Sample records for accelerated vascular aging

  1. [Vascular aging, arterial hypertension and physical activity].

    PubMed

    Schmidt-Trucksäss, A; Weisser, B

    2011-11-01

    The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Testosterone Deficiency Accelerates Neuronal and Vascular Aging of SAMP8 Mice: Protective Role of eNOS and SIRT1

    PubMed Central

    Ota, Hidetaka; Akishita, Masahiro; Akiyoshi, Takuyu; Kahyo, Tomoaki; Setou, Mitsutoshi; Ogawa, Sumito; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi

    2012-01-01

    Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD+-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging. PMID:22238626

  3. Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

    PubMed

    Del Campo, Lara; Hamczyk, Magda R; Andrés, Vicente; Martínez-González, José; Rodríguez, Cristina

    Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Both atherosclerosis and heart failure significantly contribute to age-associated CVD morbidity and mortality. Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by the synthesis of progerin, which is noted for accelerated aging and CVD. This mutant form of prelamin A induces generalised atherosclerosis, vascular calcification, and cardiac electrophysiological abnormalities, leading to premature aging and death, mainly due to myocardial infarction and stroke. This review discusses the main vascular structural and functional abnormalities during physiological and premature aging, as well as the mechanisms involved in the exacerbated CVD and accelerated aging induced by the accumulation of progerin and prelamin A. Both proteins are expressed in non-HGPS individuals, and physiological aging shares many features of progeria. Research into HGPS could therefore shed light on novel mechanisms involved in the physiological aging of the cardiovascular system. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

    PubMed

    Uryga, Anna K; Bennett, Martin R

    2016-04-15

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

  5. Expression of CGRP neurotransmitter and vascular genesis marker mRNA is age-dependent in superior cervical ganglia of senescence-accelerated prone mice.

    PubMed

    Mitsuoka, Kazuyuki; Kikutani, Takeshi; Miwa, Yoko; Sato, Iwao

    2018-01-18

    Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released from the superior cervical ganglion (SCG) and causes head and neck pain. The morphological properties of human SCG neurons, including neurotransmitter content, are altered during aging. However, morphological changes in CGRP in the SCG during aging are not known. Therefore, we investigated CGRP and other markers in the SCG during aging in an aging model of senescence-accelerated prone mouse (SAMP8) and senescence-accelerated resistant mice (SAMR1) using real-time RT-PCR mRNA analyses and in situ hybridization. The abundance of neurotransmitter (CGRP, NPY, TRPV1), vascular genesis marker (CD31, LYVE-1), and cytochrome C mRNA differed between 12-week-old and 24-week-old SAMP8 and SAMR1. Abundance of TRPV1, CD31 and cytochrome C mRNAs of SAMP8 decreased between 12- and 24-week-old. The ratio of CGRP mRNA positive cells and CGRP mRNA abundance levels of the SCG of aging mouse such as SAMP8 have already been also higher than that of SAMR1 at 12-week-old. The CGRP positive shrunken ganglion cells was increased from 12- to 24-weeks-old mouse in SAMR1 and SAMP8. The SCG primarily affected the internal and external carotid arteries, larynx thyroid gland, and pharyngeal muscle during aging. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Sirtuins, Cell Senescence, and Vascular Aging.

    PubMed

    Kida, Yujiro; Goligorsky, Michael S

    2016-05-01

    The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition; and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, and contribute to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and nicotinamide adenine dinucleotide stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  7. ALDOSTERONE DYSREGULATION WITH AGING PREDICTS RENAL-VASCULAR FUNCTION AND CARDIO-VASCULAR RISK

    PubMed Central

    Brown, Jenifer M.; Underwood, Patricia C.; Ferri, Claudio; Hopkins, Paul N.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

    2014-01-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal- and cardio-vascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1,124 visits) in a Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression-to-stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics, and the renal-vascular responses to dietary sodium manipulation and angiotensin II (AngII) infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β= -4.60, p<0.0001) and higher SASSI (β= -58.63, p=0.001) predicted lower RPF and a blunted RPF response to sodium loading and AngII infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (p<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (p<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal-vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal-vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease. PMID:24664291

  8. Menopause accelerates biological aging

    PubMed Central

    Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

    2016-01-01

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  9. Oxidative stress and vascular inflammation in aging.

    PubMed

    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2013-12-01

    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  10. Failure of vascular autoregulation in the upper limb with increased +Gz acceleration.

    PubMed

    Green, N D C; Brown, M D; Coote, J H

    2007-08-01

    Forearm pain occurring during high +Gz exposure has been linked with vascular distension from elevated transmural pressure of hydrostatic origin and is exacerbated by positive pressure breathing (PBG). We postulated that at high vascular transmural pressure vascular autoregulation might be overcome and be associated with worsened pain. Six volunteers were studied at +4, +5, +6, and +7 Gz on a human centrifuge. Forearm vascular resistance (FVR) was assessed by Doppler ultrasound resistive index (RI), and superficial forearm venous pressure (FVP) was measured via an indwelling catheter. Pain rating was assessed by numerical scale. The left arm was located at heart level (control position), or on the throttle (test position). Runs were completed with and without positive pressure breathing for G protection (PBG); subjects wore full coverage anti-G trousers and chest counter-pressure. In the test position, pain increased with increasing acceleration (P < 0.0001), and was more severe with PBG at +5 Gz and +7 Gz (P < 0.05). FVP rose substantially more in the test than control position (238 +/- 17 mmHg vs. 61 +/- 8 mmHg at +7 Gz, P < 0.0001) but the presence or absence of PBG had no effect on the FVP increase during acceleration in either position. In the test position, RI fell with increasing acceleration above +5 Gz (P < 0.0001), and the fall was greater with PBG (P < 0.05). Forearm pain was thus associated with a decrease in FVR and an increase in vascular transmural pressure. PBG exacerbated forearm pain and prompted a greater fall in RI, but had no effect on FVP response. These findings support FVR but not forearm venous distension in the aetiology of +Gz arm pain.

  11. Matrix ageing and vascular impacts: focus on elastin fragmentation.

    PubMed

    Duca, Laurent; Blaise, Sébastien; Romier, Béatrice; Laffargue, Muriel; Gayral, Stéphanie; El Btaouri, Hassan; Kawecki, Charlotte; Guillot, Alexandre; Martiny, Laurent; Debelle, Laurent; Maurice, Pascal

    2016-06-01

    Cardiovascular diseases (CVDs) are the leading cause of death worldwide and represent a major problem of public health. Over the years, life expectancy has considerably increased throughout the world, and the prevalence of CVD is inevitably rising with the growing ageing of the population. The normal process of ageing is associated with progressive deterioration in structure and function of the vasculature, commonly called vascular ageing. At the vascular level, extracellular matrix (ECM) ageing leads to molecular alterations in long half-life proteins, such as elastin and collagen, and have critical effects on vascular diseases. This review highlights ECM alterations occurring during vascular ageing with a specific focus on elastin fragmentation and also the contribution of elastin-derived peptides (EDP) in age-related vascular complications. Moreover, current and new pharmacological strategies aiming at minimizing elastin degradation, EDP generation, and associated biological effects are discussed. These strategies may be of major relevance for preventing and/or delaying vascular ageing and its complications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  12. Vascular Aging: Lessons From Pediatric Hypertension.

    PubMed

    Litwin, Mieczyslaw; Feber, Janusz; Ruzicka, Marcel

    2016-05-01

    Hypertension (HTN) in children is associated with early vascular aging (EVA) and underlying immunologic-metabolic abnormalities and accelerated biological maturation. Morphologic and functional vascular changes underlying EVA and HTN in children resemble those seen in the elderly including but not limited to an increase in intima-media thickness (IMT) and arterial stiffness and endothelial dysfunction. Although progeria syndrome leading to EVA and the development of clinically manifested cardiovascular (CV) disease in the second decade of life is a rare hereditary disorder, primary HTN, which is also associated with EVA, is much more common (reported in up to 10% in adolescents). EVA associated with HTN in children leads to the premature development of target organ injury in childhood and CV events in early adulthood. Limited evidence from prospective observational studies in children and adolescents indicates that early lifestyle measures (low salt/low sugar intake and exercise) or pharmacologic treatment of HTN, or both, partially reverses morphologic and functional changes underlying EVA such as an increase in carotid IMT and pulse wave velocity, a decrease in flow-mediated dilation of the brachial artery, and an increase in oxidative stress and visceral fat. Future mechanistic and therapeutic clinical trials are desirable to assess the mechanisms and treatment strategies of EVA in the context of HTN in children and their effect on CV events in early adulthood. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  13. Aging and vascular endothelial function in humans

    PubMed Central

    SEALS, Douglas R.; JABLONSKI, Kristen L.; DONATO, Anthony J.

    2012-01-01

    Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging. PMID

  14. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  15. Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes.

    PubMed

    Bruno, Rosa Maria; Duranti, Emiliano; Ippolito, Chiara; Segnani, Cristina; Bernardini, Nunzia; Di Candio, Giulio; Chiarugi, Massimo; Taddei, Stefano; Virdis, Agostino

    2017-01-01

    We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-l-arginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (P<0.0001) and blunted in HT versus NT for each age range. In NT, tempol enhanced endothelial function in the oldest subgroup; in HT, the potentiating effect started earlier. HT showed an increased M/L (P<0.001) versus control. In both groups, M/L was directly related to age (P<0.0001). M/L was greater in HT, starting from 31 to 45 years range. A significant age-hypertension interaction occurred (P=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper. © 2016 American Heart Association, Inc.

  16. Age-related memory decline is associated with vascular and microglial degeneration in aged rats.

    PubMed

    Zhang, Rong; Kadar, Tamar; Sirimanne, Ernest; MacGibbon, Alastair; Guan, Jian

    2012-12-01

    The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

    PubMed

    Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

    2015-05-01

    During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

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

    PubMed

    Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

    2016-10-15

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

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

    PubMed Central

    Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

    2016-01-01

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

  20. Aerobic exercise and other healthy lifestyle factors that influence vascular aging

    PubMed Central

    Santos-Parker, Jessica R.; LaRocca, Thomas J.

    2014-01-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote “resistance” against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

  1. Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

    PubMed

    Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

    2014-12-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. Copyright © 2014 The American Physiological Society.

  2. Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.

    PubMed

    Heinzel, Sebastian; Metzger, Florian G; Ehlis, Ann-Christine; Korell, Robert; Alboji, Ahmed; Haeussinger, Florian B; Wurster, Isabel; Brockmann, Kathrin; Suenkel, Ulrike; Eschweiler, Gerhard W; Maetzler, Walter; Berg, Daniela; Fallgatter, Andreas J

    2015-01-01

    Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

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

    PubMed

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

    2017-07-01

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

  4. Accelerated epigenetic aging in Werner syndrome.

    PubMed

    Maierhofer, Anna; Flunkert, Julia; Oshima, Junko; Martin, George M; Haaf, Thomas; Horvath, Steve

    2017-04-01

    Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.

  5. Arterial ageing: from endothelial dysfunction to vascular calcification.

    PubMed

    Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

    2017-05-01

    Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  6. Vascular Ageing and Exercise: Focus on Cellular Reparative Processes.

    PubMed

    Ross, Mark D; Malone, Eva; Florida-James, Geraint

    2016-01-01

    Ageing is associated with an increased risk of developing noncommunicable diseases (NCDs), such as diabetes and cardiovascular disease (CVD). The increased risk can be attributable to increased prolonged exposure to oxidative stress. Often, CVD is preceded by endothelial dysfunction, which carries with it a proatherothrombotic phenotype. Endothelial senescence and reduced production and release of nitric oxide (NO) are associated with "vascular ageing" and are often accompanied by a reduced ability for the body to repair vascular damage, termed "reendothelialization." Exercise has been repeatedly shown to confer protection against CVD and diabetes risk and incidence. Regular exercise promotes endothelial function and can prevent endothelial senescence, often through a reduction in oxidative stress. Recently, endothelial precursors, endothelial progenitor cells (EPC), have been shown to repair damaged endothelium, and reduced circulating number and/or function of these cells is associated with ageing. Exercise can modulate both number and function of these cells to promote endothelial homeostasis. In this review we look at the effects of advancing age on the endothelium and these endothelial precursors and how exercise appears to offset this "vascular ageing" process.

  7. Vascular ageing and interventions: lessons and learnings

    PubMed Central

    Williams, Bryan

    2016-01-01

    This review discusses the relationship between elevated blood pressure, hypertension, arterial stiffness and hence vascular ageing. This is a complex process and the majority of treatments target the consequences of this, rather than the pathophysiology of ageing itself. This is because preventing vascular ageing from occurring is complex and would require very early intervention and lifelong treatment. The process of arteriosclerosis is known to result from reversible and irreversible functional components, and, together, these are responsible for the increased systolic and decreased diastolic blood pressure seen with advancing age. Indeed, hypertension develops as it becomes more difficult for the heart to drive blood flow around the body, as a result of poor ventricular coupling and increased arterial stiffness. Elevated blood pressure is therefore a clinical manifestation of ageing that continues to increase with advancing years, and is also linked with an increased risk of cardiac, cerebrovascular and chronic kidney disease. These manifestations arise due to changing haemodynamics associated with ageing, and therefore treatments that reduce the development of these conditions or delay their progression have the potential to improve patient outcomes. This may be possible with existing therapies as well as new treatments currently under investigation. PMID:27102114

  8. Effect of gravitational acceleration, hypokinesia and hypodynamia on the structure of the intestinal vascular bed

    NASA Technical Reports Server (NTRS)

    Nikitin, M. V.

    1980-01-01

    A series of experiments comparing single and combined effects of hypokinesia and gravitational acceleration on morphology of intestinal blood vessels are discussed. Results indicate that hypokinesia has a whole body nonspecific effect reflected even in an organ whose activity shows little or no change due to hypokinesia. In early hypokinetic stages blood redistribution caused anorexia, intestinal atonia, and secretory disruption. Destructive changes from further exposure include aneurisms, varicoses, extravascular movement of blood elements, and vascular wall muscle fiber degeneration. The effect of acceleration is greatest in the ventrodorsal direction. Changes due to acceleration then hypokinesia are like those due to hypokinesia alone; changes due to acceleration before and after hypokinesia are like those due to acceleration. Adaptation raises acceleration tolerance but the effects do not survive four-week hypokinesia.

  9. The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

    PubMed Central

    Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

    2014-01-01

    The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

  10. Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

    PubMed

    Brown, Jenifer M; Underwood, Patricia C; Ferri, Claudio; Hopkins, Paul N; Williams, Gordon H; Adler, Gail K; Vaidya, Anand

    2014-06-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; P<0.0001) and higher SASSI (β=-58.63; P=0.001) predicted lower RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (P<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (P<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.

  11. Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities.

    PubMed

    Litwin, Mieczysław; Feber, Janusz; Niemirska, Anna; Michałkiewicz, Jacek

    2016-02-01

    There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed.

  12. Liver-Specific Knockdown of IGF-1 Decreases Vascular Oxidative Stress Resistance by Impairing the Nrf2-Dependent Antioxidant Response: A Novel Model of Vascular Aging

    PubMed Central

    Bailey-Downs, Lora C.; Mitschelen, Matthew; Sosnowska, Danuta; Toth, Peter; Pinto, John T.; Ballabh, Praveen; Valcarcel-Ares, M.Noa; Farley, Julie; Koller, Akos; Henthorn, Jim C.; Bass, Caroline; Sonntag, William E.; Csiszar, Anna

    2012-01-01

    Recent studies demonstrate that age-related dysfunction of NF-E2–related factor-2 (Nrf2)–driven pathways impairs cellular redox homeostasis, exacerbating age-related cellular oxidative stress and increasing sensitivity of aged vessels to oxidative stress–induced cellular damage. Circulating levels of insulin-like growth factor (IGF)-1 decline during aging, which significantly increases the risk for cardiovascular diseases in humans. To test the hypothesis that adult-onset IGF-1 deficiency impairs Nrf2-driven pathways in the vasculature, we utilized a novel mouse model with a liver-specific adeno-associated viral knockdown of the Igf1 gene using Cre-lox technology (Igf1f/f + MUP-iCre-AAV8), which exhibits a significant decrease in circulating IGF-1 levels (∼50%). In the aortas of IGF-1–deficient mice, there was a trend for decreased expression of Nrf2 and the Nrf2 target genes GCLC, NQO1 and HMOX1. In cultured aorta segments of IGF-1–deficient mice treated with oxidative stressors (high glucose, oxidized low-density lipoprotein, and H2O2), induction of Nrf2-driven genes was significantly attenuated as compared with control vessels, which was associated with an exacerbation of endothelial dysfunction, increased oxidative stress, and apoptosis, mimicking the aging phenotype. In conclusion, endocrine IGF-1 deficiency is associated with dysregulation of Nrf2-dependent antioxidant responses in the vasculature, which likely promotes an adverse vascular phenotype under pathophysiological conditions associated with oxidative stress (eg, diabetes mellitus, hypertension) and results in accelerated vascular impairments in aging. PMID:22021391

  13. Accelerated and accentuated neurocognitive aging in HIV infection.

    PubMed

    Sheppard, David P; Iudicello, Jennifer E; Morgan, Erin E; Kamat, Rujvi; Clark, Lindsay R; Avci, Gunes; Bondi, Mark W; Woods, Steven Paul

    2017-06-01

    There is debate as to whether the neurocognitive changes associated with HIV infection represent an acceleration of the typical aging process or more simply reflect a greater accentuated risk for age-related declines. We aimed to determine whether accelerated neurocognitive aging is observable in a sample of older HIV-infected individuals compared to age-matched seronegatives and older old (i.e., aged ≥65) seronegative adults. Participants in a cross-sectional design included 48 HIV-seronegative (O-) and 40 HIV-positive (O+) participants between the ages of 50-65 (mean ages = 55 and 56, respectively) and 40 HIV-seronegative participants aged ≥65 (OO-; mean age = 74) who were comparable for other demographics. All participants were administered a brief neurocognitive battery of attention, episodic memory, speeded executive functions, and confrontation naming (i.e., Boston Naming Test). The O+ group performed more poorly than the O- group (i.e., accentuated aging), but not differently from the OO- on digit span and initial recall of a supraspan word list, consistent with an accelerating aging profile. However, the O+ group's performance was comparable to the O- group on all other neurocognitive tests (ps > 0.05). These data partially support a model of accelerated neurocognitive aging in HIV infection, which was observed in the domain of auditory verbal attention, but not in the areas of memory, language, or speeded executive functions. Future studies should examine whether HIV-infected adults over 65 evidence accelerated aging in downstream neurocognitive domains and subsequent everyday functioning outcomes.

  14. Simultaneous Increases in Proliferation and Apoptosis of Vascular Smooth Muscle Cells Accelerate Diabetic Mouse Venous Atherosclerosis

    PubMed Central

    Liu, Shuying; Zhang, Zhengyu; Wang, Jingjing; Zhou, Yuhuan; Liu, Kefeng; Huang, Jintao; Chen, Dadi; Wang, Junmei; Li, Chaohong

    2015-01-01

    Aims This study was designed to demonstrate simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) leading to accelerated vein graft remodeling and to explore the underlying mechanisms. Methods Vein grafts were performed in non-diabetic and diabetic mice. The cultured quiescent VSMCs were subjected to mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs). Harvested vein grafts and treated VSMCs were used to detect cell proliferation, apoptosis, mitogen-activated protein kinases (MAPKs) activation and SM-α-actin expression. Results Significantly thicker vessel walls and greater increases in proliferation and apoptosis were observed in diabetic vein grafts than those in non-diabetic. Both SS and AGEs were found to induce different activation of three members of MAPKs and simultaneous increases in proliferation and apoptosis of VSMCs, and combined treatment with both had a synergistic effect. VSMCs with strong SM-α-actin expression represented more activated JNKs or p38MAPK, and cell apoptosis, while the cells with weak SM-α-actin expression demonstrated preferential activation of ERKs and cell proliferation. In contrast, inhibition of MAPKs signals triggered significant decreases in VSMC proliferation, and apoptosis. Treatment of the cells with RNA interference of receptor of AGEs (RAGE) also resulted in significant decreases in both proliferation and apoptosis. Conclusions Increased pressure-induced SS triggers simultaneous increases in proliferation and apoptosis of VSMCs in the vein grafts leading to vein arterializations, which can be synergistically accelerated by high glucose-induced AGEs resulting in vein graft atherosclerosis. Either SS or AGEs and their combination induce simultaneous increases in proliferation and apoptosis of VSMCs via different activation of three members of MAPKs resulting from different VSMC subtypes classified by SM-α-actin expression levels. PMID:26488175

  15. The relationship to age and cerebral vascular accidents of fibrin and fibrinolytic activity

    PubMed Central

    Hume, R.

    1961-01-01

    Three `normal' groups of people—young, middle-aged, and old—have been investigated with regard to the fibrin content and fibrinolytic activity of the blood. The fourth group consisted of middle-aged people who had previously sustained a cerebral vascular accident matched statistically for age with the middle-aged normals. It was concluded that fibrin increases with age but there is an interaction between age and sex, the female having a higher level in the young group and the male a higher level in the middle-aged group. There was no sex difference in the levels of fibrin in the old age group. Fibrinolytic activity increases with age and there is a positive correlation between fibrin and fibrinolytic activity but no age-sex interaction. Those with cerebral vascular accidents tended to have higher fibrin levels and lower fibrinolytic activity but the differences were not statistically significant. There did, however, appear to be an increase in antifibrinolytic activity in the cerebral vascular group. PMID:13716799

  16. The effect of accelerated aging on the wear of UHMWPE.

    PubMed

    Sakoda, H; Fisher, J; Lu, S; Buchanan, F

    2001-01-01

    Oxidative degradation of UHMWPE has been found to be a cause of elevated wear rate of the polymer in total joint replacement leading to failure of these devices. In order to evaluate long term stability of polymers, various accelerated aging methods have been developed. In this study, wear rates of shelf aged UHMWPE and "accelerated aged" UHMWPE were compared using a multi-directional pin-on-plate wear test machine in order to evaluate the effect of the accelerated aging on wear. Wear factors of the aged materials were found to depend on their density, which is a measure of oxidation level. Finally, accelerated aging was calibrated against shelf aging in terms of wear rate. Copyright 2001 Kluwer Academic Publishers

  17. Epigenetic Age Acceleration Assessed with Human White-Matter Images.

    PubMed

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-05-03

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample ( n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ pheno = -0.119, p = 0.028), with evidence of shared genetic (ρ gene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging. SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so

  18. Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing

    PubMed Central

    Seals, Douglas R.

    2016-01-01

    Abstract Calorie restriction (CR) in the absence of malnutrition exerts a multitude of physiological benefits with ageing in model organisms and in humans including improvements in vascular function. Despite the well‐known benefits of chronic CR, long‐term energy restriction is not likely to be a feasible healthy lifestyle strategy in humans due to poor sustained adherence, and presents additional concerns if applied to normal weight older adults. This review summarizes what is known about the effects of CR on vascular function with ageing including the underlying molecular ‘energy‐ and nutrient‐sensing’ mechanisms, and discusses the limited but encouraging evidence for alternative pharmacological and lifestyle interventions that may improve vascular function with ageing by mimicking the beneficial effects of long‐term CR. PMID:27641062

  19. Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

    PubMed

    Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

    2015-02-01

    Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

  20. Early Vascular Ageing - A Concept in Development.

    PubMed

    M Nilsson, Peter

    2015-04-01

    Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

  1. Accelerated DNA Methylation Age: Associations with PTSD and Neural Integrity

    PubMed Central

    Wolf, Erika J.; Logue, Mark W.; Hayes, Jasmeet P.; Sadeh, Naomi; Schichman, Steven A.; Stone, Annjanette; Salat, David H.; Milberg, William; McGlinchey, Regina; Miller, Mark W.

    2015-01-01

    Background Accumulating evidence suggests that post traumatic stress disorder (PTSD) may accelerate cellular aging and lead to premature morbidity and neurocognitive decline. Methods This study evaluated associations between PTSD and DNA methylation (DNAm) age using recently developed algorithms of cellular age by Horvath (2013) and Hannum et al. (2013). These estimates reflect accelerated aging when they exceed chronological age. We also examined if accelerated cellular age manifested in degraded neural integrity, indexed via diffusion tensor imaging. Results Among 281 male and female veterans of the conflicts in Iraq and Afghanistan, DNAm age was strongly related to chronological age (rs ~.88). Lifetime PTSD severity was associated with Hannum DNAm age estimates residualized for chronological age (β = .13, p= .032). Advanced DNAm age was associated with reduced integrity in the genu of the corpus callosum (β = −.17, p= .009) and indirectly linked to poorer working memory performance via this region (indirect β = − .05, p= .029). Horvath DNAm age estimates were not associated with PTSD or neural integrity. Conclusions Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition. PMID:26447678

  2. Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

    PubMed

    Horvath, Steve; Phillips, Nicole; Heany, Sarah J; Kobor, Michael S; Lin, David Ts; Myer, Landon; Zar, Heather J; Stein, Dan J; Levine, Andrew J; Hoare, Jacqueline

    2018-05-08

    Recent studies demonstrate that infection with the Human Immunodeficiency Virus-1 (HIV) is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth. Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) Study. The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV-) adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrolment to CTAAC. HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed). Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.

  3. Traumatic stress and accelerated DNA methylation age: A meta-analysis.

    PubMed

    Wolf, Erika J; Maniates, Hannah; Nugent, Nicole; Maihofer, Adam X; Armstrong, Don; Ratanatharathorn, Andrew; Ashley-Koch, Allison E; Garrett, Melanie; Kimbrel, Nathan A; Lori, Adriana; Va Mid-Atlantic Mirecc Workgroup; Aiello, Allison E; Baker, Dewleen G; Beckham, Jean C; Boks, Marco P; Galea, Sandro; Geuze, Elbert; Hauser, Michael A; Kessler, Ronald C; Koenen, Karestan C; Miller, Mark W; Ressler, Kerry J; Risbrough, Victoria; Rutten, Bart P F; Stein, Murray B; Ursano, Robert J; Vermetten, Eric; Vinkers, Christiaan H; Uddin, Monica; Smith, Alicia K; Nievergelt, Caroline M; Logue, Mark W

    2018-06-01

    Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic and cellular variables and accelerated DNA methylation age were also examined, as was the moderating influence of demographic variables. Meta-analysis of regression coefficients from contributing cohorts revealed that childhood trauma exposure (when measured with the Childhood Trauma Questionnaire) and lifetime PTSD severity evidenced significant, albeit small, meta-analytic associations with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex, CD4T cell proportions, and natural killer cell proportions were also significantly associated with accelerated DNA methylation age (all ps < 0.02). PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA methylation age. There was no evidence of moderation of the trauma or PTSD variables by demographic factors. Results suggest that traumatic stress is associated with advanced epigenetic age and raise the possibility that cells integral to immune system maintenance and responsivity play a role in this. This study highlights the need for additional research into the biological mechanisms linking traumatic stress to accelerated DNA methylation age and the importance of furthering our understanding of the neurobiological and health consequences of PTSD. Published by Elsevier Ltd.

  4. Challenges of accelerated aging techniques for elastomer lifetime predictions

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

    Gillen, Kenneth T.; Bernstein, R.; Celina, M.

    Elastomers are often degraded when exposed to air or high humidity for extended times (years to decades). Lifetime estimates normally involve extrapolating accelerated aging results made at higher than ambient environments. Several potential problems associated with such studies are reviewed, and experimental and theoretical methods to address them are provided. The importance of verifying time–temperature superposition of degradation data is emphasized as evidence that the overall nature of the degradation process remains unchanged versus acceleration temperature. The confounding effects that occur when diffusion-limited oxidation (DLO) contributes under accelerated conditions are described, and it is shown that the DLO magnitude canmore » be modeled by measurements or estimates of the oxygen permeability coefficient (P Ox) and oxygen consumption rate (Φ). P Ox and Φ measurements can be influenced by DLO, and it is demonstrated how confident values can be derived. In addition, several experimental profiling techniques that screen for DLO effects are discussed. Values of Φ taken from high temperature to temperatures approaching ambient can be used to more confidently extrapolate accelerated aging results for air-aged materials, and many studies now show that Arrhenius extrapolations bend to lower activation energies as aging temperatures are lowered. Furthermore, best approaches for accelerated aging extrapolations of humidity-exposed materials are also offered.« less

  5. Challenges of accelerated aging techniques for elastomer lifetime predictions

    DOE PAGES

    Gillen, Kenneth T.; Bernstein, R.; Celina, M.

    2015-03-01

    Elastomers are often degraded when exposed to air or high humidity for extended times (years to decades). Lifetime estimates normally involve extrapolating accelerated aging results made at higher than ambient environments. Several potential problems associated with such studies are reviewed, and experimental and theoretical methods to address them are provided. The importance of verifying time–temperature superposition of degradation data is emphasized as evidence that the overall nature of the degradation process remains unchanged versus acceleration temperature. The confounding effects that occur when diffusion-limited oxidation (DLO) contributes under accelerated conditions are described, and it is shown that the DLO magnitude canmore » be modeled by measurements or estimates of the oxygen permeability coefficient (P Ox) and oxygen consumption rate (Φ). P Ox and Φ measurements can be influenced by DLO, and it is demonstrated how confident values can be derived. In addition, several experimental profiling techniques that screen for DLO effects are discussed. Values of Φ taken from high temperature to temperatures approaching ambient can be used to more confidently extrapolate accelerated aging results for air-aged materials, and many studies now show that Arrhenius extrapolations bend to lower activation energies as aging temperatures are lowered. Furthermore, best approaches for accelerated aging extrapolations of humidity-exposed materials are also offered.« less

  6. Accelerated epigenetic aging in Down syndrome

    PubMed Central

    Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

    2015-01-01

    Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10−14). PMID:25678027

  7. The senescence accelerated mouse prone 8 (SAMP8): A novel murine model for cardiac aging.

    PubMed

    Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Babu, Sahana Suresh; Palaniyandi, Suresh S; Watanabe, Kenichi; Cooke, John P; Thandavarayan, Rajarajan A

    2017-05-01

    Because cardiovascular disease remains the major cause of mortality and morbidity world-wide, there remains a compelling need for new insights and novel therapeutic avenues. In this regard, the senescence-accelerated mouse prone 8 (SAMP8) line is a particularly good model for studying the effects of aging on cardiovascular health. Accumulating evidence suggests that this model may shed light on age-associated cardiac and vascular dysfunction and disease. These animals manifest evidence of inflammation, oxidative stress and adverse cardiac remodeling that may recapitulate processes involved in human disease. Early alterations in oxidative damage promote endoplasmic reticulum stress to trigger apoptosis and cytokine production in this genetically susceptible mouse strain. Conversely, pharmacological treatments that reduce inflammation and oxidative stress improve cardiac function in these animals. Therefore, the SAMP8 mouse model provides an exciting opportunity to expand our knowledge of aging in cardiovascular disease and the potential identification of novel targets of treatment. Herein, we review the previous studies performed in SAMP8 mice that provide insight into age-related cardiovascular alterations. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging.

    PubMed

    Gauthier, Claudine Joëlle; Lefort, Muriel; Mekary, Saïd; Desjardins-Crépeau, Laurence; Skimminge, Arnold; Iversen, Pernille; Madjar, Cécile; Desjardins, Michèle; Lesage, Frédéric; Garde, Ellen; Frouin, Frédérique; Bherer, Louis; Hoge, Richard D

    2015-01-01

    Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vascular degradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82 m/s, respectively) and lower VO₂ max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL O2/kg/min, respectively) than younger adults. Within the older group, faster performance of the modified Stroop task was associated with preserved aortic elasticity (lower aortic pulse wave velocity; p = 0.046) and higher cardiorespiratory fitness (VO₂ max; p = 0.036). Furthermore, VO₂ max was found to be negatively associated with blood oxygenation level dependent cerebrovascular reactivity to CO₂ in frontal regions involved in the task (p = 0.038) but positively associated with cerebrovascular reactivity in periventricular watershed regions and within the postcentral gyrus. Overall, the results of this study support the hypothesis that cognitive

  9. BrainAGE score indicates accelerated brain aging in schizophrenia, but not bipolar disorder.

    PubMed

    Nenadić, Igor; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

    2017-08-30

    BrainAGE (brain age gap estimation) is a novel morphometric parameter providing a univariate score derived from multivariate voxel-wise analyses. It uses a machine learning approach and can be used to analyse deviation from physiological developmental or aging-related trajectories. Using structural MRI data and BrainAGE quantification of acceleration or deceleration of in individual aging, we analysed data from 45 schizophrenia patients, 22 bipolar I disorder patients (mostly with previous psychotic symptoms / episodes), and 70 healthy controls. We found significantly higher BrainAGE scores in schizophrenia, but not bipolar disorder patients. Our findings indicate significantly accelerated brain structural aging in schizophrenia. This suggests, that despite the conceptualisation of schizophrenia as a neurodevelopmental disorder, there might be an additional progressive pathogenic component. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Accelerated aging: prediction of chemical stability of pharmaceuticals.

    PubMed

    Waterman, Kenneth C; Adami, Roger C

    2005-04-11

    Methods of rapidly and accurately assessing the chemical stability of pharmaceutical dosage forms are reviewed with respect to the major degradation mechanisms generally observed in pharmaceutical development. Methods are discussed, with the appropriate caveats, for accelerated aging of liquid and solid dosage forms, including small and large molecule active pharmaceutical ingredients. In particular, this review covers general thermal methods, as well as accelerated aging methods appropriate to oxidation, hydrolysis, reaction with reactive excipient impurities, photolysis and protein denaturation.

  11. Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

    PubMed Central

    Mikhed, Yuliya; Daiber, Andreas; Steven, Sebastian

    2015-01-01

    The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan. PMID:26184181

  12. Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs

    NASA Technical Reports Server (NTRS)

    Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

    2011-01-01

    Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

  13. Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

    PubMed

    Janota, C S; Brites, D; Lemere, C A; Brito, M A

    2015-09-16

    Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [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.

  15. Diffusion tensor imaging, intracranial vascular resistance and cognition in middle-aged asymptomatic subjects.

    PubMed

    López-Olóriz, Jorge; López-Cancio, Elena; Arenillas, Juan F; Hernández, María; Dorado, Laura; Dacosta-Aguayo, Rosalía; Barrios, Maite; Soriano-Raya, Juan José; Miralbell, Júlia; Bargalló, Núria; Cáceres, Cynthia; Torán, Pere; Alzamora, Maite; Dávalos, Antonio; Mataró, Maria

    2014-01-01

    The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population. Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with lower scores in all cognitive

  16. Mechanisms underlying caloric restriction and life span regulation: implications for vascular aging

    PubMed Central

    Ungvari, Zoltan; Parrado-Fernandez, Cristina; Csiszar, Anna; de Cabo, Rafael

    2008-01-01

    This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species (ROS) and inhibition of inflammatory pathways play a central role in the anti-aging cardiovascular effects of caloric restriction (CR). Particular emphasis is placed on the potential role of the plasma membrane redox system in CR-induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that CR increases bioavailability of NO, decreases vascular ROS generation, activates the Nrf2/ARE pathway inducing ROS detoxification systems, exerts anti-inflammatory effects and, thereby, suppresses initiation/progression of vascular disease that accompany aging. PMID:18340017

  17. Is biological aging accelerated in drug addiction?

    PubMed

    Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-02-01

    Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

  18. Accelerated aging, natural aging, and small punch testing of gamma-air sterilized polycarbonate urethane acetabular components.

    PubMed

    Kurtz, S M; Siskey, R; Reitman, M

    2010-05-01

    The objectives of this study were three-fold: (1) to determine the applicability of the small punch test to characterize Bionate 80A polycarbonate urethane (PCU) acetabular implants; (2) to evaluate the susceptibility of PCU acetabular implants to exhibit degradation of mechanical behavior following gamma irradiation in air and accelerated aging; and (3) to compare the oxidation of gamma-air sterilized PCU following accelerated aging and 5 years of natural shelf aging. In addition to attenuated total reflectance-Fourier transform infrared spectroscopy, we also adapted a miniature specimen mechanical test, the small punch test, for the deformable PCU cups. Accelerated aging was performed using ASTM F2003, a standard test that represents a severe oxidative challenge. The results of this study suggest that the small punch test is sufficiently sensitive and reproducible to discriminate slight differences in the large-deformation mechanical behavior of Bionate 80A following accelerated aging. The gamma-air sterilized PCU had a reduction of 9% in ultimate load after aging. Five years of shelf aging had little effect on the mechanical properties of the PCU. Overall, our findings suggest that the Bionate 80A material has greater oxidative stability than ultra-high molecular weight polyethylene following gamma irradiation in air and exposure to a severe oxidative challenge. (c) 2010 Wiley Periodicals, Inc.

  19. Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

    PubMed Central

    Perna, Giampaolo; Iannone, Giuseppe; Alciati, Alessandra; Caldirola, Daniela

    2016-01-01

    Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Aβ accumulation, and immune-inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID:26881136

  20. Accelerated aging of concrete : a literature review

    DOT National Transportation Integrated Search

    2002-02-01

    This report provides a review of the literature on accelerated aging of concrete. It was undertaken, as part of a research project : on predicting the long-term environmental performance of Portland cement concrete (PCC) pavements containing coal fly...

  1. Accelerated aging of phenolic-bonded flakeboards

    Treesearch

    Andrew J. Baker; Robert H. Gillespie

    1978-01-01

    Specimens of phenolic-bonded flakeboard, vertical-grain southern pine and Douglas-fir, and marine-grade Douglas-fir plywood were exposed to four accelerated aging situations. These consisted of: 1) Multiple cycles of boiling and elevated-temperature drying, 2) multiple cycles of vacuum- pressure soaking and intermediate-temperature drying, 3) the six-cycle ASTM D-1037...

  2. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity

    PubMed Central

    Liu, Peiying; Hebrank, Andrew C.; Rodrigue, Karen M.; Kennedy, Kristen M.; Section, Jarren; Park, Denise C.; Lu, Hanzhang

    2013-01-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right side of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions. PMID:23624491

  3. [The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

    PubMed

    Bashkireva, A S

    2012-01-01

    The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

  4. HIV-associated cellular senescence: A contributor to accelerated aging.

    PubMed

    Cohen, Justin; Torres, Claudio

    2017-07-01

    Due to the advent of antiretroviral therapy HIV is no longer a terminal disease and the HIV infected patients are becoming increasingly older. While this is a major success, with increasing age comes an increased risk for disease. The age-related comorbidities that HIV infected patients experience suggest that they suffer from accelerated aging. One possible contributor to this accelerated aging is cellular senescence, an age-associated response that can occur prematurely in response to stress, and that is emerging as a contributor to disease and aging. HIV patients experience several stressors such as the virus itself, antiretroviral drugs and to a lesser extent, substance abuse that can induce cellular senescence. This review summarizes the current knowledge of senescence induction in response to these stressors and their relation to the comorbidities in HIV patients. Cellular senescence may be a possible therapeutic target for these comorbidities. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

    PubMed

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-06-01

    Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and

  6. Activation of the NLRP3 inflammasome induces vascular dysfunction in obese OLETF rats

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

    Liu, Penghao; Xie, Qihai; Wei, Tong

    Objective: Obesity-induced vascular dysfunction is related to chronic low-grade systemic inflammation. Recent studies indicate that NLRP3, a multiprotein complex formed by NOD-like receptor (NLR) family members, is a key component mediating internal sterile inflammation, but the role in obesity-related vascular dysfunction is largely unknown. In the present study, we investigate whether NLRP3 activation is involved in vascular inflammation in obese Otsuka Long-Evans Tokushima Fatty rats (OLETF). Methods and results: Male OLETF with their control Long-Evans Tokushima Otsuka rats (LETO) were studied at 3 and 12 months of age. Aortic relaxation in response to acetylcholine decreased gradually with age in bothmore » strains, with early and persistent endothelium dysfunction in obese OLETF compared with age-matched LETO controls. These changes are associated with parallel changes of aortic endothelial nitric oxide synthase (eNOS) content, macrophage accumulation and intimal thickening. NLRP3 increased in OLETF rats compared to LETO. Consistent with inflammasome activation, the conversion of procaspase-1 to cleaved and activated forms as well as IL-1β markedly increased in OLETF rats. Additionally, we observed increased expression of dynamin-related protein-1 (Drp1) and decreased fusion-relative protein optic atropy-1(OPA1). Altered mitochondrial dynamics was associated with elevated oxidative stress level in OLETF aortas. Conclusions: These results demonstrate that obesity seems to accelerate endothelial dysfunction in OLETFs via the activation of NLRP3 and mitochondrial dysfunction. - Highlights: • NLRP3 is involved in obesity-induced vascular dysfunction. • Impaired mitochondrial dynamics may have been linked to mitochondrial defect and inflammasome activation. • Obesity seems to accelerate vascular dysfunction via NLRP3 activation and mitochondrial dysfunction.« less

  7. Accelerated Aging in Electrolytic Capacitors for Prognostics

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

    2012-01-01

    The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

  8. Effect of long-term treatment with melatonin on vascular markers of oxidative stress/inflammation and on the anticontractile activity of perivascular fat in aging mice.

    PubMed

    Agabiti-Rosei, Claudia; Favero, Gaia; De Ciuceis, Carolina; Rossini, Claudia; Porteri, Enzo; Rodella, Luigi Fabrizio; Franceschetti, Lorenzo; Maria Sarkar, Anna; Agabiti-Rosei, Enrico; Rizzoni, Damiano; Rezzani, Rita

    2017-01-01

    Some reports have suggested that inflammation in perivascular adipose tissue (PVAT) may be implicated in vascular dysfunction by causing the disappearance of an anticontractile effect. The aim of this study was to investigate the effects of chronic melatonin treatment on the functional responses of the small mesenteric arteries and on the expression of markers of inflammation/oxidative stress in the aortas of senescence-accelerated prone mice (SAMP8), a model of age-related vascular dysfunction. We investigated seven SAMP8 and seven control senescence-accelerated resistant mice (SAMR1) treated for 10 months with melatonin, as well as equal numbers of age-matched untreated SAMP8 and SAMR1. The mesenteric small resistance arteries were dissected and mounted on a wire myograph, and the concentration-response to norepinephrine was evaluated in vessels with intact PVAT and after the removal of the PVAT. The expression of markers of oxidative stress, inflammation and aging in the aortas was evaluated by immunostaining. In addition, the adiponectin content and the expression of adiponectin receptor 1 were evaluated in the visceral adipose tissue. In untreated SAMP8 mice, we observed an overexpression of oxidative stress and inflammatory markers in the vasculature compared with the controls. No anticontractile effect of the PVAT was observed in untreated SAMP8 mice. Long-term treatment of SAMP8 mice with melatonin increased the expression of some markers of vasoprotection, decreased oxidative stress and inflammation and restored the anticontractile effect of the PVAT. Decreased expression of adiponectin and adiponectin receptor 1 was also observed in visceral fat of untreated SAMP8, whereas a significant increase was observed after melatonin treatment.

  9. Vascular, inflammatory, and metabolic factors associated with cognition in aging persons with chronic epilepsy.

    PubMed

    Hermann, Bruce P; Sager, Mark A; Koscik, Rebecca L; Young, Kate; Nakamura, Keith

    2017-11-01

    We examined cognition in aging persons with chronic epilepsy; characterized targeted vascular, inflammatory, and metabolic risk factors associated with abnormal cognitive aging in the general population; and examined associations between cognition and vascular, inflammatory, and metabolic health. Participants included 40 persons with chronic localization-related epilepsy and 152 controls, aged 54.6 and 55.3, respectively. Participants underwent neuropsychological assessment, clinical examination, and fasting blood evaluation for quantification of vascular status (systolic and diastolic blood pressure, obesity/body mass index [BMI], total and high-density lipoprotein [HDL] cholesterol level, and homocysteine), inflammatory markers (high sensitivity C-reactive protein [hs-CRP], and interleukin-6 [IL-6]), and metabolic status (insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], glucose). Epilepsy participants exhibited impairment across all cognitive factor scores (all p's < 0.0001); abnormalities in BMI (p = 0.049), hs-CRP (p = 0.046), HOMA-IR (p = 0.0040), and fasting glucose (p = 0.03), with significant relationships between higher HOMA-IR with poorer Immediate Memory (p = 0.03) and Visuospatial Ability (0.03); elevated hs-CRP with poorer Visuospatial (p = 0.035) and Verbal Ability (p = 0.06); elevated BMI with poorer Speed/Flexibility (p = 0.04), Visuospatial (p = 0.001) and Verbal Ability (p = 0.02); and lower HDL with poorer Verbal Learning/Delayed Memory (p = 0.01), Speed/Flexibility (p = 0.043), and Working Memory (p = 0.008). Aging persons with chronic epilepsy exhibit multiple abnormalities in metabolic, inflammatory, and vascular health that are associated with poorer cognitive function. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  10. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

    PubMed

    Lacey, Ben; Lewington, Sarah; Clarke, Robert; Kong, Xiang Ling; Chen, Yiping; Guo, Yu; Yang, Ling; Bennett, Derrick; Bragg, Fiona; Bian, Zheng; Wang, Shaojie; Zhang, Hua; Chen, Junshi; Walters, Robin G; Collins, Rory; Peto, Richard; Li, Liming; Chen, Zhengming

    2018-06-01

    The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1

  11. Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention.

    PubMed

    Nilsson, Peter M; Boutouyrie, Pierre; Cunha, Pedro; Kotsis, Vasilios; Narkiewicz, Krzysztof; Parati, Gianfranco; Rietzschel, Ernst; Scuteri, Angelo; Laurent, Stephane

    2013-08-01

    The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

  12. [Brain Perfusion, Cognitive Functions, and Vascular Age in Middle Aged Patients With Essential Arterial Hypertension].

    PubMed

    Parfenov, V A; Ostroumova, T M; Pеrepelova, E M; Perepelov, V A; Kochetkov, A I; Ostroumova, O D

    2018-05-01

    This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10‑item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques - using Framingham Heart Study risk tables and SCORE project scales. Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, р=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (р=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml / 100 g / min) and left frontal lobes of the brain (39.2±6.2 и 45.2±3.6 ml / 100 g / min, respectively) compared to controls (р.

  13. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    PubMed

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Accelerated Aging of Lead-Free Propellant

    NASA Technical Reports Server (NTRS)

    Furrow, Keith W.; Jervey, David D.

    2000-01-01

    Following higher than expected 2-NDPA depletion rates in a lead-free doublebase formulation (RPD-422), an accelerated aging study was conducted to verify the depletion rates. A test plan was prepared to compare the aging characteristics of lead-free propellant and NOSIH-AA2. The study was also designed to determine which lead-free ballistic modifiers accelerated 2-NDPA depletion. The increased depletion rate occurred in propellants containing monobasic copper salicylate. Four lead-free propellants were then formulated to improved aging characteristics over previous lead-free propellant formulations. The new formulations reduced or replaced the monobasic copper salicylate. The new formulations had improved aging characteristics. Their burn rates, however, were unacceptable for use in a 2.75 inch rocket. To compare aging characteristics, stabilizer depletion rates of RPD-422, AA2, M28, and RLC 470/6A were measured or taken from the literature. The data were fit to a kinetic model. The model contained first and zero order terms which allowed the stabilizer concentration to go to zero. In the model, only the concentration of the primary stabilizer was considered. Derivatives beyond the first nitrated or nitroso derivative of 2-NPDA were not considered. The rate constants were fit to the Arrhenius equation and extrapolated to lower temperatures. The time to complete stabilizer depletion was estimated using the kinetic model. The four propellants were compared and the RPD-422 depleted faster at 45 C than both A22 and M28. These types of predictions depend on the validity of the model and on confidence in the Arrhenius relationship holding at lower temperatures. At 45 C, the zero order portion of the model dominates the depletion rate.

  15. miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular aging.

    PubMed

    Zhan, Jiaxin; Qin, Shanshan; Lu, Lili; Hu, Xiamin; Zhou, Jun; Sun, Yeying; Yang, Jian; Liu, Ying; Wang, Zunzhe; Tan, Ning; Chen, Jiyan; Zhang, Chunxiang

    2016-11-26

    Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC senescence was exacerbated by miR-34a overexpression. In addition, the vascular ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy-mediated vascular aging.

  16. Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

    PubMed

    Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

    2011-08-01

    Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

  17. Aerobic Exercise and Other Healthy Lifestyle Factors That Influence Vascular Aging

    ERIC Educational Resources Information Center

    Santos-Parker, Jessica R.; LaRocca, Thomas J.; Seals, Douglas R

    2014-01-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development…

  18. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    PubMed

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  19. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  20. Phospho1 deficiency transiently modifies bone architecture yet produces consistent modification in osteocyte differentiation and vascular porosity with ageing

    PubMed Central

    Javaheri, B.; Carriero, A.; Staines, K.A.; Chang, Y.-M.; Houston, D.A.; Oldknow, K.J.; Millan, J.L.; Kazeruni, Bassir N.; Salmon, P.; Shefelbine, S.; Farquharson, C.; Pitsillides, A.A.

    2015-01-01

    PHOSPHO1 is one of principal proteins involved in initiating bone matrix mineralisation. Recent studies have found that Phospho1 KO mice (Phospho1-R74X) display multiple skeletal abnormalities with spontaneous fractures, bowed long bones, osteomalacia and scoliosis. These analyses have however been limited to young mice and it remains unclear whether the role of PHOSPHO1 is conserved in the mature murine skeleton where bone turnover is limited. In this study, we have used ex-vivo computerised tomography to examine the effect of Phospho1 deletion on tibial bone architecture in mice at a range of ages (5, 7, 16 and 34 weeks of age) to establish whether its role is conserved during skeletal growth and maturation. Matrix mineralisation has also been reported to influence terminal osteoblast differentiation into osteocytes and we have also explored whether hypomineralised bones in Phospho1 KO mice exhibit modified osteocyte lacunar and vascular porosity. Our data reveal that Phospho1 deficiency generates age-related defects in trabecular architecture and compromised cortical microarchitecture with greater porosity accompanied by marked alterations in osteocyte shape, significant increases in osteocytic lacuna and vessel number. Our in vitro studies examining the behaviour of osteoblast derived from Phospho1 KO and wild-type mice reveal reduced levels of matrix mineralisation and modified osteocytogenic programming in cells deficient in PHOSPHO1. Together our data suggest that deficiency in PHOSPHO1 exerts modifications in bone architecture that are transient and depend upon age, yet produces consistent modification in lacunar and vascular porosity. It is possible that the inhibitory role of PHOSPHO1 on osteocyte differentiation leads to these age-related changes in bone architecture. It is also intriguing to note that this apparent acceleration in osteocyte differentiation evident in the hypomineralised bones of Phospho1 KO mice suggests an uncoupling of the interplay

  1. Accelerated aging test results for aerospace wire insulation constructions

    NASA Technical Reports Server (NTRS)

    Dunbar, William G.

    1995-01-01

    Several wire insulation constructions were evaluated with and without continuous glow discharges at low pressure and high temperature to determine the aging characteristics of acceptable wire insulation constructions. It was known at the beginning of the test program that insulation aging takes several years when operated at normal ambient temperature and pressure of 20 C and 760 torr. Likewise, it was known that the accelerated aging process decreases insulation life by approximately 50% for each 10 C temperature rise. Therefore, the first phases of the program, not reported in these test results, were to select wire insulation constructions that could operate at high temperature and low pressure for over 10,000 hours with negligible shrinkage and little materials' deterioration.The final phase of the program was to determine accelerated aging characteristics. When an insulation construction is subjected to partial discharges the insulation is locally heated by the bombardment of the discharges, the insulation is also subjected to ozone and other deteriorating gas particles that may significantly increase the aging process. Several insulation systems using either a single material or combinations of teflon, kapton, and glass insulation constructions were tested. All constructions were rated to be partial discharge and/or corona-free at 240 volts, 400 Hz and 260 C (500 F) for 50, 000 hours at altitudes equivalent to the Paschen law. Minimum partial discharge aging tests were preceded by screening tests lasting 20 hours at 260 C. The aging process was accelerated by subjecting the test articles to temperatures up to 370 C (700 F) with and without partial discharges. After one month operation with continuous glow discharges surrounding the test articles, most insulation systems were either destroyed or became brittle, cracked, and unsafe for use. Time with space radiation as with partial discharges is accumulative.

  2. Accelerated aging test results for aerospace wire insulation constructions

    NASA Astrophysics Data System (ADS)

    Dunbar, William G.

    1995-11-01

    Several wire insulation constructions were evaluated with and without continuous glow discharges at low pressure and high temperature to determine the aging characteristics of acceptable wire insulation constructions. It was known at the beginning of the test program that insulation aging takes several years when operated at normal ambient temperature and pressure of 20 C and 760 torr. Likewise, it was known that the accelerated aging process decreases insulation life by approximately 50% for each 10 C temperature rise. Therefore, the first phases of the program, not reported in these test results, were to select wire insulation constructions that could operate at high temperature and low pressure for over 10,000 hours with negligible shrinkage and little materials' deterioration.The final phase of the program was to determine accelerated aging characteristics. When an insulation construction is subjected to partial discharges the insulation is locally heated by the bombardment of the discharges, the insulation is also subjected to ozone and other deteriorating gas particles that may significantly increase the aging process. Several insulation systems using either a single material or combinations of teflon, kapton, and glass insulation constructions were tested. All constructions were rated to be partial discharge and/or corona-free at 240 volts, 400 Hz and 260 C (500 F) for 50, 000 hours at altitudes equivalent to the Paschen law. Minimum partial discharge aging tests were preceded by screening tests lasting 20 hours at 260 C. The aging process was accelerated by subjecting the test articles to temperatures up to 370 C (700 F) with and without partial discharges. After one month operation with continuous glow discharges surrounding the test articles, most insulation systems were either destroyed or became brittle, cracked, and unsafe for use. Time with space radiation as with partial discharges is accumulative.

  3. The influences of accelerated aging on mechanical properties of veneering ceramics used for zirconia restorations.

    PubMed

    Luo, Huinan; Tang, Xuehua; Dong, Zhen; Tang, Hui; Nakamura, Takashi; Yatani, Hirofumi

    2016-01-01

    This study evaluated the influences of accelerated aging on the mechanical properties of veneering ceramics used for zirconia frameworks. Five different veneering ceramics for zirconia frameworks were used. Twenty specimens were fabricated for each veneering ceramic. All specimens were divided into two groups. One was subjected to accelerated aging and the other was used as a control. Accelerated aging was performed in distilled water for 5 h at 200ºC and 2 atm. The density, open porosity, surface roughness, three-point flexural strength, and Vickers hardness were measured. The results showed that the density, open porosity, and surface roughness of all examined veneering ceramics were changed by the accelerated aging process. Accelerated aging was also found to have a positive effect on strength and a negative effect on the hardness.

  4. Accelerated aging and stabilization of radiation-vulcanized EPDM rubber

    NASA Astrophysics Data System (ADS)

    Basfar, A. A.; Abdel-Aziz, M. M.; Mofti, S.

    2000-03-01

    The effect of different antioxidants and their mixtures on the thermal aging and accelerated weathering of γ-radiation vulcanized EPDM rubber in presence of crosslinking coagent, was investigated. The compounds used were either a synergistic blend of phenolic and phosphite antioxidants, i.e. 1:4 Irganox 1076: Irgafos 168 or a blend of arylamine and quinoline type antioxidants, i.e. 1:1 IPPD: TMQ, at fixed concentration. Tinuvin 622 LD hindered amine light stabilized (HALS) was also used. The response was evaluated by the tensile strength and elongation at break for irradiated samples after thermal aging at 100°C for 28 days and accelerated weathering (Xenon test) up to 200 h.

  5. Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

    DTIC Science & Technology

    2011-09-01

    possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to...suffer from two damage types: matrix micro-cracks and inter- laminar delamination. When subject to fatigue loading matrix micro-cracks develop in the

  6. Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave Properties from a Single Aortic Pressure Pulse

    PubMed Central

    Chang, Chun-Yi; Chang, Ru-Wen; Hsu, Shu-Hsien; Wu, Ming-Shiou; Cheng, Ya-Jung; Kao, Hsien-Li; Lai, Liang-Chuan; Wang, Chih-Hsien; Chang, Kuo-Chu

    2017-01-01

    Changes in vascular mechanics due to aging include elevated vascular impedance, diminished aorta distensibility, and an accelerated return of pulse wave reflection, which may increase the systolic workload on the heart. Classically, the accurate measurement of vascular mechanics requires the simultaneous recording of aortic pressure and flow signals. In practice, it is feasible to estimate arterial wave properties in terms of wave transit time (τw) and wave reflection index (RI) by using aortic pressure signal alone. In this study, we determined the τw and magnitudes of the forward (∣Pf∣) and backward (∣Pb∣) pressure waves in Long–Evans male rats aged 4 (n = 14), 6 (n = 17), 12 (n = 17), and 18 (n = 24) months, based on the measured aortic pressure and an assumed triangular flow (Qtri). The pulsatile pressure wave was the only signal recorded in the ascending aorta by using a high-fidelity pressure sensor. The base of the unknown Qtri was constructed using a duration, which equals to the ejection time. The timing at the peak of the triangle was derived using the fourth-order derivative of the aortic pressure waveform. In the 18-month-old rats, the ratio of τw to left ventricular ejection time (LVET) decreased, indicating a decline in the distensibility of the aorta. The increased ∣Pb∣ associated with unaltered ∣Pf∣ enhanced the RI in the older rats. The augmentation index (AI) also increased significantly with age. A significant negative correlation between the AI and τw/LVET was observed: AI = −0.7424 − 0.9026 × (τw/LVET) (r = 0.4901; P < 0.0001). By contrast, RI was positively linearly correlated with the AI as follows: AI = −0.4844 + 2.3634 × RI (r = 0.8423; P < 0.0001). Both the decreased τw/LVET and increased RI suggested that the aging process may increase the AI, thereby increasing the systolic hydraulic load on the heart. The novelty of the study is that Qtri is constructed using the measured aortic pressure wave to

  7. Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave Properties from a Single Aortic Pressure Pulse.

    PubMed

    Chang, Chun-Yi; Chang, Ru-Wen; Hsu, Shu-Hsien; Wu, Ming-Shiou; Cheng, Ya-Jung; Kao, Hsien-Li; Lai, Liang-Chuan; Wang, Chih-Hsien; Chang, Kuo-Chu

    2017-01-01

    Changes in vascular mechanics due to aging include elevated vascular impedance, diminished aorta distensibility, and an accelerated return of pulse wave reflection, which may increase the systolic workload on the heart. Classically, the accurate measurement of vascular mechanics requires the simultaneous recording of aortic pressure and flow signals. In practice, it is feasible to estimate arterial wave properties in terms of wave transit time (τ w ) and wave reflection index (RI) by using aortic pressure signal alone. In this study, we determined the τ w and magnitudes of the forward (∣ P f ∣) and backward (∣ P b ∣) pressure waves in Long-Evans male rats aged 4 ( n = 14), 6 ( n = 17), 12 ( n = 17), and 18 ( n = 24) months, based on the measured aortic pressure and an assumed triangular flow ( Q tri ). The pulsatile pressure wave was the only signal recorded in the ascending aorta by using a high-fidelity pressure sensor. The base of the unknown Q tri was constructed using a duration, which equals to the ejection time. The timing at the peak of the triangle was derived using the fourth-order derivative of the aortic pressure waveform. In the 18-month-old rats, the ratio of τ w to left ventricular ejection time (LVET) decreased, indicating a decline in the distensibility of the aorta. The increased ∣ P b ∣ associated with unaltered ∣ P f ∣ enhanced the RI in the older rats. The augmentation index (AI) also increased significantly with age. A significant negative correlation between the AI and τ w /LVET was observed: AI = -0.7424 - 0.9026 × (τ w /LVET) ( r = 0.4901; P < 0.0001). By contrast, RI was positively linearly correlated with the AI as follows: AI = -0.4844 + 2.3634 × RI ( r = 0.8423; P < 0.0001). Both the decreased τ w /LVET and increased RI suggested that the aging process may increase the AI, thereby increasing the systolic hydraulic load on the heart. The novelty of the study is that Q tri is constructed using the measured aortic

  8. Effect of accelerated aging on the viscoelastic properties of a medical grade silicone.

    PubMed

    Mahomed, Aziza; Hukins, David W L; Kukureka, Stephen N

    2015-01-01

    The viscoelastic properties of cylinders (diameter 5 mm, height 2.2 ± 0.2 mm) of Nagor silicone elastomer of medium hardness, were investigated before and after the specimens had undergone accelerated aging in saline solution at 70°C for 38, 76 and 114 days (to simulate aging at 37°C, for 1, 2 and 3 years, respectively). All sets of specimens were immersed in physiological saline solution at 37°C during testing and the properties were measured using dynamic mechanical analysis (DMA). A sinusoidal cyclic compression of 40 N ± 5 N was applied over a frequency range, f, of 0.02-25 Hz. Values of the storage, E', and loss, E″, moduli were found to depend on f; the dependence of E' or E″ on the logarithm (base 10) of f was represented by a second-order polynomial. After accelerated aging, the E' and E″ values did not increase significantly (p<0.05). Furthermore, scanning electron microscopy (SEM) showed that accelerated aging did not affect the surface morphology of silicone. Attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) showed that accelerated aging had a negligible effect on the surface chemical structures of the material. Differential scanning calorimetry (DSC) showed no changes to the bulk properties of silicone, following accelerated aging.

  9. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

    PubMed

    Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

    2016-11-01

    The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Self-Replenishing Vascularized Fouling-Release Surfaces

    DOE PAGES

    Howell, Caitlin; Vu, Thy L.; Lin, Jennifer J.; ...

    2014-08-13

    Inspired by the long-term effectiveness of living antifouling materials, we have developed a method for the selfreplenishment of synthetic biofouling-release surfaces. These surfaces are created by either molding or directly embedding 3D vascular systems into polydimethylsiloxane (PDMS) and filling them with a silicone oil to generate a nontoxic oil-infused material. When replenished with silicone oil from an outside source, these materials are capable of self-lubrication and continuous renewal of the interfacial fouling-release layer. Under accelerated lubricant loss conditions, fully infused vascularized samples retained significantly more lubricant than equivalent nonvascularized controls. Tests of lubricant-infused PDMS in static cultures of the infectiousmore » bacteria Staphylococcus aureus and Escherichia coli as well as the green microalgae Botryococcus braunii, Chlamydomonas reinhardtii, Dunaliella salina, and Nannochloropsis oculata showed a significant reduction in biofilm adhesion compared to PDMS and glass controls containing no lubricant. Further experiments on vascularized versus nonvascularized samples that had been subjected to accelerated lubricant evaporation conditions for up to 48 h showed significantly less biofilm adherence on the vascularized surfaces. These results demonstrate the ability of an embedded lubricant-filled vascular network to improve the longevity of fouling-release surfaces.« less

  11. Effect of accelerated aging on the cross-link density of medical grade silicones.

    PubMed

    Mahomed, Aziza; Pormehr, Negin Bagheri

    2016-11-25

    Four specimens of Nagor silicone of different hardness (soft, medium and hard) were swollen, until they reached equilibrium (i.e. constant mass) in five liquids at 25°C, before and after accelerated aging. For the specimens swollen before accelerated aging, the greatest swelling was obtained in methyl cyclohexane, while for the specimens swollen after accelerated aging, the greatest swelling was obtained in cyclohexane. The cross-link density, υ, was also calculated from the swelling measurements for all the specimens, before and after accelerated aging, using the Flory-Rehner equation. The softer silicones, which swelled the most, had lower υ values than harder silicones. The amount of swelling (measured in terms of ϕ) and υ varied significantly (p<0.05) in some cases, between the different silicone hardness and between different liquids. Furthermore, the cross-link density, υ, significantly (p<0.05) increased after accelerated aging in most liquids.Note: ϕ is defined as the volume fraction of polymer in its equilibrium swollen state. A probability value of statistical significance of 0.05 or 5% was selected, hence if a p value of less than 0.05 was obtained, the null hypothesis was rejected (i.e. significant if p<0.05).

  12. Estrogen Effects on Vascular Inflammation are Age-Dependent: Role of Estrogen Receptors

    PubMed Central

    Kapadia, Akash; Chen, Yiu-Fai; Szalai, Alexander J.; Oparil, Suzanne; Hage, Fadi G.

    2014-01-01

    Objective 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones carried out in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age-dependent. Approach and Results Young (10-wk) and aged (52-wk) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pre-treatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pre-treatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER)-knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERβ. BMMs derived from aged (vs. young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. Conclusions E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age-dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. PMID:24876352

  13. Accelerated White Matter Aging in Schizophrenia: Role of White Matter Blood Perfusion

    PubMed Central

    Chiappelli, Joshua; McMahon, Robert; Muellerklein, Florian; Wijtenburg, S. Andrea; White, Michael G.; Rowland, Laura M.; Hong, L. Elliot

    2014-01-01

    Elevated rate of age-related decline in white matter integrity, indexed by fractional anisotropy (FA) from diffusion tensor imaging, was reported in patients with schizophrenia. Its etiology is unknown. We hypothesized that a decline of blood perfusion to the white matter may underlie the accelerated age-related reduction in FA in schizophrenia. Resting white matter perfusion and FA were collected using pseudo-continuous arterial spin labeling and high-angular-resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients and 70 controls (age=18-63 years). Main outcome measures were the diagnosis-by-age interaction on whole-brain white matter perfusion, and FA. Significant age-related decline in brain white matter perfusion and FA were present in both groups. Age-by-diagnosis interaction was significant for FA (p<0.001) but not white matter perfusion. Age-by-diagnosis interaction for FA values remained significant even after accounting for age-related decline in perfusion. Therefore, we replicated the finding of an increased rate of age-related white matter FA decline in schizophrenia, and observed a significant age-related decline in white matter blood perfusion, although the latter did not contribute to the accelerated age-related decline in FA. The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia. PMID:24680326

  14. Insights into accelerated aging of SSL luminaires

    NASA Astrophysics Data System (ADS)

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; Shepherd, Sarah; Yaga, Robert; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy

    2013-09-01

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6" downlights in environments of 85°C and 85% relative humidity (RH) and 75°C and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.

  15. Accelerated Aging Experiments for Capacitor Health Monitoring and Prognostics

    NASA Technical Reports Server (NTRS)

    Kulkarni, Chetan S.; Celaya, Jose Ramon; Biswas, Gautam; Goebel, Kai

    2012-01-01

    This paper discusses experimental setups for health monitoring and prognostics of electrolytic capacitors under nominal operation and accelerated aging conditions. Electrolytic capacitors have higher failure rates than other components in electronic systems like power drives, power converters etc. Our current work focuses on developing first-principles-based degradation models for electrolytic capacitors under varying electrical and thermal stress conditions. Prognostics and health management for electronic systems aims to predict the onset of faults, study causes for system degradation, and accurately compute remaining useful life. Accelerated life test methods are often used in prognostics research as a way to model multiple causes and assess the effects of the degradation process through time. It also allows for the identification and study of different failure mechanisms and their relationships under different operating conditions. Experiments are designed for aging of the capacitors such that the degradation pattern induced by the aging can be monitored and analyzed. Experimental setups and data collection methods are presented to demonstrate this approach.

  16. Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

    PubMed

    Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L

    2011-01-01

    This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

  17. Exercise training, vascular function, and functional capacity in middle-aged subjects.

    PubMed

    Maiorana, A; O'Driscoll, G; Dembo, L; Goodman, C; Taylor, R; Green, D

    2001-12-01

    The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

  18. Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression.

    PubMed

    Kochunov, Peter; Glahn, David C; Rowland, Laura M; Olvera, Rene L; Winkler, Anderson; Yang, Yi-Hong; Sampath, Hemalatha; Carpenter, Will T; Duggirala, Ravindranath; Curran, Joanne; Blangero, John; Hong, L Elliot

    2013-03-01

    Elevated rate of aging-related biological and functional decline, termed "accelerated aging," is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging derived fractional anisotropy (FA) as a biomarker of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. The SCZ cohort comprised 58 SCZ patients and 60 controls (aged 20-60 years). The MDD cohort comprised 136 MDD patients and 351 controls (aged 20-79 years). The main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from 12 major WM tracts. Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p = .04) but not the MDD (p = .80) cohort. Diagnosis-by-age interaction was nominally significant (p<.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of-peak myelination and the rates of age-related decline obtained from normative sample (r =-.61 and-.80, p<.05, respectively). No such trends existed for MDD cohort. Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: WM tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Testing the hypothesis of accelerated cerebral white matter aging in schizophrenia and major depression

    PubMed Central

    Kochunov, P.; Glahn, D.C.; Rowland, L.M.; Olvera, R.L.; Winkler, A; Yang, Y.H.; Sampath, H.; Carpenter, W.T.; Dugarrila, R.; Curran, J.; Blangero, J.; Hong, L.E.

    2012-01-01

    Introduction Elevated rate of aging-related biological and functional decline, termed accelerated aging, is reported in patients with schizophrenia (SCZ) and major depressive disorder (MDD). We used diffusion tensor imaging (DTI) derived fractional anisotropy (FA) as biomarkers of aging-related decline in white matter (WM) integrity to test the hypotheses of accelerated aging in SCZ and MDD. Methods The SCZ cohort was composed of 58/60 SCZ patients/controls (age=20–60years). MDD cohort was composed of 136/351 MDD patients/controls (age=20–79years). Main outcome measures were the diagnosis-by-age interaction on whole-brain-averaged WM FA values and FA values from twelve major WM tracts. Results Diagnosis-by-age interaction for the whole-brain average FA was significant for the SCZ (p=0.04) but not in MDD cohort (p=0.80). Diagnosis-by-age interaction was nominally significant (p<0.05) for five WM tracts for SCZ and for none of the tracts in the MDD cohort. Tract-specific heterochronicity of the onset of age-related decline in SCZ demonstrated strong negative correlations with the age-of- peak myelination and the rates of age-related decline obtained from normative sample (r=−0.61 and −0.80, p<0.05, respectively). No such trends existed for MDD cohort. Conclusion Cerebral WM showed accelerated aging in SCZ but not in MDD, suggesting some difference in the pathophysiology underlying their WM aging changes. Tract-specific heterochronicity of WM development modulated presentation of accelerated aging in SCZ: white matter tracts that matured later in life appeared more sensitive to the pathophysiology of SCZ and demonstrated more susceptibility to disorder-related accelerated decline in FA values with age. This trend was not observed in MDD cohort. PMID:23200529

  20. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake.

    PubMed

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G

    2016-05-01

    We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

  1. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

    2015-10-27

    A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

  2. Retinal Vascular Fractal Dimension, Childhood IQ, and Cognitive Ability in Old Age: The Lothian Birth Cohort Study 1936

    PubMed Central

    Taylor, Adele M.; MacGillivray, Thomas J.; Henderson, Ross D.; Ilzina, Lasma; Dhillon, Baljean; Starr, John M.; Deary, Ian J.

    2015-01-01

    Purpose Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (D f) as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability. Methods Participants from the Lothian Birth Cohort 1936 Study (LBC1936) had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648). IQ scores were available from childhood. Retinal vascular D f was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular D f and general cognitive ability (g), processing speed, and memory. Results Only three out of 24 comparisons (two eyes × four D f parameters × three cognitive measures) were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye. Conclusions The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing. PMID:25816017

  3. Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

    PubMed

    Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

    2017-07-01

    Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

  4. Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.

    PubMed

    Nam, Mi-Hyun; Son, Won-Rak; Lee, Young Sik; Lee, Kwang-Won

    Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.

  5. Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

    PubMed

    MacNee, William

    2016-12-01

    Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

  6. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging

    PubMed Central

    Ohnishi, Mutsuko; Razzaque, M. Shawkat

    2010-01-01

    Identifying factors that accelerate the aging process can provide important therapeutic targets for slowing down this process. Misregulation of phosphate homeostasis has been noted in various skeletal, cardiac, and renal diseases, but the exact role of phosphate toxicity in mammalian aging is not clearly defined. Phosphate is widely distributed in the body and is involved in cell signaling, energy metabolism, nucleic acid synthesis, and the maintenance of acid-base balance by urinary buffering. In this study, we used an in vivo genetic approach to determine the role of phosphate toxicity in mammalian aging. Klotho-knockout mice (klotho−/−) have a short life span and show numerous physical, biochemical, and morphological features consistent with premature aging, including kyphosis, uncoordinated movement, hypogonadism, infertility, severe skeletal muscle wasting, emphysema, and osteopenia, as well as generalized atrophy of the skin, intestine, thymus, and spleen. Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho−/− mice. Genetically reducing serum phosphate levels in klotho−/− mice by generating a NaPi2a and klotho double-knockout (NaPi2a−/−/klotho−/−) strain resulted in amelioration of premature aging-like features. The NaPi2a−/−/klotho−/− double-knockout mice regained reproductive ability, recovered their body weight, reduced their organ atrophy, and suppressed ectopic calcifications, with the resulting effect being prolonged survival. More important, when hyperphosphatemia was induced in NaPi2a−/−/klotho−/− mice by feeding with a high-phosphate diet, premature aging-like features reappeared, clearly suggesting that phosphate toxicity is the main cause of premature aging in klotho−/− mice. The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the

  7. Insights into accelerated aging of SSL luminaires

    DOE PAGES

    Davis, J. Lynn; Lamvik, Michael; Bittle, James; ...

    2013-09-30

    Although solid-state lighting (SSL) products are often intended to have product lifetimes of 15 years or more, the rapid change in technology has created a need for accelerated life tests (ALTs) that can be performed in the span of several months. A critical element of interpreting results from any systems-level ALT is understanding of the impact of the test environment on each component. Because of its ubiquity in electronics, the use of temperature-humidity environments as potential ALTs for SSL luminaires was investigated. Results from testing of populations of three commercial 6” downlights in environments of 85oC and 85% relative humiditymore » (RH) and 75oC and 75% RH are reported. These test environments were found to accelerate lumen depreciation of the entire luminaire optical system, including LEDs, lenses, and reflectors. The effects of aging were found to depend strongly on both the optical materials that were used and the design of the luminaire; this shows that the lumen maintenance behavior of SSL luminaires must be addressed at the optical systems level. Temperature-Humidity ALTs can be a useful test in understand lumainaire depreciation provided that proper consideration is given to the different aging rates of various materials. Since the impact of the temperature-humidity environment varies among components of the optical system, uniform aging of all system components in a single test is difficult to achieve.« less

  8. Body Acceleration as Indicator for Walking Economy in an Ageing Population.

    PubMed

    Valenti, Giulio; Bonomi, Alberto G; Westerterp, Klaas R

    2015-01-01

    In adults, walking economy declines with increasing age and negatively influences walking speed. This study aims at detecting determinants of walking economy from body acceleration during walking in an ageing population. 35 healthy elderly (18 males, age 51 to 83 y, BMI 25.5±2.4 kg/m2) walked on a treadmill. Energy expenditure was measured with indirect calorimetry while body acceleration was sampled at 60Hz with a tri-axial accelerometer (GT3X+, ActiGraph), positioned on the lower back. Walking economy was measured as lowest energy needed to displace one kilogram of body mass for one meter while walking (WCostmin, J/m/kg). Gait features were extracted from the acceleration signal and included in a model to predict WCostmin. On average WCostmin was 2.43±0.42 J/m/kg and correlated significantly with gait rate (r2 = 0.21, p<0.01) and regularity along the frontal (anteroposterior) and lateral (mediolateral) axes (r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively). Together, the three variables explained 46% of the inter-subject variance (p<0.001) with a standard error of estimate of 0.30 J/m/kg. WCostmin and regularity along the frontal and lateral axes were related to age (WCostmin: r2 = 0.44, p<0.001; regularity: r2 = 0.16, p<0.05 and r2 = 0.12, p<0.05 respectively frontal and lateral). The age associated decline in walking economy is induced by the adoption of an increased gait rate and by irregular body acceleration in the horizontal plane.

  9. Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project

    PubMed Central

    Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L.

    2011-01-01

    This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21–30, 31–40, 41–50, 51–60, 61–70, and 71–80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes. PMID:22187622

  10. Subjective memory complaints, vascular risk factors and psychological distress in the middle-aged: a cross-sectional study

    PubMed Central

    2011-01-01

    Background Subjective memory complaints (SMC) are common but their significance is still unclear. It has been suggested they are a precursor of mild cognitive impairment (MCI) or dementia and an early indicator of cognitive decline. Vascular risk factors have an important role in the development of dementia and possibly MCI. We therefore aimed to test the hypothesis that vascular risk factors were associated with SMC, independent of psychological distress, in a middle-aged community-dwelling population. Methods A cross-sectional analysis of baseline data from the 45 and Up Study was performed. This is a cohort study of people living in New South Wales (Australia), and we explored the sample of 45, 532 participants aged between 45 and 64 years. SMC were defined as 'fair' or 'poor' on a self-reported five-point Likert scale of memory function. Vascular risk factors of obesity, diabetes, hypertension, hypercholesterolemia and smoking were identified by self-report. Psychological distress was measured by the Kessler Psychological Distress Scale. We tested the model generated from a randomly selected exploratory sample (n = 22, 766) with a confirmatory sample of equal size. Results 5, 479/45, 532 (12%) of respondents reported SMC. Using multivariate logistic regression, only two vascular risk factors: smoking (OR 1.18; 95% CI = 1.03 - 1.35) and hypercholesterolaemia (OR 1.19; 95% CI = 1.04 - 1.36) showed a small independent association with SMC. In contrast psychological distress was strongly associated with SMC. Those with the highest levels of psychological distress were 7.00 (95% CI = 5.41 - 9.07) times more likely to have SMC than the non-distressed. The confirmatory sample also demonstrated the strong association of SMC with psychological distress rather than vascular risk factors. Conclusions In a large sample of middle-aged people without any history of major affective illness or stroke, psychological distress was strongly, and vascular risk factors only weakly

  11. Accelerated aging-related transcriptome changes in the female prefrontal cortex

    PubMed Central

    Yuan, Yuan; Chen, Yi-Ping Phoebe; Boyd-Kirkup, Jerome; Khaitovich, Philipp; Somel, Mehmet

    2012-01-01

    Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimer’s disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD. PMID:22783978

  12. [PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

    PubMed

    Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

    2015-01-01

    Using comparative analysis of two occupational groups we assessed the significance of psycho physiological markers of short-term memory accelerated aging in order to reveal how the age-related changes and working process affect mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that age and long driving experience affect mnestic functions which show up quantitative and qualitative changes such as reduced volume of memorized information, longer time needed to memorize it, and tendency to diminished accuracy of memorization. We also proved that premature age-related changes of psycho physiological indices in drivers are the "risk indicators", while long driving experience is a real risk factor contributing to the acceleration of aging.

  13. Neural and vascular variability and the fMRI-BOLD response in normal aging

    PubMed Central

    Kannurpatti, Sridhar S.; Motes, Michael A.; Rypma, Bart; Biswal, Bharat B.

    2010-01-01

    Neural, vascular and structural variables contributing to the BOLD signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (6M and 6F; mean age: 24 years; range: 19–27 years) and twelve older healthy subjects (5M and 7F; mean age: 58 years; range: 55–71 years) with no history of head trauma and neurological disease were scanned. FMRI measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45, 40 and 38% in the elderly group during the motor, cognitive and breath hold tasks respectively compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the inter-subject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response. PMID:20117893

  14. Neural and vascular variability and the fMRI-BOLD response in normal aging.

    PubMed

    Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B

    2010-05-01

    Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19-27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55-71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response. 2010 Elsevier Inc. All

  15. DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia.

    PubMed

    McKinney, Brandon C; Lin, Huang; Ding, Ying; Lewis, David A; Sweet, Robert A

    2017-10-05

    Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r=0.92-0.95, p<0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t=0.52, p=0.60), blood dataset #1 (t=1.51, p=0.13), or blood dataset #2 (t=0.93, p=0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  17. Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

    PubMed Central

    Wray, D. Walter; Amann, Markus

    2016-01-01

    The aging process appears to be a precursor to many age-related diseases, perhaps the most impactful of which is cardiovascular disease (CVD). Heart disease, a manifestation of CVD, is the leading cause of death in the USA, and heart failure (HF), a syndrome that develops as a consequence of heart disease, now affects almost six million American. Importantly, as this is an age-related disease, this number is likely to grow along with the ever-increasing elderly population. Hallmarks of the aging process and HF patients with a reduced ejection fraction (HFrEF) include exercise intolerance, premature fatigue, and limited oxygen delivery and utilization, perhaps as a consequence of diminished peripheral vascular function. Free radicals and oxidative stress have been implicated in this peripheral vascular dysfunction, as a redox imbalance may directly impact the function of the vascular endothelium. This review aims to bring together studies that have examined the impact of oxidative stress on peripheral vascular function and oxygen delivery and utilization with both healthy aging and HFrEF. PMID:27392715

  18. [A cohort study on the predictive value of factors influencing cardio-cerebro vascular death among people over 40 years of age].

    PubMed

    Yang, Jian-min; Lu, Fang-hong; Jin, Shi-kuan; Sun, Shang-wen; Zhao, Ying-xin; Wang, Shu-jian; Zhou, Xiao-hong

    2007-02-01

    To explore the factors influencing cardio-cerebro vascular death events among people over 40 years of age in Shandong area, China. Baseline survey was carried out in 1991. A total number of 11,008 adults over 40 years old had been studied in Shandong province. Data on cardiocerebro death was collected. The correlation between influencing factors and cardio-cerebro vascular death events was analyzed by Cox regression model. Totally, 434 cardio-cerebro death events occurred among the 11,008 subjects during the 8-year follow-up study. Cardio-cerebro death events were related to systolic blood pressure, diastolic blood pressure, smoking, stroke history and age. Data from Cox regression analysis showed that the relative risk (RR) for cardio-cerebro vascular death events increased by 2.862 [95% confidence interval (CI): 1.976-4.144] times for those people having stroke history. When systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardio-cerebro vascular death events increased by 1.171 (95% CI: 1.033-1.328), 1.214 (95% CI: 1.044-1.413) respectively. it was found that a 1.239 (95% CI: 1.088-1.553) times higher in smokers than non-smokers on relative risk for cardio-cerebro vascular death events. However, the predictive values of the influencing factors for cardio-cerebro vascular death were different among population of different years of age. The relative risk for cardio-cerebro vascular death events increased by 1.366 (95% CI: 1.102-1.678) times for each 10 mm Hg increase of diastolic blood pressure in 40-59 years old population. However, the effect was taken place by systolic blood pressure in 60-74 years old population,with a relative risk of 1.201 (95% CI: 1.017-1.418) for each 10 mm Hg increase. Age seemed the only significant factor for cardio-cerebro vascular death events on population aged more than 75 years old. Conclusion The predictive values of the risk factors were different among age groups. The different

  19. Accelerated optical polymer aging studies for LED luminaire applications

    NASA Astrophysics Data System (ADS)

    Estupiñán, Edgar; Wendling, Peter; Kostrun, Marijan; Garner, Richard

    2013-09-01

    There is a need in the lighting industry to design and implement accelerated aging methods that accurately simulate the aging process of LED luminaire components. In response to this need, we have built a flexible and reliable system to study the aging characteristics of optical polymer materials, and we have employed it to study a commercially available LED luminaire diffuser made of PMMA. The experimental system consists of a "Blue LED Emitter" and a working surface. Both the temperatures of the samples and the optical powers of the LEDs are appropriately characterized in the system. Several accelerated aging experiments are carried out at different temperatures and optical powers over a 90 hour period and the measured transmission values are used as inputs to a degradation model derived using plausibility arguments. This model seems capable of predicting the behavior of the material as a function of time, temperature and optical power. The model satisfactorily predicts the measured transmission values of diffusers aged in luminaires at two different times and thus can be used to make application recommendations for this material. Specifically, at 35000 hours (the manufacturer's stated life of the luminaire) and at the typical operational temperature of the diffuser, the model predicts a transmission loss of only a few percent over the original transmission of the material at 450 nm, which renders this material suitable for this application.

  20. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  2. Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress.

    PubMed

    Matsumoto, Takayuki; Watanabe, Shun; Ando, Makoto; Yamada, Kosuke; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

    2016-02-01

    To study the time-course relationship between vascular functions and endoplasmic reticulum (ER) stress in type 2 diabetes, we investigated vascular function and associated protein expression, including cyclo-oxygenase (COX), ER stress, and apoptotic markers, in renal arteries (RA) from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats at the young adult (4 months old) and aged (18 months old) stages. In the RA of aged OLETF (vs. young OLETF), we found: (1) Increased contractions induced by uridine adenosine tetraphosphate (Up4A) and phenylephrine, (2) decreased relaxation and increased contraction induced by acetylcholine (ACh) at lower and higher concentrations, respectively, and (3) increased expression of COX-1 and C/EBP-homologous protein (CHOP, a pro-apoptotic protein). In aged rats, the expression of COX-1, COX-2, PDI (an ER protein disulfide isomerase), Bax (a proapoptotic marker), and CHOP were increased in RA from OLETF rats (vs. age-matched control Long-Evans Tokushima Otsuka [LETO] rats). Up-regulation of PDI and Bax were seen in the RA from young OLETF (vs. young LETO) rats. No age-related alterations were apparent in the above changes in RA from LETO rats, excluding ACh-induced contraction. Short-term treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 100 mg/kg per day, intraperitoneally for 1 week) to OLETF rats at the chronic stage of the disease (12 months old) could suppress renal arterial contractions induced by Up4A and ACh. These results suggest that a long-term duration of disease may be important for the development of vascular dysfunction rather than aging per se. The early regulation of ER stress may be important against the development of diabetes-associated vascular dysfunction.

  3. Low systolic blood pressure and mortality from all causes and vascular diseases among older middle-aged men: Korean Veterans Health Study.

    PubMed

    Yi, Sang-Wook; Ohrr, Heechoul

    2015-03-01

    Recently, low systolic blood pressure (SBP) was found to be associated with an increased risk of death from vascular diseases in a rural elderly population in Korea. However, evidence on the association between low SBP and vascular diseases is scarce. The aim of this study was to prospectively examine the association between low SBP and mortality from all causes and vascular diseases in older middle-aged Korean men. From 2004 to 2010, 94 085 Korean Vietnam War veterans were followed-up for deaths. The adjusted hazard ratios (aHR) were calculated using the Cox proportional hazard model. A stratified analysis was conducted by age at enrollment. SBP was self-reported by a postal survey in 2004. Among the participants aged 60 and older, the lowest SBP (<90 mmHg) category had an elevated aHR for mortality from all causes (aHR, 1.9; 95% confidence interval [CI], 1.2 to 3.1) and vascular diseases (International Classification of Disease, 10th revision, I00-I99; aHR, 3.2; 95% CI, 1.2 to 8.4) compared to those with an SBP of 100 to 119 mmHg. Those with an SBP below 80 mmHg (aHR, 4.5; 95% CI, 1.1 to 18.8) and those with an SBP of 80 to 89 mmHg (aHR, 3.1; 95% CI, 0.9 to 10.2) also had an increased risk of vascular mortality, compared to those with an SBP of 90 to 119 mmHg. This association was sustained when excluding the first two years of follow-up or preexisting vascular diseases. In men younger than 60 years, the association of low SBP was weaker than that in those aged 60 years or older. Our findings suggest that low SBP (<90 mmHg) may increase vascular mortality in Korean men aged 60 years or older.

  4. In vitro cytotoxicity of maxillofacial silicone elastomers: effect of accelerated aging.

    PubMed

    Bal, Bilge Turhan; Yilmaz, Handan; Aydin, Cemal; Karakoca, Seçil; Yilmaz, Sükran

    2009-04-01

    The purpose of this in vitro study was to evaluate the cytotoxicity of three maxillofacial silicone elastomers at 24, 48, and 72 h on L-929 cells and to determine the effect of accelerated aging on the cytotoxicity of these silicone elastomers. Disc-shaped test samples of maxillofacial silicone elastomers (Cosmesil, Episil, Multisil) were fabricated according to manufacturers' instructions under aseptic conditions. Samples were then divided into three groups: (1) not aged; (2) aged for 150 h with an accelerated weathering tester; and (3) aged for 300 h. Then the samples were placed in Dulbecco's Modified Eagle Medium/Ham's F12 (DMEM/F12) for 24, 48, and 72 h. After the incubation periods, cytotoxicity of the extracts to cultured fibroblasts (L-929) was measured by MTT assay. The degree of cytotoxicity of each sample was determined according to the reference value represented by the cells with a control (culture without sample). Statistical significance was determined by repeated measurement ANOVA (p < 0.01) followed by Duncan's test (p < 0.05). All test materials in each group demonstrated high survival rates in MTT assay (Episil; 93.84%, Multisil; 88.30%, Cosmesil; 87.50%, respectively); however, in all groups, Episil material demonstrated significantly higher cell survival rate after each of the experimental incubation periods (p < 0.05). Accelerated aging for 150 and 300 h had no significant effect on the biocompatibility of maxillofacial silicone elastomers tested (p > 0.05).

  5. [PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS].

    PubMed

    Bashkireva, A S; Kachan, Ye Yu; Kulapina, M E

    2015-01-01

    We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short-term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity.

  6. Accelerated aging effects on surface hardness and roughness of lingual retainer adhesives.

    PubMed

    Ramoglu, Sabri Ilhan; Usumez, Serdar; Buyukyilmaz, Tamer

    2008-01-01

    To test the null hypothesis that accelerated aging has no effect on the surface microhardness and roughness of two light-cured lingual retainer adhesives. Ten samples of light-cured materials, Transbond Lingual Retainer (3M Unitek) and Light Cure Retainer (Reliance) were cured with a halogen light for 40 seconds. Vickers hardness and surface roughness were measured before and after accelerated aging of 300 hours in a weathering tester. Differences between mean values were analyzed for statistical significance using a t-test. The level of statistical significance was set at P < .05. The mean Vickers hardness of Transbond Lingual Retainer was 62.8 +/- 3.5 and 79.6 +/- 4.9 before and after aging, respectively. The mean Vickers hardness of Light Cure Retainer was 40.3 +/- 2.6 and 58.3 +/- 4.3 before and after aging, respectively. Differences in both groups were statistically significant (P < .001). Following aging, mean surface roughness was changed from 0.039 microm to 0.121 microm and from 0.021 microm to 0.031 microm for Transbond Lingual Retainer and Light Cure Retainer, respectively. The roughening of Transbond Lingual Retainer with aging was statistically significant (P < .05), while the change in the surface roughness of Light Cure Retainer was not (P > .05). Accelerated aging significantly increased the surface microhardness of both light-cured retainer adhesives tested. It also significantly increased the surface roughness of the Transbond Lingual Retainer.

  7. Solder joint aging characteristics from the MC2918 firing set of a B61 accelerated aging unit (AAU)

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

    Vianco, P.T.; Rejent, J.A.

    1997-10-01

    The B61 accelerated aging unit (AAU) provided a unique opportunity to document the effects of a controlled, long-term thermal cycling environment on the aging of materials used in the device. This experiment was of particular interest to solder technologists because thermal cycling environments are a predominant source of solder joint failures in electronic assemblies. Observations of through hole solder joints in the MC2918 Firing Set from the B61 AAU did not reveal signs of catastrophic failure. Quantitative analyses of the microstructural metrics of intermetallic compound layer thickness and Pb-rich phase particle distributions indicated solder joint aging that was commensurate withmore » the accelerated aging environment. The effects of stress-enhanced coarsening of the Pb-rich phase were also documented.« less

  8. Towards Accelerated Aging Methodologies and Health Management of Power MOSFETs (Technical Brief)

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Patil, Nishad; Saha, Sankalita; Wysocki, Phil; Goebel, Kai

    2009-01-01

    Understanding aging mechanisms of electronic components is of extreme importance in the aerospace domain where they are part of numerous critical subsystems including avionics. In particular, power MOSFETs are of special interest as they are involved in high voltage switching circuits such as drivers for electrical motors. With increased use of electronics in aircraft control, it becomes more important to understand the degradation of these components in aircraft specific environments. In this paper, we present an accelerated aging methodology for power MOSFETs that subject the devices to indirect thermal overstress during high voltage switching. During this accelerated aging process, two major modes of failure were observed - latch-up and die attach degradation. In this paper we present the details of our aging methodology along with details of experiments and analysis of the results.

  9. From hemobiology to vascular disease: a review of the potential of gliclazide to influence the pathogenesis of diabetic vascular disease.

    PubMed

    Jennings, P E

    1994-01-01

    Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity. In addition, there is increased lipid peroxidation and oxidative stress due to excess free-radical activity and impaired antioxidant defenses particularly in the presence of microvascular disease. The development of many of these abnormalities is associated with poor long-term glycemic control. However, the changes are also seen in atherosclerosis in nondiabetic patients where the progression of the disease can be modified by antiplatelet agents and antioxidants. The process of vascular damage is accelerated by diabetes, often due to co-existing disease and aging, although it is not clear that improvement in long-term glycemic control by lowering blood glucose levels to near to the nondiabetic state reduces the development of small and large vessel disease. Although the biochemical mechanism underlying this observation remains uncertain, protein glycosylation and increased platelet reactivity are implicated and interrelated. Increased oxidative stress due to excess free-radical activity may be central to diabetic vascular disease as endothelial cell damage, lipoprotein oxidation, modification of both platelet reactivity and arachidonic acid cascade are all properties of free radicals and their reaction products lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Accelerated aging of EPDM and butyl elastomers

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

    Wilson, M.H.

    1996-06-01

    This study was composed of three parts: a post cure study to optimize final properties of an ethylene-propylene-diene (EPDM) formulation, an accelerated aging study to compare the stress relaxation behavior of a butyl and an EPDM elastomer under compression, and a cursory evaluation of a new 70 Shore A EPDM. The optimum postcure for the EPDM was found to be 2 to 4 hours at 182{degrees}C in a vacuum. The EPDM was also shown to have superior aging characteristics compared to the butyl and is recommended for use instead of the butyl material. The physical properties for new 70 Shoremore » A EPDM are satisfactory, and the stress relaxation behavior was only slightly inferior to the other EPDM.« less

  11. Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents.

    PubMed

    Popa-Wagner, A; Pirici, D; Petcu, E B; Mogoanta, L; Buga, A-M; Rosen, C L; Leon, R; Huber, J

    2010-08-01

    Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic.

  12. Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction

    PubMed Central

    Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

    2012-01-01

    Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, ‘premature’ vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using ‘endothelial therapy’ aiming at maintaining or restoring vascular endothelial health. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21557734

  13. Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction.

    PubMed

    Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

    2012-02-01

    Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  14. Asynchronous arterial systolic expansion as a marker of vascular aging: assessment of the carotid artery with velocity vector imaging.

    PubMed

    Yang, Woo-In; Shim, Chi Y; Bang, Woo D; Oh, Chang M; Chang, Hyuk J; Chung, Namsik; Ha, Jong-Won

    2011-12-01

    Arterial elastic properties change with aging. Measurements of pulse wave velocity and augmentation index are useful for the evaluation of arterial stiffness. However, they likely represent only global characteristics of the arterial tree rather than local vascular alterations. The aim of this study was to evaluate whether local vascular properties assessed by velocity vector imaging differed with aging. Vascular properties of carotid arteries with ages were assessed in 100 healthy volunteers (52 men) ranging from 20 to 68 years using velocity vector imaging. The peak circumferential strain and strain rate of the six segments in left common carotid arteries were analyzed and the standard deviation of the time to peak circumferential strain and strain rate of the six segments, representing the synchronicity of the arterial expansion, were calculated. Central blood pressure, augmentation index and pulse wave velocity were assessed by commercially available radial artery tonometry, the SphygmoCor system (AtCor Medical, West Ryde, Australia). A validated generalized transfer function was used to acquire the central aortic pressures and pressure waveforms. Pulse wave velocity, augmentation index and velocity vector imaging parameters showed significant changes with age. However, the age-related changes in pulse wave velocity, augmentation index and velocity vector imaging parameters were different. The increase in pulse wave velocity was more prominent in older individuals, whereas the changes in augmentation index and carotid strain and strain rate were evident earlier, at the age of 30 years. Unlike augmentation index, which showed little change in older individuals, the standard deviation of time to peak strain and strain rate showed a steady increase from younger to older individuals. Asynchronous arterial expansion could be a useful discriminative marker of vascular aging independent of individual's age.

  15. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

    PubMed

    Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

    2017-11-01

    Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated

  16. Low Systolic Blood Pressure and Mortality From All Causes and Vascular Diseases Among Older Middle-aged Men: Korean Veterans Health Study

    PubMed Central

    Yi, Sang-Wook; Ohrr, Heechoul

    2015-01-01

    Objectives: Recently, low systolic blood pressure (SBP) was found to be associated with an increased risk of death from vascular diseases in a rural elderly population in Korea. However, evidence on the association between low SBP and vascular diseases is scarce. The aim of this study was to prospectively examine the association between low SBP and mortality from all causes and vascular diseases in older middle-aged Korean men. Methods: From 2004 to 2010, 94 085 Korean Vietnam War veterans were followed-up for deaths. The adjusted hazard ratios (aHR) were calculated using the Cox proportional hazard model. A stratified analysis was conducted by age at enrollment. SBP was self-reported by a postal survey in 2004. Results: Among the participants aged 60 and older, the lowest SBP (<90 mmHg) category had an elevated aHR for mortality from all causes (aHR, 1.9; 95% confidence interval [CI], 1.2 to 3.1) and vascular diseases (International Classification of Disease, 10th revision, I00-I99; aHR, 3.2; 95% CI, 1.2 to 8.4) compared to those with an SBP of 100 to 119 mmHg. Those with an SBP below 80 mmHg (aHR, 4.5; 95% CI, 1.1 to 18.8) and those with an SBP of 80 to 89 mmHg (aHR, 3.1; 95% CI, 0.9 to 10.2) also had an increased risk of vascular mortality, compared to those with an SBP of 90 to 119 mmHg. This association was sustained when excluding the first two years of follow-up or preexisting vascular diseases. In men younger than 60 years, the association of low SBP was weaker than that in those aged 60 years or older. Conclusions: Our findings suggest that low SBP (<90 mmHg) may increase vascular mortality in Korean men aged 60 years or older. PMID:25857648

  17. Accelerated Aging Test for Plastic Scintillator Gamma Ray Detectors

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

    Kouzes, Richard T.

    Polyvinyl toluene (PVT) and polystyrene (PS), collectively referred to as “plastic scintillator,” are synthetic polymer materials used to detect gamma radiation, and are commonly used in instrumentation. Recent studies have revealed that plastic scintillator undergoes an environmentally related material degradation that adversely affects performance under certain conditions and histories. A significant decrease in gamma ray sensitivity has been seen in some detectors in systems as they age. The degradation of sensitivity of plastic scintillator over time is due to a variety of factors, and the term “aging” is used to encompass all factors. Some plastic scintillator samples show no agingmore » effects (no significant change in sensitivity over more than 10 years), while others show severe aging (significant change in sensitivity in less than 5 years). Aging effects arise from weather (variations in heat and humidity), chemical exposure, mechanical stress, light exposure, and loss of volatile components. The damage produced by these various causes can be cumulative, causing observable damage to increase over time. Damage may be reversible up to some point, but becomes permanent under some conditions. It has been demonstrated that exposure of plastic scintillator in an environmental chamber to 30 days of high temperature and humidity (90% relative humidity and 55°C) followed by a single cycle to cold temperature (-30°C) will produce severe fogging in all PVT samples. This thermal cycle will be referred to as the “Accelerated Aging Test.” This document describes the procedure for performing this Accelerated Aging Test.« less

  18. Evaluation of hardness and colour change of soft liners after accelerated ageing.

    PubMed

    Mancuso, Daniela Nardi; Goiato, Marcelo Coelho; Zuccolotti, Bruna Carolina Rossatti; Moreno, Amália; dos Santos, Daniela Micheline

    2009-07-01

    Soft liners have been developed to offer comfort to denture wearers. However, this comfort is compromised when there is a change in the properties of the material, causing colour change, solubility, absorption and hardening. These characteristics can compromise the longevity of soft liners. The aim of this in vitro study was to investigate the effect of ageing on both the hardness and colour change of two soft liners following accelerated ageing. Two denture liners, one resin based (Trusoft, Bosworth, Illinois, USA) and one silicone based (Ufi Gel P, Voco GMBH, Cuxhaven, Germany), were tested in this study for both hardness (using the Shore A scale) and colour change (using the CIE L*a*b* colour scale), initially and after 1008 hours (6 weeks) of accelerated ageing. Statistical analysis was performed using the unpaired t-test with the Welch correction. These indicated that both materials increased in hardness and underwent colour change after accelerated ageing. The initial hardness of Trusoft was far lower than that of Ufi Gel P (18.2 Shore A units vs 34.8 Shore A units). However, for Trusoft the changes for both hardness (from 18.2 to 52.1 Shore A units) and colour change (16.85 on the CIE L*a*b* colour scale) were greater than those for Ufi Gel P, for which hardness changed from 34.8 to 36.5 Shore A units and the colour change was 5.19 on the CIE L*a*b* colour scale. Ufi Gel P underwent less hardness and colour change after accelerated ageing than Trusoft. On the other hand, the use of Trusoft may be preferable in cases where initial softness is a major consideration, such as when relining an immediate denture after implant surgery.

  19. Parasite infection accelerates age polyethism in young honey bees

    PubMed Central

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C.

    2016-01-01

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

  20. Parasite infection accelerates age polyethism in young honey bees.

    PubMed

    Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C

    2016-02-25

    Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens.

  1. Demographic Risk Factors for Vascular Lesions as Etiology of Intraventricular Hemorrhage in Prospectively Screened Cases

    PubMed Central

    Fam, Maged; Pang, Alice; Zeineddine, Hussein A.; Mayo, Steven; Stadnik, Agnieszka; Jesselson, Michael; Zhang, Lingjiao; Dlugash, Rachel; Ziai, Wendy; Hanley, Daniel; Awad, Issam A.

    2017-01-01

    Background Spontaneous intraventricular hemorrhage (IVH) is associated with high rates of morbidity and mortality despite critical care and other advances. An important step in clinical management is to confirm/rule out an underlying vascular lesion, which influences further treatment, potential for further bleeding and prognosis. Our aim is to compare demographic and clinical characteristics between IVH patients with and without an underlying vascular lesion, and among cohorts with different vascular lesions. Methods We analyzed prospectively collected data of IVH patients screened for eligibility as part of the Clot Lysis: Evaluation Accelerated Resolution of Intraventricular Hemorrhage-CLEAR Phase III clinical trial. The trial adopted a structured screening process to systematically exclude patients with an underlying vascular lesion as etiology of IVH. We collected age, sex, ethnicity and primary diagnosis on these cases and vascular lesions were categorized prospectively as aneurysm, vascular malformation (arteriovenous malformation, dural arteriovenous fistula, cavernoma), Moyamoya disease or other vascular lesion. We excluded cases < 18 or > 80 years of age. Baseline characteristics were compared between the CLEAR group (IVH screened without vascular lesion) and the group of IVH patients screened and excluded from CLEAR because of an identified vascular lesion. We further analyzed the differential demographic and clinical characteristics among subcohorts with different vascular lesions. Results 10,538 consecutive IVH cases were prospectively screened for the trial between 2011 and 2015. 496 cases (4.7%) screened negative for underlying vascular lesion, met the inclusion criteria and were enrolled in the trial (no vascular etiology group), and 1,205 cases (11.4%) were concurrently screened and excluded from the trial because of a demonstrated underlying vascular lesion (vascular etiology group). Cases with vascular lesion were less likely to be older than 45

  2. Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

    PubMed

    Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

    2017-03-01

    Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

  3. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants.

    PubMed

    Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S; Wentzell, Jill S; Kretzschmar, Doris; Giebultowicz, Jadwiga M

    2012-03-01

    Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per(01)) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni(1)), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni(1) mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per(01)sni(1) flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per(01) mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws(1)), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants

    PubMed Central

    Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S.; Wentzell, Jill S.; Kretzschmar, Doris; Giebultowicz, Jadwiga M.

    2012-01-01

    Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per01) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni1), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni1 mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per01 sni1 flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per01 mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws1), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. PMID:22227001

  5. Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

    PubMed

    Raz, Naftali; Daugherty, Ana M; Sethi, Sean K; Arshad, Muzamil; Haacke, E Mark

    2017-08-01

    Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

  6. Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

    PubMed

    Okusaga, Olaoluwa O

    2014-08-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

  7. Correlation between mechanical and chemical degradation after outdoor and accelerated laboratory aging for multilayer photovoltaic backsheets

    NASA Astrophysics Data System (ADS)

    Lin, Chiao-Chi; Lyu, Yadong; Yu, Li-Chieh; Gu, Xiaohong

    2016-09-01

    Channel cracking fragmentation testing and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were utilized to study mechanical and chemical degradation of a multilayered backsheet after outdoor and accelerated laboratory aging. A model sample of commercial PPE backsheet, namely polyethylene terephthalate/polyethylene terephthalate/ethylene vinyl acetate (PET/PET/EVA) was investigated. Outdoor aging was performed in Gaithersburg, Maryland, USA for up to 510 days, and complementary accelerated laboratory aging was conducted on the NIST (National Institute of Standards and Technology) SPHERE (Simulated Photodegradation via High Energy Radiant Exposure). Fracture energy, mode I stress intensity factor and film strength were analyzed using an analytical model based on channel cracking fragmentation testing results. The correlation between mechanical and chemical degradation was discussed for both outdoor and accelerated laboratory aging. The results of this work provide preliminary understanding on failure mechanism of backsheets after weathering, laying the groundwork for linking outdoor and indoor accelerated laboratory testing for multilayer photovoltaic backsheets.

  8. Idh2 deficiency accelerates renal dysfunction in aged mice.

    PubMed

    Lee, Su Jeong; Cha, Hanvit; Lee, Seoyoon; Kim, Hyunjin; Ku, Hyeong Jun; Kim, Sung Hwan; Park, Jung Hyun; Lee, Jin Hyup; Park, Kwon Moo; Park, Jeen-Woo

    2017-11-04

    The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP + -dependent isocitrate dehydrogenase (IDH2). Depletion of IDH2 in mice (idh2 -/- ) shortens life span and accelerates the degeneration of multiple age-sensitive traits, such as hair grayness, skin pathology, and eye pathology. Among the various internal organs tested in this study, IDH2 depletion-induced acceleration of senescence was uniquely observed in the kidney. Renal function and structure were greatly deteriorated in 24-month-old idh2 -/- mice compared with wild-type. In addition, disruption of redox status, which promotes oxidative damage and apoptosis, was more pronounced in idh2 -/- mice. These data support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice, and thus support the oxidative stress theory of aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. US Particle Accelerators at Age 50.

    ERIC Educational Resources Information Center

    Wilson, R. R.

    1981-01-01

    Reviews the development of accelerators over the past 50 years. Topics include: types of accelerators, including cyclotrons; sociology of accelerators (motivation, financing, construction, and use); impact of war; national laboratories; funding; applications; future projects; foreign projects; and international collaborations. (JN)

  10. Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication.

    PubMed

    Mironov, Vladimir; Kasyanov, Vladimir; Markwald, Roger R

    2008-06-01

    The existing methods of biofabrication for vascular tissue engineering are still bioreactor-based, extremely expensive, laborious and time consuming and, furthermore, not automated, which would be essential for an economically successful large-scale commercialization. The advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface and even help to direct the differentiation of stem cells into the vascular cell phenotype. The development of rapid nanotechnology-based methods of vascular tissue biofabrication represents one of most important recent technological breakthroughs in vascular tissue engineering because it dramatically accelerates vascular tissue assembly and, importantly, also eliminates the need for a bioreactor-based scaffold cellularization process.

  11. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling.

    PubMed

    Zannas, Anthony S; Arloth, Janine; Carrillo-Roa, Tania; Iurato, Stella; Röh, Simone; Ressler, Kerry J; Nemeroff, Charles B; Smith, Alicia K; Bradley, Bekh; Heim, Christine; Menke, Andreas; Lange, Jennifer F; Brückl, Tanja; Ising, Marcus; Wray, Naomi R; Erhardt, Angelika; Binder, Elisabeth B; Mehta, Divya

    2015-12-17

    Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.

  12. Aging accelerates memory extinction and impairs memory restoration in Drosophila.

    PubMed

    Chen, Nannan; Guo, Aike; Li, Yan

    2015-05-15

    Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. [Effect of enalapril on nitric oxide synthesis, oxidative metabolism, and vascular tone in aging rats].

    PubMed

    Sahach, V F; Baziliuk, O V; Stepanenko, L H; Korkach, Iu P; Kotsiuruba, A V

    2007-01-01

    Endothelium-dependent and endothelium-independent reactions of relaxations of vascular smooth muscle (VSM) were examined in the aorta preparations of the two groups (6-8 and 21-22 month). The studies also two NO synthase (NOS) isoform activity--inducible (iNOS) and constitutive (cNOS), activity of arginase and nitrate reductase and the content of high-molecular nitrosothiols (HMNT) and low-molecular nitrosothiols (LMNT) and stable metabolites of NO (NO(-)2, NO(-)3). Aging rats demonstrated only endothelium-dependent responses of VSM to acethylcholine lowering. This endothelial dysfunction depend on high activity of arginase, iNOS and salvage (by nitrate reductase) NO synthesis, both reactive oxigen species (ROS) (by xanthine oxidase) and peroxynitrite generation, as well as low activity of constitutive (eNOS, nNOS) NO synthesis. Angiotensin-converting enzyme inhibitor (enalapril) administration (20 mg/kg, 30 or 55 days) up regalate constitutive NO synthesis by arginase, iNOS, nitrate reductase activity and ROS and peroxynitrite generation inhibition thus restore endothelium-dependent relaxations of VSM in aging rats. The result obtained suggest a new roles for the renin-angiotensin system in vascular tone regulation. Thus enalapril might serve as a novel tool to prevent aging-associated endothelial dysfunction.

  14. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

    PubMed

    Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Davis, Simon W; Shafto, Meredith A; Taylor, Jason R; Williams, Nitin; Cam-Can; Rowe, James B

    2015-06-01

    In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task

  15. Chromatic stability of acrylic resins of artificial eyes submitted to accelerated aging and polishing.

    PubMed

    Goiato, Marcelo Coelho; Santos, Daniela Micheline dos; Souza, Josiene Firmino; Moreno, Amália; Pesqueira, Aldiéris Alves

    2010-12-01

    Esthetics and durability of materials used to fabricate artificial eyes has been an important issue since artificial eyes are essential to restore esthetics and function, protect the remaining tissues and help with patients' psychological therapy. However, these materials are submitted to degrading effects of environmental agents on the physical properties of the acrylic resin. This study assessed the color stability of acrylic resins used to fabricate sclera in three basic shades (N1, N2 and N3) when subjected to accelerated aging, mechanical and chemical polishing. Specimens of each resin were fabricated and submitted to mechanical and chemical polishing. Chromatic analysis was performed before and after accelerated aging through ultraviolet reflection spectrophotometry. All specimens revealed color alteration following polishing and accelerated aging. The resins presented statistically significant chromatic alteration (p<0.01) between the periods of 252 and 1008 h. Both polishing methods presented no significant difference between the values of color derivatives of resins.

  16. You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

    PubMed Central

    Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

    2014-01-01

    Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

  17. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging.

    PubMed

    Zarzuelo, María José; López-Sepúlveda, Rocío; Sánchez, Manuel; Romero, Miguel; Gómez-Guzmán, Manuel; Ungvary, Zoltan; Pérez-Vizcaíno, Francisco; Jiménez, Rosario; Duarte, Juan

    2013-05-01

    Vascular aging is characterized by up-regulation of NADPH oxidase, oxidative stress and endothelial dysfunction. Previous studies demonstrate that the activity of the evolutionarily conserved NAD(+)-dependent deacetylase SIRT1 declines with age and that pharmacological activators of SIRT1 confer significant anti-aging cardiovascular effects. To determine whether dysregulation of SIRT1 promotes NADPH oxidase-dependent production of reactive oxygen species (ROS) and impairs endothelial function we assessed the effects of three structurally different inhibitors of SIRT1 (nicotinamide, sirtinol, EX527) in aorta segments isolated from young Wistar rats. Inhibition of SIRT1 induced endothelial dysfunction, as shown by the significantly reduced relaxation to the endothelium-dependent vasodilators acetylcholine and the calcium ionophore A23187. Endothelial dysfunction induced by SIRT1 inhibition was prevented by treatment of the vessels with the NADPH oxidase inhibitor apocynin or superoxide dismutase. Inhibition of SIRT1 significantly increased vascular superoxide production, enhanced NADPH oxidase activity, and mRNA expression of its subunits p22(phox) and NOX4, which were prevented by resveratrol. Peroxisome proliferator-activated receptor-α (PPARα) activation mimicked the effects of resveratrol while PPARα inhibition prevented the effects of this SIRT1 activator. SIRT1 co-precipitated with PPARα and nicotinamide increased the acetylation of the PPARα coactivator PGC-1α, which was suppressed by resveratrol. In conclusion, impaired activity of SIRT1 induces endothelial dysfunction and up-regulates NADPH oxidase-derived ROS production in the vascular wall, mimicking the vascular aging phenotype. Moreover, a new mechanism for controlling endothelial function after SIRT1 activation involves a decreased PGC-1α acetylation and the subsequent PPARα activation, resulting in both decreased NADPH oxidase-driven ROS production and NO inactivation. Copyright © 2013

  18. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    PubMed

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

  19. Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

    PubMed Central

    Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

    2013-01-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals

  20. Characterization and Accelerated Ageing of UHMWPE Used in Orthopedic Prosthesis by Peroxide

    PubMed Central

    Rocha, Magda; Mansur, Alexandra; Mansur, Herman

    2009-01-01

    Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important mechanical properties to extend the longevity of knee prostheses. Though accelerated in vitro protocols have been developed to test the relative oxidation resistance of various types of UHMWPE, its mechanism is not accurately understood yet. Thus, in the present study an accelerated ageing of UHMWPE in hydrogen peroxide solution was performed and relative oxidation was extensively characterized by Fourier Transformed Infrared Spectroscopy (FTIR) spectroscopy and the morphological changes were analyzed by Scanning Electron Microscopy (SEM). Different chemical groups of UHMWPE associated with the degradation reaction were monitored for over 120 days in order to evaluate the possible oxidation mechanism(s) which may have occurred. The results have provided strong evidence that the oxidation mechanism is rather complex, and two stages with their own particular first-order kinetics reaction patterns have been clearly identified. Furthermore, hydrogen peroxide has proven to be an efficient oxidative medium to accelerate ageing of UHMWPE.

  1. Habitually exercising older men do not demonstrate age-associated vascular endothelial oxidative stress.

    PubMed

    Pierce, Gary L; Donato, Anthony J; LaRocca, Thomas J; Eskurza, Iratxe; Silver, Annemarie E; Seals, Douglas R

    2011-12-01

    We tested the hypothesis that older men who perform habitual aerobic exercise do not demonstrate age-associated vascular endothelial oxidative stress compared with their sedentary peers. Older exercising men (n=13, 62±2 years) had higher (P<0.05) physical activity (79±7 vs. 30±6 MET hours per week) and maximal exercise oxygen consumption (42±1 vs. 29±1 mL kg(-1) per minute) vs. sedentary men (n=28, 63±1 years). Brachial artery flow-mediated dilation (FMD), a measure of vascular endothelial function, was greater (P<0.05) in the exercising vs. sedentary older men (6.3±0.5 vs. 4.9±0.4%Δ) and not different than young controls (n=20, 25±1 years, 7.1±0.5%Δ). In vascular endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38±0.06 vs. 0.77±0.10 AU). This was associated with lower endothelial expression of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47(phox) subunit, 0.33±0.05 vs. 0.61±0.09 AU) and the redox-sensitive transcription factor nuclear factor kappa B (NFκB) (p65 subunit, 0.36±0.05 vs. 0.72±0.09 AU). Expression of the antioxidant enzyme manganese superoxide dismutase (SOD) (0.57±0.13 vs. 0.30±0.04 AU) and activity of endothelium-bound extracellular SOD were greater (6.4±0.5 vs. 5.0±0.6 U mL(-1) per minute) in the exercising men (both P<0.05), but differences no longer were significant after correcting for adiposity and circulating metabolic factors. Overall, values for the young controls differed with those for the sedentary, but not the exercising older men. Older men who exercise regularly do not demonstrate vascular endothelial oxidative stress, and this may be a key molecular mechanism underlying their reduced risk of cardiovascular diseases. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  2. Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

    PubMed Central

    Guachalla, Luis Miguel; Ju, Zhenyu; Koziel, Rafal; von Figura, Guido; Song, Zhangfa; Fusser, Markus; Epe, Bernd; Jansen-Dűrr, Pidder; Rudolph, K. Lenhard

    2009-01-01

    Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction. PMID:20195488

  3. Colour stability of temporary restorations with different thicknesses submitted to artificial accelerated aging.

    PubMed

    Silame, F D J; Tonani, R; Alandia-Roman, C C; Chinelatti, M; Panzeri, H; Pires-de-Souza, F C P

    2013-12-01

    This study evaluated the colour stability of temporary prosthetic restorations with different thicknesses submitted to artificial accelerated aging. The occlusal surfaces of 40 molars were grinded to obtain flat enamel surfaces. Twenty acrylic resin specimens [Polymethyl methacrylate (Duralay) and Bis-methyl acrylate (Luxatemp)] were made with two different thicknesses, 0.5 mm and 1.0 mm. Temporary restorations were fixed on enamel and CIE L*a*b* colour parameters of each specimen were assessed before and after artificial accelerated aging. All groups showed colour alterations above the clinically acceptable limit. Luxatemp showed the lowest colour alteration regardless its thickness and Duralay showed the greatest alteration with 0.5 mm.

  4. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults

    PubMed Central

    Henson, Richard N. A.; Tyler, Lorraine K.; Davis, Simon W.; Shafto, Meredith A.; Taylor, Jason R.; Williams, Nitin; Cam‐CAN; Rowe, James B.

    2015-01-01

    Abstract In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood‐oxygenation level‐dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting‐state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath‐hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age‐related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population‐based Cambridge Centre for Ageing and Neuroscience cohort (Cam‐CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task‐based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects

  5. Decrease of Perivascular Adipose Tissue Browning Is Associated With Vascular Dysfunction in Spontaneous Hypertensive Rats During Aging.

    PubMed

    Kong, Ling-Ran; Zhou, Yan-Ping; Chen, Dong-Rui; Ruan, Cheng-Chao; Gao, Ping-Jin

    2018-01-01

    Functional perivascular adipose tissue (PVAT) is necessary to maintain vascular physiology through both mechanical support and endocrine or paracrine ways. PVAT shows a brown adipose tissue (BAT)-like feature and the browning level of PVAT is dependent on the anatomic location and species. However, it is not clear whether PVAT browning is involved in the vascular tone regulation in spontaneously hypertensive rats (SHRs). In the present study, we aimed to illustrate the effect of aging on PVAT browning and subsequent vasomotor reaction in SHRs. Herein we utilized histological staining and western blot to detect the characteristics of thoracic PVAT (tPVAT) in 8-week-old and 16-week-old SHR and Wistar-Kyoto (WKY) rats. We also detected vascular reactivity analysis to determine the effect of tPVAT on vasomotor reaction during aging. The results showed that tPVAT had a similar phenotype to BAT, including smaller adipocyte size and positive uncoupling protein-1 (UCP1) staining. Interestingly, the tPVAT of 8-week-old SHR showed increased BAT phenotypic marker expression compared to WKY, whereas the browning level of tPVAT had a more dramatic decrease from 8 to 16 weeks of age in SHR than age-matched WKY rats. The vasodilation effect of tPVAT on aortas had no significant difference in 8-week-old WKY and SHR, whereas this effect is obviously decreased in 16-week-old SHR compared to WKY. In contrast, tPVAT showed a similar vasoconstriction effect in 8- or 16-week-old WKY and SHR rats. Moreover, we identified an important vasodilator adenosine, which regulates adipocyte browning and may be a potential PVAT-derived relaxing factor. Adenosine is dramatically decreased from 8 to 16 weeks of age in the tPVAT of SHR. In summary, aging is associated with a decrease of tPVAT browning and adenosine production in SHR rats. These may result in attenuated vasodilation effect of the tPVAT in SHR during aging.

  6. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

    PubMed

    Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

    2018-06-06

    Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

  7. [Oral contraception and the vascular risk].

    PubMed

    Garnier, L F; Gruel, Y

    1989-01-01

    Vascular risk, mainly thromboembolitic risk, attributed to oral contraceptives (OCs) since 1962, has been primarily linked to ethinyl estradiol (EE). OCs which combine estrogen and have been associated with cerebral vascular accidents. A 1977 study showed a 40% increase of mortality due to cardiovascular complications in women taking OCs. There were of both an arterial and a venous character. The risk of myocardial infarction was 3 times more frequent among OC users. Deep venous thrombosis and pulmonary embolism were more numerous. Some other risk factors include smoking, hypertension, diabetes, and age 35. The risk of heart attack vanishes a few years after stopping OC use. The reduction of EE (and similarly progesterone) dosage from 100-50 mcg also lower the risk of hypertension, cerebral vascular accidents, and venous thrombosis. Prolonged use of OCs causes disorders of hemostasis affecting the walls of blood vessels, modifying the viscosity of blood flow (increase of hematocrits, reduction of venous tonus), modifying plasmatic coagulation (increase of platelets, increase of factors VII and X and plasma fibrinogen, and decrease of antithrombin III activity), and increased fibrinolysis. These anomalies are exclusively associated with high doses of estrogens. 5% of women using OCs develop moderate hypertension of 5-10 mm Hg of systolic pressure 5 years later, but after cessation it is reversed. OCs stimulate the renin-angiotensin-aldosterone system causing accelerated production of angiotensin II with the resultant forceful vasotension. 3 months after quitting OC use, high blood pressure returns to normal. EE can provoke diabetes; it increases very low density lipoprotein (VLDL) and high density lipoprotein (HDL) production, but total cholesterol is hardly affected. The androgenic property of progestogens reduces HDL. Combined OCs are contraindicated for women with hypertension, hyperlipidemia, diabetes, and a family history of vascular accidents.

  8. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  9. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

    PubMed Central

    Hoffman, Jared D.; Parikh, Ishita; Green, Stefan J.; Chlipala, George; Mohney, Robert P.; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M. S.; Lin, Ai-Ling

    2017-01-01

    Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the

  10. [Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].

    PubMed

    Vatseba, M O

    2013-09-01

    Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

  11. [Characteristics of the sympathoadrenal system response to psychoemotional stress under hypoxic conditions in aged people with physiological and accelerated aging of the respiratory system].

    PubMed

    Asanov, E O; Os'mak, Ie D; Kuz'mins'ka, L A

    2013-01-01

    The peculiarities of the response of the sympathoadrenal system to psychoemotional and hypoxic stress in healthy young people and in aged people with physiological and accelerated aging of respiratory system were studied. It was shown that in aging a more pronounced response of the sympathoadrenal system to psychoemotional stress. At the same time, elderly people with different types of aging of the respiratory system did not demonstrate a difference in the response of the sympathoadrenal system to psychoemotional stress. Unlike in young people, in aged people, combination of psychoemotional and hypoxic stresses resulted in further activation of the sympathoadrenal system. The reaction of the sympathoadrenal system was more expressed in elderly people with accelerated ageing of the respiratory system.

  12. Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels

    PubMed Central

    Smiley, Dia A.; Khalil, Raouf A.

    2010-01-01

    The cardiovascular benefits of menopausal hormone therapy (MHT) remain controversial. The earlier clinical observations that cardiovascular disease (CVD) was less common in MHT users compared to non-users suggested cardiovascular benefits of MHT. Also, experimental studies have identified estrogen receptors ERα, ERβ and GPR30, which mediate genomic or non-genomic effects in vascular endothelium, smooth muscle, and extracellular matrix (ECM). However, data from randomized clinical trials (RCTs), most notably the Women's Health Initiative (WHI) study, have challenged the cardiovascular benefits and highlighted adverse cardiovascular events with MHT. The discrepancies have been attributed to the design of RCTs, the subjects' advanced age and preexisting CVD, and the form of estrogen used. The discrepancies may also stem from age-related changes in vascular ER amount, distribution, integrity, and post-receptor signaling pathways as well as structural changes in the vasculature. Age-related changes in other sex hormones such as testosterone may also alter the hormonal environment and influence the cardiovascular effects of estrogen. Investigating the chemical properties, structure-activity relationship and pharmacology of natural and synthetic estrogens should improve the effectiveness of conventional MHT. Further characterization of phytoestrogens, selective estrogen-receptor modulators (SERMs), and specific ER agonists may provide substitutes to conventional MHT. Conditions with excess or low estrogen levels such as polycystic ovary syndrome (PCOS) and Turner syndrome may provide insight into the development and regulation of ER and the mechanisms of aberrant estrogen-ER interactions. The lessons learned from previous RCTs have led to more directed studies such as the Kronos Early Estrogen Prevention Study (KEEPS). Careful design of experimental models and RCTs, coupled with the development of specific ER modulators, hold the promise of improving the actions of

  13. Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE, and hypertension.

    PubMed

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Land, Susan

    2009-01-01

    Several single nucleotide polymorphisms have been linked to neural and cognitive variation in healthy adults. We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E epsilon4) and a vascular risk factor (hypertension) in a sample of 189 volunteers (age 18-82). Genotypes were determined from buccal culture samples, and cognitive performance was assessed in 4 age-sensitive domains?fluid intelligence, executive function (inhibition), associative memory, and processing speed. We found that younger age and COMT Met/Met genotype, associated with low COMT activity and higher prefrontal dopamine content, were independently linked to better performance in most of the tested domains. Homozygotes for Val allele of BDNF polymorphism exhibited better associative memory and faster speed of processing than the Met allele carriers, with greater effect for women and persons with hypertension. Carriers of ApoE epsilon4 allele evidenced steeper age-related increase in costs of Stroop color interference, but showed no negative effects on memory. The findings indicate that age-related cognitive performance is differentially affected by distinct genetic factors and their interactions with vascular health status. (c) 2009 APA, all rights reserved.

  14. Estrogens and aging skin.

    PubMed

    Thornton, M Julie

    2013-04-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies.

  15. Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration.

    PubMed

    Sawada, Tomoko; Wang, Xiying; Sawada, Osamu; Saishin, Yoshitsugu; Ohji, Masahito

    2018-01-01

    Clinical evidence supports the efficacy of bimonthly aflibercept injection for age-related macular degeneration. The study aimed to evaluate aqueous vascular endothelial growth factor and aflibercept concentrations and the efficacy of bimonthly aflibercept in patients with age-related macular degeneration. This study is a prospective, interventional case series. Enrolled were 35 eyes with exudative age-related macular degeneration from 35 patients. Patients received three bimonthly intravitreal aflibercept without loading doses. We collected the aqueous humor just before each injection, measured vascular endothelial growth factor and aflibercept concentrations by enzyme-linked immunosorbent assay and measured best-corrected visual acuity and central retinal subfield thickness before and after the injections. Aqueous vascular endothelial growth factor and aflibercept concentrations were measured. The vascular endothelial growth factor concentration was 135.4 ± 60.5 pg/mL (mean ± standard deviation, range 60.6-323.4) at baseline and below the lowest detectable limit in all eyes at month 2 and in 32 eyes at month 4 (P < 0.001 [month 2] and P < 0.001 [month 4]). The mean aflibercept concentration was 20.3 ng/mL at month 2 and 28.0 ng/mL at month 4. The mean logarithm of the minimum angle of resolution visual acuity improved from 0.50 ± 0.36 at baseline to 0.36 ± 0.40 at month 6 (P < 0.001). The mean central retinal subfield thickness decreased from 353 ± 100 μm at baseline to 236 ± 45 μm at month 6 (P < 0.001). Bimonthly aflibercept injections without loading doses may be considered a treatment option for age-related macular degeneration. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  16. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    PubMed

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  17. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  18. Color Stability of CAD/CAM Fabricated Inlays after Accelerated Artificial Aging.

    PubMed

    Karaokutan, Isil; Yilmaz Savas, Tuba; Aykent, Filiz; Ozdere, Eda

    2016-08-01

    To investigate the influence of accelerated artificial aging on the color stability of three different inlay restorations produced with a CAD/CAM system. Thirty non-carious human mandibular molar teeth were used. The teeth were embedded in autopolymerizing acrylic resin blocks. Standard Class I inlay cavities were prepared, and the teeth were randomly divided into three groups (n = 10) to fabricate inlay restorations: (1) a feldspathic-ceramic group, (2) a resin nano-ceramic group, and (3) a leucite glass-ceramic group. Optical impressions were made with CEREC software, and the restorations were designed and then milled. The inlays were adhesively cemented with a dual-polymerizing resin cement and left in distilled water at room temperature for 1 week. Color measurements were performed with a spectrophotometer before and after accelerated aging in a weathering machine with a total energy of 150 kJ/m(2) . Changes in color (∆E, ∆L, ∆a, ∆b, ∆C) were determined using the CIE L*a*b* system. The results were assessed using a one-way ANOVA and Tukey's HSD test (p = 0.05). The color changes of the materials ranged from 2.1 to 9.29. The highest color change was seen in the resin nano-ceramic material. This change was not clinically acceptable (∆E > 5.5). No significant differences were found in the ∆L and ∆a values of the test groups. Color changes were observed in each evaluated material after accelerated aging. All CAD/CAM inlays became darker in appearance, more saturated, a little reddish, and more yellow. © 2015 by the American College of Prosthodontists.

  19. Mechanical properties experimental investigation of HTPB propellant after thermal accelerated aging

    NASA Astrophysics Data System (ADS)

    Yang, Xiaohong; Sun, Chaoxiang; Zhang, Junfa; Xu, Jinsheng; Tan, Bingdong

    2017-04-01

    To get accurate aging mechanical properties of aged HTPB propellant, the thermal accelerated aging experiment method is utilized and the uniaxial tensile experiments were conducted to obtain the mechanical data of aged HTPB propellants, and the maximum tensile strength, σm, maximum tensile strain, ɛm, and the fracture tensile strain, ɛb, of HTPB propellant with different aging time and various aging temperatures,were obtained, using universal material testing machine. The experimental results show that the σm of HTPB propellant initially increases, subsequently decreases and finally increases with aging time. The ɛm and ɛb generally decrease with increasing aging time, what's more, the decrease rate of both ɛm and ɛb reduce with the aging time. What's more, the postcure effect and oxidation reaction occurred inside HTPB matrix, including the chain degradation reaction and oxidation-induced crosslinking, were discussed to explain the mechanical aging rule of HTPB propellant.

  20. How accelerated biological aging can affect solar reflective polymeric based building materials

    NASA Astrophysics Data System (ADS)

    Ferrari, C.; Santunione, G.; Libbra, A.; Muscio, A.; Sgarbi, E.

    2017-11-01

    Among the main issues concerning building materials, in particular outdoor ones, one can identify the colonization by microorganisms referred to as biological aggression. This can affect not only the aesthetical aspect but also the thermal performance of solar reflective materials. In order to improve the reliability of tests aimed to assess the resistance to biological aggression and contextually reduce the test duration, an accelerated test method has been developed. It is based on a lab reproducible setup where specific and controlled environmental and boundary conditions are imposed to accelerate as much as possible biological growth on building materials. Due to their widespread use, polymeric materials have been selected for the present analysis, in the aim of reaching an advanced bio-aged level in a relatively short time (8 weeks or less) and at the same time comparatively evaluate different materials under a given set of ageing conditions. Surface properties before, during and after ageing have been investigated by surface, microstructural and chemical analyses, as well as by examination of time progressive images to assess bacterial and algal growth rate.

  1. The Influence of Education and Age on Neurocognitive Test Performance in Alzheimer's Disease and Vascular Dementia

    ERIC Educational Resources Information Center

    DenBesten, Nicholas P.

    2009-01-01

    This research involves an examination of the relationship between education and age on a wide array of neuropsychological test measures among patients diagnosed with Alzheimer's and vascular dementia. The purpose of this study was to investigate the role of education as an attenuating factor to neurocognitive decline in dementia. Although numerous…

  2. Does cyclic stress and accelerated ageing influence the wear behavior of highly crosslinked polyethylene?

    PubMed

    Affatato, Saverio; De Mattia, Jonathan Salvatore; Bracco, Pierangiola; Pavoni, Eleonora; Taddei, Paola

    2016-06-01

    First-generation (irradiated and remelted or annealed) and second-generation (irradiated and vitamin E blended or doped) highly crosslinked polyethylenes were introduced in the last decade to solve the problems of wear and osteolysis. In this study, the influence of the Vitamin-E addition on crosslinked polyethylene (XLPE_VE) was evaluated by comparing the in vitro wear behavior of crosslinked polyethylene (XLPE) versus Vitamin-E blended polyethylene XLPE and conventional ultra-high molecular weight polyethylene (STD_PE) acetabular cups, after accelerated ageing according to ASTM F2003-02 (70.0±0.1°C, pure oxygen at 5bar for 14 days). The test was performed using a hip joint simulator run for two millions cycles, under bovine calf serum as lubricant. Mass loss was found to decrease along the series XLPE_VE>STD_PE>XLPE, although no statistically significant differences were found between the mass losses of the three sets of cups. Micro-Raman spectroscopy was used to investigate at a molecular level the morphology changes induced by wear. The spectroscopic analyses showed that the accelerated ageing determined different wear mechanisms and molecular rearrangements during testing with regards to the changes in both the chain orientation and the distribution of the all-trans sequences within the orthorhombic, amorphous and third phases. The results of the present study showed that the addition of vitamin E was not effective to improve the gravimetric wear of PE after accelerated ageing. However, from a molecular point of view, the XLPE_VE acetabular cups tested after accelerated ageing appeared definitely less damaged than the STD_PE ones and comparable to XLPE samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. A novel approach on accelerated ageing towards reliability optimization of high concentration photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Tsanakas, John A.; Jaffre, Damien; Sicre, Mathieu; Elouamari, Rachid; Vossier, Alexis; de Salins, Jean-Edouard; Bechou, Laurent; Levrier, Bruno; Perona, Arnaud; Dollet, Alain

    2014-09-01

    This paper presents a preliminary study upon a novel approach proposed for highly accelerated ageing and reliability optimization of high concentrating photovoltaic (HCPV) cells and assemblies. The intended approach aims to overcome several limitations of some current accelerated ageing tests (AAT) adopted up today, proposing the use of an alternative experimental set-up for performing faster and more realistic thermal cycles, under real sun, without the involvement of environmental chamber. The study also includes specific characterization techniques, before and after each AAT sequence, which respectively provide the initial and final diagnosis on the condition of the tested sample. The acquired data from these diagnostic/characterization methods are then used as indices to determine both quantitatively and qualitatively the severity of degradation and, thus, the ageing level for each tested HCPV assembly or cell sample. Ultimate goal of such "initial diagnosis - AAT - final diagnosis" sequences is to provide the basis for a future work on the reliability analysis of the main degradation mechanisms and confident prediction of failure propagation in HCPV cells, by means of acceleration factor (AF) and mean-time-to-failure (MTTF) estimations.

  4. Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling.

    PubMed

    Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

    2018-01-01

    Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway.

  5. Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

    PubMed

    Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

    2016-07-01

    Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure

    PubMed Central

    Jablonski, Kristen L.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; McQueen, Matthew B.; Seals, Douglas R.

    2013-01-01

    Objectives We determined the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130–159 mmHg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11M/6F; 62±7 yrs, mean±S.D.) completed a randomized, crossover study of 4 weeks of both low and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary sodium excretion was reduced by ~50% (to 70±30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following the low sodium diet (p<0.005). Low sodium markedly enhanced NO- mediated EDD (greater ΔFBFACh with endothelial NO synthase [eNOS] inhibition) without changing eNOS expression/activation (Ser1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (p<0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reverses both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP

  7. Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging in Drosophila.

    PubMed

    Park, Joung-Sun; Jeon, Ho-Jun; Pyo, Jung-Hoon; Kim, Young-Shin; Yoo, Mi-Ae

    2018-03-07

    Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11 , Rad50 , Nbs1 , ATM , ATR , Chk1 , and Chk2 , which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

  8. Assessment of surface hardness of acrylic resins submitted to accelerated artificial aging.

    PubMed

    Tornavoi, D C; Agnelli, J A M; Lepri, C P; Mazzetto, M O; Botelho, A L; Soares, R G; Dos Reis, A C

    2012-06-01

    The aim of this study was to assess the influence of accelerated artificial aging (AAA) on the surface hardness of acrylic resins. The following three commercial brands of acrylic resins were tested: Vipi Flash (autopolymerized resin), Vipi Wave (microwave heat-polymerized resin) and Vipi Cril (conventional heat-polymerized resin). To perform the tests, 21 test specimens (65x10x3 mm) were made, 7 for each resin. Three surface hardness readings were performed for each test specimen, before and after AAA, and the means were submitted to the following tests: Kolmogorov-Smirnov (P>0.05), Levene Statistic, Two-way ANOVA, Tukey Post Hoc (P<0.05) with the SPSS Statistical Software 17.0. The analysis of the factors showed significant differences in the hardness values (P<0.05). Before aging, the autopolymerized acrylic resin Vipi Flash showed lower hardness values when compared with the heat-polymerized resin Vipi Cril (P=0.001). After aging, the 3 materials showed similar performance when compared among them. The Vipi Cril was the only one affected by AAA and showed lower hardness values after this procedure (Pp=0.003). It may be concluded that accelerated artificial aging influenced surface hardness of heat-polymerized acrylic resin Vipi Cril.

  9. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study

    PubMed Central

    Reece, Albert Stuart; Hulse, Gary Kenneth

    2016-01-01

    Objectives Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. Design Cross-sectional and longitudinal, observational. Prospective. Setting Single primary care addiction clinic in Brisbane, Australia. Participants 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. Exclusions: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. Intervention Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. Main outcome measure Algorithmically calculated VA. Secondary outcomes: other central haemodynamic variables. Results Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose–response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002). Conclusions Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose–response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular

  10. Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat.

    PubMed

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2014-10-28

    In Thai traditional medicine, rhizomes of Kaempferia parviflora (KP) have been used for treating hypertension and for the promotion of longevity with good health and well being. Ageing is one of the most important risk factors for development of cardiovascular disease. To investigate whether a 6 weeks oral administration of a dichloromethane extract of fresh rhizomes of Kaempferia parviflora (KPD) had any effects on vascular functions, on the accumulation of lipid, as well as on any signs of gross organ toxicity in middle-aged rats. Fresh rhizomes of Kaempferia parviflora were first macerated twice with 95% ethanol to remove the dark color before extracting three times with 100% dichloromethane. The dichloromethane extract was evaporated under reduced pressure to obtain the dried Kaempferia parviflora dichloromethane extract (KPD). The rats were orally administered with the KPD at a dosage of 100mg/kg body weight, or with the same volume of the vehicle (tween 80, 0.2g: carboxy-methylcellulose sodium, 0.2g: distilled water 10 ml) once or twice a day for 6 weeks. Vascular functions were studied on isolated thoracic aorta and the mesenteric artery. The vascular eNOS enzyme was measured by Western blot analysis. Blood chemistry was measured by enzymatic methods. Liver cell lipid accumulation was measured using oil red O staining. A 6 weeks treatment of KPD once a day had no significant effects on any of the studied parameters. When the KPD was given twice a day, the contractile responses to phenylephrine of the thoracic aorta and mesenteric artery were lower than the vehicle control group, and this effect was abolished by N(G)-nitro-l-arginine or by removal of the vascular endothelium. Vasorelaxation to acetylcholine, but not to glyceryl trinitrate, by the thoracic aortic and mesenteric ring precontracted with phenylephrine was higher from the KPD treated rats than those from the vehicle control groups. Western blot analysis showed a higher quantity of thoracic- and

  11. Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

    PubMed

    Shalev, Idan; Belsky, Jay

    2016-05-01

    Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Macrophage Response to UHMWPE Submitted to Accelerated Ageing in Hydrogen Peroxide

    PubMed Central

    Rocha, Magda F.G.; Mansur, Alexandra A.P.; Martins, Camila P.S.; Barbosa-Stancioli, Edel F.; Mansur, Herman S.

    2010-01-01

    Ultra-high molecular weight polyethylene (UHMWPE) has been the most commonly used bearing material in total joint arthroplasty. Wear and oxidation fatigue resistance of UHMWPE are regarded as two important properties to extend the longevity of knee prostheses. The present study investigated the accelerated ageing of UHMWPE in hydrogen peroxide highly oxidative chemical environment. The sliced samples of UHMWPE were oxidized in a hydrogen peroxide solution for 120 days with their total level of oxidation (Iox) characterized by Fourier Transformed Infrared Spectroscopy (FTIR). The potential inflammatory response, cell viability and biocompatibility of such oxidized UHMWPE systems were assessed by a novel biological in vitro assay based on the secretion of nitric oxide (NO) by activated murine macrophages with gamma interferon (IFN-γ) cytokine and lipopolysaccharide (LPS). Furthermore, macrophage morphologies in contact with UHMWPE oxidized surfaces were analyzed by cell spreading-adhesion procedure using scanning electron microscopy (SEM). The results have given significant evidence that the longer the period of accelerated aging of UHMWPE the higher was the macrophage inflammatory equivalent response based on NO secretion analysis. PMID:20721321

  13. Is HIV a model of accelerated or accentuated aging?

    PubMed

    Pathai, Sophia; Bajillan, Hendren; Landay, Alan L; High, Kevin P

    2014-07-01

    Antiretroviral therapy has reduced the incidence of adverse events and early mortality in HIV-infected persons. Despite these benefits, important comorbidities that increase with age (eg, diabetes, cardiovascular disease, cancer, liver disease, and neurocognitive impairment) are more prevalent in HIV-infected persons than in HIV-uninfected persons at every age, and geriatric syndromes such as falls and frailty occur earlier in HIV-infected persons. This raises a critical research question: Does HIV accelerate aging through pathways and mechanisms common to the aging process or is HIV simply an additional risk factor for a wide number of chronic conditions, thus accentuating aging? Extensive literature review. The purpose of this review is to briefly outline the evidence that age-related clinical syndromes are exacerbated by HIV, examine the ways in which HIV is similar, and dissimilar from natural aging, and assess the validity of HIV as a model of premature aging. Specific biomarkers of aging are limited in HIV-infected hosts and impacted by antiretroviral therapy, and a high rate of modifiable life style confounders (eg, smoking, substance abuse, alcohol) and coinfections (eg, hepatitis) in HIV-infected participants. There is a need for validated biomarkers of aging in the context of HIV. Despite these differences, welldesigned studies of HIV-infected participants are likely to provide new opportunities to better understand the mechanisms that lead to aging and age-related diseases. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

    PubMed

    Masumoto, Asuka; Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Nakashima, Yuri; Okuda, Kouji; Iwashita, Yuko; Mima, Toru; Negi, Shigeo; Shigematsu, Takashi

    2017-07-01

    Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p<0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

  15. Dysregulated physiological stress systems and accelerated cellular aging.

    PubMed

    Révész, Dóra; Verhoeven, Josine E; Milaneschi, Yuri; de Geus, Eco J C N; Wolkowitz, Owen M; Penninx, Brenda W J H

    2014-06-01

    Exposure to chronic stressors is associated with accelerated biological aging as indicated by reduced leukocyte telomere length (LTL). This impact could be because of chronic overactivation of the body's physiological stress systems. This study examined the associations between LTL and the immune system, hypothalamic-pituitary-adrenal axis and autonomic nervous system. LTL was assessed in 2936 adults from the Netherlands Study of Depression and Anxiety. Inflammation markers (interleukin-6, c-reactive protein, tumor necrosis factor-alpha), hypothalamic-pituitary-adrenal-axis indicators (salivary cortisol awakening curve [area under the curve indicators, with respect to the ground and increase], evening levels, 0.5 mg dexamethasone cortisol suppression ratio), and autonomic nervous system measures (heart rate, respiratory sinus arrhythmia, pre-ejection period) were determined. Linear regression analyses were performed and adjusted for sociodemographic, lifestyle and clinical factors. Shorter LTL was significantly associated with higher c-reactive protein, interleukin-6, area under the curve with respect to increase, and heart rate. A cumulative index score was calculated based on the number of highest tertiles of these 4 stress markers. LTL demonstrated a significant gradient within subjects ranging from having zero (5528 base pairs) to having 4 elevated stress markers (5371 base pairs, p for trend = 0.002), corresponding to a difference of 10 years of accelerated biological aging. Contrary to the expectations, shorter LTL was also associated with longer pre-ejection period, indicating lower sympathetic tone. This large-scale study showed that inflammation, high awakening cortisol response, and increased heart rate are associated with shorter LTL, especially when they are dysregulated cumulatively. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Accelerated Post-Weld Natural Ageing in Ultrasonic Welding Aluminium 6111-T4 Automotive Sheet

    NASA Astrophysics Data System (ADS)

    Chen, Ying-Chun; Prangnell, Phil

    In contrast to previously published reports, it is shown that there is an observable HAZ when ultrasonic spot welding (USW) automotive alloys, like AA6111-T4, the severity of which depends on the welding energy. Immediately after welding, softening is seen relative to the T4 condition, but this is rapidly recovered by natural ageing, which masks the presence of a HAZ, and the weld strength eventually exceeds that of the parent material. This behaviour is caused by dissolution of the solute clusters/GPZs in the T4 sheet, due to the high weld temperatures (> 400 °C), combined with accelerated post-weld natural ageing to a more advanced state than in the parent material. Modelling has demonstrated that this accelerated natural ageing behaviour can be attributed to an excess vacancy concentration generated by the USW process.

  17. Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling

    PubMed Central

    Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

    2018-01-01

    Objective(s): Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). Materials and Methods: In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. Results: AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Conclusion: Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway. PMID:29372041

  18. Monitoring migration and transformation of nanomaterials in polymeric composites during accelerated aging

    NASA Astrophysics Data System (ADS)

    Vilar, G.; Fernández-Rosas, E.; Puntes, V.; Jamier, V.; Aubouy, L.; Vázquez-Campos, S.

    2013-04-01

    The incorporation of small amounts of nanoadditives in polymeric compounds can introduce new mechanical, physical, electrical, magnetic, thermal and/or optical properties. The properties of these advanced materials have enabled new applications in several industrial sectors (electronics, automotive, textile...). In particular, for the nanomaterials (NM) described in this work, multi-walled carbon nanotubes (MWCNT) and silicon dioxide nanoparticles (SiO2 NP), the following properties have been described: MWCNT act as nucleating agents in thermoplastics, and change viscosity, affecting dispersion, orientation, and therefore mechanical, thermal, and electrical properties; and SiO2 NP act as flame retardant and display improved electrical and mechanical properties. The work described here is focused on the evaluation of the migration and transformation of NM included in polymer nanocomposites (NC) during accelerated climatic ageing. To this aim, we generated polyamide 6 (PA6) NC with different degree of compatibility between the NM and the polymeric matrix. These NC were submitted to accelerated aging conditions to simulate outdoor conditions (simulation of the use phase of the polymeric NC). The NC contain as nanofillers MWCNT and SiO2 NP with different surface properties to influence the compatibility with the polymeric matrix. The generated NC were evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) with Energy-dispersive X-ray spectroscopy (EDX), thermogravimetry (TGA) and differential scanning calorimetry (DSC) before and after the aging process, to monitor the compatibility of the NM with the matrix: dispersion within the matrix, migration during aging, and modification of the polymer properties. The dispersion of SiO2 NP in the NC depended on their compatibility with the matrix. However, independently of their compatibility with the matrix, SiO2 NP were aggregated at the end of the accelerated aging process. In addition

  19. New noninvasive index for evaluation of the vascular age of healthy and sick people

    NASA Astrophysics Data System (ADS)

    Fine, Ilya; Kuznik, Boris I.; Kaminsky, Alexander V.; Shenkman, Louis; Kustovsjya, Evgeniya M.; Maximova, Olga G.

    2012-08-01

    We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

  20. New noninvasive index for evaluation of the vascular age of healthy and sick people.

    PubMed

    Fine, Ilya; Kuznik, Boris I; Kaminsky, Alexander V; Shenkman, Louis; Kustovsjya, Evgeniya M; Elena, Evgeniya M; Maximova, Olga G

    2012-08-01

    We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

  1. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    PubMed

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p < 0.05) 24 h post-inflammation. Other indices of systolic performance were reduced in older but not younger adults; diastolic performance was attenuated in both groups 24 h post-inflammation (p < 0.05 for all). Older, but not younger, adults decreased central pressure during inflammation (p < 0.05). When controlled for age, physical activity was not related to the inflammation-induced changes in elastance (p > 0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Effect of low-intensity whole-body vibration on bone defect repair and associated vascularization in mice.

    PubMed

    Matsumoto, Takeshi; Goto, Daichi

    2017-12-01

    Low-intensity whole-body vibration (LIWBV) may stimulate bone healing, but the involvement of vascular ingrowth, which is essential for bone regeneration, has not been well examined. We thus investigated the LIWBV effect on vascularization during early-stage bone healing. Mice aged 13 weeks were subjected to cortical drilling on tibial bone. Two days after surgery (day 0), mice were exposed daily to sine-wave LIWBV at 30 Hz and 0.1 g peak-to-peak acceleration for 20 min/day (Vib) or were sham-treated (sham). Following vascular casting with a zirconium-based contrast agent on days 6, 9, or 12 and sacrifice, vascular and bone images were obtained by K-edge subtraction micro-CT using synchrotron lights. Bone regeneration advanced more in the Vib group from days 9 to 12. The vascular volume fraction decreased from days 6 to 9 in both groups; however, from days 9 to 12, it was increased in shams, while it stabilized in the Vib group. The vascular volume fraction tended to be or was smaller in the Vib group on days 6 and 12. The vessel number density was higher on day 9 but lower on day 12 in the Vib group. These results suggest that the LIWBV-promoted bone repair is associated with the modulation of vascularization, but additional studies are needed to determine the causality of this association.

  3. Do US Black Women Experience Stress-Related Accelerated Biological Aging?

    PubMed Central

    Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

    2010-01-01

    We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

  4. Acceleration of Age-Associated Methylation Patterns in HIV-1-Infected Adults

    PubMed Central

    Sehl, Mary; Sinsheimer, Janet S.; Hultin, Patricia M.; Hultin, Lance E.; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D.

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x10-200 and 0.47, p<1x10-200. Weighted gene correlation network analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage= 0.007088, p=2.08 x 10-9; βHIV= 0.099574, p=0.0011; Data set 2: βage= 0.008762, p=1.27x 10-5; βHIV= 0.128649, p= 0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10-6, odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to

  5. 175.4 The Relationship of Aging and Inflammatory Biomarkers to Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging

    PubMed Central

    Gama, Clarissa

    2017-01-01

    Abstract Background: Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL) and CCL11 (aging and inflammatory biomarkers), and gray matter volumes (GM) to episodic memory performance in individuals with SZ compared to healthy controls (HC). Methods: 112 participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Results: Participants with SZ had decreased TL and GM residual volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and they were both related to reduced GM residual volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was related with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except for between memory and GM. Conclusion: Our results are consistent with accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ. Akira Sawa, johns Hopkins University, Johns Hopkins Hospital and Medical Institutions

  6. Habitually exercising older men do not demonstrate age-associated vascular endothelial oxidative stress

    PubMed Central

    Pierce, Gary L.; Donato, Anthony J.; LaRocca, Thomas J.; Eskurza, Iratxe; Silver, Annemarie E.; Seals, Douglas R.

    2011-01-01

    SUMMARY We tested the hypothesis that older men who perform habitual aerobic exercise do not demonstrate age-associated vascular endothelial oxidative stress compared with their sedentary peers. Older exercising men (n=13, 62±2 y) had higher (P<0.05) physical activity (79±7 vs. 30±6 MET h/wk) and maximal exercise oxygen consumption (42±1 vs. 29±1 ml/kg/min) vs. sedentary men (n=28, 63±1 y). Brachial artery flow-mediated dilation, a measure of vascular endothelial function, was greater (P<0.05) in the exercising vs. sedentary older men (6.3±0.5 vs. 4.9±0.4 %Δ) and not different than young controls (n=20, 25±1 y, 7.1 ± 0.5 %Δ). In vascular endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38±0.06 vs. 0.77±0.10 AU). This was associated with lower endothelial expression of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (p47phox subunit, 0.33±0.05 vs. 0.61±0.09 AU) and the redox-sensitive transcription factor nuclear factor kappa B (NFκB) (p65 subunit, 0.36±0.05 vs. 0.72±0.09 AU). Expression of the antioxidant enzyme manganese superoxide dismutase (SOD) (0.57±0.13 vs. 0.30±0.04 AU) and activity of endothelium-bound extracellular SOD were greater (6.4±0.5 vs. 5.0±0.6 U/ml/min) in the exercising men (both P<0.05), but differences no longer were significant after correcting for adiposity and circulating metabolic factors. Overall, values for the young controls differed with those for the sedentary, but not the exercising older men. Older men who exercise regularly do not demonstrate vascular endothelial oxidative stress and this may be a key molecular mechanism underlying their reduced risk of cardiovascular diseases. PMID:21943306

  7. Brain tissue pulsatility mediates cognitive and electrophysiological changes in normal aging: Evidence from ultrasound tissue pulsatility imaging (TPI).

    PubMed

    Angel, Lucie; Bouazzaoui, Badiâa; Isingrini, Michel; Fay, Séverine; Taconnat, Laurence; Vanneste, Sandrine; Ledoux, Moïse; Gissot, Valérie; Hommet, Caroline; Andersson, Fréderic; Barantin, Laurent; Cottier, Jean-Philippe; Pasco, Jérémy; Desmidt, Thomas; Patat, Frédéric; Camus, Vincent; Remenieras, Jean-Pierre

    2018-06-01

    Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm. To assess vascular health, we used an innovative measure of the pulsatility of deep brain tissue, due to variations in cerebral blood flow over the cardiac cycle. Results showed (1) a classical effect of age on fluid neurocognitive measures (inhibition, fluid intelligence, magnitude and latency of the P3b) but not on crystallized measures, (2) that brain pulsatility decreases with advancing age, (3) that brain pulsatility is positively correlated with fluid neurocognitive measures and (4) that brain pulsatility strongly mediated the age-related variance in cognitive performance and the magnitude of the P3b component. The mediating role of the brain pulsatility in age-related effect on neurocognitive measures supports the vascular hypothesis of cognitive aging. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients.

    PubMed

    Liu, Jing; Ma, Kun Ling; Gao, Min; Wang, Chang Xian; Ni, Jie; Zhang, Yang; Zhang, Xiao Liang; Liu, Hong; Wang, Yan Li; Liu, Bi Cheng

    2012-01-01

    Chronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation. Twenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression. Inflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a

  9. Retinal vascular caliber, iris color, and age-related macular degeneration in the Irish Nun Eye Study.

    PubMed

    McGowan, Amy; Silvestri, Giuliana; Moore, Evelyn; Silvestri, Vittorio; Patterson, Christopher C; Maxwell, Alexander P; McKay, Gareth J

    2014-12-18

    To evaluate the relationship between retinal vascular caliber (RVC), iris color, and age-related macular degeneration (AMD) in elderly Irish nuns. Data from 1233 participants in the cross-sectional observational Irish Nun Eye Study were assessed from digital photographs with a standardized protocol using computer-assisted software. Macular images were graded according to the modified Wisconsin Age-related Maculopathy Grading System. Regression models were used to assess associations, adjusting for age, mean arterial blood pressure, body mass index, refraction, and fellow RVC. In total, 1122 (91%) participants had gradable retinal images of sufficient quality for vessel assessment (mean age: 76.3 years [range, 56-100 years]). In an unadjusted analysis, we found some support for a previous finding that individuals with blue iris color had narrower retinal venules compared to those with brown iris color (P < 0.05), but this was no longer significant after adjustment. Age-related macular degeneration status was categorized as no AMD, any AMD, and late AMD only. Individuals with any AMD (early or late AMD) had significantly narrower arterioles and venules compared to those with no AMD in an unadjusted analysis, but this was no longer significant after adjustment. A nonsignificant reduced risk of any AMD or late AMD only was observed in association with brown compared to blue iris color, in both unadjusted and adjusted analyses. Retinal vascular caliber was not significantly associated with iris color or early/late AMD after adjustment for confounders. A lower but nonsignificant AMD risk was observed in those with brown compared to blue iris color. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  10. Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

    PubMed

    Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

    2014-01-01

    Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

  11. Effect of melatonin on vascular responses in aortic rings of aging rats.

    PubMed

    Reyes-Toso, Carlos F; Obaya-Naredo, Daniel; Ricci, Conrado R; Planells, Fernando M; Pinto, Jorge E; Linares, Laura M; Cardinali, Daniel P

    2007-04-01

    In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10(-5)mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 m mol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity.

  12. Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial

    PubMed Central

    Larijani, Vahid Nabavi; Ahmadi, Naser; Zeb, Irfan; Khan, Faraz; Flores, Ferdinand; Budoff, Matthew

    2014-01-01

    Objective Aged garlic extract (AGE) is associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement. Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial function. A stressful lifestyle is a well-known risk factor for the presence and progression of atherosclerosis. This study investigated the effect of AGE plus CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and endothelial function measured by digital thermal monitoring (DTM) in firefighters. Methods Sixty-five Los-Angeles County firefighters who met the eligibility criteria were enrolled in this placebo-controlled, double-blinded randomized trial. The firefighters were randomized to four tablets of AGE (300 mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and at the 1-year follow-up. Results There were no significant differences in age, cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for cardiovascular risk factors and statin therapy, the mean decrease in vascular stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P = 0.005). Similarly, the mean increase in the area under the temperature curve, the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with the placebo group (P = 0.01). Conclusion The combination of AGE and CoQ10 was independently associated with significant beneficial effects on vascular elasticity and endothelial function in firefighters with high occupational stress, highlighting the important role of AGE and CoQ10 in atherosclerotic prevention of such individuals. PMID:22858191

  13. Accelerated Aging System for Prognostics of Power Semiconductor Devices

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Vashchenko, Vladislav; Wysocki, Philip; Saha, Sankalita

    2010-01-01

    Prognostics is an engineering discipline that focuses on estimation of the health state of a component and the prediction of its remaining useful life (RUL) before failure. Health state estimation is based on actual conditions and it is fundamental for the prediction of RUL under anticipated future usage. Failure of electronic devices is of great concern as future aircraft will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. Therefore, development of prognostics solutions for electronics is of key importance. This paper presents an accelerated aging system for gate-controlled power transistors. This system allows for the understanding of the effects of failure mechanisms, and the identification of leading indicators of failure which are essential in the development of physics-based degradation models and RUL prediction. In particular, this system isolates electrical overstress from thermal overstress. Also, this system allows for a precise control of internal temperatures, enabling the exploration of intrinsic failure mechanisms not related to the device packaging. By controlling the temperature within safe operation levels of the device, accelerated aging is induced by electrical overstress only, avoiding the generation of thermal cycles. The temperature is controlled by active thermal-electric units. Several electrical and thermal signals are measured in-situ and recorded for further analysis in the identification of leading indicators of failures. This system, therefore, provides a unique capability in the exploration of different failure mechanisms and the identification of precursors of failure that can be used to provide a health management solution for electronic devices.

  14. Accelerated cognitive aging following severe traumatic brain injury: A review.

    PubMed

    Wood, Rodger Ll

    2017-01-01

    The primary objective of this review was to examine relevant clinical and experimental literatures for information on the long-term cognitive impact of serious traumatic brain injury (TBI) with regard to the process of cognitive aging. Online journal databases were queried for studies pertaining to cognitive aging in neurologically healthy populations, as well as the late cognitive effects of serious TBI. Additional studies were identified through searching bibliographies of related publications and using Google search engine. Problems of cognition exhibited by young adults after TBI resemble many cognitive weaknesses of attention deficit and poor working memory that are usually seen in an elderly population who have no neurological history. The current state of the literature provides support for the argument that TBI can result in diminished cognitive reserve which may accelerate the normal process of cognitive decline, leading to premature aging, potentially increasing the risk of dementia.

  15. Acrylamide induces accelerated endothelial aging in a human cell model.

    PubMed

    Sellier, Cyril; Boulanger, Eric; Maladry, François; Tessier, Frédéric J; Lorenzi, Rodrigo; Nevière, Rémi; Desreumaux, Pierre; Beuscart, Jean-Baptiste; Puisieux, François; Grossin, Nicolas

    2015-09-01

    Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) (p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  17. Surface degradation of polymer insulators under accelerated climatic aging in weather-ometer

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

    Xu, G.; McGrath, P.B.; Burns, C.W.

    1996-12-31

    Climatic aging experiments were conducted on two types of outdoor polymer insulators by using a programmable weather-ometer. The housing materials for the insulators were silicone rubber (SR) and ethylene propylene diene monomer (EPDM). The accelerated aging stresses were comprised of ultraviolet radiation, elevated temperature, temperature cycling, thermal shock and high humidity. Their effects on the insulator surface conditions and electrical performance wee examined through visual inspection and SEM studies, contact angle measurements, thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS) analysis, and 50% impulse flashover voltage tests. The results showed a significant damage on the insulator surface caused by some ofmore » the imposed aging stresses. The EDS analysis suggested a photooxidation process that happened on the insulator surface during the aging period.« less

  18. Ageing and endurance training effects on quantity and quality of pulmonary vascular bed in healthy men

    PubMed Central

    2014-01-01

    It has recently been demonstrated that in healthy individuals, peak oxygen consumption is associated with a greater pulmonary capillary blood volume and a more distensible pulmonary circulation. Our cross-sectional study suggests that, in healthy men aged 20 to 60 years (n = 63), endurance sport practice (vigorous-intensity domain of the International Physical Activity Questionnaire) is associated with better quantity (pulmonary capillary blood volume) and quality (slope of increase in lung diffusion for carbon monoxide on exercise) of the pulmonary vascular bed, partly counterbalancing the deleterious effects of ageing, which remains to be demonstrated in a prospective longitudinal design. PMID:24460636

  19. Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response.

    PubMed

    Osorio, Fernando G; Bárcena, Clea; Soria-Valles, Clara; Ramsay, Andrew J; de Carlos, Félix; Cobo, Juan; Fueyo, Antonio; Freije, José M P; López-Otín, Carlos

    2012-10-15

    Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-κB activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice). Causal involvement of NF-κB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-κB signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging.

  20. Service Lifetime Estimation of EPDM Rubber Based on Accelerated Aging Tests

    NASA Astrophysics Data System (ADS)

    Liu, Jie; Li, Xiangbo; Xu, Likun; He, Tao

    2017-04-01

    Service lifetime of ethylene propylene diene monomer (EPDM) rubber at room temperature (25 °C) was estimated based on accelerated aging tests. The study followed sealing stress loss on compressed cylinder samples by compression stress relaxation methods. The results showed that the cylinder samples of EPDM can quickly reach the physical relaxation equilibrium by using the over-compression method. The non-Arrhenius behavior occurred at the lowest aging temperature. A significant linear relationship was observed between compression set values and normalized stress decay results, and the relationship was not related to the ambient temperature of aging. It was estimated that the sealing stress loss in view of practical application would occur after around 86.8 years at 25 °C. The estimations at 25 °C based on the non-Arrhenius behavior were in agreement with compression set data from storage aging tests in natural environment.

  1. Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

    PubMed Central

    Shao, Hongwei; Xu, Qiyuan; Wu, Qiuling; Ma, Qi; Salgueiro, Luis; Wang, Jian’An; Eton, Darwin; Webster, Keith A; Yu, Hong

    2011-01-01

    The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34+ progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses. PMID:21143386

  2. Treatment of vascular dementia. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

    PubMed Central

    Brucki, Sonia Maria Dozzi; Ferraz, Ana Cláudia; de Freitas, Gabriel R.; Massaro, Ayrton Roberto; Radanovic, Márcia; Schultz, Rodrigo Rizek

    2011-01-01

    Scientific Department of Cognitive Neurology and Aging of ABN had a consensus meeting to write recommendations on treatment of vascular dementia, there was no previous issue. This disease has numerous particularities and can be considered a preventable dementia. Prevention treatment is primary care of vascular risk factors or a secondary prevention of factors that could cause recurrence of ischemic or hemorrhagic brain modifications. In these guidelines we suggested only symptomatic treatment, pharmacologic or non-pharmacologic. We have reviewed current publications on MEDLINE (PubMed), LILACS e Cochrane Library databases. Recommendations are concern to the following factors and their prevention evidences, association, or treatment of vascular dementia: physical activity, tobacco use, diet and food supplements, arterial hypertension, diabetes mellitus, obesity, statins, cardiac failure, atrial fibrillation, antithrombotics, sleep apnea, carotid revascularization, symptomatic pharmacological treatment. PMID:29213754

  3. Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study.

    PubMed

    Reece, Albert Stuart; Norman, Amanda; Hulse, Gary Kenneth

    2016-11-07

    Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. Cross-sectional and longitudinal, observational. Prospective. Single primary care addiction clinic in Brisbane, Australia. 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. Algorithmically calculated VA. other central haemodynamic variables. Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose-response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002). Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose-response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular age, which is a powerful surrogate for the organismal-biological age. This likely underlies and bi-directionally interacts with

  4. Accelerated aging of adhesive-mediated fiber post-resin composite bonds: A modeling approach.

    PubMed

    Radovic, Ivana; Monticelli, Francesca; Papacchini, Federica; Magni, Elisa; Cury, Alvaro Hafiz; Vulicevic, Zoran R; Ferrari, Marco

    2007-08-01

    Although fiber posts luted in root canals are not directly exposed to oral fluids, water storage is considered as in vitro accelerated aging test for bonded interfaces. The aim of the study was to evaluate the influence of accelerated water aging on fiber post-resin composite adhesion. Forty fiber posts (DT Light Post, RTD) were randomly divided into two main groups, according to the surface treatment performed. Group I: XPBond adhesive (Dentsply Caulk); Group II: sandblasting (Rocatec-Pre, 3M ESPE) and XPBond. Dual-cured resin cement (Calibra, Dentsply Caulk) and flowable composite (X-Flow, Dentsply Caulk) were applied on the posts to produce cylindrical specimens. The bond strength at the interface between post and cement/composite was measured with the microtensile test according to the non-trimming technique. Half of the sticks were tested immediately for bond strength, while in the other half testing was performed after 1 month of water storage at 37 degrees C. Post-cement/composite interfaces were evaluated under SEM prior and after water aging. Statistical analysis was performed using the Kruskal-Wallis ANOVA followed by Dunn's multiple range test (p<0.05). Immediate bond strength was higher on sandblasted posts. After water aging the two post surface treatments resulted comparable in bond strength. Resin cement achieved higher bond strength to fiber posts than flowable composite. Water aging significantly reduced bond strength. Sandblasting followed by adhesive coating may improve immediate post-resin bond strength in comparison to adhesive alone. However, fiber post-resin bond strength mediated by hydrophilic adhesive tends to decrease after water aging.

  5. Predicting the need for vascular surgeons in Canada.

    PubMed

    Lotfi, Shamim; Jetty, Prasad; Petrcich, William; Hajjar, George; Hill, Andrew; Kubelik, Dalibor; Nagpal, Sudhir; Brandys, Tim

    2017-03-01

    With the introduction of direct entry (0+5) residency programs in addition to the traditional (5+2) programs, the number of vascular surgery graduates across Canada is expected to increase significantly during the next 5 to 10 years. Society's need for these newly qualified surgeons is unclear. This study evaluated the predicted requirement for vascular surgeons across Canada to 2021. A program director survey was also performed to evaluate program directors' perceptions of the 0+5 residency program, the expected number of new trainees, and faculty recruitment and retirement. The estimated and projected Canadian population numbers for each year between 2013 and 2021 were determined by the Canadian Socio-economic Information and Management System (CANSIM), Statistics Canada's key socioeconomic database. The number of vascular surgery procedures performed from 2008 to 2012 stratified by age, gender, and province was obtained from the Canadian Institute for Health Information Discharge Abstract Database. The future need for vascular surgeons was calculated by two validated methods: (1) population analysis and (2) workload analysis. In addition, a 12-question survey was sent to each vascular surgery program director in Canada. The estimated Canadian population in 2013 was 35.15 million, and there were 212 vascular surgeons performing a total of 98,339 procedures. The projected Canadian population by 2021 is expected to be 38.41 million, a 9.2% increase from 2013; however, the expected growth rate in the age group 60+ years, who are more likely to require vascular procedures, is expected to be 30% vs 3.4% in the age group <60 years. Using population analysis modeling, there will be a surplus of 10 vascular surgeons in Canada by 2021; however, using workload analysis modeling (which accounts for the more rapid growth and larger proportion of procedures performed in the 60+ age group), there will be a deficit of 11 vascular surgeons by 2021. Program directors in

  6. Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1

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

    Nakashima, Yukiko; Morimoto, Mayuka; Toda, Ken-ichi

    2015-07-03

    Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed,more » because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation. - Highlights: • CRIM1 was upregulated only in tubular endothelial cells, but not in monolayers. • Increased CRIM1 reduced the proliferation of endothelial cells. • Increased CRIM1 accelerated the migration of endothelial cells. • Increased CRIM1 had no effect on the proliferation or migration of COS-7 cells.« less

  7. Influence of artificial accelerated aging on the color stability and opacity of composites of different shades.

    PubMed

    Mundim, F M; Da Fonseca Roberti Garcia, L; Silva Sousa, A B; Cruvinel, D R; De Carvalho Panzeri Pires-De-Souza, F

    2010-10-01

    The aim of this study was to evaluate the influence of artificial accelerated aging on the color stability and opacity of composites of different shades. Four composites for direct use (Heliomolar, 4 Seasons, Tetric EvoCeram; QuiXfil) and one for indirect use (SR Adoro) in two shades were used: light (A2) and dark (C3 for direct, and D4 for indirect composite). QuiXfil was obtained in Universal shade. A Teflon matrix (12 X 2 mm) was used to obtain 54 specimens (N=6), which were submitted to color and opacity analysis (Spectrophotometer PCB 6807, Byk Gardner) before and after artificial accelerated aging for 384 hours. After the statistical analysis (2-way ANOVA - Bonferroni - P<0.05), significant color alteration was observed in the light and dark composites studied (P<0.05), with the exception of QuiXfil. Composite 4 Seasons/C3 showed less color alteration (ΔE=0.91). The opacity alteration (ΔOP) was higher for light composites. Artificial accelerated aging interfered in the optical properties assessed; however, the alterations seemed to be more related to the composites composition than to their shade.

  8. The emerging role of alternative splicing in senescence and aging.

    PubMed

    Deschênes, Mathieu; Chabot, Benoit

    2017-10-01

    Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. Evidence of accelerated aging among African Americans and its implications for mortality.

    PubMed

    Levine, M E; Crimmins, E M

    2014-10-01

    Blacks experience morbidity and mortality earlier in the life course compared to whites. Such premature declines in health may be indicative of an acceleration of the aging process. The current study uses data on 7644 black and white participants, ages 30 and above, from the third National Health and Nutrition Examination Survey, to compare the biological ages of blacks and whites as indicated from a combination of ten biomarkers and to determine if such differences in biological age relative to chronological age account for racial disparities in mortality. At a specified chronological age, blacks are approximately 3 years older biologically than whites. Differences in biological age between blacks and whites appear to increase up until ages 60-65 and then decline, presumably due to mortality selection. Finally, differences in biological age were found to completely account for higher levels of all-cause, cardiovascular and cancer mortality among blacks. Overall, these results suggest that being black is associated with significantly higher biological age at a given chronological age and that this is a pathway to early death both overall and from the major age-related diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The Role of Retinal Vascular Density as a Screening Tool for Ageing and Stroke.

    PubMed

    Sprödhuber, Andrea; Wolz, Johannes; Budai, Attila; Laumeier, Inga; Audebert, Heinrich J; Michelson, Georg

    2018-06-06

    To measure the density of retinal vessels from digitized fundus photographs in patients with recent stroke and age-matched controls. To investigate whether the parameter retinal vascular density (RVD) served as a quantitative marker for cerebrovascular events. Digitized fundus photographs of n = 158 subjects with stroke or transient ischemic attack within 1 year at the time of examination and n = 1,250 age-matched controls without any remarkable medical history were examined. Sex, hypertension, and diabetes were considered to be cofactors. Measurement of RVD was performed with a computer-aided image-analyzing program by segmenting automatically all visible retinal vessels and measuring areas of vessels in distinct circles around the optic disk. In controls RVD dwindles with increasing distance from the optic disk. RVD decreased significantly with age (p = 0.000). Stroke patients showed significantly lower values of RVD of -15% in comparison to age-matched controls. In old subjects, stroke in combination with hypertension is associated with a significant decreased RVD, and in middle-aged subjects diabetes and stroke are associated with a significant decreased RVD (p = 0.01). Age and stroke are significant risk factors for decreased RVD. Diabetes and arterial hypertension are additional significant risk factors in patients with stroke with respect to RVD. © 2018 S. Karger AG, Basel.

  11. Hyper telomere recombination accelerates replicative senescence and may promote premature aging

    PubMed Central

    Hagelstrom, R. Tanner; Blagoev, Krastan B.; Niedernhofer, Laura J.; Goodwin, Edwin H.; Bailey, Susan M.

    2010-01-01

    Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and human aging, we analyzed the dependence of sister chromatid exchange (SCE) frequencies on location [i.e., genomic (G-SCE) vs. telomeric (T-SCE) DNA] in primary human fibroblasts deficient in WRN, BLM, or ERCC1-XPF. Consistent with our other studies, we found evidence of elevated T-SCE in telomerase-negative but not telomerase-positive backgrounds. In telomerase-negative WRN-deficient cells, T-SCE—but not G-SCE—frequencies were significantly increased compared with controls. In contrast, SCE frequencies were significantly elevated in BLM-deficient cells irrespective of genome location. In ERCC1-XPF-deficient cells, neither T- nor G-SCE frequencies differed from controls. A theoretical model was developed that allowed an in silico investigation into the cellular consequences of increased T-SCE frequency. The model predicts that in cells with increased T-SCE, the onset of replicative senescence is dramatically accelerated even though the average rate of telomere loss has not changed. Premature cellular senescence may act as a powerful tumor-suppressor mechanism in telomerase-deficient cells with mutations that cause T-SCE levels to rise. Furthermore, T-SCE-driven premature cellular senescence may be a factor contributing to accelerated aging in Werner and Bloom syndromes, but not XFE progeroid syndrome. PMID:20798040

  12. Acupuncture therapy improves vascular hemodynamics and stiffness in middle-age hypertensive individuals.

    PubMed

    Terenteva, Nina; Chernykh, Oksana; Sanchez-Gonzalez, Marcos A; Wong, Alexei

    2018-02-01

    Acupuncture (ACU) is becoming a more common practice among hypertensive individuals. However, the reported therapeutic effects of ACU in lowering brachial blood pressure (BP) are ambiguous. Therefore, evaluating more sensitive markers of arterial functioning might unveil the protective effects of ACU on hypertension. We examined the effects of an 8-week ACU therapy intervention on vascular hemodynamics and stiffness in middle-age hypertensive individuals. Participants were randomly assigned to either ACU (n = 23) or a control group (n = 22). Brachial and aortic BP, wave reflection (AIx) and arterial stiffness (SI) were measured before and after 8 weeks. There was a significant group x time interaction (P < 0.05) for brachial and aortic BP, AIx and SI which significantly decreased (P < 0.05) following ACU but not after control. ACU led to reductions in brachial and aortic BP, wave reflection and arterial stiffness in middle-age hypertensive individuals. ACU might be effective in the prevention and treatment of hypertension. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Mitochondria and Cardiovascular Aging

    PubMed Central

    Dai, Dao-Fu; Ungvari, Zoltan

    2013-01-01

    Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

  14. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    PubMed Central

    Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

  15. The effect of copper, MDA, and accelerated aging on jet fuel thermal stability as measured by the gravimetric JFTOT

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

    Pande, S.G.; Hardy, D.R.

    1995-05-01

    Thermally unstable jet fuels pose operational problems. In order to adequately identify such fuels, factors that realistically impact on thermal stability were examined. Evaluation was based on a quantitative method of measuring thermal stability, viz., NRL`s recently developed gravimetric JFTOT. This method gives a quantitative measurement of both the strip deposit and filterables formed. The pertinent factors examined, included the individual and interactive effects of: soluble copper, MDA (metal deactivator), and aging. The latter was accelerated to simulate field conditions of approximately six months aging at ambient temperature and pressure. The results indicate that the individual and interactive effects ofmore » copper, MDA, and accelerated aging appear to be fuel dependent. Based on the results, the three test fuels examined (one JP-8 and two JP-5s) were categorized as exhibiting very good, typical, and poor thermal stabilities, respectively. For both the very good and poor thermal stability fuels, the effect of copper in conjunction with accelerated aging did not significantly increase the total thermal deposits of the neat fuels. In contrast, for the typical thermal stability fuel, the combined effects of copper and accelerated aging, did. Furthermore, the addition of MDA prior to aging of the copper-doped, typical stability fuel significantly counteracted the adverse effect of copper and aging. A similar beneficial effect of MDA was not observed for the poor stability fuel. These results focus on the compositional differences among fuels and the need to elucidate these differences (physical and chemical) for a better understanding and prediction of their performance.« less

  16. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease

    PubMed Central

    Allison, Beth J.; Kaandorp, Joepe J.; Kane, Andrew D.; Camm, Emily J.; Lusby, Ciara; Cross, Christine M.; Nevin-Dolan, Rhianon; Thakor, Avnesh S.; Derks, Jan B.; Tarry-Adkins, Jane L.; Ozanne, Susan E.; Giussani, Dino A.

    2016-01-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. PMID:26932929

  17. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.

    PubMed

    Allison, Beth J; Kaandorp, Joepe J; Kane, Andrew D; Camm, Emily J; Lusby, Ciara; Cross, Christine M; Nevin-Dolan, Rhianon; Thakor, Avnesh S; Derks, Jan B; Tarry-Adkins, Jane L; Ozanne, Susan E; Giussani, Dino A

    2016-05-01

    Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2-1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.-Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease. © FASEB.

  18. Nuclear lamina defects cause ATM-dependent NF-κB activation and link accelerated aging to a systemic inflammatory response

    PubMed Central

    Osorio, Fernando G.; Bárcena, Clea; Soria-Valles, Clara; Ramsay, Andrew J.; de Carlos, Félix; Cobo, Juan; Fueyo, Antonio; Freije, José M.P.; López-Otín, Carlos

    2012-01-01

    Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-κB activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24−/− and LmnaG609G/G609G mice). Causal involvement of NF-κB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-κB signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-κB pathway to slow down the progression of physiological and pathological aging. PMID:23019125

  19. The effect of accelerated ageing on colour stability of visible light-cured (VLC) chairside denture liners.

    PubMed

    Kostoulas, Ioannis; Polyzois, Gregory; Mitsoudis, Anastasios; Kavoura, Victoria; Frangou, Maria

    2012-06-01

    The purpose of this study was to assess the colour stability of seven visible light-cured (VLC) hard and soft denture liners by an in vitro accelerated ageing test and compare them with two autopolymerised hard and soft liners. Ten specimens of each material were fabricated. The initial colour was measured with a tri-stimulus colorimeter. One set of five specimens was placed in distilled water at 37°C in the dark for 15 days, while the remaining were subjected to UV/visible light-accelerated ageing initially for 24 h and then for 144 h. Colour change (ΔΕ) was calculated. Data were statistically analysed by anova, Tukey and t-tests at α = 0.05. All the liners showed clinically acceptable colour change (ΔΕ ≤ 6.8) in distilled water. The colour changes after ageing for Triad DuaLine, Lightdon U, Ufi Gel H and Light Liner Hard were clinically unacceptable (ΔΕ ≥ 6.8), whereas LightLiner Soft, Astron LC Soft, Triad Resiline and Flexacryl Soft presented slighter and clinically acceptable colour change (ΔΕ ≤ 6.8). Accelerated ageing affected significantly the colour stability of all denture liners tested except Astron LC Soft. Soft VLC denture liners were more colour-stable than hard VLC liners. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

  20. Parkin absence accelerates microtubule aging in dopaminergic neurons.

    PubMed

    Cartelli, Daniele; Amadeo, Alida; Calogero, Alessandra Maria; Casagrande, Francesca Vittoria Marialuisa; De Gregorio, Carmelita; Gioria, Mariarosa; Kuzumaki, Naoko; Costa, Ilaria; Sassone, Jenny; Ciammola, Andrea; Hattori, Nobutaka; Okano, Hideyuki; Goldwurm, Stefano; Roybon, Laurent; Pezzoli, Gianni; Cappelletti, Graziella

    2018-01-01

    Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell-derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Acute antioxidant supplementation and skeletal muscle vascular conductance in aged rats: role of exercise and fiber type.

    PubMed

    Hirai, Daniel M; Copp, Steven W; Schwagerl, Peter J; Haub, Mark D; Poole, David C; Musch, Timothy I

    2011-04-01

    Age-related increases in oxidative stress contribute to impaired skeletal muscle vascular control. However, recent evidence indicates that antioxidant treatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) attenuates flow-mediated vasodilation in isolated arterioles from the highly oxidative soleus muscle of aged rats. Whether antioxidant treatment with tempol evokes similar responses in vivo at rest and during exercise in senescent individuals and whether this effect varies based on muscle fiber type composition are unknown. We tested the hypothesis that redox modulation via acute systemic tempol administration decreases vascular conductance (VC) primarily in oxidative hindlimb locomotor muscles at rest and during submaximal whole body exercise (treadmill running at 20 m/min, 5% grade) in aged rats. Eighteen old (25-26 mo) male Fischer 344 x Brown Norway rats were assigned to either rest (n = 8) or exercise (n = 10) groups. Regional VC was determined via radiolabeled microspheres before and after intra-arterial administration of tempol (302 μmol/kg). Tempol decreased mean arterial pressure significantly by 9% at rest and 16% during exercise. At rest, similar VC in 26 out of 28 individual hindlimb muscles or muscle parts following tempol administration compared with control resulted in unchanged total hindlimb muscle VC (control: 0.18 ± 0.02; tempol: 0.17 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1); P > 0.05). During exercise, all individual hindlimb muscles or muscle parts irrespective of fiber type composition exhibited either an increase or no change in VC with tempol (i.e., ↑11 and ↔17 muscles or muscle parts), such that total hindlimb VC increased by 25% (control: 0.93 ± 0.04; tempol: 1.15 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1); P ≤ 0.05). These results demonstrate that acute systemic administration of the antioxidant tempol significantly impacts the control of regional vascular tone in vivo presumably via redox modulation and improves

  2. Reproducing ten years of road ageing--accelerated carbonation and leaching of EAF steel slag.

    PubMed

    Suer, Pascal; Lindqvist, Jan-Erik; Arm, Maria; Frogner-Kockum, Paul

    2009-09-01

    Reuse of industrial aggregates is still hindered by concern for their long-term properties. This paper proposes a laboratory method for accelerated ageing of steel slag, to predict environmental and technical properties, starting from fresh slag. Ageing processes in a 10-year old asphalt road with steel slag of electric arc furnace (EAF) type in the subbase were identified by scanning electron microscopy (SEM) and leaching tests. Samples from the road centre and the pavement edge were compared with each other and with samples of fresh slag. It was found that slag from the pavement edge showed traces of carbonation and leaching processes, whereas the road centre material was nearly identical to fresh slag, in spite of an accessible particle structure. Batches of moisturized road centre material exposed to oxygen, nitrogen or carbon dioxide (CO2) were used for accelerated ageing. Time (7-14 days), temperature (20-40 degrees C) and initial slag moisture content (8-20%) were varied to achieve the carbonation (decrease in pH) and leaching that was observed in the pavement edge material. After ageing, water was added to assess leaching of metals and macroelements. 12% moisture, CO2 and seven days at 40 degrees C gave the lowest pH value. This also reproduced the observed ageing effect for Ca, Cu, Ba, Fe, Mn, Pb, Ca (decreased leaching) and for V, Si, and Al (increased leaching). However, ageing effects on SO4, DOC and Cr were not reproduced.

  3. Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle.

    PubMed

    Popa-Wagner, A; Buga, Ana-Maria; Popescu, B; Muresanu, D

    2015-08-01

    To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aβ) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aβ deposition associated with AD. Aβ accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.

  4. Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

    PubMed

    Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

    2018-06-14

    Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at

  5. Circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats

    PubMed Central

    Vinogradova, Irina A.; Anisimov, Vladimir N.; Bukalev, Andrey V.; Semenchenko, Anna V.; Zabezhinski, Mark A.

    2009-01-01

    We evaluated the effect of various light/dark regimens on the survival, life span and tumorigenesis in rats. Two hundred eight male and 203 females LIO rats were subdivided into 4 groups and kept at various light/dark regimens: standard 12:12 light/dark (LD); natural lighting of the North-West of Russia (NL); constant light (LL), and constant darkness (DD) since the age of 25 days until natural death. We found that exposure to NL and LL regimens accelerated development of metabolic syndrome and spontaneous tumorigenesis, shortened life span both in male and females rats as compared to the standard LD regimen. We conclude that circadian disruption induced by light-at-night accelerates aging and promotes tumorigenesis in rats. This observation supports the conclusion of the International Agency Research on Cancer that shift-work that involves circadian disruption is probably carcinogenic to humans. PMID:20157558

  6. Acceleration of robust "biotube" vascular graft fabrication by in-body tissue architecture technology using a novel eosin Y-releasing mold.

    PubMed

    Nakayama, Yasuhide; Tsujinaka, Takahiro

    2014-02-01

    A novel eosin Y-releasing mold was designed to accelerate the fabrication of in vivo tissue engineered autologous vascular prosthetic tissues, called the "biotubes." The mold was prepared by addition of an aqueous solution of eosin Y (1∼6 w/v%) to the agar gel (0.3%), which was attached to the luminal surface of the microporous acrylate tube (diameter, 5 mm; length, 28 mm; pore size, 0.5 mmϕ). The eosin Y release period was controlled by the number of pores (3∼160). On embedding the molds into dorsal, subcutaneous pouches of rats for 1 week, completely encapsulated biotubes, mainly consisting of collagen, with thick walls (418.2 ± 173.4 μm) and robust mechanical properties (elastic modulus, 956.2 ± 196.5 kPa; burst pressure 5850 ± 2383 mmHg) were formed. These values were, respectively, more than 4.3, 3.8, and 5.6 times greater than the corresponding controls (acrylate rods). The high elastic modulus of the biotubes was obtained even with a small number of micropores (3), and a low concentration of eosin Y (1%) within a very short embedding period (5 days), irrespective of rat weights. This innovative method for rapid production of vascular grafts with thick walls and robust mechanical properties may be adaptable for the sub-emergency clinical use of biotubes in regenerative medicine. Copyright © 2013 Wiley Periodicals, Inc.

  7. Age-related changes in endothelial function and blood flow regulation.

    PubMed

    Toda, Noboru

    2012-02-01

    Vascular endothelial dysfunction is regarded as a primary phenotypic expression of normal human aging. This senescence-induced disorder is the likely culprit underlying the increased cardiovascular and metabolic disease risks associated with aging. The rate of this age-dependent deterioration is largely influenced by the poor-quality lifestyle choice, such as smoking, sedentary daily life, chronic alcohol ingestion, high salt intake, unbalanced diet, and mental stress; and it is accelerated by cardiovascular and metabolic diseases. Although minimizing these detrimental factors is the best course of action, nonetheless chronological age steadily impairs endothelial function through reduced endothelial nitric oxide synthase (eNOS) expression/action, accelerated nitric oxide (NO) degradation, increased phosphodiesterase activity, inhibition of NOS activity by endogenous NOS inhibitors, increased production of reactive oxygen species, inflammatory reactions, decreased endothelial progenitor cell number and function, and impaired telomerase activity or telomere shortening. Endothelial dysfunction in regional vasculatures results in cerebral hypoperfusion triggering cognitive dysfunction and Alzheimer's disease, coronary artery insufficiency, penile erectile dysfunction, and circulatory failures in other organs and tissues. Possible prophylactic measures to minimize age-related endothelial dysfunction are also summarized in this review. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Priming of microglia in a DNA-repair deficient model of accelerated aging.

    PubMed

    Raj, Divya D A; Jaarsma, Dick; Holtman, Inge R; Olah, Marta; Ferreira, Filipa M; Schaafsma, Wandert; Brouwer, Nieske; Meijer, Michel M; de Waard, Monique C; van der Pluijm, Ingrid; Brandt, Renata; Kreft, Karim L; Laman, Jon D; de Haan, Gerald; Biber, Knut P H; Hoeijmakers, Jan H J; Eggen, Bart J L; Boddeke, Hendrikus W G M

    2014-09-01

    Aging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Resin composite characterizations following a simplified protocol of accelerated aging as a function of the expiration date.

    PubMed

    D'Alpino, Paulo Henrique Perlatti; Vismara, Marcus Vinícius Gonçalves; Mello, Luciano Marcelo de Medeiros; Di Hipólito, Vinicius; González, Alejandra Hortencia Miranda; Graeff, Carlos Frederico de Oliveira

    2014-07-01

    This study evaluated the mechanical, thermal, and morphological characteristics of different classifications of dental composites as a function of the material condition (new, aged and expired). Specimens were obtained according to these factors: Composites: Filtek P60, Filtek Z250, Filtek Z350XT, and Filtek Silorane; and Material conditions: new, aged, and expired. The syringe composites underwent an accelerated aging protocol (Arrhenius model). The flexural strength (FS) and flexural modulus (E) were obtained. The thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were also performed and the glass transition temperature (Tg) and the weight loss calculated. Topographic analysis of the composites was performed under SEM. The material conditions influenced the mechanical properties of the composites. The silorane composite exhibited a characteristic thermal behavior different from that of the methacrylates. In general, the Tg increased after the accelerated aging protocol and decreased for expired ones, compared to the new composites. A significant increase in FS of Filtek Z350XT after aging was accompanied by an increase in the Tg. The filler packings were in accordance with the manufacture׳s information. The topographic aspects of the composites were modified as a function of the material condition. The mechanical properties of the composites following a simplified protocol of accelerated aging varied as a function of the expiration date. The silorane composite presented a characteristic thermal behavior. Although the dental manufacturers may not be able to control variables as storage temperature and transportation conditions, these effects on the composite clinical performance can be minimized if properly considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Overexpression of the Cell Cycle Inhibitor p16INK4a Promotes a Prothrombotic Phenotype Following Vascular Injury in Mice

    PubMed Central

    Cardenas, Jessica C.; Owens, A. Phillip; Krishnamurthy, Janakiraman; Sharpless, Norman E.; Whinna, Herbert C.; Church, Frank C.

    2011-01-01

    Objective Age-associated cellular senescence is thought to promote vascular dysfunction. p16INK4a is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging. In this study, we examine the contribution of p16INK4a overexpression on venous thrombosis. Methods and Results Mice overexpressing p16INK4a were studied with four different vascular injury models: (1) ferric chloride (FeCl3) and (2) Rose Bengal to induce saphenous vein thrombus formation; (3) FeCl3 and vascular ligation to examine thrombus resolution; and (4) LPS administration to initiate inflammation-induced vascular dysfunction. p16INK4a transgenic mice had accelerated occlusion times (13.1 ± 0.4 min) compared to normal controls (19.7 ± 1.1 min) in the FeCl3 model and 12.7 ± 2.0 and 18.6 ± 1.9, respectively in the Rose Bengal model. Moreover, overexpression of p16INK4a delayed thrombus resolution compared to normal controls. In response to LPS treatment, the p16INK4a transgenic mice showed enhanced thrombin generation in plasma-based calibrated automated thrombography (CAT) assays. Finally, bone marrow transplantation studies suggested increased p16INK4a expression in hematopoietic cells contributes to thrombosis, demonstrating a role for p16INK4a expression in venous thrombosis. Conclusions Venous thrombosis is augmented by overexpression of the cellular senescence gene p16INK4a. PMID:21233453

  11. Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats.

    PubMed

    Amor, Sara; García-Villalón, Angel Luis; Rubio, Carmen; Carrascosa, Jose Ma; Monge, Luis; Fernández, Nuria; Martín-Carro, Beatriz; Granado, Miriam

    2017-02-01

    Cardiovascular alterations are the most prevalent cause of impaired physiological function in aged individuals with kidney being one the most affected organs. Aging-induced alterations in renal circulation are associated with a decrease in endothelium-derived relaxing factors such as nitric oxide (NO) and with an increase in contracting factors such as endothelin-1(ET-1). As caloric restriction (CR) exerts beneficial effects preventing some of the aging-induced alterations in cardiovascular system, the aim of this study was to analyze the effects of age and caloric restriction in the vascular response of renal arteries to ET-1 in aged rats. Vascular function was studied in renal arteries from 3-month-old Wistar rats fed ad libitum (3m) and in renal arteries from 8-and 24-month-old Wistar rats fed ad libitum (8m and 24m), or subjected to 20% caloric restriction during their three last months of life (8m-CR and 24m-CR). The contractile response to ET-1 was increased in renal arteries from 8m and 24m compared to 3m rats. ET-1-induced contraction was mediated by ET-A receptors in all experimental groups and also by ET-B receptors in 24m rats. Caloric restriction attenuated the increased contraction to ET-1 in renal arteries from 8m but not from 24m rats possibly through NO release proceeding from ET-B endothelial receptors. In 24m rats, CR did not attenuate the aging-increased response of renal arteries to ET-1, but it prevented the aging-induced increase in iNOS mRNA levels and the aging-induced decrease in eNOS mRNA levels in arterial tissue. In conclusion, aging is associated with an increased response to ET-1 in renal arteries that is prevented by CR in 8m but not in 24m rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Assessment of risk of peripheral vascular disease and vascular care capacity in low- and middle-income countries.

    PubMed

    Gyedu, A; Stewart, B T; Nakua, E; Quansah, R; Donkor, P; Mock, C; Hardy, M; Yangni-Angate, K H

    2016-01-01

    This study aimed to describe national peripheral vascular disease (PVD) risk and health burden, and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in low- and middle-income countries was defined, and capacity improvement priorities were identified. Data to estimate PVD risk factor burden were obtained from the World Health Organization Study on Global Ageing and Adult Health (SAGE), Ghana, and the Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) database. In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were described. From the SAGE database, there were 4305 respondents aged at least 50 years with data to estimate PVD risk. Of these, 57·4 per cent were at moderate to risk high of PVD with at least three risk factors; extrapolating nationally, the estimate was 1 654 557 people. Based on IHME GBD data, the estimated disability-adjusted life-years incurred from PVD increased fivefold from 1990 to 2010 (from 6·3 to 31·7 per 100 000 persons respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, and in perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of PVD falling on healthcare systems in low- and middle-income countries. These countries are not well equipped to handle vascular surgical care, and rapid development of such capacity would be difficult and expensive. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  13. Joint scientific statement of the European Association for the Study of Obesity and the European Society of Hypertension: Obesity and early vascular ageing.

    PubMed

    Jordan, Jens; Nilsson, Peter M; Kotsis, Vasilios; Olsen, Michael H; Grassi, Guido; Yumuk, Volkan; Hauner, Hans; Zahorska-Markiewicz, Barbara; Toplak, Hermann; Engeli, Stefan; Finer, Nick

    2015-03-01

    Current cardiovascular risk scores do not include obesity or fat distribution as independent factors, and may underestimate risk in obese individuals. Assessment of early vascular ageing (EVA) biomarkers including arterial stiffness, central blood pressure, carotid intima-media thickness and flow-mediated vasodilation may help to refine risk assessment in obese individuals in whom traditional cardiovascular risk scores and factors suggest no need for specific medical attention. A number of issues need to be addressed before this approach is ready for translation into routine clinical practice. Methodologies for measurements of vascular markers need to be further standardized and less operator-dependent. The utility of these nontraditional risk factors will also need to be proven in sufficiently large and properly designed interventional studies. Indeed, published studies on vascular markers in obesity and weight loss vary in quality and study design, are sometimes conducted in small populations, use a variety of differing methodologies and study differing vascular beds. Finally, current vascular measurements are still crude and may not be sufficient to cover the different aspects of EVA in obesity.

  14. EFFECT THE CARDIOMETABOLIC RISK FACTORS ON VASCULAR AGING IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE CONCOMITANT WITH SUBCLINICAL HYPOTHYROIDISM.

    PubMed

    Kolesnikova, E; Potapenko, A

    2017-09-01

    The article presents the analysis of the relationship between thyroid function abnormality -subclinical hypothyroidism (SH) and non-alcoholic fatty liver disease (NAFLD), depending on age peculiarities (>50 years and <50 years), and the risk of cardiovascular complications in this category of patients. Research of early predictors of cardiovascular complications: dyslipidemia, insulin resistance, inflammatory marker- C-reactive protein, marker of vascular aging-telomerase activity and marker of endothelial dysfunction (ED) - CDECs and VEGF-A that have been analyzed are on the front burner. In this regard, the effect of the given values on the formation of cardiac risk in patients with NAFLD combined with SH was studied. 74 patients (29 men (39.2%) and 45 women (60.8%)), with verified NAFLD and SH have been examined. Patients were divided into two clinical groups: group 1 (n=31) - patients with NAFLD, with the mean age 47.2±2.6 years; group 2 (n=43) patients with NAFLD in combination with SH, with the mean age 56,8±6,5 years. Results of the performed tests have shown that patients with NAFLD combined with SH aged over 50 years have pro-atherogenic lipid profile and significantly more pronounced manifestations of endothelial dysfunction. The process of age-dependent shortening of telomere length predominantly in the buccal epithelium is an important point to be made. Consequently, the total effect of cardiometabolic risk factors in patients with NAFLD combined with SH probably is the determining factor of the rate of progression of vascular aging.

  15. Protective role of sulphoraphane against vascular complications in diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori

    2016-10-01

    Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes.

  16. Methodology for the evaluation of vascular surgery manpower in France.

    PubMed

    Berger, L; Mace, J M; Ricco, J B; Saporta, G

    2013-01-01

    The French population is growing and ageing. It is expected to increase by 2.7% by 2020, and the number of individuals over 65 years of age is expected to increase by 3.3 million, a 33% increase, between 2005 and 2020. As the number of vascular surgery procedures is closely associated with the age of a population, it is anticipated that there will be a significant increase in the workload of vascular surgeons. A model is presented to predict changes in vascular surgery activity according to population ageing, including other parameters that could affect workload evolution. Three types of arterial procedures were studied: infrarenal abdominal aortic aneurysm (AAA) surgery, peripheral arterial occlusive disease (PAOD) procedures and carotid artery (CEA) procedures. Data were selected and extracted from the national PMSI (Medical Information System Program) database. Data obtained from 2000 were used to predict data based on an ageing population for 2008. From this model, a weighted index was defined for each group by comparing expected and observed workloads. According to the model, over this 8-year period, there was an overall increase in vascular procedures of 52.2%, with an increase of 89% in PAOD procedures. Between 2000 and 2009, the total increase was 58.0%, with 3.9% for AAA procedures, 101.7% for PAOD procedures and 13.2% for CEA procedures. The weighted model based on an ageing population and corrected by a weighted factor predicted this increase. This weighted model is able to predict the workload of vascular surgeons over the coming years. An ageing population and other factors could result in a significant increase in demand for vascular surgical services. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  17. Increasing measurement accuracy of age-related BOLD signal change: Minimizing vascular contributions by resting-state-fluctuation-of-amplitude scaling

    PubMed Central

    Kannurpatti, Sridhar S.; Motes, Michael A.; Rypma, Bart; Biswal, Bharat B.

    2012-01-01

    In this report we demonstrate a hemodynamic scaling method with resting-state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects, that RSFA and BH performed comparably in accounting for age-related hemodynamic coupling changes, and yielded more veridical estimates of age-related differences in task-related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intra-subject amplitude variation across regions of activated cortex, and inter-subject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra- and inter-subject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the un-scaled BOLD amplitude distribution, attenuated the neural activity related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group prior to and after scaling. After accounting for vascular variability differences through scaling, age-related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA-scaled data yield age-related neural activity differences during task performance with negligible effects from non-neural (i.e., vascular) sources. PMID:20665721

  18. Increasing measurement accuracy of age-related BOLD signal change: minimizing vascular contributions by resting-state-fluctuation-of-amplitude scaling.

    PubMed

    Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B

    2011-07-01

    In this report we demonstrate a hemodynamic scaling method with resting-state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects which RSFA and BH performed comparably in accounting for age-related hemodynamic coupling changes, and yielded more veridical estimates of age-related differences in task-related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intrasubject amplitude variation across regions of activated cortex, and intersubject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra- and intersubject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the unscaled BOLD amplitude distribution, attenuated the neural activity-related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group before and after scaling. After accounting for vascular variability differences through scaling, age-related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA-scaled data yield age-related neural activity differences during task performance with negligible effects from non-neural (i.e., vascular) sources. Copyright © 2010 Wiley-Liss, Inc.

  19. Effect of accelerated ageing and surface sealing on the permanent deformation of auto-polymerising soft linings.

    PubMed

    da Silva, Joaquim; Takahashi, Jessica; Nuňez, Juliana; Consani, Rafael; Mesquita, Marcelo

    2012-09-01

    To compare the effects of different ageing methods on the permanent deformation of two permanent soft liners. The materials selected were auto-polymerising acrylic resin and silicone-based reliners. Sealer coating was also evaluated. Sixty specimens of each reliner were manufactured (12.7 mm diameter and 19 mm length). Specimens were randomly distributed into 12 groups (n = 10) and submitted to one of the accelerated ageing processes. Permanent deformation tests were conducted with a mechanical device described within the American Dental Association specification number 18 with a compressive load of 750 gf applied for 30 s. All data were submitted for statistical analysis. Mann-Whitney test compared the effect of the surface sealer on each material and the permanent deformation of the materials in the same ageing group (p = 0.05). Kruskal-Wallis and Dunn tests compared all ageing groups of each material (p = 0.05). The silicone-based reliner presented a lower permanent deformation than the acrylic resin-based reliner, regardless of the ageing procedure. The surface sealer coating was effective only for the thermocycled silicone group and the accelerated ageing processes affected only the permanent deformation of the acrylic resin-based material. The silicone-based reliner presented superior elastic properties and the thermocycling was more effective in ageing the materials. © 2010 The Gerodontology Society and John Wiley & Sons A/S.

  20. Sildenafil Increases Sympathetically Mediated Vascular Tone in Humans

    PubMed Central

    2013-01-01

    BACKGROUND Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP–mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (−73% ± 3% vs −63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic–mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the

  1. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    PubMed Central

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

  2. Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.

    PubMed

    Román, Gustavo C; Kalaria, Raj N

    2006-12-01

    Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

  3. Aging impairs transcriptional regulation of vascular endothelial growth factor in human microvascular endothelial cells: implications for angiogenesis and cell survival.

    PubMed

    Ahluwalia, A; Jones, M K; Szabo, S; Tarnawski, A S

    2014-04-01

    In some tissues, aging impairs angiogenesis and reduces expression of vascular endothelial growth factor A (VEGF), a fundamental regulator of angiogenesis. We previously examined angiogenesis in aging and young gastric mucosa in vivo and in vitro and showed that an imbalance between expressions of VEGF (pro-angiogenic factor) and endostatin (anti-angiogenic protein) results in an aging-related impairment of angiogenesis in rats. However, the human relevance of these findings, and whether these mechanisms apply to endothelial cells derived from other tissues, is not clear. Since P-STAT3 and P-CREB are transcription factors that, in association with HIF-1α, can activate VEGF gene expression in some cells (e.g., liver cancer cells, vascular smooth muscle cells), we examined the expression of these two proteins in human dermal microvascular endothelial cells (HMVECs) derived from aging and neonatal individuals. We examined and quantified in vitro angiogenesis, expression of VEGF, P-STAT3, P-CREB and importin-α in HMVECs isolated from neonates (neonatal) and a 66 year old subject (aging). We also examined the effects of treatment with exogenous VEGF and endostatin on in vitro angiogenesis in these cells. Endothelial cells isolated from aging individuals had impaired angiogenesis (vs. neonatal endothelial cells) and reduced expression of VEGF mRNA and protein. Aged HMVECs also had reduced importin-α expression, and reduced expression and nuclear translocation of P-STAT3 and P-CREB. Reduced VEGF gene expression in aged HMVECs strongly correlated with the decreased levels of P-STAT3, P-CREB and importin-α in these cells. Our study clearly demonstrates that endothelial cells from aging individuals have impaired angiogenesis and reduced expression of VEGF likely due to impaired nuclear transport of P-STAT3 and P-CREB transcription factors in these cells.

  4. THE ACCELERATION OF THE AGING PROCESS OF ALCOHOLIC BEVERAGES BY $gamma$- IRRADIATION

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

    Sumiki, Y.

    Using gamma irradiation, the aging of alcoholic beverages can be accelerated. Plain Japanese sake can be aged within l hr with a Co/sup 60/ source of 270 c (total dose l0,000 r). The taste and flavor of fresh sake can be improved with a few thousand r irr-adiation. The unpleasant flavor of poor grade sake and the yeast taste of new sake can be eliminated by irradiation. For natur-ally aged sake and compound sake, the change was very little for a dosage of l0,000 r, and beyond this limit the irradiated sakes were over-aged. For both aged sake and newmore » sake, undesirable tastes were detected for an irradiation dosage greater than 20,000 r. When the dosage approached l00,000 r, the typical irradiation odor'' was detected. Therefore, the ideal dosage range is from several thousand r to l04 r. At an irradiation dosage of l0,000 r, whisky and brandy were aged r-apidly. However, the color was somewhat faded. Distilled Japanese sakes were improved by ir-radiation, but excess irradiation caused undesirable aldehyde odors. (OID)« less

  5. Early age strength increase of fly ash blended cement by a ternary hardening accelerating admixture

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

    Hoang, Kien; Justnes, Harald; SINTEF Building and Infrastructure

    The applicability of a combination of sodium thiocyanate (NaSCN), diethanolamine (DEA) and glycerol (Gly) with small dosages as a ternary hardening accelerating admixture for fly ash blended cement (OPC-FA) was studied. The ternary admixture induced higher early and later age mortar strength at both low (5 °C) and normal (20 °C) temperature. Despite used in lower dosage the ternary admixture led to higher strength of the investigated OPC-FA system than other chemicals (e.g. sodium sulfate). Results obtained from isothermal calorimetry, thermogravimetric analysis (TGA) and X-ray diffraction (XRD) showed that the ternary admixture accelerated the cement hydration and increased the amountmore » of AFm (notably calcium hemicarboaluminate hydrate) in the hydration products. A synergistic effect between the three components of the accelerator on the hydration of OPC-FA system was observed.« less

  6. Duration to Establish an Emergency Vascular Access and How to Accelerate It: A Simulation-Based Study Performed in Real-Life Neonatal Resuscitation Rooms.

    PubMed

    Schwindt, Eva M; Hoffmann, Florian; Deindl, Philipp; Waldhoer, Thomas J; Schwindt, Jens C

    2018-05-01

    To compare the duration to establish an umbilical venous catheter and an intraosseous access in real hospital delivery rooms and as a secondary aim to assess delaying factors during establishment and to provide recommendations to accelerate vascular access in neonatal resuscitation. Retrospective analysis of audio-video recorded neonatal simulation training. Simulation training events in exact replications of actual delivery/resuscitation rooms of 16 hospitals with different levels of care (Austria and Germany). Equipment was prepared the same way as for real clinical events. Medical teams of four to five persons with birth-related background (midwives, nurses, neonatologists, and anesthesiologists) in a realistic team composition. Audio-video recorded mannequin-based simulated resuscitation of an asphyxiated newborn including the establishment of either umbilical venous catheter or intraosseous access. The duration of access establishment (time from decision to first flush/aspiration), preparation (decision to start of procedure), and the procedure itself (start to first flush/aspiration) was significantly longer for umbilical venous catheter than for intraosseous access (overall duration 199 vs 86 s). Delaying factors for umbilical venous catheter establishment were mainly due to the complex approach itself, the multitude of equipment required, and uncertainties about necessary hygiene standards. Challenges in intraosseous access establishment were handling of the unfamiliar material and absence of an intraosseous access kit in the resuscitation room. There was no significant difference between the required duration for access establishment between large centers and small hospitals, but a trend was observed that duration for umbilical venous catheter was longer in small hospitals than in centers. Duration for intraosseous access was similar in both hospital types. Vascular access establishment in neonatal resuscitation could be accelerated by infrastructural

  7. Influence of surface sealing on color stability and roughness of composite submitted to ultraviolet-accelerated aging.

    PubMed

    Catelan, Anderson; Suzuki, Thaís Yumi Umeda; Becker, Francisco; Briso, André Luiz Fraga; Dos Santos, Paulo Henrique

    2017-05-01

    In the present study, we evaluated the influence of surface sealing on color stability and surface roughness of a composite resin after accelerated artificial aging. Thirty-two specimens of a composite were prepared. After 24 h, the specimens were polished and divided into four groups (n = 8), according to the surface sealant used, including the control, which had no sealant application. Baseline color was measured according to the CIELab system using a reflection spectrophotometer. Surface roughness was determined using a profilometer with a cut-off of 0.25 mm. After these tests, specimens were aged for 252 h in an ultraviolet (UV)-accelerated aging chamber. Color stability was determined by difference between coordinates obtained before and after the aging procedure. Data of color change and roughness were evaluated by anova and Fisher's exact test (α = 0.05). The results showed that the unsealed group had the highest color change compared to other groups (P = 0.0289), and there was no significant difference between groups sealed with surface sealant (P > 0.05). The artificial aging caused an increase in roughness values independent of the experimental group studied (P = 0.0015). The sealed composites showed lower color change after UV aging, but all groups showed clinically-acceptable color change, and only liquid polish decreased roughness. © 2016 John Wiley & Sons Australia, Ltd.

  8. Validation of accelerated ageing of Thales rotary Stirling cryocoolers for the estimation of MTTF

    NASA Astrophysics Data System (ADS)

    Seguineau, C.,; Cauquil, J.-M.; Martin, J.-Y.; Benschop, T.

    2016-05-01

    The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. The current market needs tend to reliability figures higher than 15,000hrs in "standard conditions". Field returns are hardly useable mostly because of the uncertain environmental conditions of use, or the differences in user profiles. A previous paper explains how Thales Cryogenics has developed an approach based on accelerated ageing and statistical analysis [1]. The aim of the current paper is to compare results obtained on accelerated ageing on one side, and on the other side, specific field returns where the conditions of use are well known. The comparison between prediction and effective failure rate is discussed. Moreover, a specific focus is done on how some new applications of cryocoolers (continuous operation at a specific temperature) can increase the MTTF. Some assumptions are also exposed on how the failure modes, effects and criticality analysis evolves for continuous operation at a specific temperature and compared to experimental data.

  9. Displacement of plasma protein and conduction velocity in rats under action of acceleration forces and hypokinesia

    NASA Technical Reports Server (NTRS)

    Baranski, S.; Edelwejn, Z.; Wojtkowiak, M.

    1980-01-01

    The permeability of capillary vessels was investigated in order to determine if acceleration alone or following prolonged hypokinesia would induce changes in the vascular wall leading to the penetration by l-albumins and/or proteins with larger molecules. In rats undergoing action of +5 Gz accelerations, no increase in vascular permeability, as tested with the use of (Cr-5k)-globulin, was demostrated. In rats immobilized for 4 weeks before centrifugation, rather weak migration of (Cr-51)-globulin from the vessels was observed. Immobilization resulted also in lowering of conduction velocity in the sciatic nerve.

  10. Lipidomics in vascular health: current perspectives.

    PubMed

    Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

    2015-01-01

    Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

  11. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer.

    PubMed

    Durso, Danielle Fernandes; Bacalini, Maria Giulia; Sala, Claudia; Pirazzini, Chiara; Marasco, Elena; Bonafé, Massimiliano; do Valle, Ítalo Faria; Gentilini, Davide; Castellani, Gastone; Faria, Ana Maria Caetano; Franceschi, Claudio; Garagnani, Paolo; Nardini, Christine

    2017-04-04

    Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively. We show that the epigenetic age estimated from blood DNA methylation data is statistically significantly associated to future breast and male colorectal cancer development. These results are corroborated by survival analysis that shows significant association between age acceleration and cancer incidence suggesting that the chance of developing age-related diseases may be predicted by circulating epigenetic markers, with a dependence upon tumor type, sex and age estimator. These are encouraging results towards the non-invasive and perspective usage of epigenetic biomarkers.

  12. Outcomes of truncal vascular injuries in children

    PubMed Central

    Allison, Nathan D.; Anderson, Christopher M.; Shah, Shinil K.; Lally, Kevin P.; Hayes-Jordan, Andrea; Tsao, Kuo-Jen; Andrassy, Richard J.; Cox, Charles S.

    2011-01-01

    Background Pediatric truncal vascular injuries occur infrequently and have a reported mortality rate of 30% to 50%. This report examines the demographics, mechanisms of injury, associated trauma, and outcome of patients presenting for the past 10 years at a single institution with truncal vascular injuries. Methods A retrospective review (1997-2006) of a pediatric trauma registry at a single institution was undertaken. Results Seventy-five truncal vascular injuries occurred in 57 patients (age, 12 ± 3 years); the injury mechanisms were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular complications occurred more frequently in patients with abdominal vascular injuries who were hemodynamically unstable on presentation. All patients with thoracic vascular injuries presenting with hemodynamic instability died. In patients with neck vascular injuries, 1 of 2 patients who were hemodynamically unstable died, compared to 1 of 12 patients who died in those who presented hemodynamically stable. Overall survival was 75%. Conclusions Survival and complications of pediatric truncal vascular injury are related to hemodynamic status at the time of presentation. Associated injuries are higher with trauma involving the abdomen. PMID:19853755

  13. [Thrombosis in vascular accesses for haemodialysis: rescue treatment using invasive vascular radiological techniques].

    PubMed

    García Medina, J; Lacasa Pérez, N; Muray Cases, S; Pérez Garrido, I; García Medina, V

    2009-01-01

    The purpose of this paper is to communicate our experience in the salvage of thrombosed haemodialysis vascular accesses using interventional radiology techniques. In the last four years, we have treated, by radiological means, 101 thrombosed haemodialysis vascular accesses. There were 44 autologous arteriovenous fistulas (43.56%) and 57 PTFE grafts (56.44%). There were 69 men (68.3%) and 32 women (31.7%). The mean age was 67.73 years (range 33-84). The mean vascular access age was 23.79 months (range 1-132). Manual catheter-directed aspiration was used. Fragmented, triturated or pushed the thrombus against the pulmonary circulation was avoided in all cases. 78 accesses were salvaged (77.2%). Autologous fistulas average and PTFE grafts success rate were 84.44% and 71.42% respectively. Angioplasty in one or more lesions after thromboaspiration was performed in all accesses, except six (5.9%). Metallic endoprostheses were implanted in 14 accesses (13.9%). Mean follow-up was 9 months (range 0-44). Primary patency was 42.3% +/- 5 at 6 months and 32% +/- 4 at one year. Autologous fistulas patency was better than PTFE grafts patency (p < or =0,05). Our results suggest thrombosed autologous arteriovenous fistulas salvage is better than PTFE grafts. This justifies interventional radiology techniques in these situations.

  14. ACCELERATED FAILURE TIME MODELS PROVIDE A USEFUL STATISTICAL FRAMEWORK FOR AGING RESEARCH

    PubMed Central

    Swindell, William R.

    2009-01-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model “deceleration factor”. AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data. PMID:19007875

  15. Accelerated failure time models provide a useful statistical framework for aging research.

    PubMed

    Swindell, William R

    2009-03-01

    Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

  16. Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

    PubMed

    Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

    2014-08-01

    Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

  17. Factors Affecting Choroidal Vascular Density in Normal Eyes: Quantification Using En Face Swept-Source Optical Coherence Tomography.

    PubMed

    Fujiwara, Atsushi; Morizane, Yuki; Hosokawa, Mio; Kimura, Shuhei; Kumase, Fumiaki; Shiode, Yusuke; Doi, Shinichiro; Hirano, Masayuki; Toshima, Shinji; Hosogi, Mika; Shiraga, Fumio

    2016-10-01

    To quantify the vascular density of the choroid of normal eyes and to identify the influencing factors using en face images obtained with swept-source optical coherence tomography (SS OCT). Prospective cross-sectional study. One hundred and sixty-three eyes of 163 healthy volunteers (83 female; mean age 42.2 ± 22.6 years) with a corrected visual acuity of ≥1.0 were investigated. En face SS OCT images of the choroid were used for quantitative assessment of the vascular density in the large choroid vessel layer. Relationships between vascular density of the choroid and age, sex, refractive error (RE), axial length (AL), and subfoveal choroidal thickness (SCT) were also investigated. There was a significant negative relationship between vascular density of the choroid and subject age (P < .001). Analysis according to age showed a significant correlation in the group aged >30 years (P < .001), but not in the group aged ≤30 years (P = .225). SCT had a significant positive relationship with vascular density of the choroid (P < .001). However, a significant correlation was not observed between sex, RE, or AL and vascular density of the choroid (P = .981, P = .292, and P = .216, respectively). Multivariable regression analysis with vascular density of the choroid as the dependent variable and age, sex, RE, AL, and SCT as independent variables showed that age and SCT are important determinants of vascular density of the choroid (P < .001). Age and SCT affect vascular density of the choroid. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Visual evaluation of color stability after accelerated aging of pigmented and nonpigmented silicones to be used in facial prostheses.

    PubMed

    Mancuso, Daniela Nardi; Goiato, Marcelo Coelho; Dekon, Stefan Fiuza de Carvalho; Gennari-Filho, Humberto

    2009-01-01

    The objective of this study was to evaluate by a visual method of comparison the color stability of nonpigmented and pigmented facial silicones after accelerated aging. Two kinds of silicones were used in this study; one specifically formulated for facial prostheses and the other an acetic silicone for industrial use. Twenty-four trial bodies were made for each silicone. These were divided into colorless and intrinsically pigmented groups: ceramic, make-up, and iron oxide. The groups were submitted to accelerated aging for nonmetallic materials. An initial reading and subsequent readings were made at 163, 351, 692, and 1000 hours using a visual method of comparison. The values were annotated in a spreadsheet by two observers, according to scores elaborated for this study. All groups presented color stability in the visual method. According to the results obtained and analyzed in this study, we can conclude that both silicones, Silastic 732 RTV and Silastic MDX 4-4210, behaved similarly, they can therefore be indicated for use in maxillofacial prosthesis. The time factor of aging influenced negatively, independently of the pigmentation, or lack of it, and of silicones and no group had visually noticeable alterations in any of the accelerated aging time, independently of the addition or not of pigments.

  19. RECOVERY OF VASCULAR FUNCTION AFTER EXPOSURE TO A SINGLE BOUT OF SEGMENTAL VIBRATION

    PubMed Central

    Krajnak, Kristine; Waugh, Stacey; Miller, G. Roger; Johnson, Claud

    2015-01-01

    Work rotation schedules may be used to reduce the negative effects of vibration on vascular function. This study determined how long it takes vascular function to recover after a single exposure to vibration in rats (125 Hz, acceleration 5g). The responsiveness of rat-tail arteries to the vasoconstricting factor UK14304, an α2C-adrenoreceptor agonist, and the vasodilating factor acetylcholine (ACh) were measured ex vivo 1, 2, 7, or 9 d after exposure to a single bout of vibration. Vasoconstriction induced by UK14304 returned to control levels after 1 d of recovery. However, re-dilation induced by ACh did not return to baseline until after 9 d of recovery. Exposure to vibration exerted prolonged effects on peripheral vascular function, and altered vascular responses to a subsequent exposure. To optimize the positive results of work rotation schedules, it is suggested that studies assessing recovery of vascular function after exposure to a single bout of vibration be performed in humans. PMID:25072825

  20. Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure

    PubMed Central

    Jablonski, Kristen L.; Gates, Phillip E.; Pierce, Gary L.; Seals, Douglas R.

    2012-01-01

    Background Age and increasing systolic blood pressure (BP) are associated with vascular endothelial dysfunction, but the factors involved are incompletely understood. We tested the hypothesis that vascular endothelial function is related to dietary sodium intake among middle-aged and older adults (MA and O) with elevated systolic BP. Methods Data were analyzed on 25 otherwise healthy adults aged 48–73 years with high normal systolic BP or stage I systolic hypertension (130–159 mmHg). Self-reported sodium intake was <100 mmol/d in 12 (7 M) subjects (low sodium, 73 ± 6 mmol/d) and between 100 and 200 mmol/d in 13 (9 M) subjects (normal sodium, 144 ± 6 mmol/d). Results Groups did not differ in other dietary factors, age, body weight and composition, BP, metabolic risk factors, physical activity and maximal aerobic capacity. Plasma concentrations of norepinephrine, endothelin-1, oxidized low-density lipoproteins (LDL), antioxidant status and inflammatory markers did not differ between groups. Brachial artery flow-mediated dilation (FMD) was 42% (mm Δ) to 52% (% Δ) higher in the low versus normal sodium group (p <0.05). In all subjects, brachial artery FMD was inversely related to dietary sodium intake (FMD mm Δr =−0.40, p <0.05; %Δr =−0.53, p <0.01). Brachial artery FMD was not related to any other variable. In contrast, endothelium-independent dilation did not differ between groups (p ≥ 0.24) and was not related to sodium intake in the overall group (p ≥ 0.29). Conclusions Low sodium intake is associated with enhanced brachial artery FMD in MA and O with elevated systolic BP. These results suggest that dietary sodium restriction may be an effective intervention for improving vascular endothelial function in this high-risk group. PMID:19723834

  1. Vascular effects of advanced glycation end-products: content of immunohistochemically detected AGEs in radial artery samples as a predictor for arterial calcification and cardiovascular risk in asymptomatic patients with chronic kidney disease.

    PubMed

    Janda, Katarzyna; Krzanowski, Marcin; Gajda, Mariusz; Dumnicka, Paulina; Jasek, Ewa; Fedak, Danuta; Pietrzycka, Agata; Kuźniewski, Marek; Litwin, Jan A; Sułowicz, Władysław

    2015-01-01

    Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

  2. Role of α-adrenergic vasoconstriction in regulating skeletal muscle blood flow and vascular conductance during forearm exercise in ageing humans

    PubMed Central

    Richards, Jennifer C; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

    2014-01-01

    In healthy humans, ageing is typically associated with reduced skeletal muscle blood flow and vascular conductance during exercise. Further, there is a marked increase in resting sympathetic nervous system (SNS) activity with age, yet whether augmented SNS-mediated α-adrenergic vasoconstriction contributes to the age-associated impairment in exercising muscle blood flow and vascular tone in humans is unknown. We tested the hypothesis that SNS-mediated vasoconstriction is greater in older than young adults and limits muscle (forearm) blood flow (FBF) during graded handgrip exercise (5, 15, 25% maximal voluntary contraction (MVC)). FBF was measured (Doppler ultrasound) and forearm vascular conductance (FVC) was calculated in 11 young (21 ± 1 years) and 12 older (62 ± 2 years) adults in control conditions and during combined local α- and β-adrenoreceptor blockade via intra-arterial infusions of phentolamine and propranolol, respectively. Under control conditions, older adults exhibited significantly lower FBF and FVC at 15% MVC exercise (22.6 ± 1.3 vs. 29 ± 3.3 ml min−1 100 g forearm fat-free mass (FFM)−1 and 21.7 ± 1.2 vs. 33.6 ± 4.0 ml min−1 100 g FFM−1 100 mmHg−1; P < 0.05) and 25% MVC exercise (37.4 ± 1.4 vs. 46.0 ± 4.9 ml min−1 100 g FFM−1 and 33.7 ± 1.4 vs. 49.0 ± 5.7 ml min−1 100 g FFM−1 100 mmHg−1; P < 0.05), whereas there was no age group difference at 5% MVC exercise. Local adrenoreceptor blockade increased FBF and FVC at rest and during exercise in both groups, although the increase in FBF and FVC from rest to steady-state exercise was similar in young and older adults across exercise intensities, and thus the age-associated impairment in FBF and FVC persisted. Our data indicate that during graded intensity handgrip exercise, the reduced FVC and subsequently lower skeletal muscle blood flow in older healthy adults is not due to augmented sympathetic vasoconstriction, but rather due to

  3. Blood pressure at age 60-65 versus age 70-75 and vascular dementia: a population based observational study.

    PubMed

    Peng, Mingkai; Chen, Guanmin; Tang, Karen L; Quan, Hude; Smith, Eric E; Faris, Peter; Hachinski, Vladimir; Campbell, Norm R C

    2017-10-27

    Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

  4. Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.

    PubMed

    Rabin, Jennifer S; Schultz, Aaron P; Hedden, Trey; Viswanathan, Anand; Marshall, Gad A; Kilpatrick, Emily; Klein, Hannah; Buckley, Rachel F; Yang, Hyun-Sik; Properzi, Michael; Rao, Vaishnavi; Kirn, Dylan R; Papp, Kathryn V; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

    2018-05-21

    Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment. To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease. In this longitudinal observational study, we examined clinically normal older adults from the Harvard Aging Brain Study. Participants were required to have baseline imaging data (FDG-PET, Aβ-PET, and magnetic resonance imaging), baseline medical data to quantify vascular risk, and at least 1 follow-up neuropsychological visit. Data collection began in 2010 and is ongoing. Data analysis was performed on data collected between 2010 and 2017. Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. We measured Aβ burden with Pittsburgh Compound-B PET. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite. Models were corrected for baseline age, sex, years of education, and apolipoprotein E ε4 status. Of the 223 participants, 130 (58.3%) were women. The mean (SD) age was 73.7 (6.0) years, and the mean (SD) follow-up time was 3.7 (1.2) years. Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P < .001) and higher Aβ burden (β = -0.058; 95% CI, -0.079 to -0.037; P < .001). The interaction of the FHS-CVD risk score and Aβ burden with time

  5. Embolization of traumatic and non-traumatic peripheral vascular lesions with Onyx.

    PubMed

    Regine, Renato; Palmieri, Francesco; De Siero, Michele; Rescigno, Antonio; Sica, Vincenzo; Cantarela, Raffaele; Villari, Vincenzo

    2015-03-01

    The aim of our study is to verify the feasibility and the efficacy of Onyx as embolization agent in the treatment of traumatic and non-traumatic peripheral vascular lesions. In the period between September 2006 and March 2012, we treated with Onyx 26 patients (14 males/12 females; age range, 18-85 years old; mean age, 65 years old), 11 of which with traumatic peripheral vascular lesions and 15 with non-traumatic vascular lesions (9 neoplastic hemorrhagic lesions, 3 arteriovenous malformations (AVMs) and 3 aneurysms). Follow-up controls were performed with clinical examination and by multidetector computed tomography (MDCT) imaging 1, 6, and 12 months after the procedure. All peripheral vascular lesions were embolized with Onyx; 3 patients with aneurysms were treated with Onyx associated with endovascular coils. Four elective and 22 emergency embolization procedures were performed. In all patients, we obtained cessation of bleeding and the complete and permanent embolization of all vascular lesions. Onyx is an effective and safe embolization agent for peripheral vascular lesions.

  6. Volatile profile of Madeira wines submitted to traditional accelerated ageing.

    PubMed

    Pereira, Vanda; Cacho, Juan; Marques, José C

    2014-11-01

    The evolution of monovarietal fortified Madeira wines forced-aged by traditional thermal processing (estufagem) were studied in terms of volatiles. SPE extracts were analysed by GC-MS before and after heating at 45 °C for 3 months (standard) and at 70 °C for 1 month (overheating). One hundred and ninety volatile compounds were identified, 53 of which were only encountered in baked wines. Most chemical families increased after standard heating, especially furans and esters, up to 61 and 3-fold, respectively. On the contrary, alcohols, acetates and fatty acids decreased after heating. Varietal aromas, such as Malvasia's monoterpenic alcohols were not detected after baking. The accelerated ageing favoured the development of some volatiles previously reported as typical aromas of finest Madeira wines, particularly phenylacetaldeyde, β-damascenone and 5-ethoxymethylfurfural. Additionally, ethyl butyrate, ethyl 2-methylbutyrate, ethyl caproate, ethyl isovalerate, guaiacol, 5-hydroxymethylfurfural and γ-decalactone were also found as potential contributors to the global aroma of baked wines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Influence of artificial accelerated aging on dimensional stability of acrylic resins submitted to different storage protocols.

    PubMed

    Garcia, Lucas da Fonseca Roberti; Roselino, Lourenço de Moraes Rego; Mundim, Fabrício Mariano; Pires-de-Souza, Fernanda de Carvalho Panzeri; Consani, Simonides

    2010-08-01

    The aim of this study was to evaluate the influence of artificial accelerated aging on dimensional stability of two types of acrylic resins (thermally and chemically activated) submitted to different protocols of storage. One hundred specimens were made using a Teflon matrix (1.5 cm x 0.5 mm) with four imprint marks, following the lost-wax casting method. The specimens were divided into ten groups, according to the type of acrylic resin, aging procedure, and storage protocol (30 days). GI: acrylic resins thermally activated, aging, storage in artificial saliva for 16 hours, distilled water for 8 hours; GII: thermal, aging, artificial saliva for 16 hours, dry for 8 hours; GIII: thermal, no aging, artificial saliva for 16 hours, distilled water for 8 hours, GIV: thermal, no aging, artificial saliva for 16 hours, dry for 8 hours; GV: acrylic resins chemically activated, aging, artificial saliva for 16 hours, distilled water for 8 hours; GVI: chemical, aging, artificial saliva for 16 hours, dry for 8 hours; GVII: chemical, no aging, artificial saliva for 16 hours, distilled water for 8 hours; GVIII: chemical, no aging, artificial saliva for 16 hours, dry for 8 hours GIX: thermal, dry for 24 hours; and GX: chemical, dry for 24 hours. All specimens were photographed before and after treatment, and the images were evaluated by software (UTHSCSA - Image Tool) that made distance measurements between the marks in the specimens (mm), calculating the dimensional stability. Data were submitted to statistical analysis (two-way ANOVA, Tukey test, p= 0.05). Statistical analysis showed that the specimens submitted to storage in water presented the largest distance between both axes (major and minor), statistically different (p < 0.05) from control groups. All acrylic resins presented dimensional changes, and the artificial accelerated aging and storage period influenced these alterations.

  8. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.

    PubMed

    Vermeij, W P; Dollé, M E T; Reiling, E; Jaarsma, D; Payan-Gomez, C; Bombardieri, C R; Wu, H; Roks, A J M; Botter, S M; van der Eerden, B C; Youssef, S A; Kuiper, R V; Nagarajah, B; van Oostrom, C T; Brandt, R M C; Barnhoorn, S; Imholz, S; Pennings, J L A; de Bruin, A; Gyenis, Á; Pothof, J; Vijg, J; van Steeg, H; Hoeijmakers, J H J

    2016-09-15

    Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1 ∆/- ) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg -/- (also known as Ercc5 -/- ) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1 ∆/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1 ∆/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1 ∆/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.

  9. Colour stability of denture teeth submitted to different cleaning protocols and accelerated artificial aging.

    PubMed

    Freire, T S; Aguilar, F G; Garcia, L da Fonseca Roberti; Pires-de-Souza, F de Carvalho Panzeri

    2014-03-01

    Acrylic resin is widely used for artificial teeth manufacturing due to several important characteristics; however, this material do not present acceptable colour stability over the course of time. This study evaluated the effect of different cleaning protocols and accelerated artificial aging on colour stability of denture teeth made of acrylic resin. Sixty denture teeth in dark and light shades were used, and separated according to the treatment to which they were submitted. Results demonstrated that colour stability of artificial teeth is influenced by the cleaning solution and artificial aging, being dark teeth more susceptible to colour alteration than lighter ones.

  10. Shifts in bryophyte carbon isotope ratio across an elevation × soil age matrix on Mauna Loa, Hawaii: do bryophytes behave like vascular plants?

    PubMed

    Waite, Mashuri; Sack, Lawren

    2011-05-01

    The carbon isotope ratio (δ(13)C) of vascular plant leaf tissue is determined by isotope discrimination, primarily mediated by stomatal and mesophyll diffusion resistances and by photosynthetic rate. These effects lead to predictable trends in leaf δ(13)C across natural gradients of elevation, irradiance and nutrient supply. Less is known about shifts in δ(13)C for bryophytes at landscape scale, as bryophytes lack stomata in the dominant gametophyte phase, and thus lack active control over CO(2) diffusion. Twelve bryophyte species were sampled across a matrix of elevation and soil ages on Mauna Loa, Hawaii Island. We tested hypotheses based on previous findings for vascular plants, which tend to have less negative δ(13)C at higher elevations or irradiances, and for leaves with higher leaf mass per area (LMA). Across the matrix, bryophytes spanned the range of δ(13)C values typical of C(3) vascular plants. Bryophytes were remarkably similar to vascular plants in exhibiting less negative δ(13)C with increasing elevation, and with lower overstory cover; additionally δ(13)C was related to bryophyte canopy projected mass per area, a trait analogous to LMA in vascular plants, also correlated negatively with overstory cover. The similarity of responses of δ(13)C in bryophytes and vascular plants to environmental factors, despite differing morphologies and diffusion pathways, points to a strong direct role of photosynthetic rate in determining δ(13)C variation at the landscape scale.

  11. [Self-consciousness in elderly persons with cognitive impairment and vascular dementia].

    PubMed

    Dubinina, E A; Novikova, Yu G; Kalitskaya, A V; Finagentova, N V

    2016-01-01

    Self-consciousness was compared in 17 elderly (aged 65-89 years old) persons with cognitive impairment without dementia and 17 patients with vascular dementia. Neurocognitive functions and mental health complaints were evaluated. Neuropsychological assessment included evaluation of higher psychological functions, such as attention, memory, conceptualization, gnosis (optic, acoustic), manual skill, speech. Older persons with cognitive impairment assessed their neurocognitive functions adequately. Patients with vascular dementia usually denied cognitive deficit or explained it as a result of aging. Regardless of physical health, older persons with cognitive impairment have active attitude to aging. They could find ways of compensation of cognitive deficits without assistance. Patients with vascular dementia could not compensate their cognitive deficit even with support.

  12. A Model-based Prognostics Methodology for Electrolytic Capacitors Based on Electrical Overstress Accelerated Aging

    NASA Technical Reports Server (NTRS)

    Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai

    2011-01-01

    A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

  13. Early accelerated senescence of circulating endothelial progenitor cells in premature coronary artery disease patients in a developing country - a case control study.

    PubMed

    Vemparala, Kranthi; Roy, Ambuj; Bahl, Vinay Kumar; Prabhakaran, Dorairaj; Nath, Neera; Sinha, Subrata; Nandi, Pradipta; Pandey, Ravindra Mohan; Reddy, Kolli Srinath; Manhapra, Ajay; Lakshmy, Ramakrishnan

    2013-11-19

    The decreased number and senescence of circulating endothelial progenitor cells (EPCs) are considered markers of vascular senescence associated with aging, atherosclerosis, and coronary artery disease (CAD) in elderly. In this study, we explore the role of vascular senescence in premature CAD (PCAD) in a developing country by comparing the numerical status and senescence of circulating EPCs in PCAD patients to controls. EPCs were measured by flow cytometry in 57 patients with angiographically documented CAD, and 57 controls without evidence of CAD, recruited from random patients ≤ 50 years of age at All India Institute of Medical Sciences. EPC senescence as determined by telomere length (EPC-TL) and telomerase activity (EPC-TA) was studied by real time polymerase chain reaction (q PCR) and PCR- ELISA respectively. The number of EPCs (0.18% Vs. 0.039% of total WBCs, p < 0.0001), and EPC-TL (3.83 Vs. 5.10 kb/genome, p = 0.009) were markedly lower in PCAD patients compared to controls. These differences persisted after adjustment for age, sex, BMI, smoking and medications. EPC-TA was reduced in PCAD patients, but was statistically significant only after adjustment for confounding factors (1.81 Vs. 2.20 IU/cell, unadjusted p = 0.057, adjusted p = 0.044). We observed an association between increased vascular cell senescence with PCAD in a sample of young patients from India. This suggests that early accelerated vascular cell senescence may play an important mechanistic role in CAD epidemic in developing countries like India where PCAD burden is markedly higher compared to developed countries.

  14. Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

    PubMed

    Navarrete, Marisol Galván; Hernández, Alma Dalia; Collado-Ortiz, Miguel Angel; Salinas-Lara, Citlaltepetl; Tena-Suck, Martha Lilia

    2014-08-01

    Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Bioprinting for vascular and vascularized tissue biofabrication.

    PubMed

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  16. Shear banding leads to accelerated aging dynamics in a metallic glass

    NASA Astrophysics Data System (ADS)

    Küchemann, Stefan; Liu, Chaoyang; Dufresne, Eric M.; Shin, Jeremy; Maaß, Robert

    2018-01-01

    Traditionally, strain localization in metallic glasses is related to the thickness of the shear defect, which is confined to the nanometer scale. Using site-specific x-ray photon correlation spectroscopy, we reveal significantly accelerated relaxation dynamics around a shear band in a metallic glass at a length scale that is orders of magnitude larger than the defect itself. The relaxation time in the shear-band vicinity is up to ten times smaller compared to the as-cast matrix, and the relaxation dynamics occurs in a characteristic three-stage aging response that manifests itself in the temperature-dependent shape parameter known from classical stretched exponential relaxation dynamics of disordered materials. We demonstrate that the time-dependent correlation functions describing the aging at different temperatures can be captured and collapsed using simple scaling functions. These insights highlight how a ubiquitous nanoscale strain-localization mechanism in metallic glasses leads to a fundamental change of the relaxation dynamics at the mesoscale.

  17. Bisphenol A Disrupts Transcription and Decreases Viability in Aging Vascular Endothelial Cells

    PubMed Central

    Ribeiro-Varandas, Edna; Pereira, H. Sofia; Monteiro, Sara; Neves, Elsa; Brito, Luísa; Boavida Ferreira, Ricardo; Viegas, Wanda; Delgado, Margarida

    2014-01-01

    Bisphenol A (BPA) is a widely utilized endocrine disruptor capable of mimicking endogenous hormones, employed in the manufacture of numerous consumer products, thereby interfering with physiological cellular functions. Recent research has shown that BPA alters epigenetic cellular mechanisms in mammals and may be correlated to enhanced cellular senescence. Here, the effects of BPA at 10 ng/mL and 1 µg/mL, concentrations found in human samples, were analyzed on HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) transcriptional analysis of the Long Interspersed Element-1 (LINE-1) retroelement showed that BPA induces global transcription deregulation in both cell lines, although with more pronounced effects in HUVEC cells. Whereas there was an increase in global transcription in HT29 exclusively after 24 h of exposure, this chemical had prolonged effects on HUVEC. Immunoblotting revealed that this was not accompanied by alterations in the overall content of H3K9me2 and H3K4me3 epigenetic marks. Importantly, cell viability assays and transcriptional analysis indicated that prolonged BPA exposure affects aging processes in senescent HUVEC. To our knowledge this is the first report that BPA interferes with senescence in primary vascular endothelial cells, therefore, suggesting its association to the etiology of age-related human pathologies, such as atherosclerosis. PMID:25207595

  18. Effects of different surface treatments and accelerated artificial aging on the bond strength of composite resin repairs.

    PubMed

    Melo, Marco Aurélio Veiga de; Moysés, Marcos Ribeiro; Santos, Saulo Galvão dos; Alcântara, Carlos Eduardo Pinto; Ribeiro, José Carlos Rabelo

    2011-01-01

    The purpose of the present study was to assess the bond strength of composite resin repairs subjected to different surface treatments and accelerated artificial aging. 192 cylindrical samples (CSs) were prepared and divided into 24 groups (n = 8). Half of the CSs were stored in water for 24 h, and the other half were subjected to C-UV accelerated aging for non-metallic specimens. The treatments were phosphoric acid + silane + adhesive (PSA); phosphoric acid + adhesive (PA); diamond bur + phosphoric acid + silane + adhesive (DPSA); diamond bur + phosphoric acid + adhesive (DPA); air abrasion + phosphoric acid + silane + adhesive (APSA); and air abrasion + phosphoric acid + adhesive (APA). The repair was performed and the specimens were again aged as described above. A control group (n = 8) was established and did not receive any type of aging or surface treatment. The specimens were loaded to failure in shear mode with a crosshead speed of 0.5 mm/min until fracture. Data were analyzed by one-way ANOVA/Tukey's test (p < 0.05). No statistically significant differences were found among DPSA, DPA, APSA, APA, and the control group. The aged PSA and PA achieved low bonding values and were statistically different from the control group, whereas the non-aged PSA and PA presented no statistically significant difference from the control group. Repairs with the proposed surface treatments were viable on both recent and aged restorations; however, phosphoric acid + adhesive alone were effective only on recent restorations.

  19. Colour stability and opacity of resin cements and flowable composites for ceramic veneer luting after accelerated ageing.

    PubMed

    Archegas, Lucí Regina Panka; Freire, Andrea; Vieira, Sergio; Caldas, Danilo Biazzetto de Menezes; Souza, Evelise Machado

    2011-11-01

    Colour changes of the luting material can become clinically visible affecting the aesthetic appearance of thin ceramic laminates. The aim of this in vitro study was to evaluate the colour stability and opacity of light- and dual-cured resin cements and flowable composites after accelerated ageing. The luting agents were bonded (0.2 mm thick) to ceramic disks (0.75 mm thick) built with the pressed-ceramic IPS Aesthetic Empress (n=7). Colour measurements were determined using a FTIR spectrophotometer before and after accelerated ageing in a weathering machine with a total energy of 150 kJ. Changes in colour (ΔE) and opacity (ΔO) were obtained using the CIE L*a*b* system. The results were submitted to one-way ANOVA, Tukey HSD test and Student's t test (α=5%). All the materials showed significant changes in colour and opacity. The ΔE of the materials ranged from 0.41 to 2.40. The highest colour changes were attributed to RelyX ARC and AllCem, whilst lower changes were found in Variolink Veneer, Tetric Flow and Filtek Z350 Flow. The opacity of the materials ranged from -0.01 to 1.16 and its variation was not significant only for Opallis Flow and RelyX ARC. The accelerated ageing led to colour changes in all the evaluated materials, although they were considered clinically acceptable (ΔE<3). Amongst the dual-cured resin cements, Variolink II demonstrated the highest colour stability. All the flowable composites showed proper colour stability for the luting of ceramic veneers. After ageing, an increase in opacity was observed for most of the materials. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Male sex and vascular risk factors affect cystatin C-derived renal function in older people without diabetes or overt vascular disease.

    PubMed

    Werner, Karin Birgitta; Elmståhl, Sölve; Christensson, Anders; Pihlsgård, Mats

    2014-05-01

    to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes. a cross-sectional analysis of a healthy subset from the Good Aging in Skåne-cohort study representative of the Swedish general population. 1252 participants without vascular disease and diabetes (43.9% men) of whom 203 were over 80 years old were included from the original cohort of 2931. plasma cystatin C and plasma creatinine were used as markers for GFR. Estimated GFR (eGFR) was calculated with three chronic kidney disease epidemiology collaboration (CKD-EPI) formulas involving cystatin C, creatinine or both. the median for plasma cystatin C was 0.93 mg/l (60-69 years old), 1.04 (70-79 years old) and 1.24 (80+ years old). The difference in mg/l between the 5th and 95th percentile was 0.46, 0.62 and 0.90 for these age groups. Male sex increased the age effect on plasma cystatin C levels with 0.004 mg/l/year (P = 0.03), adjusted for vascular risk factors. Smoking, lower HDL and higher diastolic blood pressure were associated with higher cystatin C levels. 54.7% (CKD-EPI creatinine) to 73.9% (CKD-EPI cystatin C) of the 80+ had an eGFR < 60 ml/min/1.73 m2. non-diabetics without overt vascular disease exhibit an age related but heterogeneous decline in renal function. The ageing effect is more pronounced in men. At least half of healthy 80+ years old could be expected to have at least CKD Stage 3 with eGFR < 60 ml/min/1.73 m2.

  1. Embolization of traumatic and non-traumatic peripheral vascular lesions with Onyx

    PubMed Central

    Regine, Renato; De Siero, Michele; Rescigno, Antonio; Sica, Vincenzo; Cantarela, Raffaele; Villari, Vincenzo

    2015-01-01

    Purpose The aim of our study is to verify the feasibility and the efficacy of Onyx as embolization agent in the treatment of traumatic and non-traumatic peripheral vascular lesions. Materials and Methods In the period between September 2006 and March 2012, we treated with Onyx 26 patients (14 males/12 females; age range, 18–85 years old; mean age, 65 years old), 11 of which with traumatic peripheral vascular lesions and 15 with non-traumatic vascular lesions (9 neoplastic hemorrhagic lesions, 3 arteriovenous malformations (AVMs) and 3 aneurysms). Follow-up controls were performed with clinical examination and by multidetector computed tomography (MDCT) imaging 1, 6, and 12 months after the procedure. Results All peripheral vascular lesions were embolized with Onyx; 3 patients with aneurysms were treated with Onyx associated with endovascular coils. Four elective and 22 emergency embolization procedures were performed. In all patients, we obtained cessation of bleeding and the complete and permanent embolization of all vascular lesions. Conclusions Onyx is an effective and safe embolization agent for peripheral vascular lesions. PMID:25838923

  2. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

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

    Luo, Di-xian, E-mail: luodixian_2@163.com; Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan; First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan

    Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different staticmore » pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels

  3. Tobacco smoke exposure in either the donor or recipient before transplantation accelerates cardiac allograft rejection, vascular inflammation, and graft loss.

    PubMed

    Khanna, Ashwani K; Xu, Jianping; Uber, Patricia A; Burke, Allen P; Baquet, Claudia; Mehra, Mandeep R

    2009-11-03

    Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome. Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction. These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss

  4. Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

    PubMed

    Hotta, Kazuki; Behnke, Bradley J; Arjmandi, Bahram; Ghosh, Payal; Chen, Bei; Brooks, Rachael; Maraj, Joshua J; Elam, Marcus L; Maher, Patrick; Kurien, Daniel; Churchill, Alexandra; Sepulveda, Jaime L; Kabolowsky, Max B; Christou, Demetra D; Muller-Delp, Judy M

    2018-05-15

    In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day -1 , 5 days week -1 , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth

  5. DNA-aptamers raised against AGEs as a blocker of various aging-related disorders.

    PubMed

    Yamagishi, Sho-Ichi; Taguchi, Kensei; Fukami, Kei

    2016-08-01

    A non-enzymatic reaction between sugars or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, which could impair their structural integrity and function. This process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions, such as rearrangements and dehydration to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress in a physiological aging process and at an accelerated rate under hyperglycemic, inflammatory and oxidative stress conditions. There is a growing body of evidence that AGEs and their receptor RAGE interaction play a role in the pathogenesis of various devastating disorders, including cardiovascular disease, Alzheimer's disease, insulin resistance, osteoporosis and cancer growth and metastasis. Furthermore, diet has been recently recognized as a major environmental source of AGEs that could also elicit pro-inflammatory reactions, thereby being involved in organ damage in vivo. Therefore, inhibition of AGE formation and/or blockade of the interaction of AGEs with RAGE may be a novel therapeutic target for aging-related disorders. This article discusses a potential utility of DNA-aptamers raised against AGEs for preventing aging and/or diabetes-associated organ damage, especially focusing on diabetic microvascular complications, vascular remodeling, metabolic derangements, and melanoma growth and expansion in animal models.

  6. Effect of accelerated environmental aging on tensile properties of oil palm/jute hybrid composites

    NASA Astrophysics Data System (ADS)

    Jawaid, M.; Saba, N.; Alothman, O.; Paridah, M. T.

    2016-11-01

    Recently natural fibre based hybrid composites are receiving growing consideration due to environmental and biodegradability properties. In order to look behaviour of hybrid composites in outdoor applications, its environmental degradation properties such as UV accelerated weathering properties need to analyze. In this study oil palm empty fruit bunch (EFB) and jute fibres reinforced hybrid composites, pure EFB, pure jute and epoxy composites were fabricated through hand lay-up techniques. Hybrid composites with different layering pattern (EFB/jute/EFB and Jute/EFB/jute) while maintaining 40 wt. % total fibre loading were fabricates to compared with EFB and jute composites. Effect of UV accelerated environmental aging on tensile properties of epoxy, pure EFB, pure jute, and hybrid composites were assessed and evaluate under UV exposure. Tensile samples of all composites were subjected to accelerated weathering for 100h, at temperature (75°C), relative humidity (35%), Light (125 W/m2), and water spray off. Obtained results indicated that there is reduction in tensile strength, modulus and elongation at break values of hybrid and pure composites due to degradation of lignin and fibre-matrix interfacial bonding.

  7. Evaluation of effect of laser etching on shear bond strength between maxillofacial silicone and acrylic resin subjected to accelerated aging process.

    PubMed

    Rhea, Antonette; Ahila, S C; Kumar, B Muthu

    2017-01-01

    Maxillofacial prosthesis are supported by implants, require a retentive matrix to retain the suprastructure. The retentive matrix is made up of acrylic resin to which the silicone prostheses are anchored by micro-mechanical bond. The delamination of silicone away from the retentive matrix is a persisting problem in implant-supported maxillofacial prosthesis. This study aimed to evaluate the effect of laser etching on the shear bond strength (BS) between acrylic resin and maxillofacial silicone, after 24 h of fabrication and after 200 h of accelerated aging. The samples were prepared according to ISO/TR 11405:1994 in maxillofacial silicone and polymethyl methacrylate resin. The untreated samples were Group A (control), Group B (silicon carbide [SiC] paper abrasion 80 grit size), and Group C (erbium-doped yttrium aluminum garnet laser etching). Then, the samples were coated with primer and bonded to maxillofacial silicone. The samples were subjected to shear BS test in an universal testing machine after 24 h of fabrication and after 200 h of accelerated aging. The results were statistically analyzed using one-way ANOVA and Tukey's HSD post hoc test. The shear BS test after 24 h of fabrication showed better BS in SiC paper abrasion. The shear BS test after 200 h of accelerated aging showed better BS in laser etching compared to SiC abrasion. Laser etching produced better shear BS compared to conventional SiC paper abrasion after 200 h of accelerated aging process.

  8. The Analysis of PPG Morphology: Investigating the Effects of Aging on Arterial Compliance

    NASA Astrophysics Data System (ADS)

    Yousef, Q.; Reaz, M. B. I.; Ali, M. A. M.

    2012-12-01

    This study presents the variations of photoplethysmogram (PPG) morphology with age. PPG measurement is done noninvasively at the index finger on both right and left hands for a sample of erectile dysfunction (ED) subjects. Some parameters are derived from the analysis of PPG contour showed in association with age. The age is found to be an important factor that affects the contour of PPG signals which accelerates the disappearance of PPG’s dicrotic notch and PPG’s inflection point as well. Arterial compliance is found to be degraded with age due to the fall of arterial elasticity. This study approaches the establishment of usefulness of PPG’s contour analysis as an investigator to the changes in the elastic properties of the vascular system, and as a detector of early sub-clinical atherosclerosis.

  9. On the Use of Accelerated Aging Methods for Screening High Temperature Polymeric Composite Materials

    NASA Technical Reports Server (NTRS)

    Gates, Thomas S.; Grayson, Michael A.

    1999-01-01

    A rational approach to the problem of accelerated testing of high temperature polymeric composites is discussed. The methods provided are considered tools useful in the screening of new materials systems for long-term application to extreme environments that include elevated temperature, moisture, oxygen, and mechanical load. The need for reproducible mechanisms, indicator properties, and real-time data are outlined as well as the methodologies for specific aging mechanisms.

  10. Aging, Atherosclerosis, and IGF-1

    PubMed Central

    Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung

    2012-01-01

    Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces atherosclerosis burden and improves features of atherosclerotic plaque stability in animal models. Potential mechanisms for this atheroprotective effect include IGF-1–induced reduction in oxidative stress, cell apoptosis, proinflammatory signaling, and endothelial dysfunction. Aging is associated with increased vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert salutary effects on vascular aging processes. In this review, we will provide a comprehensive update on IGF-1's ability to modulate vascular oxidative stress and to limit atherogenesis and the vascular complications of aging. PMID:22491965

  11. Structural and functional imaging for vascular targeted photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Li, Buhong; Gu, Ying; Wilson, Brian C.

    2017-02-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

  12. Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy.

    PubMed

    He, Jian; Jiang, Ya-Feng; Liang, Liu; Wang, Du-Jin; Wei, Wen-Xin; Ji, Pan-Pan; Huang, Yao-Chan; Song, Hui; Lu, Xiao-Ling; Zhao, Yong-Xiang

    2017-08-01

    Inhibition of aging of vascular endothelial cells (VECs) may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 (AUF1) gene (CD31-PILs-AUF1) and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs. The mean particle sizes of various PEGylated immunoliposomes (PILs) were measured using a Zetasizer Nano ZS. Gel retardation assay was used to confirm whether PILs had encapsulated the AUF1 plasmid successfully. Fluorescence microscopy and flow cytometry were used to quantify binding of CD31-PILs-AUF1 to target cells. Flow cytometry was also used to analyze the cell cycles of aging bEnd3 cells treated with CD31-PILs-AUF1. We also developed an aging mouse model by treating mice with D-galactose. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The malondialdehyde (MDA) and the superoxide dismutase (SOD) levels were detected by commercial kits. Hematoxylin-eosin (HE) staining was used to determine whether treatment with CD31-PILs-AUF1 was toxic to the mice. CD31-PILs-AUF1 specifically could targeted bEnd3 VECs and increased the percentage of cells in the S and G2/M phases of aging bEnd3 cells. ELISA showed that content of the IL-6 and TNF-α decreased in CD31-PILs-AUF1 group. The level of SOD increased, whereas MDA decreased in the CD31-PILs-AUF1 group. Additionally, CD31-PILs-AUF1 was not toxic to the mice. CD31-PILs-AUF1 targets VECs and may delay their senescence.

  13. Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy

    PubMed Central

    He, Jian; Jiang, Ya-Feng; Liang, Liu; Wang, Du-Jin; Wei, Wen-Xin; Ji, Pan-Pan; Huang, Yao-Chan; Song, Hui; Lu, Xiao-Ling; Zhao, Yong-Xiang

    2017-01-01

    Background Inhibition of aging of vascular endothelial cells (VECs) may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 (AUF1) gene (CD31-PILs-AUF1) and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs. Methods The mean particle sizes of various PEGylated immunoliposomes (PILs) were measured using a Zetasizer Nano ZS. Gel retardation assay was used to confirm whether PILs had encapsulated the AUF1 plasmid successfully. Fluorescence microscopy and flow cytometry were used to quantify binding of CD31-PILs-AUF1 to target cells. Flow cytometry was also used to analyze the cell cycles of aging bEnd3 cells treated with CD31-PILs-AUF1. We also developed an aging mouse model by treating mice with D-galactose. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The malondialdehyde (MDA) and the superoxide dismutase (SOD) levels were detected by commercial kits. Hematoxylin-eosin (HE) staining was used to determine whether treatment with CD31-PILs-AUF1 was toxic to the mice. Results CD31-PILs-AUF1 specifically could targeted bEnd3 VECs and increased the percentage of cells in the S and G2/M phases of aging bEnd3 cells. ELISA showed that content of the IL-6 and TNF-α decreased in CD31-PILs-AUF1 group. The level of SOD increased, whereas MDA decreased in the CD31-PILs-AUF1 group. Additionally, CD31-PILs-AUF1 was not toxic to the mice. Conclusion CD31-PILs-AUF1 targets VECs and may delay their senescence. PMID:29089968

  14. The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice

    PubMed Central

    Koga, Mitsuhisa; Engberding, Niels; Dikalova, Anna E.; Chang, Kyung Hwa; Seidel-Rogol, Bonnie; Long, James S.; Lassègue, Bernard; Jo, Hanjoong

    2013-01-01

    Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease. PMID:23812391

  15. Aging and failure mode of electrochemical double layer capacitors during accelerated constant load tests

    NASA Astrophysics Data System (ADS)

    Kötz, R.; Ruch, P. W.; Cericola, D.

    Electrochemical double layer capacitors of the BCAP0350 type (Maxwell Technologies) were tested under constant load conditions at different voltages and temperatures. The aging of the capacitors was monitored during the test in terms of capacitance, internal resistance and leakage current. Aging was significantly accelerated by elevated temperature or increased voltage. Only for extreme conditions at voltages of 3.5 V or temperatures above 70 °C the capacitors failed due to internal pressure build-up. No other failure events such as open circuit or short circuit were detected. Impedance measurements after the tests showed increased high frequency resistance, an increased distributed resistance and most likely an increase in contact resistance between electrode and current collector together with a loss of capacitance. Capacitors aged at elevated voltages (3.3 V) exhibited a tilting of the low frequency component, which implies an increase in the heterogeneity of the electrode surface. This feature was not observed upon aging at elevated temperatures (70 °C).

  16. Hypercapnic evaluation of vascular reactivity in healthy aging and acute stroke via functional MRI.

    PubMed

    Raut, Ryan V; Nair, Veena A; Sattin, Justin A; Prabhakaran, Vivek

    2016-01-01

    Functional MRI (fMRI) is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR), which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a breath-hold fMRI task to evaluate CVR across gray matter in a group of acute stroke patients (< 10 days from stroke; N = 22) to address this question. These estimates were compared with those from both age-matched (N = 22) and younger (N = 22) healthy controls. As expected, young controls had the greatest mean CVR, as indicated by magnitude and extent of fMRI activation; however, stroke patients did not differ from age-matched controls. Moreover, the ipsilesional and contralesional hemispheres of stroke patients did not differ with respect to any of these measures. These findings suggest that fMRI remains a valid tool within the first few days of a stroke, particularly for group fMRI studies in which findings are compared with healthy subjects of similar age. However, given the relatively high variability in CVR observed in our stroke sample, caution is warranted when interpreting fMRI data from individual patients or a small cohort. We conclude that a breath-hold task can be a useful addition to functional imaging protocols for stroke patients.

  17. BENCHMARK ACCELERATED AGING OF HARVESTED HYPALON/EPR AND CSPE/XLPE POWER AND I&C CABLE IN NUCLEAR POWER PLANTS

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

    Duckworth, Robert C; Fifield, Dr Leonard S

    As part of the Light Water Reactor and Sustainability (LWRS) program in the U.S. Department of Energy (DOE) Office of Nuclear Energy, material aging and degradation research is currently geared to support the long-term operation of existing nuclear power plants (NPPs) as they move beyond their initial 40 year licenses. The goal of this research is to provide information so that NPPs can develop aging management programs (AMPs) to address replacement and monitoring needs as they look to operate for 20 years, and in some cases 40 years, beyond their initial operating lifetimes. For cable insulation and jacket materials thatmore » support instrument, control, and safety systems, accelerated aging data are needed to determine priorities in cable aging management programs. Before accelerated thermal and radiation aging of harvested, representative cable insulation and jacket materials, the benchmark performance of a new test capability at Oak Ridge National Laboratory (ORNL) was evaluated for temperatures between 70 and 135 C, dose rates between 100 and 500 Gy/h, and accumulated doses up to 20 kGy, Samples that were characterized and are representative of current materials in use were harvested from the Callaway NPP near Fulton, Missouri, and the San Onofre NPP north of San Diego, California. From the Callaway NPP, a multiconductor control rod cable manufactured by Boston Insulated Wire (BIW), with a Hypalon/ chorolosulfonated polyethylene (CSPE) jacket and ethylene-propylene rubber (EPR) insulation, was harvested from the auxiliary space during a planned outage in 2013. This cable was placed into service when the plant was started in 1984. From the San Onofre NPP, a Rockbestos Firewall III (FRIII) cable with a Hypalon/ CSPE jacket with cross-linked polyethylene (XLPE) insulation was harvested from an on-site, climate-controlled storage area. This conductor, which was never placed into service, was procured around 2007 in anticipation of future operation that did not

  18. Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

    PubMed

    Sabayan, Behnam; van Buchem, Mark A; Sigurdsson, Sigurdur; Zhang, Qian; Meirelles, Osorio; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2016-11-01

    Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. © 2016 American Heart Association, Inc.

  19. Shear banding leads to accelerated aging dynamics in a metallic glass

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

    Küchemann, Stefan; Liu, Chaoyang; Dufresne, Eric M.

    Traditionally, strain localization in metallic glasses is related to the thickness of the shear defect, which is confined to the nanometer scale. In this study, using site-specific x-ray photon correlation spectroscopy (XPCS), we reveal significantly accelerated relaxation dynamics around a shear band in a metallic glass at a length scale that is orders of magnitude larger than the defect itself. The relaxation time in the shear-band vicinity is up to ten-times smaller compared to the as-cast matrix, and the relaxation dynamics occurs in a characteristic three-stage aging response that manifests itself in the temperature-dependent shape parameter known from classical stretchedmore » exponential relaxation dynamics of disordered materials. We demonstrate that the time-dependent correlation functions describing the aging at different temperatures can be captured and collapsed using simple scaling functions. Finally, these insights highlight how an ubiquitous nano-scale strain-localization mechanism in metallic glasses leads to a fundamental change of the relaxation dynamics at the mesoscale.« less

  20. Shear banding leads to accelerated aging dynamics in a metallic glass

    DOE PAGES

    Küchemann, Stefan; Liu, Chaoyang; Dufresne, Eric M.; ...

    2018-01-11

    Traditionally, strain localization in metallic glasses is related to the thickness of the shear defect, which is confined to the nanometer scale. In this study, using site-specific x-ray photon correlation spectroscopy (XPCS), we reveal significantly accelerated relaxation dynamics around a shear band in a metallic glass at a length scale that is orders of magnitude larger than the defect itself. The relaxation time in the shear-band vicinity is up to ten-times smaller compared to the as-cast matrix, and the relaxation dynamics occurs in a characteristic three-stage aging response that manifests itself in the temperature-dependent shape parameter known from classical stretchedmore » exponential relaxation dynamics of disordered materials. We demonstrate that the time-dependent correlation functions describing the aging at different temperatures can be captured and collapsed using simple scaling functions. Finally, these insights highlight how an ubiquitous nano-scale strain-localization mechanism in metallic glasses leads to a fundamental change of the relaxation dynamics at the mesoscale.« less

  1. Effect of mouthwash and accelerated aging on the color stability of esthetic restorative materials.

    PubMed

    Lee, Y K; El Zawahry, M; Noaman, K M; Powers, J M

    2000-06-01

    To evaluate the color stability of esthetic restorative materials after immersion in mouthwashes and accelerated aging. Compomers and resin-based composites (RBC) were measured at baseline and repeatedly after immersion in three kinds of mouthwash (Listerine, Peridex, Rembrandt Age Defying) for 24 hrs and 7 days, and after aging for 150 kJ/m2. Color was measured according to CIE L*a*b* color scale on a reflection spectrophotometer. After immersion for 7 days, the mouthwash groups did not produce significantly higher color changes than the distilled water group, except with some mouthwashes used with Tetric-Ceram. After immersion for 7 days and aging for 150 kJ/m2, the mouthwash groups did not produce significantly higher color changes than the distilled water group. Aging in weathering chamber produced color change (deltaE*) of 1.1-3.9, which was mainly influenced by the material. With some exceptions, the color changes from immersion of the RBCs and compomers in mouthwashes were not perceptible (deltaE*<3.3).

  2. The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition.

    PubMed

    Wallace, Robert G; Twomey, Laura C; Custaud, Marc-Antoine; Turner, Jonathan D; Moyna, Niall; Cummins, Philip M; Murphy, Ronan P

    2017-11-16

    The cardiovascular system is responsible for transport of blood and nutrients to tissues, and is pivotal to the physiological health and longevity. Epigenetic modification is a natural, age-associated process resulting in highly contextualised gene expression with clear implications for cell differentiation and disease onset. Biological/epigenetic age is independent of chronological age, constituting a highly reflective snapshot of an individual's overall health. Accelerated vascular ageing is of major concern, effectively lowering disease threshold. Age-related chronic illness involves a complex interplay between many biological processes and is modulated by non-modifiable and modifiable risk factors. These alter the static genome by a number of epigenetic mechanisms, which change gene expression in an age and lifestyle dependent manner. This 'epigenetic drift' impacts health and contributes to the etiology of chronic illness. Lifestyle factors may cause acceleration of this epigenetic "clock", pre-disposing individuals to cardiovascular disease. Nutrition and physical activity are modifiable lifestyle choices, synergistically contributing to cardiovascular health. They represent a powerful potential epigenetic intervention point for effective cardiovascular protective and management strategies. Thus, together with traditional risk factors, monitoring the epigenetic signature of ageing may prove beneficial for tailoring lifestyle to fit biology - supporting the increasingly popular concept of "ageing well". Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

    PubMed

    Laganović, Mario; Bendix, Laila; Rubelj, Ivica; Kirhmajer, Majda Vrkić; Slade, Neda; Lela, Ivana Vuković; Premužić, Vedran; Nilsson, Peter M; Jelaković, Bojan

    2014-08-01

    The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early signs of vascular aging and whether telomere length could be a biomarker of this pathway. One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams, including blood pressure (BP) measurement routine laboratory analyses, and carotid intima-media thickness (cIMT). Leukocyte telomere length (LTL) was assessed by quantitative PCR. Birth data were obtained from medical records. The SGA group had significantly higher pulse pressure and cIMT, and a trend to increased SBP and heart rate in comparison to the AGA group. Interestingly, SGA men exhibited a 42% longer LTL than the AGA group. LTL was inversely associated with age, BMI, BP and birth parameters. In multiple regression analysis, BMI was the key determinant of SBP and cIMT. Young men born SGA show early signs of vascular aging. Unexpectedly, in our cohort, the SGA group had longer telomeres than the normal controls. Although longer telomeres are predictive of better health in the future, our findings could indicate a faster telomere attrition rate and probable early onset of cardiovascular risk in SGA participants. Follow-up of this cohort will clarify hypothesis and validate telomere dynamics as indicators of future health risks.

  4. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

    PubMed

    Latimer, Caitlin S; Searcy, James L; Bridges, Michael T; Brewer, Lawrence D; Popović, Jelena; Blalock, Eric M; Landfield, Philip W; Thibault, Olivier; Porter, Nada M

    2011-01-01

    Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  5. Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice

    PubMed Central

    Latimer, Caitlin S.; Searcy, James L.; Bridges, Michael T.; Brewer, Lawrence D.; Popović, Jelena; Blalock, Eric M.; Landfield, Philip W.; Thibault, Olivier; Porter, Nada M.

    2011-01-01

    Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging. PMID:22046366

  6. Effects of accelerated ageing on viability, leachate exudation, and fatty acid content of Dalbergia sissoo Roxb

    Treesearch

    R.C. Thapliyal; K.F. Connor

    1997-01-01

    Accelerated ageing of seeds of Dalbergia sissoo Roxb., a multi-purpose tropical legume tree, was effective as a vigour test only at temperatures in excess of 43 deg C for 72 h. Increased leakage of solutes accompanied the decrease in viability, but there was no relationship between seed size and conductivity. Analyses of D. sissoo...

  7. Analysis of the microstructure and mechanical performance of composite resins after accelerated artificial aging.

    PubMed

    De Oliveira Daltoé, M; Lepri, C Penazzo; Wiezel, J Guilherme G; Tornavoi, D Cremonezzi; Agnelli, J A Marcondes; Reis, A Cândido Dos

    2013-03-01

    Researches that assess the behavior of dental materials are important for scientific and industrial development especially when they are tested under conditions that simulate the oral environment, so this work analyzed the compressive strength and microstructure of three composite resins subjected to accelerated artificial aging (AAA). Three composites resins of 3M (P90, P60 and Z100) were analyzed and were obtained 16 specimens for each type (N.=48). Half of each type were subjected to UV-C system AAA and then were analyzed the surfaces of three aged specimens and three not aged of each type through the scanning electron microscope (SEM). After, eight specimens of each resin, aged and not aged, were subjected to compression test. After statistical analysis of compressive strength values, it was found that there was difference between groups (α <0.05). The resin specimens aged P60 presented lower values of compressive strength statistically significant when compared to the not subject to the AAA. For the other composite resins, there was no difference, regardless of aging, a fact confirmed by SEM. The results showed that the AAA influenced the compressive strength of the resin aged P60; confirmed by surface analysis by SEM, which showed greater structural disarrangement on surface material.

  8. Surface modification and endothelialization of biomaterials as potential scaffolds for vascular tissue engineering applications.

    PubMed

    Ren, Xiangkui; Feng, Yakai; Guo, Jintang; Wang, Haixia; Li, Qian; Yang, Jing; Hao, Xuefang; Lv, Juan; Ma, Nan; Li, Wenzhong

    2015-08-07

    Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts.

  9. Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

    PubMed

    Bischof, Gérard N; Park, Denise C

    2015-01-01

    This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

  10. Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

    PubMed Central

    Chen, Cheng-Hsien; Chen, Tso-Hsiao; Wu, Mei-Yi; Chou, Tz-Chong; Chen, Jia-Rung; Wei, Meng-Jun; Lee, San-Liang; Hong, Li-Yu; Zheng, Cai-Mei; Chiu, I-Jen; Lin, Yuh-Feng; Hsu, Ching-Min; Hsu, Yung-Ho

    2017-01-01

    The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury. PMID:28071754

  11. Lower Serum Irisin Levels Are Associated with Increased Vascular Calcification in Hemodialysis Patients.

    PubMed

    He, Lian; He, Wan-Yu; A, La-Ta; Yang, Wen-Ling; Zhang, Ai-Hua

    2018-01-01

    Vascular calcification, which involves an active cellular transformation of vascular smooth muscle cells into bone forming cells, is prevalent and predicts mortality in dialysis patients. Its mechanisms are complex and unclear. We presume that irisin, a newly identified myokine also may play roles in vascular calcification in hemodialysis patients. This study aims to evaluate serum irisin levels and establish their relation to vascular calcification and other parameters in hemodialysis patients. A total of 150 patients on maintenance hemodialysis treatment and 38 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentrations were measured by ELISA. Vascular calcification was evaluated by abdominal aortic calcification scores. Serum irisin concentrations were significantly lower in hemodialysis patients than in controls [52.8 (22.0, 100.0) vs. 460.8 (434.8, 483.4) ng/ml, P<0.01]. In addition, irisin was negatively correlated with the parathyroid hormone level (P=0.01). The HD patients with vascular calcification showed significantly lower serum irisin concentrations [39.0 (21.7, 86.2) vs.79.0 (39.5, 130.2) ng/mL, P<0.01]. Compared with the group without vascular calcification multivariate logistic regression analyses revealed that serum irisin, HD vintage and age were significant independent determinant factors for vascular calcification in HD patients. Our results are the first to provide a clinical evidence of the association between serum irisin and vascular calcification in HD patients. Lower irisin levels, long-term hemodialysis and old ages are independent risk factors in HD patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

  12. Peptide-modified PELCL electrospun membranes for regulation of vascular endothelial cells.

    PubMed

    Zhou, Fang; Jia, Xiaoling; Yang, Yang; Yang, Qingmao; Gao, Chao; Zhao, Yunhui; Fan, Yubo; Yuan, Xiaoyan

    2016-11-01

    The efficiency of biomaterials used in small vascular repair depends greatly on their ability to interact with vascular endothelial cells (VECs). Rapid endothelialization of the vascular grafts is a promising way to prevent thrombosis and intimal hyperplasia. In this work, modification of electrospun membranes of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) by three different peptides for regulation of VECs were studied in order to obtain ideal bioactive biomaterials as small diameter vascular grafts. QK (a mimetic peptide to vascular endothelial growth factor), Arg-Glu-Asp-Val (REDV, a specific adhesive peptide to VECs) and Val-Ala-Pro-Gly (VAPG, a specific adhesive peptide to vascular smooth muscle cells) were investigated. Surface properties of the modified membranes and the response of VECs were verified. It was found that protein adsorption and platelet adhesion were effectively suppressed with the introduction of QK, REDV or VAPG peptides on the PELCL electrospun membranes. Both QK- and REDV-modified electrospun membranes could accelerate the proliferation of VECs in the first 9days, and the QK-modified electrospun membrane promoted cell proliferation more significantly than the REDV-modified one. The REDV-modified PELCL membrane was the most favorable for VECs adhesion than QK- and VAPG-modified membranes. It was suggested that QK- or REDV-modified PELCL electrospun membranes may have great potential applications in cardiovascular biomaterials for rapid endothelialization in situ. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. GPU-Accelerated Molecular Modeling Coming Of Age

    PubMed Central

    Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

    2010-01-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

  14. [Bone metabolism and cardiovascular function Update. Vascular calcification as a manifestation of bone-vascular axis].

    PubMed

    Kurabayashi, Masahiko

    2014-07-01

    Vascular calcification is the major cause of cardiovascular morbidity and mortality in the patients with type 2 diabetes, chronic kidney disease and in aging patients. Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. While the large body of evidence that osteoblastic and osteochondrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. It is reassuring that calcium paradox is not merely due to the calcium shift from bone to artery wall, but is likely due to the differential response of both osteoblasts and osteoclasts to oxidative stress between bone and artery. To date, many studies have highlighted the important role for RANK/RANKL/OPG axis as unifying theme for the apparently opposite regulation of calcification between two tissues.

  15. Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

    PubMed

    Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

    2017-10-01

    Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease

    PubMed Central

    Ackers-Johnson, Matthew; Talasila, Amarnath; Sage, Andrew P; Long, Xiaochun; Bot, Ilze; Morrell, Nicholas W; Bennett, Martin R; Miano, Joseph M.; Sinha, Sanjay

    2015-01-01

    Objective Atherosclerosis, the cause of 50% of deaths in westernised societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local pro-inflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. Approach and Results We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic ApoE−/− mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. Conclusions We propose myocardin as a guardian of the contractile, non-inflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease. PMID:25614278

  17. [Peripheral vascular injuries in polytrauma].

    PubMed

    Richter, A; Silbernik, D; Oestreich, K; Karaorman, M; Storz, L W

    1995-09-01

    Between 1972 und 1993 a total of 68 patients were treated at the Department of Surgery of the University Clinic of Mannheim for peripheral vascular injury resulting from multiple trauma. The average age of these patients was 31.3 years, and most of them were male (88.2%; n = 60). The injured vessels were localized evenly in all the extremities: 31 patients (45.5%) presented with arterial damage of the upper extremity, and 37 (54.5%) showed lesions along the femoro-popliteal arteries. The most frequent location of injured vessels in the multiply traumatized patient was the popliteal artery (n = 18, 26.5%), the distal part of the superficial femoral artery (n = 12, 17.6%), the brachial artery (n = 14, 20.6%) and the axillary artery (n = 10, 14.6%). The dominant cause, of trauma was road traffic accidents (72%), and 20 patients (29%) acquired their vascular injuries as motorcyclists. There were also 13 occupational accidents (19%) involving vascular injuries. In addition to a vascular trauma 34 patients (50%) had complicated fractures, and a further 34 patients (50%) had multiple fractures: 12 (17.6%) had head and brain damage, 5 (7.3%) had blunt abdominal trauma and 6 (8.8%) had blunt thoracic injury. The general amputation rate was 2.9% (n = 2). One patient died on the table of a torn off subclavian artery combined with multiple other injuries. Paresis of the plexus is a particular problem after vascular lesions of the upper extremity: in 22 patients (71%) paresis of the plexus persisted after successful vascular reconstruction (follow-up period between 3 months and 16 years, median time 3.45 years).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.

    PubMed

    Reichel, J M; Bedenk, B T; Czisch, M; Wotjak, C T

    2017-01-01

    Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Atherosclerotic vascular disease in systemic lupus erythematosus.

    PubMed

    Liang, Matthew H; Mandl, Lisa A; Costenbader, Karen; Fox, Ervin; Karlson, Elizabeth

    2002-09-01

    In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority.

  20. Trends in a changing vascular practice environment for members of the Society for Vascular Surgery

    PubMed Central

    Matthews, Mika A. B.; Satiani, Bhagwan; Lohr, Joann M.

    2013-01-01

    Objective To survey the Society for Vascular Surgery (SVS) membership with regard to practice trends related to work effort, employment status, practice ownership, endovascular cases, and anticipated changes in practice in the near future. Methods A survey questionnaire was developed to gather information about member demographics and practice, hours worked, full-time (FT) or part-time status, employment status, practice ownership, competition for referrals, proportion of endovascular vs open procedures, and anticipated changes in practice in the next 3 years. We used SurveyMonkey and distributed the survey to all active vascular surgeon (VS) members of the SVS. Results The response rate was 207 of 2230 (10.7%). Two thirds were in private practice, and 21% were in solo practice. Twenty-four percent were employed by hospitals/health systems. Those VS under the age of 50 years were more likely to exclusively practice vascular surgery compared with VS over the age of 50 years (P = .0003). Sixty-eight of the physicians (32.7%) were between 50 and 59 years old, 186 (90.3%) were men, 192 (92.8%) worked FT (>36 hours of patient care per week), and almost two thirds worked >60 hours per week. Those in physician-owned practices worked >40 hours of patient care per week more often than did FT employed VS (P = .012). Younger VS (age <50 years) more frequently reported >50% of their workload being endovascular compared with older VS (age ≥50 years; P < .001). Eighty percent of FT VS planned to continue their current practice over the next 3 years. Of the 43.6% indicating loss of referrals, 82% pointed to cardiologists as the competition. Conclusions The current workforce is predominately male and works FT; one-third is between the ages of 50 and 59 years. Younger VS (age <50 years) are more likely to exclusively practice VS and have a higher caseload of endovascular procedures. Those in physician-owned practices are more likely to put in >40 hours of patient care per week

  1. Applications of the Amplatzer Vascular Plug to various vascular lesions

    PubMed Central

    Güneyli, Serkan; Çınar, Celal; Bozkaya, Halil; Parıldar, Mustafa; Oran, İsmail

    2014-01-01

    The Amplatzer® Vascular Plug (AVP) can be used to embolize medium-to-large high-flow vessels in various locations. Between 2009 and 2012, 41 AVPs (device size, 6–22 mm in diameter) were used to achieve occlusion in 31 patients (24 males, seven females) aged 9–92 years (mean age, 54.5 years). The locations and indications for embolotherapy were as follows: internal iliac artery embolization before stent-graft repair for aorto-iliac (n=6) and common iliac artery (n=3) aneurysms, subclavian artery embolization before stent-graft repair for thoracic aorta (n=3) and arcus aorta (n=1) aneurysms, brachiocephalic trunk embolization before stent-graft repair for a thoracic aorta aneurysm (n=1), embolization of aneurysms and pseudoaneurysms (n=5), embolization for carotid blow-out syndrome (n=3), closure of arteriovenous fistula (n=8), and closure of a portosystemic fistula (n=1). Of the 41 AVPs, 30 were AVP 2 and 11 were AVP 4. The mean follow-up duration was 4.7 months (range, 1–24 months). During follow-up, there was one migration, one insufficient embolization, and one recanalization. The remaining vascular lesions were successfully excluded from the circulation. The AVP, which can be used in a wide spectrum of pathologies, is easy to use and causes few complications. This essay presents our experience with the AVP. PMID:24047719

  2. Public health impact of accelerated immunization against rotavirus infection among children aged less than 6 months in the United States

    PubMed Central

    Weycker, Derek; Atwood, Mark Andrew; Standaert, Baudouin; Krishnarajah, Girishanthy

    2014-01-01

    We developed a cohort model to evaluate the expected public health impact of accelerated regimens for immunization against rotavirus gastroenteritis (RVGE). Alternative strategies for vaccination with the pentavalent human-bovine reassortant vaccine, Rotateq® (RV5, Merck) and the oral live attenuated human rotavirus vaccine, Rotarix® (RV1, GlaxoSmithKline Vaccines) were considered, including acceleration of the 1st dose only (by 2 weeks) as well as acceleration of the 1st (by 2 weeks) and subsequent doses (by up to 10 weeks). Assuming vaccine coverage levels consistent with current US clinical practice, accelerated regimens would be expected to reduce annual numbers of RVGE-related hospitalizations by 300–400, emergency department visits by 3000–4000, and outpatient visits by 3000–4000 (i.e., by 9–14%) among US children aged <6 months. Accordingly, accelerating the immunization of children against RVGE may yield substantive reductions in the number of RV-related encounters in US clinical practice. PMID:25424813

  3. Benchmark Accelerated Aging of Harvested Hypalon/Epr and Cspe/Xlpe Power and I&C Cable in Nuclear Power Plants

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

    Duckworth, Robert C.; Frame, Emily; Fifield, Leonard S.

    As part of the Light Water Reactor and Sustainability (LWRS) program in the U.S. Department of Energy (DOE) Office of Nuclear Energy, material aging and degradation research is currently geared to support the long-term operation of existing nuclear power plants (NPPs) as they move beyond their initial 40 year licenses. The goal of this research is to provide information so that NPPs can develop aging management programs (AMPs) to address replacement and monitoring needs as they look to operate for 20 years, and in some cases 40 years, beyond their initial operating lifetimes. For cable insulation and jacket materials thatmore » support instrument, control, and safety systems, accelerated aging data are needed to determine priorities in cable aging management programs. Before accelerated thermal and radiation aging of harvested, representative cable insulation and jacket materials, the benchmark performance of a new test capability at Oak Ridge National Laboratory (ORNL) was evaluated for temperatures between 70 and 135°C, dose rates between 100 and 500 Gy/h, and accumulated doses up to 20 kGy, Samples that were characterized and are representative of current materials in use were harvested from the Callaway NPP near Fulton, Missouri, and the San Onofre NPP north of San Diego, California. From the Callaway NPP, a multiconductor control rod cable manufactured by Boston Insulated Wire (BIW), with a Hypalon/ chorolosulfonated polyethylene (CSPE) jacket and ethylene-propylene rubber (EPR) insulation, was harvested from the auxiliary space during a planned outage in 2013. This cable was placed into service when the plant was started in 1984. From the San Onofre NPP, a Rockbestos Firewall III (FRIII) cable with a Hypalon/ CSPE jacket with cross-linked polyethylene (XLPE) insulation was harvested from an on-site, climate-controlled storage area. This conductor, which was never placed into service, was procured around 2007 in anticipation of future operation that did not

  4. GPU-accelerated molecular modeling coming of age.

    PubMed

    Stone, John E; Hardy, David J; Ufimtsev, Ivan S; Schulten, Klaus

    2010-09-01

    Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. (c) 2010 Elsevier Inc. All rights reserved.

  5. Colour-stability and gloss-retention of silorane and dimethacrylate composites with accelerated aging.

    PubMed

    Furuse, Adilson Y; Gordon, Kathryn; Rodrigues, Flávia P; Silikas, Nick; Watts, David C

    2008-11-01

    To evaluate the colour-stability and gloss-retention of silorane versus dimethacrylate composites exposed to accelerated aging from daylight radiation. Five disc-shaped specimens of photo-cured resin-composites were prepared and manually polished for each material (Filtek Silorane, Herculite XRV, Tetric Evoceram and QuiXfil). Colour and gloss were evaluated before and after periods (baseline, 24, 72, 120 and 192 h) of accelerated photo-aging in xenon light following ISO 7491:2000. Colour measurements were performed with a colourimeter according to the CIE-Lab colour-space. The colour change (DeltaE) for each time was calculated. The surface gloss was measured using a glossmeter. Results were evaluated using one-way ANOVA and Tukey tests (alpha=0.05). Correlations between logtime, DeltaE and gloss were evaluated using Pearson's correlation (alpha=0.05). Materials generally decreased in L and a and increased in b. The strong exception was Filtek Silorane which maintained a and b. DeltaE was found to be a positive linear function of logtime for all materials. Materials varied in the magnitude and rate of increase of DeltaE with logtime: QuiXfil>Tetric EvoCeram>(Filtek Silorane>or=Herculite XRV). DeltaE remained<3.3 for Filtek Silorane and Herculite XRV. Gloss was found to be a negative linear function of logtime. Gloss was maximal in the sequence: Filtek Silorane approximately Tetric EvoCeram>Herculite XRV>QuiXfil. Silorane gave the best overall performance in stability over time, compared to a set of representative dimethacrylate composites.

  6. Toxicity, Uptake, and Translocation of Engineered Nanomaterials in Vascular plants.

    PubMed

    Miralles, Pola; Church, Tamara L; Harris, Andrew T

    2012-09-04

    To exploit the promised benefits of engineered nanomaterials, it is necessary to improve our knowledge of their bioavailability and toxicity. The interactions between engineered nanomaterials and vascular plants are of particular concern, as plants closely interact with soil, water, and the atmosphere, and constitute one of the main routes of exposure for higher species, i.e. accumulation through the food chain. A review of the current literature shows contradictory evidence on the phytotoxicity of engineered nanomaterials. The mechanisms by which engineered nanomaterials penetrate plants are not well understood, and further research on their interactions with vascular plants is required to enable the field of phytotoxicology to keep pace with that of nanotechnology, the rapid evolution of which constantly produces new materials and applications that accelerate the environmental release of nanomaterials.

  7. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    PubMed

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  8. Microstructural modifications induced by accelerated aging and lipid absorption in remelted and annealed UHMWPEs for total hip arthroplasty

    PubMed Central

    Puppulin, Leonardo; Zhu, Wenliang; Sugano, Nobuhiko

    2014-01-01

    Three types of commercially available ultra-high molecular weight polyethylene (UHMWPE) acetabular cups currently used in total hip arthroplasty have been studied by means of Raman micro-spectroscopy to unfold the microstructural modification induced by the oxidative degradation after accelerated aging with and without lipid absorption. The three investigated materials were produced by three different manufacturing procedures, as follows: irradiation followed by remelting, one-step irradiation followed by annealing, 3-step irradiation and annealing. Clear microstructural differences were observed in terms of phase contents (i.e. amorphous, crystalline and intermediate phase fraction). The three-step annealed material showed the highest crystallinity fraction in the bulk, while the remelted polyethylene is clearly characterized by the lowest content of crystalline phase and the highest content of amorphous phase. After accelerated aging either with or without lipids, the amount of amorphous phase decreased in all the samples as a consequence of the oxidation-induced recrystallization. The most remarkable variations of phase contents were detected in the remelted and in the single-step annealed materials. The presence of lipids triggered oxidative degradation especially in the remelted polyethylene. Such experimental evidence might be explained by the highest amount of amorphous phase in which lipids can be absorbed prior to accelerated aging. The results of these spectroscopic characterizations help to rationalize the complex effect of different irradiation and post-irradiation treatments on the UHMWPE microstructure and gives useful information on how significantly any single step of the manufacturing procedures might affect the oxidative degradation of the polymer. PMID:25179830

  9. Avoidance of accelerated aging in schizophrenia?: Clinical and biological characterization of an exceptionally high functioning individual.

    PubMed

    Palmer, Barton W; Moore, Raeanne C; Eyler, Lisa T; Pinto, Luz L; Saks, Elyn R; Jeste, Dilip V

    2018-06-01

    To determine the clinical and biological characteristics of an exceptionally high functioning index person (IP) with schizophrenia in her mid-50s, which may represent compensatory mechanisms, and potentially, avoidance of the accelerated aging typically associated with schizophrenia. IP, 11 other women with schizophrenia, and 11 non-psychiatric comparison (NC) women were assessed with standard ratings of psychopathology, neurocognitive function, decisional capacity, and functional brain imaging. IP was also compared to a sample of demographically similar NCs (N=45) and persons with schizophrenia (N=42) on a set of blood-based biomarkers of aging related to metabolic function, oxidative stress, and inflammation. IP's scores on working memory, and levels of brain activation during an affective face matching task in the left fusiform, right lingual, and left precentral gyri, exceeded NCs. IP was similar to NCs in severity of negative symptoms, most neurocognitive functions, decisional capacity, and brain activation in the left inferior occipital gyrus during a selective stopping task. IP's levels on 11 of 14 metabolic and inflammatory biomarkers of aging were better than NCs and the schizophrenia group. Although speculative, results suggest a possible model in which superior working memory permits a person to be aware of the potentially psychotic nature of a thought or perception, and adjust response accordingly. Compensatory overactivity of brain regions during affective processing may also reflect heightened meta-awareness in emotional situations. Biomarker levels raise the possibility that IP partially avoided the accelerated biological aging associated with schizophrenia. Published by Elsevier B.V.

  10. Optical Coherence Tomography Angiography Reveals Mature, Tangled Vascular Networks in Eyes With Neovascular Age-Related Macular Degeneration Showing Resistance to Geographic Atrophy.

    PubMed

    Dansingani, Kunal K; Freund, K Bailey

    2015-10-01

    To demonstrate a vascular pattern seen on optical coherence tomography angiography (OCTA) that appears to correlate with reduced rates of geographic atrophy (GA) in eyes receiving long-term anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). Non-consecutive, retrospective cohort study. Patients were included if they had received more than 50 anti-VEGF injections during a period of at least 4 years for neovascular AMD in at least one eye, with absence or minimal progression of GA. Clinical charts and imaging were reviewed retrospectively; study eyes underwent OCTA. Nine eyes of eight patients were included. Mean age was 82 years, and mean follow-up of study eyes 9.1 years; study eyes received a mean of 65.8 injections. OCTA revealed tangled networks of neovessels associated with type 1 lesions. With prolonged anti-VEGF treatment, GA appears to occur less commonly in eyes with type 1 neovascularization. OCTA shows mature tangled vessels with substantial flow within type 1 lesions. Mature, tangled networks may be associated with a decreased likelihood of developing GA despite the presence of choriocapillaris atrophy. Copyright 2015, SLACK Incorporated.

  11. Aroma profile and sensory characteristics of a sulfur dioxide-free mulberry (Morus nigra) wine subjected to non-thermal accelerating aging techniques.

    PubMed

    Tchabo, William; Ma, Yongkun; Kwaw, Emmanuel; Zhang, Haining; Xiao, Lulu; Tahir, Haroon Elrasheid

    2017-10-01

    The present study was undertaken to assess accelerating aging effects of high pressure, ultrasound and manosonication on the aromatic profile and sensorial attributes of aged mulberry wines (AMW). A total of 166 volatile compounds were found amongst the AMW. The outcomes of the investigation were presented by means of geometric mean (GM), cluster analysis (CA), principal component analysis (PCA), partial least squares regressions (PLSR) and principal component regression (PCR). GM highlighted 24 organoleptic attributes responsible for the sensorial profile of the AMW. Moreover, CA revealed that the volatile composition of the non-thermal accelerated aged wines differs from that of the conventional aged wines. Besides, PCA discriminated the AMW on the basis of their main sensorial characteristics. Furthermore, PLSR identified 75 aroma compounds which were mainly responsible for the olfactory notes of the AMW. Finally, the overall quality of the AMW was noted to be better predicted by PLSR than PCR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

    PubMed

    Akiguchi, Ichiro; Pallàs, Mercè; Budka, Herbert; Akiyama, Haruhiko; Ueno, Masaki; Han, Jingxian; Yagi, Hideo; Nishikawa, Tomohumi; Chiba, Yoichi; Sugiyama, Hiroshi; Takahashi, Ryoya; Unno, Keiko; Higuchi, Keiichi; Hosokawa, Masanori

    2017-08-01

    Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders. © 2017 Japanese Society of Neuropathology.

  13. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    PubMed

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  14. Wave detection in acceleration plethysmogram.

    PubMed

    Ahn, Jae Mok

    2015-04-01

    Acceleration plethysmogram (APG) obtained from the second derivative of photoplethysmography (PPG) is used to predict risk factors for atherosclerosis with age. This technique is promising for early screening of atherosclerotic pathologies. However, extraction of the wave indices of APG signals measured from the fingertip is challenging. In this paper, the development of a wave detection algorithm including a preamplifier based on a microcontroller that can detect the a, b, c, and d wave indices is proposed. The 4(th) order derivative of a PPG under real measurements of an APG waveform was introduced to clearly separate the components of the waveform, and to improve the rate of successful wave detection. A preamplifier with a Sallen-Key low pass filter and a wave detection algorithm with programmable gain control, mathematical differentials, and a digital IIR notch filter were designed. The frequency response of the digital IIR filter was evaluated, and a pulse train consisting of a specific area in which the wave indices existed was generated. The programmable gain control maintained a constant APG amplitude at the output for varying PPG amplitudes. For 164 subjects, the mean values and standard deviation of the a wave index corresponding to the magnitude of the APG signal were 1,106.45 and ±47.75, respectively. We conclude that the proposed algorithm and preamplifier designed to extract the wave indices of an APG in real-time are useful for evaluating vascular aging in the cardiovascular system in a simple healthcare device.

  15. Evaluation of a static stretching intervention on vascular endothelial function and arterial stiffness.

    PubMed

    Shinno, Hiromi; Kurose, Satoshi; Yamanaka, Yutaka; Higurashi, Kyoko; Fukushima, Yaeko; Tsutsumi, Hiromi; Kimura, Yutaka

    2017-06-01

    Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. The study evaluated 22 healthy, non-smoking, premenopausal women aged ≥40 years. Subjects were randomly assigned to the full-intervention (n = 11; mean age: 48.6 ± 2.8 years) or a half-intervention that included a control period (n = 11; mean age: 46.9 ± 3.6 years). Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

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

    PubMed

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

    2018-02-03

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

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

    PubMed Central

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

    2018-01-01

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

  18. The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

    PubMed

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-02-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis.

  19. Lifestyle and metabolic approaches to maximizing erectile and vascular health.

    PubMed

    Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

    2012-01-01

    Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient

  20. Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

    PubMed

    Sun, Miao-Kun

    2017-10-16

    As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

    PubMed

    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular

  2. B vitamins influence vascular cognitive impairment

    USDA-ARS?s Scientific Manuscript database

    As the number of elderly in the USA and globally continues to increase, age-related neurological disorders, such as Alzheimer's disease and vascular dementia, are a growing concern. The loss of memory, emotional changes, and impairments in general cognitive functioning frequently result in social is...

  3. miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling

    PubMed Central

    Hori, Daijiro; Dunkerly-Eyring, Brittany; Nomura, Yohei; Biswas, Debjit; Steppan, Jochen; Henao-Mejia, Jorge; Adachi, Hideo; Santhanam, Lakshmi; Berkowitz, Dan E.; Steenbergen, Charles; Flavell, Richard A.

    2017-01-01

    Background Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. Methods and results qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1-/- mice. Conclusions Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway. PMID:28323879

  4. miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling.

    PubMed

    Hori, Daijiro; Dunkerly-Eyring, Brittany; Nomura, Yohei; Biswas, Debjit; Steppan, Jochen; Henao-Mejia, Jorge; Adachi, Hideo; Santhanam, Lakshmi; Berkowitz, Dan E; Steenbergen, Charles; Flavell, Richard A; Das, Samarjit

    2017-01-01

    Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1-/- mice. Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway.

  5. Rivastigmine for vascular cognitive impairment.

    PubMed

    Birks, Jacqueline; McGuinness, Bernadette; Craig, David

    2013-05-31

    included participants with dementia of different severities. The dose of rivastigmine was different in each study. No pooling of study results was attempted because of these differences between the studies.One trial included 40 participants with subcortical vascular dementia (age range 40 to 90 years) with a mean mini-mental state examination (MMSE) score of 13.0 and 13.4 in the rivastigmine and placebo arms, respectively. Treatment over 26 weeks was limited to 3 mg rivastigmine twice daily, or placebo. No significant difference was found on any outcome measure relevant to cognition, neuropsychiatric symptoms, function or global rating, or in the number of withdrawals before the end of treatment.Another trial included 710 participants with vascular dementia, including subcortical and cortical forms (age range 50 to 85 years). Over 24 weeks, a mean dose of rivastigmine of 9.4 mg/day was achieved versus placebo. Baseline MMSE was identical for both groups, at 19.1. Statistically significant advantage in cognitive response (but not with global impression of change or non-cognitive measures) was seen with rivastigmine treatment at 24 weeks (MMSE change from baseline MD 0.6, 95% CI 0.11 to 1.09, P value 0.02; Vascular Dementia Assessment Scale (VaDAS) change from baseline MD -1.3, 95% CI-2.62 to 0.02, P value 0.05 ). Significantly higher rates of vomiting, nausea, diarrhoea and anorexia and withdrawals from treatment were noted in the participants randomized to rivastigmine compared with placebo (withdrawals rivastigmine 90/365, placebo 48/345, OR 2.02, 95% CI 1.38 to 2.98) (withdrawals due to an adverse event rivastigmine 49/365, placebo 19/345, OR 2.66, 95% CI 1.53 to 4.62, P value 0.0005).The third study included 50 participants (age range 48 to 84 years) with mean MMSE scores of 23.7 and 23.9 in the rivastigmine and placebo arms, respectively. Over a 24-week period, participants labelled as having cognitive impairment but no dementia (CIND) following ischaemic stroke were

  6. Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults.

    PubMed

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G; Spartano, Nicole L; Vita, Joseph A; Benjamin, Emelia J; Murabito, Joanne M; Esliger, Dale W; Blease, Susan J; Hamburg, Naomi M; Mitchell, Gary F; Vasan, Ramachandran S

    2015-03-19

    Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. We related objective measures of moderate- to vigorous-intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid-femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10-minute increment) were associated with lower carotid-femoral pulse wave velocity (estimate -0.53 ms/m; P=0.006) and lower forward pressure wave (estimate -0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with log(e) left ventricular mass (estimate 0.006 log(e) [g/m(2)]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. In our community-based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. Current and future initiatives for vascular health management in clinical practice

    PubMed Central

    Cameron, James D; Asmar, Roland; Struijker-Boudier, Harry; Shirai, Kohji; Sirenko, Yuriy; Kotovskaya, Yulia; Topouchian, Jirar

    2013-01-01

    Central arterial structure and function comprise a primary determinant of vascular health, and are integral to the important concept of ventriculo-vascular coupling or interaction. Central aortic stiffening is a major influence on central blood pressure, and directly relates to coronary perfusion. The joint session of the International Society of Vascular Health (Eastern Region) and the Ukrainian Congress of Cardiology was held in Kiev, Ukraine, on September 23, 2011; it provided an expert forum to discuss arterial evaluations, clinical applications, and progress toward translating arterial protection into cardiovascular benefits. The conclusions of the expert panel were: Aortic stiffness is not presently a treatment target but may be useful for substratifying cardiovascular risk in individuals in order to better target the intensity of conventional therapy, and it may be useful in assessing response to treatment.Crosstalk between macro- and microcirculation in hypertension has important implications for pharmacological treatment. An antihypertensive regimen should abolish the vicious cycle between the increased resistance in the microcirculation and the increased stiffness of the larger arteries. Such treatment should be based on drugs with multiple actions on the vascular tree, or on drug combinations that target the various segments of the arterial system.Several blood pressure-independent mechanisms of large artery stiffness exist. Future considerations for clinical understanding of large artery stiffness should involve new drugs and new evaluation methods – with a focus on vascular health, for the initiation of cardiovascular prevention, for newly designed studies for treatment evaluation, and for new studies of drug combinations.Arterial stiffening is a sign of cardiovascular aging and is a major factor affecting the biomechanics of large arteries. Arterial stiffness is an attractive therapeutic target in terms of vascular aging. Healthy lifestyle, physical

  8. Low vascularity predicts favourable outcomes in leiomyoma patients treated with uterine artery embolization.

    PubMed

    Tang, Yixin; Chen, Chunlin; Duan, Hui; Ma, Ben; Liu, Ping

    2016-10-01

    To investigate the clinical factors predicting outcomes of leiomyoma treated with uterine artery embolization (UAE). A total of 183 uterine leiomyoma patients undergoing UAE were retrospectively analyzed. Patient age, characteristics of vascular supply in magnetic resonance imaging (MRI)/digital subtraction angiography (DSA), number, size and location of leiomyoma were recorded. Leiomyoma regrowth, new leiomyoma appearance and recurrence of any previously reported symptoms were carefully monitored over a mean follow-up of 30 months (median 32 months, range 12-80). Potential recurrence risk factors were analyzed by univariate and multivariate cox regression analysis. Twenty-three recurrences were recorded. The difference in the vascularity classification systems between MRI and DSA was not statistically significant (P = 0.059). High vascularity in MRI, high vascularity in DSA and multiple leiomyoma showed a significant risk of recurrence using univariate and multivariate analysis (P = 0.004, P < 0.001 and P = 0.023, respectively). The other factors were not significantly associated with leiomyoma recurrence (P > 0.05). Low vascularity and solitary leiomyoma indicated favourable outcomes in patients treated with UAE. • Low vascularity and solitary mass predicted favourable outcomes in UAE-treated patients. • MRI might provide information on vascularity in leiomyoma before UAE. • Variations in vascular supply, age, size, location were not associated with recurrence.

  9. Accelerated Aging of the M119 Simulator

    NASA Technical Reports Server (NTRS)

    Bixon, Eric R.

    2000-01-01

    This paper addresses the storage requirement, shelf life, and the reliability of M119 Whistling Simulator. Experimental conditions have been determined and the data analysis has been completed for the accelerated testing of the system. A general methodology to evaluate the shelf life of the system as a function of the storage time, temperature, and relative humidity is discussed.

  10. The relationship between gestational age and compliance in human umbilical vein and its possible application in vascular grafting.

    PubMed

    Li, Wenchun; Huang, Tiezhu; Zeng, Yanjun; Yao, Zhongjun

    2006-03-01

    The aim of this study was to provide a theoretical basis, using biomechanical properties, for the clinical application of human umbilical vein (HUV) as material for vascular grafting. This was a nonrandomized, non-controlled in vitro study. The experiment was conducted in the Laboratory of Medical Biomechanics, Yunyang Medical College. HUVs of 50 normal fetuses were collected on spontaneous miscarriage or labor with the pregnant women's permission by the Department of Obstetrics and Gynecology, Taihe Hospital, Shiyan, Hubei Province. Gestational aged ranged 24-42 weeks, and parturients were 20-30 years old. The pressure-volume (P-V) relationship of HUV was measured on the biomechanical experiment stand for soft tissues, and then compliance was calculated. The P-V relationship of HUV corresponded to a parabolic curve. The compliance of HUV increased gradually with gestational age [24-27 weeks (2.22+/-0.34) x 10(-4) mL/(kPa * cm), 28-32 weeks (3.65+/-0.46) x 10(-4) mL/(kPa * cm), 33-36 weeks (4.22+/-0.55) x 10(-4) mL/(kPa * cm), 37 weeks (7.63+/-0.48) x 10(-4) mL/(kPa * cm), 38 weeks (8.32+/-0.76) x 10(-4) mL/(kPa * cm)]. However, after 39 weeks of gestation, compliance decreased gradually with gestational age [39 weeks 7.61+/-0.46) x 10(-4) mL/(kPa * cm), 40 weeks (7.53+/-0.72) x 10(-4) mL/(kPa * cm), 41 weeks (4.13+/-0.35) x 10(-4) mL/(kPa * cm), 42 weeks (2.25+/-0.62) x 10(-4) mL/(kPa * cm)]. The compliance of HUVs collected at 37-40 weeks of gestational age was similar. When the HUVs older than 42 weeks or under 28 weeks were compared, there was significant difference in their compliance (F=65.84-86.52, p<0.01). The results of the present study suggest that HUVs collected at 37-40 weeks of gestational age have good compliance, i.e., a good P-V relationship, and therefore may be a suitable material for vascular grafting. HUV is one of several graft materials that may be used when autogenous saphenous vein is absent or inadequate. HUV is very biocompatible and

  11. Impact of laboratory treatment with coloring and fluorescent liquids on the optical properties of zirconia before and after accelerated aging.

    PubMed

    Rafael, Caroline Freitas; Cesar, Paulo Francisco; Fredel, Marcio; Magini, Ricardo de Souza; Liebermann, Anja; Maziero Volpato, Cláudia Angela

    2018-03-15

    Laboratory procedures, such as dipping in coloring and fluorescent liquids, can be used to improve the optical properties of zirconia. However, information is lacking on the effect of these liquids. The purpose of this in vitro study was to evaluate the color differences and degree of fluorescence of zirconia (3Y-TZP) treated with coloring and fluorescent liquids before and after an accelerated aging protocol. Forty disk-shaped specimens of 3Y-TZP were fabricated by milling and separated according to the laboratory treatment performed: white zirconia (control group); zirconia treated with coloring liquid (A2 group); zirconia treated with fluorescent liquid (fluorescent group); and zirconia treated with both liquids (A2 fluorescent group). The L*a*b* coordinates before aging (T 0 ) were obtained with a spectrophotometer, and the degree of fluorescence was measured. The disks were subjected to accelerated aging for 1 hour (T 1 ) and 5 hours (T 2 ). Measurements were made before and after each time interval. Color differences (ΔE 00 ) were calculated using the CIEDE2000 formula and analyzed by 2-way ANOVA. Lightness (ΔL'), chroma (ΔC'), and hue differences (ΔH') were analyzed by multivariate ANOVA. Degrees of fluorescence were obtained as percentages and were analyzed by 2-way ANOVA. Multiple comparisons were performed by the Tukey HSD test (α=.05). Color differences were observed when 3Y-TZP disks were treated with coloring (7.91 ΔE 00 ), with fluorescent liquid (5.81 ΔE 00 ), and with both liquids (5.52 ΔE 00 ). Accelerated aging resulted in color differences in the T 2 A2 group (6.74 ΔE 00 ) and at both times evaluated in the fluorescent group (T 1 =8.59 ΔE 00 and T 2 =8.47 ΔE 00 ) (P<.001). In the A2 fluorescent group, the degree of fluorescence was not influenced significantly (P>.05). The use of fluorescent liquid influenced the degree of fluorescence in the fluorescent group (T 0 =20%). Significant differences in color, lightness, chroma, and hue

  12. Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography

    NASA Astrophysics Data System (ADS)

    Spitz, Kathleen; Bozic, Ivan; Desai, Vineet; Rao, Gopikrishna M.; Pollock, Lana M.; Anand-Apte, Bela; Tao, Yuankai K.

    2017-02-01

    Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition, significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of retinal vascular disease.

  13. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    PubMed

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

  14. Color change of composite resins subjected to accelerated artificial aging.

    PubMed

    Tornavoi, Denise Cremonezzi; Agnelli, José Augusto Marcondes; Panzeri, Heitor; Dos Reis, Andréa Cândido

    2013-01-01

    The aim of this study was to evaluate the influence of accelerated artificial aging (AAA) on the color change of composite resins used in dentistry. Three composite resins were evaluated: Two microhybrids and one hybrid of higher viscosity, with different amounts and sizes of filler particles, shades C2 and B2. A total of 54 specimens were obtained (18 for each composite resin), made of a Teflon matrix (15 mm in diameter and 2 mm in height). The color measurements were obtained with a Spectrophotometer, (PCB 6807 BYK Gardner) before and after AAA. Data were submitted to the Kolmogorov-Smirnov test (α >0.05), ANOVA and Tukey test (α <0.05). After statistical analysis, the color difference among composite resins with the same shades was analyzed. All composite resins showed unacceptable color changes after AAA (ΔE > 3). Considering the variable ∆E, it was observed that the color tone C2 was already statistically different for the microhybrid composite resin prior to AAA (P < 0.05) and in shade B2 for hybrid of higher viscosity and microhybrid with barium glass fluoride aluminum and silica dioxide (P < 0.01). After this process, a statistically significant difference was observed only for shade B2 between microhybrid composite resins (P < 0.01) and for hybrid of higher viscosity and microhybrid with barium glass fluoride aluminum and silica dioxide (P < 0.05). Regarding the color difference within a same composite resin group, before aging the composite resin hybrid of higher viscosity B2 showed the highest color variation rate and microhybrid with zirconium/silica C2 showed the lowest. All composite resins presented unacceptable color changes after 382 h of aging and different composite resins with same hue, presented different colors before being subjected to the aging process (B2 and C2) and after (B2). It was also observed color difference within a group of the same composite resin and same hue.

  15. Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

    PubMed Central

    Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

    2015-01-01

    Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

  16. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    PubMed

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway.

  17. Physiological and Therapeutic Vascular Remodeling Mediated by Hypoxia-Inducible Factor 1

    NASA Astrophysics Data System (ADS)

    Sarkar, Kakali; Semenza, Gregg L.

    Angiogenesis along with arteriogenesis and vasculogenesis is a fundamental process in ischemic repair in adult animals including humans. Hypoxia-inducible factor 1 (HIF-1) plays a central role in mediating adaptive responses to hypoxia/ischemia by expressing angiogenic cytokines/growth factors and their cognate receptors. Angiogenic growth factors are the homing signal for circulating angiogenic cells (CACs), which are mobilized to peripheral blood from bone marrow, recruited to target tissues, and promote vascularization. Impairment of HIF-1-mediated gene transcription contributes to the impaired vascular responses in peripheral vascular disease that are associated with aging and diabetes. Promoting neovascularization in ischemic tissues is a promising strategy for the treatment of peripheral vascular disease when surgical or catheter-based revascularization is not possible. Intramuscular injection of an adenovirus encoding a constitutively active form of HIF-1α (AdCA5), into the ischemic limb of diabetic mice increases the recovery of limb perfusion and function, rescues the diabetes-associated impairment of CACs, and increases vascularization. Administration of AdCA5 overcomes the effect of aging on recovery of blood flow in middle-aged mice following femoral artery ligation in a mouse model of age-dependent critical limb ischemia. Intramuscular injection of AdCA5 along with intravenous injection of bone-marrow-derived angiogenic cells cultured in the presence of prolyl-4-hydroxylase inhibitor dimethyloxalylglycine, increases blood flow and limb salvage in old mice following femoral artery ligation. HIF-1α gene therapy increases homing of bone-marrow-derived cells, whereas induction of HIF-1 in these cells increases their retention in the ischemic tissue by increasing their adhesion to endothelium leading to synergistic effects of combined therapy on improving blood flow.

  18. Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

    PubMed

    Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

    2017-01-01

    Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

  19. [Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

    PubMed

    Arens, C; Glanz, H; Voigt-Zimmermann, S

    2015-11-01

    The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Vascular nutritional correlates of late-life depression.

    PubMed

    Payne, Martha E; Hybels, Celia F; Bales, Connie W; Steffens, David C

    2006-09-01

    The authors sought to examine the association of vascular nutritional factors and depression in an elderly cohort of depression (currently and recently depressed) and comparison (never depressed) subjects. Nutrient intake over the past year was assessed in 196 elderly depression and comparison individuals with a Block 1998 food-frequency questionnaire. Nutrient intake, body mass index, and Keys score (a measure of the serum cholesterol-raising capacity of the diet) were determined. Subjects were age 60 and over and were participants in a longitudinal study of major depression. All subjects received psychiatric and medical comorbidity assessments; depression subjects also received psychiatric treatment. Vascular nutritional factors differed between depression and comparison subjects. The depression group had higher intake of saturated fat and cholesterol, higher body mass indices, lower alcohol intake, and higher Keys score than the comparison group. After controlling for age, sex, education, race, and medical comorbidity, associations remained for cholesterol, alcohol, and Keys score. Depression was found to be associated with overall dietary pattern as defined by total kilocalories, saturated fat, cholesterol, body mass index, polyunsaturated fat, sodium, and alcohol. This study provides evidence that dietary vascular risk factors differ in individuals with current or prior depression when compared with individuals with no history of depression.

  1. Factors Associated with Placental Vascularization Measured by 3D Power Doppler Ultrasonographic Sphere Biopsy between 11 and 14 Weeks of Gestation.

    PubMed

    Demers, Suzanne; Boutin, Amelie; Dembickaja, Regina; Campanero, Mercedes; Nicolaides, Kypros

    2018-02-19

     Preeclampsia is associated with placental vascularization disorders. Ultrasonographic sphere biopsy (USSB) of the placenta can estimate the vascularization of the placenta and potentially the risk of preeclampsia. We aimed to explore the factors related to placental vascularization measured with USSB in the first trimester.  A prospective cohort was conducted in women recruited at 11 to 14 weeks. Three-dimensional acquisition of the placenta with power Doppler was undertaken along with crown-rump length (CRL). Using USSB of the full placental thickness at its center, vascularization index, flow index, and vascular flow index were measured. Pearson's correlation coefficients and multivariate linear regression were used to correlate the vascularization indices with CRL and maternal characteristics.  A total of 5,612 women were recruited at a mean gestational age of 12.8 ± 0.6 weeks. We observed that vascularization indices increase with CRL. After adjustment, we observed that maternal age, ethnicity other than Caucasian, and body mass index were associated with lower vascularization indices, while diabetes, smoking, and assisted reproduction technology were not. We observed that parous women without history of preeclampsia had greater vascularization indices compared with nulliparous women.  Placental vascularization indices assessed by USSB fluctuate with gestational age, ethnicity, maternal age, body mass index, and previous pregnancy history. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Holocene age of the Yuha burial: Direct radiocarbon determinations by accelerator mass spectrometry

    USGS Publications Warehouse

    Stafford, Thomas W.; Jull, A.J.T.; Zabel, T.H.; Donahue, D.J.; Duhamel, R.C.; Brendel, K.; Haynes, C.V.; Bischoff, J.L.; Payen, L.A.; Taylor, R.E.

    1984-01-01

    The view that human populations may not have arrived in the Western Hemisphere before about 12,000 radiocarbon yr BP1,2 has been challenged by claims of much greater antiquity for a small number of archaeological sites and human skeleton samples. One such site is the Homo sapiens sapiens cairn burial excavated in 1971 from the Yuha desert, Imperial County, California3-5. Radiocarbon analysis of caliche coating one of the bones of the skeleton yielded a radiocarbon age of 21,500??1,000 yr BP4, while radiocarbon and uranium series analyses of caliche coating a cairn boulder yielded ages of 22,125??400 and 19,000??3,000 yr BP, respectively5. The late Pleistocene age assignment to the Yuha burial has been challenged by comparing the cultural context of the burial with other cairn burials in the same region6, on the basis of the site's geomorphological context and from radiocarbon analyses of soil caliches. 7,8 In rebuttal, arguments in defence of the original age assignment have been presented9,10 as well as an amino acid racemization analysis on the Yuha skeleton indicating an age of 23,600??2,600 yr BP11. The tandem accelerator mass spectrometer at the University of Arizona has now been used to measure the ratio of 14C/13C in several organic and inorganic fractions of post-cranial bone from the Yuha H. sapiens sapiens skeleton. Isotope ratios from six chemical fractions all yielded radiocarbon ages for the skeleton of less than 4,000 yr BP. These results indicate that the Yuha skeleton is of Holocene age, in agreement with the cultural context of the burial, and in disagreement with the previously assigned Pleistocene age of 19,000-23,000 yr. ?? 1984 Nature Publishing Group.

  3. Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

    PubMed

    Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

    2011-11-01

    Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. The influence of the accelerated ageing on the black screen element of the Electroink prints

    NASA Astrophysics Data System (ADS)

    Majnaric, I.; Bolanca, Z.; Bolanca Mirkovic, I.

    2010-06-01

    Printing material and prints undergo changes during ageing which can be recognized in deterioration in the physical, chemical and optical properties. The aim of this work is to determine the optical changes of the prints caused by ageing of the printing material and of the prints obtained by the application of the indirect electrophotography. The change of the screen elements in lighter halftone areas, which was obtained by the usage of the microscopic image analysis, has been discussed in the article. For the preparation of samples the following papers were used: fine art paper, recycled paper and offset paper as well as black Electroink. Three sample series were observed: prints on nonaged paper and ElectroInk, prints on aged paper and ElectroInk and prints on aged paper and nonaged ElectroInk. The investigation results show that by ageing of the uncoated printing substrates the decrease of the dots on prints can be expected, while the printing on the aged paper results in the increased reproduction of the halftone dots. The obtained results are the contribution to the explanation of the influence of the accelerated ageing process of papers which are used for printing and the aged prints on the halftone dot changes. Except the mentioned determined scientific contribution the results are applicable in the area of the printing product quality as well as in the forensic science.

  5. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  6. Calcitriol accelerates vascular calcification irrespective of vitamin K status in a rat model of CKD with hyperphosphatemia and secondary hyperparathyroidism.

    PubMed

    McCabe, Kristin M; Zelt, Jason G; Kaufmann, Martin; Laverty, Kimberly; Ward, Emilie; Barron, Henry; Jones, Glenville; Adams, Michael A; Holden, Rachel M

    2018-06-14

    Patients with chronic kidney disease have a markedly increased risk for developing cardiovascular disease. Non-traditional risk factors, such as increased phosphate retention, and deficiencies in vitamins D and K metabolism, likely play key roles in the development of vascular calcification during CKD progression. Calcitriol (1,25-(OH)2-D3) is a key transcriptional regulator of Matrix Gla protein (MGP), a vitamin K dependent protein that inhibits vascular calcification. The objective of this study was to determine if calcitriol treatment could inhibit the development of vascular calcification and if this inhibition was dependent on vitamin K status in a rat model of CKD. Rats were treated with dietary adenine (0.25%) to induce CKD, with either 0, 20 or 80 ng/kg of calcitriol with low or high dietary vitamin K1 (0.2 or 100 mg/kg) for 7 weeks. Calcitriol at both low (20 ng/kg) and moderate (80 ng/kg) doses increased the severity of vascular calcification and, contrary to our hypothesis, this was unaffected by high dietary vitamin K1. Calcitriol had a dose-dependent effect on: (i) lowering serum PTH, (ii) increasing serum calcium and (iii) increasing serum FGF-23. Calcitriol treatment significantly increased aortic expression of the calcification genes Runx2 and Pit-1. This data also implicates impaired vitamin D catabolism in CKD, which may contribute to the development of calcitriol toxicity and increased vascular calcification. The present findings demonstrate that in an adenine-induced rat model of CKD, calcitriol treatment at doses as low as 20 ng/kg can increase the severity of vascular calcification regardless of vitamin K status. The American Society for Pharmacology and Experimental Therapeutics.

  7. Predicting vascular complications in percutaneous coronary interventions.

    PubMed

    Piper, Winthrop D; Malenka, David J; Ryan, Thomas J; Shubrooks, Samuel J; O'Connor, Gerald T; Robb, John F; Farrell, Karen L; Corliss, Mary S; Hearne, Michael J; Kellett, Mirle A; Watkins, Matthew W; Bradley, William A; Hettleman, Bruce D; Silver, Theodore M; McGrath, Paul D; O'Mears, John R; Wennberg, David E

    2003-06-01

    Using a large, current, regional registry of percutaneous coronary interventions (PCI), we identified risk factors for postprocedure vascular complications and developed a scoring system to estimate individual patient risk. A vascular complication (access-site injury requiring treatment or bleeding requiring transfusion) is a potentially avoidable outcome of PCI. Data were collected on 18,137 consecutive patients undergoing PCI in northern New England from January 1997 to December 1999. Multivariate regression was used to identify characteristics associated with vascular complications and to develop a scoring system to predict risk. The rate of vascular complication was 2.98% (541 cases). Variables associated with increased risk in the multivariate analysis included age >or=70, odds ratio (OR) 2.7, female sex (OR 2.4), body surface area <1.6 m(2) (OR 1.9), history of congestive heart failure (OR 1.4), chronic obstructive pulmonary disease (OR 1.5), renal failure (OR 1.9), lower extremity vascular disease (OR 1.4), bleeding disorder (OR 1.68), emergent priority (OR 2.3), myocardial infarction (OR 1.7), shock (1.86), >or=1 type B2 (OR 1.32) or type C (OR 1.7) lesions, 3-vessel PCI (OR 1.5), use of thienopyridines (OR 1.4) or use of glycoprotein IIb/IIIa receptor inhibitors (OR 1.9). The model performed well in tests for significance, discrimination, and calibration. The scoring system captured 75% of actual vascular complications in its highest quintiles of predicted risk. Predicting the risk of post-PCI vascular complications is feasible. This information may be useful for clinical decision-making and institutional efforts at quality improvement.

  8. IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

    PubMed

    Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the

  9. Drinking citrus fruit juice inhibits vascular remodeling in cuff-induced vascular injury mouse model.

    PubMed

    Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

    2015-01-01

    Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI.

  10. Drinking Citrus Fruit Juice Inhibits Vascular Remodeling in Cuff-Induced Vascular Injury Mouse Model

    PubMed Central

    Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-no, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

    2015-01-01

    Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI. PMID:25692290

  11. Effect of healthy aging on renal vascular responses to local cooling and apnea

    PubMed Central

    Patel, Hardikkumar M.; Mast, Jessica L.; Sinoway, Lawrence I.

    2013-01-01

    Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects. Beat-by-beat MAP, heart rate (HR), and renal blood flow velocity (from Doppler) were measured in the supine posture, and changes from baseline were compared between groups. In response to 1°C forehead cooling, aging was associated with an augmented MAP (20 ± 3 vs. 6 ± 2 mmHg) and RVRI (35 ± 6 vs. 16 ± 9%) but not HR. In older adults, there was a positive correlation between the cold-induced pressor response and forehead pain (R = 0.726), but this effect was not observed in young subjects. The CPT raised RVRI in both young (56 ± 13%) and older (45 ± 8%) subjects, but this was not different between groups. Relative to baseline, end-expiratory apnea increased RVRI to a similar extent in both young (46 ± 14%) and older (41 ± 9%) subjects. During sympathetic activation, renal vasoconstriction occurred in both groups. Forehead cooling caused an augmented pressor response in older adults that was related to pain perception. PMID:23640587

  12. Puberty as an accelerator for diabetes complications.

    PubMed

    Cho, Yoon Hi; Craig, Maria E; Donaghue, Kim C

    2014-02-01

    Much is written about how difficult it is to deal with diabetes during adolescence, and rightly so. Less is understood as to how puberty may be an accelerator of vascular complications. With the increase in childhood diabetes, complication risks need to be revisited in relation to puberty and the secular increase in adiposity. Recent data suggest greater risk for severe vascular complications in those with diabetes during puberty, compared with young people who develop diabetes after puberty. It is also widely recognized that higher hemoglobin A1c (HbA1c) results are often seen during the pubertal period. This article will review complication outcomes in relation to puberty and examine mechanisms by which puberty may modify risk above glycemic exposure, and possible gender disparities in the risk of complications in the adolescent period. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Descriptive study of relationship between cardio-ankle vascular index and biomarkers in vascular-related diseases.

    PubMed

    Liu, Jinbo; Liu, Huan; Zhao, Hongwei; Shang, Guangyun; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

    2017-01-01

    Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

  14. Outcomes of Elderly Patients after Predialysis Vascular Access Creation

    PubMed Central

    Lee, Timmy; Thamer, Mae; Zhang, Yi; Zhang, Qian

    2015-01-01

    Uniform vascular access guidelines for elderly patients may be inappropriate because of the competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes in this population. However, the outcomes in elderly patients with advanced CKD who receive permanent vascular access before dialysis initiation are unclear. We identified a large nationally representative cohort of 3418 elderly patients (aged ≥70 years) with CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to 2009, and assessed the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. In all, 67% of patients with predialysis AVF and 71% of patients with predialysis AVG creation initiated dialysis within 2 years of access placement, but the overall risk of dialysis initiation was modified by patient age and race. Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8% of AVFs were created <90 days before dialysis initiation. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF than in patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 2 years. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may serve as a “catheter-sparing” approach and allow delay of permanent access placement in selected elderly patients with CKD. PMID:25855782

  15. Endothelial transplantation rejuvenates aged hematopoietic stem cell function

    PubMed Central

    Poulos, Michael G.; Gutkin, Michael C.; Llanos, Pierre; Gilleran, Katherine; Rabbany, Sina Y.; Butler, Jason M.

    2017-01-01

    Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, HSC-supportive BM ECs enhanced hematopoietic recovery following myelosuppressive injury and restored endogenous HSC function in aged mice. Coinfusion of young ECs augmented aged HSC engraftment and enhanced overall survival in lethally irradiated mice by mitigating damage to the BM vascular microenvironment. These data lay the groundwork for the exploration of EC therapies that can serve as adjuvant modalities to enhance HSC engraftment and accelerate hematopoietic recovery in the elderly population following myelosuppressive regimens. PMID:29035282

  16. A national survey of evolving management patterns for vascular injury.

    PubMed

    Burkhardt, Gabriel E; Rasmussen, Todd E; Propper, Brandon W; Lopez, Peter L; Gifford, Shaun M; Clouse, W Darrin

    2009-01-01

    The modern era has witnessed an increase in endovascular techniques used by physicians to treat vascular injury and age-related disease. As a consequence, the number of open vascular operations available for general surgical education has decreased dramatically. This changing paradigm threatens competence in vascular injury management achieved during surgical residency. The objective of this study is to sample perceptions on vascular injury treatment in the United States to highlight the need for planning for this important tenet of surgical education. An electronic survey was extended to board-certified surgeons through 3 professional societies, the Peripheral Vascular Surgery Society (PVSS), the Eastern Association for the Surgery of Trauma (EAST), and the American College of Surgeons (ACS). A total of 520 respondents were self-categorized as trauma (59%; n = 307), vascular (17%; n = 90), or general (19%; n = 99) surgeons. Respondents reported that general surgeons currently manage less than 10% of vascular injuries at their respective institutions. A 2.5-fold increase in endovascular treatment of vascular injury during the past decade was reported with interventional radiologists now involved in the management of up to 25% of injuries. Few general or trauma surgeons surveyed possessed a catheter-based skill set, although 38% of trauma surgeons expressed great interest in endovascular training. Additionally, a cadre of vascular surgeons (67%) affirmed a commitment to teaching vascular injury management. The results of this study confirm a diminished role for non-fellowship-trained surgeons in managing vascular injury. Despite an increased acceptance of endovascular techniques to manage trauma, general and trauma surgeons do not possess the skill set. Collaboration between surgical communities will be especially important to maintain high standards in vascular injury management.

  17. Treating vascular lesions.

    PubMed

    Astner, Susanne; Anderson, R Rox

    2005-01-01

    The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

  18. Vascular Cognitive Impairment in a Memory Clinic Population: Rationale and Design of the "Utrecht-Amsterdam Clinical Features and Prognosis in Vascular Cognitive Impairment" (TRACE-VCI) Study.

    PubMed

    Boomsma, Jooske Marije Funke; Exalto, Lieza Geertje; Barkhof, Frederik; van den Berg, Esther; de Bresser, Jeroen; Heinen, Rutger; Koek, Huiberdina Lena; Prins, Niels Daniël; Scheltens, Philip; Weinstein, Henry Chanoch; van der Flier, Wiesje Maria; Biessels, Geert Jan

    2017-04-19

    Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction due to vascular brain injury, as a single cause or in combination with other, often neurodegenerative, etiologies. VCI is a broad construct that captures a heterogeneous patient population both in terms of cognitive and noncognitive symptoms and in terms of etiology and prognosis. This provides a challenge when applying this construct in clinical practice. This paper presents the rationale and design of the TRACE-VCI study, which investigates the clinical features and prognosis of VCI in a memory clinic setting. The TRACE-VCI project is an observational, prospective cohort study of 861 consecutive memory clinic patients with possible VCI. Between 2009 and 2013, patients were recruited through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC) (N=665) and the outpatient memory clinic and VCI cohort of the University Medical Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients with a primary etiology other than vascular brain injury or neurodegeneration were excluded. Patients underwent an extensive 1-day memory clinic evaluation including an interview, physical and neurological examination, assessment of biomarkers (including those for Alzheimer-type pathologies), extensive neuropsychological testing, and an MRI scan of the brain. For prognostic analyses, the composite primary outcome measure was defined as accelerated cognitive decline (change of clinical dementia rating ≥1 or institutionalization) or (recurrent) major vascular events or death over the course of 2 years. The mean age at baseline was 67.7 (SD 8.5) years and 46.3% of patients (399/861) were female. At baseline, the median Clinical Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini-Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at baseline was

  19. Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

    PubMed

    Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

    2017-11-15

    Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

  20. The association of maternal prenatal psychosocial stress with vascular function in the child at age 10-11 years: findings from the Avon longitudinal study of parents and children.

    PubMed

    van Dijk, Aimée E; Dawe, Karen; Deanfield, John; Stronks, Karien; Gemke, Reinoud J B J; Vrijkotte, Tanja G M; Lawlor, Debbie A

    2014-09-01

    To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress. Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10-11 years (n = 4,318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP. We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10-12 years via intrauterine mechanisms. © Authors 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Cross-talk between Aβ and endothelial SSAO/VAP-1 accelerates vascular damage and Aβ aggregation related to CAA-AD.

    PubMed

    Solé, Montse; Miñano-Molina, Alfredo J; Unzeta, Mercedes

    2015-02-01

    An association between semicarbazide-sensitive amine oxidase (SSAO) and cerebral amyloid angiopathy (CAA) related to Alzheimer's disease (AD) has been largely postulated. Increased SSAO activity and expression have been detected in cerebrovascular tissue and plasma of AD patients, colocalizing with cerebrovascular amyloid-beta (Aβ) deposits. As an enzyme, SSAO metabolizes primary amines generating hydrogen peroxide, ammonia, and aldehydes. The ability of these products to generate oxidative stress, to enhance the advanced glycation end-product generation, to promote the Aβ aggregation in vitro, and to induce apoptosis supports its role in CAA-related vascular pathology. However, whether the SSAO increase constitutes a cause or it is a consequence of the pathologic process has not been elucidated so far. To set up the nature of this relationship, vascular cell models expressing SSAO were treated with different Aβ forms, simulating the CAA conditions in vitro. It was found that the presence of the vasculotropic Dutch-mutated Aβ1-40 increases (Aβ1-40 D) the SSAO-dependent toxicity, which is accompanied by an increase of SSAO protein availability in endothelial cell membranes. In addition, SSAO enhances Aβ1-40 D and Aβ1-42 deposition on vascular cells by both activity-dependent and -independent mechanisms. Thus, we provide evidences indicating that Aβ itself could be one of the factors inducing SSAO increase in AD, enhancing its toxic effect, and inducing the vascular dysfunction and, in turn, that SSAO stimulates Aβ deposition on the vascular walls, thereby contributing to the CAA-AD progression. Therefore, molecules inhibiting SSAO could provide an alternative treatment for preventing/delaying the progress of CAA-AD-associated vasculopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease.

    PubMed

    Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C

    2014-02-07

    Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular

  3. Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging.

    PubMed

    Bailey-Downs, Lora C; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C; Ballabh, Praveen; Koller, Akos; Farley, Julie A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2012-06-01

    Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.

  4. Growth Hormone and IGF-1 Deficiency Exacerbate High-Fat Diet–Induced Endothelial Impairment in Obese Lewis Dwarf Rats: Implications for Vascular Aging

    PubMed Central

    Bailey-Downs, Lora C.; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C.; Ballabh, Praveen; Koller, Akos; Farley, Julie A.; Sonntag, William E.; Csiszar, Anna

    2012-01-01

    Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1–deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity. PMID:22080499

  5. The electrical performance of polymeric insulating materials under accelerated aging in a fog chamber

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

    Gorur, R.S.; Cherney, E.A.; Hackam, R.

    1988-07-01

    A comparative study of the ac (60 Hz) surface aging in a fog chamber is reported on cylindrical rod samples of high temperature vulcanized (HTV) silicone rubber and ethylene propylene diene monomer (EPDM) rubber containing various amounts of alumina trihydrate (ATH) and/or silica fillers. In low conductivity (250 ..mu..S/cm) fog, silicone rubber performed better than EPDM samples whereas in high conductivity (1000 ..mu..S/cm) fog, the order of performance was reversed. The mechanisms by which fillers impart tracking and erosion resistance to materials is discussed as influenced by the experimental conditions of the accelerated aging tests. Surface studies by ESCA (Electronmore » Spectroscopy for Chemical Analysis) demonstrate that the hydrophobicity of silicone rubber, despite the accumulation of surface contamination, can be attributed to migration of low molecular weight polymer chains and/or mobile fluids, such as silicone oil.« less

  6. [Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

    PubMed

    Voigt-Zimmermann, S; Arens, C

    2014-12-01

    In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

    PubMed

    Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

    2018-05-01

    Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  8. Stroke injury, cognitive impairment and vascular dementia☆

    PubMed Central

    Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

    2016-01-01

    The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

  9. Arterial complications of vascular Ehlers-Danlos syndrome.

    PubMed

    Eagleton, Matthew J

    2016-12-01

    Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates. A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1. The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention. With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  10. D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

    PubMed

    Cardoso, Armando; Magano, Sara; Marrana, Francisco; Andrade, José P

    2015-12-01

    The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

  11. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

    PubMed Central

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

    2016-01-01

    Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  12. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

    PubMed

    Egeberg, Alexander; Skov, Lone; Joshi, Aditya A; Mallbris, Lotus; Gislason, Gunnar H; Wu, Jashin J; Rodante, Justin; Lerman, Joseph B; Ahlman, Mark A; Gelfand, Joel M; Mehta, Nehal N

    2017-10-01

    Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a β-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (β = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). These studies utilized observational data. We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

  13. Age-related changes in dorsal root ganglia, circulating and vascular calcitonin gene-related peptide (CGRP) concentrations in female rats: Effect of female sex steroid hormones

    PubMed Central

    Gangula, Pandu R.R.; Chauhan, Madhu; Reed, Luckey; Yallampalli, Chandra

    2009-01-01

    The aim of the present study is to investigate whether immunoreactive (I) calcitonin gene-related peptide (CGRP) content is decreased in plasma and mesenteric arteries (resistance arteries) in middle-aged rats and if so, whether sex steroid hormones enhance I-CGRP in middle-aged female rats. We also examined whether vascular CGRP receptor components, calcitonin receptor like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) are elevated by sex steroid hormones treatment in middle-aged female rats. Young adult (3 months old) and middle-aged (10–12 months old) ovariectomized rats were treated subcutaneously with estradiol-17β (E2; 2 mg), progesterone (P4; 5 mg), E2 +P4 (2 mg + 20 mg) or placebo (control). Radioimmunoassay and Western blot analysis were performed to measure I-CGRP content and CGRP receptor components in dorsal root ganglia (DRG), in resistance arteries and in plasma. Immunofluorescent staining methods were employed to determine cellular localization of CRLR, RAMP1 in resistance arteries. Our data demonstrated that I-CGRP content was significantly (p < 0.05) lower in the plasma and resistance arteries of middle-aged female rats compared to young controls. Both RAMP1 and CRLR were concentrated in vascular endothelium and the underlying smooth muscle cells. RAMP1 but not CRLR appeared to be decreased in middle-aged rat vasculature. Chronic perfusion of sex steroid hormones to ovariectomized rats: (1) significantly (p < 0.05) elevated I-CGRP in the DRG and in the plasma, and (2) significantly elevated RAMP1 (p < 0.05) but did not alter CRLR in resistance arteries. These data suggest that female sex steroid treatment enhances I-CGRP and its receptors, and thus regulate the blood pressure in aged female rats. PMID:19429067

  14. Vascular invasion is a prognostic indicator in hepatoblastoma.

    PubMed

    Shi, Yan; Commander, Sarah J; Masand, Prakash M; Heczey, Andras; Goss, John A; Vasudevan, Sanjeev A

    2017-06-01

    The data regarding vascular invasion as a prognostic factor in hepatoblastoma (HB) are conflicted. The purpose of this study is to examine the relationship between vascular invasion and outcomes. This is a retrospective review of patients <18 years old who underwent resection for hepatoblastoma from 1998 to 2015. Pathology reports were used to identify patients who had pathologic vascular invasion (VI), and those who did not (NVI). Sixty-six children were identified with a median age at diagnosis of 21months (interquartile range: 10-33months). Pathologic vascular invasion was present in 42/66 (64%) patients. A significant difference (P=0.02) in 3-year overall survival (3YOS) was detected between NVI (95%) and VI (61%). Recurrent disease was present in 8/66 (12%) patients. A marginally significant difference (P=0.08) was found in 3-year recurrence free survival (3YRFS) between NVI (94%) and the VI (76%) groups. Patients with NVI had no metastatic disease, had a lower recurrence rate, universally responded to neoadjuvant chemotherapy, and were less likely to have small cell undifferentiated histology. Twenty-one children underwent orthotopic liver transplant (OLT), with no difference in 3YROS or 3YRFS. Pathologic vascular invasion is associated with significantly worse 3YOS in HB, and lack of vascular invasion was associated with more favorable disease characteristics. The presence of pathologic vascular invasion did not confer a worse outcome in patients treated with liver transplantation in this cohort of patients. Retrospective review. Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Vascular Factors and Cognitive Dysfunction in Alzheimer Disease.

    PubMed

    Pąchalska, Maria; Bidzan, Leszek; Bidzan, Mariola; Góral-Półrola, Jolanta

    2015-11-12

    The purpose of the present study was to assess the influence of vascular factors on the degree of intensity and rate of progression of cognitive disorders in the course of Alzheimer Disease (AD). The research group consisted of 39 persons, all of whom were diagnosed with AD according to the NINCDS/ADRDA criteria. We divided these patients into 2 subgroups, based on the vascular factors measured by the modified Hachinski Ischemic Scale (Ha-mod): group A, without the vascular component (HA-mod score of 0-1 point), and group B, with the vascular component (a score over 1 point). Cognitive functions were evaluated at baseline and again 2 years later, using the Cognitive Part of the Alzheimer Disease Assessment Scale (ADAS-cog). We found that the patients from subgroup B, with the stronger vascular component, demonstrated the highest intensity of cognitive disorders at baseline, both in terms of the overall ADAS-cog score, and in the subscores for ideational praxis, orientation, spoken language ability, comprehension of spoken language, and word-finding difficulty in spontaneous speech. Another variable which was connected with the intensity of dementia was age. After 2 years, however, the rate of progression of cognitive disorders was not significantly different between the 2 groups. The severity of vascular factors correlates directly with the intensity of cognitive disturbances. At the 2-year follow-up examination, however, no correlation was observed in the research group between greater vascular involvement and more rapid progression of cognitive disorders, as measured by the ADAS-cog scale.

  16. Two-year performance study of porous, thermoset, shape memory polyurethanes intended for vascular medical devices

    NASA Astrophysics Data System (ADS)

    Weems, Andrew C.; Boyle, Anthony J.; Maitland, Duncan J.

    2017-03-01

    The long-term shape-recovery behavior of shape memory polymers has often been shown to be dependent on the length of time the material has been stored in the secondary shape. Typically, recovery performance and shape fixity will decrease with increased time in the secondary shape. In medical materials, a shelf-life is crucial to establish as it sets the upper threshold for device performance in a clinical setting, and a reduction in shape recovery would limit the development of SMP medical devices. Here, we present a two-year study of strain recovery, strain fixity, and shape recovery kinetics for passively and actively actuated SMPs intended for vascular devices. While kinetic experiments using immersion DMA indicate slight material relaxation and a decrease in the time to recovery, these changes are not found for bulk recovery experiments. The results indicate that a two-year shelf-life for these SMPs is very reasonable, as there is no change in the recovery kinetics, strain recovery, or strain fixity associated with this aging time. Further, a thermal accelerated aging test is presented for more rapid testing of the shape memory behavior of these SMPs and is compared with the real time aging results, indicating that this test is a reasonable indicator of the two-year behavior.

  17. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

  18. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  19. Depression, insight, and personality changes in Alzheimer's disease and vascular dementia.

    PubMed

    Verhey, F R; Ponds, R W; Rozendaal, N; Jolles, J

    1995-01-01

    Although it is generally believed that depression, retained insight, and preserved personality occur more frequently in vascular dementia than in Alzheimer's disease, there is little empiric evidence for this presumption. Most studies on this subject have been carried out with severely demented inpatients, and confounding factors such as age, sex, and severity of dementia have not been sufficiently taken into account. We compared 48 patients with relatively mild vascular dementia with 48 patients with Alzheimer's disease, matched for age, sex, and stage of dementia, to investigate if depression, lack of insight, and personality changes were related to the cause of dementia. The two groups did not differ regarding the incidence of major depression, the mean depression score, the awareness score, or the sum of scores on the items of the Blessed Dementia Scale concerning personality changes. We conclude that depression, lack of insight, and personality changes do not favor an etiology of vascular dementia over that of Alzheimer's disease. The present findings underscore the notion that the severity of the dementia should be considered in studies on the differences between vascular dementia and Alzheimer's disease.

  20. Branding of vascular surgery.

    PubMed

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  1. Accelerated life testing of spacecraft subsystems

    NASA Technical Reports Server (NTRS)

    Wiksten, D.; Swanson, J.

    1972-01-01

    The rationale and requirements for conducting accelerated life tests on electronic subsystems of spacecraft are presented. A method for applying data on the reliability and temperature sensitivity of the parts contained in a sybsystem to the selection of accelerated life test parameters is described. Additional considerations affecting the formulation of test requirements are identified, and practical limitations of accelerated aging are described.

  2. Visfatin and cardio-cerebro-vascular disease.

    PubMed

    Wang, Pei; Vanhoutte, Paul M; Miao, Chao-Yu

    2012-01-01

    Nicotinamide phosphoribosyltransferase is the rate-limiting enzyme that catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide from nicotinamide. This protein was originally cloned as a putative pre-B cell colony-enhancing factor and also found to be a visceral fat-derived adipokine (visfatin). As a multifunctional protein, visfatin plays an important role in immunity, metabolism, aging, inflammation, and responses to stress. Visfatin also participates in several pathophysiological processes contributing to cardio-cerebro-vascular diseases, including hypertension, atherosclerosis, ischemic heart disease, and ischemic stroke. However, whether visfatin is a friend or a foe in these diseases remains uncertain. This brief review focuses on the current understanding of the complex role of visfatin in the cardio-cerebro-vascular system under normal and pathophysiological conditions.

  3. Assessment of cardiovascular risk and vascular age in overweight/obese adults with primary hypertension: the EXERDIET-HTA study.

    PubMed

    Gorostegi-Anduaga, Ilargi; Pérez-Asenjo, Javier; Aispuru, Gualberto Rodrigo; Fryer, Simon M; Alonso-Colmenero, Ainara; Romaratezabala, Estíbaliz; Maldonado-Martín, Sara

    2017-06-01

    Hypertension (HTN), obesity and low cardiorespiratory fitness (CRF) are associated with an increased risk for a cardiovascular event. Enrolling overweight/obese individuals with HTN, the current study aimed to estimate cardiovascular risk (CVR) and vascular age (VA) profiles analyzing potential sex differences, determine whether VA is higher than chronological age, and whether CVR is associated with a low level of CRF. Overweight/obese non-Hispanic White participants (n=209; 141 men and 68 women) with primary HTN had their CVR and VA determined using the New Pooled Cohort Risk Equations and The Framingham method, respectively. Considering values of peak oxygen uptake, participants were divided into tertiles for each sex. The CVR, but not VA (P=0.339), was higher (P<0.001) in men compared with women irrespective of age. Irrespective of sex, VA was higher than chronological age (P<0.001). Age and BMI were higher (P<0.05) in the low CRF group compared with that in other groups. There were no differences in CVR (P=0.907) and VA (P=1.643) when values were separated into CRF groups. Pooled Cohort Equations could underestimate the risk of suffering a cardiovascular event in the following 10 years in overweight/obese non-Hispanic White women with HTN compared with men. The VA appears to be a useful tool in communicating CVR in this population irrespective of sex. The CRF alone may not be enough to moderate the CVR.

  4. Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: Evidence for a protective role for glucosamine in atherosclerosis

    PubMed Central

    Duan, Wenlan; Paka, Latha; Pillarisetti, Sivaram

    2005-01-01

    Accelerated atherosclerosis is one of the major vascular complications of diabetes. Factors including hyperglycemia and hyperinsulinemia may contribute to accelerated vascular disease. Among the several mechanisms proposed to explain the link between hyperglycemia and vascular dysfunction is the hexosamine pathway, where glucose is converted to glucosamine. Although some animal experiments suggest that glucosamine may mediate insulin resistance, it is not clear whether glucosamine is the mediator of vascular complications associated with hyperglycemia. Several processes may contribute to diabetic atherosclerosis including decreased vascular heparin sulfate proteoglycans (HSPG), increased endothelial permeability and increased smooth muscle cell (SMC) proliferation. In this study, we determined the effects of glucose and glucosamine on endothelial cells and SMCs in vitro and on atherosclerosis in apoE null mice. Incubation of endothelial cells with glucosamine, but not glucose, significantly increased matrix HSPG (perlecan) containing heparin-like sequences. Increased HSPG in endothelial cells was associated with decreased protein transport across endothelial cell monolayers and decreased monocyte binding to subendothelial matrix. Glucose increased SMC proliferation, whereas glucosamine significantly inhibited SMC growth. The antiproliferative effect of glucosamine was mediated via induction of perlecan HSPG. We tested if glucosamine affects atherosclerosis development in apoE-null mice. Glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects. PMID:16207378

  5. Mechanical and Chemical Properties of Harvested Hypalon Cable Jacket Subjected to Accelerated Thermal Aging

    DOE PAGES

    Duckworth, Robert C.; Kidder, Michelle K.; Aytug, Tolga; ...

    2018-02-27

    We report that for nuclear power plants (NPPs) considering second license renewal for operation beyond 60 years, knowledge of long-term operation, condition monitoring, and viability for the reactor components including reactor pressure vessel, concrete structures, and cable systems is essential. Such knowledge will provide NPP owners/operators with a basis for predicting performance and estimating the costs associated with monitoring or replacement programs for the affected systems. For cable systems that encompass a wide variety of materials, manufacturers, and in-plant locations, accelerated aging of harvested cable jacket and insulation can provide insight into a remaining useful life and methods for monitoring.more » Accelerated thermal aging in air at temperatures between 80°C and 120°C was conducted on a multiconductor control rod drive mechanism cable manufactured by Boston Insulated Wire (BIW). The cable, which had been in service for over 30 years, was jacketed with Hypalon and insulated with ethylene propylene rubber. From elongation at break (EAB) measurements and supporting Arrhenius analysis of the jacket material, an activation energy of 97.84 kJ/mol was estimated, and the time to degradation, as represented by 50% EAB at the expected maximum operating temperature of 45°C, was estimated to be 80 years. These values were slightly below previous measurements on similar BIW Hypalon cable jacket and could be attributed to either in-service degradation or variations in material properties from production variations. Lastly, results from indenter modulus measurements and Fourier transform infrared spectroscopy suggest possible markers that could be beneficial in monitoring cable conditions.« less

  6. Mechanical and Chemical Properties of Harvested Hypalon Cable Jacket Subjected to Accelerated Thermal Aging

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

    Duckworth, Robert C.; Kidder, Michelle K.; Aytug, Tolga

    We report that for nuclear power plants (NPPs) considering second license renewal for operation beyond 60 years, knowledge of long-term operation, condition monitoring, and viability for the reactor components including reactor pressure vessel, concrete structures, and cable systems is essential. Such knowledge will provide NPP owners/operators with a basis for predicting performance and estimating the costs associated with monitoring or replacement programs for the affected systems. For cable systems that encompass a wide variety of materials, manufacturers, and in-plant locations, accelerated aging of harvested cable jacket and insulation can provide insight into a remaining useful life and methods for monitoring.more » Accelerated thermal aging in air at temperatures between 80°C and 120°C was conducted on a multiconductor control rod drive mechanism cable manufactured by Boston Insulated Wire (BIW). The cable, which had been in service for over 30 years, was jacketed with Hypalon and insulated with ethylene propylene rubber. From elongation at break (EAB) measurements and supporting Arrhenius analysis of the jacket material, an activation energy of 97.84 kJ/mol was estimated, and the time to degradation, as represented by 50% EAB at the expected maximum operating temperature of 45°C, was estimated to be 80 years. These values were slightly below previous measurements on similar BIW Hypalon cable jacket and could be attributed to either in-service degradation or variations in material properties from production variations. Lastly, results from indenter modulus measurements and Fourier transform infrared spectroscopy suggest possible markers that could be beneficial in monitoring cable conditions.« less

  7. Outcomes of Elderly Patients after Predialysis Vascular Access Creation.

    PubMed

    Lee, Timmy; Thamer, Mae; Zhang, Yi; Zhang, Qian; Allon, Michael

    2015-12-01

    Uniform vascular access guidelines for elderly patients may be inappropriate because of the competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes in this population. However, the outcomes in elderly patients with advanced CKD who receive permanent vascular access before dialysis initiation are unclear. We identified a large nationally representative cohort of 3418 elderly patients (aged ≥ 70 years) with CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to 2009, and assessed the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. In all, 67% of patients with predialysis AVF and 71% of patients with predialysis AVG creation initiated dialysis within 2 years of access placement, but the overall risk of dialysis initiation was modified by patient age and race. Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8% of AVFs were created <90 days before dialysis initiation. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF than in patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 2 years. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may serve as a "catheter-sparing" approach and allow delay of permanent access placement in selected elderly patients with CKD. Copyright © 2015 by the American Society of Nephrology.

  8. Exercise Versus +Gz Acceleration Training

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.; Simonson, S. R.; Stocks, J. M.; Evans, J. M.; Knapp, C. F.; Dalton, Bonnie P. (Technical Monitor)

    2002-01-01

    Decreased working capacity and "orthostatic" intolerance are two major problems for astronauts during and after landing from spaceflight in a return vehicle. The purpose was to test the hypotheses that (1) supine-passive-acceleration training, supine-interval-exercise plus acceleration training, and supine exercise plus acceleration training will improve orthostatic tolerance (OT) in ambulatory men; and that (2) addition of aerobic exercise conditioning will not influence this enhanced OT from that of passive-acceleration training. Seven untrained men (24-38 yr) underwent 3 training regimens (30 min/d x 5d/wk x 3wk on the human-powered centrifuge - HPC): (a) Passive acceleration (alternating +1.0 Gz to 50% Gzmax); (b) Exercise acceleration (alternating 40% - 90% V02max leg cycle exercise plus 50% of HPCmax acceleration); and (c) Combined intermittent exercise-acceleration at 40% to 90% HPCmax. Maximal supine exercise workloads increased (P < 0.05) by 8.3% with Passive, by 12.6% with Exercise, and by 15.4% with Combined; but maximal V02 and HR were unchanged in all groups. Maximal endurance (time to cessation) was unchanged with Passive, but increased (P < 0.05) with Exercise and Combined. Resting pre-tilt HR was elevated by 12.9% (P < 0.05) only after Passive training, suggesting that exercise training attenuated this HR response. All resting pre-tilt blood pressures (SBP, DBP, MAP) were not different pre- vs. post-training. Post-training tilt-tolerance time and HR were increased (P < 0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training attenuated the increased Passive tilt tolerance. Resting (pre-tilt) and post-tilt cardiac R-R interval, stroke volume, end-diastolic volume, and cardiac output were all uniformly reduced (P < 0.05) while peripheral resistance was uniformly increased (P < 0.05) pre-and post-training for the three regimens indicating no effect of any training regimen on those cardiovascular

  9. Management of war-related vascular injuries: experience from the second gulf war.

    PubMed

    Jawas, Ali; Abbas, Alaa K; Nazzal, Munier; Albader, Marzoog; Abu-Zidan, Fikri M

    2013-07-01

    To study the biomechanism, pattern of injury, management, and outcome of major vascular injuries treated at Mubarak Al-Kabeer Teaching Hospital, Kuwait during the Second Gulf War. This is a descriptive retrospective study. War-related injured patients who had major vascular injuries and were treated at Mubarak Al-Kabeer Teaching Hospital from August 1990 to September 1991 were studied. Studied variables included age, gender, anatomical site of vascular injury, mechanism of injury, associated injuries, type of vascular repair, and clinical outcome. 36 patients having a mean (SD) age of 29.8 (10.2) years were studied. 32 (89%) were males and 21 (58%) were civilians. Majority of injuries were caused by bullets (47.2%) and blast injuries (47.2%). Eight patients (22%) presented with shock.There were 31 arterial injuries, common and superficial femoral artery injuries were most common (10/31). Arterial repair included interposition saphenous vein graft in seven patients, thrombectomy with end-to-end / lateral repair in twelve patients, vein patch in two patients, and arterial ligation in four patients. Six patients had arterial ligation as part of primary amputation. 3/21 (14.3%) patients had secondary amputation after attempted arterial vascular repair of an extremity. There were a total of 17 venous injuries, 13 managed by lateral suture repair and 4 by ligation. The median (range) hospital stay was 8 (1-76) days. 5 patients died (14%). Major vascular injuries occurred in 10% of hospitalized war-related injured patients. Our secondary amputation rate of extremities was 14%. The presence of a vascular surgeon within a military surgical team is highly recommended. Basic principles and techniques of vascular repair remain an essential part of training general surgeons because it may be needed in unexpected wars.

  10. Non-invasive vascular biomarkers in patients with Behçet's disease: review of the data and future perspectives.

    PubMed

    Protogerou, Athanase D; Nasothimiou, Efthimia G; Sfikakis, Petros P; Tzioufas, Athanasios G

    2017-01-01

    Vascular inflammation in small to large veins and arteries contributes substantially to mortality above that of the general population in Behçet's disease. Recent data verified also the presence of accelerated classical subclinical arterial damage (atheromatosis, arteriosclerosis, arterial hypertrophy) even in patients free of overt vascular complications, and may be complementary to that of vasculitis. Early detection of such vascular damage might provide helpful pathophysiological insight and potentially even guide treatment management. Herein, we review the existing literature for each one of the most widely applied non-invasive vascular biomarkers (assessing endothelial dysfunction, atheromatosis/hypertrophy, arteriosclerosis and central haemodynamic parameters) that are clinically used in primary cardiovascular prevention. We aim to: (i) identify early pathophysiological vascular pathways, complementary to vasculitis, in the development of vascular complications and (ii) identify gaps in knowledge and suggest future research topics. We identified evidence of proof of concept for some of the widely applied non-invasive vascular biomarkers (carotid plaques, pulse wave velocity, flow mediated dilatation). Yet, several steps in their clinical validation process are lacking. Extensive vascular phenotyping of a large prospective observational patient cohort with the application of these easy-to-use, low-cost, free of any adverse effect, non-invasive methods should be performed in order to test their ability to provide clinically meaningful guidance regarding the prognosis and treatment of Behçet's disease.

  11. IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging.

    PubMed

    Toth, Peter; Tarantini, Stefano; Ashpole, Nicole M; Tucsek, Zsuzsanna; Milne, Ginger L; Valcarcel-Ares, Noa M; Menyhart, Akos; Farkas, Eszter; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Aging is associated with marked deficiency in circulating IGF-1, which has been shown to contribute to age-related cognitive decline. Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of age-related cognitive impairment. To establish the link between IGF-1 deficiency and cerebromicrovascular impairment, neurovascular coupling mechanisms were studied in a novel mouse model of IGF-1 deficiency (Igf1(f/f) -TBG-Cre-AAV8) and accelerated vascular aging. We found that IGF-1-deficient mice exhibit neurovascular uncoupling and show a deficit in hippocampal-dependent spatial memory test, mimicking the aging phenotype. IGF-1 deficiency significantly impaired cerebromicrovascular endothelial function decreasing NO mediation of neurovascular coupling. IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impairing mediation of CBF responses by eicosanoid gliotransmitters. Collectively, we demonstrate that IGF-1 deficiency promotes cerebromicrovascular dysfunction and neurovascular uncoupling mimicking the aging phenotype, which are likely to contribute to cognitive impairment. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts.

    PubMed

    Chang, C S; Su, C Y; Lin, T C

    1999-01-01

    An intimate relationship exists between the regenerative response of the vascular and osseous elements following hydroxyapatite (HA) implantation. In order to fully comprehend the 3-dimensional vascular architecture around HA, dense HA particles were implanted into the tibiae of dogs. Following healing periods of 2 weeks, 1 month, and 3 months, the tibiae were prepared by the corrosion cast technique. Under scanning electron microscopy (SEM) observation, the characteristic vascular morphology of the HA-implanted cavity was successfully demonstrated. The initial vascularization began in the form of loose sinusoidal capillaries. Many sinusoids formed a complex network by anastomosing with each other. The newly formed vessels extended centripetally from the peripheral cavity wall and from the periosteal surface. Under greater magnification, the tapered vascular sprouting was shown to project into the space that was previously occupied by an HA particle. The presence of vascular sprouting is clearly an important indicator of angiogenesis. Increasing vascularization was demonstrated with time. The presence of vessels in the Haversian's canal indicated the more established vascularization. Almost full vascularization of the HA-implanted cavity was seen 3 months after implantation. The vascular organizational layout of the cavity was also clearly shown in the fractured transverse-sectioned sample. In the control without HA implantation, the central region of the cavity showed a hollow pattern in the initial stage. The vascularization looked like it was collapsing and not fully filling the cavity. However, remarkable differences of the final vascular pattern could not be found between the study and control group after 3-month implantation. The study provides the time-lapsed 3-dimensional vascular changes of the HA-implanted cavity, as well as the value of the corrosion cast technique in examining the bony circulation. Copyright 1999 John Wiley & Sons, Inc.

  13. Is There a Relationship Between Use of Anti-Vascular Endothelial Growth Factor Agents and Atrophic Changes in Age-Related Macular Degeneration Patients?

    PubMed

    Kaynak, Süleyman; Kaya, Mahmut; Kaya, Derya

    2018-04-01

    Choroidal neovascularization due to age-related macular degeneration (AMD) is currently treated successfully with anti-vascular endothelial growth factor (VEGF) intravitreal agents. Emerging evidence suggests that anti-VEGF treatment may potentially increase development of geographic atrophy. However, there is not yet direct proof of a causal relationship between geographic atrophy and use of anti-VEGF agents in neovaskuler AMD. The aim of this review is to discuss the evidence concerning the association between anti-VEGF therapy and progression of geographic atrophy.

  14. Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice

    PubMed Central

    Wang, Jie; Guo, Tao; Peng, Qi-Sheng; Yue, Shou-Wei; Wang, Shuang-Xi

    2015-01-01

    Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic approaches abolished the berberine-induced reduction in intracellular Ca2+ concentration in VSMCs and attenuated berberine-elicited vessel dilation in mice aortas. In deoxycorticosterone acetate (DOCA)-induced hypertensive model, treatment of mice with berberine or RN-1734, a pharmacological inhibitor of TRPV4, significantly decreased systemic blood pressure (BP) in control mice or mice infected with an adenovirus vector. However, berberine-induced effects of lowering BP were reversed by overexpressing TRPV4 in mice by infecting with adenovirus. Furthermore, long-term administration of berberine decreased mean BP and pulse BP, increased artery response to vasodilator and reduced vascular collagen content in aged mice deficient in apolipoprotein E (Apoe-KO), but not in Apoe-KO old mice with lentivirus-mediated overexpression of TRPV4 channel. In conclusion, berberine induces direct vasorelaxation to lower BP and reduces vascular stiffness in aged mice through suppression of TRPV4. PMID:26177349

  15. Exercise, cognitive function, and aging

    PubMed Central

    2015-01-01

    Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. PMID:26031719

  16. Paracrine control of vascularization and neurogenesis by neurotrophins.

    PubMed

    Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

    2003-10-01

    The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

  17. Chronic Inflammation: Accelerator of Biological Aging.

    PubMed

    Fougère, Bertrand; Boulanger, Eric; Nourhashémi, Fati; Guyonnet, Sophie; Cesari, Matteo

    2017-09-01

    Biological aging is characterized by a chronic low-grade inflammation level. This chronic phenomenon has been named "inflamm-aging" and is a highly significant risk factor for morbidity and mortality in the older persons. The most common theories of inflamm-aging include redox stress, mitochondrial dysfunction, glycation, deregulation of the immune system, hormonal changes, epigenetic modifications, and dysfunction telomere attrition. Inflamm-aging plays a role in the initiation and progression of age-related diseases such as type II diabetes, Alzheimer's disease, cardiovascular disease, frailty, sarcopenia, osteoporosis, and cancer. This review will cover the identification of pathways that control age-related inflammation across multiple systems and its potential causal role in contributing to adverse health outcomes. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Fucoidan-induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair.

    PubMed

    Kim, Beom-Su; Yang, Sun-Sik; You, Hyung-Keun; Shin, Hong-In; Lee, Jun

    2018-03-01

    Osteogenesis and angiogenesis, including cell-cell communication between blood vessel cells and bone cells, are essential for bone repair. Fucoidan is a chemical compound that has a variety of biological activities. It stimulates osteoblast differentiation in human mesenchymal stem cells (MSCs), which in turn induces angiogenesis. However, the mechanism by which this communication between osteoblasts and endothelial cells is mediated remains unclear. Thus, the aim of this study was to clarify the relationship between fucoidan-induced osteoblastic differentiation in MSCs and angiogenesis in endothelial cells. First, the effect was confirmed of fucoidan on osteoblast differentiation in MSCs and obtained conditioned media from these cells (Fucoidan-MSC-CM). Next, the angiogenic activity of Fucoidan-MSC-CM was investigated and it was found that it stimulated angiogenesis, demonstrated by proliferation, tube formation, migration and sprout capillary formation in human umbilical vein endothelial cells. Messenger ribonucleic acid expression and protein secretion of vascular endothelial growth factor (VEGF) were dramatically increased during fucoidan-induced osteoblast differentiation and that its angiogenic activities were reduced by a VEGF/VEGF receptor-specific binding inhibitor. Furthermore, Fucoidan-MSC-CM increased the phosphorylation of mitogen-activated protein kinase and PI3K/AKT/eNOS signalling pathway, and that its angiogenic effects were markedly suppressed by SB203580 and AKT 1/2 inhibitor. Finally, an in vivo study was conducted and it was found that fucoidan accelerated new blood vessel formation and partially promoted bone formation in a rabbit model of a calvarial bone defect. This is the first study to investigate the angiogenic effect of fucoidan-induced osteoblastic differentiation through VEGF secretion, suggesting the therapeutic potential of fucoidan for enhancing bone repair. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Towards A Model-Based Prognostics Methodology for Electrolytic Capacitors: A Case Study Based on Electrical Overstress Accelerated Aging

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan S.; Biswas, Gautam; Goebel, Kai

    2012-01-01

    A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.

  20. Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization.

    PubMed

    Joanisse, Sophie; Nederveen, Joshua P; Snijders, Tim; McKay, Bryon R; Parise, Gianni

    2017-01-01

    Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults. © 2016 S. Karger AG, Basel.

  1. Quantitative analysis of vascular parameters for micro-CT imaging of vascular networks with multi-resolution.

    PubMed

    Zhao, Fengjun; Liang, Jimin; Chen, Xueli; Liu, Junting; Chen, Dongmei; Yang, Xiang; Tian, Jie

    2016-03-01

    Previous studies showed that all the vascular parameters from both the morphological and topological parameters were affected with the altering of imaging resolutions. However, neither the sensitivity analysis of the vascular parameters at multiple resolutions nor the distinguishability estimation of vascular parameters from different data groups has been discussed. In this paper, we proposed a quantitative analysis method of vascular parameters for vascular networks of multi-resolution, by analyzing the sensitivity of vascular parameters at multiple resolutions and estimating the distinguishability of vascular parameters from different data groups. Combining the sensitivity and distinguishability, we designed a hybrid formulation to estimate the integrated performance of vascular parameters in a multi-resolution framework. Among the vascular parameters, degree of anisotropy and junction degree were two insensitive parameters that were nearly irrelevant with resolution degradation; vascular area, connectivity density, vascular length, vascular junction and segment number were five parameters that could better distinguish the vascular networks from different groups and abide by the ground truth. Vascular area, connectivity density, vascular length and segment number not only were insensitive to multi-resolution but could also better distinguish vascular networks from different groups, which provided guidance for the quantification of the vascular networks in multi-resolution frameworks.

  2. Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation.

    PubMed

    Hadoke, Patrick W F; Kipari, Tiina; Seckl, Jonathan R; Chapman, Karen E

    2013-05-01

    Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/inhibition causes hypertension, whereas deficiency/inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis.

  3. Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?

    PubMed

    Soh, M C; Nelson-Piercy, C; Westgren, M; McCowan, L; Pasupathy, D

    2017-11-01

    Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.

  4. Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX).

    PubMed

    Burgos, P I; Vilá, L M; Reveille, J D; Alarcón, G S

    2009-12-01

    To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.

  5. Temporal deconvolution of vascular plant signatures delivered to coastal sediments

    NASA Astrophysics Data System (ADS)

    Vonk, J.; Drenzek, N. J.; Hughen, K. A.; Stanley, R.; Montluçon, D. B.; McIntyre, C.; Southon, J. R.; Santos, G.; Andersson, A.; Sköld, M.; Eglinton, T. I.

    2017-12-01

    Presently, relatively little is known about the amount of time that lapses between the photosynthetic fixation of carbon by vascular land plants and its incorporation into the marine sedimentary record. It is clear that there are multiple potential intermediate storage pools and transport trajectories that vascular plant carbon may experience, and the age of vascular plant carbon accumulating in marine sediments will reflect these different pre-depositional histories. Here we use molecular-level radiocarbon (14C) analysis to develop down-core 14C profiles for higher plant leaf wax-derived fatty acids isolated from sediments from three sites across a 60-degrees latitudinal gradient (Cariaco Basin, Saanich Inlet, and Mackenzie Delta). The sediment profiles were used as a direct measure of the storage and transport times experienced by these biomolecular tracer compounds. Residence times are evaluated by comparing these records to the 14C history of atmospheric CO2. Using a modeling framework, we conclude that there is, in addition to a variable "young" pool, a millennial pool of compounds that consists of 49-78 % of the fractional contribution of organic carbon (OC) that exhibits variable ages for the different depositional settings. For the Mackenzie Delta sediments, we find a mean age of the millennial pool of 28 ky, suggesting pre-aging in permafrost soils, whereas the millennial pool in Saanich Inlet and Cariaco Basin sediments is younger with 7.9 and 2.4-3.2 ky, respectively, suggesting limited storage in terrestrial reservoirs. The "young" pool, conditionally defined as < 50 years showed clear annual contributions for Saanich Inlet and Mackenzie Delta sediments (24% and 16% of young pool, respectively) that can likely be explained by transport of OC from steep hillside slopes near the Saanich Inlet and annual spring flood deposition in the Mackenzie Delta. These results show that a significant fraction of vascular plant C in deltaic and marine settings

  6. Vascular injury is associated with increased mortality in winter sports trauma.

    PubMed

    Eun, John C; Bronsert, Michael; Hansen, Kristine; Moulton, Steven L; Jazaeri, Omid; Nehler, Mark; Greenberg, Joshua I

    2015-01-01

    Trauma is the leading cause of injury and death for individuals aged 1-44 years. Up to 8% of the US population participates in winter sports, and although vascular injuries are uncommon in these activities, little is published in this area. We sought to identify the incidence, injury patterns, and outcomes of vascular injuries resulting from winter sports trauma. Patients with winter sports trauma and the subset with vascular injuries were identified by accessing the National Trauma Data Bank querying years 2007-2010. Patients with and without vascular injuries were then compared. Admission variables included transport time, emergency department hypotension (systolic blood pressure < 90), Glasgow Coma Scale ≤ 8, Injury Severity Score ≥ 25, fractures, solid organ injury, and vascular injury. Outcomes were analyzed and associations with vascular injuries were determined. A total of 2,298 patients were identified with winter sports-related trauma and 28 (1.2%) had associated vascular injuries. Overall, the top 3 injuries were head trauma (16.7%), thoracic vertebral fractures (5.5%), and lumbar vertebral fractures (5.1%). The most common associated vascular injures were to the popliteal artery (17.7%), splenic artery (14.7%), and brachial blood vessels (14.7%). In the entire cohort, 1 patient (0.04%) suffered an amputation and 15 patients (0.7%) died. There were no amputations in the vascular injury group. Mortality was 0.6% in patients without a vascular injury compared with 7.1% of those with a vascular injury (P = 0.01). Although vascular injury is an uncommon associated finding in winter sports trauma, it is associated with a significant increase in mortality. These findings highlight the need for rapid identification of traumatic vascular injuries, which predicts worse overall outcomes in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. [Analysis of vascular complications of IABP therapy in open-heart surgery patients 1999-2004].

    PubMed

    Kovács, Endre; Becker, Dávid; Daróczi, László; Gálfy, Ildikó; Hüttl, Tivadar; Laczkó, Agnes; Paukovits, Tamas; Vargha, Péter; Szabolcs, Zoltán

    2006-04-01

    Intraaortic balloon pump (IABP) is being used in cardiac surgery in an increased ratio. IABP therapy involves considerable risk, mainly vascular complications, postoperative bleeding and infection can represent danger. Between 1999 and 2004 out of 4443 open heart surgery operations we have performed intraaortic balloon pump treatment in case of 75 patients. The mean age was 64 years, 23 patients had diabetes mellitus, 47 patients had hypertension, 20 patients had peripheral vascular disease as well. We performed IABP therapy most frequently during isolated coronary bypass operations (42 cases), but also combined operations (implantation of valve prosthesis + coronary bypass) represent a significant part (implantation of aortic valve prosthesis + CABG: 5 cases, implantation of mitral valve prosthesis + CABG: 8 cases). Vascular complications occurred in 10 cases--13.3%--out of 75 patients, including 7 fatal ones. Three cases are due to the IABP treatment itself: Crush syndrome was developed leading to the loss of the patient. Applying the multiple logistic regression model we have examined the effect of the following factors on the occurrence of vascular complications: gender, age, body surface, accompanying diseases (hypertension, diabetes, peripheral vascular disease), the method and timing of insertion. Peripheral vascular disease (p < 0.005) and hypertension (p = 0.01) represent independent risk factors regarding the occurrence of complications. Having performed chi-square test we have not identified significant correlations between mortality and vascular complications. In case of prevailing peripheral vascular disease, the application of alternative insertion techniques--via the ascending aorta, the axillary artery--are recommended.

  8. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    PubMed

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  9. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  10. Comparison of cable ageing

    NASA Astrophysics Data System (ADS)

    Plaček, Vít; Kohout, Tomáš

    2010-03-01

    Two cable types, which currently are used in nuclear power plants (NPP) and which are composed by jacket/insulation materials, i.e. PVC/PVC and PVC/PE, were exposed to accelerated ageing conditions, in order to simulate their behavior after 10 years in service. The cables were aged under two different test conditions: With relatively high accelerating ageing speed:Radiation ageing was carried out at room temperature at a dose rate of 2900 Gy/h, followed by thermal ageing at 100 °C. This accelerated ageing condition was fairly fast, but still in compliance with the standards. With moderate ageing speed:The radiation and thermal ageing was performed simultaneously (superimposed) at a dose rate of 2.7-3.7Gy/h and a temperature of 68-70 °C. Such a test condition seems to be very close to the radiation and temperature impact onto the cables in the real NPP service. Finally, mechanical properties were measured to characterize the ageing status of the cables. The purpose of this study was to compare degradation effects, derived from both ageing methods, and to demonstrate that results obtained from high values of accelerating parameters and from fast ageing simulation can be very different from reality. The observed results corroborated this assumption.

  11. Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular Cognitive Impairment.

    PubMed

    Ferro, Doeschka A; van Veluw, Susanne J; Koek, Huiberdina L; Exalto, Lieza G; Biessels, Geert Jan

    2017-01-01

    Cerebral microinfarcts (CMIs) are small ischemic lesions that are a common neuropathological finding in patients with stroke or dementia. CMIs in the cortex can now be detected in vivo on 3 Tesla MRI. To determine the occurrence of CMIs and associated clinical features in patients with possible vascular cognitive impairment (VCI). 182 memory-clinic patients (mean age 71.4±10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI) underwent a standardized work-up including 3 Tesla MRI and cognitive assessment. A control group consisted of 70 cognitively normal subjects (mean age 70.6±4.7, 60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury were rated according to established criteria. Occurrence of CMIs was higher (20%) in patients compared to controls (10%). Among patients, the presence of CMIs was associated with male sex, history of stroke, infarcts, and white matter hyperintensities. CMI presence was also associated with a diagnosis of vascular dementia and reduced performance in multiple cognitive domains. CMIs on 3 Tesla MRI are common in patients with possible VCI and co-occur with imaging markers of small and large vessel disease, likely reflecting a heterogeneous etiology. CMIs are associated with worse cognitive performance, independent of other markers of vascular brain injury.

  12. Chemical vs. Physical Acceleration of Cement Hydration

    PubMed Central

    Bentz, Dale P.; Zunino, Franco; Lootens, Didier

    2016-01-01

    Cold weather concreting often requires the use of chemical accelerators to speed up the hydration reactions of the cement, so that setting and early-age strength development will occur in a timely manner. While calcium chloride (dihydrate – CaCl2·2H2O) is the most commonly used chemical accelerator, recent research using fine limestone powders has indicated their high proficiency for physically accelerating early-age hydration and reducing setting times. This paper presents a comparative study of the efficiency of these two approaches in accelerating hydration (as assessed via isothermal calorimetry), reducing setting times (Vicat needle), and increasing early-age mortar cube strength (1 d and 7 d). Both the CaCl2 and the fine limestone powder are used to replace a portion of the finest sand in the mortar mixtures, while keeping both the water-to-cement ratio and volume fractions of water and cement constant. Studies are conducted at 73.4 °F (23°C) and 50 °F (10 °C), so that activation energies can be estimated for the hydration and setting processes. Because the mechanisms of acceleration of the CaCl2 and limestone powder are different, a hybrid mixture with 1 % CaCl2 and 20 % limestone powder (by mass of cement) is also investigated. Both technologies are found to be viable options for reducing setting times and increasing early-age strengths, and it is hoped that concrete producers and contractors will consider the addition of fine limestone powder to their toolbox of techniques for assuring performance in cold weather and other concreting conditions where acceleration may be needed. PMID:28077884

  13. Does erectile tissue angioarchitecture modify with aging? An immunohistological and morphometric approach.

    PubMed

    Costa, Carla; Vendeira, Pedro

    2008-04-01

    Introduction. Erectile dysfunction is a common problem in aged men; however, which vascular cavernosal alterations occur with age progression remain unclarified. Aim. Using cavernosal tissue from rats of various ages, we aimed to thoroughly assess erectile vascular-associated morphologic, immunohistological, and morphometric alterations during aging. Methods. Male Wistar rats were divided according to age in groups of 2, 6, 12, 18, 24 months old (N = 5). Cavernosal tissue of all groups was collected and processed for morphologic evaluation, immunodetection of alpha-smooth muscle actin and von Willebrand factor and morphometric quantification of vascular and smooth muscle cell (SMC) areas. Main Outcome Measures. The morphometric assessment of age-related alterations in cavernosal vascular and SMCs using the ImageJ image-processing program. Results. Morphologic and immunohistological evaluation showed a similar structure of erectile tissue among all age groups, divided in two cavernosal bodies containing numerous sinusoidal vascular spaces surrounded by SMCs. Additionally, we observed a reduction of SMC content and an increase in the caliber of vascular spaces, with aging. This was confirmed by the morphometric quantification of the vascular and SMC areas (mean area x10(3) microm(2) +/- x10(3) standard error). Two-month-old animals had a mean vascular area of 4.21 +/- 0.51, approximately 3.5-fold less than the 6-month-old group. The differences increased when comparing the youngest groups with the 12-, 18-, and 24-month-old animals, with mean measurements of 18.99 +/- 1.91, 25.23 +/- 2.76, and 26.34 +/- 2.97. Conversely, SMC areas progressively decreased between 2- and 6-month-old animals, from 6.75 +/- 0.90 to 6.38 +/- 1.24. The elderly 12-, 18-, and 24-month-old groups presented an approximated 1.5-fold reduction on SMCs area, showed by the respective measurements of 4.11 +/- 0.50, 4.01 +/- 0.35, and 4.02 +/- 0.44. Conclusions. We demonstrated that cavernosal

  14. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice.

    PubMed

    Reis, Felipe C G; Branquinho, Jéssica L O; Brandão, Bruna B; Guerra, Beatriz A; Silva, Ismael D; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C Ronald; Festuccia, William T; Kowaltowski, Alicia J; Mori, Marcelo A

    2016-06-01

    Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance.

  15. Fat-specific Dicer deficiency accelerates aging and mitigates several effects of dietary restriction in mice

    PubMed Central

    Reis, Felipe C. G.; Branquinho, Jéssica L. O.; Brandão, Bruna B.; Guerra, Beatriz A.; Silva, Ismael D.; Frontini, Andrea; Thomou, Thomas; Sartini, Loris; Cinti, Saverio; Kahn, C. Ronald; Festuccia, William T.; Kowaltowski, Alicia J.; Mori, Marcelo A.

    2016-01-01

    Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO. These profiles were associated with reduced oxidative metabolism and increased lactate in WAT of AdicerKO mice and were accompanied by structural and functional changes in mitochondria, particularly under DR. AdicerKO mice displayed increased mTORC1 activation in WAT and skeletal muscle, where Dicer expression is not affected. This was accompanied by accelerated age-associated insulin resistance and premature mortality. Moreover, DR-induced insulin sensitivity was abrogated in AdicerKO mice. This was reverted by rapamycin injection, demonstrating that insulin resistance in AdicerKO mice is caused by mTORC1 hyperactivation. Our study evidences a DR-modulated role for WAT Dicer in controlling metabolism and insulin resistance. PMID:27241713

  16. Explosive and pyrotechnic aging demonstration

    NASA Technical Reports Server (NTRS)

    Rouch, L. L., Jr.; Maycock, J. N.

    1976-01-01

    The survivability was experimentally verified of fine selected explosive and pyrotechnic propellant materials when subjected to sterilization, and prolonged exposure to space environments. This verification included thermal characterization, sterilization heat cycling, sublimation measurements, isothermal decomposition measurements, and accelerated aging at a preselected elevated temperature. Temperatures chosen for sublimation and isothermal decomposition measurements were those in which the decomposition processess occurring would be the same as those taking place in real-time aging. The elevated temperature selected (84 C) for accelerated aging was based upon the parameters calculated from the kinetic data obtained in the isothermal measurement tests and was such that one month of accelerated aging in the laboratory approximated one year of real-time aging at 66 C. Results indicate that HNS-IIA, pure PbN6, KDNBF, and Zr/KC10 are capable of withstanding sterilization. The accelerated aging tests indicated that unsterilized HNS-IIA and Zr/KC104 can withstand the 10 year, elevated temperature exposure, pure PbN6 and KDNBF exhibit small weight losses (less than 2 percent) and B/KC104 exhibits significant changes in its thermal characteristics. Accelerated aging tests after sterilization indicated that only HNS-IIA exhibited high stability.

  17. Soiling of building envelope surfaces and its effect on solar reflectance – Part III: Interlaboratory study of an accelerated aging method for roofing materials

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

    Sleiman, Mohamad; Chen, Sharon; Gilbert, Haley E.

    A laboratory method to simulate natural exposure of roofing materials has been reported in a companion article. Here in the current article, we describe the results of an international, nine-participant interlaboratory study (ILS) conducted in accordance with ASTM Standard E691-09 to establish the precision and reproducibility of this protocol. The accelerated soiling and weathering method was applied four times by each laboratory to replicate coupons of 12 products representing a wide variety of roofing categories (single-ply membrane, factory-applied coating (on metal), bare metal, field-applied coating, asphalt shingle, modified-bitumen cap sheet, clay tile, and concrete tile). Participants reported initial and laboratory-agedmore » values of solar reflectance and thermal emittance. Measured solar reflectances were consistent within and across eight of the nine participating laboratories. Measured thermal emittances reported by six participants exhibited comparable consistency. For solar reflectance, the accelerated aging method is both repeatable and reproducible within an acceptable range of standard deviations: the repeatability standard deviation sr ranged from 0.008 to 0.015 (relative standard deviation of 1.2–2.1%) and the reproducibility standard deviation sR ranged from 0.022 to 0.036 (relative standard deviation of 3.2–5.8%). The ILS confirmed that the accelerated aging method can be reproduced by multiple independent laboratories with acceptable precision. In conclusion, this study supports the adoption of the accelerated aging practice to speed the evaluation and performance rating of new cool roofing materials.« less

  18. mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

    PubMed

    Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

    2018-01-01

    We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

  19. Birt-Hogg-Dubé syndrome and intracranial vascular pathologies.

    PubMed

    Kapoor, Rahul; Evins, Alexander I; Steitieh, Diala; Bernardo, Antonio; Stieg, Philip E

    2015-12-01

    Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome. We present three cases (three female; age range 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including two aneurysms and one arteriovenous malformation, and review one previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. We hypothesize that increased transcription of hypoxia-inducible factor 1-alpha, resulting from a mutated form of the protein folliculin transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

  20. Sox17 is required for normal pulmonary vascular morphogenesis

    PubMed Central

    Lange, Alexander W.; Haitchi, Hans Michael; LeCras, Timothy D.; Sridharan, Anusha; Xu, Yan; Wert, Susan E.; James, Jeanne; Udell, Nicholas; Thurner, Philipp J.; Whitsett, Jeffrey A.

    2015-01-01

    The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature. While survival of Dermo1-Cre;Sox17Δ/Δ mice (herein termed Sox17Δ/Δ) was unaffected at E18.5, most Sox17Δ/Δ mice died by 3 weeks of age. After birth, the density of the pulmonary microvasculature was decreased in association with alveolar simplification, biventricular cardiac hypertrophy, and valvular regurgitation. The severity of the postnatal cardiac phenotype was correlated with the severity of pulmonary vasculature abnormalities. Sox17 is required for normal formation of the pulmonary vasculature and postnatal cardiovascular homeostasis. PMID:24418654

  1. Comparison of clinical explants and accelerated hydrolytic aging to improve biostability assessment of silicone-based polyurethanes.

    PubMed

    Cosgriff-Hernandez, Elizabeth; Tkatchouk, Ekaterina; Touchet, Tyler; Sears, Nick; Kishan, Alysha; Jenney, Christopher; Padsalgikar, Ajay D; Chen, Emily

    2016-07-01

    Although silicone-based polyurethanes have demonstrated increased oxidative stability, there have been conflicting reports of the long-term hydrolytic stability of Optim™ and PurSil(®) 35 based on recent temperature-accelerated hydrolysis studies. The goal of the current study was to identify in vitro-in vivo correlations to determine the relevance of this accelerated in vitro model for predicting clinical outcomes. Temperature-accelerated hydrolytic aging of three commonly used cardiac lead insulation materials, Optim™, Elasthane™ 55D, Elasthane™ 80A, and a related silicone-polyurethane, PurSil(®) 35, was performed. After 1 year at 85°C, similar losses in Mn and Mz were observed for the poly(ether urethanes), but an increase in Mz loss as compared to Mn loss was observed for the silicone-based polyurethanes. A similar trend of increased Mz loss as compared to Mn loss was observed in explanted Optim™ leads after 2-3 years; however, no statistically significant Mn loss was detected between 2-3 and 7-8 years of implantation. Given this preferential loss of high molecular weight chains, it was hypothesized that the observed differences between the polyurethanes were due to allophanate dissociation rather than backbone chain scission. Following full dissociation of the small percentage of allophanates in vivo, the observed molecular weight stability and proven clinical performance of Optim™ was attributed to the well-documented stability of the urethane bond under physiological conditions. This allophanate dissociation reaction is incompatible with the first order mechanism proposed in previous temperature-accelerated hydrolysis studies and may be the reason for the model's inaccurate prediction of significant and progressive molecular weight loss in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1805-1816, 2016. © 2016 Wiley Periodicals, Inc.

  2. Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide.

    PubMed

    Li, Yue; McRobb, Lucinda S; Khachigian, Levon M

    2016-10-01

    Percutaneous coronary intervention is widely used for the treatment of coronary artery disease; however, significant challenges such as restenosis remain. Key to solving these problems is to inhibit smooth muscle cell activation while enhancing re-endothelialization. Early growth response-1 (Egr-1) is a transcription factor that regulates vascular smooth muscle cell (SMC) proliferation and migration through its control of an array of downstream genes. A "cocktail" of vascular endothelial growth factor (VEGF)-A, VEGF-D and cyclic RGD was tested for its ability to inhibit neointima formation and accelerate re-endothelialization following balloon injury to carotid arteries of rats. In vitro, the cocktail stimulated endothelial cell growth yet inhibited smooth muscle cell growth. In vivo, cocktail-treated injured arteries exhibited reduced intimal thickening by >50% (P<0.05). It increased both re-endothelialization and endothelial nitric oxide synthase (NOS) expression. Cocktail reduced Egr-1 expression, an effect blocked by the NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) that also prevented cocktail inhibition of neointima inhibition. This combination may potentially be useful for the treatment of restenosis with concomitant stimulation of revascularization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients.

    PubMed

    Bansal, Savita; Chawla, Diwesh; Banerjee, Basu Dev; Madhu, Sri Venkata; Tripathi, Ashok Kumar

    2013-09-10

    Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM). The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A, -429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM). A total of 265 diabetic patients, including DM without any complications (n=135), DM-MVC (n=130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically. Of the three examined SNPs, association of -429T/C polymorphism with MVC in T2DM was observed (OR=3.001, p=0.001) in the dominant model. Allele 'A' of -374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (-429T/C) and S allele (G82S) had significantly higher AGEs levels. -429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of -429T/C polymorphism and a higher level of AGEs (OR=1.343, p=0.040). RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of -429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Development of a lifetime prediction model for lithium-ion batteries based on extended accelerated aging test data

    NASA Astrophysics Data System (ADS)

    Ecker, Madeleine; Gerschler, Jochen B.; Vogel, Jan; Käbitz, Stefan; Hust, Friedrich; Dechent, Philipp; Sauer, Dirk Uwe

    2012-10-01

    Battery lifetime prognosis is a key requirement for successful market introduction of electric and hybrid vehicles. This work aims at the development of a lifetime prediction approach based on an aging model for lithium-ion batteries. A multivariable analysis of a detailed series of accelerated lifetime experiments representing typical operating conditions in hybrid electric vehicle is presented. The impact of temperature and state of charge on impedance rise and capacity loss is quantified. The investigations are based on a high-power NMC/graphite lithium-ion battery with good cycle lifetime. The resulting mathematical functions are physically motivated by the occurring aging effects and are used for the parameterization of a semi-empirical aging model. An impedance-based electric-thermal model is coupled to the aging model to simulate the dynamic interaction between aging of the battery and the thermal as well as electric behavior. Based on these models different drive cycles and management strategies can be analyzed with regard to their impact on lifetime. It is an important tool for vehicle designers and for the implementation of business models. A key contribution of the paper is the parameterization of the aging model by experimental data, while aging simulation in the literature usually lacks a robust empirical foundation.

  5. Cardiorespiratory Fitness is a Strong Predictor of the Cardio-ankle Vascular Index in Hypertensive Middle-aged and Elderly Japanese Men.

    PubMed

    Tanisawa, Kumpei; Ito, Tomoko; Sun, Xiaomin; Kawakami, Ryoko; Oshima, Satomi; Gando, Yuko; Cao, Zhen-Bo; Sakamoto, Shizuo; Higuchi, Mitsuru

    2015-01-01

    This study aimed to examine whether cardiorespiratory fitness (CRF) is associated with arterial stiffening, evaluated using the cardio-ankle vascular index (CAVI), independent of visceral fat (VF) in middle-aged and elderly Japanese men. We also examined whether the relationship between CRF and the CAVI is modified by age and/or hypertension. The CAVI was determined in 157 Japanese men (age range, 30-79 years), including 96 hypertensive subjects (61.1%). CRF was assessed by measuring the peak oxygen uptake (VO2peak). The subjects were divided into low- and high-CRF groups, and the VF area was assessed using magnetic resonance imaging. The VO2peak correlated with the CAVI following adjustment for age and body mass index in the middle-aged and elderly groups (all the subjects: r=-0.285, p<0.001; middle-aged: r=-0.240, p=0.040; elderly: r=-0.225, p=0.049). VF also correlated with the CAVI (r=0.230, p=0.004). A multiple linear regression analysis revealed that age (β=0.406, p<0.001) and the VO2peak (β=-0.186, p=0.015) were associated with the CAVI independently of VF and the mean blood pressure. Two way ANCOVA adjusted for age demonstrated that the hypertensive individuals had higher CAVI values than the normotensive individuals in the low-CRF group, whereas no significant differences in the CAVI were observed in the high-CRF group (p for interaction <0.05). In the present study, CRF was found to be associated with the CAVI, independent of age and VF, in hypertensive middle-aged and elderly Japanese men.

  6. [Menopause: Hypertension and vascular disease].

    PubMed

    Zilberman, J M

    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. RETINAL VASCULAR PATHOLOGY RISK DEVELOPMENT IN THE IRRADIATED AT DIFFERENT AGES AS A RESULT OF CHERNOBYL NPP ACCIDENT.

    PubMed

    Fedirko, P A; Babenko, T F; Dorichevska, R Yu; Garkava, N A

    2015-12-01

    To assess the relationship between the age at which a person undergoes radiation exposure and risk of developing eye lesions (case study of the retinal angiopathy prevalence). The object of the study was the state of the retinal vessels in 2,531 persons (1,948 evacuated from the city of Pripyat under the age of 20 and 583 exposed to radiation in utero as a result of the Chernobyl NPP disaster. The results of standardized ophthalmic examination conducted from 1993 to 2000 within the framework of Clinical and epidemiological registry are used for the analysis. The evacuees were subdivided into different age groups of the exposed to radiation. The cohort of control group formed corresponding age groups of the unirradiated control. Statistical analysis of the survey results was carried out using the free trial version of «Open Epi 2.2.1» software package. The results obtained revealed a significant prevalence of retinal vessels pathology in all groups. The difference in angiopathy prevalence in exposed in utero persons was significant compared to age-control. The prevalence of retinal vascular pathology was also significantly higher in all groups of evacuees. Angiopathy prevalence was higher in the group exposed in utero and at the age of 8-12 years, and in the group of people who were exposed at the age of 4-7 years, the risk of angiopathy was lower. It is proved that the occurrence of distant radiation effects mainly depends on the age at which a person has undergone irradiation. It should be noted that all the other conditions were approximately the same. If working conditions of the persons who were exposed in utero or were aged 8 to 20 years when the Chernobyl disaster happened are connected with occupational radiation exposure it is necessary to take additional preventive measures. P. А. Fedirko, T. F. Babenko, R. Yu. Dorichevska, N. А. Garkava.

  8. 2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

    PubMed

    Ziegler, Kenneth R; Dardik, Alan

    2011-07-01

    The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

  9. Bipolar patients with vascular risk display a steeper age-related negative slope in inhibitory performance but not processing speed: A preliminary study

    PubMed Central

    Dev, Sheena I.; Eyler, Lisa T.

    2017-01-01

    Objective Bipolar disorder (BD) is associated with cognitive deficits, yet little is known about associations between cognition, vascular risk (VR) and age in this population. This study investigated whether BD patients with VR demonstrate stronger apparent age-related decline in inhibitory performance and processing speed (PS). Methods A full medical history was obtained for 34 euthymic BD and 41 healthy comparison (HC) individuals. The Delis-Kaplan Executive Functions Color Word Interference Subtests was administered to all participants to assess for inhibitory performance (condition 3) and PS (condition 1 and 2). VR positive (VRPos) and VR negative (VRNeg) groups were created based on the presence of one or more VR factors. Results VRPos-BD participants demonstrated significantly worse inhibitory performance with older age, while age and inhibition were not significantly related in the VRPOS-HC group or in those who were VRNeg. The same was not true for PS. Conclusion BD patients with VR may also be at risk for greater decline in inhibitory performance, but not PS, with age. Longitudinal studies are needed to further investigate the contributions of VR to cognitive decline among older BD patients. PMID:28041763

  10. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

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

    Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans},more » and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.« less

  11. Impaired vascular function in physically active premenopausal women with functional hypothalamic amenorrhea is associated with low shear stress and increased vascular tone.

    PubMed

    O'Donnell, Emma; Goodman, Jack M; Mak, Susanna; Harvey, Paula J

    2014-05-01

    Exercise-trained hypoestrogenic premenopausal women with functional hypothalamic amenorrhea (ExFHA) exhibit impaired endothelial function. The vascular effects of an acute bout of exercise, a potent nitric oxide stimulus, in these women are unknown. Three groups were studied: recreationally active ExFHA women (n = 12; 24.2 ± 1.2 years of age; mean ± SEM), and recreationally active (ExOv; n = 14; 23.5 ± 1.2 years of age) and sedentary (SedOv; n = 15; 23.1 ± 0.5 years of age) ovulatory eumenorrheic women. Calf blood flow (CBF) and brachial artery flow-mediated dilation (FMD) were evaluated using plethysmographic and ultrasound techniques, respectively, both before and 1 hour after 45 minutes of moderate-intensity exercise. Endothelium-independent dilation was assessed at baseline using glyceryl trinitrate. Calf vascular resistance (CVR) and brachial peak shear rate, as determined by the area under the curve (SRAUCpk), were also calculated. FMD and glyceryl trinitrate responses were lower (P < .05) in ExFHA (2.8% ± 0.4% and 11.6% ± 0.7%, respectively) than ExOv (8.8% ± 0.7% and 16.7% ± 1.3%) and SedOv (8.0% ± 0.5% and 17.1% ± 1.8%). SRAUCpk was also lower (P < .05) in ExFHA. Normalization of FMD for SRAUCpk (FMD/SRAUCpk) did not alter (P > .05) the findings. CBF was lower (P < .05) and CVR higher (P < .05) in ExFHA. After exercise, FMD and SRAUCpk were augmented (P < .05), but remained lower (P < .05), in ExFHA. FMD/SRAUCpk no longer differed (P > .05) between the groups. CBF in ExFHA was increased (P < .05) and CVR decreased (P < .05) to levels observed in ovulatory women. Acute dynamic exercise improves vascular function in ExFHA women. Although the role of estrogen deficiency per se is unclear, our findings suggest that low shear rate and increased vasoconstrictor tone may play a role in impaired basal vascular function in these women.

  12. Social-emotional characteristics of gifted accelerated and non-accelerated students in the Netherlands.

    PubMed

    Hoogeveen, Lianne; van Hell, Janet G; Verhoeven, Ludo

    2012-12-01

    In the studies of acceleration conducted so far a multidimensional perspective has largely been neglected. No attempt has been made to relate social-emotional characteristics of accelerated versus non-accelerated students in perspective of environmental factors. In this study, social-emotional characteristics of accelerated gifted students in the Netherlands were examined in relation to personal and environmental factors. Self-concept and social contacts of accelerated (n = 148) and non-accelerated (n = 55) gifted students, aged 4 to 27 (M = 11.22, SD = 4.27) were measured. Self-concept and social contacts of accelerated and non-accelerated gifted students were measured using a questionnaire and a diary, and parents of these students evaluated their behavioural characteristics. Gender and birth order were studied as personal factors and grade, classroom, teachers' gender, teaching experience, and the quality of parent-school contact as environmental factors. The results showed minimal differences in the social-emotional characteristics of accelerated and non-accelerated gifted students. The few differences we found favoured the accelerated students. We also found that multiple grade skipping does not have negative effects on social-emotional characteristics, and that long-term effects of acceleration tend to be positive. As regards the possible modulation of personal and environmental factors, we merely found an impact of such factors in the non-accelerated group. The results of this study strongly suggest that social-emotional characteristics of accelerated gifted students and non-accelerated gifted students are largely similar. These results thus do not support worries expressed by teachers about the acceleration of gifted students. Our findings parallel the outcomes of earlier studies in the United States and Germany in that we observed that acceleration does not harm gifted students, not even in the case of multiple grade skipping. On the contrary, there is a

  13. Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease

    PubMed Central

    2014-01-01

    Aims/hypothesis Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Methods Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Results Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Conclusions/interpretations Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease

  14. A drug-induced accelerated senescence (DIAS) is a possibility to study aging in time lapse.

    PubMed

    Alili, Lirija; Diekmann, Johanna; Giesen, Melanie; Holtkötter, Olaf; Brenneisen, Peter

    2014-06-01

    Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. Accordingly, a stress-induced senescence-like phenotype of human dermal fibroblasts can be induced in vitro by the exposure of human diploid fibroblasts to subcytotoxic concentrations of hydrogen peroxide. However, several biomarkers of replicative senescence e.g. cell cycle arrest and enlarged morphology are abrogated 14 days after treatment, indicating that reactive oxygen species (ROS) rather acts as a trigger for short-term senescence (1-3 days) than being responsible for the maintenance of the senescence-like phenotype. Further, DNA-damaging factors are discussed resulting in a permanent senescent cell type. To induce long-term premature senescence and to understand the molecular alterations occurring during the aging process, we analyzed mitomycin C (MMC) as an alkylating DNA-damaging agent and ROS producer. Human dermal fibroblasts (HDF), used as model for skin aging, were exposed to non-cytotoxic concentrations of MMC and analyzed for potential markers of cellular aging, for example enlarged morphology, activity of senescence-associated-ß-galactosidase, cell cycle arrest, increased ROS production and MMP1-activity, which are well-documented for HDF in replicative senescence. Our data show that mitomycin C treatment results in a drug-induced accelerated senescence (DIAS) with long-term expression of senescence markers, demonstrating that a combination of different susceptibility factors, here ROS and DNA alkylation, are necessary to induce a permanent senescent cell type.

  15. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  16. Thrombospondin-2 Expression During Retinal Vascular Development and Neovascularization.

    PubMed

    Fei, Ping; Palenski, Tammy L; Wang, Shoujian; Gurel, Zafer; Hankenson, Kurt D; Sorenson, Christine M; Sheibani, Nader

    2015-09-01

    To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. The TSP2-deficient (TSP2(-/-)) mice and a line of TSP2 reporter mice were used to assess the expression of TSP2 during postnatal retinal vascular development and neovascularization. The postnatal retinal vascularization was evaluated using immunostaining of wholemount retinas prepared at different postnatal days by collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP) expression. The organization of astrocytes was evaluated by glial fibrillary acidic protein (GFAP) staining. Retinal vascular densities were determined using trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age. Retinal neovascularization was assessed during the oxygen-induced ischemic retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser-induced CNV. Using the TSP2-GFP reporter mice, we observed significant expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased by P7 and remained high up to P42. Similar results were observed in retinal wholemount preparations, and western blotting for GFP with the highest level of GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP fluorescence or protein level was dramatically downregulated. The primary retinal vasculature developed at a faster rate in TSP2(-/-) mice compared with TSP2(+/+) mice up to P5. However, the developing retinal vasculature in TSP2(+/+) mice caught up with that of TSP2(-/-) mice after P7. No significant differences in retinal vascular density were observed at 3- or 6-weeks of age. TSP2(-/-) mice also exhibited a similar sensitivity to the hyperoxia-mediated vessel obliteration and similar level of neovascularization during OIR as TSP2(+/+) mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with TSP2(+/+) mice. Lack of TSP2 expression was associated with

  17. Soiling of building envelope surfaces and its effect on solar reflectance – Part II: Development of an accelerated aging method for roofing materials

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

    Sleiman, Mohamad; Kirchstetter, Thomas W.; Berdahl, Paul

    2014-01-09

    Highly reflective roofs can decrease the energy required for building air conditioning, help mitigate the urban heat island effect, and slow global warming. However, these benefits are diminished by soiling and weathering processes that reduce the solar reflectance of most roofing materials. Soiling results from the deposition of atmospheric particulate matter and the growth of microorganisms, each of which absorb sunlight. Weathering of materials occurs with exposure to water, sunlight, and high temperatures. This study developed an accelerated aging method that incorporates features of soiling and weathering. The method sprays a calibrated aqueous soiling mixture of dust minerals, black carbon,more » humic acid, and salts onto preconditioned coupons of roofing materials, then subjects the soiled coupons to cycles of ultraviolet radiation, heat and water in a commercial weatherometer. Three soiling mixtures were optimized to reproduce the site-specific solar spectral reflectance features of roofing products exposed for 3 years in a hot and humid climate (Miami, Florida); a hot and dry climate (Phoenix, Arizona); and a polluted atmosphere in a temperate climate (Cleveland, Ohio). A fourth mixture was designed to reproduce the three-site average values of solar reflectance and thermal emittance attained after 3 years of natural exposure, which the Cool Roof Rating Council (CRRC) uses to rate roofing products sold in the US. This accelerated aging method was applied to 25 products₋single ply membranes, factory and field applied coatings, tiles, modified bitumen cap sheets, and asphalt shingles₋and reproduced in 3 days the CRRC's 3-year aged values of solar reflectance. In conclusion, this accelerated aging method can be used to speed the evaluation and rating of new cool roofing materials.« less

  18. The Influence of Passive Acceleration and Exercise+Acceleration on Work Capacity and Orthostasis

    NASA Technical Reports Server (NTRS)

    Simonson, S. R.; Cowell, S. A.; Stocks, J. M.; Biagini, H. W.; Vener, J. M.; Evetts, S. N.; Bailey, K. N.; Evans, J.; Knapp, C.; Greenleaf, J. E.

    1999-01-01

    The losses of aerobic power and orthostatic tolerance are significant effects of manned C) spaceflight that can negatively impact crew health and safety. Daily acceleration and aerobic training may ameliorate these effects. To determine the influence of passive intermittent +Gz acceleration (PA) training and active acceleration + interval exercise (AE) training on work 0 0 capacity and the acute (1 min) response to 70 deg head-up tilt, 6 men (X-Bar SD: age, 33 +/- 6 y; height, 178.3 +/- 4.6 cm; mass, 86.3 +/- 6.6 kg) participated in two 3-wk training protocols. It was hypothesized that PA and AE training would improve orthostatic tolerance and that the addition of aerobic conditioning, would not alter this effect.

  19. Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly.

    PubMed

    Hartog, Renee; Bolignano, Davide; Sijbrands, Eric; Pucci, Giacomo; Mattace-Raso, Francesco

    2018-01-01

    Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages. We included 62 participants, who were divided into three age categories: 20-40 (n=22), 41-60 (n=20), and 61-80 (n=20) years. Vascular hemodynamics were measured using the Mobil-o-Graph ® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise. After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10 m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) ( r =0.878, P <0.01). After isometric exercise, the mean change of systolic blood pressure (SBP) was -1.9% in the youngest, 0.6% in the middle-aged, and 8.2% in the oldest subjects. Increasing handgrip strength was associated with an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip strength, respectively, P =0.01). Finally, PWV was significantly associated with increasing handgrip strength with an increase of 0.05 m/s per 1 kg higher handgrip strength ( P =0.01). This study found increased blood pressure levels after isometric challenge and a strong association between handgrip strength and change in blood pressure levels and aortic stiffness in elderly subjects.

  20. Statin cost-effectiveness in the United States for people at different vascular risk levels.

    PubMed

    2009-03-01

    Statins reduce the rates of heart attacks, strokes, and revascularization procedures (ie, major vascular events) in a wide range of circumstances. Randomized controlled trial data from 20,536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the populations currently recommended for treatment in clinical guidelines is indicated. Randomized controlled trial data, an internally validated vascular disease model, and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily. For an average of 5 years, allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by approximately 20% (95% CI, 15 to 24) in the different subcategories of participants studied. At a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $1300 (95% CI, $15,600 saving to $13,200 cost) among participants with a 42% 5-year major vascular event risk to a net cost of $216,500 ($123,700 to $460,000 cost) among those with a 12% 5-year risk. The costs per life year gained with lifetime simvastatin treatment ranged from $2500 (-$40 to $3820) in people aged 40 to 49 years with a 42% 5-year major vascular event risk to $10,990 ($9430 to $14,700) in people aged 70 years and older with a 12% 5-year risk. Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines.

  1. 3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

    PubMed

    Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

    2017-07-17

    Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

  2. Comparison of in vivo immune responses following transplantation of vascularized and non-vascularized human dermo-epidermal skin substitutes.

    PubMed

    Klar, Agnes S; Biedermann, Thomas; Simmen-Meuli, Claudia; Reichmann, Ernst; Meuli, Martin

    2017-03-01

    Autologous bio-engineered dermo-epidermal skin substitutes (DESS) represent an alternative therapeutic option for a definitive treatment of skin defects in human patients. Largely, the interaction of host immune cells with transplanted DESS is considered to be essential for the granulation tissue formation, graft take, and its functionality. The aim of this study was to compare the spatiotemporal distribution and density of host-derived monocytes/macrophages and granulocytes in vascularized (vascDESS) versus non-vascularized DESS (non-vascDESS) in a rat model. Keratinocytes and the stromal vascular fraction (SVF) were derived from human skin or human adipose tissue, respectively. Human SVF containing both endothelial and mesenchymal/stromal progenitors was used to develop a vascularized collagen type I-based dermal component in vitro. The donor-matched, monolayer-expanded adipose stromal cells lacking endothelial cells were used as a negative control. Subsequently, human keratinocytes were seeded on top of hydrogels to build dermo-epidermal skin grafts. After transplantation onto full-thickness skin wounds on the back of immuno-incompetent rats, grafts were excised and analyzed after 1 and 3 weeks. The expression of distinct inflammatory cell markers specific for host-derived monocytes/macrophages (CD11b, CD68) or granulocytes (HIS48) was analyzed by immunofluorescence microscopy. All skin grafts were infiltrated by host-derived monocytes/macrophages (CD11b + , CD68 + ) and granulocytes (HIS48 + ) between 1-3 week post-transplantation. When compared to non-vascDESS, the vascDESS showed an increased granulocyte infiltration at all time points analyzed with the majority of cells scattered throughout the whole dermal part. Whereas a moderate number of rat monocytes/macrophages (CD11b + , CD68 + ) were found in vascDESS at 1 week, only a few cells were detected in non-vascDESS. We observed a time-dependent decrease of monocytes/macrophages in all transplants at 3

  3. Uterine Vascular Lesions

    PubMed Central

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  4. Characterization of vascular complications in experimental model of fructose-induced metabolic syndrome.

    PubMed

    El-Bassossy, Hany M; Dsokey, Nora; Fahmy, Ahmed

    2014-12-01

    Vascular dysfunction is an important complication associated with metabolic syndrome (MS). Here we fully characterized vascular complications in a rat model of fructose-induced MS. MS was induced by adding fructose (10%) to drinking water to male Wistar rats of 6 weeks age. Blood pressure (BP) and isolated aorta responses phenylephrine (PE), KCl, acetylcholine (ACh), and sodium nitroprusside (SNP) were recorded after 6, 9, and 12 weeks of fructose administration. In addition, serum levels of glucose, insulin, uric acid, tumor necrosis factor α (TNFα), lipids, advanced glycation end products (AGEs), and arginase activity were determined. Furthermore, aortic reactive oxygen species (ROS) generation, hemeoxygenase-1 expression, and collagen deposition were examined. Fructose administration resulted in a significant hyperinslinemia after 6 weeks which continued for 12 weeks. It was also associated with a significant increase in BP after 6 weeks which was stable for 12 weeks. Aorta isolated from MS animals showed exaggerated contractility to PE and KCl and impaired relaxation to ACh compared with control after 6 weeks which were clearer at 12 weeks of fructose administration. In addition, MS animals showed significant increases in serum levels of lipids, uric acid, AGEs, TNFα, and arginase enzyme activity after 12 weeks of fructose administration. Furthermore, aortae isolated from MS animals were characterized by increased ROS generation and collagen deposition. In conclusion, adding fructose (10%) to drinking water produces a model of MS with vascular complications after 12 weeks that are characterized by insulin resistance, hypertension, disturbed vascular reactivity and structure, hyperuricemia, dyslipidemia, and low-grade inflammation.

  5. Accelerated Testing Of Photothermal Degradation Of Polymers

    NASA Technical Reports Server (NTRS)

    Kim, Soon Sam; Liang, Ranty Hing; Tsay, Fun-Dow

    1989-01-01

    Electron-spin-resonance (ESR) spectroscopy and Arrhenius plots used to determine maximum safe temperature for accelerated testing of photothermal degradation of polymers. Aging accelerated by increasing illumination, temperature, or both. Results of aging tests at temperatures higher than those encountered in normal use valid as long as mechanism of degradation same throughout range of temperatures. Transition between different mechanisms at some temperature identified via transition between activation energies, manifesting itself as change in slope of Arrhenius plot at that temperature.

  6. Accelerated aging tests on ENEA-ASE solar coating for receiver tube suitable to operate up to 550 °C

    NASA Astrophysics Data System (ADS)

    Antonaia, A.; D'Angelo, A.; Esposito, S.; Addonizio, M. L.; Castaldo, A.; Ferrara, M.; Guglielmo, A.; Maccari, A.

    2016-05-01

    A patented solar coating for evacuated receiver, based on innovative graded WN-AlN cermet layer, has been optically designed and optimized to operate at high temperature with high performance and high thermal stability. This solar coating, being designed to operate in solar field with molten salt as heat transfer fluid, has to be thermally stable up to the maximum temperature of 550 °C. With the aim of determining degradation behaviour and lifetime prediction of the solar coating, we chose to monitor the variation of the solar absorptance αs after each thermal annealing cycle carried out at accelerated temperatures under vacuum. This prediction method was coupled with a preliminary Differential Thermal Analysis (DTA) in order to give evidence for any chemical-physical coating modification in the temperature range of interest before performing accelerated aging tests. In the accelerated aging tests we assumed that the temperature dependence of the degradation processes could be described by Arrhenius behaviour and we hypothesized that a linear correlation occurs between optical parameter variation rate (specifically, Δαs/Δt) and degradation process rate. Starting from Δαs/Δt values evaluated at 650 and 690 °C, Arrhenius plot gave an activation energy of 325 kJ mol-1 for the degradation phenomenon, where the prediction on the coating degradation gave a solar absorptance decrease of only 1.65 % after 25 years at 550 °C. This very low αs decrease gave evidence for an excellent stability of our solar coating, also when employed at the maximum temperature (550 °C) of a solar field operating with molten salt as heat transfer fluid.

  7. Vitamin D in Vascular Calcification: A Double-Edged Sword?

    PubMed

    Wang, Jeffrey; Zhou, Jimmy J; Robertson, Graham R; Lee, Vincent W

    2018-05-22

    Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification. Therefore, more complex underlying processes involving physiochemical changes to mineral balance, vascular remodelling and perturbed hormonal responses such as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) are likely to contribute to VC. In particular, VC resulting from modifications to calcium, phosphate and vitamin D homeostasis has been recently elucidated. Notably, deregulation of vitamin D metabolism, dietary calcium intake and renal mineral handling are associated with imbalances in systemic calcium and phosphate levels and endothelial cell dysfunction, which can modulate both bone and soft tissue calcification. This review addresses the current understanding of VC pathophysiology, with a focus on the pathogenic role of vitamin D that has provided new insights into the mechanisms of VC.

  8. Hypoglycemia in Diabetes Mellitus as a Coronary Artery Disease Risk Factor in Patients at Elevated Vascular Risk

    PubMed Central

    Leong, Aaron; Berkowitz, Seth A.; Triant, Virginia A.; Porneala, Bianca; He, Wei; Atlas, Steven J.; Wexler, Deborah J.

    2016-01-01

    Context: Although clinical trials have shown that hypoglycemia is associated with coronary artery disease (CAD), little is known whether hypoglycemia is a CAD risk factor in primary care. Objective: We sought to determine whether previous hypoglycemia was associated with incident CAD, and whether this association differed in patients of different underlying vascular risk. Design, setting and participants: This is a longitudinal cohort study of diabetes patients without CAD before January 1, 2006 (n = 9173) followed at an academic network of 13 primary care practices from January 1, 2006 to June 30, 2012. Hypoglycemic events before January 1, 2006 were identified via International Classification of Diseases Ninth Revision codes from emergency department, inpatient and outpatient visits. Main Outcome Measure: Patients were followed until incident CAD or June 30, 2012. Cox regression with time interaction was used to determine the association between hypoglycemia and CAD (significance set at P ≤ .05). We then tested the association among high vascular risk patients (age ≥ 55 y, hemoglobin A1c ≥ 7.5%, ≥2 risk factors [dyslipidemia, hypertension or obesity]), a subset of high vascular risk patients aged 65 years or older, and the remaining patients with lower vascular risk. Results: Three percent of patients (n = 285) had previous hypoglycemia. Hypoglycemia was associated with a 2-fold CAD risk (hazard ratio [HR] 2.15; 95% confidence interval [95%CI] 1.24–3.74), adjusting for time interaction and vascular risk factors. Among high vascular risk patients, the risk was 3-fold (HR 3.01 [95%CI 1.15–7.91], n = 1823 [20% of cohort]), and over 4-fold (HR 4.62 [95%CI 1.65–12.9], n = 996) in the subset aged more than or equal to 65 years. No association was found in the remaining 80% of the cohort with lower vascular risk. Conclusions: Previous hypoglycemia was associated with CAD among high vascular risk patients. Hypoglycemia may not be a CAD risk factor for the

  9. Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Goebel, Kai Frank; Larrosa, Cecilia C.; Janapati, Vishnuvardhan; Roy, Surajit; Chang, Fu-Kuo

    2011-01-01

    Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images.

  10. Chronic hyperglicemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications

    PubMed Central

    De Filippis, Elena Anna

    2007-01-01

    Diabetes is associated with accelerated atherosclerosis and macrovascular complications are a major cause of morbidity and mortality in this disease. Although our understanding of vascular pathology has lately greatly improved, the mechanism(s) underlying enhanced atherosclerosis in diabetes remain unclear. Endothelial cell dysfunction is emerging as a key component in the pathophysiology of cardiovascular abnormalities associated with diabetes. Although it has been established that endothelium plays a critical role in overall homeostasis of the vessels, vascular smooth muscle cells (vSMC) in the arterial intima have a relevant part in the development of atherosclerosis in diabetes. However, high glucose induced alterations in vSMC behaviour are not fully characterized. Several studies have reported that impaired nitric oxide (NO) synthesis and/or actions are often present in diabetes and endothelial dysfunction. Furthermore, although endothelial cells are by far the main site of vascular NO synthesis, vSMC do express nitric oxyde synthases (NOSs) and NO synthesis in vSMC might be important in vessel’s function. Although it is known that vSMC contribute to vascular pathology in diabetes by their change from a quiescent state to an activated proliferative and migratory phenotype (termed phenotypic modulation), whether this altered phenotypic modulation might also involve alterations in the nitrergic systems is still controversial. Our recent data indicate that, in vivo, chronic hyperglycemia might induce an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O2− production. Since NO bioavailabilty might not be increased in high glucose stimulated vSMC, it is tempting to hypothesize that the proliferative phenotype observed in cells from diabetic rats is associated

  11. [A paradox of a parasite prolonging the life of its host. Pearl mussel can cancel the accelerated aging program in salmon].

    PubMed

    Ziuganov, V V

    2005-01-01

    A unique case is analyzed when the accelerated aging program (progeria) in salmons (Salmonidae) can be canceled by larval parasite of the gills--freshwater pearl mussel Margaritifera margaritifera. As a result, the maximum age of Salmo fishes hosting the mussel can be as high as 13 years. The mollusk-fish system made it possible to demonstrate that the parasite can inhibit aging of the host and stimulate nonspecific resistance to stress, i.e., can control longevity. The mussel proved to increase the resistance to epitheliomata and cutaneous mycoses. The parasite is perceived to neutralize the senile changes in the regulatory system hypothalamus-pituitary-peripheral endocrine glands-hypothalamus of salmon.

  12. Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

    PubMed

    Galassi, Andrea; Spiegel, David M; Bellasi, Antonio; Block, Geoffrey A; Raggi, Paolo

    2006-11-01

    Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.

  13. Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis.

    PubMed

    Ping, Suning; Liu, Shuying; Zhou, Yuhuan; Li, Ziqing; Li, Yuhuang; Liu, Kefeng; Bardeesi, Adham Sa; Wang, Linli; Chen, Jingbo; Deng, Lie; Wang, Jingjing; Wang, Hong; Chen, Dadi; Zhang, Zhengyu; Sheng, Puyi; Li, Chaohong

    2017-05-25

    Protein disulfide isomerase (PDI) involves cell survival and death. Whether PDI mediates mechanical stretch stress (SS) and/or advanced glycosylation end products (AGEs) -triggered simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells (VSMCs) is unknown. Here, we hypothesized that different expression levels of PDI trigger completely opposite cell fates among the different VSMC subtypes. Mouse veins were grafted into carotid arteries of non-diabetic and diabetic mice for 8 weeks; the grafted veins underwent simultaneous increases in proliferation and apoptosis, which triggered vein graft arterializations in non-diabetic or atherosclerosis in diabetic mice. A higher rate of proliferation and apoptosis was seen in the diabetic group. SS and/or AGEs stimulated the quiescent cultured VSMCs, resulting in simultaneous increases in proliferation and apoptosis; they could induce increased PDI activation and expression. Both in vivo and in vitro, the proliferating VSMCs indicated weak co-expression of PDI and SM-α-actin while apoptotic or dead cells showed strong co-expression of both. Either SS or AGEs rapidly upregulated the expression of PDI, NOX1 and ROS, and their combination had synergistic effects. Inhibiting PDI simultaneously suppressed the proliferation and apoptosis of VSMCs, while inhibition of SM-α-actin with cytochalasin D led to increased apoptosis and cleaved caspases-3 but had no effect on proliferation. In conclusion, different expression levels of PDI in VSMCs induced by SS and/or AGEs triggered a simultaneous increase in proliferation and apoptosis, accelerated vein graft arterializations or atherosclerosis, leading us to propose PDI as a novel target for the treatment of vascular remodeling and diseases.

  14. Universality of accelerating change

    NASA Astrophysics Data System (ADS)

    Eliazar, Iddo; Shlesinger, Michael F.

    2018-03-01

    On large time scales the progress of human technology follows an exponential growth trend that is termed accelerating change. The exponential growth trend is commonly considered to be the amalgamated effect of consecutive technology revolutions - where the progress carried in by each technology revolution follows an S-curve, and where the aging of each technology revolution drives humanity to push for the next technology revolution. Thus, as a collective, mankind is the 'intelligent designer' of accelerating change. In this paper we establish that the exponential growth trend - and only this trend - emerges universally, on large time scales, from systems that combine together two elements: randomness and amalgamation. Hence, the universal generation of accelerating change can be attained by systems with no 'intelligent designer'.

  15. VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases.

    PubMed

    Le, Yun-Zheng

    2017-10-01

    Müller glia (MG) are major retinal supporting cells that participate in retinal metabolism, function, maintenance, and protection. During the pathogenesis of diabetic retinopathy (DR), a neurovascular disease and a leading cause of blindness, MG modulate vascular function and neuronal integrity by regulating the production of angiogenic and trophic factors. In this article, I will (1) briefly summarize our work on delineating the role and mechanism of MG-modulated vascular function through the production of vascular endothelial growth factor (VEGF) and on investigating VEGF signaling-mediated MG viability and neural protection in diabetic animal models, (2) explore the relationship among VEGF and neurotrophins in protecting Müller cells in in vitro models of diabetes and hypoxia and its potential implication to neuroprotection in DR and hypoxic retinal diseases, and (3) discuss the relevance of our work to the effectiveness and safety of long-term anti-VEGF therapies, a widely used strategy to combat DR, diabetic macular edema, neovascular age-related macular degeneration, retinopathy of prematurity, and other hypoxic retinal vascular disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Disparity between online and offline tests in accelerated aging tests of LED lamps under electric stress.

    PubMed

    Wang, Yao; Jing, Lei; Ke, Hong-Liang; Hao, Jian; Gao, Qun; Wang, Xiao-Xun; Sun, Qiang; Xu, Zhi-Jun

    2016-09-20

    The accelerated aging tests under electric stress for one type of LED lamp are conducted, and the differences between online and offline tests of the degradation of luminous flux are studied in this paper. The transformation of the two test modes is achieved with an adjustable AC voltage stabilized power source. Experimental results show that the exponential fitting of the luminous flux degradation in online tests possesses a higher fitting degree for most lamps, and the degradation rate of the luminous flux by online tests is always lower than that by offline tests. Bayes estimation and Weibull distribution are used to calculate the failure probabilities under the accelerated voltages, and then the reliability of the lamps under rated voltage of 220 V is estimated by use of the inverse power law model. Results show that the relative error of the lifetime estimation by offline tests increases as the failure probability decreases, and it cannot be neglected when the failure probability is less than 1%. The relative errors of lifetime estimation are 7.9%, 5.8%, 4.2%, and 3.5%, at the failure probabilities of 0.1%, 1%, 5%, and 10%, respectively.

  17. Vascular dementia: Diagnostic criteria and supplementary exams. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Part I

    PubMed Central

    Engelhardt, Eliasz; Tocquer, Carla; André, Charles; Moreira, Denise Madeira; Okamoto, Ivan Hideyo; Cavalcanti, José Luiz de Sá

    2011-01-01

    Vascular dementia (VaD) is the most prevalent form of secondary dementia and the second most common of all dementias. The present paper aims to define guidelines on the basic principles for treating patients with suspected VaD (and vascular cognitive impairment - no dementia) using an evidence-based, systematized approach. The knowledge used to define these guidelines was retrieved from searches of several databases (Medline, Scielo, Lilacs) containing scientific articles, systematic reviews, meta-analyses, largely published within the last 15 years or earlier when pertinent. Information retrieved and selected for relevance was used to analyze diagnostic criteria and to propose a diagnostic system encompassing diagnostic criteria, anamnesis, as well as supplementary and clinical exams (neuroimaging and laboratory). Wherever possible, instruments were selected that had versions previously adapted and validated for use in Brazil that take into account both schooling and age. This task led to proposed protocols for supplementary exams based on degree of priority, for application in clinical practice and research settings. PMID:29213752

  18. Vascular malformations: an update.

    PubMed

    Gloviczki, Peter; Duncan, Audra; Kalra, Manju; Oderich, Gustavo; Ricotta, Joseph; Bower, Thomas; McKusick, Michael; Bjarnason, Haraldur; Driscoll, David

    2009-06-01

    Vascular malformations occur as a result of an arrest in the development of the vascular system. The modified Hamburg classification distinguishes arterial, venous, arteriovenous, capillary, lymphatic, and mixed vascular malformations. Each malformation is further subdivided based on anatomy and on the time when arrest in development of the embryogenesis occurred; malformations can be truncular or extratruncular. Progress in the last decade in management has been significant because of improvements in open surgical procedures and perfection of percutaneous and hybrid endovascular interventions and devices, such as balloons, stents, and stent-grafts. There has been increasing use of embolization for the treatment of malformations with coils, other particles, glue, or with endovascular placement of occlusive plugs. Absolute alcohol, detergent liquids, or foam have been used for sclerotherapy with improved efficacy. The agents are delivered percutaneously or through a catheter placed either into the feeding arteries or the draining veins. This review aims to aid vascular and endovascular specialists in staying familiar with vascular malformations. These specialists need to be able to evaluate the patients, perform treatment if appropriate, or refer complex cases to multidisciplinary vascular malformation clinics and vascular centers.

  19. Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1

    PubMed Central

    Cole, Sarah L.; Vassar, Robert

    2012-01-01

    The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733

  20. Large scale serial two-photon microscopy to investigate local vascular changes in whole rodent brain models of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Delafontaine-Martel, P.; Lefebvre, J.; Damseh, R.; Castonguay, A.; Tardif, P.; Lesage, F.

    2018-02-01

    In this study, an automated serial two-photon microscope was used to image a fluorescent gelatin filled rodent's brain in 3D. A method to compute vascular density using automatic segmentation was combined with coregistration techniques to build group-level vasculature metrics. By studying the medial prefrontal cortex and the hippocampal formation of 3 age groups (2, 4.5 and 8 months old), we compared vascular density for both WT and an Alzheimer model transgenic brain (APP/PS1). We observe a loss of vascular density caused by the ageing process and we propose further analysis to confirm our results.