in Canada: Review of the Epidemiology of Vaccine-Preventable Diseases and Current Recommendations for Primary Prevention

Directory of Open Access Journals (Sweden)

Michael D Parkins

2009-01-01

Full Text Available Vaccination is one of the greatest achievements in public health of the 20th century. However, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult Canadians. As a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. Accordingly, morbidity and mortality due to vaccine-preventable illnesses now occur disproportionately in adults. All Canadians, irrespective of age, should have immunity to measles, mumps, rubella, tetanus, diphtheria, pertussis and varicella. All adult Canadians with significant medical comorbidities or those older than 65 years of age should receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate influenza vaccines. The present review summarizes the burden of illness of these vaccine-preventable diseases in the Canadian adult population and reviews the current immunization recommendations. Vaccination of all Canadians to these common agents remains a vital tool to decrease individual morbidity and mortality and reduce the overall burden of preventable disease in Canada.

77 FR 29351 - Disease, Disability, and Injury Prevention and Control; Special Interest Projects (SIPs): Initial...

Science.gov (United States)

2012-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control; Special Interest Projects (SIPs): Initial Review The meeting.... L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the aforementioned...

The role of infant nutrition in the prevention of future disease

Directory of Open Access Journals (Sweden)

Ron eShaoul

2014-07-01

Full Text Available There is growing evidence that nutrition is part of the environmental factors affecting the incidence of various diseases. The effect starts in the prenatal life and affects fetal growth and continues in early life and throughout childhood. The effect has been shown on various disease states such as allergic diseases, hyperlipidemia and cardiovascular diseases, obesity, type II diabetes and metabolic syndrome and immunologic diseases such as celiac disease and type 1 diabetes mellitus. It seems that the recommendations of exclusive breastfeeding until the age of 4 months and subsequently exposure to various solid foods has beneficial effect in terms of allergic, immune and cardiovascular diseases prevention. Will these recommendations change the natural course of these diseases is unknown yet, but there is an accumulating evidence that indeed this is the case. In this review we review the evidence of early nutritional intervention and future disease prevention.

Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

Science.gov (United States)

Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-12-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer

Science.gov (United States)

... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer The U.S. Preventive Services Task Force ( ... and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer. This final recommendation statement applies to ...

Teleosts Genomics: Progress and Prospects in Disease Prevention and Control.

Science.gov (United States)

Munang'andu, Hetron Mweemba; Galindo-Villegas, Jorge; David, Lior

2018-04-04

Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs) as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL) mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

Teleosts Genomics: Progress and Prospects in Disease Prevention and Control

Directory of Open Access Journals (Sweden)

Hetron Mweemba Munang’andu

2018-04-01

Full Text Available Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

CAPS--pathogenesis, presentation and treatment of an autoinflammatory disease.

Science.gov (United States)

Kuemmerle-Deschner, Jasmin B

2015-07-01

The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare diseases. CAPS comprises the three conditions previously described as familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID), also known as chronic infantile neurologic, cutaneous, and articular (CINCA) syndrome. The clinical phenotype of CAPS is characterized by systemic inflammation. General symptoms are fatigue and fever. Local manifestations affect multiple tissues such as skin, joints, muscles, eyes, and the central nervous system. Distinct clinical features are characteristic for each subphenotype. In FCAS, these are cold-induced urticaria and fever, in MWS systemic amyloidosis and hearing loss and in NOMID/CINCA central nervous system inflammation and bone deformities. CAPS is caused by single heterozygous germline or somatic gain of function mutations in the NLRP3 gene encoding the protein cryopyrin. Cryopyrin nucleates an NLRP3 inflammasome, which regulates the activation and cleavage of caspase-1 that cleaves the pro-inflammatory cytokines, IL-1β and IL-18. IL-1β plays the key role in the induction of inflammation in CAPS. This has been confirmed by the application of IL-1 blocking agents, which lead not only to a rapid and sustained reversal of daily symptoms but also to some extent of long-term disease sequelae. To prevent CAPS-induced organ damage, early diagnosis and swift initiation of effective treatment are mandatory.

Simple Screening Instruments for Chronic Disease & Personalised Prevention at the Workplace

NARCIS (Netherlands)

M.A.J. Niessen (Maurice)

2014-01-01

markdownabstract__Abstract__ Prevention refers to actions directed to preventing illness and promoting health. It includes the assessment of disease risk and early diagnosis. Preventive strategies are most commonly classified based on the level of selection being applied in the target group or

76 FR 28789 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

Science.gov (United States)

2011-05-18

... NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office... Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC), announces the availability of a draft Alert entitled ``Preventing Occupational Respiratory Disease from...

76 FR 30366 - Draft Alert Entitled “Preventing Occupational Respiratory Disease From Dampness in Office...

Science.gov (United States)

2011-05-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-238] Draft Alert Entitled ``Preventing Occupational Respiratory Disease From Dampness in Office... Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. [FR Doc. 2011...

76 FR 27649 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

Science.gov (United States)

2011-05-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial Review The meeting... Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the...

75 FR 30410 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Provider...

Science.gov (United States)

2010-06-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Provider and Public Health... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC...

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

Pathogenesis of Mycobacterium bovis Infection: the Badger Model As a Paradigm for Understanding Tuberculosis in Animals

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Eamonn Gormley

2018-01-01

Full Text Available Tuberculosis in animals is caused principally by infection with Mycobacterium bovis and the potential for transmission of infection to humans is often the fundamental driver for surveillance of disease in livestock and wild animals. However, with such a vast array of species susceptible to infection, it is often extremely difficult to gain a detailed understanding of the pathogenesis of infection––a key component of the epidemiology in all affected species. This is important because the development of disease control strategies in animals is determined chiefly by an understanding of the epidemiology of the disease. The most revealing data from which to formulate theories on pathogenesis are that observed in susceptible hosts infected by natural transmission. These data are gathered from detailed studies of the distribution of gross and histological lesions, and the presence and distribution of infection as determined by highly sensitive bacteriology procedures. The information can also be used to establish the baseline for evaluating experimental model systems. The European badger (Meles meles is one of a very small number of wild animal hosts where detailed knowledge of the pathogenesis of M. bovis infection has been generated from observations in natural-infected animals. By drawing parallels from other animal species, an experimental badger infection model has also been established where infection of the lower respiratory tract mimics infection and the disease observed in natural-infected badgers. This has facilitated the development of diagnostic tests and testing of vaccines that have the potential to control the disease in badgers. In this review, we highlight the fundamental principles of how detailed knowledge of pathogenesis can be used to evaluate specific intervention strategies, and how the badger model may be a paradigm for understanding pathogenesis of tuberculosis in any affected wild animal species.

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

Energy Technology Data Exchange (ETDEWEB)

Iwakiri, Dai [Institute for Genetic Medicine, Hokkaido University, N15 W7 Kita-Ku, Sapporo 060-0815 (Japan)

2014-08-06

The Epstein-Barr virus (EBV) is known as an oncogenic herpesvirus that has been implicated in the pathogenesis of various malignancies. EBV-encoded RNAs (EBERs) are non-coding RNAs expressed abundantly in latently EBV-infected cells. Herein, I summarize the current understanding of the functions of EBERs, including the interactions with cellular factors through which EBERs contribute to EBV-mediated pathogenesis. Previous studies have demonstrated that EBERs are responsible for malignant phenotypes in lymphoid cells, and can induce several cytokines that can promote the growth of various EBV-infected cancer cells. EBERs were also found to bind retinoic acid-inducible gene I (RIG-I) and thus activate its downstream signaling. Furthermore, EBERs induce interleukin-10, an autocrine growth factor for Burkitt’s lymphoma cells, by activating RIG-I/interferon regulatory factor 3 pathway, suggesting that EBER-mediated innate immune signaling modulation contributes to EBV-mediated oncogenesis. Recently, EBV-infected cells were reported to secret EBERs, which were then recognized by toll-like receptor 3 (TLR3), leading to the induction of type I interferon and inflammatory cytokines, and subsequent immune activation. Furthermore, EBER1 was detected in the sera of patients with active EBV-infectious diseases, suggesting that EBER1-meidated TLR3 signaling activation could account for the pathogenesis of active EBV-infectious diseases.

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

International Nuclear Information System (INIS)

Iwakiri, Dai

2014-01-01

The Epstein-Barr virus (EBV) is known as an oncogenic herpesvirus that has been implicated in the pathogenesis of various malignancies. EBV-encoded RNAs (EBERs) are non-coding RNAs expressed abundantly in latently EBV-infected cells. Herein, I summarize the current understanding of the functions of EBERs, including the interactions with cellular factors through which EBERs contribute to EBV-mediated pathogenesis. Previous studies have demonstrated that EBERs are responsible for malignant phenotypes in lymphoid cells, and can induce several cytokines that can promote the growth of various EBV-infected cancer cells. EBERs were also found to bind retinoic acid-inducible gene I (RIG-I) and thus activate its downstream signaling. Furthermore, EBERs induce interleukin-10, an autocrine growth factor for Burkitt’s lymphoma cells, by activating RIG-I/interferon regulatory factor 3 pathway, suggesting that EBER-mediated innate immune signaling modulation contributes to EBV-mediated oncogenesis. Recently, EBV-infected cells were reported to secret EBERs, which were then recognized by toll-like receptor 3 (TLR3), leading to the induction of type I interferon and inflammatory cytokines, and subsequent immune activation. Furthermore, EBER1 was detected in the sera of patients with active EBV-infectious diseases, suggesting that EBER1-meidated TLR3 signaling activation could account for the pathogenesis of active EBV-infectious diseases

Prevention and management of non-communicable disease: the IOC consensus statement, Lausanne 2013.

Science.gov (United States)

Matheson, Gordon O; Klügl, Martin; Engebretsen, Lars; Bendiksen, Fredrik; Blair, Steven N; Börjesson, Mats; Budgett, Richard; Derman, Wayne; Erdener, Uğur; Ioannidis, John P A; Khan, Karim M; Martinez, Rodrigo; van Mechelen, Willem; Mountjoy, Margo; Sallis, Robert E; Schwellnus, Martin; Shultz, Rebecca; Soligard, Torbjørn; Steffen, Kathrin; Sundberg, Carl Johan; Weiler, Richard; Ljungqvist, Arne

2013-11-01

Morbidity and mortality from preventable, non-communicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April, 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: 1. Focus on behavioural change as the core component of all clinical programs for the prevention and management of chronic disease. 2. Establish actual centres to design, implement, study, and improve preventive programs for chronic disease. 3. Use human-centered design in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. 4. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet and lifestyle. 5. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad-hoc Working Group charged with the responsibility of moving this

Is the high-risk strategy to prevent cardiovascular disease equitable?

DEFF Research Database (Denmark)

Wallach Kildemoes, Helle; Diderichsen, Finn; Krasnik, Allan

2012-01-01

ABSTRACT: BACKGROUND: Statins are increasingly prescribed to prevent cardiovascular disease (CVD) in asymptomatic individuals. Yet, it is unknown whether those at higher CVD risk - i.e. individuals in lower socio-economic position (SEP) - are adequately reached by this high-risk strategy. Aim......: To examine whether the Danish implementation of the strategy to prevent cardiovascular disease (CVD) by initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals is equitable across socioeconomic groups. METHODS: Design: Cohort study. Setting and participants: Applying individual...

Prevention programs for chronic kidney disease in low-income countries.

Science.gov (United States)

Perico, Norberto; Remuzzi, Giuseppe

2016-04-01

Chronic kidney disease (CKD) is an important determinant of the poor health outcome for major noncommunicable diseases that are the leading cause of death worldwide. Early recognition with screening programs of CKD and co-morbid conditions, like hypertension, diabetes, or toxic environments, can potentially slow progression to renal failure, improve quality of life and reduce healthcare cost. Effective multimodal tools are available to prevent CKD by managing its risk factors, and to slow or even halt disease progression to end-stage renal failure (ESRF). They can be adapted even to poor-resource settings of low- and middle-income countries for individual at high risk of CKD. CKD is also linked to acute kidney injury (AKI), that in poorest part of Africa, Asia and Latin America is preventable, treatable and often reversible, if managed adequately and in timely manner as proposed by the program "AKI 0by25" launched by the international Society of Nephrology in 2013. In addition to saving lives, prevention programs will create major heath gains, eventually reducing the current health inequity that arises from unaffordable or unobtainable renal replacement therapies in many part of the developing world if ESRF is not prevented.

The re-emergency and persistence of vaccine preventable diseases

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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.

The microbiome-metabolome crosstalk in the pathogenesis of respiratory fungal diseases.

Science.gov (United States)

Gonçalves, Samuel M; Lagrou, Katrien; Duarte-Oliveira, Cláudio; Maertens, Johan A; Cunha, Cristina; Carvalho, Agostinho

2017-08-18

Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and pathogen exposure. There is increasing evidence that the individual microbiome supervises the outcome of the host-fungus interaction by influencing mechanisms of immune regulation, inflammation, metabolism, and other physiological processes. Microbiome-mediated mechanisms of resistance allow therefore the control of fungal colonization, preventing the onset of overt disease, particularly in patients with underlying immune dysfunction. Here, we review this emerging area of research and discuss the contribution of the microbiota (and its dysbiosis), including its immunoregulatory properties and relationship with the metabolic activity of commensals, to respiratory fungal diseases. Finally, we highlight possible strategies aimed at decoding the microbiome-metabolome dialog and at its exploitation toward personalized medical interventions in patients at high risk of infection.

Research advances in animal models of nonalcoholic fatty liver disease

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HUANG Haiyan

2014-09-01

Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.

Therapeutic approaches to preventing cell death in Huntington disease.

Science.gov (United States)

Kaplan, Anna; Stockwell, Brent R

2012-12-01

Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influenza vaccines for preventing cardiovascular disease

OpenAIRE

Clar,Christine; Oseni,Zainab; Flowers,Nadine; Keshtkar-Jahromi,Maryam; Rees,Karen

2015-01-01

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 Coch...

Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage.

Science.gov (United States)

Hill, Sarah J; Mordes, Daniel A; Cameron, Lisa A; Neuberg, Donna S; Landini, Serena; Eggan, Kevin; Livingston, David M

2016-11-29

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function of at least one of these proteins leads to an accumulation of transcription-associated DNA damage contributing to motor neuron cell death and progressive neurological symptoms. In support of this hypothesis, we find that FUS or TDP43 depletion leads to increased sensitivity to a transcription-arresting agent due to increased DNA damage. Thus, these proteins normally contribute to the prevention or repair of transcription-associated DNA damage. In addition, both FUS and TDP43 colocalize with active RNA polymerase II at sites of DNA damage along with the DNA damage repair protein, BRCA1, and FUS and TDP43 participate in the prevention or repair of R loop-associated DNA damage, a manifestation of aberrant transcription and/or RNA processing. Gaining a better understanding of the role(s) that FUS and TDP43 play in transcription-associated DNA damage could shed light on the mechanisms underlying ALS pathogenesis.

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

Science.gov (United States)

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

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MILENA B. P. SOARES

2001-12-01

Full Text Available Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC, the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.A doença de Chagas constitui um grave problema de saúde pública na América Latina, onde é uma das principais causas de problemas cardíacos. A cardiopatia chagásica crônica (CChC, forma mais grave da doença, manifesta-se em cerca de 25% dos indivíduos infectados pelo Trypanosoma cruzi, e é caracterizada, a nível histopatológico, pela presença de infiltrados

Probiotics: their role in the treatment and prevention of disease.

Science.gov (United States)

Doron, Shira; Gorbach, Sherwood L

2006-04-01

A probiotic is a "live microbial food ingredients that, when ingested in sufficient quantities, exerts health benefits on the consumer". Probiotics exert their benefits through several mechanisms; they prevent colonization, cellular adhesion and invasion by pathogenic organisms, they have direct antimicrobial activity and they modulate the host immune response. The strongest evidence for the clinical effectiveness of probiotics has been in their use for the prevention of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of antibiotic-associated gastrointestinal side effects and the prevention and treatment of allergy manifestations. More research needs to be carried out to clarify conflicting findings on the use of probiotics for prevention of travelers' diarrhea, infections in children in daycare and dental caries, and elimination of nasal colonization with potentially pathogenic bacteria. Promising ongoing research is being conducted on the use of probiotics for the treatment of Clostridium difficile colitis, treatment of Helicobacter pylori infection, treatment of inflammatory bowel disease and prevention of relapse, treatment of irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis patients, and prevention of necrotizing enterocolitis in premature infants. Finally, areas of future research include the use of probiotics for the treatment of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus-host disease in bone marrow transplant recipients.

Psoriatic arthritis: from pathogenesis to therapy.

LENUS (Irish Health Repository)

Fitzgerald, Oliver

2012-02-01

Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

An Overview on the Role of α -Synuclein in Experimental Models of Parkinson's Disease from Pathogenesis to Therapeutics.

Science.gov (United States)

Javed, Hayate; Kamal, Mohammad Amjad; Ojha, Shreesh

2016-01-01

Parkinson's disease (PD) is a devastating and progressive movement disorder characterized by symptoms of muscles rigidity, tremor, postural instability and slow physical movements. Biochemically, PD is characterized by lack of dopamine production and its action due to loss of dopaminergic neurons and neuropathologically by the presence of intracytoplasmic inclusions known as Lewy bodies, which mainly consist of presynaptic neuronal protein, α-synuclein (α-syn). It is believed that alteration in α-syn homeostasis leads to increased accumulation and aggregation of α-syn in Lewy body. Based on the important role of α-syn from pathogenesis to therapeutics, the recent researches are mainly focused on deciphering the critical role of α-syn at advanced level. Being a major protein in Lewy body that has a key role in pathogenesis of PD, several model systems including immortalized cell lines (SH-SY5Y), primary neuronal cultures, yeast (saccharomyces cerevisiae), drosophila (fruit flies), nematodes (Caenorhabditis elegans) and rodents are being employed to understand the PD pathogenesis and treatment. In order to study the etiopathogensis and develop novel therapeutic target for α -syn aggregation, majority of investigators rely on toxin (rotenone, 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine, 6-hydroxydopamine, paraquat)-induced animal models of PD as a tool for basic research. Whereas, cell and tissue based models are mostly utilized to elucidate the mechanistic and molecular pathways underlying the α -syn induced toxicity and therapeutic approaches in PD. Gene modified mouse models based on α-syn expression are fascinating for modeling familial PD and toxin induced models provide a suitable approach for sporadic PD. The purpose of this review is to provide a summary and a critical review of the involvement of α-syn in various in vitro and in vivo models of PD based on use of neurotoxins as well as genetic modifications.

Syringic Acid Extracted from Herba dendrobii Prevents Diabetic Cataract Pathogenesis by Inhibiting Aldose Reductase Activity

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Xiaoyong Wei

2012-01-01

Full Text Available Objective. Effects of Syringic acid (SA extracted from dendrobii on diabetic cataract (DC pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17 μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC.

Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

Science.gov (United States)

Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects

DEFF Research Database (Denmark)

Allez, Matthieu; Karmiris, Konstantinos; Louis, Edouard

2010-01-01

The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts....... This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists...

Astrovirus Pathogenesis

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Cydney Johnson

2017-01-01

Full Text Available Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1 in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems.

76 FR 4911 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational...

Science.gov (United States)

2011-01-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Occupational Safety and Health...)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and...

Aspirin for Primary Prevention of Cardiovascular Disease and Cancer. A Benefit and Harm Analysis

NARCIS (Netherlands)

Stegeman, Inge; Bossuyt, Patrick M.; Yu, Tsung; Boyd, Cynthia; Puhan, Milo A.

2015-01-01

Aspirin is widely used for prevention of cardiovascular disease. In recent years randomized trials also suggested a preventive effect for various types of cancer. We aimed to assess, in a quantitative way, benefits and harms of aspirin for primary prevention of both cardiovascular disease and cancer

[Current situation of human resources of parasitic disease control and prevention organizations in Henan Province].

Science.gov (United States)

Ya-Lan, Zhang; Yan-Kun, Zhu; Wei-Qi, Chen; Yan, Deng; Peng, Li

2018-01-10

To understand the current status of human resources of parasitic disease control and prevention organizations in Henan Province, so as to provide the reference for promoting the integrative ability of the prevention and control of parasitic diseases in Henan Province. The questionnaires were designed and the method of census was adopted. The information, such as the amounts, majors, education background, technical titles, working years, and turnover in each parasitic disease control and prevention organization was collected by the centers for disease control and prevention (CDCs) at all levels. The data were descriptively analyzed. Totally 179 CDCs were investigated, in which only 19.0% (34/179) had the independent parasitic diseases control institution (department) . There were only 258 full-time staffs working on parasitic disease control and prevention in the whole province, in which only 61.9% (159/258) were health professionals. Those with junior college degree or below in the health professionals accounted for 60.3% (96/159) . Most of them (42.1%) had over 20 years of experience, but 57.9% (92/159) of their technical post titles were at primary level or below. The proportion of the health professionals is low in the parasitic disease control and prevention organizations in Henan Province. The human resource construction for parasitic disease control and prevention at all levels should be strengthened.

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD in Choline Deficient Diet Fed Rats

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Lopasso Fabio P

2003-10-01

Full Text Available Abstract Aim Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD. Vitamin C and vitamin E are known to react with reactive oxygen species (ROS blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E in its prevention. Methods Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6 – (200 mg/day, vitamin C (n = 6 (30 mg/Kg/day or vehicle orally. Results In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx103 as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx103, respectively (p Conclusions 1 Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Prevention of Alzheimer disease: The roles of nutrition and primary care.

Science.gov (United States)

Bane, Tabitha J; Cole, Connie

2015-05-15

Risk factors for developing Alzheimer disease include hypercholesterolemia, hypertension, obesity, and diabetes. Due to lack of effective treatments for Alzheimer disease, nutrition and primary prevention becomes important.

78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Science.gov (United States)

2013-10-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Health Promotion and Disease Prevention Research Centers, Funding Opportunity...

Preventing Occupational Skin Disease: A Review of Training Programs.

Science.gov (United States)

Zack, Bethany; Arrandale, Victoria H; Holness, D Linn

Occupational contact dermatitis (OCD) is a common occupational disease that impacts a variety of worker groups. Skin protection and disease prevention training programs have shown promise for improving prevention practices and reducing the incidence of OCD. This review details the features of training programs for primary prevention of OCD and identifies gaps in the literature. Twelve studies were identified for in-depth review: many studies included wet workers employed in health care, hairdressing, cleaning, and food preparation; 1 program featured manufacturing workers. Few programs provided content on allergic contact dermatitis, and only 1 was evaluated for long-term effectiveness. Effective programs were similar in content, delivery method, and timing and were characterized by industry specificity, multimodal learning, participatory elements, skin care resource provision, repeated sessions, and management engagement. Long-term effectiveness, generalizability beyond OCD, workplace health and safety culture impact, and translation of programs in the North American context represent areas for future research.

Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

Science.gov (United States)

Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

2016-02-14

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

Tibetan medicine "RNSP" in treatment of Alzheimer disease.

Science.gov (United States)

Shi, Jing-Ming; He, Xue; Lian, Hui-Juan; Yuan, Dong-Ya; Hu, Qun-Ying; Sun, Zheng-Qi; Li, Yan-Song; Zeng, Yu-Wen

2015-01-01

Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD.

Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance.

Directory of Open Access Journals (Sweden)

Caihong Zhu

Full Text Available Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.

The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.

Science.gov (United States)

Kerr, Jonathan R

2016-04-01

Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. 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/

Primary and Secondary Prevention Trials in Alzheimer Disease: Looking Back, Moving Forward

Science.gov (United States)

Hsu, David C.; Marshall, Gad A.

2015-01-01

The field of Alzheimer disease (AD) prevention has been a culmination of basic science, clinical, and translational research. In the past three years since the new 2011 AD diagnostic guidelines, large-scale collaborative efforts have embarked on new clinical trials with the hope of someday preventing AD. This review will shed light on the historical and scientific contexts in which these trials were based on, as well as discuss potential challenges these trials may face in the coming years. Primary preventive measures, such as lifestyle, multidomain, medication, and supplemental interventions, will be analyzed. Secondary prevention as represented by disease-modifying interventions, such as anti-amyloid therapy and pioglitazone, will also be reviewed. Finally, hypotheses on future directions for AD prevention trials will be proposed. PMID:27697063

78 FR 35035 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review

Science.gov (United States)

2013-06-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review The meeting announced below concerns Centers for Disease Control and Prevention Public Health Preparedness and Response...

78 FR 36785 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Science.gov (United States)

2013-06-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Centers for Disease Control and Prevention Public Health Preparedness and Response...

76 FR 29756 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Science.gov (United States)

2011-05-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Centers for Agricultural Disease and Injury Research, Education, and Prevention...

Immune regulation in T1D and T2D: prospective role of Foxp3+ Treg cells in disease pathogenesis and treatment

Directory of Open Access Journals (Sweden)

Mara eKornete

2013-06-01

Full Text Available There is increasing evidence that dysregulated immune responses play key roles in the pathogenesis and complications of type 1 but also type 2 diabetes. Indeed, chronic inflammation and autoimmunity, which are salient features of type 1 diabetes, are now believed to actively contribute to the pathogenesis of type 2 diabetes. The accumulation of activated innate and adaptive immune cells in various metabolic tissues results in the release of inflammatory mediators, which promote insulin resistance and β-cell damage. Moreover, these dysregulated immune responses can also mutually influence the prevalence of both type 1 and 2 diabetes. In this review article, we discuss the central role of immune responses in the patho-physiology and complications of type 1 and 2 diabetes, and provide evidence that regulation of these responses, particularly through the action of regulatory T cells, may be a possible therapeutic avenue for the treatment of these disease and their respective complications.

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.

Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

Directory of Open Access Journals (Sweden)

Nancy Magee

2016-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL to nonalcoholic steatohepatitis (NASH and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning, inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.

Preventable Deaths from Heart Disease and Stroke PSA (:60)

Centers for Disease Control (CDC) Podcasts

2013-09-03

This 60 second public service announcement is based on the September 2013 CDC Vital Signs report. More than 800,000 Americans die each year from heart disease and stroke. Learn how to manage all the major risk factors.  Created: 9/3/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/3/2013.

Biomechanical considerations in the pathogenesis of osteoarthritis of the knee

NARCIS (Netherlands)

Heijink, Andras; Gomoll, Andreas H.; Madry, Henning; Drobnič, Matej; Filardo, Giuseppe; Espregueira-Mendes, João; van Dijk, C. Niek

2012-01-01

Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an

Epidemiology and prevention of coronary heart disease in families.

Science.gov (United States)

Higgins, M

2000-04-01

Although family histories are used primarily to aid in diagnosis and risk assessment, their value is enhanced when the family is considered as a unit for research and disease prevention. The value of a family history of coronary heart disease (CHD) is increased when the age, sex, number of relatives, and age at onset of disease are incorporated in a quantitative family risk score. Medical and lifestyle risk factors that aggregate in families include dyslipidemia, hypertension, obesity, hyperfibrinogenemia, diabetes mellitus, smoking habits, eating patterns, alcohol consumption, physical activity, and socioeconomic status. Advances in detecting and understanding interactions between genetic susceptibility and modifiable risk factors should lead to improvements in prevention and treatment. However, working with families can be difficult. In the United States, families are usually small, are often widely dispersed, and may not be intact. Family histories may be unknown, affected relatives may be dead, and secular trends mask similarities among generations. Many exposures occur outside the home, and families change over time. Ethical, legal, and social issues arise when dealing with families. Nevertheless, opportunities are missed when research, clinical practice, and prevention focus on individual patients. Greater emphasis on families is needed to reduce the burden of CHD.

Vaccines for prevention of group B meningococcal disease: Not your father's vaccines.

Science.gov (United States)

Harrison, Lee H

2015-11-27

For decades, there was no licensed vaccine for prevention of endemic capsular group B meningococcal disease, despite the availability of vaccines for prevention of the other most common meningococcal capsular groups. Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease. These issues are discussed in this review. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

[Problem of motivation of the population to prevention and treatment dental diseases].

Science.gov (United States)

Kochlashvili, L Sh; Gogilashvili, K T; Gerzmava, O Kh

2012-10-01

Dental health is an integral part of a normal state of a human body and, first of all, depends on knowledge of the population of bases of individual hygiene of an oral cavity and ability to use them in practical life. Numerous researches indicate low level of knowledge of the population in questions of prevention of dental diseases and individual hygiene of an oral cavity that testifies to existence of problems in the organization of sanitary education. Existing practice of hygienic training and education, in a certain measure, lags behind modern requirements, and some questions demand specification and optimization. For efficiency of sanitary and preventive actions it is necessary to study character and motivation structure to prevention and treatment of dental diseases and to develop an effective method of its increase. Therefore actual search of new forms of psycho hygiene and psycho prevention with use of modern information technologies which should provide high level of dental health of the military personnel is represented. The purpose of the real research was establishment of the factors forming motivation to prevention and treatment of the main dental diseases, and development of a psycho physiological method of its increase. The carried-out research allows to expand and systematize ideas necessary for the practical doctor of the major factors forming motivation to prevention and treatment of the main dental diseases. Development of an objective technique of a complex assessment of level of motivation of patients to prevention and treatment of dental pathology will allow to prove the new perspective direction of the sanitary educational work, allowing to reduce fobiya level, effectively to increase motivation of the patient to receiving the timely dental help. It especially is important if to consider that numerous programs of hygienic training and the education, applied in our country, didn't lead to change of hygienic skills of the population in expected

Prediabetes and Lifestyle Modification: Time to Prevent a Preventable Disease

Science.gov (United States)

Tuso, Phillip

2014-01-01

More than 100 million Americans have prediabetes or diabetes. Prediabetes is a condition in which individuals have blood glucose levels higher than normal but not high enough to be classified as diabetes. People with prediabetes have an increased risk of Type 2 diabetes. An estimated 34% of adults have prediabetes. Prediabetes is now recognized as a reversible condition that increases an individual’s risk for development of diabetes. Lifestyle risk factors for prediabetes include overweight and physical inactivity. Increasing awareness and risk stratification of individuals with prediabetes may help physicians understand potential interventions that may help decrease the percentage of patients in their panels in whom diabetes develops. If untreated, 37% of the individuals with prediabetes may have diabetes in 4 years. Lifestyle intervention may decrease the percentage of prediabetic patients in whom diabetes develops to 20%. Long-term data also suggest that lifestyle intervention may decrease the risk of prediabetes progressing to diabetes for as long as 10 years. To prevent 1 case of diabetes during a 3-year period, 6.9 persons would have to participate in the lifestyle intervention program. In addition, recent data suggest that the difference in direct and indirect costs to care for a patient with prediabetes vs a patient with diabetes may be as much as $7000 per year. Investment in a diabetes prevention program now may have a substantial return on investment in the future and help prevent a preventable disease. PMID:25102521

75 FR 78997 - Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA...

Science.gov (United States)

2010-12-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA) Advisory Committee... and other committee management activities, for both the Centers for Disease Control and Prevention and...

75 FR 28626 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): SIP 10...

Science.gov (United States)

2010-05-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): SIP 10-029, Pilot Study... Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the...

Making the workplace a more effective site for prevention of noncommunicable diseases in adults.

Science.gov (United States)

Tryon, Katherine; Bolnick, Howard; Pomeranz, Jennifer L; Pronk, Nicolaas; Yach, Derek

2014-11-01

Efforts to realize the potential of disease prevention in the United States have fallen behind those of peer countries, and workplace disease prevention is a major gap. This article investigates the reasons for this gap. Literature review and expert discussions. Obstacles to effective use of workplace disease prevention include limited leadership and advocacy, poor alignment of financial incentives, limitations in research quality and investment, regulation that does not support evidence-based practice, and a dearth of community-employer partnerships. We make recommendations to address these obstacles, such as the inclusion of health metrics in corporate reporting, making the workplace a central component of the strategy to combat the effect of noncommunicable diseases, and linking prevention directly benefit businesses' bottom lines.

The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease

DEFF Research Database (Denmark)

Hua, Xiaoqin; Deuse, Tobias; Chen, Yi-Je

2013-01-01

The calcium-activated potassium channel KCa3.1 is critically involved in T-cell activation as well as in the proliferation of smooth muscle cells and fibroblasts. We sought to investigate whether KCa3.1 contributes to the pathogenesis of obliterative airway disease (OAD) and whether knockout or p...

Care provision to prevent chronic disease by community mental health clinicians.

Science.gov (United States)

Bartlem, Kate M; Bowman, Jennifer A; Freund, Megan; Wye, Paula M; McElwaine, Kathleen M; Wolfenden, Luke; Campbell, Elizabeth M; Gillham, Karen E; Wiggers, John H

2014-12-01

People with a mental illness have higher prevalence of behavioral risks for chronic disease than the general population. Despite recommendations regarding the provision of preventive care by mental health services, limited research has examined the extent to which such care is provided. To examine mental health clinician provision of care for preventable chronic disease risks, and whether such care was associated with the availability of practice support strategies. A cross-sectional survey was undertaken of 151 community mental health clinicians in New South Wales, Australia regarding the provision of three elements of preventive care (i.e., assessment, brief advice, and referral/follow-up) for four health risk behaviors (i.e., tobacco smoking, inadequate fruit and vegetable consumption, harmful alcohol consumption, and inadequate physical activity). Clinicians reported the availability of 16 strategies to support such care delivery. Data were collected in 2010 and analyzed in 2012-2013. Preventive care provision varied by both care element and risk behavior. Optimal care (each care element provided to at least 80% of clients for all health behaviors) was provided by few clinicians: assessment (8.6%), brief advice (24.5%), and referral/follow-up (9.9%). Less than half of clinicians reported more than four support strategies were available (44.4%). The availability of five or more strategies was associated with increased optimal preventive care. The provision of preventive care focused on chronic disease prevention in community mental health services is suboptimal. Interventions to increase the routine provision of such care should involve increasing the availability of evidence-based strategies to support care provision. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

Science.gov (United States)

D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-01-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

Pasos Adelante: the effectiveness of a community-based chronic disease prevention program.

Science.gov (United States)

Staten, Lisa K; Scheu, Linda L; Bronson, Dan; Peña, Veronica; Elenes, JoJean

2005-01-01

Implementing programs that target primary prevention of chronic diseases is critical for at-risk populations. Pasos Adelante, or "Steps Forward," is a curriculum aimed at preventing diabetes, cardiovascular disease, and other chronic diseases in Hispanic populations. Pasos Adelante is adapted from the National Heart, Lung, and Blood Institute's cardiovascular disease prevention curriculum, Su Corazon, Su Vida, and includes sessions on diabetes and community advocacy and incorporates walking clubs. The Pasos Adelante curriculum was implemented in two Arizona, United States-Sonora, Mexico border counties. Key issues in these communities are safety, access to recreational facilities, climate, and cultural beliefs. Pasos Adelante is a 12-week program facilitated by community health workers. The program includes interactive sessions on chronic disease prevention, nutrition, and physical activity. Evaluation of the program included precurriculum and postcurriculum questionnaires with self-reported measures of physical activity and dietary patterns. Approximately 250 people participated in the program in Yuma and Santa Cruz counties. Postprogram evaluation results demonstrate a significant increase in moderate to vigorous walking among participants and shifts in nutritional patterns. The Pasos Adelante program demonstrates that an educational curriculum in conjunction with the support of community health workers can motivate people in Arizona/Sonora border communities to adopt healthy lifestyle behaviors.

Immunological Mechanisms Implicated in the Pathogenesis of Chronic Urticaria and Hashimoto Thyroiditis.

Science.gov (United States)

Berghi, Nicolae Ovidiu

2017-08-01

Autoimmunity represents the attack of the immune system of an organism against its own cells and tissues. Autoimmune diseases may affect one organ (Hashimoto thyroiditis) or can be systemic (chronic urticaria). Many factors are implicated in the pathogenesis of autoimmunity (white cells, cytokines, chemokines). Hashimoto thyroiditis has been associated with chronic urticaria in the last 3 decades in a number of clinical studies. Anti-thyroid antibodies have been documented in a proportion ranging from 10% to 30% in chronic urticaria patients in different countries from 3 continents. Two of the factors involved in the mechanism of autoimmunity are present both in the pathophysiology of Hashimoto thyroiditis and chronic urticaria. According to recent studies, IL6 is implicated in the pathogenesis of both diseases. TregsCD4+CD25+Foxp3+ cells have also been implicated in the pathological mechanisms of these 2 entities. This review offers an explanation of the clinical and statistical association between these two diseases from the pathophysiological point of view.

Diabetic nephropathy. Is end-stage renal disease inevitable?

Science.gov (United States)

Bogusky, R T

1983-10-01

The appearance of proteinuria in an insulin-dependent diabetic patient is an ominous sign. Proteinuria heralds the presence of diabetic nephropathy and early death, or chronic renal failure requiring dialysis or transplantation, in 50% of patients. The pathogenesis of diabetic nephropathy is unknown. Adequate insulin administration is the most important preventive measure. Hypertension, if present, should be aggressively treated to delay progression of renal disease. Good nutrition, prompt treatment of urinary tract infections, and caution in the use of radiocontrast agents are other important preventive measures. Hemodialysis, peritoneal dialysis, and transplantation are options for patients with end-stage renal disease. No matter which is selected, the patient may still have multiple amputations, blindness, congestive heart failure, infections, and uncontrolled glycemia. Advancements are being made, however, that promise a better future for insulin-dependent diabetics.

Leaky gut and autoimmune diseases.

Science.gov (United States)

Fasano, Alessio

2012-02-01

Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

Science.gov (United States)

Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

2014-01-01

Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular

78 FR 23768 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Science.gov (United States)

2013-04-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting... Centers for Disease Control and Prevention (CDC) announces the aforementioned SEP: Time and Date: 1:00 p.m...

Primary prevention of cardiovascular diseases: A cost study in family practices

NARCIS (Netherlands)

E.W. de Bekker-Grob (Esther); S. van Dulmen (Sandra); M. van den Berg (Martha); R.A. Verheij (Robert A.); L.C. Slobbe (Laurentius C.)

2011-01-01

textabstractBackground: Considering the scarcity of health care resources and the high costs associated with cardiovascular diseases, we investigated the spending on cardiovascular primary preventive activities and the prescribing behaviour of primary preventive cardiovascular medication (PPCM) in

Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

African Journals Online (AJOL)

Acute pancreatitis is an inflammatory disease with the clinical manifestation of acute abdominal pain. Several factors are involved in the pathogenesis of acute pancreatitis. The exact mechanism(s) by which diverse etiological factors induce an attack are still unclear. However, one of the proposed mechanisms for induction ...

Role of Phytochemicals in Prevention of Oral Diseases

Directory of Open Access Journals (Sweden)

Sunira Chandra

2007-01-01

The aim of this paper is to highlight and discuss the importance of natural chemical substances available in fruits, vegetables and herbs as they interfere with multiple important cellular pathways and this property is utilized for the prevention and treatment of oral diseases.

Neuroinflammation in Alzheimer's Disease

Science.gov (United States)

Heneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederik; Feinstein, Douglas L.; Jacobs, Andreas H.; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M.; Herrup, Karl; Frautschy, Sally A.; Finsen, Bente; Brown, Guy C.; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C.; Town, Terrence; Morgan, Dave; Shinohara, Mari L.; Perry, V. Hugh; Holmes, Clive; Bazan, Nicolas G.; Brooks, David J.; Hunot, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.

2018-01-01

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment but strongly interacts with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on micro- and astroglia and trigger an innate immune response, characterized by the release of inflammatory mediators, which contribute to disease progression and severity. Genome wide analysis suggests that several genes, which increase the risk for sporadic Alzheimer's disease en-code for factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity are likely to interfere with the immunological processes of the brain and further promote disease progression. This re-view provides an overview on the current knowledge and focuses on the most recent and exciting findings. Modulation of risk factors and intervention with the described immune mechanisms are likely to lead to future preventive or therapeutic strategies for Alzheimer's disease. PMID:25792098

Primary prevention of cardiovascular diseases: a cost study in family practices.

NARCIS (Netherlands)

Bekker-Grob, E.W. de; Dulmen, S. van; Berg, M. van den; Verheij, R.A.; Slobbe, L.C.J.