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Sample records for age-related chronic diseases

  1. Parabiosis for the study of age-related chronic disease

    PubMed Central

    Eggel, Alexander; Wyss-Coray, Tony

    2014-01-01

    Summary Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago. In view of this tremendous achievement, it can seem as if progress has slowed, and we have been unable to impact the most devastating diseases of our time. Chronic diseases of age such as cardiovascular disease, diabetes, osteoarthritis, or Alzheimer’s disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which mimics aspects of the naturally occurring shared blood supply in conjoined twins in humans and certain animals, may just have the power to be such a transformative experimental paradigm. Forgotten and now shunned in many countries, it has contributed to major breakthroughs in tumor biology, endocrinology, and transplantation research in the past century, and a set of new studies in the US and Britain report stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited especially if one is to study complex age-related, chronic disorders. PMID:24496774

  2. [Relationship between educational level and dementia: social factor and age-related chronic disease].

    PubMed

    Dartigues, J-F; Foubert-Samier, A; Helmer, C

    2013-08-01

    Dementia is an age-related chronic syndrome, whose the first cause is a neurodegenerative disease: Alzheimer's disease (AD). In spite of some controversies, educational level is now considered as a major risk factor for dementia and AD. The protective effect of a high level of education could be related to a preservation of cognitive reserve and a reinforcement of brain reserve. Moreover, subjects with a high level of education have a better access to health care and a better management of vascular risk factors. With the general improvement of the educational level, the age-related incidence of AD and dementia should decrease in the future.

  3. Gender differences in age-related decline in glomerular filtration rates in healthy people and chronic kidney disease patients

    PubMed Central

    2010-01-01

    Background Since men with chronic kidney disease (CKD) progress faster than women, an accurate assessment of CKD progression rates should be based on gender differences in age-related decline of glomerular filtration rate (GFR) in healthy individuals. Methods A Chinese sample population from a stratified, multistage, and clustered CKD screening study was classified into healthy, at-risk, and CKD groups. The gender differences in estimated GFR (eGFR) and age-related eGFR decline were calculated for each group after controlling for blood pressure, fasting glucose levels, serum lipids levels, education level, and smoking status. After referencing to the healthy group, gender-specific multivariate-adjusted rates of decline in eGFR and differences in the rates of decline were calculated for both CKD and at-risk groups. Results The healthy, at-risk, and CKD groups consisted of 4569, 7434, and 1573 people, respectively. In all the 3 groups, the multivariate-adjusted eGFRs in men were lower than the corresponding eGFRs in women. In addition, in the healthy and at-risk groups, the rates of decline in eGFR in men were lower than the corresponding rates of decline in women (healthy group: 0.51 mL·min-1·1.73 m-2·yr-1 vs. 0.74 mL·min-1·1.73 m-2·yr-1 and at-risk group: 0.60 mL·min-1·1.73 m-2·yr-1 vs. 0.73 mL·min-1·1.73 m-2·yr-1). However, in the CKD group, the rates of decline in eGFR in men were similar to those in women (0.96 mL·min-1·1.73 m-2·yr-1 vs. 0.91 mL·min-1·1.73 m-2·yr-1). However, after referencing to the healthy group, the rates of decline in eGFR in men in the at-risk and CKD groups were greater faster than the corresponding rates in women (at-risk group: 0.10 mL·min-1·1.73 m-2·yr-1 vs. -0.03 mL·min-1·1.73 m-2·yr-1 and CKD group: 0.44 mL·min-1·1.73 m-2·yr-1 vs. 0.15 mL·min-1·1.73 m-2·yr-1). Conclusion To accurately assess gender differences in CKD progression rates, gender differences in age-related decline in GFR should be considered

  4. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  5. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  6. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  7. Aging, frailty and age-related diseases.

    PubMed

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  8. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  9. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  10. Genetic evidence for common pathways in human age-related diseases.

    PubMed

    Johnson, Simon C; Dong, Xiao; Vijg, Jan; Suh, Yousin

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

  11. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  12. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    PubMed

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  13. Stem cell transplantation improves aging-related diseases

    PubMed Central

    Ikehara, Susumu; Li, Ming

    2014-01-01

    Aging is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. The number of patients with age-associated diseases such as type 2 diabetes mellitus (T2DM), osteoporosis, Alzheimer's disease (AD), Parkinson's disease, atherosclerosis, and cancer has increased recently. Aging-related diseases are related to a deficiency of the immune system, which results from an aged thymus and bone marrow cells. Intra bone marrow-bone marrow transplantation (IBM-BMT) is a useful method to treat intractable diseases. This review summarizes findings that IBM-BMT can improve and treat aging-related diseases, including T2DM, osteoporosis and AD, in animal models. PMID:25364723

  14. Nutritional influences on epigenetics and age-related disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  15. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  16. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  17. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  18. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  19. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  20. The potential of chitosan and its derivatives in prevention and treatment of age-related diseases.

    PubMed

    Kerch, Garry

    2015-04-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed.

  1. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process.

  2. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  3. Curcumin, inflammation, ageing and age-related diseases.

    PubMed

    Sikora, E; Scapagnini, Giovanni; Barbagallo, Mario

    2010-01-17

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha, encoded by genes activated by the transcription factor NF-kappaB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-kappaB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly.

  4. MicroRNAs in age-related diseases.

    PubMed

    Dimmeler, Stefanie; Nicotera, Pierluigi

    2013-02-01

    Aging is a complex process that is linked to an increased incidence of major diseases such as cardiovascular and neurodegenerative disease, but also cancer and immune disorders. MicroRNAs (miRNAs) are small non-coding RNAs, which post-transcriptionally control gene expression by inhibiting translation or inducing degradation of targeted mRNAs. MiRNAs target up to hundreds of mRNAs, thereby modulating gene expression patterns. Many miRNAs appear to be dysregulated during cellular senescence, aging and disease. However, only few miRNAs have been so far linked to age-related changes in cellular and organ functions. The present article will discuss these findings, specifically focusing on the cardiovascular and neurological systems.

  5. Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases.

    PubMed

    Blokh, David; Stambler, Ilia

    2014-08-01

    The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of "early aging" of the diseased subjects, or alternatively a "disease-like" aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes. PMID:25110613

  6. Neuropharmacology of depression in aging and age-related diseases.

    PubMed

    Gareri, Pietro; De Fazio, Pasquale; De Sarro, Giovambattista

    2002-02-01

    Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and non-suicide mortality. Depression may be also caused by a various number of drugs currently administered; this is remarkable especially in elderly people, where polypathology is often associated with polypharmacotherapy. However, the pathogenesis of geriatric depression is not well understood; major depression may arise from dysfunction of the limbic-hypothalamic-pituitary-adrenal axis. Some clinical observations also suggest that striato-frontal dysfunction is associated with late life depression. A number of hypotheses have been made, focusing that mood disturbances are probably linked to a disturbed central metabolism of monoamines 5-hydroxytryptamine, noradrenaline and dopamine; however most of this knowledge is derived from animal models. Parkinson's and Alzheimer's diseases are age-related diseases associated to decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. These observations lead to the hypothesis that the dysfunction of one or more of the cortical basal ganglia-thalamic neuronal loops are involved in the pathophysiology of primary and secondary depression. This dysfunction may be mediated by decreased serotonin release and probably, also by reduction in serotonin receptors. Development of novel approaches such as dynamic brain imaging methods, together with indirect knowledge coming from the effects of new antidepressants, will increase the understanding of neurochemistry of depression in old age. PMID:12039452

  7. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  8. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  9. The Marmoset as a Model of Aging and Age-Related Diseases

    PubMed Central

    Tardif, Suzette D.; Mansfield, Keith G.; Ratnam, Rama; Ross, Corinna N.; Ziegler, Toni E.

    2013-01-01

    The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16.5 years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change—for example, reduced neurogenesis, β-amyloid deposition in the cerebral cortex, loss of calbindin D28k binding, and evidence of presbycusis—appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age. PMID:21411858

  10. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  11. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  12. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    PubMed

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

  13. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  14. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    PubMed Central

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

    Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in

  15. Chronic acarbose treatment alleviates age-related behavioral and biochemical changes in SAMP8 mice.

    PubMed

    Tong, Jing-Jing; Chen, Gui-Hai; Wang, Fang; Li, Xue-Wei; Cao, Lei; Sui, Xu; Tao, Fei; Yan, Wen-Wen; Wei, Zhao-Jun

    2015-05-01

    The administration of maintaining the homeostasis of insulin/insulin-like growth factor 1 (IGF-1) signaling and/or glucose metabolism may reverse brain aging. In the present study, we investigated the effect of acarbose, an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. The SAMP8 mice were randomly divided into old control group and acarbose-treatment group. The mice in the acarbose group were administered acarbose (20 mg/kg/d, dissolved in drinking water) orally from 3 to 9 months of age when a new group of 3-month-old mice was added as young controls. The results showed that the aged controls exhibited declines in sensorimotor ability, open field anxiety, spatial and non-spatial memory abilities, decreased serum insulin levels, increased IGF-1 receptor and synaptotagmin 1 (Syt1) levels and decreased insulin receptor, brain-derived neurotrophic factor (BDNF) and syntaxin 1 (Stx1) levels in the hippocampal layers. The age-related behavioral deficits correlated with the serological and histochemical data. Chronic acarbose treatment relieved these age-related changes, especially with respect to learning and memory abilities. This protective effect of acarbose on age-related behavioral impairments might be related to changes in the insulin system and the levels of BDNF, IGF-1R, and the pre-synaptic proteins Syt1 and Stx1. In conclusion, long-term treatment with acarbose ameliorated the behavioral deficits and biochemical changes in old SAMP8 mice and promoted successful aging. This study provides insight into the potential of acarbose for the treatment of brain aging.

  16. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    PubMed

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  17. Complexity in caring for an ageing heart failure population: concomitant chronic conditions and age related impairments.

    PubMed

    De Geest, Sabina; Steeman, Els; Leventhal, Marcia E; Mahrer-Imhof, Romy; Hengartner-Kopp, Beatrice; Conca, Antoinette; Bernasconi, Arlette T; Petry, Heidi; Brunner-La Rocca, Hanspeter

    2004-12-01

    The complexity of caring for the ageing heart failure (HF) population is further complicated by concomitant chronic conditions (i.e., polypharmacy, depression), age related impairments (i.e., hearing, visual and cognitive impairments, impairments in activities of daily living (ADL/IADL), and other issues (e.g., health illiteracy, lack of social support). This paper provides an overview of these risk factors, outlines how they individually and in interplay endanger favourable outcome by putting patients at risk for poor self-management. Moreover, suggestions are made on how these issues could be addressed and integrated in heart failure management by applying gerontological care principles in caring for the ageing heart failure population.

  18. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    PubMed

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  19. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  20. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  1. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration.

    PubMed

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-02-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1(-/-) mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1(-/-) mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1(-/-) mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD.

  2. Apolipoprotein E promotes subretinal mononuclear phagocyte survival and chronic inflammation in age-related macular degeneration

    PubMed Central

    Levy, Olivier; Calippe, Bertrand; Lavalette, Sophie; Hu, Shulong J; Raoul, William; Dominguez, Elisa; Housset, Michael; Paques, Michel; Sahel, José-Alain; Bemelmans, Alexis-Pierre; Combadiere, Christophe; Guillonneau, Xavier; Sennlaub, Florian

    2015-01-01

    Physiologically, the retinal pigment epithelium (RPE) expresses immunosuppressive signals such as FAS ligand (FASL), which prevents the accumulation of leukocytes in the subretinal space. Age-related macular degeneration (AMD) is associated with a breakdown of the subretinal immunosuppressive environment and chronic accumulation of mononuclear phagocytes (MPs). We show that subretinal MPs in AMD patients accumulate on the RPE and express high levels of APOE. MPs of Cx3cr1−/− mice that develop MP accumulation on the RPE, photoreceptor degeneration, and increased choroidal neovascularization similarly express high levels of APOE. ApoE deletion in Cx3cr1−/− mice prevents pathogenic age- and stress-induced subretinal MP accumulation. We demonstrate that increased APOE levels induce IL-6 in MPs via the activation of the TLR2-CD14-dependent innate immunity receptor cluster. IL-6 in turn represses RPE FasL expression and prolongs subretinal MP survival. This mechanism may account, in part, for the MP accumulation observed in Cx3cr1−/− mice. Our results underline the inflammatory role of APOE in sterile inflammation in the immunosuppressive subretinal space. They provide rationale for the implication of IL-6 in AMD and open avenues toward therapies inhibiting pathogenic chronic inflammation in late AMD. PMID:25604058

  3. Molecular links between cellular senescence, longevity and age-related diseases - a systems biology perspective.

    PubMed

    Tacutu, Robi; Budovsky, Arie; Yanai, Hagai; Fraifeld, Vadim E

    2011-12-01

    The role of cellular senescence (CS) in age-related diseases (ARDs) is a quickly emerging topic in aging research. Our comprehensive data mining revealed over 250 genes tightly associated with CS. Using systems biology tools, we found that CS is closely interconnected with aging, longevity and ARDs, either by sharing common genes and regulators or by protein-protein interactions and eventually by common signaling pathways. The most enriched pathways across CS, ARDs and aging-associated conditions (oxidative stress and chronic inflammation) are growth-promoting pathways and the pathways responsible for cell-extracellular matrix interactions and stress response. Of note, the patterns of evolutionary conservation of CS and cancer genes showed a high degree of similarity, suggesting the co-evolution of these two phenomena. Moreover, cancer genes and microRNAs seem to stand at the crossroad between CS and ARDs. Our analysis also provides the basis for new predictions: the genes common to both cancer and other ARD(s) are highly likely candidates to be involved in CS and vice versa. Altogether, this study shows that there are multiple links between CS, aging, longevity and ARDs, suggesting a common molecular basis for all these conditions. Modulating CS may represent a potential pro-longevity and anti-ARDs therapeutic strategy. PMID:22184282

  4. Chronic endurance exercise training offsets the age-related attenuation in contraction-induced rapid vasodilation.

    PubMed

    Hughes, William E; Ueda, Kenichi; Casey, Darren P

    2016-06-01

    Aging is associated with attenuated contraction-induced rapid onset vasodilation (ROV). We sought to examine whether chronic exercise training would improve ROV in older adults. Additionally, we examined whether a relationship between cardiorespiratory fitness and ROV exists in young and older adults. Chronically exercise-trained older adults (n = 16; 66 ± 2 yr, mean ± SE) performed single muscle contractions in the forearm and leg at various intensities. Brachial and femoral artery diameter and blood velocity were measured using Doppler ultrasound. Vascular conductance (VC) was calculated as the quotient of blood flow (ml/min) and mean arterial pressure (mmHg). These data were compared with our previously published work from an identical protocol in 16 older untrained (66 ± 1 yr, mean ± SE) and 14 young (23 ± 1 yr) adults. Peak (ΔVCpeak) and total vasodilator (VCtotal) responses were greater in trained compared with untrained older adults across leg exercise intensities (P < 0.05). There were no differences in responses between trained older and young adults in the arm or leg at any exercise intensity (P > 0.05). Comparison of ΔVCpeak in a subset of subjects at an absolute workload in the leg revealed that trained older adults exhibited augmented responses relative to untrained older adults. Exercise capacity (V̇o2 peak) was associated with ΔVCpeak and VCtotal across arm (r = 0.59-0.64) and leg exercise intensities (r = 0.55-0.68, P < 0.05) in older adults. Our data demonstrate that 1) chronic exercise training improves ROV in the arm and leg of trained older adults, such that age-related differences in ROV are abolished, and 2) VO2peak is associated with ΔVCpeak responses in both limbs of older adults. PMID:27032899

  5. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  6. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease. PMID:26937969

  7. Chronic kidney disease

    MedlinePlus

    Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...

  8. Chronic obstructive pulmonary disease

    MedlinePlus

    COPD; Chronic obstructive airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... can do to relieve symptoms and keep the disease from getting worse. If you smoke, now is ...

  9. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    PubMed Central

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  10. Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

    PubMed Central

    Farid, Marjan; Agrawal, Anshu; Fremgen, Daniel; Tao, Jeremiah; Chuyi, He; Nesburn, Anthony B.; BenMohamed, Lbachir

    2014-01-01

    Dry eye disease (DED) is a prevalent public health concern that affects up to 30% of adults and is particularly chronic and severe in the elderly. Two interconnected mechanisms cause DED: (1) an age-related dysfunction of lacrimal and meibomian glands, which leads to decreased tear production and/or an increase in tear evaporation; and (2) an age-related uncontrolled inflammation of the surface of the eye triggered by yet-to-be-determined internal immunopathological mechanisms, independent of tear deficiency and evaporation. In this review we summarize current knowledge on animal models that mimic both the severity and chronicity of inflammatory DED and that have been reliably used to provide insights into the immunopathological mechanisms of DED, and we provide an overview of the opportunities and limitations of the rabbit model in investigating the role of both ocular and nasal mucosal immune systems in the immunopathology of inflammatory DED and in testing novel immunotherapies aimed at delaying or reversing the uncontrolled age-related inflammatory DED. PMID:25535823

  11. Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease.

    PubMed

    Farid, Marjan; Agrawal, Anshu; Fremgen, Daniel; Tao, Jeremiah; Chuyi, He; Nesburn, Anthony B; BenMohamed, Lbachir

    2016-06-01

    Dry eye disease (DED) is a prevalent public health concern that affects up to 30% of adults and is particularly chronic and severe in the elderly. Two interconnected mechanisms cause DED: (1) an age-related dysfunction of lacrimal and meibomian glands, which leads to decreased tear production and/or an increase in tear evaporation; and (2) an age-related uncontrolled inflammation of the surface of the eye triggered by yet-to-be-determined internal immunopathological mechanisms, independent of tear deficiency and evaporation. In this review we summarize current knowledge on animal models that mimic both the severity and chronicity of inflammatory DED and that have been reliably used to provide insights into the immunopathological mechanisms of DED, and we provide an overview of the opportunities and limitations of the rabbit model in investigating the role of both ocular and nasal mucosal immune systems in the immunopathology of inflammatory DED and in testing novel immunotherapies aimed at delaying or reversing the uncontrolled age-related inflammatory DED.

  12. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment.

    PubMed

    Cheung, C M G; Wong, T Y

    2014-08-01

    Age-related macular degeneration (AMD) is a common vision-threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted.

  13. What determines age-related disease: do we know all the right questions?

    PubMed Central

    2009-01-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant ~7% of the age-related disease deaths from 1938 to 1998 and have been consistently ~2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming. PMID:19904627

  14. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases

    PubMed Central

    Bär, Christian; Blasco, Maria A.

    2016-01-01

    Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself. PMID:27081482

  15. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  16. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

    PubMed Central

    Potter, Paul K.; Bowl, Michael R.; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E.; Simon, Michelle M.; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V.; Law, Gemma; MacLaren, Robert E.; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H.; Foster, Russell G.; Jackson, Ian J.; Peirson, Stuart N.; Thakker, Rajesh V.; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M.; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D. M.

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  17. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  18. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    PubMed

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-01-01

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss. PMID:27534441

  19. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    PubMed Central

    He, Liang; Kernogitski, Yelena; Kulminskaya, Irina; Loika, Yury; Arbeev, Konstantin G.; Loiko, Elena; Bagley, Olivia; Duan, Matt; Yashkin, Arseniy; Ukraintseva, Svetlana V.; Kovtun, Mikhail; Yashin, Anatoliy I.; Kulminski, Alexander M.

    2016-01-01

    the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases. PMID:27790247

  20. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    PubMed

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  1. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    PubMed Central

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2016-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy. PMID:26646499

  2. Cellular senescence in aging and age-related disease: from mechanisms to therapy.

    PubMed

    Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M

    2015-12-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

  3. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  4. iPSCs as a major opportunity to understand and cure age-related diseases.

    PubMed

    Lemey, Camille; Milhavet, Ollivier; Lemaitre, Jean-Marc

    2015-08-01

    Cellular senescence plays an important role in the process of aging and is often associated with age-related diseases. Senescence was originally considered as a barrier to cell reprogramming, however we developed a strategy to overcome this hurdle and derive induced pluripotent stem cells (iPSCs) from senescent cells and cells from centenarians. Furthermore we showed that the newly generated iPSCs could be re-differentiated into fully rejuvenated cells. That has increased the known beneficial properties of iPSCs to include them as a tool to model age-related diseases or even to cure them through cell therapy. In this review, we describe the hallmarks of cellular senescence before presenting how we reprogrammed aged and senescent cells into iPSCs and obtained rejuvenated re-differentiated cells. Finally, we take an interest in the way iPSCs can be used to understand and cure age-related diseases and we present their advantages for patient-specific therapy.

  5. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  6. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

  7. Discover the network mechanisms underlying the connections between aging and age-related diseases.

    PubMed

    Yang, Jialiang; Huang, Tao; Song, Won-Min; Petralia, Francesca; Mobbs, Charles V; Zhang, Bin; Zhao, Yong; Schadt, Eric E; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named "GeroNet" to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to "response to decreased oxygen levels", "insulin signalling pathway", "cell cycle", etc. Based on subnetwork connectivity, we can correctly "predict" if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer's disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  8. Discover the network mechanisms underlying the connections between aging and age-related diseases

    PubMed Central

    Yang, Jialiang; Huang, Tao; Song, Won-min; Petralia, Francesca; Mobbs, Charles V.; Zhang, Bin; Zhao, Yong; Schadt, Eric E.; Zhu, Jun; Tu, Zhidong

    2016-01-01

    Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named “GeroNet” to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to “response to decreased oxygen levels”, “insulin signalling pathway”, “cell cycle”, etc. Based on subnetwork connectivity, we can correctly “predict” if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer’s disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease. PMID:27582315

  9. Monograph series on aging-related diseases: VIII. Non-insulin-dependent diabetes mellitus (NIDDM)

    PubMed

    Barceló, A

    1996-01-01

    Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and by disturbances of carbohydrate, fat and protein metabolism. Diabetes mellitus is associated with absolute or relative deficiency in the secretion and/or action of the hormone insulin.

  10. The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1

    PubMed Central

    2006-01-01

    The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. PMID:10588299

  11. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  12. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  13. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  14. The role of DNA methylation in aging, rejuvenation, and age-related disease.

    PubMed

    Johnson, Adiv A; Akman, Kemal; Calimport, Stuart R G; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro

    2012-10-01

    DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

  15. The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

    PubMed Central

    Johnson, Adiv A.; Akman, Kemal; Calimport, Stuart R.G.; Wuttke, Daniel; de Magalhães, João Pedro

    2012-01-01

    Abstract DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. PMID:23098078

  16. Strategic white matter tracts for processing speed deficits in age-related small vessel disease

    PubMed Central

    Duering, Marco; Gesierich, Benno; Seiler, Stephan; Pirpamer, Lukas; Gonik, Mariya; Hofer, Edith; Jouvent, Eric; Duchesnay, Edouard; Chabriat, Hugues; Ropele, Stefan; Schmidt, Reinhold

    2014-01-01

    Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brain MRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the Trail Making Test part B. Clusters were located bilaterally in the forceps minor and anterior thalamic radiation. Region of interest–based Bayesian network analyses on lesion volumes within major white matter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease. PMID:24793184

  17. Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.

    PubMed

    Syed, Farhan A; Mödder, Ulrike Il; Roforth, Matthew; Hensen, Ira; Fraser, Daniel G; Peterson, James M; Oursler, Merry Jo; Khosla, Sundeep

    2010-11-01

    While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age-related bone loss, we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six-month-old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham-operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham-operated mice. As compared with cells from young mice, lin- cells from aged/sham-operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. PMID:20499336

  18. What can we learn about age-related macular degeneration from other retinal diseases?

    PubMed

    Zack, D J; Dean, M; Molday, R S; Nathans, J; Redmond, T M; Stone, E M; Swaroop, A; Valle, D; Weber, B H

    1999-11-01

    Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

  19. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases.

    PubMed

    Suksuphew, Sarawut; Noisa, Parinya

    2015-03-26

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.

  20. NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?

    PubMed Central

    Sahoo, Sanghamitra; Meijles, Daniel N.; Pagano, Patrick J.

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress have long been linked to aging and diseases prominent in the elderly such as hypertension, atherosclerosis, diabetes and atrial fibrillation (AF). NADPH oxidases (Nox) are a major source of ROS in the vasculature and are key players in mediating redox signalling under physiological and pathophysiological conditions. In this review, we focus on the Nox-mediated ROS signalling pathways involved in the regulation of ‘longevity genes’ and recapitulate their role in age-associated vascular changes and in the development of age-related cardiovascular diseases (CVDs). This review is predicated on burgeoning knowledge that Nox-derived ROS propagate tightly regulated yet varied signalling pathways, which, at the cellular level, may lead to diminished repair, the aging process and predisposition to CVDs. In addition, we briefly describe emerging Nox therapies and their potential in improving the health of the elderly population. PMID:26814203

  1. Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory.

    PubMed

    Thornton, P L; Ingram, R L; Sonntag, W E

    2000-02-01

    The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.

  2. Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

    PubMed

    Zech, Michael; Nübling, Georg; Castrop, Florian; Jochim, Angela; Schulte, Eva C; Mollenhauer, Brit; Lichtner, Peter; Peters, Annette; Gieger, Christian; Marquardt, Thorsten; Vanier, Marie T; Latour, Philippe; Klünemann, Hans; Trenkwalder, Claudia; Diehl-Schmid, Janine; Perneczky, Robert; Meitinger, Thomas; Oexle, Konrad; Haslinger, Bernhard; Lorenzl, Stefan; Winkelmann, Juliane

    2013-01-01

    Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563), FTLD (n = 133) and PSP (n = 94), and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1%) and seven control subjects (0.8%), but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted. PMID:24386122

  3. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    PubMed Central

    Davalli, Pierpaola; Mitic, Tijana; Caporali, Andrea; Lauriola, Angela; D'Arca, Domenico

    2016-01-01

    The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. PMID:27247702

  4. Chronic granulomatous disease

    MedlinePlus

    CGD; Fatal granulomatosis of childhood; Chronic granulomatous disease of childhood; Progressive septic granulomatosis ... In chronic granulomatous disease (CGD), immune system cells called phagocytes are unable to kill some types of bacteria and fungi. This ...

  5. Chronic Kidney Diseases

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  6. Principles and practice of hormetic treatment of aging and age-related diseases.

    PubMed

    Rattan, Suresh Is

    2008-02-01

    Aging is characterized by stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. Studies on the beneficial biological effects of repeated mild heat shock on human cells in culture, and other studies on the anti-aging and life-prolonging effects of proxidants, hypergravity, irradiation and ethanol on cells and organisms suggest that hormesis as an antiaging and gerontomodulatory approach has a promising future. Its clinical applications include prevention and treatment of diabetes, cataract, osteoporosis, dementia and some cancers.

  7. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  8. Advantage of a low glycemic index and low phosphate diet on diabetic nephropathy and aging-related diseases.

    PubMed

    Taketani, Yutaka; Shuto, Emi; Arai, Hidekazu; Nishida, Yuka; Tanaka, Rieko; Uebanso, Takashi; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Takeda, Eiji

    2007-08-01

    Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Japan and other Westernized countries. Over 50% of the ESRD patients die from cardiovascular events. Cardiovascular disease (CVD) in ESRD patients with diabetes mellitus (DM) are implicated in the endothelial dysfunction caused by hyperglycemia, hyperlipidemia, and hypertension, and in the vascular calcification of intimal and medial arterial blood vessels caused by hyperphosphatemia. Therefore, dietary control of hyperglycemia and hyperphosphatemia should play an important role in the management of ESRD patients with DM. Furthermore, recent findings suggest that high concentrations of serum phosphate, even if within the normal range, may be a risk factor for CVD and mortality. An in vivo study using klotho knockout mice and fibroblast growth factor 23 (FGF-23) knockout mice has revealed that correction of hyperphosphatemia and hypervitaminosis D could ameliorate the premature aging-like phenotype. A low glycemic index and low phosphate diet may provide an advantage in the prevention of aging-related diseases in healthy individuals as well as in those with chronic kidney disease.

  9. A review of creatine supplementation in age-related diseases: more than a supplement for athletes.

    PubMed

    Smith, Rachel N; Agharkar, Amruta S; Gonzales, Eric B

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement's usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer's disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.

  10. What's on TV? Detecting age-related neurodegenerative eye disease using eye movement scanpaths

    PubMed Central

    Crabb, David P.; Smith, Nicholas D.; Zhu, Haogang

    2014-01-01

    Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie. Methods: Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64–75 years) and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63–77 years) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD). All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada). Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA). Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI) of classification sensitivity and specificity. Results: Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was −7 [−13 to −5] dB and −9 [−15 to −4] dB, respectively). Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58–86%). The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82–0.87). Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement

  11. Age-related macular degeneration and coronary heart disease: evaluation of genetic and environmental associations.

    PubMed

    Keilhauer, Claudia N; Fritsche, Lars G; Guthoff, Rainer; Haubitz, Imme; Weber, Bernhard H

    2013-02-01

    An association between coronary heart disease (CHD) and age-related macular degeneration (AMD) has long been postulated but results from epidemiological case-control studies, and genetic analyses have been ambiguous. In this study we illuminate the association between AMD and CHD with respect to genetic and environmental risk factors, age of disease onset and AMD subgroups. AMD patients (n = 1036) and age-matched control subjects (n = 412) between 68 and 95 years of age were included in the case-control study. A medical history of CHD, cerebral stroke and arterial hypertension was determined for each individual. The assessment of interacting factors included the current use of systemic medications and smoking habits. Analysis of AMD associated genetic variants included frequent polymorphisms at the complement factor H (CFH, MIM 134370) gene (rs1061170 [p.Y402H], rs800292 [p.I62V]), the complement factor H-related 3 (CFHR3, MIM 605336)/complement factor H-related 1 (CFHR1, MIM 134371) locus (rs6677604; proxy for ΔCFHR3/CFHR1; r(2) = 0.97) as well as the age-related maculopathy susceptibility 2 (ARMS2, MIM 611313) gene (rs10490924 [p.A69S]). Logistic regression identified a significant positive association of AMD with AMD-risk variants in CFH, ARMS2, and smoking ≥ 20 packs/year. A history of CHD and the current use of antihyperuricemic agents were inversely associated with the disease. Significantly fewer patients with rs6677604 nonrisk genotype A/A regularly used statins. ARMS2:p.A69S risk variant was significantly associated with exsudative AMD. AMD patients with risk variants at rs1061170 (CFH:p.Y402H) and ARMS2 and smokers (≥20 packs/year) were significantly earlier affected by AMD than those carrying the non-risk variants at each locus. Our data support three major conclusions. First, the age of AMD onset is significantly influenced by genetic and environmental risk factors. Second, in support of previous reports we also show that the ARMS2 rs10490924:T

  12. Cognitive Reserve Modifies Age-Related Alterations in CSF Biomarkers of Alzheimer's Disease

    PubMed Central

    Almeida, Rodrigo P.; Schultz, Stephanie A.; Austin, Benjamin P.; Boots, Elizabeth A.; Dowling, N. Maritza; Gleason, Carey E.; Bendlin, Barbara B.; Sager, Mark; Hermann, Bruce P.; Zetterberg, Henrik; Carlsson, Cindy; Johnson, Sterling; Asthana, Sanjay; Okonkwo, Ozioma C.

    2015-01-01

    Importance Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer's disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. Objective In this study, we investigated whether cognitive reserve modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. Design, Setting, and Participants Cross-sectional cohort of 268 individuals (211 cognitively normal and 57 cognitively impaired) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. Additionally, we computed t-tau/Aβ42 and p-tau/Aβ42 ratios. Cognitive reserve was indexed by years of education, with ≥16 years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by cognitive reserve. Main outcome measures CSF levels of Aβ42, t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42. Results There were significant age*cognitive reserve interactions for CSF t-tau (p=.019), p-tau (p=.009), t-tau/Aβ42 (p=.021), and p-tau/Aβ42 (p=.004). Specifically, with advancing age, individuals with high cognitive reserve exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low cognitive reserve. This attenuation of age effects by cognitive reserve tended to be more pronounced in the cognitively-impaired group compared with the cognitively-normal group. Lastly, there was modest evidence of a dose response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. Conclusions and Relevance In a sample comprised of both cognitively

  13. Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.

    PubMed

    Delplace, Vianney; Payne, Samantha; Shoichet, Molly

    2015-12-10

    Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery.

  14. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  15. Carotenoids and chronic diseases.

    PubMed

    Agarwal, S; Rao, A V

    2000-01-01

    Chronic diseases such as cancer and cardiovascular diseases are the major causes of deaths in North America. Dietary intake of fruits and vegetables has been suggested to have protective effects against such chronic diseases. Carotenoids are important plant pigments which are thought to contribute towards the beneficial effects of fruit and vegetable consumption. This review focuses on the role of carotenoids and particularly lycopene in chronic diseases.

  16. Common drugs and treatments for cancer and age-related diseases: revitalizing answers to NCI's provocative questions

    PubMed Central

    Blagosklonny, Mikhail V.

    2012-01-01

    In 2011, The National Cancer Institute (NCI) has announced 24 provocative questions on cancer. Some of these questions have been already answered in “NCI's provocative questions on cancer: some answers to ignite discussion” (published in Oncotarget, 2011, 2: 1352.) The questions included “Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?” “Can we extend patient survival by using approaches that keep tumors static?” “Why are some disseminated cancers cured by chemotherapy alone?” “Can we develop methods to rapidly test interventions for cancer treatment or prevention?” “Can we use our knowledge of aging to enhance prevention or treatment of cancer?” “What is the mechanism by which some drugs commonly and chronically used for other indications protect against cancer?” “How does obesity contribute to cancer risk?” I devoted a single subchapter to each the answer. As expected, the provocative questions were very diverse and numerous. Now I choose and combine, as a single problem, only three last questions, all related to common mechanisms and treatment of age-related diseases including obesity and cancer. Can we use common existing drugs for cancer prevention and treatment? Can we use some targeted “cancer-selective” agents for other diseases and … aging itself. PMID:23565531

  17. Nutraceutical properties of extra-virgin olive oil: a natural remedy for age-related disease?

    PubMed

    Virruso, Claudia; Accardi, Giulia; Colonna-Romano, Giuseppina; Candore, Giuseppina; Vasto, Sonya; Caruso, Calogero

    2014-04-01

    The health benefits of the Mediterranean diet can be largely ascribed to the nutraceutical properties of extra-virgin olive oil (EVOO). Mono-unsaturated fatty acids and various phenolic compounds, such as oleocanthal, oleuropein, hydroxytyrosol, and tyrosol, are the main nutraceutical substances of EVOO. These substances have been suggested to have the ability to modulate aging-associated processes. In experimental models, it has been shown that EVOO with high concentrations of polyphenols has anti-inflammatory and anti-oxidant properties. Indeed, it was observed that hydroxytyrosol and oleocanthal inhibit the cyclooxygenases (COX-1 and -2) responsible for prostaglandin production; oleuropein is a radical scavenger that blocks the oxidation of low-density lipoproteins. Due to the relevance of olive oil in the economy of Sicily, our group has been funded to assess the nutraceutical properties of different kinds of olive oil. Indeed, the aim of the study is to evaluate effects of EVOOs, with low and high polyphenols content, on immuno-inflammatory and oxidative stress responses in young and old people. A further objective of our group is to evaluate effects of EVOO, with low and high polyphenol content, on the expression of genes encoding proteins that take part in the insulin/insulin-like growth factor-1 signaling pathway involved in longevity. The results of the study will be useful for producing olive oil enriched in nutraceutical properties that may be likely helpful in the prevention of age-related diseases. PMID:24219356

  18. NAD+ metabolism, a therapeutic target for age-related metabolic disease

    PubMed Central

    Auwerx, Johan

    2013-01-01

    Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein Sir2, the founding member of the sirtuin protein family, as being NAD+-dependent reignited interest in this metabolite. The sirtuins (SIRT1-7 in mammals) utilize NAD+ to deacetylate proteins in different subcellular compartments with a variety of functions, but with a strong convergence on optimizing mitochondrial function. Since cellular NAD+ levels are limiting for sirtuin activity, boosting its levels is a powerful means to activate sirtuins as a potential therapy for mitochondrial, often age-related, diseases. Indeed, supplying excess precursors, or blocking its utilization by PARP enzymes or CD38/CD157, boosts NAD+ levels, activates sirtuins and promotes healthy aging. Here, we discuss the current state of knowledge of NAD+ metabolism, primarily in relation to sirtuin function. We highlight how NAD+ levels change in diverse physiological conditions, and how this can be employed as a pharmacological strategy. PMID:23742622

  19. Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.

    PubMed

    Tedone, Enzo; Arosio, Beatrice; Gussago, Cristina; Casati, Martina; Ferri, Evelyn; Ogliari, Giulia; Ronchetti, Francesco; Porta, Alessandra; Massariello, Francesca; Nicolini, Paola; Mari, Daniela

    2014-10-01

    Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109years old), centenarians (CENT) (100-104years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p=0.027), angina (p=0.016) and depression (p=0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p=0.034) and hypertension (p=0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p<0.001) and the shortest (p<0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.

  20. Neighborhood Deprivation and Risk of Age-Related Eye Diseases: A Follow-up Study in Sweden

    PubMed Central

    Hamano, Tsuyoshi; Li, Xinjun; Tanito, Masaki; Nabika, Toru; Shiwaku, Kuninori; Sundquist, Jan; Sundquist, Kristina

    2016-01-01

    Purpose To examine whether there is an association between neighborhood deprivation and age-related eye diseases, particularly macular degeneration, cataract, diabetes-related eye complications, and glaucoma. Methods The study population comprised a nationwide sample of 2,060,887 men and 2,250,851 women aged 40 years or older living in Sweden who were followed from 1 January 2000 until the first hospitalization/outpatient registration for age-related eye disease during the study period, death, emigration, or the end of the study period on 31 December 2010. Multilevel logistic regression was used to estimate the association between neighborhood deprivation and age-related eye diseases. Results In men, the odds ratio (OR) for age-related eye diseases for those living in high-deprivation neighborhoods compared to those living in low-deprivation neighborhoods remained significant after adjustment for potential confounding factors (macular degeneration, OR 1.08, 95% confidence interval, CI, 1.03–1.12; cataract, OR 1.31, 95% CI 1.26–1.35; diabetes-related eye complications, OR 1.36, 95% CI 1.30–1.43; glaucoma, OR 1.11, 95% CI 1.06–1.15). In women, similar patterns were observed (macular degeneration, OR 1.11, 95% CI 1.07–1.15; cataract, OR 1.36, 95% CI 1.31–1.40; diabetes-related eye complications, OR 1.50, 95% CI 1.42–1.59; glaucoma, OR 1.12, 95% CI 1.08–1.17). Conclusion Our results suggest that neighborhood deprivation is associated with age-related eye diseases in both men and women. These results implicate that individual- as well as neighborhood-level factors are important for preventing age-related eye diseases. PMID:26395658

  1. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  2. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown

    PubMed Central

    Bartzokis, George

    2011-01-01

    The amyloid hypothesis (AH) of Alzheimer’s disease (AD) posits that the fundamental cause of AD is the accumulation of the peptide amyloid beta (Aβ) in the brain. This hypothesis has been supported by observations that genetic defects in amyloid precursor protein (APP) and presenilin increase Aβ production and cause familial AD (FAD). The AH is widely accepted but does not account for important phenomena including recent failures of clinical trials to impact dementia in humans even after successfully reducing Aβ deposits. Herein, the AH is viewed from the broader overarching perspective of the myelin model of the human brain that focuses on functioning brain circuits and encompasses white matter and myelin in addition to neurons and synapses. The model proposes that the recently evolved and extensive myelination of the human brain underlies both our unique abilities and susceptibility to highly prevalent age-related neuropsychiatric disorders such as late onset AD (LOAD). It regards oligodendrocytes and the myelin they produce as being both critical for circuit function and uniquely vulnerable to damage. This perspective reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits such as Aβ and tau as by-products of homeostatic myelin repair processes. It delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides “upstream” treatment targets. Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin. PMID:19775776

  3. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer’s Disease

    PubMed Central

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer’s Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer’s Disease. PMID:26937969

  4. Chronic Kidney Disease

    MedlinePlus

    ... control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged and ... don't have any symptoms until their kidney disease is very advanced. Blood and urine tests are ...

  5. Chronic Lyme disease.

    PubMed

    Lantos, Paul M

    2015-06-01

    Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm.

  6. Chronic Lyme disease.

    PubMed

    Lantos, Paul M

    2015-06-01

    Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm. PMID:25999227

  7. Beta-Amyloid Precursor Protein (βAPP) Processing in Alzheimer's Disease (AD) and Age-Related Macular Degeneration (AMD).

    PubMed

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, James M; Clement, Christian; Sambamurti, Kumar; Dua, Prerna; Lukiw, Walter J

    2015-08-01

    Amyloid is a generic term for insoluble, often intensely hydrophobic, fibrous protein aggregates that arise from inappropriately folded versions of naturally-occurring polypeptides. The abnormal generation and accumulation of amyloid, often referred to as amyloidogenesis, has been associated with the immune and pro-inflammatory pathology of several progressive age-related diseases of the human central nervous system (CNS) including Alzheimer's disease (AD) and age-related macular degeneration (AMD). This 'research perspective' paper reviews some of the research history, biophysics, molecular-genetics and environmental factors concerning the contribution of amyloid beta (Aβ) peptides, derived from beta-amyloid precursor protein (βAPP), to AD and AMD that suggests an extensive similarity in immune and inflammatory degenerative mechanisms between these two CNS diseases.

  8. Chronic wasting disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD) is an emerging prion disease of deer, elk, and moose in North America. This fatal neurodegenerative disease was first recognized 50 years ago and its distribution was limited to the Rocky Mountains for several decades. In the past few years, CWD has been found in the ea...

  9. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  10. Diet - chronic kidney disease

    MedlinePlus

    ... food instead of salt. DO NOT use salt substitutes because they contain potassium. People with chronic kidney disease also need to limit their potassium. POTASSIUM Normal blood levels of potassium help keep your heart beating ...

  11. Sleep and Chronic Disease

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Sleep and Sleep Disorders Note: Javascript is disabled or is not supported ... CDC.gov . Sleep About Us About Sleep Key Sleep Disorders Sleep and Chronic Disease How Much Sleep Do ...

  12. Age-Related Declines and Disease-Associated Variation in Immune Cell Telomere Length in a Wild Mammal

    PubMed Central

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes (‘immune cells’), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  13. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    PubMed

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells'), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  14. Rejuvenation of senescent cells-the road to postponing human aging and age-related disease?

    PubMed

    Sikora, Ewa

    2013-07-01

    Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. PMID:23064316

  15. The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases.

    PubMed

    Balistreri, Carmela Rita; Madonna, Rosalinda; Melino, Gerry; Caruso, Calogero

    2016-08-01

    Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until now there is a confounding evidence about the related mechanisms. Here, we discuss mechanisms through which Notch signaling acts in a very complex network of pathways, where it seems to have the crucial role of hub. Thus, we stress the possibility to use Notch pathway, the related molecules and pathways constituting this network, both as innovative (predictive, diagnostic and prognostic) biomarkers and targets for personalised treatments for age-related diseases. PMID:27328278

  16. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - ...

  17. Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides.

    PubMed

    Babizhayev, Mark A; Vishnyakova, Khava S; Yegorov, Yegor E

    2014-01-01

    It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated crosssectionally with cardiovascular disorders and their risk factors, including pulse pressure and vascular aging, obesity, vascular dementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease. It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state and in this article these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular, the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality, point to new and important treatment strategies or the therapeutic manipulation during treatment of age related disorders and cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines that accompany aging. In this work, we raise and support a therapeutic concept of using non-hydrolyzed forms of naturally occurring imidazoledipeptide based compounds carnosine and

  18. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

    PubMed

    Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

    2014-01-01

    This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus.

  19. Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes.

    PubMed

    Garagnani, Paolo; Giuliani, Cristina; Pirazzini, Chiara; Olivieri, Fabiola; Bacalini, Maria Giulia; Ostan, Rita; Mari, Daniela; Passarino, Giuseppe; Monti, Daniela; Bonfigli, Anna Rita; Boemi, Massimo; Ceriello, Antonio; Genovese, Stefano; Sevini, Federica; Luiselli, Donata; Tieri, Paolo; Capri, Miriam; Salvioli, Stefano; Vijg, Jan; Suh, Yousin; Delledonne, Massimo; Testa, Roberto; Franceschi, Claudio

    2013-05-01

    Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10⁻⁷). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared.

  20. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.

    PubMed

    Jonsson, Thorlakur; Atwal, Jasvinder K; Steinberg, Stacy; Snaedal, Jon; Jonsson, Palmi V; Bjornsson, Sigurbjorn; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R; Huttenlocher, Johanna; Bjornsdottir, Gyda; Andreassen, Ole A; Jönsson, Erik G; Palotie, Aarno; Behrens, Timothy W; Magnusson, Olafur T; Kong, Augustine; Thorsteinsdottir, Unnur; Watts, Ryan J; Stefansson, Kari

    2012-08-01

    The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.

  1. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    SciTech Connect

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  2. Chronic Obstructive Pulmonary Disease (COPD)

    MedlinePlus

    Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease that makes it difficult to empty air out of the lungs. This difficulty in ...

  3. Age-related differences in celiac disease: Specific characteristics of adult presentation

    PubMed Central

    Vivas, Santiago; Vaquero, Luis; Rodríguez-Martín, Laura; Caminero, Alberto

    2015-01-01

    Celiac disease may appear both in early childhood and in elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients. PMID:26558154

  4. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  5. Gender-related immune-inflammatory factors, age-related diseases, and longevity.

    PubMed

    Candore, Giuseppina; Balistreri, Carmela Rita; Colonna-Romano, Giuseppina; Lio, Domenico; Listì, Florinda; Vasto, Sonya; Caruso, Calogero

    2010-01-01

    This review discusses the role of estrogens as pro- or antiinflammatory players in immune-inflammatory responses. In particular, their role in Alzheimer's disease (AD), an example of immune-inflammatory disease, is discussed briefly. AD is a progressive neurodegenerative disease, which in Western societies accounts for the majority of cases of clinical senile dementia. However, sexual dimorphism of diseases may also depend on factors independent of sex hormones (i.e., a gender effect), as demonstrated by our data on differential longevity in females and males. In fact, differences in mortality between men and women are not only a question of sex that refers to biological differences, but rather a question of "socially constructed sex," a question of gender (i.e., the characteristics that a society or culture delineates as masculine or feminine). In gender medicine, we conclude that it is important to consider the role played both by hormones, customs, and educational levels regarding the different propensity of males and females to fall ill. So, in programming antiaging strategies, we have also to take these aspects into account.

  6. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    PubMed

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.

  7. Preface: The aging eye: normal changes, age-related diseases, and sight-saving approaches.

    PubMed

    Chader, Gerald J; Taylor, Allen

    2013-12-13

    This volume presents articles based on a workshop held June 14 to 16, 2013 in Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation (ORSF). The mission of the ORSF is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In this workshop, the subject of the "The Aging Eye" was addressed, including the prevalence of eye diseases in aging and the economic burden imposed by these diseases. New research work was highlighted on the genetics, biology, biochemistry, neurochemistry, and the impact of nutrition and the environment on function in the older eye. By identifying "low-hanging fruit" (i.e., the best opportunities for successful transition of laboratory research for the prevention of and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future.

  8. [Progress in induced pluripotent stem cell research for age-related neurodegenerative diseases].

    PubMed

    Ito, Daisuke; Yagi, Takuya; Suzuki, Norihiro

    2013-03-01

    In 2006, Takahashi et al. established a method for reprogramming somatic cells by introducing definite transcription factors, which enabled the generation of induced pluripotent stem cells (iPSCs) with pluripotency comparable to that of embryonic stem cells. In turn, it has become possible to use these iPSCs for producing various tissues needed for the treatment of neurodegenerative disorders, which have been difficult to obtain from living bodies. This advancement is expected to bring forth rapid progress in the clarification of mechanisms underlying the diseases and discovery of new innovative drugs and lead to rapid progress in regenerative medicine. In recent years, recapitulation and analysis of disease conditions using iPSCs derived from the patients themselves have been reported, and remarkable advances have been made, even for late-onset neurodegenerative disorders. These findings show that the phenotypes of late-onset neurodegenerative disorders can be recapitulated in iPSC-derived neuronal cells, which are reflected the early developmental stages, indicating cellular abnormalities exist from the prenatal period, despite the late onset diseases. In this review, we summarize the state of iPSCs research in the context of neurodegenerative disorders, discuss the possible ways for understanding the mechanisms underlying neurodegenerative disorders and discovering new drugs, and describe some other aspects of regenerative medicine.

  9. Drugs, nutrients, and phytoactive principles improving the health span of rodent models of human age-related diseases.

    PubMed

    Lebel, Michel; Picard, Frédéric; Ferland, Guylaine; Gaudreau, Pierrette

    2012-02-01

    Rodents are often the species of choice to examine the effect of drugs on survival and on the progression of specific diseased tissues. This statement is also true for research laboratories working in the field of nutrition and aging. In addition to diets that can reduce the life expectancy of rodents, such as diabetogenic or high-fat diets, genetically modified rodents exhibiting different accelerated age-associated diseases also provide important biologic tools to decipher the impact of drugs, nutrients, or phytoactive compounds on their health and life span. This review covers some of the chemicals believed to decelerate the appearance of age-related diseases in different rodent models. Such chemicals include antioxidants, anti-inflammatory molecules, modulators of metabolic sensors, calorie restriction mimetics, and vegetal polyphenolic compounds that affect mitochondrial functions, cellular proliferation or differentiation as well as cell functionality.

  10. Cell-based therapies of liver diseases: age-related challenges

    PubMed Central

    Yarygin, Konstantin N; Lupatov, Alexei Y; Kholodenko, Irina V

    2015-01-01

    The scope of this review is to revise recent advances of the cell-based therapies of liver diseases with an emphasis on cell donor’s and patient’s age. Regenerative medicine with cell-based technologies as its integral part is focused on the structural and functional restoration of tissues impaired by sickness or aging. Unlike drug-based medicine directed primarily at alleviation of symptoms, regenerative medicine offers a more holistic approach to disease and senescence management aimed to achieve restoration of homeostasis. Hepatocyte transplantation and organ engineering are very probable forthcoming options of liver disease treatment in people of different ages and vigorous research and technological innovations in this area are in progress. Accordingly, availability of sufficient amounts of functional human hepatocytes is crucial. Direct isolation of autologous hepatocytes from liver biopsy is problematic due to related discomfort and difficulties with further expansion of cells, particularly those derived from aging people. Allogeneic primary human hepatocytes meeting quality standards are also in short supply. Alternatively, autologous hepatocytes can be produced by reprogramming of differentiated cells through the stage of induced pluripotent stem cells. In addition, fibroblasts and mesenchymal stromal cells can be directly induced to undergo advanced stage hepatogenic differentiation. Reprogramming of cells derived from elderly people is accompanied by the reversal of age-associated changes at the cellular level manifesting itself by telomere elongation and the U-turn of DNA methylation. Cell reprogramming can provide high quality rejuvenated hepatocytes for cell therapy and liver tissue engineering. Further technological advancements and establishment of national and global registries of induced pluripotent stem cell lines homozygous for HLA haplotypes can allow industry-style production of livers for immunosuppression-free transplantation. PMID

  11. Chronic Wasting Disease

    USGS Publications Warehouse

    Richards, Bryan

    2007-01-01

    Chronic wasting disease (CWD) is an always-fatal, neurological illness occurring in North American cervids (members of the deer family), including white-tailed deer, mule deer, elk and moose. Since its discovery in 1967, CWD has spread geographically and increased in prevalence locally. CWD is contagious; it can be transmitted freely within and among free-ranging populations. It is likely that diseased animals can transmit CWD to healthy animals long before they become clinically ill. Managing CWD in free-ranging populations is extremely difficult, therefore preventative measures designed to reduce the chance for disease spread are critically important.

  12. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

    PubMed Central

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

    2013-01-01

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

  13. Positive oxidative stress in aging and aging-related disease tolerance.

    PubMed

    Yan, Liang-Jun

    2014-01-01

    It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

  14. Positive Lysosomal Modulation As a Unique Strategy to Treat Age-Related Protein Accumulation Diseases

    PubMed Central

    Wisniewski, Meagan L.; Butler, David

    2012-01-01

    Abstract Lysosomes are involved in degrading and recycling cellular ingredients, and their disruption with age may contribute to amyloidogenesis, paired helical filaments (PHFs), and α-synuclein and mutant huntingtin aggregation. Lysosomal cathepsins are upregulated by accumulating proteins and more so by the modulator Z-Phe-Ala-diazomethylketone (PADK). Such positive modulators of the lysosomal system have been studied in the well-characterized hippocampal slice model of protein accumulation that exhibits the pathogenic cascade of tau aggregation, tubulin breakdown, microtubule destabilization, transport failure, and synaptic decline. Active cathepsins were upregulated by PADK; Rab proteins were modified as well, indicating enhanced trafficking, whereas lysosome-associated membrane protein and proteasome markers were unchanged. Lysosomal modulation reduced the pre-existing PHF deposits, restored tubulin structure and transport, and recovered synaptic components. Further proof-of-principle studies used Alzheimer disease mouse models. It was recently reported that systemic PADK administration caused dramatic increases in cathepsin B protein and activity levels, whereas neprilysin, insulin-degrading enzyme, α-secretase, and β-secretase were unaffected by PADK. In the transgenic models, PADK treatment resulted in clearance of intracellular amyloid beta (Aβ) peptide and concomitant reduction of extracellular deposits. Production of the less pathogenic Aβ1–38 peptide corresponded with decreased levels of Aβ1–42, supporting the lysosome's antiamyloidogenic role through intracellular truncation. Amelioration of synaptic and behavioral deficits also indicates a neuroprotective function of the lysosomal system, identifying lysosomal modulation as an avenue for disease-modifying therapies. From the in vitro and in vivo findings, unique lysosomal modulators represent a minimally invasive, pharmacologically controlled strategy against protein accumulation disorders

  15. Preimplantation genetic diagnosis for Pelizaeus-Merzbacher disease with testing for age-related aneuploidies.

    PubMed

    Verlinsky, Y; Rechitsky, S; Laziuk, K; Librach, C; Genovese, R; Kuliev, A

    2006-01-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive demyelinating disorder of the central nervous system, caused by mutations of the proteolipid protein 1 gene (PLP1 gene). As no specific therapy is available for PMD, preimplantation genetic diagnosis (PGD) may be a useful option for couples carrying this mutation. PGD was performed for a couple who had had one child with the L86P mutation in exon 3 of the PLP1 gene. Because of advanced maternal age, PGD for this single-gene disorder was performed together with testing for chromosomal abnormalities. Polar bodies and blastomeres were tested for the presence of maternal mutation and closely linked markers DXS8020 and PLP5' (CA)n. The same blastomeres were also tested for the copy number of chromosomes 13, 16, 18, 21, 22, X and Y, and five chromosomally abnormal embryos were identified. A total of three embryos predicted to be unaffected and free of chromosomal disorder were transferred back to the patient, resulting in a twin pregnancy and the birth of two healthy female infants confirmed to be free of PMD, representing the first PGD for PMD combined with aneuploidy testing.

  16. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  17. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease in non diabetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains...

  18. [Coping with chronic disease].

    PubMed

    Bachmann, Silke

    2014-03-26

    Patients suffering form chronic diseases have to deal with several problems, the illness itself only being one of them. Health care providers have to undergo a paradigm shift to be able to meet the new challenges which differ from those in acute care. From the patient's perspective, coping with a chronic disease is not a limited process, but encompasses different, often recurring phases (trajectory model). The treating physician's support may comprise the offering of information on general and specific stress factors (physical, emotional, social), empathy, respecting the individual's expertise and activating a patient's resources and self-efficacy. The amount of support given is limited by the treating physician's expert knowledge in this area. Physicians should respect their own limits and involve specialists, supervision or Balint groups.

  19. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  20. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.

    PubMed

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-09-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions.

  1. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    PubMed Central

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  2. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration.

    PubMed

    Bondy, Stephen C

    2016-01-01

    Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer's disease. Epidemiological data is reinforced by indications that aluminum exposure can result in excess inflammatory activity within the brain. Activation of the immune system not initiated by an infectious agent, typifies the aging brain and is even more augmented in several neurodegenerative diseases. The origin of most age-related neurological disorders is generally not known but as they are largely not of genetic derivation, their development is likely triggered by unknown environmental factors. There is a growing and consistent body of evidence that points to aluminum as being one such significant influence. Evidence is presented that reinforces the likelihood that aluminum is a factor speeding the rate of brain aging. Such acceleration would inevitably enlarge the incidence of age-related neurological diseases.

  3. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration.

    PubMed

    Bondy, Stephen C

    2016-01-01

    Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer's disease. Epidemiological data is reinforced by indications that aluminum exposure can result in excess inflammatory activity within the brain. Activation of the immune system not initiated by an infectious agent, typifies the aging brain and is even more augmented in several neurodegenerative diseases. The origin of most age-related neurological disorders is generally not known but as they are largely not of genetic derivation, their development is likely triggered by unknown environmental factors. There is a growing and consistent body of evidence that points to aluminum as being one such significant influence. Evidence is presented that reinforces the likelihood that aluminum is a factor speeding the rate of brain aging. Such acceleration would inevitably enlarge the incidence of age-related neurological diseases. PMID:26687397

  4. The Prevalence of Age-Related Eye Diseases and Cataract Surgery among Older Adults in the City of Lodz, Poland

    PubMed Central

    Nowak, Michal Szymon; Smigielski, Janusz

    2015-01-01

    Purpose. To determine the prevalence of age-related eye diseases and cataract surgery among older adults in the city of Lodz, in central Poland. Material and Methods. The study design was cross-sectional and observational study. A total of 1107 women and men of predominantly Caucasian origin were successfully enumerated and recruited for the study. All selected subjects were interviewed and underwent detailed ophthalmic examinations. Results. Overall 8.04% (95% CI 6.44–9.64) subjects had cataract surgery in either eye. After excluding subjects with bilateral cataract surgery, the prevalence of cataract was 12.10% (95% CI 10.18–14.03). AMD was found in 4.33% (95% CI 3.14–5.54 ) of all subjects. Of them 3.25% (95% CI 2.21–4.30 ) had early AMD and 1.08% (95% CI 0.47–1.69) had late AMD. Various types of glaucoma were diagnosed in 5.51% (95% CI 4.17–6.85) of subjects and 2.62% (95% CI 1.68–3.56) had OHT. The prevalence rates of DR and myopic macular degeneration were 1.72% (95% CI 0.95–2.48) and 0.45% (95% CI 0.06–0.85), respectively. All multiple logistic regression models were only significantly associated with older age. The highest rate of visual impairment was observed among subjects with retinal diseases. Conclusions. The study revealed high prevalence of age-related eye diseases in this older population. PMID:25789169

  5. The Age-Related Eye Disease Study 2 (AREDS2): Study Design and Baseline Characteristics (AREDS2 Report Number 1)

    PubMed Central

    Chew, Emily Y.; Clemons, Traci; SanGiovanni, John Paul; Danis, Ronald; Domalpally, Amitha; McBee, Wendy; Sperduto, Robert; Ferris, Frederick L.

    2012-01-01

    Purpose The Age-Related Eye Disease Study (AREDS) demonstrated beneficial effects of oral supplementation with antioxidant vitamins and minerals on the development of advanced age-related macular degeneration (AMD) in persons with at least intermediate AMD (bilateral large drusen with or without pigment changes). Observational data suggest that other oral nutrient supplements might further reduce the risk of progression to advanced AMD. The primary purpose of Age-Related Eye Disease Study 2 (AREDS2) is to evaluate the efficacy and safety of lutein+zeaxanthin (L+Z) and/or omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation in reducing the risk of developing advanced AMD. The study will also assess the reduction in zinc and the omission of beta-carotene from original AREDS formulation. Design Multicenter phase 3 randomized controlled clinical trial Participants Persons age 50 to 85 with bilateral intermediate AMD or advanced AMD in one eye Methods All participants were randomly assigned to: 1) placebo (n=1012); 2) L+Z (10 mg/2 mg, n=1044); 3) ω-3 LCPUFAs (eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) [650gmg/350 mg] n=1069); or 4) the combination of L+Z and ω -3 LCPUFAs (n=1078). All participants were offered a secondary randomization to 1 of 4 variations of the original AREDS formulation keeping vitamins C (500 mg), E (400 IU), and copper (2 mg) unchanged while varying zinc and beta-carotene as follows: zinc remains at the original level (80mg), lower only zinc to 25mg, omit beta-carotene only, or lower zinc to 25 mg and omit beta-carotene. Main Outcome Measures Progression to advanced AMD determined by centralized grading of annual fundus photographs. Results 4,203 participants were enrolled at 82 clinical centers located in the U.S. Population characteristics at baseline were as follows: mean age 74 years, 57% female, 97% white, 7% current smokers, 19% with prior cardiovascular disease and 44% and 50% taking statin-class cholesterol

  6. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  7. Silver paper: the future of health promotion and preventive actions, basic research, and clinical aspects of age-related disease--a report of the European Summit on Age-Related Disease.

    PubMed

    Cruz-Jentoft, Alfonso J; Franco, Alain; Sommer, Pascal; Baeyens, Jean Pierre; Jankowska, Ewa; Maggi, Adriana; Ponikowski, Piotr; Rys, Andrzej; Szczerbinska, Kataryna; Michel, Jean-Pierre; Milewicz, Andrzej

    2009-12-01

    BACKGROUND. In September 2008, under the French Presidency of the European Union and with the support of the Polish Minister of Health, a European Summit on Age-Related Disease was organised inWroclaw (Poland). At this meeting, European politicians, gerontologists and geriatricians gathered to discuss a common approach to future challenges related to age-related disease. Politicians and decision-makers from the European Union and Ministers of Health and their deputies from many European countries raised the problems and difficulties to be tackled in a growing population with a high burden of disease, and asked scientists to write a consensus document with recommendations for future actions and decisions. Scientists and clinicians worked in parallel in three different groups, on health promotion and preventive actions, basic research in age-related disease, and clinical aspects of disease in older people. Beforehand, the format of the paper with recommendations was discussed, and it was finally agreed that, for a better understanding by decision- makers, it would be divided in two different columns: one with facts that were considered settled and agreed by most experts (under the heading We know), and a second with recommendations related to each fact (We recommend). No limit on the number of topics to be discussed was settled. After careful and detailed discussion in each group, which in most cases included the exact wording of each statement, chairpersons presented the results in a plenary session, and new input from all participants was received, until each of the statements and recommendations were accepted by a large majority. Areas with no consensus were excluded from the document. Immediately after the Summit, the chairpersons sent the document both to the main authors and to a list of experts (see footnote) who had made presentations at the summit and agreed to review and critically comment on the final document, which is presented below. As regards the

  8. Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration.

    PubMed

    Lucke-Wold, Brandon P; Turner, Ryan C; Logsdon, Aric F; Simpkins, James W; Alkon, Daniel L; Smith, Kelly E; Chen, Yi-Wen; Tan, Zhenjun; Huber, Jason D; Rosen, Charles L

    2015-01-01

    Ischemic stroke and Alzheimer's disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

  9. Compliance and chronic disease.

    PubMed

    German, P S

    1988-03-01

    The shifting demographics of the population and increasing skill in treatment of chronic disease in this country have combined to make compliance a topic of greater salience than ever before. General issues of compliance are a necessary background to specific issues of compliance with regimens for single diseases such as hypertension. The definition of compliance continues to be modified, and examination of past work reveals certain consistencies in studies of compliance. Non-compliance is higher in chronic conditions, in activities requiring change in life-style, and in clinician-initiated visits. Noncomprehension of instructions is held to be the most frequent cause of noncompliance. Noncompliance is a threat to the course of treatment, increases unnecessary diagnostic procedures, and confounds evaluation of effectiveness. Factors related to compliance have been identified with regard to certain patient and disease characteristics, amount of support in the immediate environment, and the nature of the doctor-patient relationship. Older patients are often at greater risk in understanding regimens because clinicians educate this group less often, because symptoms are misunderstood by both patient and provider, and because of greater complexity in both conditions that are being treated and number of drugs and other aspects of treatment required. Methods of improving the doctor-patient relationship have been urged most recently as a means through which compliance can be increased.

  10. Stem cells: a new paradigm for disease modeling and developing therapies for age-related macular degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 55 in the U.S. and the developed world. This condition leads to the progressive impairment of central visual acuity. There are significant limitations in the understanding of disease progression in AMD as well as a lack of effective methods of treatment. Lately, there has been considerable enthusiasm for application of stem cell biology for both disease modeling and therapeutic application. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) have been used in cell culture assays and in vivo animal models. Recently a clinical trial was approved by FDA to investigate the safety and efficacy of the human embryonic stem cell-derived retinal pigment epithelium (RPE) transplantation in sub-retinal space of patients with dry AMD These studies suggest that stem cell research may provide both insight regarding disease development and progression, as well as direction for therapeutic innovation for the millions of patients afflicted with AMD. PMID:23452406

  11. Late and chronic Lyme disease.

    PubMed

    Donta, Sam T

    2002-03-01

    This article reviews the late and chronic manifestations of Lyme disease. Special attention is given to the chronic manifestations of the disease, detailing its pathogenesis, clinical spectrum, and laboratory criteria for the diagnosis. Based on experimental evidence and experience, approaches to the successful treatment of the late and chronic disease are outlined. Much additional work is needed to improve the understanding of the underlying pathophysiology of the disease, its diagnosis and treatment.

  12. Chronic granulomatous disease.

    PubMed

    Nair, Pradeep S; Moorthy, Prasanna K; Suprakasan, S; Jayapalan, Sabeena; Preethi, K

    2005-01-01

    A 2(1/2)-year-old child presented with multiple discrete granulomatous lesions on the face and flexural regions since the age of 2 months along with lymphadenopathy. The patient also had recurrent bouts of pyodermas and respiratory tract infections. Biopsy of the lesion showed necrosis of tissue with suppuration and histiocytes but no evidence of tuberculosis, fungal infections or atypical mycobacteria. Lymph node biopsy also showed necrosis with suppuration but no infective organism. Nitroblue tetrazolium test was negative indicating that the neutrophils failed to oxidize the dye. We are reporting here a rare case of chronic granulomatous disease. PMID:16394414

  13. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation)

    PubMed Central

    Nita, Małgorzata; Ascaso, Francisco J.; Huerva, Valentín

    2014-01-01

    The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation) process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH) and facilitates chronic inflammation mediated by C-reactive protein (CRP). Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2) and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages); however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages). PMID:25214719

  14. A critical review of Vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease

    PubMed Central

    Harrison, Fiona E

    2013-01-01

    Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer’s disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes, and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer’s disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet. PMID:22366772

  15. β-amyloidopathy in the Pathogenesis of Age-Related Macular Degeneration in Correlation with Neurodegenerative Diseases.

    PubMed

    Ermilov, Victor V; Nesterova, Alla A

    2016-01-01

    Involvement of new biotechnology and genetic engineering methods to the study of the aging organism allowed to select a group of neurodegenerative diseases (NDD) which have a similar mechanism of pathogenesis including pathological processes of protein aggregation and its deposition in the structures of nerve tissue. The development of eye and brain from one embryonic germ layer, community of ethiopathogenetic and morphological manifestations of age-related macular degeneration (AMD) and Alzheimer's disease (AD), a common pathway of β-amyloid precursor protein (APP) are associated with the pathological aggregation of fibrillar β-amyloid (Aβ) protein and the development of β-amyloidopathy in structural elements of the eye and the brain. The review demonstrates the keynote of AMD and AD pathogenesis is β-amyloidopathy that is a manifestation of proteinopathy leading to cytotoxicity, neurodegeneration and the development of pathological apoptosis activated by the formation of intracellular Aβ. This view on the problem predetermines the development of new strategies for the creating of ophthalmogeriatric and neuroprotective drugs affecting the pathogenesis and including all stages of Aβ formation and pathological aggregation. PMID:26427402

  16. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  17. Mechanism of All-trans-retinal Toxicity with Implications for Stargardt Disease and Age-related Macular Degeneration*

    PubMed Central

    Chen, Yu; Okano, Kiichiro; Maeda, Tadao; Chauhan, Vishal; Golczak, Marcin; Maeda, Akiko; Palczewski, Krzysztof

    2012-01-01

    Compromised clearance of all-trans-retinal (atRAL), a component of the retinoid cycle, increases the susceptibility of mouse retina to acute light-induced photoreceptor degeneration. Abca4−/−Rdh8−/− mice featuring defective atRAL clearance were used to examine the one or more underlying molecular mechanisms, because exposure to intense light causes severe photoreceptor degeneration in these animals. Here we report that bright light exposure of Abca4−/−Rdh8−/− mice increased atRAL levels in the retina that induced rapid NADPH oxidase-mediated overproduction of intracellular reactive oxygen species (ROS). Moreover, such ROS generation was inhibited by blocking phospholipase C and inositol 1,4,5-trisphosphate-induced Ca2+ release, indicating that activation occurs upstream of NADPH oxidase-mediated ROS generation. Because multiple upstream G protein-coupled receptors can activate phospholipase C, we then tested the effects of antagonists of serotonin 2A (5-HT2AR) and M3-muscarinic (M3R) receptors and found they both protected Abca4−/−Rdh8−/− mouse retinas from light-induced degeneration. Thus, a cascade of signaling events appears to mediate the toxicity of atRAL in light-induced photoreceptor degeneration of Abca4−/−Rdh8−/− mice. A similar mechanism may be operative in human Stargardt disease and age-related macular degeneration. PMID:22184108

  18. Understanding anemia of chronic disease.

    PubMed

    Fraenkel, Paula G

    2015-01-01

    The anemia of chronic disease is an old disease concept, but contemporary research in the role of proinflammatory cytokines and iron biology has shed new light on the pathophysiology of the condition. Recent epidemiologic studies have connected the anemia of chronic disease with critical illness, obesity, aging, and kidney failure, as well as with the well-established associations of cancer, chronic infection, and autoimmune disease. Functional iron deficiency, mediated principally by the interaction of interleukin-6, the iron regulatory hormone hepcidin, and the iron exporter ferroportin, is a major contributor to the anemia of chronic disease. Although anemia is associated with adverse outcomes, experimental models suggest that iron sequestration is desirable in the setting of severe infection. Experimental therapeutic approaches targeting interleukin-6 or the ferroportin-hepcidin axis have shown efficacy in reversing anemia in either animal models or human patients, although these agents have not yet been approved for the treatment of the anemia of chronic disease.

  19. Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

    PubMed Central

    Anderson, R. M.; May, R. M.

    1985-01-01

    Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of 'who acquires infection from whom', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in 'virgin' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and

  20. [Cell senescence and pathophysiology of chronic lung diseases: role in chronic obstructive pulmonary disease].

    PubMed

    Adnot, Serge

    2014-01-01

    Knowledge of the biology of cellular senescence has improved markedly in recent years, helping us to understand the aging process. It is now clear that cellular senescence is involved in the pathogenesis of many age-related diseases, including respiratory diseases such as chronic obstructive pulmonary disease (COPD). COPD occupies a special place among chronic respiratory diseases because of its frequency and socio-economic impact. The high morbidity and mortality associated with COPD are related to multiple systemic manifestations independent of the severity of airway obstruction. COPD, although most often due to smoking, is also an aging-related respiratory disease. According to a newly developed concept, lung-cell senescence could play a key role in the pathophysiology of COPD, including remodeling of blood vessels and lung parenchyma, as well as the characteristic inflammatory process. Systemic manifestations of COPD, including cardiovascular disease, weight loss, bone demineralization and muscle dysfunction, may reflect a general process of premature aging secondary to the pulmonary changes.

  1. Genetic Determinants of Macular Pigments in Women of the Carotenoids in Age-Related Eye Disease Study

    PubMed Central

    Meyers, Kristin J.; Johnson, Elizabeth J.; Bernstein, Paul S.; Iyengar, Sudha K.; Engelman, Corinne D.; Karki, Chitra K.; Liu, Zhe; Igo, Robert P.; Truitt, Barbara; Klein, Michael L.; Snodderly, D. Max; Blodi, Barbara A.; Gehrs, Karen M.; Sarto, Gloria E.; Wallace, Robert B.; Robinson, Jennifer; LeBlanc, Erin S.; Hageman, Gregory; Tinker, Lesley; Mares, Julie A.

    2013-01-01

    Purpose. To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. Methods. 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. Results. Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10−4). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10−11). Conclusions. Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD. PMID:23404124

  2. Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples.

    PubMed

    Wijesinghe, Printha; Shankar, S K; Chickabasaviah, Yasha T; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo Hun; Steinbusch, H W; De Silva, K Ranil D

    2016-01-01

    Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations.

  3. Cytoskeletal Pathologies of Age-Related Diseases between Elderly Sri Lankan (Colombo) and Indian (Bangalore) Brain Samples.

    PubMed

    Wijesinghe, Printha; Shankar, S K; Chickabasaviah, Yasha T; Gorrie, Catherine; Amaratunga, Dhammika; Hulathduwa, Sanjayah; Kumara, K Sunil; Samarasinghe, Kamani; Suh, Yoo Hun; Steinbusch, H W; De Silva, K Ranil D

    2016-01-01

    Within South Asia, Sri Lanka represents fastest aging with 13% of the population was aged over 60's in 2011, whereas in India it was 8%. Majority of the Sri Lankan population based genetic studies have confirmed their origin on Indian mainland. As there were inadequate data on aging cytoskeletal pathologies of these two nations with their close genetic affiliations, we performed a comparison on their elderly. Autopsy brain samples of 50 individuals from Colombo, Sri Lanka (mean age 72.1 yrs ± 7.8, mean ± S.D.) and 42 individuals from Bangalore, India (mean age 65.9 yrs ± 9.3) were screened for neurodegenerative pathologies using immunohistochemical techniques. A total of 79 cases with incomplete clinical history (Colombo- 47 and Bangalore- 32) were subjected to statistical analysis and 13 cases, clinically diagnosed with dementia and/or Parkinsonism disorders were excluded. As per National Institute on Aging- Alzheimer's Association guidelines, between Colombo and Bangalore samples, Alzheimer's disease neuropathologic change for intermediate/ high level was 4.25% vs. 3.12% and low level was 19.15% vs. 15.62% respectively. Pathologies associated with Parkinsonism including brainstem predominant Lewy bodies- 6.4% and probable progressive supra nuclear palsy- 2.13% were found solely in Colombo samples. Alzheimer related pathologies were not different among elders, however, in Colombo males, neurofibrillary tangle grade was significantly higher in the region of hippocampus (odds ratio = 1.46, 95% confidence interval = 0.07-0.7) and at risk in midbrain substantia nigra (p = 0.075). Other age-related pathologies including spongiform changes (p < 0.05) and hippocampus cell loss in dentate gyrus region (p < 0.05) were also identified prominently in Colombo samples. Taken together, aging cytoskeletal pathologies are comparatively higher in elderly Sri Lankans and this might be due to their genetic, dietary and/ or environmental variations. PMID:26906356

  4. Patients with chronic pulmonary disease.

    PubMed

    Hong, Caron M; Galvagno, Samuel M

    2013-11-01

    Chronic pulmonary disease is common among the surgical population and the importance of a thorough and detailed preoperative assessment is monumental for minimizing morbidity and mortality and reducing the risk of perioperative pulmonary complications. These comorbidities contribute to pulmonary postoperative complications, including atelectasis, pneumonia, and respiratory failure, and can predict long-term mortality. The important aspects of the preoperative assessment for patients with chronic pulmonary disease, and the value of preoperative testing and smoking cessation, are discussed. Specifically discussed are preoperative pulmonary assessment and management of patients with chronic obstructive pulmonary disease, asthma, restrictive lung disease, obstructive sleep apnea, and obesity. PMID:24182721

  5. Chronic Granulomatous Disease.

    PubMed

    Rawat, Amit; Bhattad, Sagar; Singh, Surjit

    2016-04-01

    Chronic granulomatous disease (CGD) is the most common symptomatic phagocytic defect. It is caused by mutations in genes encoding protein subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD is characterized by a defective intracellular killing of phagocytosed organisms due to a defective oxidative burst in the neutrophils and macrophages. It is inherited in either X-linked recessive or autosomal recessive pattern. Staphylococcus aureus and Aspergillus species are the most common organisms reported. Infections with Burkholderia, Serratia, and Nocardia warrant a screen for CGD. Suppurative lymphadenitis, cutaneous abscesses, pneumonia and diarrhea constitute the most common problems in children with CGD. A small percentage of children develop autoimmune manifestations (e.g., rheumatoid arthritis, systemic lupus erythematosus, colitis, autoimmune hepatitis) and warrant immunosuppression. X-linked carriers of CGD are at an increased risk of developing autoimmune diseases. Nitroblue-tetrazolium dye reduction test and dihydro-rhodamine assay by flow cytometry are the screening tests for this disorder. While most children do well on long term antibiotic and antifungal prophylaxis, those with severe forms warrant hematopoietic stem cell transplant. The role of regular interferon-γ injections is debatable. Evidence for white cell transfusions is sparse, and gene therapy is under trial.This current review highlights various aspects and studies in CGD. X-linked form of CGD has been noted to carry a poorer prognosis compared to autosomal recessive variants. However, recent evidence suggests that outcome in CGD is determined by the amount of residual NADPH oxidase activity irrespective of mode of inheritance. PMID:26865172

  6. [Chronic granulomatous disease].

    PubMed

    Alvarez-Cardona, Aristóteles; Yamazaki-Nakashimada, Marco Antonio; Espinosa-Padilla, Sara Elva

    2009-01-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency, a phagocyte defect that appears in 1:200,000 live births and is produced by mutations in the genes that codify for the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). The inheritance form is X linked (> 60%) or autosomic recesive (30-40%). The NADPH oxidase is responsible for the production of reactive oxygen species (ROS) in the activated phagocyte ("respiratory burst"). When present, mutations on the NAPDH oxidase genes do not allow the ROS production, making the neutrophils of these patients incapable to destroy pathogens. These patients are especially susceptible to infections by staphylococcus, fungi and some gram-negative bacteria. The main clinical manifestations include recurrent life-threatening episodes of lymphadenitis, abscess, pneumonias, osteomyelitis, granuloma formation and sepsis. The diagnosis is suggested by a history of recurrent infections, familiar cases, fail to grow and confirmed with an altered test of ROS production and the specific mutation. Allogenic stem cells transplant is the curative treatment. The early diagnosis and the treatment with prophylactic antibiotics and interferon-gamma have modified favorably the morbidity and mortality of these patients.

  7. Chronic Granulomatous Disease

    PubMed Central

    2015-01-01

    Chronic Granulomatous Disease (CGD) is an inherited immunodeficiency disorder characterized by defective functioning of NADPH oxidase enzyme in the phagocytes. This leads to recurrent infections by catalase positive organisms and later, granuloma formation in multiple organs. This condition usually presents in the age group of 2-5 y and is uncommon in neonates. In this case report, we describe a rare case of CGD in a 40-day-old male child who initially presented with a history of erythematous pustular rash on left forearm and refusal to feeds. He remained unresponsive to regular antibiotics. CT chest and abdomen revealed multiple ill-defined lesions suggestive of granulomas or developing abscesses. Immunodeficiency workup showed negative Nitroblue Tetrazolium test and positive Dihydrorhodamine test (flow cytometry). A diagnosis of CGD was then made and treated accordingly. The aim of this report is to highlight the fact that although it is rare for CGD to present at such an early age, but in a neonate with multiple granulomas or abscesses, it should be considered as a differential and worked up accordingly. Early diagnosis and treatment can significantly improve the prognosis. PMID:26155526

  8. Age-Related Macular Degeneration and the Incidence of Cardiovascular Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Wu, Juan; Uchino, Miki; Sastry, Srinivas M.; Schaumberg, Debra A.

    2014-01-01

    Importance Research has indicated some shared pathogenic mechanisms between age-related macular degeneration (AMD) and cardiovascular disease (CVD). However, results from prior epidemiologic studies have been inconsistent as to whether AMD is predictive of future CVD risk. Objective To systematically review population-based cohort studies of the association between AMD and risk of total CVD and CVD subtypes, coronary heart disease (CHD) and stroke. Data Sources A systematic search of the PubMed and EMBASE databases and reference lists of key retrieved articles up to December 20, 2012 without language restriction. Data Extraction Two reviewers independently extracted data on baseline AMD status, risk estimates of CVD and methods used to assess AMD and CVD. We pooled relative risks using random or fixed effects models as appropriate. Results Thirteen cohort studies (8 prospective and 5 retrospective studies) with a total of 1,593,390 participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included in this meta-analysis. Among all studies, early AMD was associated with a 15% (95% CI, 1.08–1.22) increased risk of total CVD. The relative risk was similar but not significant for late AMD (RR, 1.17; 95% CI, 0.98–1.40). In analyses restricted to the subset of prospective studies, the risk associated with early AMD did not appreciably change; however, there was a marked 66% (95% CI, 1.31–2.10) increased risk of CVD among those with late AMD. Conclusion Whereas the results from all cohort studies suggest that both early and late AMD are predictive of a small increase in risk of future CVD, subgroup analyses limited to prospective studies demonstrate a markedly increased risk of CVD among people with late AMD. Retrospective studies using healthcare databases may have inherent methodological limitations that obscure such association. Additional prospective studies are needed to further elucidate the associations between AMD and specific CVD outcomes

  9. The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population

    PubMed Central

    Jin, Kunlin; Simpkins, James W.; Ji, Xunming; Leis, Miriam; Stambler, Ilia

    2015-01-01

    Due to the aging of the global population and the derivative increase in aging-related non-communicable diseases and their economic burden, there is an urgent need to promote research on aging and aging-related diseases as a way to improve healthy and productive longevity for the elderly population. To accomplish this goal, we advocate the following policies: 1) Increasing funding for research and development specifically directed to ameliorate degenerative aging processes and to extend healthy and productive lifespan for the population; 2) Providing a set of incentives for commercial, academic, public and governmental organizations to foster engagement in such research and development; and 3) Establishing and expanding coordination and consultation structures, programs and institutions involved in aging-related research, development and education in academia, industry, public policy agencies and at governmental and supra-governmental levels. PMID:25657847

  10. A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology [ISRCTN78467674

    PubMed Central

    Bartlett, Hannah; Eperjesi, Frank

    2003-01-01

    Background Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition. PMID:14594455

  11. Chronic Liver Disease and Hispanic Americans

    MedlinePlus

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While the ...

  12. Chronic Kidney Disease and Medicines

    MedlinePlus

    ... Alternate Language URL Español Chronic Kidney Disease and Medicines: What You Need to Know Page Content What ... pharmacist and provider need to know about your medicine and supplement use Your kidneys do not filter ...

  13. Age-Related Renal Disease in Dahl Salt Sensitive Rats is Attenuated with 17β-Estradiol Supplementation by Modulating Nitric Oxide Synthase Expression

    PubMed Central

    Maric, Christine; Xu, Qin; Sandberg, Kathryn; Hinojosa-Laborde, Carmen

    2011-01-01

    Background The incidence of chronic renal disease in women increases with aging especially after menopause suggesting that the loss of sex hormones contributes to the development and progression of renal disease. However, the mechanisms by which sex hormones, estrogens in particular, contribute to the disease process are unclear. Objective The present study examined the effects of ovariectomy (OVX) with or without 17β-estadiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney. Methods The study was performed in young (4 months, 4M) and aged (12 months, 12M) Dahl salt sensitive (DSS) rats fed a low salt (0.1% NaCl) diet. Results OVX in the aged rats was associated with 35% and 25% decreases, respectively, in medullary iNOS (4M OVX, 1.81±0.14 vs. 12M OVX, 1.17±0.16, P<0.05) and eNOS (4M OVX, 1.91±0.09 vs. 12M OVX, 1.43±0.15, P<0.05) protein expression and a 25-fold increase in the abundance of CD68-positive cells indicating macrophage infiltration (4M OVX, 1.18±0.09 vs. 12M OVX, 30.0±0.74, P<0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (4M OVX+E2, 2.26±0.08 vs. 12M OVX+E2, 1.70±0.09, P<0.05), eNOS (4M OVX+E2, 2.03±0.07 vs 12M OVX+E2, 1.77±0.11) and CD68 (4M OVX+E2, 1.46±0.07 vs. 12M OVX+E2, 6.87±1.6, P<0.01) associated with OVX in the aging kidney. Conclusions These data suggest that ovarian E2 loss with aging may contribute to the development of age-related renal disease through downregulation of iNOS and eNOS protein abundance and increased renal inflammation. Furthermore, E2 supplementation may be protective in the aging kidney by attenuating these changes. PMID:18573482

  14. Chronic Beryllium Disease

    MedlinePlus

    ... an immune response or “allergy” to beryllium metal, ceramic or alloy, termed beryllium sensitization (BeS). Beryllium sensitization ... Mroz MM, Newman LS. Beryllium disease screening in ceramics industry: Blood test performance and exposure-disease relations. ...

  15. Children, Sports, and Chronic Disease.

    ERIC Educational Resources Information Center

    Goldberg, Barry

    1990-01-01

    Discusses four chronic diseases (cystic fibrosis, congenital heart disease, rheumatoid arthritis, and asthma) that affect American children. Many have their physical activities unnecessarily restricted, though sports and exercise can actually alleviate symptoms and improve their psychosocial development. Physicians are encouraged to prescribe…

  16. Chronic diseases in captive geriatric female Chimpanzees (Pan troglodytes).

    PubMed

    Nunamaker, Elizabeth A; Lee, D Rick; Lammey, Michael L

    2012-04-01

    The current aging population of captive chimpanzees is expected to develop age-related diseases and present new challenges to providing their veterinary care. Spontaneous heart disease and sudden cardiac death are the main causes of death in chimpanzees (especially of male animals), but little is known about the relative frequency of other chronic diseases. Furthermore, female chimpanzees appear to outlive the males and scant literature addresses clinical conditions that affect female chimpanzees. Here we characterize the types and prevalence of chronic disease seen in geriatric (older than 35 y) female chimpanzees in the colony at Alamogordo Primate Facility. Of the 16 female chimpanzees that fit the age category, 87.5% had some form of chronic age-related disease. Cardiovascular-related disease was the most common (81.25%) followed by metabolic syndrome (43.75%) and renal disease (31.25%). These data show the incidence of disease in geriatric female chimpanzees and predict likely medical management challenges associated with maintaining an aging chimpanzee population. PMID:22546920

  17. Chronic Diseases in Captive Geriatric Female Chimpanzees (Pan troglodytes)

    PubMed Central

    Nunamaker, Elizabeth A; Lee, D Rick; Lammey, Michael L

    2012-01-01

    The current aging population of captive chimpanzees is expected to develop age-related diseases and present new challenges to providing their veterinary care. Spontaneous heart disease and sudden cardiac death are the main causes of death in chimpanzees (especially of male animals), but little is known about the relative frequency of other chronic diseases. Furthermore, female chimpanzees appear to outlive the males and scant literature addresses clinical conditions that affect female chimpanzees. Here we characterize the types and prevalence of chronic disease seen in geriatric (older than 35 y) female chimpanzees in the colony at Alamogordo Primate Facility. Of the 16 female chimpanzees that fit the age category, 87.5% had some form of chronic age-related disease. Cardiovascular-related disease was the most common (81.25%) followed by metabolic syndrome (43.75%) and renal disease (31.25%). These data show the incidence of disease in geriatric female chimpanzees and predict likely medical management challenges associated with maintaining an aging chimpanzee population. PMID:22546920

  18. Chronic Granulomatous Disease (CGD)

    MedlinePlus

    ... on ClinicalTrials.gov . Related Links​ Primary Immune Deficiency Diseases (PIDDs) Immune System National Library of Medicine, Genetics Home Reference ​​​ Javascript Error Your browser JavaScript is turned off causing certain ... and Infectious Diseases web site to work incorrectly. Please visit your ...

  19. Nutrigerontology: why we need a new scientific discipline to develop diets and guidelines to reduce the risk of aging-related diseases

    PubMed Central

    Verburgh, Kris

    2015-01-01

    Many diets and nutritional advice are circulating, often based on short- or medium-term clinical trials and primary outcomes, like changes in LDL cholesterol or weight. It remains difficult to assess which dietary interventions can be effective in the long term to reduce the risk of aging-related disease and increase the (healthy) lifespan. At the same time, the scientific discipline that studies the aging process has identified some important nutrient-sensing pathways that modulate the aging process, such as the mTOR and the insulin/insulin-like growth factor signaling pathway. A thorough understanding of the aging process can help assessing the efficacy of dietary interventions aimed at reducing the risk of aging-related diseases. To come to these insights, a synthesis of biogerontological, nutritional, and medical knowledge is needed, which can be framed in a new discipline called ‘nutrigerontology’. PMID:25470422

  20. The chronic enteropathogenic disease schistosomiasis.

    PubMed

    Olveda, David U; Olveda, Remigio M; McManus, Donald P; Cai, Pengfei; Chau, Thao N P; Lam, Alfred K; Li, Yuesheng; Harn, Donald A; Vinluan, Marilyn L; Ross, Allen G P

    2014-11-01

    Schistosomiasis is a chronic enteropathogenic disease caused by blood flukes of the genus Schistosoma. The disease afflicts approximately 240 million individuals globally, causing approximately 70 million disability-adjusted life years lost. Chronic infections with morbidity and mortality occur as a result of granuloma formation in the intestine, liver, or in the case of Schistosoma haematobium, the bladder. Various methods are utilized to diagnose and evaluate liver fibrosis due to schistosomiasis. Liver biopsy is still considered the gold standard, but it is invasive. Diagnostic imaging has proven to be an invaluable method in assessing hepatic morbidity in the hospital setting, but has practical limitations in the field. The potential of non-invasive biological markers, serum antibodies, cytokines, and circulating host microRNAs to diagnose hepatic fibrosis is presently undergoing evaluation. This review provides an update on the recent advances made with respect to gastrointestinal disease associated with chronic schistosomiasis.

  1. Chronic thyroiditis (Hashimoto disease)

    MedlinePlus

    Laboratory tests to determine thyroid function include: Free T4 test Serum TSH T3 Thyroid autoantibodies Imaging studies and fine needle biopsy are generally not needed to diagnose Hashimoto thyroiditis. This disease may ...

  2. Age-related effects of smoking on coronary artery disease assessed by gray scale and virtual histology intravascular ultrasound.

    PubMed

    Kang, Soo-Jin; Mintz, Gary S; Weisz, Giora; Mehran, Roxana; Rabbani, LeRoy E; Verheye, Stefan; Serruys, Patrick W; Xu, Ke; Stone, Gregg W; Maehara, Akiko

    2015-04-15

    Although smoking is a risk factor for coronary atherosclerosis, the age-related impact on lesion morphology has not been studied. The aim of this study was to assess the age-related impact of smoking on the extent of atherosclerosis and arterial remodeling. In Providing Regional Observations to Study Predictors of Events in the Coronary Tree, 687 patients with acute coronary syndrome underwent 3-vessel gray scale and virtual histology intravascular ultrasound imaging of 3,185 nonculprit lesions. In 207 patients ≤65 years, current (smoking within 1 month) and former (no smoking for >1 month) smokers showed significantly smaller normalized volumes of external elastic membrane (EEM), lumen, and P + M (plaque + media) compared with nonsmokers. At the minimal lumen area site, current and former smokers had significantly smaller EEM, lumen, and P + M areas than nonsmokers. Conversely, in 480 patients >65 years, current smokers had greater normalized P + M volumes than nonsmokers with no difference in normalized EEM or lumen volumes. Finally, in patients >65 years (but not in patients ≤65 years), current smokers showed more plaque ruptures (4.7% vs 1.8%, p = 0.05) and echolucent plaques (8.3% vs 3.9%, p = 0.05) compared with nonsmokers. On multivariable analysis, a history of smoking (combining current and former smoking) predicted smaller normalized EEM volumes compared with nonsmokers ≤65 years. In conclusion, in patients ≤65 years, but not in patients >65 years, smoking had a vascular constrictive effect that contributed to severe luminal stenosis. Conversely, smokers >65 years had more plaque with greater plaque instability. PMID:25726380

  3. Age-related effects of smoking on coronary artery disease assessed by gray scale and virtual histology intravascular ultrasound.

    PubMed

    Kang, Soo-Jin; Mintz, Gary S; Weisz, Giora; Mehran, Roxana; Rabbani, LeRoy E; Verheye, Stefan; Serruys, Patrick W; Xu, Ke; Stone, Gregg W; Maehara, Akiko

    2015-04-15

    Although smoking is a risk factor for coronary atherosclerosis, the age-related impact on lesion morphology has not been studied. The aim of this study was to assess the age-related impact of smoking on the extent of atherosclerosis and arterial remodeling. In Providing Regional Observations to Study Predictors of Events in the Coronary Tree, 687 patients with acute coronary syndrome underwent 3-vessel gray scale and virtual histology intravascular ultrasound imaging of 3,185 nonculprit lesions. In 207 patients ≤65 years, current (smoking within 1 month) and former (no smoking for >1 month) smokers showed significantly smaller normalized volumes of external elastic membrane (EEM), lumen, and P + M (plaque + media) compared with nonsmokers. At the minimal lumen area site, current and former smokers had significantly smaller EEM, lumen, and P + M areas than nonsmokers. Conversely, in 480 patients >65 years, current smokers had greater normalized P + M volumes than nonsmokers with no difference in normalized EEM or lumen volumes. Finally, in patients >65 years (but not in patients ≤65 years), current smokers showed more plaque ruptures (4.7% vs 1.8%, p = 0.05) and echolucent plaques (8.3% vs 3.9%, p = 0.05) compared with nonsmokers. On multivariable analysis, a history of smoking (combining current and former smoking) predicted smaller normalized EEM volumes compared with nonsmokers ≤65 years. In conclusion, in patients ≤65 years, but not in patients >65 years, smoking had a vascular constrictive effect that contributed to severe luminal stenosis. Conversely, smokers >65 years had more plaque with greater plaque instability.

  4. A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

    PubMed Central

    Li, Qi-Gang; Wu, Huan; Luo, Long-Hai; Kong, Qing-Peng

    2015-01-01

    It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs) were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer’s disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3)] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2)] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity. PMID:25793257

  5. Chronic venous disease.

    PubMed

    Wolinsky, Claire D; Waldorf, Heidi

    2009-11-01

    Identifying characteristic cutaneous findings is important in determining the appropriate management of certain venous diseases. The health care provider should be familiar with the classic description of patterns and distributions of skin manifestations, such as varicose veins, stasis dermatitis, palpable cord, petechiae, and telangiectasias. In addition to the gross appearance of the skin, a skin biopsy may help elucidate a diagnosis. General treatment and prevention of the underlying venous pathology is essential. Furthermore, specific management of skin findings should include therapy to ameliorate progression of disease and symptomatology when warranted.

  6. Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Criner, Gerard J.

    2013-01-01

    Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can develop CB, and small airway pathology has been linked to worse clinical outcomes, such as increased mortality and lesser improvement in lung function after lung volume reduction surgery. However, in recent years, a greater understanding of the importance of CB as a phenotype to identify patients with a beneficial response to therapy has been described. Herein we review the epidemiology of CB, the evidence behind its clinical consequences, the current understanding of the pathophysiology of goblet cell hyperplasia in COPD, and current therapies for CB. PMID:23204254

  7. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women’s Health Initiative

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to examine the relationship between lutein and zeaxanthin in the diet and serum and prevalence of age-related nuclear cataract in older women. Women’s Health Initiative Observational Study participants aged 50 y+, at 3 sites, who reported high (above the 78th percentile...

  8. NAFLD and Chronic Kidney Disease

    PubMed Central

    Marcuccilli, Morgan; Chonchol, Michel

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases. PMID:27089331

  9. The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress.

    PubMed

    Skibska, Beata; Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

  10. The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

    PubMed Central

    Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system. PMID:25949771

  11. Chronic Lyme disease: a review.

    PubMed

    Marques, Adriana

    2008-06-01

    Studies have shown that most patients diagnosed with chronic Lyme disease either have no objective evidence of previous or current infection with Borrelia burgdorferi or are patients who should be classified as having post-Lyme disease syndrome, which is defined as continuing or relapsing nonspecific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a patient previously treated for Lyme disease. Despite extensive study, there is currently no clear evidence that post-Lyme disease syndrome is caused by persistent infection with B burgdorferi. Four randomized placebo-controlled studies have shown that antibiotic therapy offers no sustained benefit to patients who have post-Lyme disease syndrome. These studies also showed a substantial placebo effect and a significant risk of treatment-related adverse events. Further research to elucidate the mechanisms underlying persistent symptoms after Lyme disease and controlled trials of new approaches to the treatment and management of these patients are needed.

  12. Perspectives on "chronic Lyme disease".

    PubMed

    Baker, Phillip J

    2008-07-01

    There is much controversy about the treatment of Lyme disease with respect to 2 poorly defined entities: "chronic Lyme disease" and "posttreatment Lyme disease syndrome." In the absence of direct evidence that these conditions are the result of a persistent infection, some mistakenly advocate extended antibiotic therapy (>/=6 months), which can do great harm and has resulted in at least 1 death. The purpose of this brief report is to review what is known from clinical research about these conditions to assist both practicing physicians and lawmakers in making sound and safe decisions with respect to treatment.

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

    PubMed

    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.

  14. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics).

    PubMed

    Uchiki, Tomoaki; Weikel, Karen A; Jiao, Wangwang; Shang, Fu; Caceres, Andrea; Pawlak, Dorota; Handa, James T; Brownlee, Michael; Nagaraj, Ram; Taylor, Allen

    2012-02-01

    Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains the salutary effect is a barrier to implementing dietary practices that capture the benefits of consuming lower GI diets. We established a simple murine model of age-related retinal lesions that precede AMD (hereafter called AMD-like lesions). We found that consuming a higher GI diet promotes these AMD-like lesions. However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (P < 0.02) and severity (P < 0.05) of hallmark age-related retinal lesions such as basal deposits. Consuming higher GI diets was associated with > 3 fold higher accumulation of advanced glycation end products (AGEs) in retina, lens, liver, and brain in the age-matched mice, suggesting that higher GI diets induce systemic glycative stress that is etiologic for lesions. Data from live cell and cell-free systems show that the ubiquitin-proteasome system (UPS) and lysosome/autophagy pathway [lysosomal proteolytic system (LPS)] are involved in the degradation of AGEs. Glycatively modified substrates were degraded significantly slower than unmodified substrates by the UPS. Compounding the detriments of glycative stress, AGE modification of ubiquitin and ubiquitin-conjugating enzymes impaired UPS activities. Furthermore, ubiquitin conjugates and AGEs accumulate and are found in lysosomes when cells are glycatively stressed or the UPS or LPS/autophagy are inhibited, indicating that the UPS and LPS interact with one another to degrade AGEs. Together, these data explain why AGEs accumulate as glycative stress increases. PMID:21967227

  15. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    MedlinePlus

    ... 1.5 MB] More Data Age-adjusted death rates for selected causes of death, by sex, race, and Hispanic origin (chronic lower respiratory disease includes chronic bronchitis, emphysema, asthma, and other ...

  16. Molecular promiscuity of plant polyphenols in the management of age-related diseases: far beyond their antioxidant properties.

    PubMed

    Barrajón-Catalán, Enrique; Herranz-López, María; Joven, Jorge; Segura-Carretero, Antonio; Alonso-Villaverde, Carlos; Menéndez, Javier A; Micol, Vicente

    2014-01-01

    The use of plant-derived polyphenols for the management of diseases has been under debate in the last decades. Most studies have focused on the specific effects of polyphenols on particular targets, while ignoring their pleiotropic character. The multitargeted character of polyphenols, a plausible consequence of their molecular promiscuity, may suppose an opportunity to fight multifactorial diseases. Therefore, a wider perspective is urgently needed to elucidate whether their rational use as bioactive food components may be valid for the management of diseases. In this chapter, we discuss the most likely targets of polyphenols that may account for their salutary effects from a global perspective. Among these targets, the modulation of signalling and energy-sensitive pathways, oxidative stress and inflammation-related processes, mitochondrial functionality, epigenetic machinery, histone acetylation and membrane-dependent processes play central roles in polyphenols' mechanisms of action.Sufficient evidence on polyphenols has accumulated for them to be considered a serious option for the management of non-communicable diseases, such as cancer and obesity, as well as infectious diseases. The remaining unresolved issues that must be seriously addressed are their bioavailability, metabolite detection, specific molecular targets, interactions and toxicity. The Xenohormesis hypothesis, which postulates that polyphenols are the product of plant evolutive adaptation to stress and conferee their resistance to mammals, offers a reasonable explanation to justify the beneficial and non-toxic effects of plant mixtures, but do not fully meet expectations. Hence, future research must be supported by the use of complex polypharmacology approaches and synergic studies focused on the understanding of the pleiotropic effects of polyphenols. Revisiting polyphenol mechanisms of action with the help of these techniques may allow for the improvement of human health and wellness by using

  17. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement.

    PubMed

    Candore, G; Caruso, C; Jirillo, E; Magrone, T; Vasto, S

    2010-01-01

    Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and age-related diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling age-related low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

  18. Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 1*

    PubMed Central

    Mayeux, Richard; Reitz, Christiane; Brickman, Adam M.; Haan, Mary N.; Manly, Jennifer J.; Glymour, M. Maria; Weiss, Christopher C.; Yaffe, Kristine; Middleton, Laura; Hendrie, Hugh C.; Warren, Lauren H.; Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.; Breitner, John C. S.; Morris, John C.

    2011-01-01

    Population studies strive to determine the prevalence of Alzheimer dementia but prevalence estimates vary widely. The challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer’s disease (AD) are reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD are considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies as may occur should a plasma biomarker be developed. Biomarkers for AD also could facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in “mixed dementia”. PMID:21255741

  19. Biological, psychological and clinical markers of caregiver's stress in impaired elderly with dementia and age-related disease.

    PubMed

    Neri, M; Bonati, P A; Pinelli, M; Borella, P; Tolve, I; Nigro, N

    2007-01-01

    Stress refers to the experience, produced through a person-environment transaction, that results in psychological or physiological distress. Everyday stress or hassles have a larger impact on health, in this frame caring for elderly disabled and/or demented persons have been shown to be a chronic role strain. The concept of stress and strain encompasses different levels of individual functioning (physiological, cognitive, affective, social). We studied whether 3 different distressing conditions show (i) different profiles in biological, psychological and clinical indices of stress, and (ii) different response to temporary environmental manipulation. A sample of 29 caregivers of elderly subjects temporarily institutionalized for (i) respite program, (ii) behavioral psychological symptoms of dementia (BPSD) in dementia-control and, (iii) a rehabilitation program after hip fracture, was assessed with clinical, psychological and biological measures. The BPSD appear to be the most powerful distressing factor, both at the beginning and at the end of the study. On the whole, to an improvement of patient's clinical picture, it corresponds only a partial improvement in stress indices of the caregiver. The slope of biological indices don not parallel those of psychological ones. Among psychometric indices, the pattern of recovery differentiate affective and cognitive domains. The "respite" care condition seems to be the less effective in reducing stress in the caregivers. The stress process should be considered in its different domains to allow a tailored intervention.

  20. Age-Related Alterations in Blood Biochemical Characterization of Hepatorenal Function in the PCK Rat: A Model of Polycystic Kidney Disease.

    PubMed

    Shimomura, Yuichi; Brock, William J; Ito, Yuko; Morishita, Katsumi

    2015-01-01

    PCK rats develop age-related polycystic kidney disease (PKD) and liver disease and have been used to investigate pharmacotherapies to ameliorate hepatorenal lesions for patients with PKD. The PCK rat may be useful to understand the possible susceptibility to hepatotoxicity observed in the patient with PKD having hepatic polycystic lesions. Therefore, the purpose of this study was to investigate the background blood biochemical changes that reflect the hepatorenal function of PCK rats as well as the terminal histopathology in order to determine whether this model would be suitable for extrapolating the susceptibility of hepatotoxicity in patients. The blood biochemical parameters of hepatorenal function and histopathology were investigated in PCK rats at ages 5 to 19 weeks and compared to those outcomes in the Sprague Dawley (SD) rat. There were notable blood biochemical changes possibly due to biliary dysgenesis in the PCK rat as early as 5 weeks of age. High levels of γ-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and total bile acids persisted throughout the study compared to the SD rat. Increased aspartate aminotransferase, total bilirubin, and hyperlipidemia and a decrease in albumin were also evident at 10 to 19 weeks of age possibly due to progression of cholestatic liver dysfunction secondary to age-related liver cystic progression. Increased liver weights generally correlated with the severity of biliary and hepatic histopathological changes. In male PCK rats, age-related increases in blood urea nitrogen and creatinine at 10 to 19 weeks of age were observed, and the cystic progression was more severe than that in females. These data indicate that the PCK rat showed notable blood biochemical changes reflecting alteration of the liver function compared to the SD rat. Also, there was a large individual variation in these parameters possibly due to variable progression rate of biliary dysgenesis and subsequent liver damages in PCK

  1. Beyond and behind the fingerprints of oxidative stress in age-related diseases: Secrets of successful aging.

    PubMed

    Polidori, M Cristina; Scholtes, Marlies

    2016-04-01

    Several years after the first publication of the definition of oxidative stress by Helmut Sies, this topic is still focus of a large body of attention and research in the field of aging, neurodegeneration and disease prevention. The conduction of clinical and epidemiological research without a solid biochemical rationale has led to largely frustrating results without being able to disprove the oxidative stress hypothesis. The present work is dedicated to Helmut Sies and describes the successful scientific approach to bench-to-bedside (-to-behavior) oxidative stress clinical research. PMID:27095215

  2. Progressive age-related changes in sleep and EEG profiles in the PLB1Triple mouse model of Alzheimer's disease.

    PubMed

    Jyoti, Amar; Plano, Andrea; Riedel, Gernot; Platt, Bettina

    2015-10-01

    Sleep disturbances are common in Alzheimer's disease (AD) and now assumed to contribute to disease onset and progression. Here, we investigated whether activity, sleep/wake pattern, and electroencephalogram (EEG) profiles are altered in the knock-in PLB1Triple mouse model from 5 to 21 months of age. PLB1Triple mice displayed a progressive increase in wakefulness and non-rapid eye movement sleep fragmentation from 9 months onward, whereas PLB1WT wild type controls showed such deterioration only at 21 months. Impaired habituation to spatial novelty was also detected in PLB1Triple mice. Hippocampal power spectra of transgenic mice revealed progressive, vigilance stage-, brain region-, and age-specific changes. Age had an impact on EEG spectra in both cohorts but led to accelerated genotype-dependent differences, ultimately affecting all bands at 21 months. Overall, although PLB1Triple animals display only subtle amyloid and tau pathologies, robust sleep-wake and EEG abnormalities emerged. We hypothesize that such endophenotypes are sensitive, noninvasive, and reliable biomarker to identify onset and progression of AD.

  3. Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer's disease

    PubMed Central

    Nisticò, Robert; Ferraina, Caterina; Marconi, Veronica; Blandini, Fabio; Negri, Lucia; Egebjerg, Jan; Feligioni, Marco

    2014-01-01

    Alzheimer's disease (AD) is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP, and JNK, are in fact subject to protein SUMO modifications or interactions. Here, we have investigated the SUMO/deSUMOylation balance and SUMO-related proteins during the onset and progression of the pathology in the Tg2576 mouse model of AD. We examined four age-stages (1.5, 3, 6, 17 months old) and observed shows an increase in SUMO-1 protein conjugation at 3 and 6 months in transgenic mice with respect to WT in both cortex and hippocampus. Interestingly this is paralleled by increased expression levels of Ubc9 and SENP1 in both brain regions. At 6 months of age also the SUMO-1 mRNA resulted augmented. SUMO-2-ylation was surprisingly decreased in old transgenic mice and was unaltered in the other time windows. The fact that alterations in SUMO/deSUMOylation equilibrium occur from the early phases of AD suggests that global posttranslational modifications may play an important role in the mechanisms underlying disease pathogenesis, thus providing potential targets for pharmacological interventions. PMID:24778618

  4. Placental Origins of Chronic Disease.

    PubMed

    Burton, Graham J; Fowden, Abigail L; Thornburg, Kent L

    2016-10-01

    Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions. PMID:27604528

  5. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease.

    PubMed

    Noto, Nobutaka; Okada, Tomoo; Karasawa, Kensuke; Ayusawa, Mamoru; Sumitomo, Naokata; Harada, Kensuke; Mugishima, Hideo

    2009-04-01

    The objective of this study was to test the hypothesis that accelerated endothelial dysfunction and the development of premature atherosclerosis are associated with age in subjects with coronary artery lesions after Kawasaki disease (KD). A case-control study was performed at a university hospital that included 35 post-KD subjects across a wide age range (range, 8-42 years) without traditional cardiovascular risk factors and 35 age- and sex-matched healthy control subjects (Cont). Flow-mediated dilatation (FMD) of the brachial artery-induced by reactive hyperemia, intima media thickness (IMT), and elastic modulus (Ep) of the common carotid artery were compared between KD and Cont subjects assessed against age. KD subjects had slightly higher levels of body mass index, lipid profile, and HbA1c than Cont subjects, but the differences were not significant. The mean IMT (p < 0.001), age-adjusted percentage normal IMT (%N IMT; p < 0.0001), and Ep (p < 0.001) were significantly higher in KD than Cont subjects, and the peak FMD% (p < 0.01) was significantly lower in KD than Cont subjects. There were significant correlations between FMD% and age (r = -0.51 p < 0.0001), IMT and age (r = 0.68, p < 0.001), and Ep and age (r = 0.58, p < 0.01) in KD but not Cont subjects. When the difference in FMD% between KD and matched Cont subjects (DeltaFMD%) was plotted against age, no significant relationship was found, although significant correlations between DeltaIMT and age (r = 0.52, p < 0.01) as well as between DeltaEp and age (r = 0.46, p < 0.05) were observed. When we defined values that were +2.0 SD over the mean control values (i.e., %N IMT >or= 120% and/or Ep >or= 50 kPa) as markers of subclinical atherosclerosis, 15 subjects met the criteria. Subjects over the age of 22 years were more likely to have (OR = 16.54, p = 0.0001) subclinical atherosclerosis in this cohort. Our results suggest that endothelial dysfunction and the development of premature atherosclerosis were

  6. Is age-related failure of metabolic reprogramming a principal mediator in idiopathic Parkinson's disease? Implications for treatment and inverse cancer risk.

    PubMed

    Engel, Peter A

    2016-08-01

    Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder characterized by selective degeneration of the substantia nigra pars compacta (SNc), dorsal motor nucleus of the vagus and other vulnerable nervous system regions characterized by extensive axonal arborization and intense energy requirements. Systemic age-related depression of mitochondrial function, oxidative phosphorylation (OXPHOS) and depressed expression of genes supporting energy homeostasis is more severe in IPD than normal aging such that energy supply may exceed regional demand. In IPD, the overall risk of malignancy is reduced. Cancer is a collection of proliferative diseases marked by malignant transformation, dysregulated mitosis, invasion and metastasis. Many cancers demonstrate normal mitochondrial function, preserved OXPHOS, competent mechanisms of energy homeostasis, and metabolic reprogramming capacities that are lacking in IPD. Metabolic reprogramming adjusts OXPHOS and glycolytic pathways in response to changing metabolic needs. These opposite metabolic features form the basis of a two component hypothesis. First, that depressed mitochondrial function, OXPHOS deficiency and impaired metabolic reprogramming contribute to focal energy failure, neurodegeneration and disease expression in IPD. Second, that the same systemic metabolic deficits inhibit development and proliferation of malignancies in IPD. Studies of mitochondrial aging, familial PD (FPD), the lysosomal storage disorder, Gaucher's disease, Parkinson's disease cybrids, the mitochondrial cytopathies, and disease-related metabolic reprogramming both in IPD and cancer provide support for this model. PMID:27372878

  7. Neuropsychological functioning in chronic Lyme disease.

    PubMed

    Westervelt, Holly James; McCaffrey, Robert J

    2002-09-01

    Lyme disease is currently the most common vector-borne illness in the United States. The disease is multisystemic, and chronic disease, in particular, may be associated with neuropsychological deficits. However, to date, only a few empirical studies exist, which examine the neuropsychological sequelae associated with chronic Lyme disease. A review of the literature shows that the deficits observed in adults with chronic Lyme disease are generally consistent with the deficits that can be seen in processes with primarily frontal systems involvement. These observations are generally consistent with neuroradiologic findings. The clinical presentation in chronic Lyme disease and the nature of the neuropsychological deficits are discussed, as are several central issues in understanding neuropsychological functioning in chronic Lyme disease, such as the impact of chronic illness, response to treatment, and the relationship between neuropsychological performance and depression, fatigue, and neurological indicators of disease.

  8. [Skin and chronic kidney disease].

    PubMed

    Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

    2014-01-01

    Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process. PMID:25315722

  9. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  10. HIV and chronic kidney disease.

    PubMed

    Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B

    2015-01-01

    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV

  11. Chronic polyneuropathy and Lyme disease.

    PubMed

    Mygland, A; Skarpaas, T; Ljøstad, U

    2006-11-01

    Infection of the peripheral nervous system with Borrelia burgdorferi can present as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF) pleocytosis and intrathecal antibody production against B. burgdorferi, or as an asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA) and normal CSF findings. According to North American studies, it can also present as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations. Our purpose was to investigate the prevalence of B. burgdorferi antibodies in patients presenting with isolated chronic polyneuropathy (PN) in a European region with high incidence of Lyme disease. Sera from 209 PN patients and 247 healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%) healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal spinal fluid white cell count and they did not differ clinically or electrophysiologically from PN patients without antibodies. None of 20 antibody-positive PN patients responded to antimicrobial treatment. The study shows that, in Europe, chronic distal PN without ACA or other Lyme manifestations is very rarely caused by a B. burgdorferi infection.

  12. Economic aspects of chronic diseases in Vietnam

    PubMed Central

    Van Minh, Hoang; Lan Huong, Dao; Bao Giang, Kim; Byass, Peter

    2009-01-01

    Introduction There remains a lack of information on economic aspects of chronic diseases. This paper, by gathering available and relevant research findings, aims to report and discuss current evidence on economic aspects of chronic diseases in Vietnam. Methods Data used in this paper were obtained from various information sources: international and national journal articles and studies, government documents and publications, web-based statistics and fact sheets. Results In Vietnam, chronic diseases were shown to be leading causes of deaths, accounting for 66% of all deaths in 2002. The burdens caused by chronic disease morbidity and risk factors are also substantial. Poorer people in Vietnam are more vulnerable to chronic diseases and their risk factors, other than being overweight. The estimated economic loss caused by chronic diseases for Vietnam in 2005 was about US$20 million (0.033% of annual national GDP). Chronic diseases were also shown to cause economic losses for families and individuals in Vietnam. Both population-wide and high-risk individual interventions against chronic disease were shown to be cost-effective in Vietnam. Conclusion Given the evidence from this study, actions to prevent chronic diseases in Vietnam are clearly urgent. Further research findings are required to give greater insights into economic aspects of chronic diseases in Vietnam. PMID:20057939

  13. New Directions in Chronic Disease Management

    PubMed Central

    Kim, Hun-Sung; Cho, Jae-Hyoung

    2015-01-01

    A worldwide epidemic of chronic disease, and complications thereof, is underway, with no sign of abatement. Healthcare costs have increased tremendously, principally because of the need to treat chronic complications of non-communicable diseases including cardiovascular disease, blindness, end-stage renal disease, and amputation of extremities. Current healthcare systems fail to provide an appropriate quality of care to prevent the development of chronic complications without additional healthcare costs. A new paradigm for prevention and treatment of chronic disease and the complications thereof is urgently required. Several clinical studies have clearly shown that frequent communication between physicians and patients, based on electronic data transmission from medical devices, greatly assists in the management of chronic disease. However, for various reasons, these advantages have not translated effectively into real clinical practice. In the present review, we describe current relevant studies, and trends in the use of information technology for chronic disease management. We also discuss limitations and future directions. PMID:26194075

  14. New Directions in Chronic Disease Management.

    PubMed

    Kim, Hun Sung; Cho, Jae Hyoung; Yoon, Kun Ho

    2015-06-01

    A worldwide epidemic of chronic disease, and complications thereof, is underway, with no sign of abatement. Healthcare costs have increased tremendously, principally because of the need to treat chronic complications of non-communicable diseases including cardiovascular disease, blindness, end-stage renal disease, and amputation of extremities. Current healthcare systems fail to provide an appropriate quality of care to prevent the development of chronic complications without additional healthcare costs. A new paradigm for prevention and treatment of chronic disease and the complications thereof is urgently required. Several clinical studies have clearly shown that frequent communication between physicians and patients, based on electronic data transmission from medical devices, greatly assists in the management of chronic disease. However, for various reasons, these advantages have not translated effectively into real clinical practice. In the present review, we describe current relevant studies, and trends in the use of information technology for chronic disease management. We also discuss limitations and future directions.

  15. Chronic kidney disease in children

    PubMed Central

    Becherucci, Francesca; Roperto, Rosa Maria; Materassi, Marco; Romagnani, Paola

    2016-01-01

    Chronic kidney disease (CKD) is a major health problem worldwide. Although relatively uncommon in children, it can be a devastating illness with many long-term consequences. CKD presents unique features in childhood and may be considered, at least in part, as a stand-alone nosologic entity. Moreover, some typical features of paediatric CKD, such as the disease aetiology or cardiovascular complications, will not only influence the child's health, but also have long-term impact on the life of the adult that they will become. In this review we will focus on the unique issues of paediatric CKD, in terms of aetiology, clinical features and treatment. In addition, we will discuss factors related to CKD that start during childhood and require appropriate treatments in order to optimize health outcomes and transition to nephrologist management in adult life. PMID:27478602

  16. [Anemia in chronic kidney disease].

    PubMed

    Amador-Medina, Lauro Fabián

    2014-01-01

    Anemia is almost unavoidable in the last stages of chronic kidney disease. It is defined as a condition where hemoglobin concentration is below 2 standard deviations from the mean hemoglobin level of the general population, corrected for age and sex (typically, hemoglobin < 13 g/dL in adults and 12 g/dL in women). Although the cause is multi-factorial, the most known is inadequate erythropoietin production. Anemia has been associated with poor prognosis in patients with several conditions such as cancer, chronic kidney disease and congestive heart failure. Treatment with erythropoiesis-stimulating agents, such as erythropoietin, is a logical strategy that has enabled clinical improvement and reduced transfusion requirements for the patients; however, total correction of anemia with erythropoiesis-stimulating agents has demonstrated an increase in the risk of mortality or cardiovascular complications associated with these agents. In randomized trials, the achievement of normal or nearly normal hemoglobin levels is not associated with improved survival and reduced cardiovascular risk; however the ideal hemoglobin level with the use of erythropoiesis-stimulating agents seems to be problematic. More information is needed in order to obtain definite conclusions; in the meantime, using the lowest possible dose of erythropoietin seems to be the most prudent approach.

  17. Kidneys in chronic liver diseases

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof

    2012-01-01

    Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support. PMID:22791939

  18. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease

    SciTech Connect

    Oppenheimer, D.A.; Jones, H.H.

    1982-12-01

    The case of a 14-year old girl with painful periostitis and ulcerative colitis is reported. The association of chronic inflammatory bowel disease with osteoarthropathy is rare and has previously been reported in eight patients. The periosteal reaction found in association with inflammatory bowel disease is apparently related to a chronic disease course and may cause extreme localized pain.

  19. Chronic non-communicable diseases.

    PubMed

    Unwin, N; Alberti, K G M M

    2006-01-01

    Chronic non-communicable diseases (NCD) account for almost 60% of global mortality, and 80% of deaths from NCD occur in low- and middle-income countries. One quarter of these deaths--almost 9 million in 2005--are in men and women aged <60 years. Taken together, NCD represent globally the single largest cause of mortality in people of working age, and their incidences in younger adults are substantially higher in the poor countries of the world than in the rich. The major causes of NCD-attributable mortality are cardiovascular disease (30% of total global mortality), cancers (13%), chronic respiratory disease (7%) and diabetes (2%). These conditions share a small number of behavioural risk factors, which include a diet high in saturated fat and low in fresh fruit and vegetables, physical inactivity, tobacco smoking, and alcohol excess. In low- and middle-income countries such risk factors tend to be concentrated in urban areas and their prevalences are increasing as a result of rapid urbanization and the increasing globalisation of the food, tobacco and alcohol industries. Because NCD have a major impact on men and women of working age and their elderly dependents, they result in lost income, lost opportunities for investment, and overall lower levels of economic development. Reductions in the incidences of many NCD and their complications are, however, already possible. Up to 80% of all cases of cardiovascular disease or type-2 diabetes and 40% of all cases of cancer, for example, are probably preventable based on current knowledge. In addition, highly cost-effective measures exist for the prevention of some of the complications of established cardiovascular disease and diabetes. Achieving these gains will require a broad range of integrated, population-based interventions as well as measures focused on the individuals at high risk. At present, the international-assistance community provides scant resources for the control of NCD in poor countries, partly, at least

  20. Chronic non-communicable diseases.

    PubMed

    Unwin, N; Alberti, K G M M

    2006-01-01

    Chronic non-communicable diseases (NCD) account for almost 60% of global mortality, and 80% of deaths from NCD occur in low- and middle-income countries. One quarter of these deaths--almost 9 million in 2005--are in men and women aged <60 years. Taken together, NCD represent globally the single largest cause of mortality in people of working age, and their incidences in younger adults are substantially higher in the poor countries of the world than in the rich. The major causes of NCD-attributable mortality are cardiovascular disease (30% of total global mortality), cancers (13%), chronic respiratory disease (7%) and diabetes (2%). These conditions share a small number of behavioural risk factors, which include a diet high in saturated fat and low in fresh fruit and vegetables, physical inactivity, tobacco smoking, and alcohol excess. In low- and middle-income countries such risk factors tend to be concentrated in urban areas and their prevalences are increasing as a result of rapid urbanization and the increasing globalisation of the food, tobacco and alcohol industries. Because NCD have a major impact on men and women of working age and their elderly dependents, they result in lost income, lost opportunities for investment, and overall lower levels of economic development. Reductions in the incidences of many NCD and their complications are, however, already possible. Up to 80% of all cases of cardiovascular disease or type-2 diabetes and 40% of all cases of cancer, for example, are probably preventable based on current knowledge. In addition, highly cost-effective measures exist for the prevention of some of the complications of established cardiovascular disease and diabetes. Achieving these gains will require a broad range of integrated, population-based interventions as well as measures focused on the individuals at high risk. At present, the international-assistance community provides scant resources for the control of NCD in poor countries, partly, at least

  1. Decreased cerebrospinal fluid levels of neurosin (KLK6), an aging-related protease, as a possible new risk factor for Alzheimer's disease.

    PubMed

    Mitsui, Shinichi; Okui, Akira; Uemura, Hidetoshi; Mizuno, Toshiki; Yamada, Tatsuo; Yamamura, Yoshio; Yamaguchi, Nozomi

    2002-11-01

    Neurosin is a kallikrein-like serine protease expressed preferentially in the human brain. It is localized in senile plaques and neurofibrillary tangles in the brains of individuals with Alzheimer's disease (AD) and in Lewy bodies in patients with Parkinson's disease. Neurosin is present in the cerebrospinal fluid (CSF) as a proenzyme and does not show any enzymatic activity. We have developed a sandwich ELISA system using monoclonal and polyclonal antibodies against human neurosin and have measured neurosin levels in the CSF from AD and non-CNS disease patients. Both male and female patients with peripheral neuropathy showed statistically positive correlations between CSF neurosin concentrations and age (males, n = 52, r = 0.482, p < 0.005; females, n = 43, r = 0.365, p < 0.005). In contrast, such positive correlation was not observed in the CSF from patients with AD. Further, some such patients showed extremely low levels of CSF neurosin. Our results suggest that neurosin is an aging-related protease and that a decreased CSF concentration of neurosin may be a risk factor for developing AD.

  2. Myeloperoxidase in chronic kidney disease.

    PubMed

    Madhusudhana Rao, A; Anand, Usha; Anand, C V

    2011-01-01

    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II-V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = -0.85, P < 0.001) and creatinine (r = -0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.

  3. Age-related intraneuronal accumulation of αII-spectrin breakdown product SBDP120 in the human cerebrum is enhanced in Alzheimer's disease.

    PubMed

    Zhu, Hai-Xia; Xue, Zhi-Qin; Qiu, Wen-Ying; Zeng, Zhao-Jun; Dai, Jia-Pei; Ma, Chao; Luo, Xue-Gang; Yan, Xiao-Xin

    2015-09-01

    Spectrins are a part of cytoskeletal platform that lines the intracellular side of plasma membrane, which can be proteolyzed by calcium-sensitive enzymes including calpains and caspases. Caspase-3 mediated αII-spectrin proteolysis results in the release of a 120kDa spectrin breakdown product (SBDP120), known to occur in conditions with cell death. In rodents, intraneuronal SBDP120 accumulation in the forebrain develops with age, which is enhanced in transgenic models of Alzheimer's disease (AD). The present study was set to explore age-related SBDP120 formation and its relevance to AD-type hallmark lesions in the human brains. SBDP120 immunoreactivity (IR) was detected in neuronal somata and dendrites in the cortex and hippocampal formation in postmortem brains from aged (n=10, mean age=84.2) and AD (n=10, mean age=84.8) subjects, but not mid-aged controls (n=10, mean age=58.2). The overall density of SBDP120 IR quantified in the temporal neocortex was increased in the aged and AD groups, more robust in the latter, relative to mid-aged control, while no regional, laminar or cellular association was found between SBDP120 accumulation and Aβ deposition or phosphorylated-tau aggregation. In cultured rat retinal ganglion cells (RGC-5), SBDP120 elevation occurred with caspase-3 activation following oxygen as well as serum deprivation, suggestive of SBDP120 formation in stressful conditions with and without apparent neuronal death. These results confirm an age-related intraneuronal SBDP120 accumulation in the human cerebrum that is enhanced in AD. This neuronal change appears to occur independent of amyloid deposition, tau pathology and overt neuronal death.

  4. Associations of Mortality With Ocular Disorders and an Intervention of High-Dose Antioxidants and Zinc in the Age-Related Eye Disease Study

    PubMed Central

    2006-01-01

    Objective To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). Methods Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. Results During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08–1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12–1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12–1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18–2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61–0.89). Conclusions The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study. PMID:15136320

  5. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

    PubMed

    Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

    2014-08-01

    Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS.

  6. Chronic kidney disease prevention in Singapore.

    PubMed

    Ramirez, Sylvia P B

    2008-03-01

    In consideration of the epidemiologic basis for screening and surveillance, a comprehensive program for chronic kidney disease prevention was initiated in Singapore by the National Kidney Foundation Singapore (NKF Singapore) in 1997. Reasons for developing this include the rising rate of end-stage renal disease in the country, and the projected escalation because of the increase in chronic diseases that lead to end-stage renal disease (ESRD) such as diabetes mellitus and hypertension. Presented are progress and preliminary findings of this program, as well as that of the parallel initiative of Singapore's Ministry of Health. The NKF Singapore program incorporates primary, secondary and tertiary approaches to the prevention of chronic kidney disease. These include the population-based screening for early chronic kidney disease and chronic diseases that are associated with kidney disease and the implementation of disease management programs that aim to improve the multi-faceted care of patients with chronic diseases that lead to ESRD, including the development of community-based "Prevention Centers." The screening program identified risk factors for proteinuria, including the Malay race, increasing age, family history of kidney disease, and higher levels of systolic and diastolic BP even within the normal ranges. Longitudinal follow-up of both prevention programs are critical to provide evidence for the efficacy of such screening and intervention programs in improving chronic kidney disease outcomes, while reducing the cost of care.

  7. Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease

    PubMed Central

    Zeginigg, Marion; Wiltgen, Marco; Freudenberger, Paul; Petrovic, Katja; Cavalieri, Margherita; Gider, Pierre; Enzinger, Christian; Fornage, Myriam; Debette, Stephanie; Rotter, Jerome I.; Ikram, Mohammad A.; Launer, Lenore J.; Schmidt, Reinhold

    2011-01-01

    Cerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3′-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n = 888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P = 0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3′-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently

  8. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    PubMed

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  9. Anemia of Inflammation and Chronic Disease

    MedlinePlus

    ... Disease Organizations (PDF, 270 KB). Alternate Language URL Anemia of Inflammation and Chronic Disease Page Content On ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which a person ...

  10. Nephrology Update: Chronic Kidney Disease.

    PubMed

    Saha, Sharmeela; Rahman, Mahboob

    2016-05-01

    Chronic kidney disease (CKD) affects more than 1 in 10 individuals in the United States. The care of these patients must be managed by family physicians and nephrology subspecialists. The kidneys often are affected by systemic processes such as diabetes and hypertension, and optimal management of these conditions is critical to slow decline in renal function in CKD patients. These patients are at high risk of cardiovascular disease, and statin therapy is recommended for adults with CKD who are at least age 50 years and not receiving dialysis. Patients with CKD and anemia can be treated with iron therapy and often with an erythropoietin-stimulating agent. Electrolyte abnormalities are managed with dietary changes and drugs. Sodium restriction and modification of dietary protein intake also may be needed. Consultation with a renal dietitian may be helpful. Because many drugs are metabolized by the kidneys, physicians should ensure that drug dosages are appropriate for the level of renal function. Early consultation with or referral to a nephrology subspecialist for patients with reduced renal function, resistant hypertension or electrolyte levels, and other conditions have been associated with improved outcomes in CKD patients.

  11. Nephrology Update: Chronic Kidney Disease.

    PubMed

    Saha, Sharmeela; Rahman, Mahboob

    2016-05-01

    Chronic kidney disease (CKD) affects more than 1 in 10 individuals in the United States. The care of these patients must be managed by family physicians and nephrology subspecialists. The kidneys often are affected by systemic processes such as diabetes and hypertension, and optimal management of these conditions is critical to slow decline in renal function in CKD patients. These patients are at high risk of cardiovascular disease, and statin therapy is recommended for adults with CKD who are at least age 50 years and not receiving dialysis. Patients with CKD and anemia can be treated with iron therapy and often with an erythropoietin-stimulating agent. Electrolyte abnormalities are managed with dietary changes and drugs. Sodium restriction and modification of dietary protein intake also may be needed. Consultation with a renal dietitian may be helpful. Because many drugs are metabolized by the kidneys, physicians should ensure that drug dosages are appropriate for the level of renal function. Early consultation with or referral to a nephrology subspecialist for patients with reduced renal function, resistant hypertension or electrolyte levels, and other conditions have been associated with improved outcomes in CKD patients. PMID:27163761

  12. Pathophysiology of chronic venous disease.

    PubMed

    Raffetto, J D; Mannello, F

    2014-06-01

    Chronic venous disease (CVD) is a debilitating condition with a prevalence between 60-70%. The disease pathophysiology is complex and involves genetic susceptibility and environmental factors, with individuals developing visible telengiectasias, reticular veins, and varicose veins. Patient with significant lower extremity symptoms have pain, dermal irritation, swelling, skin changes, and are at risk of developing debilitating venous ulceration. The signature of CVD is an increase in venous pressure referred to as venous hypertension. The various symptoms presenting in CVD and the clinical signs that are observed indicate that there is inflammation, secondary to venous hypertension, and it leads to a number of inflammatory pathways that become activated. The endothelium and glycocalyx via specialized receptors are critical at sensing changes in shear stress, and expression of adhesion molecules allows the activation of leukocytes leading to endothelial attachment, diapedisis, and transmigration into the venous wall/valves resulting in venous wall injury and inflammatory cells in the interstitial tissues. There is a complex of cytokines, chemokines, growth factors, proteases and proteinases, produced by activated leukocytes, that are expressed and unbalanced resulting in an environment of persistent inflammation with the clinical changes that are commonly seen, consisting of varicose veins to more advanced presentations of skin changes and venous ulceration. The structural integrity of protein and the extracellular matrix is altered, enhancing the progressive events of CVD. Work focusing on metabolic changes, miRNA regulation, inflammatory modulation and the glycocalyx will further our knowledge in the pathophysiology of CVD, and provide answers critical to treatment and prevention.

  13. Niacin and Chronic Kidney Disease.

    PubMed

    Taketani, Yutaka; Masuda, Masashi; Yamanaka-Okumura, Hisami; Tatsumi, Sawako; Segawa, Hiroko; Miyamoto, Ken-ichi; Takeda, Eiji; Yamamoto, Hironori

    2015-01-01

    Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD.

  14. Niacin and Chronic Kidney Disease.

    PubMed

    Taketani, Yutaka; Masuda, Masashi; Yamanaka-Okumura, Hisami; Tatsumi, Sawako; Segawa, Hiroko; Miyamoto, Ken-ichi; Takeda, Eiji; Yamamoto, Hironori

    2015-01-01

    Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD. PMID:26598845

  15. Chronic kidney disease and premature ageing.

    PubMed

    Kooman, Jeroen P; Kotanko, Peter; Schols, Annemie M W J; Shiels, Paul G; Stenvinkel, Peter

    2014-12-01

    Chronic kidney disease (CKD) shares many phenotypic similarities with other chronic diseases, including heart failure, chronic obstructive pulmonary disease, HIV infection and rheumatoid arthritis. The most apparent similarity is premature ageing, involving accelerated vascular disease and muscle wasting. We propose that in addition to a sedentary lifestyle and psychosocial and socioeconomic determinants, four major disease-induced mechanisms underlie premature ageing in CKD: an increase in allostatic load, activation of the 'stress resistance response', activation of age-promoting mechanisms and impairment of anti-ageing pathways. The most effective current interventions to modulate premature ageing-treatment of the underlying disease, optimal nutrition, correction of the internal environment and exercise training-reduce systemic inflammation and oxidative stress and induce muscle anabolism. Deeper mechanistic insight into the phenomena of premature ageing as well as early diagnosis of CKD might improve the application and efficacy of these interventions and provide novel leads to combat muscle wasting and vascular impairment in chronic diseases.

  16. Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease.

    PubMed

    Cioffi, Christopher L; Racz, Boglarka; Freeman, Emily E; Conlon, Michael P; Chen, Ping; Stafford, Douglas G; Schwarz, Daniel M C; Zhu, Lei; Kitchen, Douglas B; Barnes, Keith D; Dobri, Nicoleta; Michelotti, Enrique; Cywin, Charles L; Martin, William H; Pearson, Paul G; Johnson, Graham; Petrukhin, Konstantin

    2015-08-13

    Antagonists of retinol-binding protein 4 (RBP4) impede ocular uptake of serum all-trans retinol (1) and have been shown to reduce cytotoxic bisretinoid formation in the retinal pigment epithelium (RPE), which is associated with the pathogenesis of both dry age-related macular degeneration (AMD) and Stargardt disease. Thus, these agents show promise as a potential pharmacotherapy by which to stem further neurodegeneration and concomitant vision loss associated with geographic atrophy of the macula. We previously disclosed the discovery of a novel series of nonretinoid RBP4 antagonists, represented by bicyclic [3.3.0]-octahydrocyclopenta[c]pyrrolo analogue 4. We describe herein the utilization of a pyrimidine-4-carboxylic acid fragment as a suitable isostere for the anthranilic acid appendage of 4, which led to the discovery of standout antagonist 33. Analogue 33 possesses exquisite in vitro RBP4 binding affinity and favorable drug-like characteristics and was found to reduce circulating plasma RBP4 levels in vivo in a robust manner (>90%). PMID:26181715

  17. The Association of Dietary Lutein/Zeaxanthin and B Vitamins with Cataracts in the Age- Related Eye Disease Study AREDS Report No. 37

    PubMed Central

    Glaser, Tanya S.; Doss, Lauren E.; Shih, Grace; Nigam, Divya; Sperduto, Robert D.; Ferris, Frederick L.; Agrón, Elvira; Clemons, Traci E; Chew, Emily Y.

    2015-01-01

    Purpose To evaluate whether dietary intake of lutein/zeaxanthin and B vitamins is associated with cataract prevalence and incidence. Design Clinic-based, baseline cross-sectional and prospective cohort study designs. Participants 3115 (6129 eyes) persons enrolled in the Age-Related Eye Disease Study, aged 55 to 80 years, followed for mean of 9.6 years. Methods Participants completed baseline food frequency questionnaires. Baseline and annual lens photographs were graded centrally. Multivariable models controlling for previously identified risk factors for cataracts were used to measure the association of cataracts with reported dietary intake, using the lowest quintile as reference. Main Outcome Measures Cataract surgery, cataract status (type and severity) at baseline, development of cataracts. Results At baseline, increased dietary riboflavin and B12 were inversely associated with nuclear and cortical lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake vs. those with the lowest intake had the following associations: odds ratio (OR): 0.78, 95% confidence interval (CI): 0.63–0.97 for mild nuclear, OR: 0.62, 95% CI: 0.43–0.90 for moderate nuclear, and OR: 0.80, 95% CI: 0.65–0.99 for mild cortical cataracts. For B12, the results were: OR: 0.78, 95% CI: 0.63–0.96 for mild nuclear, OR: 0.62, 95% CI: 0.43–0.88 for moderate nuclear, and OR: 0.77, 95% CI: 0.63–0.95 for mild cortical cataracts. Highest dietary B6 intake was associated with a decreased risk of developing moderate nuclear lens opacity compared with the lowest quintile, OR: 0.67, 95% CI: 0.45–0.99. Highest dietary intake levels of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts in participants not taking Centrum® multivitamin. For participants taking Centrum® during the study, highest intake of dietary folate was associated with an increased risk of development of mild

  18. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  19. Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus

    PubMed Central

    Uhrlaub, Jennifer L.; Pulko, Vesna; DeFilippis, Victor R.; Streblow, Daniel N.; Coleman, Gary D.; Lindo, John F.; Vickers, Ivan; Anzinger, Joshua J.; Nikolich-Žugich, Janko

    2016-01-01

    Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFβ production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFβ levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFβ levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFβ secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD. PMID:27736984

  20. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  1. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  2. [Chronic diseases. Definition and basic concept].

    PubMed

    Raspe, H

    2011-01-01

    The baroque deity Chronos symbolizes much of what we intuitively connect with "chronic", but it must not obscure our view of the diversity of chronic diseases. Common to all forms is a prognostic implication: a chronic disease and all associated burden will accompany the patient for the rest of his/her life. Chronic diseases are in general multifocal disorders simultaneously affecting biological, psychic, and social equilibria. This requires systematic problem-screening and -assessment, including possible comorbidities. Comorbidity in a strict sense should be distinguished from risk factors, implications, complications, and consequences of the index disorder of interest. The assessment is usually followed by the shared identification of therapeutic goals and indications. In chronic disorders, a wide spectrum of diagnostic and therapeutic approaches, methods, and professions becomes relevant. PMID:21246322

  3. HIV/AIDS, chronic diseases and globalisation.

    PubMed

    Colvin, Christopher J

    2011-08-26

    HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART), it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the use of this language of chronicity to interpret the HIV/AIDS pandemic and calls into question some of the consequences of an uncritical acceptance of concepts of chronicity.

  4. HIV/AIDS, chronic diseases and globalisation.

    PubMed

    Colvin, Christopher J

    2011-01-01

    HIV/AIDS has always been one of the most thoroughly global of diseases. In the era of widely available anti-retroviral therapy (ART), it is also commonly recognised as a chronic disease that can be successfully managed on a long-term basis. This article examines the chronic character of the HIV/AIDS pandemic and highlights some of the changes we might expect to see at the global level as HIV is increasingly normalised as "just another chronic disease". The article also addresses the use of this language of chronicity to interpret the HIV/AIDS pandemic and calls into question some of the consequences of an uncritical acceptance of concepts of chronicity. PMID:21871074

  5. [Chronic inflammatory bowel diseases in cats].

    PubMed

    Ghermai, A K

    1989-01-01

    The aetiology of chronic idiopathic intestinal inflammation is unknown. It is characterized by a diffuse infiltration with inflammatory cells into the intestinal mucosa and sometimes submucosa. Cats with chronic intermittent vomiting and diarrhoea, later on accompanied by anorexia and weight loss, are presented. Definitive diagnosis can be obtained by intestinal biopsy only. An immune pathogenesis is suspected, which is supported by the fact, that chronic inflammatory bowel disease responds to steroid therapy.

  6. How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases.

    PubMed

    Rodriguez-Teja, Mercedes; Breit, Claudia; Clarke, Mitchell; Talar, Kamil; Wang, Kai; Mohammad, Mohammad A; Pickwell, Sage; Etchandy, Guillermina; Stasiuk, Graeme J; Sturge, Justin

    2016-01-01

    Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under

  7. Cardiovascular complications of pediatric chronic kidney disease

    PubMed Central

    2006-01-01

    Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD. PMID:17120060

  8. A Review of Pediatric Chronic Kidney Disease.

    PubMed

    Kaspar, C D W; Bholah, R; Bunchman, T E

    2016-01-01

    Chronic kidney disease is complex in both adults and children, but the disease is far from the same between these populations. Here we review the marked differences in etiology, comorbidities, impact of disease on growth and quality of life, issues unique to adolescents and transitions to adult care, and special considerations of congenital kidney and urinary tract anomalies for transplantation. PMID:26766175

  9. Chronic wasting disease of cervids.

    PubMed

    Miller, M W; Williams, E S

    2004-01-01

    Chronic wasting disease (CWD) has recently emerged in North America as an important prion disease of captive and free-ranging cervids (species in the deer family). CWD is the only recognized transmissible spongiform encephalopathy (TSE) affecting free-ranging species. Three cervid species, mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni), are the only known natural hosts of CWD. Endemic CWD is well established in southern Wyoming and northern Colorado, and has been present in this 'core area' for two decades or more. Apparently CWD has also infected farmed cervids in numerous jurisdictions, and has probably been endemic in North America's farmed deer and elk for well over a decade. Several free-ranging foci distant to the Colorado-Wyoming core area have been discovered since 2000, and new or intensified surveillance may well identify even more foci of infection. Whether all of the identified captive and free-ranging foci are connected via a common original exposure source remains undetermined. Some of this recently observed 'spread' may be attributable to improved detection or natural movements of infected deer and elk, but more distant range extensions are more likely caused by movements of infected captive deer and elk in commerce, or by some yet unidentified exposure risk factor. Research on CWD over the last 5 years has resulted in a more complete understanding of its pathogenesis and epidemiology. CWD is infectious, transmitting horizontally from infected to susceptible cervids. Early accumulation of PrP(CWD) in alimentary tract-associated lymphoid tissues during incubation suggests agent shedding in feces or saliva as plausible transmission routes. Residual infectivity in contaminated environments also appears to be important in sustaining epidemics. Improved tests allow CWD to be reliably diagnosed long before clinical signs appear. Implications of CWD are not entirely clear at this time

  10. Chronic granulomatous disease with renal stones.

    PubMed

    Mohammed, S H; Vyas, H

    1992-01-01

    A case of chronic granulomatous disease with hydronephrosis and renal calculi is presented. This is to our knowledge the first such case to be reported. The calculi were successfully ablated by extracorporeal shockwave lithotripsy.

  11. Dispelling the chronic Lyme disease myth.

    PubMed

    Kemperman, Melissa M; Bakken, Johan S; Kravitz, Gary R

    2008-07-01

    Lyme disease is a tick-borne illness endemic to Minnesota that can have potentially severe complications. As the incidence of Lyme disease continues to increase, it is important for physicians in Minnesota to become familiar with its clinical aspects, including the concept of "chronic Lyme disease." Chronic Lyme disease is a misnomer that is often applied to patients with nonspecific presentations who may or may not have a history of infection with Borrelia burgdorferi, the agent that causes Lyme disease. When a patient does present with persistent nonspecific symptoms attributed to chronic Lyme disease, clinicians should ascertain the presence of objective manifestations, obtain laboratory results, and get a history of tick exposure. If active infection with B. burgdorferi is unlikely, they should avoid prescribing empiric antibiotic therapy and instead thoroughly evaluate the patient for other possible causes of the complaints and recommend appropriate care.

  12. Chronic diseases and injuries in India.

    PubMed

    Patel, Vikram; Chatterji, Somnath; Chisholm, Dan; Ebrahim, Shah; Gopalakrishna, Gururaj; Mathers, Colin; Mohan, Viswanathan; Prabhakaran, Dorairaj; Ravindran, Ravilla D; Reddy, K Srinath

    2011-01-29

    Chronic diseases (eg, cardiovascular diseases, mental health disorders, diabetes, and cancer) and injuries are the leading causes of death and disability in India, and we project pronounced increases in their contribution to the burden of disease during the next 25 years. Most chronic diseases are equally prevalent in poor and rural populations and often occur together. Although a wide range of cost-effective primary and secondary prevention strategies are available, their coverage is generally low, especially in poor and rural populations. Much of the care for chronic diseases and injuries is provided in the private sector and can be very expensive. Sufficient evidence exists to warrant immediate action to scale up interventions for chronic diseases and injuries through private and public sectors; improved public health and primary health-care systems are essential for the implementation of cost-effective interventions. We strongly advocate the need to strengthen social and policy frameworks to enable the implementation of interventions such as taxation on bidis (small hand-rolled cigarettes), smokeless tobacco, and locally brewed alcohols. We also advocate the integration of national programmes for various chronic diseases and injuries with one another and with national health agendas. India has already passed the early stages of a chronic disease and injury epidemic; in view of the implications for future disease burden and the demographic transition that is in progress in India, the rate at which effective prevention and control is implemented should be substantially increased. The emerging agenda of chronic diseases and injuries should be a political priority and central to national consciousness, if universal health care is to be achieved.

  13. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    ClinicalTrials.gov

    2016-10-20

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  14. Asthma and chronic obstructive pulmonary disease overlap: asthmatic chronic obstructive pulmonary disease or chronic obstructive asthma?

    PubMed

    Slats, Annelies; Taube, Christian

    2016-02-01

    Asthma and chronic obstructive pulmonary disease (COPD) are different disease entities. They are both clinical diagnoses, with diagnostic tools to discriminate between one another. However, especially in older patients (>55 years) it seems more difficult to differentiate between asthma and COPD. This has led to the definition of a new phenotype called asthma COPD overlap syndrome (ACOS). However, our understanding of ACOS is at a very preliminary stage, as most research has involved subjects with existing diagnoses of asthma or COPD from studies with different definitions for ACOS. This has led to different and sometimes opposing results between studies on several features of ACOS, also depending on the comparison with COPD alone, asthma alone or both, which are summarized in this review.We suggest not using the term ACOS for a patient with features of both asthma and COPD, but to describe a patient with chronic obstructive airway disease as completely as possible, with regard to characteristics that determine treatment response (e.g. eosinophilic inflammation) and prognosis (such as smoking status, exacerbation rate, fixed airflow limitation, hyperresponsiveness, comorbidities). This will provide a far more clinically relevant diagnosis, and would aid in research on treatment in more homogenous groups of patients with chronic airways obstruction. More research is certainly needed to develop more evidence-based definitions for this patient group and to evaluate biomarkers, which will help to further classify these patients, treat them more adequately and unravel the underlying pathophysiological mechanism.

  15. Managing systemic symptoms in chronic liver disease.

    PubMed

    Newton, Julia L; Jones, David E J

    2012-01-01

    Improved medical management and the changing disease demographic mean that the majority of patients with chronic liver disease are living with the disease rather than dying from it. Historically, the perception has been that the impact of chronic liver disease is related entirely to the consequences of endstage liver disease; however, more recently a number of systemic symptoms have been recognised that can occur at any point in the natural history of chronic liver disease and which can be associated with functional impairment and reduced quality of life. The most characteristic of these systemic symptoms is fatigue, which frequently associates with sleep disturbance and autonomic dysfunction, particularly manifest as abnormality of blood pressure regulation. Cognitive symptoms can occur even in non-cirrhotic patients. Falls can present in patients with autonomic dysfunction, complicated by the presence of peripheral muscle strength problems. Importantly for clinicians managing chronic liver disease, the severity of these systemic symptoms is typically not related to liver disease severity, and therefore despite optimal liver disease management, patients can often continue to experience debilitating symptoms. The similarity in systemic symptoms between different chronic liver diseases (and indeed chronic inflammatory conditions affecting other organs) suggests the possibility of shared pathogenetic processes and raises the possibility of common management strategies, although further research is urgently needed to confirm this. In primary biliary cirrhosis, where our understanding of systemic symptoms is arguably most developed, structured management strategies have been shown to improve the quality of life of patients. It is highly likely that similar approaches will have comparable benefits for other chronic liver disease groups. Here, we review the current understanding of systemic symptoms in chronic liver disease and offer recommendations regarding the

  16. Pneumocystis jirovecii colonization in chronic pulmonary disease

    PubMed Central

    Gutiérrez, S.; Respaldiza, N.; Campano, E.; Martínez-Risquez, M.T.; Calderón, E.J.; De La Horra, C.

    2011-01-01

    Pneumocystis jirovecii causes pneumonia in immunosuppressed individuals. However, it has been reported the detection of low levels of Pneumocystis DNA in patients without signs and symptoms of pneumonia, which likely represents colonization. Several studies performed in animals models and in humans have demonstrated that Pneumocystis induces a local and a systemic response in the host. Since P. jirovecii colonization has been found in patients with chronic pulmonary diseases it has been suggested that P. jirovecii may play a role in the physiopathology and progression of those diseases. In this report we revise P. jirovecii colonization in different chronic pulmonary diseases such us, chronic obstructive pulmonary disease, interstitial lung diseases, cystic fibrosis and lung cancer. PMID:21678787

  17. Chronic sequelae of foodborne disease.

    PubMed Central

    Lindsay, J. A.

    1997-01-01

    In the past decade the complexity of foodborne pathogens, as well as their adaptability and ability to cause acute illness, and in some cases chronic (secondary) complications, have been newly appreciated. This overview examines long-term consequences of foodborne infections and intoxications to emphasize the need for more research and education. PMID:9366595

  18. The Chronic Gastrointestinal Manifestations of Chagas Disease

    PubMed Central

    Matsuda, Nilce Mitiko; Miller, Steven M.; Evora, Paulo R. Barbosa

    2009-01-01

    Chagas disease is an infectious disease caused by the protozoan Trypanosoma cruzi. The disease mainly affects the nervous system, digestive system and heart. The objective of this review is to revise the literature and summarize the main chronic gastrointestinal manifestations of Chagas disease. The chronic gastrointestinal manifestations of Chagas disease are mainly a result of enteric nervous system impairment caused by T. cruzi infection. The anatomical locations most commonly described to be affected by Chagas disease are salivary glands, esophagus, lower esophageal sphincter, stomach, small intestine, colon, gallbladder and biliary tree. Chagas disease has also been studied in association with Helicobacter pylori infection, interstitial cells of Cajal and the incidence of gastrointestinal cancer. PMID:20037711

  19. Chronic wasting disease agents in nonhuman primates.

    PubMed

    Race, Brent; Meade-White, Kimberly D; Phillips, Katie; Striebel, James; Race, Richard; Chesebro, Bruce

    2014-05-01

    Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

  20. Chronic kidney disease and cardiovascular complications.

    PubMed

    Di Lullo, Luca; House, Andrew; Gorini, Antonio; Santoboni, Alberto; Russo, Domenico; Ronco, Claudio

    2015-05-01

    Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Pathogenesis includes close linkage between heart and kidneys and involves traditional and non-traditional cardiovascular risk factors. According to a well-established classification of cardiorenal syndrome, cardiovascular involvement in CKD is known as "type-4 cardiorenal syndrome" (chronic renocardiac). The following review makes an overview about epidemiology, pathophysiology, diagnosis and treatment of cardiovascular complications in CKD patients. PMID:25344016

  1. Chronic kidney disease - pediatric risk factors.

    PubMed

    Tasic, Velibor; Janchevska, Aleksandra; Emini, Nora; Sahpazova, Emilija; Gucev, Zoran; Polenakovic, Momir

    2016-01-01

    The knowledge about the progression of chronic kidney disease is an important issue for every pediatric nephrologist and pediatrician in order to implement appropriate measures to prevent wasting of renal function and the final consequence - end stage renal disease with the need for the dialysis and transplantation. Therefore it is important to know, treat or ameliorate the standard risk factors such as hypertension, proteinuria, anemia, hyperparathyroidism etc. In this review devoted to the World Kidney Day 2016 we will pay attention to the low birth parameters, obesity, hyperuricemia and smoking which emerged as particularly important risk factors for children and adolescent with chronic kidney disease. PMID:27442412

  2. Exercise as a Polypill for Chronic Diseases.

    PubMed

    Pareja-Galeano, Helios; Garatachea, Nuria; Lucia, Alejandro

    2015-01-01

    Exercise may be described as a polypill to prevent and/or treat almost every chronic disease, with obvious benefits such as its low cost and practical lack of adverse effects. Implementing physical activity interventions in public health is therefore a goal at the medical, social, and economic levels. This chapter describes the importance of health promotion through physical activity and discusses the impacts of exercise on the most prevalent chronic diseases, namely metabolic syndrome-related disorders, cardiovascular diseases, cancer, and Alzheimer's disease. For each of these chronic conditions, we discuss the epidemiological evidence supporting a beneficial role of exercise, provide guidelines for exercise prescription, and describe the biological mechanisms whereby exercise exerts its modulatory effects. PMID:26477928

  3. Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

    PubMed

    Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

    2015-01-01

    Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity. PMID:26682690

  4. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  5. Addressing Chronic Disease Within Supportive Housing Programs

    PubMed Central

    Henwood, Benjamin F.; Stanhope, Victoria; Brawer, Rickie; Weinstein, Lara Carson; Lawson, James; Stwords, Edward; Crossan, Cornelius

    2015-01-01

    Background Tenants of supportive housing have a high burden of chronic health conditions. Objectives To examine the feasibility of developing a tenant-involved health promotion initiative within a “housing first” agency using a community-based participatory research (CBPR) framework. Methods Qualitative analyses of nine research capacity-building group meetings and fifteen individual pre- and post-interviews with those who completed a chronic disease self-management program, resulting in the development of several themes. Results Tenants of supportive housing successfully partnered with health care providers to implement a chronic disease self-management program, noting that “health care becomes ‘relevant’ with housing.” Conclusions Supportive housing organizations are well-situated to implement health promotion initiatives. Such publicly subsidized housing that is accompanied by comprehensive supports must also include self-management training to help people overcome both internal and external barriers to addressing chronic health needs. PMID:23543023

  6. Dermatological diseases in patients with chronic kidney disease

    PubMed Central

    Gagnon1, Amy L.; Desai, Tejas

    2013-01-01

    Context: There are a variety of dermatological diseases that are more commonly seen in patients with chronic kidney disease (CKD) and renal transplants than the general population. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Results: Some cutaneous diseases are clearly unique to this population. Of them, Lindsay’s Nails, xerosis cutis, dryness of the skin, nephrogenic systemic fibrosis and acquired perforating dermatosis have been described in chronic kidney disease patients. The most common malignancy found in all transplant recipients is non-melanoma skin cancer. Conclusions: It is important for patients and physicians to recognize the manifestations of skin disease in patients suffering from chronic kidney disease to mitigate the morbidity associated with these conditions. PMID:24475435

  7. Community networks in chronic disease management.

    PubMed

    Pyne, Diane

    2009-01-01

    Community networks are being established as part of the Chronic Disease Management program in Edmonton, Alberta. These networks are programs and services from profit and not-for-profit organizations that support people with chronic conditions to address lifestyle choices and issues. Evidence-informed standards and criteria have been developed that have to be met to belong to such a network. The community network approach is developing a "community" of resources that are available and committed to assist healthcare professionals and the public with health promotion for people with chronic conditions.

  8. Framing international trade and chronic disease

    PubMed Central

    2011-01-01

    There is an emerging evidence base that global trade is linked with the rise of chronic disease in many low and middle-income countries (LMICs). This linkage is associated, in part, with the global diffusion of unhealthy lifestyles and health damaging products posing a particular challenge to countries still facing high burdens of communicable disease. We developed a generic framework which depicts the determinants and pathways connecting global trade with chronic disease. We then applied this framework to three key risk factors for chronic disease: unhealthy diets, alcohol, and tobacco. This led to specific 'product pathways', which can be further refined and used by health policy-makers to engage with their country's trade policy-makers around health impacts of ongoing trade treaty negotiations, and by researchers to continue refining an evidence base on how global trade is affecting patterns of chronic disease. The prevention and treatment of chronic diseases is now rising on global policy agendas, highlighted by the UN Summit on Noncommunicable Diseases (September 2011). Briefs and declarations leading up to this Summit reference the role of globalization and trade in the spread of risk factors for these diseases, but emphasis is placed on interventions to change health behaviours and on voluntary corporate responsibility. The findings summarized in this article imply the need for a more concerted approach to regulate trade-related risk factors and thus more engagement between health and trade policy sectors within and between nations. An explicit recognition of the role of trade policies in the spread of noncommunicable disease risk factors should be a minimum outcome of the September 2011 Summit, with a commitment to ensure that future trade treaties do not increase such risks. PMID:21726434

  9. Transcending chronic liver disease: a qualitative study.

    PubMed

    Wainwright, S P

    1997-01-01

    This study explores and describes experiences of chronic liver disease from the patient's perspective. No qualitative research studies appear to have examined the experiences of these patients. In-depth focused interviews and grounded theory data collection and data analysis methods were used. A two-stage theoretical framework (becoming ill, and not living) of the experience of transcending chronic liver disease is presented. Sociological and psychological literature on common sense models of health and illness are briefly reviewed. Several suggestions for further research are made. The way in which this qualitative research study is leading to a quantitative and qualitative appraisal of the psychological adjustment in end-stage chronic liver disease patients is outlined.

  10. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  11. Quality of Life in Chronic Disease Patients

    PubMed Central

    Megari, Kalliopi

    2013-01-01

    During the past decades there was an increasing predominance of chronic disorders, with a large number of people living with chronic diseases that can adversely affect their quality of life. The aim of the present paper is to study quality of life and especially Health-related quality of life (HRQoL) in chronic diseases. HRQOL is a multidimensional construct that consists of at least three broad domains – physical, psychological, and social functioning – that are affected by one’s disease and/or treatment. HRQoL is usually measured in chronic conditions and is frequently impaired to a great extent. In addition, factors that are associated with good and poor HRQoL, as well as HRQoL assessment will be discussed. The estimation of the relative impact of chronic diseases on HRQoL is necessary in order to better plan and distribute health care resources aiming at a better HRQoL. [«All the people perceive the concept of living good or being well, that is the same as being happy». (Aristotle. 384-322 BC. Ethica Nichomachea)] PMID:26973912

  12. SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

    PubMed Central

    Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

    2013-01-01

    Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

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

    PubMed

    Machalińska, Anna

    2013-01-01

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

  14. Chronic Liver Disease and Asian Americans/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Asian Americans/Pacific Islanders Among Asian Americans, chronic liver disease is ... women. At a glance – Cancer Rates for Asian/Pacific Islanders (2008-2012) Cancer Incidence Rates per 100, ...

  15. Autoimmune thyroid disease and chronic urticaria.

    PubMed

    Monge, Cecilia; Demarco, Paul; Burman, Kenneth D; Wartofsky, Leonard

    2007-09-01

    We report six cases of autoimmune thyroid disease associated with chronic urticaria and briefly review the literature, including the histopathological nature of such lesions, and their aetiology and pathogenesis. In view of the prevalence of thyroid disease in patients with chronic urticaria, screening measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended, although negative antibodies do not exclude a relationship between urticaria and thyroid autoimmunity. After failure of conventional therapy for urticaria, patients who are apparently clinically euthyroid may be considered for a trial with levothyroxine. Improvement of urticaria was seen with levothyroxine treatment in three of four patients with only marginal abnormalities in thyroid function.

  16. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  17. Anemia in Chronic Kidney Disease

    MedlinePlus

    ... Disease Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Anemia in CKD Page Content On this page: What ... Nutrition Points to Remember Clinical Trials What is anemia? Anemia is a condition in which the body ...

  18. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-01

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip. PMID:27444019

  19. Adverse environmental conditions influence age-related innate immune responsiveness

    PubMed Central

    May, Linda; van den Biggelaar, Anita HJ; van Bodegom, David; Meij, Hans J; de Craen, Anton JM; Amankwa, Joseph; Frölich, Marijke; Kuningas, Maris; Westendorp, Rudi GJ

    2009-01-01

    Background- The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods- We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results- We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion- We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions. PMID:19480711

  20. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  1. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  2. [Chronic kidney disease and cellular calcium homeostasis].

    PubMed

    Lajdová, I; Okša, A; Spustová, A; Dzúrik, R

    2012-01-01

    Free intracellular calcium represents a critical signaling mediator in a number of biological systems. Calcium cations (Ca2+) are an important ubiquitous messenger, controlling a broad range of cellular processes. Free cytosolic calcium concentration ([Ca2+]i) is controlled by mechanisms that regulate Ca2+ entry from the extracellular space and Ca2+ release from intracellular stores, and by the activity of ATP-dependent Ca2+ pumps and antiporters that move Ca2+ back into stores or out of cells. Chronic kidney disease is associated with a significant elevation in [Ca2+]i which is toxic to the cells and may be responsible for a multiple organ dysfunction. Disturbances in cellular calcium homeostasis in patients with chronic kidney disease represent a complex process. Our studies elucidate pathophysiological mechanisms of altered cellular calcium homeostasis in the peripheral blood mononuclear cells which represent the model of nonexcitable cells in patients with chronic kidney disease. The results demonstrate that [Ca2+]i is significantly increased in peripheral blood mononuclear cells already in early stages of chronic kidney disease. The calcium concentration of intracellular stores and the capacitative calcium entry into the cells of these patients are significantly higher in comparison with healthy volunteers. Also the pore-forming P2X7 receptors participate in increased [Ca2+]i in peripheral blood mononuclear cells of patients with chronic kidney disease. An altered P2X7 receptor function and increased P2X7 receptor expression may contribute to the complex disturbances in intracellular calcium homeostasis in chronic kidney disease. On the other hand, the activity of plasmatic membrane Ca2+-ATPases which is responsible for removing excessive calcium out of the cell, was found to be decreased by 25 % when compared to healthy subjects. It means that not only the mechanisms of entry, but also of the removal are impaired by the disease. All these alterations in

  3. Vitamin D deficiency in chronic liver disease

    PubMed Central

    Iruzubieta, Paula; Terán, Álvaro; Crespo, Javier; Fábrega, Emilio

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required. PMID:25544877

  4. Social inequality in chronic disease outcomes.

    PubMed

    Nordahl, Helene

    2014-11-01

    Socioeconomic differences in morbidity and mortality, particularly across educational groups, are widening. Differential exposures to behavioural risk factors have been shown to play an important mediating role on the social inequality in chronic diseases such as heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and lung cancer. However, much less attention has been given to the potential role of interaction, where the same level of exposure to a behavioural risk factor has different effect across socioeconomic groups, creating subgroups that are more vulnerable than others. In this thesis, Paper 1 describes the unique cohort consortium which was established by pooling and harmonising prospective data from existing cohort studies in Denmark. This consortium generated a large study population with long follow-up sufficient to study power demanding questions of mechanisms underlying social inequalities in chronic disease outcomes. In Paper 2 on incidence of coronary heart disease, smoking and body mass index partially mediated the observed educational differences. This result suggested that some of the social inequality in coronary heart disease may be enhanced by differential exposure to behavioural risk factors (i.e. smoking and obesity). In Paper 3 on incidence of stroke, an observed interaction between education and smoking indicated that participants, particularly men, with low level of education may be more vulnerable to the effect of smoking than those with high level of education in terms of ischemic stroke. Finally, Paper 4 revealed that behavioural risk factors, primarily smoking, explained a considerable part of the educational differences in cause-specific mortality. Further, this paper added important knowledge about the considerable part of the mediated effect, which could be due to interaction between education and smoking. In conclusion, the research in this thesis is a practical implementation of contemporary statistical

  5. An Update on Coronary Artery Disease and Chronic Kidney Disease

    PubMed Central

    Covic, Adrian; Kanbay, Mehmet

    2014-01-01

    Despite the improvements in diagnostic tools and medical applications, cardiovascular diseases (CVD), especially coronary artery disease (CAD), remain the most common cause of morbidity and mortality in patients with chronic kidney disease (CKD). The main factors for the heightened risk in this population, beside advanced age and a high proportion of diabetes and hypertension, are malnutrition, chronic inflammation, accelerated atherosclerosis, endothelial dysfunction, coronary artery calcification, left ventricular structural and functional abnormalities, and bone mineral disorders. Chronic kidney disease is now recognized as an independent risk factor for CAD. In community-based studies, decreased glomerular filtration rate (GFR) and proteinuria were both found to be independently associated with CAD. This paper will discuss classical and recent epidemiologic, pathophysiologic, and clinical aspects of CAD in CKD patients. PMID:24734178

  6. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program.

    PubMed

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-03-31

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.

  7. A Customizable Model for Chronic Disease Coordination: Lessons Learned From the Coordinated Chronic Disease Program

    PubMed Central

    Sequeira, Sonia; Chavez, Amy Holmes

    2016-01-01

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managed resources, and 6) relationship building. These elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs. PMID:27032986

  8. Age-related atrial fibrosis.

    PubMed

    Gramley, Felix; Lorenzen, Johann; Knackstedt, Christian; Rana, Obaida R; Saygili, Erol; Frechen, Dirk; Stanzel, Sven; Pezzella, Francesco; Koellensperger, Eva; Weiss, Christian; Münzel, Thomas; Schauerte, Patrick

    2009-03-01

    Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis. PMID:19234766

  9. Case Management of Adolescents with Chronic Disease.

    ERIC Educational Resources Information Center

    Lankard, Bettina A.

    This training guide presents a model for optimum delivery of the primary duties, tasks, and steps required in the comprehensive case management of adolescents with chronic disease. Using a team approach to coordinated health care, the guide involves the patient and family as key members of the care team along with the physician, nurse, dietitian,…

  10. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease.

    PubMed

    Okazaki, Ryo; Watanabe, Reiko; Inoue, Daisuke

    2016-08-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients. PMID:27622174

  11. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Watanabe, Reiko; Inoue, Daisuke

    2016-01-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients.

  12. Preventive Care in Chronic Liver Disease

    PubMed Central

    Riley, Thomas R; Smith, Jill P

    1999-01-01

    OBJECTIVE To identify preventive care measures that are appropriate for and specific to patients with chronic liver disease and to provide recommendations and information that can be shared with patients. MEASUREMENTS A review of the literature was undertaken using medlinefrom 1970 to present. Priority was given to randomized controlled studies, but case reports, case-control studies, and reviews were included. MAIN RESULTS Evidence for the avoidance of alcohol and other toxic substances, immunizations, and dietary modifications for chronic liver disease is summarized. In addition, measures that are effective in the mitigation of the complications of cirrhosis are reviewed. CONCLUSIONS Preventive care can play an important role in patients with chronic liver diseases. Based on the existing data, the preventive strategies of alcohol avoidance, hepatitis vaccination, avoidance of NSAIDs nonsteroidal anti-inflammatory drugs, iron supplementation when appropriate, and a low-fat diet are prudent in patients with chronic liver disease. Once cirrhosis develops, screening for hepatocellular cancer with α-fetoprotein testing and ultrasound, and screening for varices by endoscopy are justified. PMID:10571719

  13. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Watanabe, Reiko; Inoue, Daisuke

    2016-01-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients. PMID:27622174

  14. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  15. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  16. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b)...

  17. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  18. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  19. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b)...

  20. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by...

  1. Anorexia during acute and chronic disease.

    PubMed

    Plata-Salamán, C R

    1996-02-01

    Anorexia is associated with disorders of all systems. Anorexia represents a consistent clinical manifestation during acute and chronic pathophysiological processes (infection, inflammation, injury, toxins, immunological reactions, malignancy and necrosis). Anorexia during disease can be beneficial or deleterious depending on the timing and duration. Temporary anorexia during acute disease may be beneficial to an organism since a restriction in the intake of micro- and macro-nutrients will inhibit bacterial growth. Long-term anorexia during chronic disease, however, is deleterious to an organism and may be associated with cachexia, which can ultimately result in death. Various mechanisms participate in the anorexia observed during disease, including cytokine action. Anorexia induced by cytokines is proposed to involve modulation of hypothalamic-feeding associated sites, prostaglandin-dependent mechanisms, modifications of neurotransmitter systems, gastrointestinal, metabolic, and endocrine factors. In addition, the anorexia-cachexia syndrome is multifactorial and may involve chronic pain, depression or anxiety, hypogeusia and hyposmia, chronic nausea, early satiety, malfunction of the gastrointestinal system, metabolic alterations, cytokine action, production of other anorexigenic substances and/or iatrogenic causes (chemotherapy, radiotherapy). Cachexia may result not only from anorexia and a decreased caloric intake, but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions), or a change in body metabolism. Research has focused on potential interventions to modify anorexia during disease and the anorexia-cachexia syndrome. Nutritional modifications and the use of specific steroids (such as megestrol acetate) are being tested in the clinical setting. Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexia (during a critical

  2. A Prediction Model for Chronic Kidney Disease Includes Periodontal Disease

    PubMed Central

    Fisher, Monica A.; Taylor, George W.

    2009-01-01

    Background An estimated 75% of the seven million Americans with moderate-to-severe chronic kidney disease are undiagnosed. Improved prediction models to identify high-risk subgroups for chronic kidney disease enhance the ability of health care providers to prevent or delay serious sequelae, including kidney failure, cardiovascular disease, and premature death. Methods We identified 11,955 adults ≥18 years of age in the Third National Health and Nutrition Examination Survey. Chronic kidney disease was defined as an estimated glomerular filtration rate of 15 to 59 ml/minute/1.73 m2. High-risk subgroups for chronic kidney disease were identified by estimating the individual probability using β coefficients from the model of traditional and non-traditional risk factors. To evaluate this model, we performed standard diagnostic analyses of sensitivity, specificity, positive predictive value, and negative predictive value using 5%, 10%, 15%, and 20% probability cutoff points. Results The estimated probability of chronic kidney disease ranged from virtually no probability (0%) for an individual with none of the 12 risk factors to very high probability (98%) for an older, non-Hispanic white edentulous former smoker, with diabetes ≥10 years, hypertension, macroalbuminuria, high cholesterol, low high-density lipoprotein, high C-reactive protein, lower income, and who was hospitalized in the past year. Evaluation of this model using an estimated 5% probability cutoff point resulted in 86% sensitivity, 85% specificity, 18% positive predictive value, and 99% negative predictive value. Conclusion This United States population–based study suggested the importance of considering multiple risk factors, including periodontal status, because this improves the identification of individuals at high risk for chronic kidney disease and may ultimately reduce its burden. PMID:19228085

  3. Animal models of chronic liver diseases.

    PubMed

    Liu, Yan; Meyer, Christoph; Xu, Chengfu; Weng, Honglei; Hellerbrand, Claus; ten Dijke, Peter; Dooley, Steven

    2013-03-01

    Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the "corresponding" human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases. PMID:23275613

  4. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  5. Alcoholic Beverage Consumption and Chronic Diseases

    PubMed Central

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations. PMID:27231920

  6. Alcoholic Beverage Consumption and Chronic Diseases.

    PubMed

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations. PMID:27231920

  7. Alcoholic Beverage Consumption and Chronic Diseases.

    PubMed

    Zhou, Yue; Zheng, Jie; Li, Sha; Zhou, Tong; Zhang, Pei; Li, Hua-Bin

    2016-01-01

    Epidemiological and experimental studies have consistently linked alcoholic beverage consumption with the development of several chronic disorders, such as cancer, cardiovascular diseases, diabetes mellitus and obesity. The impact of drinking is usually dose-dependent, and light to moderate drinking tends to lower risks of certain diseases, while heavy drinking tends to increase the risks. Besides, other factors such as drinking frequency, genetic susceptibility, smoking, diet, and hormone status can modify the association. The amount of ethanol in alcoholic beverages is the determining factor in most cases, and beverage types could also make an influence. This review summarizes recent studies on alcoholic beverage consumption and several chronic diseases, trying to assess the effects of different drinking patterns, beverage types, interaction with other risk factors, and provide mechanistic explanations.

  8. Comorbidity in chronic obstructive pulmonary disease.

    PubMed

    Negewo, Netsanet A; McDonald, Vanessa M; Gibson, Peter G

    2015-11-01

    Patients with chronic obstructive pulmonary diseases (COPD) often experience comorbid conditions. The most common comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions. Not only are comorbidities common but they also considerably influence disease prognosis and patients׳ health status, and are associated with poor clinical outcomes. However, perusal of literature indicates that little has been done so far to effectively assess, manage, and treat comorbidities in patients with COPD. The aim of this review is to comprehensively narrate the comorbid conditions that often coexist with COPD, along with their reported prevalence and their significant impacts in the disease management of COPD. A perspective on integrated disease management approaches for COPD is also discussed. PMID:26521102

  9. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

    PubMed Central

    Frederiksen, Brittni N.; Barón, Anna; Lamb, Molly M.; Crume, Tessa L.; Sontag, Marci K.; Norris, Jill M.

    2015-01-01

    Type 1 diabetes (T1D), a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA) where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW) ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA) levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases. PMID:25883970

  10. [Disease management for chronic heart failure patient].

    PubMed

    Bläuer, Cornelia; Pfister, Otmar; Bächtold, Christa; Junker, Therese; Spirig, Rebecca

    2011-02-01

    Patients with chronic heart failure (HF) are limited in their quality of life, have a poor prognosis and face frequent hospitalisations. Patient self-management was shown to improve quality of life, reduce rehospitalisations and costs in patients with chronic HF. Comprehensive disease management programmes are critical to foster patient self-management. The chronic care model developed by the WHO serves as the basis of such programmes. In order to develop self-management skills a needs orientated training concept is mandatory, as patients need both knowledge of the illness and the ability to use the information to make appropriate decisions according to their individual situation. Switzerland has no established system for the care of patients with chronic diseases in particular those with HF. For this reason a group of Swiss experts for HF designed a model for disease management for HF patients in Switzerland. Since 2009 the Swiss Heart Foundation offers an education programme based on this model. The aim of this programme is to offer education and support for practitioners, patients and families. An initial pilot evaluation of the program showed mixed acceptance by practitioners, whereas patient assessed the program as supportive and in line with their requirements.

  11. Helping to Combat Chronic Wasting Disease

    USGS Publications Warehouse

    ,

    2003-01-01

    Chronic wasting disease (CWD) is a disease of the nervous system that results in distinctive brain lesions. CWD affects elk, white-tailed deer, and mule deer, but has not been documented in livestock or humans. The origins of the disease, as well as the modes of transmission, remain unknown. Infected deer and elk appear robust and healthy in the early stages of CWD; clinical signs might not show for years. Mortality typically occurs within months after the appearance of clinical signs. The route of transmission is unknown; likely routes include direct transmission between infected and noninfected animals and infected animals contaminating local environments.

  12. Chronic Disease Modeling and Simulation Software

    PubMed Central

    Barhak, Jacob; Isaman, Deanna JM; Ye, Wen; Lee, Donghee

    2010-01-01

    Computers allow describing the progress of a disease using computerized models. These models allow aggregating expert and clinical information to allow researchers and decision makers to forecast disease progression. To make this forecast reliable, good models and therefore good modeling tools are required. This paper will describe a new computer tool designed for chronic disease modeling. The modeling capabilities of this tool were used to model the Michigan model for diabetes. The modeling approach and its advantages such as simplicity, availability, and transparency are discussed. PMID:20558320

  13. Pharmacologic issues in management of chronic disease.

    PubMed

    DeSevo, Gina; Klootwyk, Jacqueline

    2012-06-01

    A significant portion of the adult population uses one or more medications on a regular basis to manage chronic conditions. As the number of medications that patients are prescribed increases, an increase in pharmacologic-related issues and complications may occur, such as polypharmacy, inappropriate prescribing, medication nonadherence and nonpersistence, and adverse drug reactions and events. Risk factors and consequences of these issues have been identified and are discussed in this article. In addition, a review is presented of the numerous methods that have been evaluated to help prevent and minimize these pharmacologic issues in the management of chronic disease.

  14. Haemostasis in chronic kidney disease.

    PubMed

    Lutz, Jens; Menke, Julia; Sollinger, Daniel; Schinzel, Helmut; Thürmel, Klaus

    2014-01-01

    The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.

  15. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    PubMed

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis.

  16. Mediterranean dietary pattern and chronic diseases.

    PubMed

    Panico, Salvatore; Mattiello, Amalia; Panico, Camilla; Chiodini, Paolo

    2014-01-01

    The study of the relationship between the Mediterranean way of eating and the occurrence of diseases typical of the economically developed countries has been considered the starting point of nutritional epidemiology. From the Seven Countries Study in the 1950s to the recent European EPIC collaboration, the evaluation of the components of diet-affecting chronic diseases such as cardiovascular disease and cancer has been crucially based on the analysis of foods and nutrients characterizing the Mediterranean dietary habits. This long research history has been marked by a consistency of data over time when either single nutrients/food groups or more complex dietary patterns have been analyzed: The Mediterranean way of eating is a protective tool from cardiovascular diseases and many cancers. Italy has been a natural point of observation, starting from cardiovascular disease in the mid-1950s and continuing with major cancers. In spite of unfavorable lifestyle changes in the Italian population mostly due to globalization of unhealthy habits (richer diet and lower levels of physical activity), those individuals still close to the Mediterranean style are significantly protected. The very recent Italian data derived from the observation of about 50,000 individuals, participating in the Italian cohorts of the EPIC study, confirm these findings and are consistent with results from other European populations and in some cases also from North American populations. Moreover, several dietary trials suggest that such a way of eating improves both the metabolic risk condition for chronic disease and the occurrence of those diseases. In conclusion, a way of eating inspired by a Mediterranean dietary pattern is not only based on evidence but is also a palatable style that has contributed to protection from the epidemic of chronic diseases. PMID:24114475

  17. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  18. Chronic Inflammatory Diseases and Endothelial Dysfunction

    PubMed Central

    Castellon, Xavier; Bogdanova, Vera

    2016-01-01

    Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall’s structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors. PMID:26815098

  19. The vital signs of chronic disease management.

    PubMed

    Harries, Anthony D; Zachariah, Rony; Kapur, Anil; Jahn, Andreas; Enarson, Donald A

    2009-06-01

    The vital signs of pulse rate, blood pressure, temperature and respiratory rate are the 'nub' of individual patient management. At the programmatic level, vital signs could also be used to monitor the burden and treatment outcome of chronic disease. Case detection and treatment outcome constitute the vital signs of tuberculosis control within the WHO's 'DOTS' framework, and similar vital signs could be adapted and used for management of chronic diseases. The numbers of new patients started on therapy in each month or quarter (new incident cases) are sensitive indicators for programme performance and access to services. Using similar reporting cycles, treatment outcomes for all patients can be assessed, the vital signs being: alive and retained on therapy at the respective facility; died; stopped therapy; lost to follow-up; and transferred out to another facility. Retention on treatment constitutes the prevalent number of cases, the burden of disease, and this provides important strategic information for rational drug forecasting and logistic planning. If case numbers and outcomes of chronic diseases were measured reliably and consistently as part of an integrated programmatic approach, this would strengthen the ability of resource-poor countries to monitor and assess their response to these growing epidemics.

  20. Mechanisms of Cachexia in Chronic Disease States.

    PubMed

    Yoshida, Tadashi; Delafontaine, Patrice

    2015-10-01

    Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases, such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme inhibitor treatment improves weight loss. It was found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones, such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system and decreased appetite resulting from the downregulation of hypothalamic orexigenic neuropeptides, such as Npy and orexin. Ang II also inhibits 5' adenosine monophosphate-activated protein kinase activity and disrupts normal energy balance via the activation of 5' adenosine monophosphate-activated protein kinase phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for the regulation of muscle regeneration. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states, and it is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD.

  1. Hypertension and chronic kidney disease in Turkey.

    PubMed

    Sengul, Sule; Erdem, Yunus; Batuman, Vecihi; Erturk, Sehsuvar

    2013-12-01

    Worldwide, both hypertension and chronic kidney disease are major public health problems, due to their epidemic proportions and their association with high cardiovascular mortality. In 2003, the first Prevalence, awareness, treatment, and control of hypertension in Turkey (the PatenT) study was conducted in a nationally representative population (n=4910) by the Turkish Society of Hypertension and Renal Diseases, and showed that overall age- and sex-adjusted prevalence of hypertension in Turkey was 31.8%. The PatenT study also reported that overall awareness (40.7%), treatment (31.1%), and control rates (8.1%) of hypertension were strikingly low. Only 20.7% of the patients who were aware of their hypertension and receiving treatment had their blood pressure controlled to <140/90 mm Hg. In the Chronic Renal Disease in Turkey (CREDIT) study (n=10,748), the overall prevalence of chronic kidney (including all stages) disease was 15.7% and increased with advancing age. In the same population, the prevalence of hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome were reported as 32.7%, 12.7%, 76.3%, 20.1%, and 31.3%, respectively. The prevalence and awareness of hypertension in CREDIT population was 32.7% and 48.6%, respectively. According to the data obtained from national surveys, the prevalence of hypertension and chronic kidney disease in Turkey is alarmingly high. To improve prevention, early diagnosis, and treatment of these major public health problems, appropriate health strategies should be implemented by the government, together with medical societies, non-governmental organizations, industry, health-care providers, and academia. PMID:25019009

  2. [Pneumococcal vaccine recommendations in chronic respiratory diseases].

    PubMed

    Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

    2014-09-01

    Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD.

  3. [Pneumococcal vaccine recommendations in chronic respiratory diseases].

    PubMed

    Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

    2014-09-01

    Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD. PMID:25107494

  4. [Nutritional abnormalities in chronic obstructive pulmonary disease].

    PubMed

    Gea, Joaquim; Martínez-Llorens, Juana; Barreiro, Esther

    2014-07-22

    Nutritional abnormalities are associated with chronic obstructive pulmonary disease with a frequency ranging from 2 to 50%, depending on the geographical area and the study design. Diagnostic tools include anthropometry, bioelectrical impedance, dual energy radioabsortiometry and deuterium dilution, being the body mass and the lean mass indices the most frequently used parameters. While the most important consequences of nutritional abnormalities are muscle dysfunction and exercise limitation, factors implicated include an imbalance between caloric intake and consumption, and between anabolic and catabolic hormones, inflammation, tobacco smoking, poor physical activity, hypoxemia, some drugs and aging/comorbidities. The most important molecular mechanism for malnutrition associated with chronic obstructive pulmonary disease appears to be the mismatching between protein synthesis and breakdown. Among the therapeutic measures proposed for these nutritional abnormalities are improvements in lifestyle and nutritional support, although the use of anabolic drugs (such as secretagogues of the growth hormone) offers a new therapeutic strategy.

  5. Sleep disorders and chronic kidney disease

    PubMed Central

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-01-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD. PMID:27152260

  6. Sleep disorders and chronic kidney disease.

    PubMed

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-05-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.

  7. [Nutritional abnormalities in chronic obstructive pulmonary disease].

    PubMed

    Gea, Joaquim; Martínez-Llorens, Juana; Barreiro, Esther

    2014-07-22

    Nutritional abnormalities are associated with chronic obstructive pulmonary disease with a frequency ranging from 2 to 50%, depending on the geographical area and the study design. Diagnostic tools include anthropometry, bioelectrical impedance, dual energy radioabsortiometry and deuterium dilution, being the body mass and the lean mass indices the most frequently used parameters. While the most important consequences of nutritional abnormalities are muscle dysfunction and exercise limitation, factors implicated include an imbalance between caloric intake and consumption, and between anabolic and catabolic hormones, inflammation, tobacco smoking, poor physical activity, hypoxemia, some drugs and aging/comorbidities. The most important molecular mechanism for malnutrition associated with chronic obstructive pulmonary disease appears to be the mismatching between protein synthesis and breakdown. Among the therapeutic measures proposed for these nutritional abnormalities are improvements in lifestyle and nutritional support, although the use of anabolic drugs (such as secretagogues of the growth hormone) offers a new therapeutic strategy. PMID:24054776

  8. Sleep disorders and chronic kidney disease.

    PubMed

    Maung, Stephanie C; El Sara, Ammar; Chapman, Cherylle; Cohen, Danielle; Cukor, Daniel

    2016-05-01

    Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease (CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD. PMID:27152260

  9. Chronic granulomatous disease associated with atypical Kawasaki disease.

    PubMed

    Yamazaki-Nakashimada, M A; Ramírez-Vargas, N; De Rubens-Figueroa, J

    2008-01-01

    Chronic granulomatous disease (CGD) is an infrequent inherited disorder characterized by recurrent infections and abnormal granuloma formation. Patients with CGD have an exuberant inflammatory response and an increased risk of developing autoimmunity. We present the case of a 1-year-old boy with CGD who developed several of the characteristic clinical features of Kawasaki Disease. His illness responded to intravenous immunoglobulin, aspirin, and corticosteroids.

  10. Chronic disease management for patients with respiratory disease.

    PubMed

    Bryant, Elizabeth

    National and international awareness of the heavy burden of chronic disease has led to the development of new strategies for managing care. Elisabeth Bryant explains how self-care, education and support for more patients with complex needs should be built into planned care delivery, and emphasises that the patient is the key member of the care team.

  11. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  12. Sustainable chronic disease management in remote Australia.

    PubMed

    Wakerman, John; Chalmers, Elizabeth M; Humphreys, John S; Clarence, Christine L; Bell, Andrew I; Larson, Ann; Lyle, David; Pashen, Dennis R

    2005-11-21

    The Sharing Health Care Initiative (SHCI) demonstration project, which aimed to improve management of chronic diseases, was implemented in four small remote communities in the Katherine region which are serviced by the Katherine West Health Board, a remote Aboriginal-community-controlled health organisation in the Northern Territory. We reviewed the project proposal, final report, evaluation reports and transitional funding proposal, and supplemented these with in-depth interviews with key individuals. We determined factors critical to the sustainability of the SHCI project in relation to context, community engagement, systems flexibility and adaptability, the availability and effect of information systems, and the human nature of health care and policy. The project had a significant impact on community awareness of chronic disease and an improvement in clinic processes. We found that a number of interrelated factors promoted sustainability, including: An implementation strategy sufficiently flexible to take account of local conditions; A high level of community engagement; Appropriate timeframes, timing and congruence between national policy and local readiness to implement a chronic disease project; Effective communication between participating organisations; Project champions (key individuals) in participating organisations; Effective use of monitoring and evaluation data; and Adequate and ongoing funding. The absence of a number of these factors, such as poor communication, inhibited sustainability. Other factors could both promote and inhibit. For example, the impact of key individuals was important, but could be idiosyncratic and have negative effects.

  13. A Clear Cell Renal Cell Carcinoma Inhibiting the Response to Intravitreal Antivascular Endothelial Growth Factor Therapy in Wet Age-Related Macular Disease

    PubMed Central

    Falcão, Manuel S.; Vinagre, João; Soares, Paula; Lopes, José Manuel; Brandão, Elisete; Carneiro, Ângela M.

    2012-01-01

    Purpose Wet age-related macular degeneration (AMD) is an ocular disorder that can be successfully treated with intravitreal antivascular endothelial growth factor (VEGF) therapy. We report a case of incomplete response to intravitreal therapy associated with a clear cell renal cell carcinoma (ccRCC). Methods A 72-year-old male with wet AMD responded poorly to intravitreal bevacizumab and ranibizumab injections. The removal of a ccRCC led to the spontaneous stabilization of the choroidal neovascular lesion. The renal carcinoma was examined for Von Hippel-Lindau (VHL) gene alterations. Immunohistochemical profiling of the hypoxia-inducible factor (HIF) pathway addressing the marker HIF-1α and its downstream targets VEGF, glucose transporter 1 and carbonic anhydrase IX was performed. Results Genotyping of the ccRCC revealed the presence of a truncating VHL mutation (p.E134fs*25). Immunohistochemistry displayed HIF pathway target activation and VEGF expression in the ccRCC tumour cells. Following tumour removal, the neovascular lesion remained stable for 6 months without any further anti-VEGF therapy. Conclusion The somatic VHL mutation correlates with persistent high levels of HIF-1α pathway targets and VEGF expression in the ccRCC. We postulate that this increased VEGF in the tumour and subsequently in the plasma levels could have caused the incomplete response to intravitreal anti-VEGF therapy. Stabilization of the wet AMD following tumour removal indicates that the angiogenic secreting tumour (ccRCC) abrogates the response to VEGF inhibitor therapy. Thus, in cases of poor response to intravitreal anti-VEGF therapy, systemic evaluation including plasma levels of VEGF and/or systemic screening for VEGF-producing tumours should be considered. PMID:23341823

  14. Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes.

    PubMed

    Khan, Kamron N; Mahroo, Omar A; Khan, Rehna S; Mohamed, Moin D; McKibbin, Martin; Bird, Alan; Michaelides, Michel; Tufail, Adnan; Moore, Anthony T

    2016-07-01

    Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research. PMID:27173377

  15. Skin manifestations of chronic kidney disease.

    PubMed

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

    2015-10-01

    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions.

  16. Coagulation factors in chronic liver disease.

    PubMed

    Donaldson, G W; Davies, S H; Darg, A; Richmond, J

    1969-03-01

    Coagulation studies were carried out on 30 patients with chronic liver disease. The clotting defect was complex and involved factors V, VII, IX (Christmas factor), and prothrombin. Some patients showed a significant depression of factor IX in the presence of a normal one-stage prothrombin time. Thrombotest was found to be a good indicator of factor IX deficiency in this group of patients and may be of use as an additional liver function test. The screening of patients with liver disease for surgery or liver biopsy should assess the coagulation factors involved in both intrinsic and extrinsic thromboplastin generation.

  17. Exercise training as a preventive tool for age-related disorders: a brief review

    PubMed Central

    Ciolac, Emmanuel Gomes

    2013-01-01

    Aging populations are a worldwide phenomenon affecting both developed and developing countries. This issue raises serious concerns for both governments and the general population. Regular participation in physical activity and/or exercise training programs can minimize the physiological alterations that occur during aging and may contribute to improvements in health and well-being. The present review will discuss the role of regular exercise training in preventing age-related physiological decline and, consequently, associated chronic diseases. Compelling evidence that regular exercise and/or physical activity can improve quality of life, prevent or control the development of chronic disease and increase life expectancy is shown. In summary, regular exercise training and/or physical activity has an important influence on aging and may help to prevent age-related disorders. PMID:23778419

  18. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  19. Chronic beryllium disease: Diagnosis and management

    SciTech Connect

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  20. Chronic liver disease in Aboriginal North Americans

    PubMed Central

    Scott, John D; Garland, Naomi

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population. PMID:18698674

  1. Chronic obstructive pulmonary disease in Japan.

    PubMed

    Izumi, Takateru

    2002-03-01

    In Japan, the term chronic obstructive pulmonary disease (COPD) has only recently come to be used as it is in Western countries, especially with respect to its classification as a tobacco-related disease. The disease, COPD, did not appear in Japanese government statistics until 1995. The main reason for the nearly 20-year lag behind the West in recognizing this disease was the small number of COPD cases caused by smoking. Cigarette consumption in Japan increased with the increase in personal income that accompanied rapid ecomomic growth from 1955 to 1974. Since approximately 1980, the number of deaths caused by COPD (emphysema) started increasing. Although cigarette consumption stopped increasing after 1995, COPD (emphysema) mortality is still increasing as a repercussion of the earlier increases of cigarette consumption. However, the number of COPD patients and the scale of medical expenditure for COPD in Japan is somewhat smaller than in Western countries.

  2. Chronic Recurrent Multifocal Osteomyelitis and Thalidomide in Chronic Granulomatous Disease.

    PubMed

    Martín-Nalda, Andrea; Roca, Isabel; Fontecha, Cesar Galo; Fernández-Polo, Aurora; Barber, Ignasi; Martinez-Gallo, Mónica; Soler-Palacin, Pere

    2016-08-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency that leads to severe recurrent infection and inflammatory complications that are usually difficult to diagnose and treat. Several hyperinflammation mechanisms, such as decreased neutrophil apoptosis, toll-like receptor activation imbalance, Th17 cell induction, Nrf2 activity deficiency, and inflammasome activation, have been described in CGD patients However, there have been no reports of chronic recurrent multifocal osteomyelitis as an inflammatory complication in CGD, and the differential diagnosis of this condition with infectious osteomyelitis is challenging. Thalidomide has been used to treat several inflammatory manifestations in CGD patients with good clinical results. Here, we report the case of a previously asymptomatic 11-year-old boy who consulted for difficulty walking and pain at the back of the right thigh, with increased inflammatory markers. Multifocal bone involvement was seen on bone scintigraphy, and acute-phase reactants were elevated. On the basis of a suspected diagnosis of infectious osteomyelitis, broad-spectrum antibiotic therapy was started, with no clinical response. Bone biopsy and microbiological tests yielded negative results; at that point, chronic recurrent multifocal osteomyelitis was suspected. The patient was unresponsive to nonsteroidal antiinflammatory drugs and corticosteroids. Thalidomide was started, and within 6 months, clinical and radiologic resolution of the condition was achieved with no adverse effects. More than 1 year after stopping thalidomide, the patient remained free of symptoms and inflammatory parameters are within normal levels. Thalidomide has a favorable safety profile compared with other alternatives and could be considered a feasible therapeutic option for this type of condition in selected patients. PMID:27436506

  3. Neprilysin inhibition in chronic kidney disease

    PubMed Central

    Judge, Parminder; Haynes, Richard; Landray, Martin J.; Baigent, Colin

    2015-01-01

    Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin–angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population. PMID:25140014

  4. Secondary Care Clinic for Chronic Disease: Protocol

    PubMed Central

    St-Pierre, Michèle; Juneau, Lucille; Legault-Mercier, Samuel; Bernardino, Elizabeth

    2015-01-01

    Background The complexity of chronic disease management activities and the associated financial burden have prompted the development of organizational models, based on the integration of care and services, which rely on primary care services. However, since the institutions providing these services are continually undergoing reorganization, the Centre hospitalier affilié universitaire de Québec wanted to innovate by adapting the Chronic Care Model to create a clinic for the integrated follow-up of chronic disease that relies on hospital-based specialty care. Objective The aim of the study is to follow the project in order to contribute to knowledge about the way in which professional and management practices are organized to ensure better care coordination and the successful integration of the various follow-ups implemented. Methods The research strategy adopted is based on the longitudinal comparative case study with embedded units of analysis. The case study uses a mixed research method. Results We are currently in the analysis phase of the project. The results will be available in 2015. Conclusions The project’s originality lies in its consideration of the macro, meso, and micro contexts structuring the creation of the clinic in order to ensure the integration process is successful and to allow a theoretical generalization of the reorganization of practices to be developed. PMID:25689840

  5. Respiratory Conditions Update: Chronic Obstructive Pulmonary Disease.

    PubMed

    Karel, Daphne J

    2016-09-01

    Chronic obstructive pulmonary disease (COPD) is defined as persistent airflow limitation due to irritant-induced chronic inflammation. A postbronchodilator forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio of 0.7 or less is diagnostic in a patient with dyspnea, chronic cough or sputum production, and a history of irritant exposure. Tobacco smoking is the most significant etiology, and smoking cessation is the only intervention shown to slow disease progression. Long-acting beta2-agonists and long-acting muscarinic antagonists are first-line treatments for patients with persistently symptomatic COPD with an FEV1 of 80% or less of predicted. When COPD is uncontrolled with a long-acting bronchodilator, combination therapy with a long-acting muscarinic antagonist-long-acting beta2-agonist or long-acting beta2-agonist-inhaled corticosteroid should be prescribed. Patients with COPD and reduced exercise tolerance should undergo pulmonary rehabilitation and be evaluated for supplemental oxygen therapy. Other treatment options for persistently symptomatic COPD include inhaler triple therapy (ie, long-acting muscarinic antagonist, long-acting beta2-agonist, inhaled corticosteroid), phosphodiesterase type 4 inhibitors, oxygen, and surgical interventions. PMID:27576232

  6. Recent updates in chronic obstructive pulmonary disease.

    PubMed

    Garvey, Christine

    2016-01-01

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airways inflammation and progressive airflow limitation, is a common, preventable and treatable disease. Worldwide, COPD is a major cause of morbidity and mortality; smoking tobacco is the most important risk factor. This translational review of recent updates in COPD care for the primary care audience, includes recommendations from the 2015 Global Initiative for chronic obstructive lung disease (GOLD) report on diagnosis, pharmacological and non-pharmacological treatment, prevalence of comorbidities, management of exacerbations and the asthma and COPD overlap syndrome, with a focus on the importance and benefit of physical activity and exercise in COPD patients. Exacerbations and comorbidities contribute to the overall severity of COPD in individual patients. Management of exacerbations includes reducing the impact of the current exacerbation and preventing development of subsequent episodes. Healthcare professionals need to be alert to comorbidities, such as cardiovascular disease, anxiety/depression, lung cancer, infections and diabetes, which are common in COPD patients and can have a significant impact on HRQoL and prognosis. Pulmonary rehabilitation is recommended by a number of guidelines for all symptomatic COPD patients, regardless of severity, and involves exercise training, patient education, nutritional advice and psychosocial support. At all stages of COPD, regular physical activity and exercise can aid symptom control, improve HRQoL, reduce rates of hospitalization, and improve morbidity and respiratory mortality. Healthcare professionals play a pivotal role in improving HRQoL and health-related outcomes in COPD patients to meet their specific needs and in providing appropriate diagnosis, management and advice on smoking cessation.

  7. Recent updates in chronic obstructive pulmonary disease.

    PubMed

    Garvey, Christine

    2016-01-01

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airways inflammation and progressive airflow limitation, is a common, preventable and treatable disease. Worldwide, COPD is a major cause of morbidity and mortality; smoking tobacco is the most important risk factor. This translational review of recent updates in COPD care for the primary care audience, includes recommendations from the 2015 Global Initiative for chronic obstructive lung disease (GOLD) report on diagnosis, pharmacological and non-pharmacological treatment, prevalence of comorbidities, management of exacerbations and the asthma and COPD overlap syndrome, with a focus on the importance and benefit of physical activity and exercise in COPD patients. Exacerbations and comorbidities contribute to the overall severity of COPD in individual patients. Management of exacerbations includes reducing the impact of the current exacerbation and preventing development of subsequent episodes. Healthcare professionals need to be alert to comorbidities, such as cardiovascular disease, anxiety/depression, lung cancer, infections and diabetes, which are common in COPD patients and can have a significant impact on HRQoL and prognosis. Pulmonary rehabilitation is recommended by a number of guidelines for all symptomatic COPD patients, regardless of severity, and involves exercise training, patient education, nutritional advice and psychosocial support. At all stages of COPD, regular physical activity and exercise can aid symptom control, improve HRQoL, reduce rates of hospitalization, and improve morbidity and respiratory mortality. Healthcare professionals play a pivotal role in improving HRQoL and health-related outcomes in COPD patients to meet their specific needs and in providing appropriate diagnosis, management and advice on smoking cessation. PMID:26560514

  8. Independent effects of age-related changes in waist circumference and BMI z scores in predicting cardiovascular disease risk factors in a prospective cohort of adolescent females

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Cross-sectional data indicate that central adiposity is associated with cardiovascular disease risk, independent of total adiposity. The use of longitudinal data to investigate the relation between changes in fat distribution and the emergence of risk factors is limited. OBJECTIVE: We ...

  9. Chronic kidney disease: considerations for nutrition interventions.

    PubMed

    Steiber, Alison L

    2014-05-01

    Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition-related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian-style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention.

  10. "Exercise as medicine" in chronic kidney disease.

    PubMed

    Wilkinson, T J; Shur, N F; Smith, A C

    2016-08-01

    Exercise and physical activity are increasingly becoming key tools in the treatment and prevention of several medical conditions including arthritis and diabetes; this notion has been termed "exercise as medicine". Exercise has favorable effects on reducing cardiovascular risk, inflammation, cachexia, and hypertension, in addition to increasing physical functioning, strength, and cardio-respiratory capacity. Chronic kidney disease, a condition that affects around 10% of the population, is often overlooked as a target for exercise-based therapy. Despite the vast range of severity in kidney disease (e.g., pre-dialysis, dialysis, transplant), exercise has a potential role in all patients suffering from the condition. In this review, we summarise the important role exercise may have in the clinical management of kidney disease and how this form of 'medicine' should be best administered and 'prescribed'. PMID:27334146

  11. Mechanisms of Chronic Obstructive Pulmonary Disease Exacerbations.

    PubMed

    Wedzicha, Jadwiga A

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) exacerbations are important events that contribute to worsening health status, disease progression, and mortality. They are mainly triggered by respiratory viruses (especially rhinovirus, the cause of the common cold), but airway bacteria are also involved in their pathogenesis. Exacerbations are associated with both airway and systemic inflammation and, this is mainly neutrophilic in origin. Some patients are especially prone to develop exacerbations, and these have been identified as a high-risk group with increased airway inflammation and greater disease progression. Management of acute exacerbations involves therapy with oral corticosteroids and/or antibiotics, and new therapies are needed. A number of interventions may prevent exacerbations, including vaccination, long-acting bronchodilators, antiinflammatory agents, and long-term antibiotic therapy. Understanding of the pathophysiological mechanisms of COPD exacerbations is important to develop novel therapies.

  12. Chronic kidney disease and bone metabolism.

    PubMed

    Kazama, Junichiro James; Matsuo, Koji; Iwasaki, Yoshiko; Fukagawa, Masafumi

    2015-05-01

    Chronic kidney disease-related mineral and bone disease (CKD-MBD) is a syndrome defined as a systemic mineral metabolic disorder associated with CKD, and the term renal osteodystrophy indicates a pathomorphological concept of bone lesions associated with CKD-MBD. Cortical bone thinning, abnormalities in bone turnover and primary/secondary mineralization, elevated levels of circulating sclerostin, increased apoptosis in osteoblasts and osteocytes, disturbance of the coupling phenomenon, iatrogenic factors, accumulated micro-crackles, crystal/collagen disorientation, and chemical modification of collagen crosslinks are all possible candidates found in CKD that could promote osteopenia and/or bone fragility. Some of above factors are the consequences of abnormal systemic mineral metabolism but for others it seem unlikely. We have used the term uremic osteoporosis to describe the uremia-induced bone fragility which is not derived from abnormal systemic mineral metabolism. Interestingly, the disease aspect of uremic osteoporosis appears to be similar to that of senile osteoporosis. PMID:25653092

  13. Methylotroph Infections and Chronic Granulomatous Disease.

    PubMed

    Falcone, E Liana; Petts, Jennifer R; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M; Neves, João Farela; Simões, Maria João; Tierce, Millard L; de la Morena, M Teresa; Greenberg, David E; Zerbe, Christa S; Zelazny, Adrian M; Holland, Steven M

    2016-03-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

  14. [Pulmonary obstructive chronic disease and physical exercise].

    PubMed

    António, Carla; Gonçalves, Ana Paula; Tavares, Alcina

    2010-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a disease that can be prevented and treated, with a pulmonary component and with significant systemic effects that contribute to the severity of clinical manifestations. COPD causes a number of changes, including those which lead to exercise tolerance limitation and to a progressive deterioration of life quality of the patients. Respiratory rehabilitation (RR) represents a key part of the treatment. The benefits of RR are independent of sex, age and disease severity. At the end of the program, the patient should have acquired a life style as independent and healthy as possible. With this article the authors intend to review the benefits of physical exercise in rehabilitation of patients with COPD and the different types of training used in the respiratory rehabilitation program established for each patient. PMID:20700562

  15. Chronic kidney disease in disadvantaged populations

    PubMed Central

    Garcia-Garcia, G.; Jha, V.

    2015-01-01

    The increased burden of chronic kidney disease (CKD) in disadvantaged populations is due to both global factors and population-specific issues. Low socioeconomic status and poor access to care contribute to health care disparities and exacerbate the negative effects of genetic or biological predisposition. Provision of appropriate renal care to these populations requires a two-pronged approach: expanding the reach of dialysis through development of low-cost alternatives that can be practiced in remote locations, and implementation and evaluation of cost-effective prevention strategies. Kidney transplantation should be promoted by expansion of deceased donor transplant programs and use of inexpensive, generic immunosuppressive drugs. The message of World Kidney Day 2015 is that a concerted attack against the diseases that lead to end-stage renal disease, by increasing community outreach, better education, improved economic opportunity, and access to preventive medicine for those at highest risk, could end the unacceptable relationship between CKD and disadvantage in these communities. PMID:25760025

  16. An Informatics-based Chronic Disease Practice

    PubMed Central

    Nordyke, Robert A.; Kulikowski, Casimir A.

    1998-01-01

    The authors present the case study of a 35-year informatics-based single subspecialty practice for the management of patients with chronic thyroid disease. This extensive experience provides a paradigm for the organization of longitudinal medical information by integrating individual patient care with clinical research and education. The kernel of the process is a set of worksheets easily completed by the physician during the patient encounter. It is a structured medical record that has been computerized since 1972, enabling analysis of different groups of patients to answer questions about chronic conditions and the effects of therapeutic interventions. The recording process and resulting studies severe as an important vehicle for medical education about the nuances of clinical practice. The authors suggest ways in which computerized medical records can become an integral part of medical practice, rather than a luxury or novelty. PMID:9452988

  17. The Indiana Chronic Disease Management Program

    PubMed Central

    Rosenman, Marc B; Holmes, Ann M; Ackermann, Ronald T; Murray, Michael D; Doebbeling, Caroline Carney; Katz, Barry; Li, Jingjin; Zillich, Alan; Prescott, Victoria M; Downs, Stephen M; Inui, Thomas S

    2006-01-01

    The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation. PMID:16529571

  18. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  19. Costs of Chronic Diseases at the State Level: The Chronic Disease Cost Calculator

    PubMed Central

    Murphy, Louise B.; Khavjou, Olga A.; Li, Rui; Maylahn, Christopher M.; Tangka, Florence K.; Nurmagambetov, Tursynbek A.; Ekwueme, Donatus U.; Nwaise, Isaac; Chapman, Daniel P.; Orenstein, Diane

    2015-01-01

    Introduction Many studies have estimated national chronic disease costs, but state-level estimates are limited. The Centers for Disease Control and Prevention developed the Chronic Disease Cost Calculator (CDCC), which estimates state-level costs for arthritis, asthma, cancer, congestive heart failure, coronary heart disease, hypertension, stroke, other heart diseases, depression, and diabetes. Methods Using publicly available and restricted secondary data from multiple national data sets from 2004 through 2008, disease-attributable annual per-person medical and absenteeism costs were estimated. Total state medical and absenteeism costs were derived by multiplying per person costs from regressions by the number of people in the state treated for each disease. Medical costs were estimated for all payers and separately for Medicaid, Medicare, and private insurers. Projected medical costs for all payers (2010 through 2020) were calculated using medical costs and projected state population counts. Results Median state-specific medical costs ranged from $410 million (asthma) to $1.8 billion (diabetes); median absenteeism costs ranged from $5 million (congestive heart failure) to $217 million (arthritis). Conclusion CDCC provides methodologically rigorous chronic disease cost estimates. These estimates highlight possible areas of cost savings achievable through targeted prevention efforts or research into new interventions and treatments. PMID:26334712

  20. Chronic Obstructive Pulmonary Disease in the elderly.

    PubMed

    Incalzi, Raffaele Antonelli; Scarlata, Simone; Pennazza, Giorgio; Santonico, Marco; Pedone, Claudio

    2014-04-01

    The prevalence of Chronic Obstructive Pulmonary Disease (COPD) dramatically increases with age, and COPD complicated by chronic respiratory failure may be considered a geriatric condition. Unfortunately, most cases remain undiagnosed because of atypical clinical presentation and difficulty with current respiratory function diagnostic standards. Accordingly, the disease is under-recognized and undertreated. This is expected to impact noticeably the health status of unrecognized COPD patients because a timely therapy could mitigate the distinctive and important effects of COPD on the health status. Comorbidity also plays a pivotal role in conditioning both the health status and the therapy of COPD besides having major prognostic implication. Several problems affect the overall quality of the therapy for the elderly with COPD, and current guidelines as well as results from pharmacological trials only to some extent apply to this patient. Finally, physicians of different specialties care for the elderly COPD patient: physician's specialty largely determines the kind of approach. In conclusion, COPD, in itself a complex disease, becomes difficult to identify and to manage in the elderly. Interdisciplinary efforts are desirable to provide the practicing physician with a multidisciplinary guide to the identification and treatment of COPD. PMID:24183233

  1. Interdisciplinary care clinics in chronic kidney disease.

    PubMed

    Johns, Tanya S; Yee, Jerry; Smith-Jules, Terrian; Campbell, Ruth C; Bauer, Carolyn

    2015-01-01

    The burden of chronic kidney disease (CKD) is substantial, and is associated with high hospitalization rates, premature deaths, and considerable health care costs. These factors provide strong rationale for quality improvement initiatives in CKD care. The interdisciplinary care clinic (IDC) has emerged as one solution to improving CKD care. The IDC team may include other physicians, advanced practice providers, nurses, dietitians, pharmacists, and social workers--all working together to provide effective care to patients with chronic kidney disease. Studies suggest that IDCs may improve patient education and preparedness prior to kidney failure, both of which have been associated with improved health outcomes. Interdisciplinary care may also delay the progression to end-stage renal disease and reduce mortality. While most studies suggest that IDC services are likely cost-effective, financing IDCs is challenging and many insurance providers do not pay for all of the services. There are also no robust long-term studies demonstrating the cost-effectiveness of IDCs. This review discusses IDC models and its potential impact on CKD care as well as some of the challenges that may be associated with implementing these clinics. PMID:26458811

  2. Genetic Considerations in Pediatric Chronic Kidney Disease.

    PubMed

    Harshman, Lyndsay A; Zepeda-Orozco, Diana

    2016-03-01

    Chronic kidney disease (CKD) in children is an irreversible process that, in some cases, may lead to end-stage renal disease. The majority of children with CKD have a congenital disorder of the kidney or urological tract arising from birth. There is strong evidence for both a genetic and epigenetic component to progression of CKD. Utilization of gene-mapping strategies, ranging from genome-wide association studies to single-nucleotide polymorphism analysis, serves to identify potential genetic variants that may lend to disease variation. Genome-wide association studies evaluating population-based data have identified different loci associated with CKD progression. Analysis of single-nucleotide polymorphisms on an individual level suggests that secondary systemic sequelae of CKD are closely related to dysfunction of the cardiovascular-inflammatory axis and may lead to advanced cardiovascular disease through abnormal vascular calcification and activation of the renin-angiotensin system. Similarly, genetic variants affecting cytokine control, fibrosis, and parenchymal development may modulate CKD through development and acceleration of renal interstitial fibrosis. Epigenetic studies evaluate modification of the genome through DNA methylation, histone modification, or RNA interference, which may be directly influenced by external or environmental factors directing genomic expression. Lastly, improved understanding of the genetic and epigenetic contribution to CKD progression may allow providers to identify a population at accelerated risk for disease progression and apply novel therapies targeted at the genetic mechanism of disease. PMID:27617141

  3. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

    PubMed

    Franceschi, Claudio; Campisi, Judith

    2014-06-01

    Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session.

  4. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases.

    PubMed

    Franceschi, Claudio; Campisi, Judith

    2014-06-01

    Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging." Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Nevertheless, the precise etiology of inflammaging and its potential causal role in contributing to adverse health outcomes remain largely unknown. The identification of pathways that control age-related inflammation across multiple systems is therefore important in order to understand whether treatments that modulate inflammaging may be beneficial in old people. The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging. This article reports the main outcomes of this session. PMID:24833586

  5. A customizable model for chronic disease coordination: Lessons learned from the coordinated chronic disease program

    DOE PAGES

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-03-31

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managedmore » resources, and 6) relationship building. Furthermore, these elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.« less

  6. Chronic Wasting Disease Positive Tissue Bank

    USGS Publications Warehouse

    Wright, Scott D.

    2007-01-01

    In 2005, the USGS National Wildlife Health Center entered into an agreement with the Wyoming Game and Fish Department and the Department of Veterinary Sciences at the University of Wyoming to produce a collection of positive tissues from cervids intentionally infected with chronic wasting disease. This agreement was facilitated through the University of Wyoming Cooperative Fish and Wildlife Unit. Also, the investigators on this project sampled the animals incrementally over 2 years to show changes over time, and examined tissues from the animals by immunohistochemistry. CWD positive tissues are catalogued by species, sample site and time of infection. These data and more will soon be published.

  7. Vitamin K status in chronic kidney disease.

    PubMed

    McCabe, Kristin M; Adams, Michael A; Holden, Rachel M

    2013-11-07

    The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population.

  8. Baroreflex dysfunction in chronic kidney disease

    PubMed Central

    Kaur, Manpreet; Chandran, Dinu S; Jaryal, Ashok Kumar; Bhowmik, Dipankar; Agarwal, Sanjay Kumar; Deepak, Kishore Kumar

    2016-01-01

    Chronic kidney disease (CKD) patients have high cardiovascular mortality and morbidity. The presence of traditional and CKD related risk factors results in exaggerated vascular calcification in these patients. Vascular calcification is associated with reduced large arterial compliance and thus impaired baroreflex sensitivity (BRS) resulting in augmented blood pressure (BP) variability and hampered BP regulation. Baroreflex plays a vital role in short term regulation of BP. This review discusses the normal baroreflex physiology, methods to assess baroreflex function, its determinants along with the prognostic significance of assessing BRS in CKD patients, available literature on BRS in CKD patients and the probable patho-physiology of baroreflex dysfunction in CKD. PMID:26788464

  9. [Treatment adherence and chronic inflammatory bowel diseases].

    PubMed

    Tahri, Nabil

    2007-09-01

    For inflammatory bowel disease, unlike other chronic illnesses, there are sparse data available about patients' adherence to medication. The few studies vary widely, but noncompliance rates tend to be high, about 30-40%. Psychiatric disorders, including depression and anxiety, and poor patient-physician relationships are the most common causes of these patients' lack of adherence. Failure to adhere to prescribed medications increases risk of relapse and of colorectal cancer. Strategies that can improve adherence include establishing a partnership with the patient, simplifying the treatment regimen and increasing awareness through education and feedback.

  10. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs. PMID:23459977

  11. Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Dacks, P A; Shineman, D W; Fillit, H M

    2013-03-01

    An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer's disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer's disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ε4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.

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

    PubMed

    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). PMID:27545630

  13. ISCHEMIA in chronic kidney disease: improving the representation of patients with chronic kidney disease in cardiovascular trials.

    PubMed

    Wyatt, Christina M; Shineski, Matthew; Chertow, Glenn M; Bangalore, Sripal

    2016-06-01

    Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in patients with advanced chronic kidney disease.

  14. Chronic kidney disease of unknown etiology should be renamed chronic agrochemical nephropathy.

    PubMed

    Jayasinghe, Saroj

    2014-04-01

    Epidemics of chronic kidney disease not attributable to common causes have recently been observed in Central America and Asia. Since the etiology is unclear, the disease is often known by terms such as chronic kidney disease of unknown etiology. There is growing evidence that risk factors include rural agricultural work and agrochemical exposure. The disease should be renamed chronic agrochemical nephropathy to highlight the most likely etiology and draw attention to the condition.

  15. Ginkgo biloba extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease: a research perspective.

    PubMed

    Lautenschlager, Nicola T; Ihl, Ralf; Müller, Walter E

    2012-08-01

    In June 2011 a two-day expert meeting "The Ageing Brain" took place in Amsterdam, The Netherlands. The main aim was to discuss the available preclinical and clinical data on Ginkgo biloba special extract EGb 761® in the context of current developments in the diagnosis and treatment of age-related cognitive decline and Alzheimer's disease. 19 dementia experts covering the disciplines bio- and neurochemistry, gerontology, neurology, pharmacology, and psychiatry from Australia, Asia, Europe and North America reviewed available preclinical and clinical data for EGb 761® and identified core topics for future research. Based on a wide range of preclinical effects demonstrated for Ginkgo biloba, EGb 761® can be conceptualized as a multi-target compound with activity on distinct pathophysiological pathways in Alzheimer's disease (AD) and age-related cognitive decline. While symptomatic efficacy in dementia and mild cognitive impairment (MCI) has been demonstrated, interpretation of data from dementia prevention trials is complicated by important methodological issues. Bridging pre-clinical research and clinical research as well as deciding on suitable study designs for future trials with EGb 761® remain important questions. The participants of the "Ageing Brain" meeting on Ginkgo biloba special extract EGb 761® concluded that there is plenty of promising data, both pre-clinical and clinical, to consider future research with the compound targeting cognitive impairment in old age as a worthwhile activity.

  16. Proteome-wide Changes in Protein Turnover Rates in C. elegans Models of Longevity and Age-Related Disease.

    PubMed

    Visscher, Marieke; De Henau, Sasha; Wildschut, Mattheus H E; van Es, Robert M; Dhondt, Ineke; Michels, Helen; Kemmeren, Patrick; Nollen, Ellen A; Braeckman, Bart P; Burgering, Boudewijn M T; Vos, Harmjan R; Dansen, Tobias B

    2016-09-13

    The balance between protein synthesis and protein breakdown is a major determinant of protein homeostasis, and loss of protein homeostasis is one of the hallmarks of aging. Here we describe pulsed SILAC-based experiments to estimate proteome-wide turnover rates of individual proteins. We applied this method to determine protein turnover rates in Caenorhabditis elegans models of longevity and Parkinson's disease, using both developing and adult animals. Whereas protein turnover in developing, long-lived daf-2(e1370) worms is about 30% slower than in controls, the opposite was observed in day 5 adult worms, in which protein turnover in the daf-2(e1370) mutant is twice as fast as in controls. In the Parkinson's model, protein turnover is reduced proportionally over the entire proteome, suggesting that the protein homeostasis network has a strong ability to adapt. The findings shed light on the relationship between protein turnover and healthy aging. PMID:27626671

  17. The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease

    NASA Astrophysics Data System (ADS)

    Minton, Allen

    2014-08-01

    A linear increase in the concentration of "inert" macromolecules with time is incorporated into simple excluded volume models for protein condensation or fibrillation. Such models predict a long latent period during which no significant amount of protein aggregates, followed by a steep increase in the total amount of aggregate. The elapsed time at which these models predict half-conversion of model protein to aggregate varies by less than a factor of two when the intrinsic rate constant for condensation or fibril growth of the protein is varied over many orders of magnitude. It is suggested that this concept can explain why the symptoms of neurodegenerative diseases associated with the aggregation of very different proteins and peptides appear at approximately the same advanced age in humans.

  18. Telomeres, NAFLD and Chronic Liver Disease.

    PubMed

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  19. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-04-15

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging. PMID:26965220

  20. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-01-01

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging. PMID:27102136

  1. Ghrelin and cachexia in chronic kidney disease.

    PubMed

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2013-04-01

    Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

  2. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-04-15

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.

  3. [Chronic ischaemic heart disease in the elderly].

    PubMed

    Martínez-Sellés, Manuel; Gómez Huelgas, Ricardo; Abu-Assi, Emad; Calderón, Alberto; Vidán, María Teresa

    2016-01-01

    It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.

  4. [Chronic obstructive pulmonary disease in women].

    PubMed

    de Torres Tajes, Juan Pablo; Macario, Ciro Casanova

    2010-01-01

    The prevalence of chronic obstructive pulmonary disease (COPD) is increasing worldwide, mainly due to the increase in women. In developed countries, COPD in women is mainly a result of exposure to tobacco smoke and in developing countries to inhalation of biomass combustion products. Underdiagnosis of COPD is more common in women since this disease has classically been associated with men. Moreover, COPD in women shows certain differential features, such as a greater expression of aspects related to perception (dyspnea and health-related quality of life), a high prevalence of malnutrition, anxiety and depression, and a distinct distribution of emphysema from that in men. Better phenotypical characterization of COPD in women would allow its impact on the health system to be more accurately evaluated and more individualized therapeutic strategies to be designed.

  5. Mass spectrometry in Chronic Kidney Disease research

    PubMed Central

    Merchant, Michael L.

    2010-01-01

    Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application to analyze biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in mass spectrometers and their ability to analyze complex tryptic peptide mixtures with high sensitivity and high mass accuracy in a high throughput fashion (such as the LTQ-Orbitrap). It should not be surprising that this occurred coincident with dramatic improvements in our understanding chronic kidney disease (CKD), the mechanisms through which CKD progresses and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research and a discussion of CKD research that was driven by mass spectrometry. PMID:21044768

  6. Pharmacological treatment of chronic obstructive pulmonary disease

    PubMed Central

    Montuschi, Paolo

    2006-01-01

    None of the drugs currently available for chronic obstructive pulmonary disease (COPD) are able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has proved effective. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators, such as selective β2-adrenergic agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Glucocorticoids are not generally recommended for patients with stable mild to moderate COPD due to their lack of efficacy, side effects, and high costs. However, glucocorticoids are recommended for severe COPD and frequent exacerbations of COPD. New pharmacological strategies for COPD need to be developed because the current treatment is inadequate. PMID:18044097

  7. Integrative Genomics of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Hobbs, Brian D.; Hersh, Craig P.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex disease with both environmental and genetic determinants, the most important of which is cigarette smoking. There is marked heterogeneity in the development of COPD among persons with similar cigarette smoking histories, which is likely partially explained by genetic variation. Genomic approaches such as genomewide association studies and gene expression studies have been used to discover genes and molecular pathways involved in COPD pathogenesis; however, these “first generation” omics studies have limitations. Integrative genomic studies are emerging which can combine genomic datasets to further examine the molecular underpinnings of COPD. Future research in COPD genetics will likely use network-based approaches to integrate multiple genomic data types in order to model the complex molecular interactions involved in COPD pathogenesis. This article reviews the genomic research to date and offers a vision for the future of integrative genomic research in COPD. PMID:25078622

  8. Chronic disease management: the primary care perspective.

    PubMed

    Bragaglia, Pauline; O'Brien, Lewis

    2007-01-01

    This response to the essay is a "view from the trenches" by two doctors who have worked over 23 years at the Group Health Centre in Sault Ste. Marie, Ontario. We would agree wholeheartedly that reducing wait times for selected procedures will not transform our health system, although they are a start that does provide improved quality of life for a relatively small number of people. We have struggled with the care gap between known best practices and the reality of care provided, from the perspectives of both prevention and chronic disease management. This has resulted in an acute awareness of the need for an across-the-system, "bottom-up" approach to the prevention of disease and management of healthcare. Limited resources must be carefully leveraged in innovative ways if we are to eliminate this care gap, decrease morbidity and minimize expensive "rescue" procedures that make our system increasingly unaffordable.

  9. Musculoskeletal Disorders in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Cielen, Nele; Maes, Karen

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airway obstruction and inflammation but also accompanied by several extrapulmonary consequences, such as skeletal muscle weakness and osteoporosis. Skeletal muscle weakness is of major concern, since it leads to poor functional capacity, impaired health status, increased healthcare utilization, and even mortality, independently of lung function. Osteoporosis leads to fractures and is associated with increased mortality, functional decline, loss of quality of life, and need for institutionalization. Therefore, the presence of the combination of these comorbidities will have a negative impact on daily life in patients with COPD. In this review, we will focus on these two comorbidities, their prevalence in COPD, combined risk factors, and pathogenesis. We will try to prove the clustering of these comorbidities and discuss possible preventive or therapeutic strategies. PMID:24783225

  10. Health disparities in chronic diseases: where the money is.

    PubMed

    Crook, Errol D; Peters, Mosha

    2008-04-01

    Chronic diseases account for three-quarters of the U.S. health care expenditures and a majority of early deaths and lost of productive years of life. Health disparities exist among the common chronic diseases, such as hypertension, diabetes mellitus, HIV/AIDS, cancer, cardiovascular disease, and obesity, with ethnic minorities and the poor having higher incidence or worse outcomes. Strategies to eliminate these disparities in chronic diseases need to be multidisciplinary and focus on increasing access to all aspects of health care, including prevention. This article discusses the impact of health disparities on chronic diseases and offers some factors to consider for solutions to the problem.

  11. Community-based partnerships for improving chronic disease management.

    PubMed

    Plumb, James; Weinstein, Lara Carson; Brawer, Rickie; Scott, Kevin

    2012-06-01

    With the growing burden of chronic disease, the medical and public health communities are re-examining their roles and opportunities for more effective prevention and clinical interventions. The potential to significantly improve chronic disease prevention and have an impact on morbidity and mortality from chronic conditions is enhanced by adopting strategies that incorporate a social ecology perspective, realigning the patient-physician relationship, integrating population health perspectives into the Chronic Care Model, and effectively engaging communities using established principles of community engagement.

  12. Chronic Pulmonary Complications of Sickle Cell Disease.

    PubMed

    Mehari, Alem; Klings, Elizabeth S

    2016-05-01

    Sickle cell disease (SCD), the most common genetic hemolytic anemia worldwide, affects 250,000 births annually. In the United States, SCD affects approximately 100,000 individuals, most of African descent. Hemoglobin S (HbS) results from a glutamate-to-valine mutation of the sixth codon of the β-hemoglobin allele; the homozygous genotype (HbSS) is associated with the most prevalent and severe form of the disease. Other SCD genotypes include HbSC, composed of one HbS allele and one HbC (glutamate-to-lysine mutation) allele; and HbS-β-thalassemia(0) or HbS-β-thalassemia(+), composed of one HbS allele and one β-thalassemia allele with absent or reduced β-chain production, respectively. Despite advances in care, median survival remains in the fifth decade, due in large part to chronic complications of the disease. Chronic pulmonary complications in SCD are major contributors to this early mortality. Although our understanding of these conditions has improved much over the past 10 to 15 years, there remains no specific treatment for pulmonary complications of SCD. It is unclear whether conventional treatment regimens directed at non-SCD populations have equivalent efficacy in patients with SCD. This represents a critical research need. In this review, the authors review the state-of-the-art understanding of the following pulmonary complications of SCD: (1) pulmonary hypertension; (2) venous thromboembolic disease; (3) sleep-disordered breathing; (4) asthma and recurrent wheezing; and (5) pulmonary function abnormalities. This review highlights the advances as well as the knowledge gaps in this field to update clinicians and other health care providers and to garner research interest from the medical community. PMID:26836905

  13. Chronic disease risk factors among hotel workers

    PubMed Central

    Gawde, Nilesh Chandrakant; Kurlikar, Prashika R.

    2016-01-01

    Context: Non-communicable diseases have emerged as a global health issue. Role of occupation in pathogenesis of non-communicable diseases has not been explored much especially in the hospitality industry. Aims: Objectives of this study include finding risk factor prevalence among hotel workers and studying relationship between occupational group and chronic disease risk factors chiefly high body mass index. Settings and Design: A cross-sectional study was conducted among non-managerial employees from classified hotels in India. Materials and Methods: The study participants self-administered pre-designed pilot-tested questionnaires. Statistical analysis used: The risk factor prevalence rates were expressed as percentages. Chi-square test was used for bi-variate analysis. Overweight was chosen as ‘outcome’ variable of interest and binary multi-logistic regression analysis was used to identify determinants. Results: The prevalence rates of tobacco use, alcohol use, inadequate physical activity and inadequate intake of fruits and vegetables were 32%, 49%, 24% and 92% respectively among hotel employees. Tobacco use was significantly common among those in food preparation and service, alcohol use among those in food service and security and leisure time physical activity among front office workers. More than two-fifths (42.7%) were overweight. Among the hotel workers, those employed in food preparation and security had higher odds of 1.650 (CI: 1.025 – 2.655) and 3.245 (CI: 1.296 – 8.129) respectively of being overweight. Conclusions: Prevalence of chronic disease risk factors is high among hotel workers. Risk of overweight is significantly high in food preparation and security departments and workplace interventions are necessary to address these risks PMID:27390474

  14. Tetracycline therapy for chronic Lyme disease.

    PubMed

    Donta, S T

    1997-07-01

    Two hundred seventy-seven patients with chronic Lyme disease were treated with tetracycline for 1 to 11 months (mean, 4 months); the outcomes for these patients were generally good. Overall, 20% of the patients were cured; 70% of the patients' conditions improved, and treatment failed for 10% of the patients. Improvement frequently did not take place for several weeks; after 2 months of treatment, 33% of the patients' conditions were significantly improved (degree of improvement, 75%-100%), and after 3 months of treatment, 61% of the patients' conditions were significantly improved. Treatment outcomes for seronegative patients (20% of all patients) were similar to those for seropositive patients. Western immunoblotting showed reactions to one or more Borrelia burgdorferi-specific proteins for 65% of the patients for whom enzyme-linked immunosorbent assays were negative. Whereas age, sex, and prior erythema migrans were not correlated with better or worse treatment outcomes, a history of longer duration of symptoms or antibiotic treatment was associated with longer treatment times to achieve improvement and cure. These results support the use of longer courses of treatment in the management of patients with chronic Lyme disease. Controlled trials need to be conducted to validate these observations.

  15. Oxygen Therapy in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Kim, Victor; Benditt, Joshua O.; Wise, Robert A.; Sharafkhaneh, Amir

    2008-01-01

    Since the introduction of oxygen as a therapeutic agent 70 years ago, much has been learned regarding the detrimental effects of hypoxemia and the beneficial impact of oxygen therapy. It is projected that there are close to 800,000 patients receiving long-term oxygen therapy (LTOT) in the United States, at a cost of approximately $1.8 billion annually. The large numbers of patients receiving supplemental oxygen as treatment and the high costs incurred in providing oxygen therapy necessitate the practitioner to know the indications for LTOT as well its effects on survival, pulmonary hemodynamics, sleep, and exercise capacity. It is now recognized that the basis for LTOT prescription for all patients is founded on data that are over 25 years old and that only involve a very select cohort of patients. It is clear that further studies are required to assess the effects of oxygen on patients with chronic obstructive pulmonary disease with only mild hypoxemia, not only survival but also on neurocognitive function, quality of life, exercise physiology, and sleep quality. In addition, although proven to be safe when prescribed long term to individuals with lung disease, there are some concerns about worsening carbon dioxide retention and increased oxidant injury. The goals of this article are to briefly describe the indications for chronic oxygen administration, the physiologic effects of treatment, and potential toxicities, as well as its effect on morbidity and mortality. PMID:18453364

  16. Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan

    PubMed Central

    Huang, Chu-Chung; Liu, Mu-En; Kao, Hung-Wen; Chou, Kun-Hsien; Yang, Albert C.; Wang, Ying-Hsiu; Chen, Tong-Ru; Tsai, Shih-Jen; Lin, Ching-Po

    2016-01-01

    Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21–92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan. PMID:26996954

  17. Health Technologies for the Improvement of Chronic Disease Management

    PubMed Central

    Nikitovic, M; Brener, S

    2013-01-01

    Background As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). Objective The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. Data Sources The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. Review Methods Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence-based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. Results Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. Conclusions The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient

  18. Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations in patients with dementia due to Alzheimer disease

    PubMed Central

    Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

    2016-01-01

    Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. PMID:27546928

  19. Inflammation in age-related macular degeneration.

    PubMed

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

  20. Chronic Disease Medication Administration Rates in a Public School System

    ERIC Educational Resources Information Center

    Weller, Lawrence; Fredrickson, Doren D.; Burbach, Cindy; Molgaard, Craig A.; Ngong, Lolem

    2004-01-01

    Anecdotal reports suggest school nurses and staff treat increasing numbers of public school students with chronic diseases. However, professionals know little about actual disease burden in schools. This study measured prevalence of chronic disease medication administration rates in a large, urban midwestern school district. Data from daily…

  1. Chronic Liver Disease and American Indians/Alaska Natives

    MedlinePlus

    ... Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, chronic liver disease is ... 54. 1 At a glance – Cancer Rates for American Indian/Alaska Natives (2008-2012) Cancer Incidence Rates per 100,000 – ...

  2. Pulmonary hypertension in chronic lung diseases.

    PubMed

    Seeger, Werner; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, Simon; Martinez, Fernando J; Semigran, Marc J; Simonneau, Gerald; Wells, Athol U; Vachiéry, Jean-Luc

    2013-12-24

    Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on

  3. Improved management of chronic disease using health information technology.

    PubMed

    Dixon, Brian E; Samarth, Anita; Starmer, Jack

    2007-10-11

    Technology can be used effectively to improve chronic disease management, impacting health care costs, safety, and quality. The Agency for Healthcare Research and Quality has funded several studies to examine best practices in using technology to impact chronic disease management. These projects have employed a variety of technologies to improve care delivery processes, patient education, and continuity of care. Their stories contain valuable lessons for others looking to enhance chronic disease care.

  4. Development and application of chronic disease risk prediction models.

    PubMed

    Oh, Sun Min; Stefani, Katherine M; Kim, Hyeon Chang

    2014-07-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea.

  5. [New insights on hepcidin in anemia of chronic disease].

    PubMed

    Wang, Feng-Dan; Zhou, Dao-Bin

    2009-12-01

    Anemia of chronic disease is normocytic and normochromic. One of the mechanisms is misbalance of iron metabolism. Hepcidin, a kind of protein secreted by liver is considered to be the hormone regulating iron metabolism. It binds to ferroportin and induces the latter one's internalization. Thus, iron transportation from iron storage cells to serum is reduced. Cytokines are elevated in chronic disease. They stimulate hepcidin expression in liver through JAK2/STAT3 pathway. As a result, iron absorption and reabsorption is blocked, which leads to the misbalance of iron metabolism in anemia of chronic disease. In this article, the hepcidin and its relation to iron metabolism and anemia in chronic disease are reviewed.

  6. Metabolic syndrome and chronic kidney disease.

    PubMed

    Belarbia, Anis; Nouira, Safa; Sahtout, Wissal; Guedri, Yosra; Achour, Abdellatif

    2015-09-01

    To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

  7. Comorbidity in chronic obstructive pulmonary disease. Related to disease severity?

    PubMed Central

    Echave-Sustaeta, Jose M; Comeche Casanova, Lorena; Cosio, Borja G; Soler-Cataluña, Juan Jose; Garcia-Lujan, Ricardo; Ribera, Xavier

    2014-01-01

    Background and objective Several diseases commonly co-exist with chronic obstructive pulmonary disease (COPD), especially in elderly patients. This study aimed to investigate whether there is an association between COPD severity and the frequency of comorbidities in stable COPD patients. Patients and methods In this multicenter, cross-sectional study, patients with spirometric diagnosis of COPD attended to by internal medicine departments throughout Spain were consecutively recruited by 225 internal medicine specialists. The severity of airflow obstruction was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and data on demographics, smoking history, comorbidities, and dyspnea were collected. The Charlson comorbidity score was calculated. Results Eight hundred and sixty-six patients were analyzed: male 93%, mean age 69.8 (standard deviation [SD] 9.7) years and forced vital capacity in 1 second 42.1 (SD 17.7)%. Even, the mean (SD) Charlson score was 2.2 (2.2) for stage I, 2.3 (1.5) for stage II, 2.5 (1.6) for stage III, and 2.7 (1.8) for stage IV (P=0.013 between stage I and IV groups), independent predictors of Charlson score in the multivariate analysis were age, smoking history (pack-years), the hemoglobin level, and dyspnea, but not GOLD stage. Conclusion COPD patients attended to in internal medicine departments show high scores of comorbidity. However, GOLD stage was not an independent predictor of comorbidity. PMID:25429213

  8. Arterial Stiffness and Chronic Kidney Disease

    PubMed Central

    Garnier, Anne-Sophie; Briet, Marie

    2016-01-01

    Chronic kidney disease (CKD) is a major public health concern due to the high prevalence of associated cardiovascular (CV) disease. CV mortality is 10-30 times higher in end-stage renal disease patients than in the age-adjusted general population. The last 20 years have been marked by a huge effort in the characterization of the vascular remodeling process associated with CKD and its consequences on the renal, CV and general prognosis. By comparison with patients with normal renal function, with or without hypertension, an increase in large artery stiffness has been described in end-stage renal disease as well as in CKD stages 2-5. Most clinical studies are consistent with the observation that damage to large arteries may contribute to the high incidence of CV disease. By contrast, the impact of large artery stiffening and remodeling on CKD progression is still a matter of debate. Concomitant exposure to other CV risk factors, including diabetes, seems to play a major role in the association between aortic stiffness and estimated GFR. The conflicting results obtained from longitudinal studies designed to evaluate the impact of baseline aortic stiffness on GFR progression are detailed in the present review. Only pulse pressure, central and peripheral, is almost constantly associated with incident CKD and GFR decline. Kidney transplantation improves patients’ CV prognosis, but its impact on arterial stiffness is still controversial. Donor age, living kidney donation and mean blood pressure appear to be the main determinants of improvement in aortic stiffness after kidney transplantation. PMID:27195244

  9. Palliative care in chronic obstructive pulmonary disease.

    PubMed

    Lilly, Evan J; Senderovich, Helen

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is the only major worldwide cause of mortality that is currently increasing in prevalence. Furthermore, COPD is incurable, and the only therapy that has been shown to increase survival is oxygen therapy in selected patients. Compared to patients with cancer, patients with COPD experience similar levels of pain, breathlessness, fatigue, depression, and anxiety and have a worse quality of life but have comparatively little access to palliative care. When these patients do receive palliative care, they tend to be referred later than patients with cancer. Many disease, patient-, and provider-related factors contribute to this phenomenon, including COPD's unpredictable course, misperceptions of palliative care among patients and physicians, and lack of advance care planning discussions outside of crisis situations. A new paradigm for palliative care would introduce palliative treatments alongside, rather than at the exclusion of disease-modifying interventions. This integrated approach would circumvent the issue of difficult prognostication in COPD, as any patient would receive individualized palliative interventions from the time of diagnosis. These points will be covered in this review, which discusses the challenges in providing palliative care to COPD patients, the strategies to mitigate the challenges, management of common symptoms, and the evidence for integrated palliative care models as well as some suggestions for future development.

  10. Chronic kidney disease in kidney stone formers.

    PubMed

    Rule, Andrew D; Krambeck, Amy E; Lieske, John C

    2011-08-01

    Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed.

  11. Optimism's Explicative Role for Chronic Diseases.

    PubMed

    Avvenuti, Giulia; Baiardini, Ilaria; Giardini, Anna

    2016-01-01

    The increasing interest about dispositional optimism's role in health status and its positive modulating effect on health outcomes has led to a remarkable scientific production in the last decade. To date lot is known for which diseases optimism is relevant, instead much less is known about how optimism interacts with other factors, both biological and psychological, in determining health status. The aim of this mini review is to explore the literature derived from clinical and experimental research assessing the associations between dispositional optimism and health status. Dispositional optimism can be considered as facet of personality that is cognitive in nature which holds the global expectation that the future will be plenty of good events. Optimists view desired goals as obtainable, so they often confront adversities in active manners resulting in perseverance and increased goal attainment. Only studies that explicitly included optimism and health outcomes, as measurable variables, and that reported a clear association between them have been reviewed. Cancer, cardiovascular disease, respiratory failure, and aging with multimorbidity were considered. Among the possible explicative hypotheses, two seem to best describe results: optimism may have a direct effect on the neuroendocrine system and on immune responses, and it may have an indirect effect on health outcomes by promoting protective health behaviors, adaptive coping strategies and enhancing positive mood. The research on optimism and health status has already shed light on important mechanisms regarding chronic diseases' management, however, further studies are needed to deepen the knowledge. PMID:26973582

  12. Addressing Health Disparities in Chronic Kidney Disease

    PubMed Central

    Chan, Ta-Chien; Fan, I.-Chun; Liu, Michael Shi-Yung; Su, Ming-Daw; Chiang, Po-Huang

    2014-01-01

    According to the official health statistics, Taiwan has the highest prevalence of end stage renal disease (ESRD) in the world. Each year, around 60,000 ESRD patients in Taiwan consume 6% of the national insurance budget for dialysis treatment. The prevalence of chronic kidney disease (CKD) has been climbing during 2008–2012. However, the spatial disparities and clustering of CKD at the public health level have rarely been discussed. The aims of this study are to explore the possible population level risk factors and identify any clusters of CKD, using the national health insurance database. The results show that the ESRD prevalence in females is higher than that in males. ESRD medical expenditure constitutes 87% of total CKD medical expenditure. Pre-CKD and pre-ESRD disease management might slow the progression from CKD to ESRD. After applying ordinary least-squares regression, the percentages of high education status and the elderly in the townships are positively correlated with CKD prevalence. Geographically weighted regression and Local Moran’s I are used for identifying the clusters in southern Taiwan. The findings can be important evidence for earlier and targeted community interventions and reducing the health disparities of CKD. PMID:25514144

  13. Methylotroph Infections and Chronic Granulomatous Disease

    PubMed Central

    Petts, Jennifer R.; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M.; Neves, João Farela; Simões, Maria João; Tierce, Millard L.; de la Morena, M. Teresa; Greenberg, David E.; Zerbe, Christa S.; Zelazny, Adrian M.; Holland, Steven M.

    2016-01-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis. PMID:26886412

  14. Skin problems in chronic kidney disease.

    PubMed

    Kuypers, Dirk R J

    2009-03-01

    Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking. PMID:19190625

  15. Addressing health disparities in chronic kidney disease.

    PubMed

    Chan, Ta-Chien; Fan, I -Chun; Liu, Michael Shi-Yung; Su, Ming-Daw; Chiang, Po-Huang

    2014-12-01

    According to the official health statistics, Taiwan has the highest prevalence of end stage renal disease (ESRD) in the world. Each year, around 60,000 ESRD patients in Taiwan consume 6% of the national insurance budget for dialysis treatment. The prevalence of chronic kidney disease (CKD) has been climbing during 2008–2012.However, the spatial disparities and clustering of CKD at the public health level have rarely been discussed. The aims of this study are to explore the possible population level risk factors and identify any clusters of CKD, using the national health insurance database.The results show that the ESRD prevalence in females is higher than that in males. ESRD medical expenditure constitutes 87% of total CKD medical expenditure. Pre-CKD and pre-ESRD disease management might slow the progression from CKD to ESRD. After applying ordinary least-squares regression, the percentages of high education status and the elderly in the townships are positively correlated with CKD prevalence. Geographically weighted regression and Local Moran's I are used for identifying the clusters in southern Taiwan. The findings can be important evidence for earlier and targeted community interventions and reducing the health disparities of CKD.

  16. Addressing health disparities in chronic kidney disease.

    PubMed

    Chan, Ta-Chien; Fan, I-Chun; Liu, Michael Shi-Yung; Su, Ming-Daw; Chiang, Po-Huang

    2014-12-11

    According to the official health statistics, Taiwan has the highest prevalence of end stage renal disease (ESRD) in the world. Each year, around 60,000 ESRD patients in Taiwan consume 6% of the national insurance budget for dialysis treatment. The prevalence of chronic kidney disease (CKD) has been climbing during 2008-2012. However, the spatial disparities and clustering of CKD at the public health level have rarely been discussed. The aims of this study are to explore the possible population level risk factors and identify any clusters of CKD, using the national health insurance database. The results show that the ESRD prevalence in females is higher than that in males. ESRD medical expenditure constitutes 87% of total CKD medical expenditure. Pre-CKD and pre-ESRD disease management might slow the progression from CKD to ESRD. After applying ordinary least-squares regression, the percentages of high education status and the elderly in the townships are positively correlated with CKD prevalence. Geographically weighted regression and Local Moran's I are used for identifying the clusters in southern Taiwan. The findings can be important evidence for earlier and targeted community interventions and reducing the health disparities of CKD.

  17. Palliative care in chronic obstructive pulmonary disease.

    PubMed

    Lilly, Evan J; Senderovich, Helen

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is the only major worldwide cause of mortality that is currently increasing in prevalence. Furthermore, COPD is incurable, and the only therapy that has been shown to increase survival is oxygen therapy in selected patients. Compared to patients with cancer, patients with COPD experience similar levels of pain, breathlessness, fatigue, depression, and anxiety and have a worse quality of life but have comparatively little access to palliative care. When these patients do receive palliative care, they tend to be referred later than patients with cancer. Many disease, patient-, and provider-related factors contribute to this phenomenon, including COPD's unpredictable course, misperceptions of palliative care among patients and physicians, and lack of advance care planning discussions outside of crisis situations. A new paradigm for palliative care would introduce palliative treatments alongside, rather than at the exclusion of disease-modifying interventions. This integrated approach would circumvent the issue of difficult prognostication in COPD, as any patient would receive individualized palliative interventions from the time of diagnosis. These points will be covered in this review, which discusses the challenges in providing palliative care to COPD patients, the strategies to mitigate the challenges, management of common symptoms, and the evidence for integrated palliative care models as well as some suggestions for future development. PMID:27481751

  18. Phosphorus and Nutrition in Chronic Kidney Disease

    PubMed Central

    González-Parra, Emilio; Gracia-Iguacel, Carolina; Egido, Jesús; Ortiz, Alberto

    2012-01-01

    Patients with renal impairment progressively lose the ability to excrete phosphorus. Decreased glomerular filtration of phosphorus is initially compensated by decreased tubular reabsorption, regulated by PTH and FGF23, maintaining normal serum phosphorus concentrations. There is a close relationship between protein and phosphorus intake. In chronic renal disease, a low dietary protein content slows the progression of kidney disease, especially in patients with proteinuria and decreases the supply of phosphorus, which has been directly related with progression of kidney disease and with patient survival. However, not all animal proteins and vegetables have the same proportion of phosphorus in their composition. Adequate labeling of food requires showing the phosphorus-to-protein ratio. The diet in patients with advanced-stage CKD has been controversial, because a diet with too low protein content can favor malnutrition and increase morbidity and mortality. Phosphorus binders lower serum phosphorus and also FGF23 levels, without decreasing diet protein content. But the interaction between intestinal dysbacteriosis in dialysis patients, phosphate binder efficacy, and patient tolerance to the binder could reduce their efficiency. PMID:22701173

  19. Management of hyperkalaemia in chronic kidney disease.

    PubMed

    Kovesdy, Csaba P

    2014-11-01

    Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because of the effects of kidney dysfunction on potassium homeostasis and in part because of the cluster of comorbidities (and their associated treatments) that occur in patients with CKD. Owing to its electrophysiological effects, severe hyperkalaemia represents a medical emergency that usually requires prompt intervention, whereas the prevention of hazardous hyperkalaemic episodes in at-risk patients requires measures aimed at the long-term normalization of potassium homeostasis. The options for effective and safe medical interventions to restore chronic potassium balance are few, and long-term management of hyperkalaemia is primarily limited to the correction of modifiable exacerbating factors. This situation can result in a difficult trade-off in patients with CKD, because drugs that are beneficial to these patients (for example, renin-angiotensin-aldosterone-system antagonists) are often the most prominent cause of their hyperkalaemia. Maintaining the use of these beneficial medications while implementing various strategies to control potassium balance is desirable; however, discontinuation rates remain high. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift, emphasizing preventive management over ad hoc treatment of incidentally discovered elevations in serum potassium levels.

  20. Chronic Beryllium Disease Prevention Program Report

    SciTech Connect

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  1. Management of hypertension in chronic kidney disease.

    PubMed

    Zamboli, Pasquale; De Nicola, Luca; Minutolo, Roberto; Bertino, Valerio; Catapano, Fausta; Conte, Giuseppe

    2006-12-01

    Optimal blood pressure control (<130/80 mm Hg) in patients with chronic kidney disease (CKD), despite being the main objective of conservative therapy, is rarely achieved in clinical practice. A major area of improvement is the correction of the extracellular volume expansion. This goal can be reached by means of dietary salt restriction (100 mEq/d of NaCl). If this intervention fails, hypertension can be treated by thiazide diuretics in patients with mild CKD, whereas loop diuretics at adequate doses are indicated in patients with more advanced CKD. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are more effective than other drugs in slowing progression of proteinuric diabetic and nondiabetic CKD. However, the control rates of blood pressure are usually inadequate with antihypertensive therapy including only these drugs; therefore, addition of other classes of antihypertensive drugs is often required.

  2. Skeletal Implications of Chronic Obstructive Pulmonary Disease.

    PubMed

    Misof, Barbara M; Moreira, Carolina A; Klaushofer, Klaus; Roschger, Paul

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) is associated with numerous comorbidities, among which osteoporosis is of high significance. Low bone mass and the occurrence of fragility fractures is a common finding in patients with COPD. Typical risk factors related directly or indirectly to these skeletal complications include systemic inflammation, tobacco smoking, vitamin D deficiency, and treatment with oral or inhaled corticosteroids. In particular, treatment with glucocorticoids appears to be a strong contributor to bone changes in COPD, but does not fully account for all skeletal complications. Additional to the effects of COPD on bone mass, there is evidence for COPD-related changes in bone microstructure and material properties. This review summarizes the clinical outcomes of low bone mass and increased fracture risk, and reports on recent observations in bone tissue and material in COPD patients. PMID:26861899

  3. Cough in chronic obstructive pulmonary disease.

    PubMed

    Smith, J A; Calverley, P M A

    2004-01-01

    Patients with chronic obstructive pulmonary disease (COPD) most commonly complain of cough, production of phlegm and breathlessness. The cough reflex sensitivity is heightened compared with that in healthy volunteers and is similar to that in subjects with asthma. The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process. Objective cough rates seem to be relatively low in COPD, despite frequent reporting of the symptom by patients. The relative contribution of cough to disability in COPD seems to be small, if assessed by subjective reporting. Effective treatments for cough in COPD have not yet been identified. Improved outcome measures of cough, a better understanding of the mechanisms underlying cough, and the importance of cough to patients is required to progress in this field.

  4. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  5. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  6. Skin autofluorescence is a predictor of cardiovascular disease in chronic kidney disease patients.

    PubMed

    Furuya, Fumihiko; Shimura, Hiroki; Takahashi, Kazuya; Akiyama, Daiichiro; Motosugi, Ai; Ikegishi, Yukinobu; Haraguchi, Kazutaka; Kobayashi, Tetsuro

    2015-02-01

    Accelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non-Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3-year follow-up. During follow-up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran-Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes.

  7. Skin autofluorescence is a predictor of cardiovascular disease in chronic kidney disease patients.

    PubMed

    Furuya, Fumihiko; Shimura, Hiroki; Takahashi, Kazuya; Akiyama, Daiichiro; Motosugi, Ai; Ikegishi, Yukinobu; Haraguchi, Kazutaka; Kobayashi, Tetsuro

    2015-02-01

    Accelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non-Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3-year follow-up. During follow-up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran-Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes. PMID:25545539

  8. Con: Phosphate binders in chronic kidney disease.

    PubMed

    Kestenbaum, Bryan

    2016-02-01

    Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications. PMID:26681747

  9. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/Pacific Islanders were seven times ... At a glance – Cancer Rates for Native Hawaiian/Pacific Islander Liver & IBD Cancer Incidence Rates per 100, ...

  10. Chronic Respiratory Diseases of School-Age Children

    ERIC Educational Resources Information Center

    McGovern, John P.

    1976-01-01

    The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)

  11. Hormones and arterial stiffness in patients with chronic kidney disease.

    PubMed

    Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

    2013-01-01

    Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

  12. Macular degeneration - age-related

    MedlinePlus

    ... smoke, a combination of certain vitamins, antioxidants, and zinc may prevent the disease from getting worse. But ... international units of beta-carotene 80 (mg) of zinc 2 (mg) of copper Only take this vitamin ...

  13. Chronic obstructive pulmonary disease and oxidative stress.

    PubMed

    Domej, W; Földes-Papp, Z; Flögel, E; Haditsch, B

    2006-04-01

    The respiratory tract as the main entrance for various inhalative substances has great potential to generate reactive species directly or indirectly in excess. Thus, heavy smokers are at high risk for development, impairment and failed response to treatment of chronic obstructive pulmonary disease (COPD). The article is an update regarding the influence of reactive oxygen (ROS) and nitrogen (RNS) species on COPD; however, we do not intend to describe ROS and RNS actions on the entire lung tissue. Here, we focus on the airways, because in human most of the described effects of ROS and RNS species are measured on respiratory epithelial cells obtained by bronchoscopy. ROS and RNS species are physiological compounds in cells and risk factors for several respiratory diseases. In general, both kinds of species are thermodynamically stabile, but their reaction behaviors in cellular environments are very different. For example, the life times of the superoxide anion radical range from micro/milliseconds up to minutes and even hours in in-vitro model systems. Oxidative stress by cigarette smoke was investigated in detail by the authors of this article. In addition, original studies by the authors on the amount of fine particulate matter and trace elements in lung biopsies after defined inhalation indicate a distortion of the equilibrium between oxidants and antioxidants. We also try to present some modern views with respect to genomic medicine for future therapeutic perspectives, although this is an upcoming sector of COPD therapy. PMID:16724946

  14. Global cardiovascular protection in chronic kidney disease.

    PubMed

    Ruiz-Hurtado, Gema; Sarafidis, Pantelis; Fernández-Alfonso, María S; Waeber, Bernard; Ruilope, Luis M

    2016-10-01

    The development and progression of cardiovascular disease (CVD) and renal disorders are very closely related. In patients with chronic kidney disease (CKD), therapies proven to protect the cardiovascular and renal systems simultaneously are generally used only at low doses or not at all. In particular, patients with CKD who receive angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid-receptor antagonists (MRAs) often do not experience complete blockade of the renin-angiotensin-aldosterone system, primarily owing to the risk of hyperkalaemia. In this Review, we provide an overview of the available treatments required for adequate cardiorenal protection in patients with CKD. Drugs such as β-blockers that interfere with renin secretion will be discussed, in addition to agents that can prevent hyperkalaemia, such as potassium binders and nonsteroidal MRAs. Furthermore, the current literature on the role of statins, in addition to new compounds and dosing recommendations for the treatment of patients with CKD will also be reviewed. Further studies with these new compounds and doses are needed to ascertain whether these approaches can improve the long-term cardiovascular and renal prognosis in patients with CKD. PMID:27053454

  15. Building the chronic kidney disease management team.

    PubMed

    Spry, Leslie

    2008-01-01

    The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.

  16. Chronic kidney disease and erectile dysfunction

    PubMed Central

    Suzuki, Etsu; Nishimatsu, Hiroaki; Oba, Shigeyoshi; Takahashi, Masao; Homma, Yukio

    2014-01-01

    Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack. PMID:25374815

  17. Global cardiovascular protection in chronic kidney disease.

    PubMed

    Ruiz-Hurtado, Gema; Sarafidis, Pantelis; Fernández-Alfonso, María S; Waeber, Bernard; Ruilope, Luis M

    2016-10-01

    The development and progression of cardiovascular disease (CVD) and renal disorders are very closely related. In patients with chronic kidney disease (CKD), therapies proven to protect the cardiovascular and renal systems simultaneously are generally used only at low doses or not at all. In particular, patients with CKD who receive angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid-receptor antagonists (MRAs) often do not experience complete blockade of the renin-angiotensin-aldosterone system, primarily owing to the risk of hyperkalaemia. In this Review, we provide an overview of the available treatments required for adequate cardiorenal protection in patients with CKD. Drugs such as β-blockers that interfere with renin secretion will be discussed, in addition to agents that can prevent hyperkalaemia, such as potassium binders and nonsteroidal MRAs. Furthermore, the current literature on the role of statins, in addition to new compounds and dosing recommendations for the treatment of patients with CKD will also be reviewed. Further studies with these new compounds and doses are needed to ascertain whether these approaches can improve the long-term cardiovascular and renal prognosis in patients with CKD.

  18. Central blood pressure and chronic kidney disease

    PubMed Central

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  19. Molecular diagnosis of chronic granulomatous disease.

    PubMed

    Roos, D; de Boer, M

    2014-02-01

    Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (∼1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis. PMID:24016250

  20. Building the chronic kidney disease management team.

    PubMed

    Spry, Leslie

    2008-01-01

    The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing. PMID:18155107

  1. Vegetarian diets, chronic diseases and longevity.

    PubMed

    Ginter, E

    2008-01-01

    Vegetarians form a non-homogenous group consisting of semivegetarians (plant food, dairy products, eggs and fish), lacto-ovo vegetarians (plant food, dairy products, eggs) and vegans (plant food only). According to pure vegetarian ideologists, people consuming vegetarian diet have better health and live longer than nonvegetarians, because persons consuming milk, dairy products, meat, eggs and fish are at health risk. In fact the most healthy people in Europe are inhabitants of Iceland, Switzerland and Scandinavia, consuming great amounts of food of animal origin. Meta-analysis of several prospective studies showed no significant differences in the mortality caused by colorectal, stomach, lung, prostate or breast cancers and stroke between vegetarians and "health-conscious" nonvegetarians. In vegetarians, a decrease of ischemic heart disease mortality was observed probably due to lower total serum cholesterol levels, lower prevalence of obesity and higher consumption of antioxidants. Very probably, an ample consumption of fruits and vegetables and not the exclusion of meat make vegetarians healthful. Now, the largest cohort study of diet and health on more than half million of persons, the European Prospective Investigation into Cancer and Nutrition (EPIC) study, will bring new data on the relationships between diet, lifestyle and environmental factors and the incidence of cancer, cardiovascular and other chronic diseases. Vegetarianism is a form of food restriction; and in our overfed society, food restriction is a plus unless it results in a nutritional deficiency (Fig. 1, Tab. 2, Ref. 18). PMID:19166134

  2. Chronic kidney disease and the skeleton.

    PubMed

    Miller, Paul D

    2014-01-01

    Fractures across the stages of chronic kidney disease (CKD) could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease-mineral and bone disorder (CKD-MBD). CKD-MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKD-MBD. Differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization (WHO) bone mineral density (BMD) criteria for osteoporosis can be used in patients with stages 1-3 CKD, the disorders of bone turnover become so aberrant by stages 4 and 5 CKD that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKD is one of the exclusion-excluding either renal osteodystrophy or CKD-MBD as the cause of low BMD or fragility fractures. Differentiations among the disorders of renal osteodystrophy, CKD-MBD or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone (PTH) and/or quantitative bone histomorphometry. Management of fractures in stages 1-3 CKD does not differ in persons with or without CKD with osteoporosis assuming that there is no evidence for CKD-MBD, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKD. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKD is not evidence-based, with the exception of post-hoc analysis suggesting efficacy and safety of specific

  3. Chronic kidney disease and the skeleton.

    PubMed

    Miller, Paul D

    2014-01-01

    Fractures across the stages of chronic kidney disease (CKD) could be due to osteoporosis, some form of renal osteodystrophy defined by specific quantitative histomorphometry or chronic kidney disease-mineral and bone disorder (CKD-MBD). CKD-MBD is a systemic disease that links disorders of mineral and bone metabolism due to CKD to either one or all of the following: abnormalities of calcium, phosphorus, parathyroid hormone or vitamin D metabolism; abnormalities in bone turnover, mineralization, volume, linear growth or strength; or vascular or other soft-tissue calcification. Osteoporosis, as defined by the National Institutes of Health, may coexist with renal osteodystrophy or CKD-MBD. Differentiation among these disorders is required to manage correctly the correct disorder to reduce the risk of fractures. While the World Health Organization (WHO) bone mineral density (BMD) criteria for osteoporosis can be used in patients with stages 1-3 CKD, the disorders of bone turnover become so aberrant by stages 4 and 5 CKD that neither the WHO criteria nor the occurrence of a fragility fracture can be used for the diagnosis of osteoporosis. The diagnosis of osteoporosis in stages 4 and 5 CKD is one of the exclusion-excluding either renal osteodystrophy or CKD-MBD as the cause of low BMD or fragility fractures. Differentiations among the disorders of renal osteodystrophy, CKD-MBD or osteoporosis are dependent on the measurement of specific biochemical markers, including serum parathyroid hormone (PTH) and/or quantitative bone histomorphometry. Management of fractures in stages 1-3 CKD does not differ in persons with or without CKD with osteoporosis assuming that there is no evidence for CKD-MBD, clinically suspected by elevated PTH, hyperphosphatemia or fibroblast growth factor 23 due to CKD. Treatment of fractures in persons with osteoporosis and stages 4 and 5 CKD is not evidence-based, with the exception of post-hoc analysis suggesting efficacy and safety of specific

  4. Clinical Scenarios in Chronic Kidney Disease: Parenchymal Chronic Renal Diseases - Part 2.

    PubMed

    Petrucci, Ilaria; Samoni, Sara; Meola, Mario

    2016-01-01

    Secondary nephropathies can be associated with disreactive immunological disorders or with a non-inflammatory glomerular damage. In systemic lupus erythematosus (SLE), scleroderma and rheumatoid arthritis as in other connective tissue diseases, kidney volume and cortex echogenicity are the parameters that best correlate with clinical severity of the disease, even if the morphological aspect is generally non-specific. Doppler studies in SLE document the correlation between resistance indexes (RIs) values and renal function. Acquired immunodeficiency syndrome (HIV) causes different types of renal damage. At ultrasound (US), kidneys have almost a normal volume, while during superinfection they enlarge (coronal diameter >13 cm) and become globular, loosing their normal aspect. Cortex appears highly hyperechoic, uniform or patchy. Microcalcifications of renal cortex and medulla are a US sign that can suggest HIV. In amyloidosis, kidneys appear normal or increased in volume in the early stages of disease. Renal cortex is diffusely hyperechoic and pyramids can show normal size and morphology, but more often they appear poorly defined and hyperechoic. RIs are very high since the early stages of the disease. Nephromegaly with normal kidney shape is the first sign of lymphoma or multiple myeloma. In systemic vasculitis, renal cortex is diffusely hyperechoic, while pyramids appear hypoechoic and globular due to interstitial edema. When vasculitis determines advanced chronic kidney disease stages, kidneys show no specific signs. Microcirculation damage is highlighted by increased RIs values >0.70 in the chronic phase. PMID:27169551

  5. Prevalence of Chronic Diseases in Adolescents with Intellectual Disability

    ERIC Educational Resources Information Center

    Oeseburg, B.; Jansen, D. E. M. C.; Dijkstra, G. J.; Groothoff, J. W.; Reijneveld, S. A.

    2010-01-01

    Valid community-based data on the prevalence of chronic diseases in adolescents (12-18 years) with intellectual disability (ID-adolescents) are scarce. The aim of this study was to assess the prevalence rates and the nature of chronic diseases in a population of ID-adolescents and to compare them with the rates among adolescents in the general…

  6. Theory in Chronic Disease Prevention and Health Promotion

    ERIC Educational Resources Information Center

    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…

  7. Can Incentives Improve Medicaid Patient Engagement and Prevent Chronic Diseases?

    PubMed

    Hoerger, Thomas J; Perry, Rebecca; Farrell, Kathleen; Teixeira-Poit, Stephanie

    2015-01-01

    Under the Medicaid Incentives for the Prevention of Chronic Diseases model, 10 states are testing whether incentives can encourage Medicaid beneficiaries to lose weight, stop smoking, work to prevent diabetes, or control risk factors for other chronic diseases. This commentary describes these incentive programs and how they will be evaluated. PMID:26510225

  8. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in Aging Populations.

    PubMed

    Fragoso, Carlos A Vaz

    2016-01-01

    Current epidemiologic practice evaluates COPD based on self-reported symptoms of chronic bronchitis, self-reported physician-diagnosed COPD, spirometry confirmed airflow obstruction, or emphysema diagnosed by volumetric computed chest tomography (CT). Because the highest risk population for having COPD includes a predominance of middle-aged or older persons, aging related changes must also be considered, including: 1) increased multimorbidity, polypharmacy, and severe deconditioning, as these identify mechanisms that underlie respiratory symptoms and can impart a complex differential diagnosis; 2) increased airflow limitation, as this impacts the interpretation of spirometry confirmed airflow obstruction; and 3) "senile" emphysema, as this impacts the specificity of CT-diagnosed emphysema. Accordingly, in an era of rapidly aging populations worldwide, the use of epidemiologic criteria that do not rigorously consider aging related changes will result in increased misidentification of COPD and may, in turn, misinform public health policy and patient care. PMID:26629987

  9. Occupational causes of chronic obstructive pulmonary disease.

    PubMed

    Rushton, Lesley

    2007-01-01

    The relation between Chronic Obstructive Pulmonary Disease (COPD, including chronic bronchitis and emphysema (CBE), and exposure to coal dust is well established. This paper reviews the evidence relating to other occupational causes of COPD, including industries associated with exposure to fumes, chemical substances, and dusts. A review of key literature has been carried out with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests that elevated risks of developing COPD are clearly associated with several occupations, with risk estimates being high in some, even after taking into account the effect of confounders, such as smoking. Of particular concern are agricultural workers who can be exposed to a variety of gases and organic dusts, among whom CBE is clearly elevated, particularly for pig farmers and exposure to endotoxins, with an increased annual decline in lung function. Similarly, cotton textile workers are exposed to a mixture of substances affecting development of atopy, byssinosis, and CBE, and across-shift and long-term decline in lung function. Atopy also has an important role in the development of COPD in flour mill workers and bakers, with those sensitized to bakery allergens having a greater lung function decline than non-sensitized individuals. Welding processes involve a range of potential chemical, physical and radiation hazards. The average reduction in FEV1 associated with welding fumes is similar to that associated with smoking. Challenges in assessing the evidence include variation in diagnostic methods; concurrent exposure to cigarette smoke (direct or second-hand) and multiple work-place irritants; healthy worker selection/survivor effects; poor exposure definition. Raising awareness of occupational causes of COPD among employers, employees, and health service professionals is important.

  10. Common lung conditions: chronic obstructive pulmonary disease.

    PubMed

    Delzell, John E

    2013-06-01

    The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are

  11. Interactions between chronic renal disease and periodontal disease.

    PubMed

    Craig, R G

    2008-01-01

    The incidence of end-stage renal disease (ESRD) is increasing and patients receiving renal replacement therapy including hemodialysis, peritoneal dialysis or renal transplantation will comprise an enlarging segment of the dental patient population. Renal replacement therapy can affect periodontal tissues including gingival hyperplasia in immune suppressed renal transplantation patients and increased levels of plaque, calculus and gingival inflammation and possible increased prevalence and severity of destructive periodontal diseases in ESRD patients on dialysis maintenance therapy. Also, the presence of undiagnosed periodontitis may have significant effects on the medical management of the ESRD patient. Periodontitis has been found to contribute to systemic inflammatory burden including the elevation of C-reactive protein (CRP) in the general population. Atherosclerotic complications including myocardial infarction and stroke are the primary causes of mortality in the ESRD population and, in contrast to that of the general population, the best predictor of all cause and cardiac death in this population is CRP. Consequently, periodontitis may be a covert but treatable source of systemic inflammation in the ESRD population. The objective of this review was to explore the interaction between chronic renal disease, renal replacement therapy and periodontal diseases based upon the results of studies published within the last decade.

  12. 582 Chronic Urticaria Associated with Thyroid Disease

    PubMed Central

    de Guadalupe Peñaloza-González, Flor; Velasco-Medina, Andrea Aida; Gonzalez-Carsolio, Aida; Burbano-Ceron, Andres-Leonardo; Barreto-Sosa, Adriana; Velázquez-Sámano, Guillermo

    2012-01-01

    Background Chronic urticaria has an incidence of 15% in the general population and sometimes is associated with chronic diseases such as rheumatoid arthritis, vitiligo and thyroid disorders. Chronic urticarial is characterized by wheals lasting more than 6 weeks, with alterations of the upper layers of the skin only. On histopathology there is a perivascular infiltrate characterized by T CD4 and CD8 lymphocytes and other inflammatory cells. Cytokines produced by lymphocytes, mast cells and other cells increase the expression of vascular adhesion molecules. Other mediators such as histamine increase vascular permeability causing edema, clinically represented by wheals. Treatment of chronic urticaria includes first and second generation antihistamines as first line treatment. Sometimes there is a poor response to there drugs and second line treatments such as immunosupressors are indicated. A search for systemic disorders is helpful to identify associated pathology which makes chronic urticaria reluctant to therapy. Methods We performed a retrospective study considering patients with chronic urticaria attending our clinic during the last 5 years. Three hundred patients with urticaria were considered, with 16% (50 patients) with a chronic disease. Six patients with chronic urticaria were associated with thyroid disease. Results We considered 6 patients with chronic urticaria with altered thyroid function tests; 4 with subclinical hypothyroidism and 2 with subclinical hyperthyroidism. All of them had a poor response to antihistamines. When a thyroid disorder was identified, they received appropriate treatment achieving control of chronic urticaria. Treatment with antihistamines was continued. Conclusions Chronic urticaria is a disease often associated with systemic disorders including thyroid disease. We found an association with thyroid pathology in 2% of patients with chronic urticaria, with remission of cutaneous symptoms after treatment of endocrinologic disorder

  13. [Role of vaccination in chronic disease prevention and control].

    PubMed

    Wang, Zhuoqun; Huang, Shue; Zhao, Yanfang; Zhao, Wenhua; Liang, Xiaofeng

    2015-08-01

    Chronic non-communicable disease is a major public health problem affecting the health of residents in china. Evidence shows that, in addition to four major risk factors, i.e. unreasonable dietary, lack of physical activity, smoking and drinking, epidemic and severe outcome of chronic disease is associated with many infectious diseases. Increasingly cancers have been shown to have an infectious etiology. There is also a significantly increased risk of infectious disease such as influenza, pneumonia and other infectious disease in people with pre-existing chronic non-communicable diseases like diabetes, heart disease, and lung diseases. And more than that, there is a high risk of susceptibility to death and severe outcomes among them. Epidemiological studies has confirmed, that through targeted vaccine inoculation, liver cancer, cervical cancer can be effectively prevented, while influenza or pneumonia vaccine are related to reduced risk of hospitalization or death and hospitalization expenses regarding with a variety of chronic diseases. World Health Organization and several other professional organizations have put forward recommendations on vaccine inoculation of chronic disease patients. Programs targeting infectious factors are also an important aspect of chronic diseases prevention and control, therefore, related researches need to be strengthened in the future. PMID:26733040

  14. Review article: hepatitis vaccination in patients with chronic liver disease.

    PubMed

    Reiss, G; Keeffe, E B

    2004-04-01

    Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

  15. Stop chronic kidney disease progression: Time is approaching

    PubMed Central

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-01-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  16. Risk factors and early origins of chronic obstructive pulmonary disease.

    PubMed

    Postma, Dirkje S; Bush, Andrew; van den Berge, Maarten

    2015-03-01

    Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40-50 years, its origins can begin very early in life. Different risk factors in very early life--ie, in utero and during early childhood--drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life.

  17. Stop chronic kidney disease progression: Time is approaching.

    PubMed

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-05-01

    Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the anti-senescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression. PMID:27152262

  18. Contextual Poverty, Nutrition and Chronic Kidney Disease

    PubMed Central

    Gutiérrez, Orlando M.

    2014-01-01

    Nutrition plays an important role in chronic kidney disease (CKD) outcomes. One of the strongest factors that impacts nutrition is socioeconomic status as evidenced by the large body of epidemiologic data showing that income and education are directly associated with diet quality. Apart from individual-level markers of socioeconomic status such as income and education, contextual factors such as availability of and transportation to food outlets that provide healthy food options and the density of fast food restaurants within particular regions markedly impact the ability of individuals to comply with nutrition recommendations. This is particularly true for nutrition guidelines most specific to individuals with CKD such as the consumption of protein, saturated fat, sodium and phosphorus, all of which have been shown to impact CKD health and are influenced by the availability of healthy food options within individual neighborhood food environments. Because of the strong association of contextual poverty with the diet quality, any serious attempt to improve the diet of CKD patients must include a discussion of the environmental barriers that each individual faces in trying to access healthy foods and health care providers should take account of these barriers when tailoring specific recommendations. PMID:25573510

  19. Proof that chronic lyme disease exists.

    PubMed

    Cameron, Daniel J

    2010-01-01

    The evidence continues to mount that Chronic Lyme Disease (CLD) exists and must be addressed by the medical community if solutions are to be found. Four National Institutes of Health (NIH) trials validated the existence and severity of CLD. Despite the evidence, there are physicians who continue to deny the existence and severity of CLD, which can hinder efforts to find a solution. Recognizing CLD could facilitate efforts to avoid diagnostic delays of two years and durations of illness of 4.7 to 9 years described in the NIH trials. The risk to society of emerging antibiotic-resistant organisms should be weighed against the societal risks associated with failing to treat an emerging population saddled with CLD. The mixed long-term outcome in children could also be examined. Once we accept the evidence that CLD exists, the medical community should be able to find solutions. Medical professionals should be encouraged to examine whether: (1) innovative treatments for early LD might prevent CLD, (2) early diagnosis of CLD might result in better treatment outcomes, and (3) more effective treatment regimens can be developed for CLD patients who have had prolonged illness and an associated poor quality of life.

  20. [Phenotypic heterogeneity of chronic obstructive pulmonary disease].

    PubMed

    Garcia-Aymerich, Judith; Agustí, Alvar; Barberà, Joan A; Belda, José; Farrero, Eva; Ferrer, Antoni; Ferrer, Jaume; Gáldiz, Juan B; Gea, Joaquim; Gómez, Federico P; Monsó, Eduard; Morera, Josep; Roca, Josep; Sauleda, Jaume; Antó, Josep M

    2009-03-01

    A functional definition of chronic obstructive pulmonary disease (COPD) based on airflow limitation has largely dominated the field. However, a view has emerged that COPD involves a complex array of cellular, organic, functional, and clinical events, with a growing interest in disentangling the phenotypic heterogeneity of COPD. The present review is based on the opinion of the authors, who have extensive research experience in several aspects of COPD. The starting assumption of the review is that current knowledge on the pathophysiology and clinical features of COPD allows us to classify phenotypic information in terms of the following dimensions: respiratory symptoms and health status, acute exacerbations, lung function, structural changes, local and systemic inflammation, and systemic effects. Twenty-six phenotypic traits were identified and assigned to one of the 6 dimensions. For each dimension, a summary is provided of the best evidence on the relationships among phenotypic traits, in particular among those corresponding to different dimensions, and on the relationship between these traits and relevant events in the natural history of COPD. The information has been organized graphically into a phenotypic matrix where each cell representing a pair of phenotypic traits is linked to relevant references. The information provided has the potential to increase our understanding of the heterogeneity of COPD phenotypes and help us plan future studies on aspects that are as yet unexplored.

  1. Immunological aspects of chronic venous disease pathogenesis

    PubMed Central

    Grudzińska, Ewa

    2014-01-01

    Chronic venous disease (CVD) is a very common health problem concerning up to 1/3 of the society. Although venous hypertension and valvular incompetence have been long known to be crucial for development of the illness, its exact aetiology remains unclear. Recent findings indicate that inflammatory processes may be crucial for development of incompetent valves and vein wall remodelling. One of the most interesting theories describes “leucocyte trapping” as the mechanism responsible for elevated vein wall permeability and oxidative stress in the veins. At the same time, the cytokine profile of the blood in incompetent veins has not been thoroughly examined. Popular anti-inflammatory drugs relieve some symptoms but do not have much proved effects in prevention and treatment. We intend to summarize the existing knowledge of the immunological aspects of CVD in order to emphasize its importance for understanding the aetiology of this illness. We also wish to indicate some aspects that remain to be studied in more detail. PMID:26155174

  2. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients. PMID:27284847

  3. Resistant Hypertension in Nondialysis Chronic Kidney Disease

    PubMed Central

    Stanzione, Giovanna; Conte, Giuseppe

    2013-01-01

    Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called “pseudoresistance.” This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that “true” RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients. PMID:23710342

  4. [Treatment of hypertension in chronic kidney disease].

    PubMed

    Palomo-Piñón, Silvia; Rosas-Peralta, Martín; Paniagua-Sierra, José Ramón

    2016-01-01

    Systemic arterial hypertension (SAH) is a progressive cardiovascular syndrome caused by complex and interrelated causes. The early markers of this syndrome are often present even before the blood pressure (BP) elevation; therefore, SAH cannot only be classified by the BP elevation threshold, which sometimes is discreet. Its progression is strongly associated with structural and functional cardiovascular abnormalities, which lead to end-organ damage (heart, kidney, brain, blood vessels and other organs), and cause premature morbidity and death. In this sense, the BP is only a biomarker of this cardiovascular syndrome, which is why it is more useful to consider individual BP patterns of the ill patient rather than a single BP threshold. The study and treatment of hypertension in chronic kidney disease (CKD) has made some progresses, especially in patients requiring dialysis. The use of non-invasive technology to register the BP has reconfigured health care of patients in regards to the diagnosis, circadian pattern, clinical surveillance, pharmacological prescription, prognosis, and risk of cardiovascular events (as well as mortality). The opportunity in the diagnosis and treatment means a delay in the onset of complications and, also, of dialysis. The blockade of the renin-aldotensin-aldosterone system (RAAS), a regular monitoring of the dry weight of the population in dialysis, and non-pharmacological interventions to modify lifestyle are the maneuvers with greater impact on the morbidity and mortality of patients.

  5. [Use of bisphosphonates in chronic kidney disease].

    PubMed

    Torregrosa, J V; Ramos, A M

    2010-01-01

    Bisphosphonates are synthetic compounds similar to organic pyrophosphates. The bioavailability of intravenous preparations is 100%, whereas the availability of oral therapy ranges from 1 to 5%. About 50% to 80% of free bisphosphonates are incorporated into bone. Because of their urinary elimination, bisphosphonates must be carefully administered in chronic kidney disease (CKD) patients. In spite of this, bisphosphonates can safely be used in all CKD stages, including dialysis and kidney transplant. The renal toxicity seems different among these compounds, and it is due basically to their protein binding and the average lifespan in renal tissues. In practice, renal toxicity have been associate to the infusion velocity and excessive dosage In patients with CKD, it is very relevant to maintain the time of infusion and in haemodialysis patients we recommend the administration during the haemodialysis session. When bisphosphonates are given to 4-5 CKD patients it seems reasonable to reduce the dose to 50%. No renal pathology has been associated to oral administration. The indications of bisphosphonates in CKD include: hypercalcemia episodes, prevention of bone loss after renal transplantation, treatment of low bone mineral density in all CKD stage including transplantation. They are too a promising therapy of calciphylaxis and to prevent vascular calcifications. When suppressed bone turnover is suspected, bone biopsy is mandatory before bisphosphonates therapy.

  6. Thiazide Diuretics in Chronic Kidney Disease.

    PubMed

    Sinha, Arjun D; Agarwal, Rajiv

    2015-03-01

    Widely prevalent in the general population, chronic kidney disease (CKD) is frequently complicated with hypertension. Control of hypertension in this high-risk population is a major modifiable cardiovascular and renal risk factor but often requires multiple medications. Although thiazides are an attractive agent, guidelines have previously recommended against thiazide use in stage 4 CKD. We review the updated guidelines on thiazide use in advanced CKD, the antihypertensive mechanism of thiazides, and the clinical studies of thiazides in CKD. Older uncontrolled studies have shown that metolazone reduces blood pressure in CKD, but more recently small randomized controlled trials of hydrochlorothiazide in CKD have shown significant improvement in mean arterial pressure of 15 mmHg. Two recent uncontrolled studies of chlorthalidone including one that used ambulatory blood pressure monitoring found significant improvements in blood pressure. These findings all suggest that thiazides may be efficacious even in advanced CKD; however, electrolyte abnormalities were common in the studies reviewed so close monitoring is necessary during use. Adequately powered randomized trials are now needed before the routine use of thiazide diuretics in advanced CKD can be recommended.

  7. Acupuncture for chronic obstructive pulmonary disease (COPD)

    PubMed Central

    Feng, Junfei; Wang, Xuehui; Li, Xing; Zhao, Dejun; Xu, Jinquan

    2016-01-01

    Abstract Background: Acupuncture has been suggested to treat chronic obstructive pulmonary disease (COPD) in China. However, current evidence is insufficient to draw a firm conclusion regarding the effectiveness of acupuncture in COPD. Therefore, this multicenter, randomized, sham-controlled study was designed to evaluate the efficacy of acupuncture for treating patients with COPD. Methods: This is a two-arm, parallel group, multicenter, randomized, sham-controlled trial with concealed allocation, and participants, assessor, and analyst blinding. Seventy-two participants with COPD were recruited and randomly divided into 2 groups (real acupuncture group and sham acupuncture group) in a 1:1 ratio. Patients received either real or sham needling at the same acupoints 3 times weekly for 8 weeks. The primary outcome was dyspnea on exertion evaluated using the 6-minute walk test. In addition, health-related quality of life was also evaluated. Measurements were obtained at baseline and after 8 weeks of treatment. Results: Six-minute walking distance measurements and health-related quality of life were significantly better in the real acupuncture group than that in the sham acupuncture group. Conclusion: The findings suggest that acupuncture can be used as an adjunctive therapy to reduce dyspnea in patients with COPD. PMID:27749542

  8. Mechanism and novel therapeutic approaches to wasting in chronic disease.

    PubMed

    Ebner, Nicole; Springer, Jochen; Kalantar-Zadeh, Kamyar; Lainscak, Mitja; Doehner, Wolfram; Anker, Stefan D; von Haehling, Stephan

    2013-07-01

    Cachexia is a multifactorial syndrome defined by continuous loss of skeletal muscle mass - with or without loss of fat mass - which cannot be fully reversed by conventional nutritional support and which may lead to progressive functional impairment and increased death risk. Its pathophysiology is characterized by negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Muscle wasting is encountered in virtually all chronic disease states in particular during advanced stages of the respective illness. Several pre-clinical and clinical studies are ongoing to ameliorate this clinical problem. The mechanisms of muscle wasting and cachexia in chronic diseases such as cancer, chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease are described. We discuss therapeutic targets and such potential modulators as appetite stimulants, selective androgen receptor modulators, amino acids and naturally occurring peptide hormones.

  9. [Chronic non-communicable diseases in Brazil: priorities for disease management and research].

    PubMed

    Duncan, Bruce Bartholow; Chor, Dóra; Aquino, Estela M L; Bensenor, Isabela M; Mill, José Geraldo; Schmidt, Maria Inês; Lotufo, Paulo Andrade; Vigo, Alvaro; Barreto, Sandhi Maria

    2012-12-01

    Chronic Non-Communicable Diseases are the main source of disease burden in Brazil. In 2011, the Brazilian Ministry of Health launched the Strategic Plan of Action for Management of Chronic Non-Communicable Diseases focusing on population-based interventions to manage cardiovascular diseases, diabetes, cancer, and chronic respiratory diseases mainly through fighting tobacco use, unhealthy diets, physical inactivity and the harmful use of alcohol. Although a significant number of scientific studies on chronic diseases and their risk factors have been undertaken in Brazil, few are of cohort design. In this context, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort study of 15,105 Brazilian public servants reflects the reality of high prevalences of diabetes, hypertension and the main chronic diseases risk factors. The diversity of information that the Study will produce can provide important input to better understand the causes of chronic diseases and to support public policies for fighting them.

  10. The kalpa method of therapy in chronic diseases.

    PubMed

    Singh, N K; Singh, R H

    1989-07-01

    In chronic diseases, the Kalpa method of therapy prescribed in Ayurveda for revitalization and overall improvement of health is discussed in this paper. Also reports here that clinical trial of Agrogyavardhini Kalpa in chronic GIT disease confirms the efficacy of Kalps therapy in boosting the general health of the patient as reflected by its nutritional status etc. Clinical symptoms also improve and thus moving that the Arogyavardhini exerts multi dimensional influence on the disease. PMID:22557666

  11. The cytokine network in asthma and chronic obstructive pulmonary disease

    PubMed Central

    Barnes, Peter J.

    2008-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases. PMID:18982161

  12. 77 FR 43092 - Agency Information Collection Activities; Proposed Collection; Comment Request; Chronic Disease...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... Collection; Comment Request; Chronic Disease Self-Management Education Program Standardized Data Collection... collection requirements relating to the Chronic Disease Self-Management Education Program. DATES: Submit... Disabilities through Chronic Disease Self-Management Education (CDSME) Programs'' cooperative agreement...

  13. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults.

    PubMed

    Angulo, Javier; El Assar, Mariam; Rodríguez-Mañas, Leocadio

    2016-08-01

    Frailty is a functional status that precedes disability and is characterized by decreased functional reserve and increased vulnerability. In addition to disability, the frailty phenotype predicts falls, institutionalization, hospitalization and mortality. Frailty is the consequence of the interaction between the aging process and some chronic diseases and conditions that compromise functional systems and finally produce sarcopenia. Many of the clinical manifestations of frailty are explained by sarcopenia which is closely related to poor physical performance. Reduced regenerative capacity, malperfusion, oxidative stress, mitochondrial dysfunction and inflammation compose the sarcopenic skeletal muscle alterations associated to the frailty phenotype. Inflammation appears as a common determinant for chronic diseases, sarcopenia and frailty. The strategies to prevent the frailty phenotype include an adequate amount of physical activity and exercise as well as pharmacological interventions such as myostatin inhibitors and specific androgen receptor modulators. Cell response to stress pathways such as Nrf2, sirtuins and klotho could be considered as future therapeutic interventions for the management of frailty phenotype and aging-related chronic diseases.

  14. Chronic Lyme disease: the controversies and the science.

    PubMed

    Lantos, Paul M

    2011-07-01

    The diagnosis of chronic Lyme disease has been embroiled in controversy for many years. This is exacerbated by the lack of a clinical or microbiologic definition, and the commonality of chronic symptoms in the general population. An accumulating body of evidence suggests that Lyme disease is the appropriate diagnosis for only a minority of patients in whom it is suspected. In prospective studies of Lyme disease, very few patients go on to have a chronic syndrome dominated by subjective complaints. There is no systematic evidence that Borrelia burgdorferi, the etiology of Lyme disease, can be identified in patients with chronic symptoms following treated Lyme disease. Multiple prospective trials have revealed that prolonged courses of antibiotics neither prevent nor alleviate such post-Lyme syndromes. Extended courses of intravenous antibiotics have resulted in severe adverse events, which in light of their lack of efficacy, make them contraindicated.

  15. Macrophage Chitinase 1 Stratifies Chronic Obstructive Lung Disease

    PubMed Central

    Agapov, Eugene; Battaile, John T.; Tidwell, Rose; Hachem, Ramsey; Patterson, G. Alexander; Pierce, Richard A.; Atkinson, Jeffrey J.; Holtzman, Michael J.

    2009-01-01

    Diagnosis and therapy of chronic inflammatory lung disease is limited by the need for individualized biomarkers that provide insight into pathogenesis. Herein we show that mouse models of chronic obstructive lung disease exhibit an increase in lung chitinase production but cannot predict which chitinase family member may be equivalently increased in humans with corresponding lung disease. Moreover, we demonstrate that lung macrophage production of chitinase 1 is selectively increased in a subset of subjects with severe chronic obstructive pulmonary disease, and this increase is reflected in plasma levels. The findings provide a means to noninvasively track alternatively activated macrophages in chronic lung disease and thereby better differentiate molecular phenotypes in heterogeneous patient populations. PMID:19491341

  16. Thinking the unthinkable: Alzheimer's, Creutzfeldt-Jakob and Mad Cow disease: the age-related reemergence of virulent, foodborne, bovine tuberculosis or losing your mind for the sake of a shake or burger.

    PubMed

    Broxmeyer, Lawrence

    2005-01-01

    The possibility of the age-related reemergence of foodborne Mycobacterium bovis (bovine tuberculosis) as a vector for Creutzfeldt-Jakob Disease (CJD or human Mad Cow Disease) and Mad Cow disease itself is real. The CDC reported last May of an outbreak of CJD linked to the consumption of meat contaminated "with the agent causing" bovine spongiform encephalopathy (BSE) in a New Jersey racetrack between the time frame 1995-2004. In the opinion of experts, ample justification exists for considering a similar pathogenesis for Alzheimer's, Creutzfeldt-Jakob and the other spongiform encephalopathies such as Mad Cow disease. In fact, Creutzfeldt-Jakob and Alzheimer's often coexist and at this point are thought to differ merely by time-dependent physical changes. A recent study links up to 13% of all "Alzheimer's" victims as really having Creutzfeldt-Jakob disease. Bovine tuberculosis, which includes Mycobacterium bovis and M. avium-intracellulare or paratuberculosis, is and has always been the most prevalent threat to the cattle industry, and the USDA reports that between 20% and 40% of US dairy herds are infected with paratuberculosis alone. The health risk for milk tainted with M. bovis has been known for decades and there was a time not so long ago when "tuberculin-tested" was printed on every milk container. Schliesser stated that meat from tuberculous animals may also constitute a significant risk of infection. At the turn of the 20th century 25% of the many US deaths from TB in adults were caused by M. bovis. Dairy products aside, when past and present meat consumption are factored in, there is three times the risk of developing Alzheimer's in meat eaters as opposed to vegetarians. The investigation into the causal trail for Creutzfeldt-Jakob, indistinguishable from Alzheimer's except for its shorter, lethal course might have grown cold where it not for Roel's and others who linked mad cow in cattle with M. bovis and related paratuberculosis on clinical, pathologic

  17. Thinking the unthinkable: Alzheimer's, Creutzfeldt-Jakob and Mad Cow disease: the age-related reemergence of virulent, foodborne, bovine tuberculosis or losing your mind for the sake of a shake or burger.

    PubMed

    Broxmeyer, Lawrence

    2005-01-01

    The possibility of the age-related reemergence of foodborne Mycobacterium bovis (bovine tuberculosis) as a vector for Creutzfeldt-Jakob Disease (CJD or human Mad Cow Disease) and Mad Cow disease itself is real. The CDC reported last May of an outbreak of CJD linked to the consumption of meat contaminated "with the agent causing" bovine spongiform encephalopathy (BSE) in a New Jersey racetrack between the time frame 1995-2004. In the opinion of experts, ample justification exists for considering a similar pathogenesis for Alzheimer's, Creutzfeldt-Jakob and the other spongiform encephalopathies such as Mad Cow disease. In fact, Creutzfeldt-Jakob and Alzheimer's often coexist and at this point are thought to differ merely by time-dependent physical changes. A recent study links up to 13% of all "Alzheimer's" victims as really having Creutzfeldt-Jakob disease. Bovine tuberculosis, which includes Mycobacterium bovis and M. avium-intracellulare or paratuberculosis, is and has always been the most prevalent threat to the cattle industry, and the USDA reports that between 20% and 40% of US dairy herds are infected with paratuberculosis alone. The health risk for milk tainted with M. bovis has been known for decades and there was a time not so long ago when "tuberculin-tested" was printed on every milk container. Schliesser stated that meat from tuberculous animals may also constitute a significant risk of infection. At the turn of the 20th century 25% of the many US deaths from TB in adults were caused by M. bovis. Dairy products aside, when past and present meat consumption are factored in, there is three times the risk of developing Alzheimer's in meat eaters as opposed to vegetarians. The investigation into the causal trail for Creutzfeldt-Jakob, indistinguishable from Alzheimer's except for its shorter, lethal course might have grown cold where it not for Roel's and others who linked mad cow in cattle with M. bovis and related paratuberculosis on clinical, pathologic

  18. The relevance of chemokine signalling in modulating inherited and age-related retinal degenerations.

    PubMed

    Luhmann, Ulrich Fo; Robbie, Scott J; Bainbridge, James Wb; Ali, Robin R

    2014-01-01

    Systemic monocytes, tissue resident macrophages, dendritic cells and microglia have specific roles in immune surveillance and maintenance of tissue homeostasis and are key regulator and effector cells of the local immune response to acute and chronic tissue injury.Two major signalling pathways that differentially define trafficking behaviour and activation of systemic and local myeloid cell populations in response to exogenous and endogenous inflammatory stimuli are the Ccl2-Ccr2 and the Cx3cl1-Cx3cr1 chemokine pathways.Alterations in these pathways have been implicated in controlling myeloid cell activation during normal ageing and in age-related retinal degenerations, including age-related macular degeneration (AMD).We review the evidence for how altered chemokine signalling in acute and chronic inflammatory conditions regulate local and systemic myeloid cell responses in the retina and how this may contribute to or attenuate pathology in inherited and age-related retinal diseases. We discuss the role of environmental factors (e.g. light exposure) and the influence of genetic factors on the manifestation of pathology in experimental models and in human patients and how we envisage harnessing this knowledge for the development of targeted, more broadly applicable anti-inflammatory treatment strategies for a wide range of retinal degenerations.

  19. Reporting of ethnicity in research on chronic disease: update

    PubMed Central

    O'Loughlin, J; Dugas, E; Maximova, K; Kishchuk, N

    2006-01-01

    This paper examines the inclusion of ethnicity and race as variables in current, leading edge research on chronic disease and its risk factors. Of 100 randomly selected original research articles published in high‐impact journals in 2005, 85% did not report either a definition of ethnicity or its conceptualisation in terms of theoretical reasoning, and 98% did not report an actual measurement item. Ethnicity and race remain non‐standardised and largely underdescribed variables in research on chronic disease. This represents an important loss of opportunity to articulate and test hypotheses about the mechanisms underlying ethnic group differences in chronic disease. PMID:17099093

  20. [Chronic obstructive pulmonary disease: The golden decade. Implications for the diagnosis, prevention and treatment of chronic obstructive pulmonary disease].

    PubMed

    López-Giraldo, Alejandra; Rodríguez-Roisin, Robert; Agustí, Alvar

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous illness, which causes an important socio-economic burden. The last decade has witnessed significant advances in the understanding and knowledge of COPD with a paradigm shift in both the assessment and management of the disease. The article here reviews these changes with a particular focus on the last revision (2013) of the Global Strategy for the Diagnosis, Management, and Prevention of chronic obstructive pulmonary disease.

  1. Subclinical intestinal inflammation in chronic granulomatous disease patients.

    PubMed

    Broides, Arnon; Sagi, Orli; Pinsk, Vered; Levy, Jacov; Yerushalmi, Baruch

    2016-02-01

    Chronic granulomatous disease is a primary immunodeficiency caused by impaired neutrophil production of reactive oxygen species. Non-infectious colitis is common in chronic granulomatous disease, and high levels of antimicrobial antibodies that are associated with Crohn's disease are common even without colitis. Fecal calprotectin concentration is a marker for intestinal inflammation. We sought to determine whether subclinical intestinal inflammation occurs in asymptomatic chronic granulomatous disease patients. Asymptomatic chronic granulomatous disease patients without overt gastrointestinal symptoms suggestive of colitis at the time of enrollment were studied for fecal calprotectin concentration, antibodies associated with Crohn's disease and systemic inflammatory markers. Eight patients were included, aged 54-176 months. In 7/8 (87.5 %) fecal calprotectin concentration was normal (<50) and elevated (137 mg/kg) in only one patient. This patient later developed colitis. In 7/8 (87.5 %) anti-Saccharomyces cerevisiae antibody was positive. C-reactive protein, albumin, complete blood count and p-anti-neutrophil cytoplasmic antibody were normal in all 8 patients. Subclinical colitis is not evident in most asymptomatic chronic granulomatous disease patients; however, in some patients, fecal calprotectin concentration may be elevated, possibly indicating the presence of subclinical colitis and predicting the occurrence of clinically relevant colitis. Serum anti-Saccharomyces cerevisiae antibody concentrations do not seem to correlate with fecal calprotectin concentration in asymptomatic chronic granulomatous disease patients.

  2. Subclinical intestinal inflammation in chronic granulomatous disease patients.

    PubMed

    Broides, Arnon; Sagi, Orli; Pinsk, Vered; Levy, Jacov; Yerushalmi, Baruch

    2016-02-01

    Chronic granulomatous disease is a primary immunodeficiency caused by impaired neutrophil production of reactive oxygen species. Non-infectious colitis is common in chronic granulomatous disease, and high levels of antimicrobial antibodies that are associated with Crohn's disease are common even without colitis. Fecal calprotectin concentration is a marker for intestinal inflammation. We sought to determine whether subclinical intestinal inflammation occurs in asymptomatic chronic granulomatous disease patients. Asymptomatic chronic granulomatous disease patients without overt gastrointestinal symptoms suggestive of colitis at the time of enrollment were studied for fecal calprotectin concentration, antibodies associated with Crohn's disease and systemic inflammatory markers. Eight patients were included, aged 54-176 months. In 7/8 (87.5 %) fecal calprotectin concentration was normal (<50) and elevated (137 mg/kg) in only one patient. This patient later developed colitis. In 7/8 (87.5 %) anti-Saccharomyces cerevisiae antibody was positive. C-reactive protein, albumin, complete blood count and p-anti-neutrophil cytoplasmic antibody were normal in all 8 patients. Subclinical colitis is not evident in most asymptomatic chronic granulomatous disease patients; however, in some patients, fecal calprotectin concentration may be elevated, possibly indicating the presence of subclinical colitis and predicting the occurrence of clinically relevant colitis. Serum anti-Saccharomyces cerevisiae antibody concentrations do not seem to correlate with fecal calprotectin concentration in asymptomatic chronic granulomatous disease patients. PMID:26603166

  3. Comparison of chronic analgesic drugs prevalence in Parkinson's disease, other chronic diseases and the general population.

    PubMed

    Brefel-Courbon, Christine; Grolleau, Sabrina; Thalamas, Claire; Bourrel, Robert; Allaria-Lapierre, Valérie; Loï, Robert; Micallef-Roll, Joelle; Lapeyre-Mestre, Maryse

    2009-01-01

    Patients with Parkinson's disease (PD) frequently experienced pain. Nevertheless, there are no epidemiological data about frequency of pain in PD. We compare pain prevalence using analgesic prescription in PD patients, in the general population and in two samples of painful patients: diabetics and osteoarthritis patients in France. Data were obtained from the French System of Health Insurance for the year 2005. Medications (antiparkinsonian, antidiabetics drugs and osteoarthritis drugs) were used for identification of PD, diabetic and osteoarthritis patients. We estimated the prevalence of analgesic drugs prescription (at least one analgesic drug) and the prevalence of chronic analgesic drugs prescription (more than 90 DDD of analgesic drug). The study included 11,466 PD patients. PD patients significantly received more prescription of analgesics than the general population (82% versus 77%,) and fewer than patients with osteoarthritis (82% versus 90%). No significant difference was found between PD and diabetic patients. The chronic prescription of analgesic drugs was more prevalent in PD patients (33%) than in the general population (20%) and in diabetic patients (26%) and similar to that in osteoarthritis patients. PD patients were more exposed than the general population and diabetics to opiates, acetaminophen, and adjuvant analgesics chronic use.

  4. [Significance of Minimal Residual Disease in Chronic Lymphocytic Leukemia].

    PubMed

    Doubek, M

    2015-01-01

    Newly introduced highly effective treatment options increase the importance of minimal residual disease measurement in chronic lymphocytic leukemia. Minimal residual disease is gaining interest mainly as a predictive marker; however, clinical significance of minimal residual dis-ease in chronic lymphocytic leukemia in many different situations remains unresolved. Factors with a possible impact on the clinical significance of minimal residual disease are as follows: technique for minimal residual disease quantification, treatment regimen, peripheral blood vs. bone marrow analysis or time -point for sampling. Highly sensitive methods now available to evaluate minimal residual disease can detect a single chronic lymphocytic leukemia cell in 10(-4)- 10(-5) leukocytes using either allele -specific oligonucleotide polymerase chain reaction or multicolor flow cytometry. Minimal residual disease quantification as a surrogate marker to assess treatment efficacy in routine hematological practice has to be further evaluated.

  5. Age-Related Conjunctival Disease in the C57BL/6.NOD-Aec1Aec2 Mouse Model of Sjögren Syndrome Develops Independent of Lacrimal Dysfunction

    PubMed Central

    You, In-Cheon; Bian, Fang; Volpe, Eugene A.; de Paiva, Cintia S.; Pflugfelder, Stephen C.

    2015-01-01

    Purpose. To investigate parameters of ocular surface disease in C57BL/6.NOD-Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjögren syndrome (SS)–like lacrimal gland (LG) disease. Methods. Aec and C57BL/6 wild-type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and eyes and adnexa were excised for histology and gene expression analysis and evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell density was measured. Quantitative PCR evaluated T-cell–related cytokine expression in cornea and conjunctiva. Results. Both strains showed age-related conjunctival goblet cell loss that was more pronounced in the Aec strain and significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T-cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks. Aec mice had higher levels of IL-17A, IL-17R, IL-1α, IL-1β, and TNF-α in the conjunctiva, and they significantly increase with aging. Aec mice had greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume was significantly increased in both strains at 20 weeks. Conclusions. Aec mice developed greater conjunctival goblet cell loss associated with lymphocytic infiltration of the LG and conjunctiva with aging. Increased expression of certain T helper or inflammatory cytokines in these tissues was observed in Aec mice. The conjunctival disease appeared to be due to inflammation and not a decrease in tear volume. PMID:25758816

  6. Smoking Cessation in Chronic Obstructive Pulmonary Disease.

    PubMed

    Tashkin, Donald P

    2015-08-01

    Smoking cessation is the most effective strategy for slowing down the progression of chronic obstructive pulmonary disease (COPD) and reducing mortality in the approximately 50% of patients with diagnosed COPD who continue to smoke. While behavioral interventions (including simple advice) have modest efficacy in improving smoking quit rates, the combination of counseling and pharmacotherapy is more effective than either alone. When combined with even brief counseling, nicotine replacement therapy (NRT), bupropion SR, and varenicline have all been shown to be effective in promoting smoking cessation and sustained abstinence in smokers with COPD to a degree comparable to that observed in the general smoking population. However, the recidivism rate is high after initial quitting so that at the end of 1 year, approximately 80% or more of patients are still smoking. Thus, new approaches to smoking cessation are needed. One approach is to combine different pharmacotherapies, for example, nicotine patch plus rapidly acting NRT (e.g., gum or nasal spray) and/or bupropion or even varenicline plus either NRT or bupropion, in a stepwise approach over a varying duration depending on the severity of nicotine dependence and nicotine withdrawal symptoms during the quit attempt, as proposed in the American College of Chest Physicians Tobacco Dependence Took Kit. Electronic (e)-cigarettes, which deliver vaporized nicotine without most of the noxious components in the smoke from burning tobacco cigarettes, also has potential efficacy as a smoking cessation aid, but their efficacy and safety as either substitutes for regular cigarettes or smoking cessation aids require additional study. This task is complicated because e-cigarettes are currently unregulated and hundreds of different brands are currently available.

  7. Smoking Cessation in Chronic Obstructive Pulmonary Disease.

    PubMed

    Tashkin, Donald P

    2015-08-01

    Smoking cessation is the most effective strategy for slowing down the progression of chronic obstructive pulmonary disease (COPD) and reducing mortality in the approximately 50% of patients with diagnosed COPD who continue to smoke. While behavioral interventions (including simple advice) have modest efficacy in improving smoking quit rates, the combination of counseling and pharmacotherapy is more effective than either alone. When combined with even brief counseling, nicotine replacement therapy (NRT), bupropion SR, and varenicline have all been shown to be effective in promoting smoking cessation and sustained abstinence in smokers with COPD to a degree comparable to that observed in the general smoking population. However, the recidivism rate is high after initial quitting so that at the end of 1 year, approximately 80% or more of patients are still smoking. Thus, new approaches to smoking cessation are needed. One approach is to combine different pharmacotherapies, for example, nicotine patch plus rapidly acting NRT (e.g., gum or nasal spray) and/or bupropion or even varenicline plus either NRT or bupropion, in a stepwise approach over a varying duration depending on the severity of nicotine dependence and nicotine withdrawal symptoms during the quit attempt, as proposed in the American College of Chest Physicians Tobacco Dependence Took Kit. Electronic (e)-cigarettes, which deliver vaporized nicotine without most of the noxious components in the smoke from burning tobacco cigarettes, also has potential efficacy as a smoking cessation aid, but their efficacy and safety as either substitutes for regular cigarettes or smoking cessation aids require additional study. This task is complicated because e-cigarettes are currently unregulated and hundreds of different brands are currently available. PMID:26238637

  8. Chronic kidney disease: effects on the cardiovascular system.

    PubMed

    Schiffrin, Ernesto L; Lipman, Mark L; Mann, Johannes F E

    2007-07-01

    Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.

  9. Patient Experiences of Depression and Anxiety with Chronic Disease

    PubMed Central

    DeJean, D; Giacomini, M; Vanstone, M; Brundisini, F

    2013-01-01

    Background Depression and anxiety are highly prevalent in patients with chronic disease, but remain undertreated despite significant negative consequences on patient health. A number of clinical groups have developed recommendations for depression screening practices in the chronic disease population. Objectives The objective of this analysis was to review empirical qualitative research on the experiences of patients with chronic disease (e.g., COPD, diabetes, heart disease, stroke) and comorbid depression or anxiety, and to highlight the implications of the screening and management of anxiety and/or depression on chronic disease outcomes. Review Methods We performed literature searches for studies published from January 2002 to May 2012. We applied a qualitative mega-filter to nine condition-specific search filters. Titles and abstracts were reviewed by two reviewers and, for the studies that met the eligibility criteria, full-text articles were obtained. Qualitative meta-synthesis was used to integrate findings across relevant published primary research studies. Qualitative meta-synthesis produced a synthesis of evidence that both retained the original meaning of the authors and offered a new, integrative interpretation of the phenomenon through a process of comparing and contrasting findings across studies. Results The findings of 20 primary qualitative studies were synthesized. Patients tended to experience their chronic conditions and anxiety or depression as either independent or inter-related (i.e., the chronic disease lead to depression/anxiety, the depression/anxiety lead to the chronic disease, or the two conditions exacerbated each other). Potential barriers to screening for depression or anxiety were also identified. Limitations A wider array of issues might have been captured if the analysis had focused on broader psychological responses to the chronic disease experience. However, given the objective to highlight implications for screening for anxiety

  10. 78 FR 17214 - Agency Information Collection Activities; Proposed Collection; Comment Request; Chronic Disease...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... Collection; Comment Request; Chronic Disease Self-Management Education Program Standardized Data Collection... through Chronic Disease Self-Management Education (CDSME) Programs'' cooperative agreement program...

  11. The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults

    PubMed Central

    Nita, Małgorzata; Grzybowski, Andrzej

    2016-01-01

    The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration. PMID:26881021

  12. Chronic Wasting Disease Prions in Elk Antler Velvet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy or prion disease of captive and free ranging white tailed deer, mule deer, Rocky Mountain elk and moose in the some parts of the United States and Canada. The presence of the disease has sharply curtailed movement of captive...

  13. Management of Chronic Infectious Diseases in School Children.

    ERIC Educational Resources Information Center

    Illinois State Board of Education, Springfield.

    This document contains guidelines for developing policies and procedures related to chronic infectious diseases, as recommended by the Illinois Task Force on School Management of Infectious Disease. It is designed to help school personnel understand how infectious diseases can be transmitted, and to assist school districts in the development and…

  14. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of chronic renal disease. 79.57 Section 79.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Uranium Millers § 79.57 Proof of chronic...

  15. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of chronic renal disease. 79.57 Section 79.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Uranium Millers § 79.57 Proof of chronic...

  16. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.57 Section 79.57 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Uranium Millers § 79.57 Proof of chronic...

  17. Oral disease profiles in chronic graft versus host disease.

    PubMed

    Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

    2015-04-01

    At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral c

  18. Oral disease profiles in chronic graft versus host disease.

    PubMed

    Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

    2015-04-01

    At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral c

  19. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  20. Mechanisms of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Fowler, Benjamin J.

    2012-01-01

    Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed. PMID:22794258