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Sample records for age-related myocardial metabolic

  1. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    Science.gov (United States)

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  2. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

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    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  3. Gender differences in age-related decline in regional cerebral glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  4. Age-Related Sex-Specific Changes in Brain Metabolism and Morphology.

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    Kakimoto, Akihiro; Ito, Shigeru; Okada, Hiroyuki; Nishizawa, Sadahiko; Minoshima, Satoshi; Ouchi, Yasuomi

    2016-02-01

    With a large database, we aimed to evaluate sex-specific distinctive changes in brain glucose metabolism and morphology during normal aging using MRI and (18)F-FDG PET. A total of 963 cognitively healthy adults were included in this study. All subjects completed a medical questionnaire, took the mini-mental state examination, and underwent brain MRI and whole-body (18)F-FDG PET. The MR and PET images were statistically analyzed using 3-dimensional stereotactic surface projection. All images were corrected for whole-brain pixel value to identify the brain regions with significant changes, and regions of interest were set up with reference to Brodmann areas. We evaluated morphologic and glucose metabolic changes by cross-sectional analysis. The baseline database consisted of subjects from 30 to 40 y old, and the age-step for comparison was 5-y ranges. We also compared sex-specific differences in MR and PET images in each age group. Regarding age-related changes, in both sexes brain atrophy was observed in the lateral frontal and parietal regions and glucose hypometabolism in the medial frontal regions. There were significant differences in these parameters between the sexes; parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals 66 y or older. Our brain mapping study with a large number of reference human brain data demonstrated age-related parallel changes between morphology and metabolism in the medial frontal regions and sex-specific hypometabolism in the parietal (male) and ventrolateral prefrontal (female) cortices. These findings may suggest an aging vulnerability in sex-specific brain regions: the parietal cortex for

  5. Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57bl/6 Mice.

    Science.gov (United States)

    Jeon, Jang Su; Oh, Jeong-Ja; Kwak, Hui Chan; Yun, Hwi-Yeol; Kim, Hyoung Chin; Kim, Young-Mi; Oh, Soo Jin; Kim, Sang Kyum

    2017-06-14

    Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.

  6. Session III: Mechanisms of age-related cognitive change and targets for intervention: inflammatory, oxidative, and metabolic processes.

    Science.gov (United States)

    Craft, Suzanne; Foster, Thomas C; Landfield, Philip W; Maier, Steven F; Resnick, Susan M; Yaffe, Kristine

    2012-06-01

    There is increasing evidence from basic science and human epidemiological studies that inflammation, oxidative stress, and metabolic abnormalities are associated with age-related cognitive decline and impairment. This article summarizes selected research on these topics presented at the Cognitive Aging Summit II. Speakers in this session presented evidence highlighting the roles of these processes and pathways on age-related cognitive decline, pointing to possible targets for intervention in nondemented older adults. Specific areas discussed included age differences in the production of cytokines following injury or infection, mechanisms underlying oxidative stress-induced changes in memory consolidation, insulin effects on brain signaling and memory, and the association between metabolic syndrome and cognitive decline in older adults. These presentations emphasize advances in our understanding of mechanisms and modifiers of age-related cognitive decline and provide insights into potential targets to promote cognitive health in older adults.

  7. Sex- and age-related differences of myocardial perfusion at rest assessed with multidetector computed tomography

    DEFF Research Database (Denmark)

    Byrne, Christina; Kühl, J Tobias; Zacho, Mette;

    2013-01-01

    The clinical presentation of ischemic heart disease in women differs from men, which could reflect sex-related differences of normal physiology. Cardiac CT angiography provides a noninvasive method to assess both regional and transmural myocardial perfusion in addition to coronary atherosclerosis....

  8. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p ....02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p ....05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered...

  9. Age-related differences in glucose abnormalities in women with ST-elevation myocardial infarction submitted to percutaneous coronary intervention: a single-center experience.

    Science.gov (United States)

    Lazzeri, Chiara; Gensini, Gian Franco; D'Alfonso, Maria Grazia; Chiostri, Marco; Attanà, Paola; Valente, Serafina

    2015-05-01

    No datum is so far available on the relation between age and the acute glucose response to stress in women with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI).We evaluated the age-related differences in the acute glucose response in 373 STEMI women submitted to PCI. The oldest women, when compared to the other age subgroups, showed the higher admission and peak glycemia (P acute glucose response to myocardial injury since older women showed the higher admission glucose values and the poorer in-hospital glucose control, in the lack of differences of insulin-resistance incidence. Glucose values were independent predictors of in-hospital mortality, but were not related to long-term survival.

  10. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

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    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  11. Exercise as an intervention for the age-related decline in brain metabolic support

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    Brenda J Anderson

    2010-08-01

    Full Text Available To identify interventions for brain aging, we must first identify the processes in which we hope to intervene. Brain aging is a period of decreasing functional capacity and increasing vulnerability, which reflect a reduction in morphological organization and perhaps degeneration. Since life is ultimately dependent upon the ability to maintain cellular organization through metabolism, this review explores evidence for a decline in neural metabolic support during aging, which includes a reduction in whole brain cerebral blood flow, and cellular metabolic capacity. Capillary density may also decrease with age, although the results are less clear. Exercise may be a highly effective intervention for brain aging, because it improves the cardiovascular system as a whole, and increases regional capillary density and neuronal metabolic capacity. Although the evidence is strongest for motor regions, more work may yield additional evidence for exercise-related improvement in metabolic support in non-motor regions. The protective effects of exercise may be specific to brain region and the type of insult. For example, exercise protects striatal cells from ischemia, but it produces mixed results after hippocampal seizures. Exercise can improve metabolic support and bioenergetic capacity in adult animals, but it remains to be determined whether it has similar effects in aging animals. What is clear is that exercise can influence the multiple levels of support necessary for maintaining optimal neuronal function, which is unique among proposed interventions for aging.

  12. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases

    NARCIS (Netherlands)

    Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L.; Kim, Myung K.; Beaven, Michael A.; Burgin, Alex B.; Manganiello, Vincent; Chung, Jay H.

    2012-01-01

    Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resverat

  13. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases

    NARCIS (Netherlands)

    Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L.; Kim, Myung K.; Beaven, Michael A.; Burgin, Alex B.; Manganiello, Vincent; Chung, Jay H.

    2012-01-01

    Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resverat

  14. Dietary hyperglycemia, glycemic index and age-related metabolic retinal diseases

    Science.gov (United States)

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during ...

  15. Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases

    Science.gov (United States)

    Park, Sung-Jun; Ahmad, Faiyaz; Philp, Andrew; Baar, Keith; Williams, Tishan; Luo, Haibin; Ke, Hengming; Rehmann, Holger; Taussig, Ronald; Brown, Alexandra L.; Kim, Myung K.; Beaven, Michael A.; Burgin, Alex B.; Manganiello, Vincent; Chung, Jay H.

    2012-01-01

    SUMMARY Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. PMID:22304913

  16. Towards finding the linkage between metabolic and age-related disorders using semantic gene data network analysis

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    Uzzal Hossain, Mohammad; Zaffar Shibly, Abu; Md. Omar, Taimur; Tous Zohora, Fatama; Sara Santona, Umme; Hossain, Md. Jakir; Hosen Khoka, Md. Sadek; Ara Keya, Chaman; Salimullah, Md.

    2016-01-01

    A metabolic disorder (MD) occurs when the metabolic process is disturbed. This process is carried out by thousands of enzymes participating in numerous inter-dependent metabolic pathways. Critical biochemical reactions that involve the processing and transportation of carbohydrates, proteins and lipids are affected in metabolic diseases. Therefore, it is of interest to identify the common pathways of metabolic disorders by building protein-protein interactions (PPI) for network analysis. The molecular network linkages between MD and age related diseases (ARD) are intriguing. Hence, we created networks of protein-protein interactions that are related with MD and ARD using relevant known data in the public domain. The network analysis identified known MD associated proteins and predicted genes and or its products of ARD in common pathways. The genes in the common pathways were isolated from the network and further analyzed for their co-localization and shared domains. Thus, a model hypothesis is proposed using interaction networks that are linked between MD and ARD. This data even if less conclusive finds application in understanding the molecular mechanism of known diseases in relation to observed molecular events PMID:27212841

  17. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

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    Nady Braidy

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

  18. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

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    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  19. Age-related effects of dexmedetomidine on myocardial contraction and coronary circulation in isolated guinea pig hearts.

    Science.gov (United States)

    Hongo, Maiko; Fujisawa, Susumu; Adachi, Takeshi; Shimbo, Tomonori; Shibata, Shigehiro; Ohba, Takayoshi; Ono, Kyoichi

    2016-06-01

    Dexmedetomidine is a selective α2 adrenergic agonist. Although dexmedetomidine is widely used for sedation and analgesia, it frequently produces hypotension and bradycardia. The present study aimed to evaluate the effects of dexmedetomidine on cardiac function and coronary circulation using Langendorff-perfused guinea pig hearts. Coronary perfusion pressure (CPP) and left ventricular pressure (LVP) were continuously monitored, and electric field stimulation (EFS) was applied to stimulate sympathetic nerve terminals. Dexmedetomidine almost completely inhibited the EFS-induced increase in LVP at all ages. The effect of dexmedetomidine on coronary artery resistance varied according to postnatal age, i.e., dexmedetomidine had little effect on CPP in young hearts (8 weeks. The increase in CPP in adult hearts was inhibited by imiloxan, an α2B antagonist, and prazosin, an α1 antagonist. The results suggest that dexmedetomidine acts on α2 adrenergic receptors at sympathetic nerve terminals to suppress the release of norepinephrine. In addition, the findings suggest that dexmedetomidine directly affects α1 adrenoceptors and/or α2B adrenoceptors on coronary smooth muscles to increase CPP. The age-related changes in α adrenoceptor subtypes may be linked to the cardiodepressant effects of dexmedetomidine.

  20. Metabolic syndrome, its components and risk of age-related cataract extraction: a case-control study in Italy.

    Science.gov (United States)

    Galeone, Carlotta; Petracci, Elisabetta; Pelucchi, Claudio; Zucchetto, Antonella; La Vecchia, Carlo; Tavani, Alessandra

    2010-05-01

    We sought to explore the relationship between age-related cataract extraction and the metabolic syndrome or its various components separately and in various combinations in an Italian case-control study. A total of 761 cases and 1,522 controls in hospital for acute, non-neoplastic, non-ophthalmologic, non-metabolic diseases were interviewed between 1991 and 2003. Odds ratios (ORs), and their 95% confidence intervals (CIs), were computed from multiple logistic regression models, conditioned on sex, age, and study center and adjusted for education and smoking. The ORs were 1.41 for a history of central obesity, 1.42 for hypertension, 1.25 for hyperlipidemia, and 1.16 for diabetes. Patients with the metabolic syndrome (defined as the simultaneous presence of central obesity and at least two other factors among hypertension, hyperlipidemia, diabetes) had an increased risk of cataract, with an OR of 2.01 (95% CI: 1.43-2.83). The ORs were 1.75 for the presence of any of two components and 2.50 for three to four components, with a linear trend in risk. This study indicates that the metabolic syndrome, its components, and their combination are associated with an increased risk of cataract extraction in this Italian population. 2010 Elsevier Inc. All rights reserved.

  1. In vitro effects of vitamin supplements on platelet-activating factor and its metabolism in age-related macular degeneration.

    Science.gov (United States)

    Moschos, Marilita M; Chatziralli, Irini P; Stamatakis, George; Papakonstantinou, Vasiliki D; Demopoulos, Constantinos A

    2014-09-01

    The purpose of our study was to investigate for the first time a series of vitamin supplements used for age-related macular degeneration (AMD) as potential inhibitors of platelet-activating factor (PAF). Various vitamin supplements were tested in washed rabbit platelets (WRPs), in order to investigate the interaction between vitamin supplements (InShape, Nutrof, Ocuvite, Vitalux) and inhibition of PAF-induced platelet aggregation. Additionally, we examined their ability to affect PAF-metabolism, through their in vitro effect on PAF basic metabolic enzymes (PAF-CPT, lyso PAF-AT, and PAF-AH). Nutrof exhibited the strongest anti-PAF activity, while Vitalux was the most potent anti-inflammatory factor. This is the first study to bring in surface potent anti-inflammatory and anti-angiogenic activities of some vitamin supplements used against AMD, through their in vitro anti-PAF effects in WRPs and the rabbit plasma and leukocyte PAF metabolism, suggesting a promising role of vitamin supplements and especially resveratrol, concerning its potent anti-angiogenic activity in AMD.

  2. Aging-Related Correlation between Serum Sirtuin 1 Activities and Basal Metabolic Rate in Women, but not in Men

    Science.gov (United States)

    2017-01-01

    Sirtuin (SIRT) is a main regulator of metabolism and lifespan, and its importance has been implicated in the prevention against aging-related diseases. The purpose of this study was to identify the pattern of serum SIRT1 activity according to age and sex, and to investigate how serum SIRT1 activity is correlated with other metabolic parameters in Korean adults. The Biobank of Jeju National University Hospital, a member of the Korea Biobank Network, provided serum samples from 250 healthy adults. Aging- and metabolism-related factors were analyzed in serum, and the data were compared by the stratification of age and sex. Basal metabolic rate (BMR) decreased with age and was significantly lower in men in their fifties and older and in women in their forties and older compared with twenties in men and women, respectively. SIRT1 activities were altered by age and sex. Especially, women in their thirties showed the highest SIRT1 activities. Correlation analysis displayed that SIRT1 activity is positively correlated with serum triglyceride (TG) in men, and with waist circumference, systolic blood pressure, diastolic blood pressure, and serum TG in women. And, SIRT1 activity was negatively correlated with aspartate aminotransferase/alanine aminotransferase ratio in women (r = −0.183, p = 0.039). Positive correlation was observed between SIRT1 activity and BMR in women (r = 0.222, p = 0.027), but not in men. Taken together, these findings suggest the possibility that serum SIRT1 activities may be utilized as a biomarker of aging. In addition, positive correlation between SIRT1 activity and BMR in women suggests that serum SIRT1 activity may reflect energy expenditure well in human. PMID:28168178

  3. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

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    K. A. Mirzabekova

    2014-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  4. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2015-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  5. Effects of activation of endocannabinoid system on myocardial metabolism

    Directory of Open Access Journals (Sweden)

    Agnieszka Polak

    2016-05-01

    Full Text Available Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

  6. Age-related alterations in behavioral and cerebral metabolic responses to the serotonin agonist meta-chlorophenylpiperazine in rats.

    Science.gov (United States)

    Freo, U; Rapoport, S I; Soncrant, T T

    1991-01-01

    To determine the functional relevance of the age-related neurochemical changes that occur in brain serotonin systems during aging, we measured the effects of the serotonin receptor agonist meta-chlorophenylpiperazine (MCPP) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in awake rats. rCMRglc was determined in 74 regions of Fischer-344 rats aged 3, 12 and 24 months, at 15 and 90 min after MCPP 2.5 mg/kg IP, using the quantitative, autoradiographic [14C]2-deoxy-D-glucose technique. The time-course of motor performance following MCPP was assessed with a rotating rod. MCPP impaired motor performance in all ages maximally at 15-30 min. Three-month-old rats recovered completely within 60 min, whereas 12-month-old animals exhibited partial recovery and 24-month-old rats did not recover by 120 min. At 15 min after MCPP, rCMRglc was reduced in 51 of the 74 studied regions (overall decrease, 20%) of 3-month-old rats, in 21 regions (13% decrease) of 12-month-old rats and in 14 regions (2% decrease) of 24-month-old animals. Similar MCPP brain concentrations were achieved at 15 min in rats of all ages. The results suggest that the functional integrity of serotonergic transmission is reduced in aged rats and that the dysregulation is presynaptic.

  7. Metabolic risk factors, coping with stress, and psychological well-being in patients with age-related macular degeneration.

    Science.gov (United States)

    Cavar, Ivan; Lovrić, Sanjin; Vukojević, Mladenka; Sesar, Irena; Petric-Vicković, Ivanka; Sesar, Antonio

    2014-03-01

    The aim of this study was to determine the relationship between the risk factors (age, obesity, hypertension, hyperlipidemia, smoking, consumption of alchohol and drugs, positive family history, and exposure to sunlight), coping with stress, psychological well-being and age-related macular degeneration (ARMD). Forty patients with ARMD (case group) and 63 presbyopes (control group) participated in the study. Patient data were collected through general information questionnaire including patient habits, the COPE questionnaire that showed the way the patients handling stress, and the GHQ that analyzed the psychological aspects of their quality of life. These questionnaires were administered to the patients during ophthalmologic examination. The study involved 46 (44.66%) men and 57 (55.33%) women. Statistical analysis showed that the major risks for the development of ARMD were elevated cholesterol, triglycerides and LDL cholesterol in plasma. A significantly higher number ofARMD patients had a positive family history when compared with presbyopes. This study showed presbyopes to cope with emotional problems significantly better and to have a lower level of social dysfunction when compared with ARMD patients. However, it is necessary to conduct further studies in a large number of patients to determine more accurately the pathophysiological mechanisms of metabolic factors as well as the impact of the disease on the quality of life in patients with ARMD.

  8. Adaptation of Myocardial Substrate Metabolism to a Ketogenic Nutrient Environment*

    Science.gov (United States)

    Wentz, Anna E.; d'Avignon, D. André; Weber, Mary L.; Cotter, David G.; Doherty, Jason M.; Kerns, Robnet; Nagarajan, Rakesh; Reddy, Naveen; Sambandam, Nandakumar; Crawford, Peter A.

    2010-01-01

    Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor α-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial 13C enrichment of glutamate when 13C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. PMID:20529848

  9. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

    Science.gov (United States)

    Briones, T L; Darwish, H

    2014-03-14

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

  10. Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia.

    Science.gov (United States)

    Martin, Claus; Schulz, Rainer; Post, Heiner; Gres, Petra; Heusch, Gerd

    2003-06-01

    Nitric oxide (NO) is involved in the control of myocardial metabolism. In normoperfused myocardium, NO synthase inhibition shifts myocardial metabolism from free fatty acid (FFA) toward carbohydrate utilization. Ischemic myocardium is characterized by a similar shift toward preferential carbohydrate utilization, although NO synthesis is increased. The importance of NO for myocardial metabolism during ischemia has not been analyzed in detail. We therefore assessed the influence of NO synthase inhibition with N(G)-nitro-l-arginine (l-NNA) on myocardial metabolism during moderate ischemia in anesthetized pigs. In control animals, the increase in left ventricular pressure with l-NNA was mimicked by aortic constriction. Before ischemia, l-NNA decreased myocardial FFA consumption (MV(FFA); P < 0.05), while consumption of carbohydrate and O(2) (MVo(2)) remained constant. ATP equivalents [calculated with the assumption of complete oxidative substrate decomposition (ATP(eq))] decreased with l-NNA (P < 0.05), associated with a decrease of regional myocardial function (P < 0.05). In contrast, aortic constriction had no effect on MV(FFA), while MVo(2) increased (P < 0.05) and ATP(eq) and regional myocardial function remained constant. During ischemia, alterations in myocardial metabolism were similar in control and l-NNA-treated animals: MV(FFA) decreased (P < 0.05) and net lactate consumption was reversed to net lactate production (P < 0.05). Regional myocardial function was decreased (P < 0.05), although more markedly in animals receiving l-NNA (P < 0.05). We conclude that the efficiency of oxidative metabolism was impaired by l-NNA per se, paralleled by impaired regional myocardial function. During ischemia, l-NNA had no effect on myocardial substrate consumption, indicating that NO synthases were no longer effectively involved in the control of myocardial metabolism.

  11. Early obesity and age-related mimicry of metabolic syndrome in female mice with sex hormonal imbalances.

    Science.gov (United States)

    Sairam, M Ram; Wang, Min; Danilovich, Natalia; Javeshghani, Danesh; Maysinger, Dusica

    2006-07-01

    To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages. Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild-type, null, and haploinsufficient follitropin receptor knockout female mice at different ages. Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator-activated receptor gamma expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age-dependent decline in glucose tolerance with high insulin and altered pancreatic beta cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance. In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot-specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy.

  12. Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.

    Directory of Open Access Journals (Sweden)

    Admane H Shanthanagouda

    Full Text Available BACKGROUND: In human, a reduction in estrogen has been proposed as one of the key contributing factors for postmenopausal osteoporosis. Rodents are conventional models for studying postmenopausal osteoporosis, but the major limitation is that ovariectomy is needed to mimic the estrogen decline after menopause. Interestingly, in medaka fish (Oryzias latipes, we observed a natural drop in plasma estrogen profile in females during aging and abnormal spinal curvature was apparent in old fish, which are similar to postmenopausal women. It is hypothesized that estrogen associated disorders in bone metabolism might be predicted and prevented by estrogen supplement in aging O. latipes, which could be corresponding to postmenopausal osteoporosis in women. PRINCIPAL FINDINGS: In O. latipes, plasma estrogen was peaked at 8 months old and significantly declined after 10, 11 and 22 months in females. Spinal bone mineral density (BMD and micro-architecture by microCT measurement progressively decreased and deteriorated from 8 to 10, 12 and 14 months old, which was more apparent in females than the male counterparts. After 10 months old, O. latipes were supplemented with 17α-ethinylestradiol (EE2, a potent estrogen mimic at 6 and 60 ng/mg fish weight/day for 4 weeks, both reduction in spinal BMD and deterioration in bone micro-architecture were significantly prevented. The estrogenic effect of EE2 in O. latipes was confirmed by significant up-regulation of four key estrogen responsive genes in the liver. In general, bone histomorphometric analyses indicated significantly lowered osteoblasts and osteoclasts numbers and surfaces on vertebrae of EE2-fed medaka. SIGNIFICANCE: We demonstrate osteoporosis development associated with natural drop in estrogen level during aging in female medaka, which could be attenuated by estrogen treatment. This small size fish is a unique alternative non-mammalian vertebrate model for studying estrogen-related molecular

  13. Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium.

    Science.gov (United States)

    Biswas, Shankar K; Sarai, Masayoshi; Toyama, Hiroshi; Hishida, Hitoshi; Ozaki, Yukio

    2012-01-01

    Following acute myocardial infarction (AMI) the area of myocardial perfusion and metabolism mismatch is designated as dysfunctional viable myocardium. (123)I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) is clinically very useful for evaluating myocardial fatty acid metabolism, and (99)mTc-Tetrofosmin (TF) is a widely used tracer for myocardial perfusion. This study was designed to evaluate the degree of discrepancy between BMIPP and TF at the subacute state of AMI. Fifty-two patients (aged 59 ± 10 years; mean 46 years) with AMI were enrolled, and all of them underwent percutaneous coronary intervention (PCI). Patients were classified according to ST-T change and PCI timing. (123)I-beta-methyl iodophenyl pentadecanoic acid and TF cardiac scintigraphy were performed on 7 ± 3.5 days of admission using a dual headed gamma camera. Perfusion and fatty acid metabolism defect were scored on a 17 segments model. The mean BMIPP defect score on early and delayed images were 16.67 ± 10.19 and 16.25 ± 10.40, respectively. The mean TF defect score was 10 ± 7.69. Defect score of BMIPP was significantly higher than that of the TF (P TF), and 5 (10%) patients showed matched defect (BMIPP = TF). Mismatched defect score (MMDS) was significantly higher in patients with ST-segment elevation myocardial infarction (STEMI) than that of non-ST-segment elevation myocardial infarction (NSTEMI) (P < 0.041; 95% CI 0.11-5.19). At the subacute state of AMI, most of the patients showed perfusion-metabolism mismatch, which represents the dysfunctional viable myocardium, and patients with STEMI showed higher mismatch. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  14. Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

    Science.gov (United States)

    Minehira, K; Inoue, S; Nonaka, M; Osada, K; Yamada, K; Sugano, M

    2000-01-03

    Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in

  15. Myocardial hipertrophy in hypertensive patients with and without metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Ivanović Branislava

    2008-01-01

    Full Text Available Background/Aim. Beside arterial hypertension as the most important factor of a myocardial hypertension development, very important risk factors are obesity, hypercholesterolemia, insulin resistance, etc. The aim of the study was to examine the influence of metabolic syndrome (MetS on left ventricular hypertrophy in patients with arterial hypertension. Methods. We checked medical records for 138 patients with arterial hypertension, and compared them with the control group of 44 normotensive subjects. The patients with arterial hypertension were divided into two groups considering the presence of MetS: with MetS (59 patients, and without MetS (79 patients. We defined MetS as presence of three (or more within five criteria: central obesity (> 102 cm male, > 88 cm female, raised triglycerides (> 1.7 mmol/L, or drug treatment for elevated triglycerides, reduced high density lipoprotein (HDL cholesterol (< 1.03 mmol/L male, < 1.3 mmol/L female, raised blood pressure (> 130 mmHg systolic, > 90 mmHg diastolic, raised fasting glucose (> 6.11 mmol/L, or drug treatment for elevated glucose level. In each group routine laboratory, echocardiography and 24-hour ambulatory blood pressure monitoring were performed. Results. We found statisticaly significant higher left ventricular mass in both subgroups hypertensive patients in comparison with the control group (p < 0.05. We did not find statistically significant difference (227.31±63.44 vs 219±59.5, p > 0.05 in left ventricular mass between these two groups of patients. In the patients with arterial hypertension and MetS we found hypertrophy more frequently than in the subgroup without MetS (43/57 vs 34/69, p < 0.001. Conclusion. Our results suggest that associated cardiometabolic risks increase the prevalence of myocardial hypertrophy, but do not influence left ventricular mass.

  16. Assessment of myocardial fatty acid metabolism in patients with angina pectoris and diabetes mellitus using {sup 123}I-BMIPP myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Kazuki; Tanabe, Takuji; Yuba, Tatsuya; Doue, Tomoki; Adachi, Yoshihiko; Katoh, Shuuji [Asahi Univ., Gifu (Japan). Murakami Memorial Hospital; Sugihara, Hiroki; Azuma, Akihiro; Nakagawa, Masao

    2001-11-01

    We studied the effect of myocardial ischemia and diabetes mellitus (DM) on the myocardial fatty acid metabolism using {sup 123}I-BMIPP myocardial scintigraphy. We performed {sup 123}I-BMIPP myocardial scintigraphy in 50 patients with myocardial ischemia and without DM (AP), in 30 patients with myocardial ischemia and DM (AP+DM), 12 patients with DM and without myocardial ischemia (DM), and in 10 normal subjects (N). Myocardial uptake rate of {sup 123}I-BMIPP was obtained using the time activity curve. Myocardial washout rate of {sup 123}I-BMIPP was calculated using the polar images of early and delayed SPECT images. Myocardial uptake rate of {sup 123}I-BMIPP (%) were AP: 4.9{+-}0.6, AP+DM: 5.5{+-}0.5, DM 5.7{+-}0.5 and N: 5.0{+-}0.4. {sup 123}I-BMIPP myocardial uptake rate was increased in AP+DM and DM. {sup 123}I-BMIPP myocardial washout rate (%) were AP: 30.2{+-}4.3, AP+DM: 24.5{+-}3.9, DM: 16.1{+-}2.8 and N: 19.4{+-}3.2. {sup 123}I-BMIPP myocardial washout rate was increased in AP and AP+DM. {sup 123}I-BMIPP myocardial washout rate was increased particularly in patients with multi-vessels disease. {sup 123}I-BMIPP myocardial washout rate was decreased in DM. The present study suggested that diabetes mellitus increased myocardial fatty acid uptake and decreased myocardial fatty acid washout, and that myocardial ischemia increased myocardial fatty acid washout. (author)

  17. Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction.

    Science.gov (United States)

    Aoki, Hirofumi; Matsunari, Ichiro; Nomura, Yusuke; Fujita, Wataru; Komatsu, Ryoko; Miyazaki, Yoshiharu; Nekolla, Stephan G; Kajinami, Kouji

    2013-07-01

    The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction. In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by (11)C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using (11)C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique. The (11)C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P infarcted myocardium (r = -0.561, P infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced (11)C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups. This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.

  18. Pharmacological Agents Targeting Myocardial Metabolism for the Management of Chronic Stable Angina : an Update.

    Science.gov (United States)

    Guarini, Giacinta; Huqi, Alda; Morrone, Doralisa; Marzilli, Mario

    2016-08-01

    Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases. Accordingly, revascularization procedures are performed with the aim to remove the flow limiting stenosis, whereas traditional medical therapy (hemodynamic agents) aims at reducing myocardial oxygen demands. However, although effective, none of these treatment strategies or their combination is either able to confer symptomatic relief in all patients, nor to reduce mortality. Failure to significantly improve QoL and prognosis may be attributed at least in part to this "restrictive" understanding of IHD. Despite for many years myocardial metabolic derangement has been overlooked, recently it has gained increased attention with the development of new pharmacological agents (metabolic modulators) able to influence myocardial substrate selection and utilization thus improving cardiac efficiency. Shifting cardiac metabolism from free fatty acids (FA) towards glucose is a promising approach for the treatment of patients with stable angina, independently of the underling disease (macrovascular and/or microvascular disease). In this sense cardiac metabolic modulators open the way to a "revolutionary" understanding of ischemic heart disease and its common clinical manifestations, where myocardial ischemia is no longer considered as the mere oxygen and metabolites demand/supply unbalance, but as an energetic disorder. Keeping in mind such an alternative approach to the disease, development of new pharmacological agents directed toward multiple metabolic

  19. Age-related changes to vascular protease-activated receptor 2 in metabolic syndrome: a relationship between oxidative stress, receptor expression, and endothelium-dependent vasodilation.

    Science.gov (United States)

    Maruyama, Kana; Kagota, Satomi; McGuire, John J; Wakuda, Hirokazu; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2017-04-01

    Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO) - cyclic GMP-mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome. Here we investigated mechanisms linking PAR2's vascular effects to phenotypic characteristics of male SHRSP.ZF rats at 10, 20, and 30 weeks of age. We found vasodilation responses to either 2fLIGRLO or enzyme-mediated PAR2 activation by trypsin were sustained until 20 weeks and lessened at 30 weeks. PAR2 protein and mRNA levels were lower in aortas at 30 weeks than at 10 and 20 weeks. PAR2-mediated responses positively correlated with PAR2 protein and mRNA levels. Decreased cGMP accumulation in the presence of 2fLIGRLO paralleled the decreased relaxations elicited by nitroprusside and the cGMP analog 8-pCPT-cGMP, and the less soluble guanylyl cyclase protein at 30 weeks. 2fLIGRLO-induced relaxation was negatively correlated with serum thiobarbituric acid reactive substances, an index of oxidative stress, which increased with age. Forward stepwise data regression supported a model of age-related decreases in PAR2 function resulting from decreased PAR2 mRNA and increased oxidative stress. We conclude that decreased responsiveness of aortic smooth muscle to NO and downregulation of receptor expression impair PAR2 functions at later stages of metabolic syndrome in SHRSP.ZF rats.

  20. Humanin and Age-related diseases: A new link?

    Directory of Open Access Journals (Sweden)

    Zhenwei eGong

    2014-12-01

    Full Text Available Humanin (HN is 24-amino acid mitochondria-associated peptide. Since its initial discovery over a decade ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response and response to stressors such as oxidative stress, ischemia and starvation. HN and its potent analogs have been shown to have beneficial effects in many age-related diseases including Alzheimer’s disease (AD, stroke, diabetes, myocardial ischemia and reperfusion (MI-R, atherosclerosis, amyotrophic lateral sclerosis (ALS and certain types of cancer both in vitro and in vivo. More recently, an association between HN levels, growth hormone/ insulin-like growth factor-1 (GH/IGF axis and life span was demonstrated using various mouse models with mutations in the GH/IGF axis. The goal of this review is to summarize the current understanding of the role of HN in aging and age-related diseases.

  1. Dietary nitrate improves age-related hypertension and metabolic abnormalities in rats via modulation of angiotensin II receptor signaling and inhibition of superoxide generation.

    Science.gov (United States)

    Hezel, Michael; Peleli, Maria; Liu, Ming; Zollbrecht, Christa; Jensen, Boye L; Checa, Antonio; Giulietti, Alessia; Wheelock, Craig E; Lundberg, Jon O; Weitzberg, Eddie; Carlström, Mattias

    2016-10-01

    Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted that increased angiotensin II (ANG II) signaling is also implicated in the pathogenesis of endothelial dysfunction and hypertension by accelerating formation of reactive oxygen species. This study was designed to test the hypothesis that dietary nitrate supplementation could reduce blood pressure and improve glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling. Dietary nitrate supplementation for two weeks reduced blood pressure (10-15mmHg) and improved glucose clearance in old, but not in young rats. These favorable effects were associated with increased insulin responses, reduced plasma creatinine as well as improved endothelial relaxation to acetylcholine and attenuated contractility to ANG II in resistance arteries. Mechanistically, nitrate reduced NADPH oxidase-mediated oxidative stress in the cardiovascular system and increased cGMP signaling. Finally, nitrate treatment in aged rats normalized the gene expression profile of ANG II receptors (AT1A, AT2, AT1A/AT2 ratio) in the renal and cardiovascular systems without altering plasma levels of renin or ANG II. Our results show that boosting the nitrate-nitrite-NO pathway can partly compensate for age-related disturbances in endogenous NO generation via inhibition of NADPH oxidase and modulation of ANG II receptor expression. These novel findings may have implications for nutrition-based preventive and therapeutic strategies against cardiovascular and metabolic diseases.

  2. [{sup 18}F] labeled diacylglycerol analogue as a potential agent to trace myocardial phosphoinositide metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Chida, Masanobu; Kagaya, Yutaka; Nagata, Shinji; Mukoyoshi, Masanori; Namiuchi, Shigeto; Yamane, Yuriko; Ishide, Nobumasa; Watanabe, Jun; Takahashi, Toshihiro; Ido, Tatsuo; Shirato, Kunio E-mail: shirato@int1.med.tohoku.ac.jp

    2001-10-01

    Phosphoinositide metabolism plays an important role in cardiac pathophysiology. To investigate whether [{sup 18}F]diacylglycerol could be used to trace myocardial phosphoinositide metabolism, lipids were extracted from rat myocardium after the injection. 1-[8-[{sup 18}F]fluorooctanoyl]-2-palmitoylglycerol and 1-[8-[{sup 18}F]fluoropalmitoyl]-2-palmitoylglycerol were predominantly metabolized to phosphatidylethanolamine and triacylglycerol, respectively. The radioactivity incorporated into phosphoinositide metabolism was 51, 44, 32, and 30% 3, 5, 10, and 30 minutes after the injection of 1-[4-[{sup 18}F]fluorobutyryl]-2-palmitoylglycerol, respectively. 1-[4-[{sup 18}F]fluorobutyryl]-2-palmitoylglycerol might be a potential tracer to evaluate myocardial phosphoinositide metabolism early after the injection.

  3. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

    Science.gov (United States)

    Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

    2015-01-01

    Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

  4. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    Energy Technology Data Exchange (ETDEWEB)

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. (Univ. of California, San Francisco (USA))

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  5. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration.

    Science.gov (United States)

    Morrison, Margaux A; Silveira, Alexandra C; Huynh, Nancy; Jun, Gyungah; Smith, Silvia E; Zacharaki, Fani; Sato, Hajime; Loomis, Stephanie; Andreoli, Michael T; Adams, Scott M; Radeke, Monte J; Jelcick, Austin S; Yuan, Yang; Tsiloulis, Aristoteles N; Chatzoulis, Dimitrios Z; Silvestri, Giuliana; Kotoula, Maria G; Tsironi, Evangelia E; Hollis, Bruce W; Chen, Rui; Haider, Neena B; Miller, Joan W; Farrer, Lindsay A; Hageman, Gregory S; Kim, Ivana K; Schaumberg, Debra A; DeAngelis, Margaret M

    2011-10-01

    Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD) and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH) and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based cohort. Initial findings were then

  6. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Morrison Margaux A

    2011-10-01

    Full Text Available Abstract Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1, and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001. Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OHD] was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1 in this same family-based cohort. Initial

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-20

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

  9. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity.

    Science.gov (United States)

    Dobson, R; Burgess, M I; Sprung, V S; Irwin, A; Hamer, M; Jones, J; Daousi, C; Adams, V; Kemp, G J; Shojaee-Moradie, F; Umpleby, M; Cuthbertson, D J

    2016-01-01

    The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy. We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals. Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome. Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography. Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition. Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.

  10. Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

    Science.gov (United States)

    Stanley, W C; Hall, J L; Smith, K R; Cartee, G D; Hacker, T A; Wisneski, J A

    1994-01-01

    We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Role of ketone bodies in perinatal myocardial energy metabolism

    NARCIS (Netherlands)

    Bartelds, B; van der Leij, FR; Kuipers, JRG

    Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not

  12. Role of ketone bodies in perinatal myocardial energy metabolism

    NARCIS (Netherlands)

    Bartelds, B; van der Leij, FR; Kuipers, JRG

    2001-01-01

    Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not availa

  13. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

    Science.gov (United States)

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p equivalents, p metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  14. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    1998-03-01

    Reversible thallium-201 ({sup 201}Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise {sup 201}Tl and rest {sup 123}I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise {sup 201}Tl in 19/28 patients with HCM. {sup 123}I-BMIPP uptake was decreased compared with delayed {sup 201}Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between {sup 123}I-BMIPP and {sup 201}Tl was observed more often in the 49/75 (65%) segments with reversible exercise {sup 201}Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of {sup 123}I-BMIPP and {sup 201}Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  15. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Yii Michael

    2011-09-01

    Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

  16. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  17. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Domenico Tricò

    2016-01-01

    Full Text Available Dilated cardiomyopathy (DCM is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT. In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT and 5 with AGT (DCM-AGT, and 5 non-DCM subjects with AGT (N-AGT, we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min, and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p<0.05, did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p<0.05, while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  18. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man.

  19. Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome

    DEFF Research Database (Denmark)

    Thomsen, Mette; Nordestgaard, Børge G

    2014-01-01

    IMPORTANCE: Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. OBJECTIVE: To test the hypothesis that overweight and obesity with and without metabolic syndrome...... syndrome. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. RESULTS: During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted...... hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1...

  20. Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy.

    Science.gov (United States)

    Kronenberg, Marvin W; Cohen, Gerald I; Leonen, Marlo F; Mladsi, Thomas A; Di Carli, Marcelo F

    2006-07-01

    Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

  1. [Modifications in myocardial energy metabolism in diabetic patients

    Science.gov (United States)

    Grynberg, A.

    2001-01-01

    The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

  2. [Modifications in myocardial energy metabolism in diabetic patients

    Science.gov (United States)

    Grynberg, A.

    2001-01-01

    The capacity of cardiac myocyte to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. Because FA is the main heart fuel (although the most expensive one in oxygen, and prompt to induce deleterious effects), this process is based on a balanced fatty acid (FA) metabolism. Several pathological situations are associated with an accumulation of FA or derivatives, or with an excessive b-oxidation. The diabetic cardiomyocyte is characterised by an over consumption of FA. The control of the FA/glucose balance clearly appears as a new strategy for cytoprotection, particularly in diabetes and requires a reduced FA contribution to ATP production. Cardiac myocytes can control FA mitochondrial entry, but display weak ability to control FA uptake, thus the fate of non beta-oxidized FA appear as a new impairment for the cell. Both the trigger and the regulation of cardiac contraction result from membrane activity, and the other major FA function in the myocardium is their role in membrane homeostasis, through the phospholipid synthesis and remodeling pathways. Sudden death, hypercatecholaminemia, diabetes and heart failure have been associated with an altered PUFA content in cardiac membranes. Experimental data suggest that the 2 metabolic pathways involved in membrane homeostasis may represent therapeutic targets for cytoprotection. The drugs that increase cardiac phospholipid turnover (trimetazidine, ranolazine,...) display anti-ischemic non hemodynamic effect. This effect is based on a redirection of FA utilization towards phospholipid synthesis, which decrease their availability for energy production. A nutritional approach gave also promising results. Besides its anti-arrhythmic effect, the dietary docosahexaenoic acid is able to reduce FA energy consumption and hence oxygen demand. The cardiac metabolic pathways involving FA should be considered as a whole, precariously balanced. The diabetic heart being characterised by

  3. Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography

    NARCIS (Netherlands)

    Brom, van den C.E.; Huisman, M.C.; Vlasblom, R.; Boontje, N.; Duijst, S.; Lubberink, J.M.; Molthoff, C.F.M.; Lammertsma, A.A.; Velden, van der J.; Boer, C.; Ouwens, D.M.; Diamant, M.

    2009-01-01

    0.05). CONCLUSION: Using PET and echocardiography, we found increases in myocardial FA oxidation with a concomitant decrease of insulin-mediated myocardial glucose utilisation in early DCM. In addition, the latter was associated with impaired myocardial function. These in vivo data expand previous i

  4. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  5. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  6. L-(4-/sup 11/C)aspartic acid: enzymatic synthesis, myocardial uptake, and metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, J.R.; Egbert, J.E.; Henze, E.; Schelbert, H.R.; Baumgartner, F.J.

    1982-01-01

    Sterile, pyrogen-free L-(4-/sup 11/C)aspartic acid was prepared from /sup 11/CO/sub 2/ using phosphoenolpyruvate carboxylase and glutamic/oxaloacetic acid transaminase immobilized on Sepharose supports to determine if it is a useful indicator for in vivo, noninvasive determination of myocardial metabolism. An intracoronary bolus injection of L-(4-/sup 11/C)aspartic acid into dog myocardium showed a triexponential clearance curve with maximal production of /sup 11/CO/sub 2/ 100 s after injection. Inactivation of myocardial transaminase activity modified the tracer clearance and inhibited the production of /sup 11/CO/sub 2/. Positron-computed tomography imaging showed that the /sup 11/C activities retained in rhesus monkey myocardium are higher than those observed in dog heart after intravenous injection of L-(4-/sup 11/C)aspartic acid. These findings demonstrated the rapid incorporation of the carbon skeleton of L-aspartic acid into the tricarboxylic acid cycle after enzymatic transamination in myocardium and suggested that L-(4-/sup 11/C)aspartic acid could be of value for in vivo, noninvasive assessment of local myocardial metabolism.

  7. [Influence of microtubule depolymerization of myocardial cells on mitochondria distribution and energy metabolism in adult rats].

    Science.gov (United States)

    Dang, Yong-ming; Fang, Ya-dong; Hu, Jiong-yu; Zhang, Jia-ping; Song, Hua-pei; Zhang, Yi-ming; Zhang, Qiong; Huang, Yue-sheng

    2010-02-01

    To investigate the influence of microtubule depolymerization of myocardial cells on distribution and activity of mitochondria, and energy metabolism of cells in adult rats. Myocardial cells of SD adult rats and SD suckling rats were isolated and cultured. They were divided into adult and suckling rats control groups (AC and SC, normally cultured without any stimulating factor), adult and suckling rats microtubule depolymerization agent groups (AMDA and SMDA, cultured with 8 micromol/L colchicine containing nutrient solution for 30 minutes) according to the random number table. (1) The expression of polymerized beta tubulin in myocardial cells of adult and suckling rats was detected with Western blot. (2) Myocardial cells of rats in AC and AMDA groups were collected. The expression of cytochrome c was detected with Western blot. Distribution of voltage-dependent anion channels (VDAC) and polymerized beta tubulin in myocardial cells were observed with immunofluorescent staining. Mitochondrial inner membrane potential was determined with immunocytochemical method. Activity of myocardial cells was detected with MTT method. Contents of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) and energy charge of cells were determined with high performance liquid chromatography. (1) The expression of polymerized beta tubulin:in AMDA group it was 0.52 + or - 0.07, which was obviously lower than that (1.25 + or - 0.12) in AC group (F = 31.002, P = 0.000); in SMDA group it was 0.76 + or - 0.12, which was significantly lower than that (1.11 + or - 0.24) in SC group (F = 31.002, P = 0.000), but was obviously higher than that in AMDA group (F = 31.002, P = 0.009). (2) The expression of cytochrome c in AC group was 0.26 + or - 0.03, which was obviously lower than that (1.55 + or - 0.13) in AMDA group (t = -24.056, P = 0.000). (3) Immunofluorescent staining result: in AC group, microtubules of myocardial cells were in linear tubiform, distributed in parallel with

  8. Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner.

    Directory of Open Access Journals (Sweden)

    Samuel P Hoile

    Full Text Available Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456 in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.

  9. Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

    Science.gov (United States)

    Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

    2016-02-01

    Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states.

  10. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    Science.gov (United States)

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  11. Effect of unsaturated fatty acids on myocardial performance, metabolism and morphology

    Directory of Open Access Journals (Sweden)

    M.F. Pinotti

    2006-02-01

    Full Text Available Diets rich in saturated fatty acids are one of the most important causes of atherosclerosis in men, and have been replaced with diets rich in unsaturated fatty acids (UFA for the prevention of this disorder. However, the effect of UFA on myocardial performance, metabolism and morphology has not been completely characterized. The objective of the present investigation was to evaluate the effects of a UFA-rich diet on cardiac muscle function, oxidative stress, and morphology. Sixty-day-old male Wistar rats were fed a control (N = 8 or a UFA-rich diet (N = 8 for 60 days. Myocardial performance was studied in isolated papillary muscle by isometric and isotonic contractions under basal conditions after calcium chloride (5.2 mM and ß-adrenergic stimulation with 1.0 µM isoproterenol. Fragments of the left ventricle free wall were used to study oxidative stress and were analyzed by light microscopy, and the myocardial ultrastructure was examined in left ventricle papillary muscle. After 60 days the UFA-rich diet did not change myocardial function. However, it caused high lipid hydroperoxide (176 ± 5 vs 158 ± 5, P < 0.0005 and low catalase (7 ± 1 vs 9 ± 1, P < 0.005 and superoxide-dismutase (18 ± 2 vs 27 ± 5, P < 0.005 levels, and discrete morphological changes in UFA-rich diet hearts such as lipid deposits and mitochondrial membrane alterations compared to control rats. These data show that a UFA-rich diet caused myocardial oxidative stress and mild structural alterations, but did not change mechanical function.

  12. Regional myocardial blood flow, metabolism and function assessed noninvasively by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schelbert, H.R.; Phelps, M.E.; Hoffman, E.; Huang, S.; Kuhl, D.E.

    1979-01-01

    Positron emission computed tomography is a new technique for the noninvasive measure of myocardial blood flow, mechanical function and, in particular, metabolism. The capability of this new study means is due to the technological innovations of the imaging device and the availability of radioactive tracers that are specific for blood flow and metabolism. The device permits recording of cross-sectional images of the left ventricular myocardium that reflect quantitatively regional tracer tissue concentrations. By employing tracer kinetic models this new technique permits the measurement of regional glucose and fatty acid metabolism of the heart. While already an important new tool for investigative studies into cardiac physiology and pathophysiology, the clinical utility of positron emission tomography remains to be defined.

  13. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

    1981-01-01

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc.

  14. Age-related coronary risk factors in Chinese patients with acute myocardial infarction%中国急性心肌梗死患者不同年龄组心血管危险因素分析

    Institute of Scientific and Technical Information of China (English)

    高晓津; 杨进刚; 杨跃进; 李卫; 许海燕; 吴元; 严若华; 金辰

    2016-01-01

    目的 描述中国不同年龄组急性心肌梗死(AMI)患者心血管危险因素的分布状况.方法 中国急性心肌梗死注册登记(CAMI)研究在2013年1月1日至2014年9月30日期间,共连续入选全国31个省市自治区107家医院从发病至医院就诊时间在7d之内、并填报了完整的危险因素信息的AMI患者24 394例.采用调查问卷收集可干预的危险因素,包括吸烟、超重/肥胖、高血压、血脂异常、糖尿病;不良生活方式包括吸烟、缺乏运动、喜肥腻饮食.将24 394例患者分为< 45岁(2 307例)、45~54岁(4 448例)、55~64岁(7 029例)、65~74岁(6 147例)和≥75岁(4 463例)5个组进行比较.结果 24 394例入选患者平均年龄(62.2士13.8)岁,男性18 162例(74.5%),18 209例(74.6%)为ST段抬高型心肌梗死(STEMI).24.7%的患者合并3个及以上可干预的危险因素.总体而言,随着年龄增加,女性、高血压、糖尿病比例逐渐升高;年轻患者中,吸烟、肥胖/超重、高脂血症比例较高.在<55岁的AMI患者中,男性约占90%.按照年龄分组,从<45岁组到≥75岁组,男性(从92.3%到58.0%)、肥胖/超重(从63.9%到37.4%)、目前吸烟率(从68.7%到19.8%)、合并血脂异常(从9.1%到4.5%)、早发冠心病家族史(从6.2%到1.2%)以及喜肥腻饮食(从86.1%到66.2%)患者的比例均呈现显著下降趋势,在男性患者中上述因素的年龄趋势尤为明显.合并高血压患者的比例呈现显著上升趋势(从34.3%到57.9%);合并糖尿病的比例则呈现先升后降的曲线趋势(< 45岁组最低,为11.1%;65~74岁组最高,为22.1%;≥75岁组则又有所下降,为19.3%).结论 不同年龄组的AMI患者危险因素存在差异,年轻AMI患者合并不良生活方式相关危险因素的比例更高.%Objective To determine the age-related coronary risk factors in Chinese patients with acute myocardial infarction (AMI).Methods Among 31 provinces

  15. Age-Related Inducibility of Carboxylesterases by the Antiepileptic Agent Phenobarbital and Implications in Drug Metabolism and Lipid Accumulation 1, 2

    Science.gov (United States)

    Xiao, Da; Chen, Yi-Tzai; Yang, Dongfang; Yan, Bingfang

    2014-01-01

    Carboxylesterases (CES) constitute a class of hydrolytic enzymes that play critical roles in drug metabolism and lipid mobilization. Previous studies with a large number of human liver samples have suggested that the inducibility of carboxylesterases is inversely related with age. To directly test this possibility, neonatal (10 days of age) and adult mice were treated with the antiepileptic agent phenobarbital. The expression and hydrolytic activity were determined on six major carboxylesterases including ces1d, the ortholog of human CES1. Without exception, all carboxylesterases tested were induced to a greater extent in neonatal than adult mice. The induction was detected at mRNA, protein and catalytic levels. Ces1d was greatly induced and found to rapidly hydrolyze the antiplatelet agent clopidogrel and support the accumulation of neutral lipids. Phenobarbital represents a large number of therapeutic agents that induce drug metabolizing enzymes and transporters in a species-conserved manner. The higher inducibility of carboxylesterases in the developmental age likely represents a general phenomenon cross species including human. Consequently, individuals in the developmental age may experience greater drug-drug interactions. The greater induction of ces1d also provides a molecular explanation to the clinical observation that children on antiepileptic drugs increase plasma lipids. PMID:22513142

  16. Age-related effects on markers of inflammation and cartilage metabolism in response to an intra-articular lipopolysaccharide challenge in horses.

    Science.gov (United States)

    Kahn, M K; Coverdale, J A; Leatherwood, J L; Arnold, C E; Dabareiner, R A; Bradbery, A N; Millican, A A; Welsh, T H

    2017-02-01

    Eighteen Quarter Horses were used in a randomized complete design for a 28-d experiment to evaluate age-related effects on inflammation and cartilage turnover after induction of a single inflammatory insult using lipopolysaccharide (LPS). Horses were grouped by age as yearlings (3 males and 3 females), 2 to 3 yr olds (2/3 yr old; 2 males and 4 females), and skeletally mature 5 to 8 yr olds (mature; 2 males and 4 females). On d 0, all horses were individually housed and fed diets that met or exceeded requirements. On d 14, horses were challenged with an intra-articular injection of LPS. Radial carpal joints were randomly assigned to receive 0.5 ng LPS solution obtained from O55:B5 or 0.8 mL sterile lactated Ringer's solution as a contralateral control. Synovial fluid was collected prior to LPS injection at h 0 before injection and at 6, 12, 24, 168, and 336 h after injection. Samples were analyzed using commercial ELISA kits for PGE, collagenase cleavage neoepitope (C2C), and carboxypropeptide of type II collagen (CPII). Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were monitored over the initial 24 h and carpal circumference and surface temperature were also recorded, with additional measurements at 168 and 336 h. Data were analyzed using PROC MIXED of SAS. Values for RT, HR, and RR were within the normal range for each age group. Heart rate and RT were influenced by age ( horse ( = 0.84), but circumference and surface temperature increased ( horses. Concentrations of synovial C2C were affected by age of horse, with yearlings and 2/3 yr olds having lower ( horses. Similarly, synovial CPII was influenced by age, with yearlings and 2/3 yr olds having lower ( ≤ 0.02) concentrations than mature horses. Ratios of anabolic CPII to catabolic C2C varied by age, with mature and 2/3-yr-old horses having greater ( < 0.01) values compared with yearlings. These results indicate that inflammation and the corresponding cartilage turnover in response to

  17. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa [Osaka Univ., Suita (Japan). Medical School; Ishida, Yoshio; Hayashida, Kohei [and others

    1998-04-01

    In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75{+-}0.34%, 0.65{+-}0.25%, and 0.43{+-}0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17{+-}0.49%, 0.80{+-}0.44% and 0.99{+-}0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38{+-}0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy. (author)

  18. Myocardial perfusion/metabolism mismatch and ventricular arrhythmias in the chronic post infarction state

    Energy Technology Data Exchange (ETDEWEB)

    Krause, B.J.; Poeppel, T.D.; Vosberg, H.; Mueller, H.W. [Dept. of Nuclear Medicine, Heinrich Heine Univ., Duesseldorf (Germany); Reinhardt, M. [Praxis fuer Radiologie und Nuklearmedizin, Dorsten (Germany); Vester, E.G. [Dept. of Cardiology, Evangelisches Krankenhaus, Duesseldorf (Germany); Yong, M.; Mau, J. [Dept. of Statistics in Medicine, Heinrich Heine Univ., Duesseldorf (Germany); Strauer, B.E. [Dept. of Medicine, Div. of Cardiology, Angiology and Pulmonary Disease, Heinrich Heine Univ., Duesseldorf (Germany)

    2005-07-01

    Aim: Ventricular arrhythmias have been shown to originate in the myocardial peri-infarct region due to irregular heterotopic conduction. Hypoperfused but viable myocardium is often localised in those areas and may be involved in the pathogenesis of arrhythmias. We tested the hypothesis that these myocardial perfusion/metabolism mismatches (MM) are significantly associated with ventricular arrhythmias in the chronic post infarction state. Patients, methods: 47 post infarction patients were included in the study. 33 suffered from ventricular arrhythmia whereas 14 did not. All patients underwent {sup 99m}Tc tetrofosmin SPECT and {sup 18}F-FDG PET. A region-of-interest(ROI)-analysis was used to assess viable myocardium based on predefined MM-criteria. Univariate analyses as well as a logistic regression model for the multivariate analysis were carried out. Results: 94% of the arrhythmic patients displayed at least one MM-segment as compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed a statistically significant relation (p=0.018). The logistic regression model predicted the occurrence or absence of arrhythmia in 85% of all cases. Multivariate analysis gave consistent results, after adjusting for symptomatic chronic heart failure (CHF), aneurysms and age. Conclusion: Our results support the hypothesis that hypoperfused but viable myocardium represents an arrhyhmogenic substrate and is a relevant risk factor for developing ventricular arrhythmias following myocardial infarction. Therefore, the detection of MM-segments allows the identification of patients with a higher risk for future cardiac events. (orig.)

  19. Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention

    Energy Technology Data Exchange (ETDEWEB)

    Crane, P.; Laliberte, R.; Heminway, S.; Thoolen, M.; Orlandi, C. (Du Pont Merck Pharmaceutical Co., Billerica, MA (United States). Radiopharmaceutical Div.)

    1993-01-01

    This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi. [sup 99m]Tc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial [sup 99m]Tc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release [sup 99m]Tc-sestamibi from the mitochondrial fraction, with an IC[sub 50] of 2.54[+-]0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of [sup 99m]Tc-sestamibi was found to increase from 10.5%[+-]3.0% to 61.2%[+-]0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium 'overload,' and loss of mitochondrial metabolic function, [sup 99m]Tc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability. (orig.).

  20. Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention.

    Science.gov (United States)

    Crane, P; Laliberté, R; Heminway, S; Thoolen, M; Orlandi, C

    1993-01-01

    This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi. 99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial 99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release 99mTc-sestamibi from the mitochondrial fraction, with an IC50 of 2.54 +/- 0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of 99mTc-sestamibi was found to increase from 10.5% +/- 3.0% to 61.2% +/- 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium "overload" and loss of mitochondrial metabolic function, 99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.

  1. Age-related changes in protein metabolism of beech (Fagus sylvatica L.) seeds during alleviation of dormancy and in the early stage of germination.

    Science.gov (United States)

    Ratajczak, Ewelina; Kalemba, Ewa M; Pukacka, Stanislawa

    2015-09-01

    The long-term storage of seeds generally reduces their viability and vigour. The aim of this work was to evaluate the effect of long-term storage on beech (Fagus sylvatica L.) seeds at optimal conditions, over 9 years, on the total and soluble protein levels and activity of proteolytic enzymes, including endopeptidases, carboxypeptidases and aminopeptidases, as well as free amino acid levels and protein synthesis, in dry seeds, after imbibition and during cold stratification leading to dormancy release and germination. The same analyses were conducted in parallel on seeds gathered from the same tree in the running growing season and stored under the same conditions for only 3 months. The results showed that germination capacity decreased from 100% in freshly harvested seeds to 75% in seeds stored for 9 years. The levels of total and soluble proteins were highest in freshly harvested seeds and decreased significantly during storage, these proportions were retained during cold stratification and germination of seeds. Significant differences between freshly harvested and stored seeds were observed in the activities of proteolytic enzymes, including endopeptidases, aminopeptidases and carboxypeptidases, and in the levels of free amino acids. The neosynthesis of proteins during dormancy release and in the early stage of seed germination was significantly weaker in stored seeds. These results confirm the importance of protein metabolism for seed viability and the consequences of its reduction during seed ageing.

  2. Age-related skin changes

    Directory of Open Access Journals (Sweden)

    Božanić Snežana

    2012-01-01

    Full Text Available Age-related skin changes can be induced by chronological ageing, manifested in subcutaneous fat reduction, and photo-ageing eliciting increased elastotic substance in the upper dermis, destruction of its fibrilar structure, augmented intercellular substance and moderate inflammatory infiltrate. Forty-five biopsy skin samples of the sun-exposed and sun-protected skin were analyzed. The patients were both males and females, aged from 17 to 81 years. The thickness of the epidermal layers and the number of cellular living layers is greater in younger skin. The amount of keratohyaline granules is enlarged in older skin. Dermoepidermal junction is flattened and the presence of elastotic material in the dermis is pronounced with age. The amount of inflammatory infiltrate is increased, the fibrous trabeculae are thickened in older skin and the atrophy of the hypodermis is observed. Chronological ageing alters the fibroblasts metabolism by reducing their life span, capacity to divide and produce collagen. During ageing, the enlargement of collagen fibrils diminishes the skin elasticity.

  3. Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Michihiro; Kurihara, Tadashi [Sumitomo Hospital, Osaka (Japan)

    2000-01-01

    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress {sup 99m}Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest {sup 123}I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and {sup 123}I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by {sup 123}I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in {sup 123}I-BMIPP). Eighteen normotensive patients with apical defect by {sup 123}I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by {sup 123}I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by {sup 123}I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and {sup 123}I-BMIPP imaging are useful for the identification of these patients. (author)

  4. A possible relationship between gluconeogenesis and glycogen metabolism in rabbits during myocardial ischemia

    Directory of Open Access Journals (Sweden)

    RAQUEL R. DE AGUIAR

    2017-08-01

    Full Text Available ABSTRACT Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

  5. A possible relationship between gluconeogenesis and glycogen metabolism in rabbits during myocardial ischemia.

    Science.gov (United States)

    Aguiar, Raquel R DE; Vale, Daniela F; Silva, Renato M DA; Muniz, Yolanda P; Antunes, Fernanda; Logullo, Carlos; Oliveira, André L A; Almeida, Adriana J DE

    2017-08-31

    Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

  6. Myocardial infarction and ischemic heart disease in overweight and obesity with and without metabolic syndrome.

    Science.gov (United States)

    Thomsen, Mette; Nordestgaard, Børge G

    2014-01-01

    Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD. We examined 71,527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome. Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1.81-3.00) in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Normal weight vs overweight vs obesity and presence vs absence of metabolic syndrome did not interact on risk of MI or IHD (P = .90 and P = .44). Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals (log-rank trend P = .006 to P metabolic syndrome was 1.54 (95% CI, 1.32-1.81) across all BMI categories, addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41). These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that

  7. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation.

    Science.gov (United States)

    Crawford, Peter A; Crowley, Jan R; Sambandam, Nandakumar; Muegge, Brian D; Costello, Elizabeth K; Hamady, Micah; Knight, Rob; Gordon, Jeffrey I

    2009-07-07

    Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of the diet when these components are plentiful. Here we examine how the microbiota shapes host metabolic and physiologic adaptations to periods of nutrient deprivation. Germ-free (GF) mice and mice who had received a gut microbiota transplant from conventionally raised donors were compared in the fed and fasted states by using functional genomic, biochemical, and physiologic assays. A 24-h fast produces a marked change in gut microbial ecology. Short-chain fatty acids generated from microbial fermentation of available glycans are maintained at higher levels compared with GF controls. During fasting, a microbiota-dependent, Ppar alpha-regulated increase in hepatic ketogenesis occurs, and myocardial metabolism is directed to ketone body utilization. Analyses of heart rate, hydraulic work, and output, mitochondrial morphology, number, and respiration, plus ketone body, fatty acid, and glucose oxidation in isolated perfused working hearts from GF and colonized animals (combined with in vivo assessments of myocardial physiology) revealed that the fasted GF heart is able to sustain its performance by increasing glucose utilization, but heart weight, measured echocardiographically or as wet mass and normalized to tibial length or lean body weight, is significantly reduced in both fasted and fed mice. This myocardial-mass phenotype is completely reversed in GF mice by consumption of a ketogenic diet. Together, these results illustrate benefits provided by the gut microbiota during periods of nutrient deprivation, and emphasize the importance of further exploring the relationship between gut microbes and cardiovascular health.

  8. Assessment of myocardial metabolism by positron emission tomography; Stoffwechseluntersuchungen des Herzens mit der Positronenemissionstomographie

    Energy Technology Data Exchange (ETDEWEB)

    Bengel, F.M.; Schwaiger, M. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik

    1999-06-01

    In combination with a variety of tracers, positron emission tomography does provide noninvasive quantitative information not only about myocardial utilisation of substrates such as glucose or free fatty acids, but also about overall oxidative metabolism. PET studies of myocardial metabolism have substantially contributed to an improved understanding of regulatory mechanism as well as interaction between different substrates under normal conditions as well as under pathologic conditions such as ischemia, heart failure or diabetes mellitus, and will continue to do so in the future. (orig.) [German] Fuer die Positronenemissionstomographie stehen verschiedene Tracer zur Verfuegung, die am menschlichen Herzen nichtinvasive Quantifizierung der Utilisation von Substraten wie Glukose oder freien Fettsaeuren, aber auch des gesamten sauerstoffabhaengigen Metabolismus ermoeglichen. Stoffwechseluntersuchungen des Herzens mit der PET haben zu einem genaueren Verstaendnis von Regulationsmechanismen und Interaktionen zwischen verschiedenen Substraten sowohl im Normalzustand als auch unter pathologischen Bedingungen wie etwa bei ischaemischen Syndromen, Herzinsuffizienz oder Diabetis mellitus beigetragen. Insbesondere durch Untersuchungen von metabolischen Auswirkungen verschiedener Therapieansaetze bei Herzerkrankungen und zur Vorhersage der Effektivitaet solcher therapeutischer Strategien kann die PET auch in Zukunft einen Beitrag zur Weiterentwicklung der Kardiologie leisten. (orig.)

  9. Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure.

    Science.gov (United States)

    Bedi, Kenneth C; Snyder, Nathaniel W; Brandimarto, Jeffrey; Aziz, Moez; Mesaros, Clementina; Worth, Andrew J; Wang, Linda L; Javaheri, Ali; Blair, Ian A; Margulies, Kenneth B; Rame, J Eduardo

    2016-02-23

    The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate. These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart. © 2016 American Heart Association, Inc.

  10. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Cade W Todd

    2011-12-01

    Full Text Available Abstract Background In the general population, peripheral metabolic complications (MC increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV and combination anti-retroviral therapy (cART are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC. Methods Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT, and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs, 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs, 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs, and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs. Left ventricular function parameters were quantified using echocardiography. Results Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS was lower (p Conclusion Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin. Trial Registration NIH Clinical Trials NCT00656851

  11. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

    Directory of Open Access Journals (Sweden)

    Luz Ibarra-Lara

    2016-12-01

    Full Text Available Renin-angiotensin system (RAS activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II/Angiotensin II type 1 receptor (AT1 and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a sham; (b vehicle-treated myocardial infarction (MI (MI-V; and (c fenofibrate-treated myocardial infarction (MI-F. Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C, insulin levels and insulin resistance index (HOMA-IR in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH oxidase 4 (NOX4, decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD1, SOD2 and catalase and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K/protein kinase B (PkB, also known as Akt/Glut-4/endothelial nitric oxide synthase (eNOS. In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

  12. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II.

    Science.gov (United States)

    Ibarra-Lara, Luz; Sánchez-Aguilar, María; Sánchez-Mendoza, Alicia; Del Valle-Mondragón, Leonardo; Soria-Castro, Elizabeth; Carreón-Torres, Elizabeth; Díaz-Díaz, Eulises; Vázquez-Meza, Héctor; Guarner-Lans, Verónica; Rubio-Ruiz, María Esther

    2016-12-28

    Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

  13. Depressive disorder and gastrointestinal dysfunction after myocardial infarct are associated with abnormal tryptophan-5-hydroxytryptamine metabolism in rats

    Science.gov (United States)

    Liu, Chunyan; Wang, Yangang

    2017-01-01

    In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test. Gastric retention and intestinal transit were detected using the carbon powder labeling method. Immunohistochemical staining was used to detect indoleamine 2,3-dioxygenase expression in the hippocampus and ileum. High-performance liquid chromatography with fluorescence and ultraviolet detection determined the levels of 5-hydroxytryptamine, its precursor tryptophan, and its metabolite 5-hydroxyindoleacetic acid in the hippocampus, distal ileum, and peripheral blood. All data were analyzed using one-way analyses of variance. Three weeks after arterial occlusion, rats in the model group began to exhibit depression-like symptoms. For example, the rate of sucrose consumption was reduced, the total and central distance traveled in the open field test were reduced, and immobility time was increased, while swimming, struggling and latency to immobility were decreased in the forced swim test. Moreover, the gastric retention rate and gastrointestinal transit rate were increased in the model group. Expression of indoleamine 2,3-dioxygenase was increased in the hippocampus and ileum, whereas 5-hydroxytryptamine metabolism was decreased, resulting in lower 5-hydroxytryptamine and 5-hydroxyindoleacetic acid levels in the hippocampus and higher levels in the ileum. Depressive disorder and gastrointestinal dysfunction after myocardial infarction involve abnormal tryptophan-5-hydroxytryptamine metabolism, which may explain the somatic, cognitive

  14. The characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Naoki; Toyama, Takuji; Hoshizaki, Hiroshi [Gunma Prefectural Cardiovascular Center (Japan)] (and others)

    1999-09-01

    We evaluated the characteristics of myocardial fatty acid metabolism in patients with left ventricular hypertrophy (LVH). Myocardial imaging with {sup 123}I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) was performed in 28 patients with hypertrophic cardiomyopathy (HCM), 15 patients with hypertensive heart disease (HHD), 13 patients with aortic stenosis (AS) and 8 normal controls (NC). The patients with HCM consisted of 13 patients of asymmetric septal hypertrophy (ASH), 7 patients of diffuse hypertrophy (Diffuse-HCM) and 8 patients of apical hypertrophy (APH). Planar and SPECT images of BMIPP were acquired 15 minutes and 4 hours after tracer injection. Resting {sup 201}Tl SPECT images and echocardiography were also performed on other days. We calculated heart/mediastinum count ratio and washout rate of BMIPP by using planar image. In patients with LVH, the incidence of reduced BMIPP uptake was more frequent than that of reduced {sup 201}Tl uptake. In delayed images, more than 60% of patients with LVH reduced BMIPP uptake, especially remarkable for patients with ASH and APH. The washout rate of all cardiac hypertrophic disorders was tended to be higher than that of normal subjects. Reduced BMIPP uptake was frequently found in septal portion of anterior and inferior wall in patients with ASH, in inferior wall in patients with Diffuse-HCM and HHD, in apex in patients with APH and AS. These results suggest that BMIPP scintigraphy can differentiate three types of cardiac hypertrophy. (author)

  15. Age-Related Macular Degeneration

    Science.gov (United States)

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  16. Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, André Luiz Cerqueira de, E-mail: andrealmeida@cardiol.br [Johns Hopkins University, Baltimore, MD (United States); Universidade Estadual de Feira de Santana, Bahia (Brazil); Teixido-Tura, Gisela; Choi, Eui-Young; Opdahl, Anders; Fernandes, Verônica R. S. [Johns Hopkins University, Baltimore, MD (United States); Wu, Colin O. [National Heart, Lung and Blood Institute, Bethesda, MD (United States); Bluemke, David A. [National Institutes of Health Clinical Center, National Institute for Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Lima, João A. C. [Johns Hopkins University, Baltimore, MD (United States)

    2014-04-15

    Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (ε{sub CC}) and longitudinal strain (ε{sub LL}), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower ε{sub CC} and lower ε{sub LL} than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative ε{sub CC} (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative ε{sub LL} after adjustment for ethnicity, LVEF, and creatinine. Left ventricular ε{sub CC} and ε{sub LL}, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.

  17. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  18. The relationship between biventricular myocardial performance and metabolic parameters during incremental exercise and recovery in healthy adolescents.

    Science.gov (United States)

    Pieles, Guido E; Gowing, Lucy; Forsey, Jonathan; Ramanujam, Paramanantham; Miller, Felicity; Stuart, A Graham; Williams, Craig A

    2015-12-15

    Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m(2)) completed an incremental cardiopulmonary exercise test (25 W · 3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o 2peak) of 40.6 ± 8.9 ml · kg(-1) · min(-1) and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P strain, V̇o 2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P myocardial performance and metabolic parameters during exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology.

  19. Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease.

    Science.gov (United States)

    Kazmaier, S; Weyland, A; Buhre, W; Stephan, H; Rieke, H; Filoda, K; Sonntag, H

    1998-10-01

    Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter. The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels. In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.

  20. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy; [sup 18]F-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa; Nishimura, Tsunehiko; Kozuka, Takahiro (Osaka Univ. (Japan). Faculty of Medicine); Ishida, Yoshio; Shimonagata, Tsuyoshi; Nagata, Seiki; Miyatake, Kunio; Tokuda, Takahiro

    1994-01-01

    To find a clue to elucidate pathophysiology of hypertrophic cardiomyopathy (HCM), myocardial glucose metabolism was investigated by using positron computed tomography (PET) with F-18-fluorodeoxyglucose (F-18 FDG) in 28 HCM patients and 9 hypetensive (H) patients. The degree of F-18 FDG uptake in the myocardium was quantitatively determined by %dose uptake per myocardium of 30 g. A group of H patients had almost normal pattern; i.e., fasting F-18 FDG uptake was low (0.13[+-]0.07%/myocardium of 30 g) and was remarkably increased on glucose loading (0.30[+-]0.14%). In all HCM patients but 4 of apical type (AT), however, fasting F-18 FDG uptake was remarkably high (0.20[+-]0.08% for 12 patients with asymmetrical septal hypertrophy (ASH), 0.17[+-]0.07% for 6 of diffuse type (DT) and 0.20[+-]0.07% for 6 of dilated phase (DP)). Decreased uptake of F-18 FDG was seen on glucose loading for DP (0.19[+-]0.08%) and AT (0.17[+-]0.11%), although it was almost normal for ASH (0.33[+-]0.15%). According to regional myocardium, fasting F-18 FDG uptake was decreased in the entire myocardium in all HCM patients but those of AT. F-18 FDG was decreased on glucose loading in bokth DT and DP patients, suggesting the presence of myocardial disturbance. In conclusion, HCM patients were characterized by having increased uptake of F-18 FDG on fasting. This has an important implication for the understanding of its pathophysiology and diagnosis of hyertrophic myocardium. (N.K.).

  1. Myocardial blood flow and metabolism in patients with hypertrophic cardiomyopathy. A study with carbon-11 acetate and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Sugao; Maruno, Hirotaka; Nishiyama, Shinichiro; Seki, Akira [Toranomon Hospital, Tokyo (Japan); Senda, Michio; Toyama, Hinako

    1997-03-01

    The underlying pathophysiology of hypertrophic cardiomyopathy (HCM) is still unclear. Positron emission tomography is a suitable and promising technique for the detection of possible metabolic consequences of the disease. To assess regional myocardial blood flow and metabolism, 19 asymptomatic or only mildly symptomatic patients with HCM and 10 normal control subjects were studied using carbon-11 acetate and fluorine-18-labelled deoxyglucose (FDG) as tracers of myocardial blood flow (Ao), oxygen consumption (k), and exogenous glucose utilization. In the patients, regional Ao in the hypertrophied septum and apex (H) was similar to that in the nonhypertrophied free wall (N) (91.3{+-}3.9% vs 92.9{+-}3.1%; p=NS). However, the k values were significantly lower in H than in N (0.044{+-}0.012 vs 0.060{+-}0.016/min, p<0.0001). The k value in N and normal control subjects (0.062{+-}0.013) was similar. Postprandial FDG uptake was lower in H than in N (70{+-}16 vs 91{+-}7%; p<0.0001) in 16 patients and slightly higher in 3 patients. Fasting FDG study showed increased FDG uptake in H in 3 out of 13 patients, suggesting a disorder of the myocardial microvascular circulation. A relative decrease in hypertrophied septal and apical oxidative metabolism and glucose utilization without any corresponding perfusion defect could reflect abnormal regional aerobic metabolism in the disproportionately thickened myocardium in patients with HCM. This suggests that a primary myocardial metabolic defect might be present in patients with HCM. (author)

  2. [Effect of rehabilitation after myocardial infarction on muscular metabolism. Contribution of phosphorus 31 NMR spectroscopy].

    Science.gov (United States)

    Cottin, Y; Marcer, I; Walker, P; Verges, B; Caillaux, B X; Louis, P; Didier, J P; Casillas, J M; Brunotte, F; Wolf, J E

    1994-06-01

    P 31 NMR spectroscopy is a recent technique which allows a non-invasive and direct analysis of oxidative metabolism and pH changes, an indicator of acidosis due to lactic acid accumulation in the skeletal muscles. The authors investigated oxidative muscular metabolism of the sural triceps in 10 patients after myocardial infarction by performing a study after the acute phase and repeating the study after a programme of physical training. At rest, there were no significant differences. On the other hand, for the same level of maximal effort, the depletion in phosphocreatinine (PCr) and the accumulation of inorganic phosphate (Pi) were significantly lower after physical training: the PCr/PCr + Pi increased from 0.467 +/- 0.179 to 0.538 +/- 0.20 (p < 0.02) and the Pi/PCr ratio decreased from 1.570 +/- 1.440 to 1.181 +/- 1.069 (p < 0.05). The pH at the same level of maximal exercise did not change significantly between the two periods: 6.85 +/- 0.16 vs 6.88 +/- 0.15 (NS). The peak oxygen consumption (VO2) measured during bicycle ergometry increased significantly from 23.4 +/- 10.5 to 28.3 +/- 12.14 ml/min/kg after exercise training (p < 0.01). In addition, a correlation was observed between the improvement of the peripheral parameters (PCr/PCr + Pi) and the increase in VO2 max (r = 0.757, p < 0.01). The authors results confirm the effects of physical training on oxidative metabolisms of the peripheral muscles and its influence on improvement of global performance of coronary patients.

  3. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  4. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa; Takeyama, Daiya; Yamane, Yuriko; Chida, Masanobu; Otani, Hiroki; Shirato, Kunio [Tohoku Univ., Sendai (Japan). School of Medicine; Ido, Tatsuo

    1997-06-01

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using {sup 18}F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6{+-}1.6 vs. 4.1{+-}0.5, p<0.01) and posterolateral wall (5.9{+-}0.7 vs. 3.8{+-}0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  5. Features of the in-hospital course of myocardial infarction in patients with glucose metabolism disorders

    Directory of Open Access Journals (Sweden)

    B. U. Mardanov

    2015-01-01

    Full Text Available Aim. To study the clinical course of acute myocardial infarction (MI with ST segment elevation (STEMI and the features of inpatient treatment in patients with and without diabetes mellitus (DM. Material and methods. STEMI patients (n=83, who were hospitalized in 2014, were included into the study. The patients were divided into two groups according to the presence or absence of glucose metabolism disorders: Group 1 (patients with type 2 DM; n=38 and Group 2 (patients without glucose metabolism disorders; n=45. Baseline demographic, clinical, laboratory and instrumental characteristics of the patients, along with the features of hospital treatment, were studied. Results. In group 1 compared with group 2 hypertension was detected significantly more frequently (73.7% vs 49%; p<0.05, and a class of acute heart failure (Killip at admission was higher (1.46±0.6 vs 1.23±0.57; p<0.05. STEMI was complicated by an acute left ventricular aneurysm 12% more often in patients of group 1 (p<0.05. The duration of inpatient treatment was also higher in patients of group 1 (18±4.1 vs 16±3.6 days; p<0.05. Conclusion. Only 21% of the patients with DM and STEMI had adequate treatment of ischemic heart disease and a quarter of the patients in this group had no adequate DM therapy before the admission. Patients with DM had a higher incidence of in-hospital STEMI complications and a higher duration of inpatient treatment. 

  6. The relationship between biventricular myocardial performance and metabolic parameters during incremental exercise and recovery in healthy adolescents

    Science.gov (United States)

    Gowing, Lucy; Forsey, Jonathan; Ramanujam, Paramanantham; Miller, Felicity; Stuart, A Graham; Williams, Craig A.

    2015-01-01

    Background left ventricular (LV) and right ventricular (RV) myocardial reserve during exercise in adolescents has not been directly characterized. The aim of this study was to quantify myocardial performance response to exercise by using two-dimensional (2-D) speckle tracking echocardiography and describe the relationship between myocardial reserve, respiratory, and metabolic exercise parameters. A total of 23 healthy boys and girls (mean age 13.2 ± 2.7 yr; stature 159.1 ± 16.4 cm; body mass 49.5 ± 16.6 kg; BSA 1.47 ± 0.33 m2) completed an incremental cardiopulmonary exercise test (25 W·3 min increments) with simultaneous acquisition of 2-D transthoracic echocardiography at rest, each exercise stage up to 100 W, and in recovery at 2 min and 10 min. Two-dimensional LV (LV Sl) and RV (RV Sl) longitudinal strain and LV circumferential strain (LV Sc) were analyzed to define the relationship between myocardial performance reserve and metabolic exercise parameters. Participants achieved a peak oxygen uptake (V̇o2peak) of 40.6 ± 8.9 ml·kg−1·min−1 and a work rate of 154 ± 42 W. LV Sl and LV Sc and RV Sl increased significantly across work rates (P exercise was significantly correlated to resting strain, V̇o2peak, oxygen pulse, and work rate (0.530 ≤ r ≤ 0.784, P exercise by using a novel methodology. Relationships detected present novel data directly describing myocardial adaptation at different stages of exercise and recovery that in the future can help directly assess cardiac reserve in patients with cardiac pathology. PMID:26475589

  7. Impact of metabolic disorders on the relation between overweight/obesity and incident myocardial infarction and ischaemic stroke in fertile women

    DEFF Research Database (Denmark)

    Andersen, S S; Andersson, C; Berger, S M

    2015-01-01

    AIMS: Whether overweight is a risk factor for cardiovascular disease in the absence of metabolic disorders remains under debate and is largely unexamined in young women. We evaluated the risk of myocardial infarction and ischaemic stroke in fertile women conditional on time-dependent presence...... and smoking, the risk of the composite outcome of myocardial infarction and ischaemic stroke was assessed with metabolic disorders (i.e. hypertensive conditions, abnormal glucose metabolism and/or dyslipidaemia) included as time-dependent variables. RESULTS: The population comprised 261,489 women with median.......1 (CI = 67.6-112.2) and IRR 4.24 (CI = 5 3.11-5.79) in overweight. CONCLUSIONS: The risk of myocardial infarction and ischaemic stroke was more strongly associated with the presence of metabolic disorders than with overweight per se in fertile women. Targeting prevention of metabolic disorders might...

  8. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    Science.gov (United States)

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  9. Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Schnohr, Peter

    2014-01-01

    BACKGROUND: Cardiovascular disease is 1 of the most common age-related diseases, and also 1 of the most common causes of death in the general population. We tested the hypothesis that visible age-related signs associate with risk of ischemic heart disease (IHD), myocardial infarction (MI), and de...

  10. Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

    Science.gov (United States)

    Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

    2016-03-15

    Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM.

  11. The effect of right ventricular pacing on myocardial oxidative metabolism and efficiency: relation with left ventricular dyssynchrony

    Energy Technology Data Exchange (ETDEWEB)

    Ukkonen, Heikki; Saraste, Antti; Koistinen, Juhani [Turku University Hospital, Department of Medicine, P.O. Box 52, Turku (Finland); Tops, Laurens; Bax, Jeroen [Leiden University Medical Center, Leiden (Netherlands); Naum, Alexander [University of Turku, Turku PET Centre, Turku (Finland); Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Turku University Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland)

    2009-12-15

    Right ventricular (RV) apical pacing induces dyssynchrony by a left bundle branch block type electrical activation sequence in the heart and may impair left ventricular (LV) function. Whether these functional changes are accompanied by changes in myocardial perfusion, oxidative metabolism and efficiency, and the relation with the induction of LV dyssynchrony are unknown. Our study was designed to investigate the acute effects of RV pacing on these parameters. Ten patients with normal LV ejection fraction and VVI/DDD pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing-OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [{sup 15}O]water and [{sup 11}C]acetate positron emission tomography was used to measure perfusion and oxidative metabolism (k{sub mono}) of the LV. An echocardiographic examination was used to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of forward work was calculated as systolic blood pressure x cardiac output/LV mass/k{sub mono}. RV pacing decreased SV in all subjects (mean decrease 13%, from 76 {+-} 7 to 66 {+-} 7 ml, p = 0.004), but global perfusion and k{sub mono} were unchanged. The efficiency tended to be lower with pacing-ON (70 {+-} 20 vs 81 {+-} 21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6) efficiency decreased by 23% (from 78 {+-} 25 to 60 {+-} 14 mmHg l/g, p = 0.02), but in patients without dyssynchrony no change in efficiency was detected. Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was detected during pacing in patients with dyssynchrony but not in those without dyssynchrony. RV pacing resulted in a significant decrease in SV. However, deleterious effects on LV oxidative metabolism and efficiency were observed only in patients with dyssynchrony during RV pacing. (orig.)

  12. Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome.

    Science.gov (United States)

    Ilkun, Olesya; Wilde, Nicole; Tuinei, Joseph; Pires, Karla M P; Zhu, Yi; Bugger, Heiko; Soto, Jamie; Wayment, Benjamin; Olsen, Curtis; Litwin, Sheldon E; Abel, E Dale

    2015-08-01

    Cardiac dysfunction in obesity is associated with mitochondrial dysfunction, oxidative stress and altered insulin sensitivity. Whether oxidative stress directly contributes to myocardial insulin resistance remains to be determined. This study tested the hypothesis that ROS scavenging will improve mitochondrial function and insulin sensitivity in the hearts of rodent models with varying degrees of insulin resistance and hyperglycemia. The catalytic antioxidant MnTBAP was administered to the uncoupling protein-diphtheria toxin A (UCP-DTA) mouse model of insulin resistance (IR) and obesity, at early and late time points in the evolution of IR, and to db/db mice with severe obesity and type-two diabetes. Mitochondrial function was measured in saponin-permeabilized cardiac fibers. Aconitase activity and hydrogen peroxide emission were measured in isolated mitochondria. Insulin-stimulated glucose oxidation, glycolysis and fatty acid oxidation rates were measured in isolated working hearts, and 2-deoxyglucose uptake was measured in isolated cardiomyocytes. Four weeks of MnTBAP attenuated glucose intolerance in 13-week-old UCP-DTA mice but was without effect in 24-week-old UCP-DTA mice and in db/db mice. Despite the absence of improvement in the systemic metabolic milieu, MnTBAP reversed cardiac mitochondrial oxidative stress and improved mitochondrial bioenergetics by increasing ATP generation and reducing mitochondrial uncoupling in all models. MnTBAP also improved myocardial insulin mediated glucose metabolism in 13 and 24-week-old UCP-DTA mice. Pharmacological ROS scavenging improves myocardial energy metabolism and insulin responsiveness in obesity and type 2 diabetes via direct effects that might be independent of changes in systemic metabolism.

  13. Application of Positron Emission TomographyintheDetection of Myocardial Metabolism inPigVentricularFibrillation and Asphyxiation Cardiac Arrest ModelsafterResuscitation

    Institute of Scientific and Technical Information of China (English)

    WUCaiJun; LIChunSheng; ZHANGYi; YANGJun

    2014-01-01

    ObjectiveTo study the application of positron emission tomography (PET) in detection of myocardial metabolism in pig ventricular fibrillation and asphyxiation cardiac arrest models after resuscitation. MethodsThirty-two healthyminiature pigs were randomized into aventricular fibrillation cardiac arrest (VFCA) group (n=16) and an asphyxiation cardiac arrest (ACA)group (n=16). Cardiac arrest (CA) was induced byprogrammed electric stimulationorendotracheal tube clamping followed by cardiopulmonary resuscitation (CPR) anddefibrillation. At four hours and 24 h afterspontaneous circulation was achieved, myocardial metabolism was assessed by PET.18F-FDG myocardial uptake in PET was analyzed and the maximum standardized uptake value (SUVmax) was measured. ResultsSpontaneous circulation was 100% and 62.5% in VFCA group and ACA group, respectively.PET demonstrated that the myocardial metabolism injuries was more severe and widespread after ACA than after VFCA. The SUVmax was higher in VFCA group than in ACA group (P<0.01).In VFCA group,SUVmaxat 24h after spontaneous circulation increased to the level of baseline. ConclusionACA causes more severe cardiac metabolism injuries than VFCA. Myocardial dysfunction is associated with less successful resuscitation. Myocardial stunning does occur with VFCA but not with ACA.

  14. Time course of metabolic findings in coronary occlusion and reperfusion and their role for assessing myocardial salvage

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, M.

    1986-08-01

    The techniques currently used to assess myocardial infarction are limited in their ability to determine the amount of viable myocardium after a temporary ischemic event. Blood flow and segmental function may not necessarily demonstrate salvage, whereas metabolic parameters will determine cell survival. In a dog open chest model, short occlusion times of 20 min and subsequent reperfusion using C-11 palmitate as an index of fatty acid metabolism showed depresssion of fatty acid oxidation, which recovered after 3 hours of reperfusion, indicating the partial reversibility of the ischemic condition. In more extensive studies, using positron emission tomography (PET) and, as an indicator of glucose metabolism, fluoro-F-18-deoxyglucose (FDG); N-13 ammonia in addition to C-11 palmitate for the determination of blood flow; and ultrasonic crystals to measure shortening in the reperfused and control territories, the duration of occlusion was 3h. Metabolic studies were repeated 24 h, 1 week, and 4 weeks after the ischemic injury. Reperfused viable myocardium exhibited residual glucose metabolism with FDG, whereas fatty acid oxidation remained impaired for a longer period. Gradual metabolic recovery during a 4-week period was associated with the prolonged recovery of regional function, whereas a lack of residual metabolic activity indicated that little change in function was likely to occur. Increased FDG uptake and impaired C-11 palmitate turnover are characteristic of reversibly injured tissue. Therefore, PET studies may offer a unique potential for the evaluation of therapeutic measures such as thrombolysis and early revascularization.

  15. Effects of exercise training on myocardial fatty acid metabolism in rats with depressed cardiac function induced by transient ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liguang; Nohara, Ryuji; Hirai, Taku [Kyoto Univ. (Japan). Graduate School of Medicine] (and others)

    2001-06-01

    The effects of exercise training on metabolic and functional recovery after myocardial transient ischemia were investigated in a rat model. Male Wistar Kyoto rats were subjected either to a 30-min left coronary artery occlusion followed by reperfusion or to a sham operation. At 4 weeks after operation, the rats were randomly assigned either to sedentary conditions or to exercise training for 6 weeks. In the ischemic rats, pinhole SPECT (single photon emission computed tomography) imaging with thallium-201 ({sup 201}Tl) and {sup 123}I-({rho}-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) showed a reduction of both myocardial perfusion and fatty acid metabolism in the risk zone of the left ventricle (LV). The LV was dilated and the ejection fraction was decreased after ischemic injury. The severity score showed a significant decrease on both {sup 201}Tl and BMIPP ({sup 201}Tl, from 19.9{+-}2.7 to 17.0{+-}2.2, p<0.05; BMIPP, from 21.5{+-}2.4 to 18.6{+-}1.9, p<0.05) after exercise training in the ischemic trained rats, but did not change significantly in their sedentary counterparts. Plasma levels of free fatty acids normalized in the ischemic trained rats, but elevated in the ischemic sedentary rats (0.53{+-}0.05 vs 0.73{+-}0.06 mmol/L, p<0.05). Furthermore, the trained rats had a significant increase in LV stroke volume (0.25{+-}0.02 vs 0.21{+-}0.01 ml/beat, p<0.05) and adaptive cardiac hypertrophy. These findings demonstrate that adaptive improvements in myocardial perfusion, fatty-acid metabolism and LV function were induced by exercise training after transient ischemia. (author)

  16. Research Status of Myocardial Energy Metabolism in Patients with Sepsis%脓毒症患者心肌能量代谢的研究现状

    Institute of Scientific and Technical Information of China (English)

    彭良善

    2011-01-01

    心肌能量代谢障碍是导致脓毒症患者心脏功能衰竭的重要影响因素,改善患者心肌能量代谢是治疗脓毒症患者心肌损伤和改善预后的重要途径.目前心肌能量代谢障碍机制仍不明了.在正常情况下,线粒体是心肌能量代谢的重要场所,心肌主要是由脂肪酸和葡萄糖氧化代谢转换成的三磷酸腺苷为心脏提供能量.现从线粒体功能损伤、脂肪酸氧化代谢紊乱、糖代谢异常等与脓毒症心肌能量代谢障碍相关性方面的研究现状予以综述.%The disorder of myocardial energy metabolism is an important factor leading to heart failure in patients with sepsis; to improve myocardial energy metabolism is an important way for treating myocardial injury in patients with sepsis and improving the prognosis. So far mechanism of myocardial energy metabolism failure is still unclear. Normally , mitochondria are important sites of myocardial energy metabolism. Adenosine triphosphate produced from the oxidative metabolism of fatty acids and glucose provide energy for the heart.Here is to review the research situation of damage of mitochondria oxidation, fatty acid oxidation disorder, and the abnormal of glucose metabolism which are closely related to the disorder of myocardial energy metabolism in sepsis.

  17. Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine.

    Science.gov (United States)

    Mobini, Reza; Fu, Michael; Jansson, Per-Anders; Bergh, Claes-Håkan; Scharin Täng, Margareta; Waagstein, Finn; Andersson, Bert

    2006-03-01

    Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

  18. Quantitative proteomic changes during post myocardial infarction remodeling reveals altered cardiac metabolism and Desmin aggregation in the infarct region.

    Science.gov (United States)

    Datta, Kaberi; Basak, Trayambak; Varshney, Swati; Sengupta, Shantanu; Sarkar, Sagartirtha

    2017-01-30

    Myocardial infarction is one of the leading causes of cardiac dysfunction, failure and sudden death. Post infarction cardiac remodeling presents a poor prognosis, with 30%-45% of patients developing heart failure, in a period of 5-25years. Oxidative stress has been labelled as the primary causative factor for cardiac damage during infarction, however, the impact it may have during the process of post infarction remodeling has not been well probed. In this study, we have implemented iTRAQ proteomics to catalogue proteins and functional processes, participating both temporally (early and late phases) and spatially (infarct and remote zones), during post myocardial infarction remodeling of the heart as functions of the differential oxidative stress manifest during the remodeling process. Cardiac metabolism was the dominant network to be affected during infarction and the remodeling time points considered in this study. A distinctive expression pattern of cytoskeletal proteins was also observed with increased remodeling time points. Further, it was found that the cytoskeletal protein Desmin, aggregated in the infarct zone during the remodeling process, mediated by the protease Calpain1. Taken together, all of these data in conjunction may lay the foundation to understand the effects of oxidative stress on the remodeling process and elaborate the mechanism behind the compromised cardiac function observed during post myocardial infarction remodeling.

  19. Infarto del miocardio y metabolismo lipídico Myocardial infarction and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Lidia Margarita González González

    2003-12-01

    Full Text Available Se estudiaron 75 pacientes de ambos sexos que ingresaron en nuestra sala de Cuidados Intensivos con el diagnóstico de infarto agudo del miocardio a los cuales se les realizaron estudios del metabolismo lipídico. De ellos, 47 eran del sexo masculino para un 62, 6 %, 28 del sexo femenino para un 37,3 %, y la edad promedio fue de 60 años. Los principales antecedentes patológicos personales (APP encontrados fueron el tabaquismo, la hipertensión arterial y la diabetes mellitus, aunque en un grupo de enfermos (6, no tenían antecedentes patológicos recogidos en la historia clínica, pero quizás sí otros factores de riesgos como el sedentarismo, los malos hábitos dietéticos, el estrés, etc. Como resultado se encontró a un total de 52 pacientes (69,3 % con alteraciones lipídicas (siendo 19 correspondientes al colesterol y 33 a los triglicéridos, con 13,3 % de coincidencias en elevación de ambos. La edad promedio en la cual se observó la elevación lipídica fue de 58 años.75 patients of both sexes that were admitted in the Intensive Care Unit with the diagnosis of acute myocardial infarction and that underwent lipid metabolism studies, were studied. Of them, 47 were males, (62.6 %, and 28 were females (37.3 %. Average age was 60 years old. The main personal pathological antecedents were smoking and arterial hypertension. No pathological antecedents of diabetes mellitus were found in the medical history of 6 patients, but other risk factors such as sedentarism, bad diet habtis, stress, etc., were observed. As a result, it was found that 52 patients (69.3 % had lipid alterations (19 corresponded to cholesterol and 33 to triglycerides with 13.3 % of coincidences in the increase of both. The lipid increase was observed at an average age of 58 years old.

  20. Effects of Ropivacaine and Bupivacaine on Rabbit Myocardial Energetic Metabolism and Mitochondria Oxidation

    Institute of Scientific and Technical Information of China (English)

    张诗海; 姚尚龙; 李晴

    2003-01-01

    Summary: To compare the cardiotoxicity induced by ropivacaine and bupivacaine and to investigatethe mechanism of cardiotoxicity, 24 mature New Zealand rabbits were divided randomly into controlgroup (group C), ropivacaine group (group R) and bupivacaine group (group B). Hearts were drawnout rapidly from the anesthetized animals and cardiac perfusion was performed immediately. Ropiva-caine 500 ng/ml (group R) or bupivacaine 500 ng/ml (group B) was added to the perfusion solution.Ventricular myocardial ATP, ADP and AMP were measured with high performance liquid chro-matogram. The ability of myocardial mitochondria oxidation to pyruvate or palmitoylcarnitine wasdetected with Clark electrode. Our results showed that myocardial ATP and ADP decreased signifi-cantly (P<0. 05) in group R and most significantly (P<0. 01) in group B as compared with groupC. Myocardial ATP and ADP decreased most significantly (P<0. 01) in group B as compared withgroup R. The changes of myocardial AMP revealed significant difference among three groups. Thechanges of pyruvate oxidation exibited no significant difference among the three groups. Palmitoyl-carnitine oxidation decreased markedly (P<0. 05) in group R and most significantly (P<0. 01) ingroup B as compared with group C. The present study indicated that the inhibition of lipid substrateoxidation may be responsible for the cardiotoxicity induced by bupivacaine and ropivacaine. The car-diotoxicity induced by ropivacaine is far more less than bupivacaine.

  1. Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.

    Science.gov (United States)

    Skinner, F P; Levitzky, M G; Scott, R F; Fricks, J

    1975-05-01

    Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.

  2. Facts about Age-Related Macular Degeneration

    Science.gov (United States)

    ... Degeneration (AMD) > Facts About Age-Related Macular Degeneration Facts About Age-Related Macular Degeneration This information was ... an Eye Care Professional Last Reviewed: September 2015 Fact Sheet Blurb The National Eye Institute (NEI) is ...

  3. Reduced chronotropic reserve to the metabolic requirement during exercise in advanced heart failure with old myocardial infarction.

    Science.gov (United States)

    Yamabe, H; Kobayashi, K; Takata, T; Fukuzaki, H

    1987-03-01

    We studied the metabolic and cardiac responses to exercise by expiratory gas analysis in 40 patients with old myocardial infarction and 33 normal sedentary males. On the basis of exercise energy metabolism, the elevation of the respiratory quotient (RQ; RQ = VCO2/VO2) during exercise is caused by the increase of blood lactate due to the augmented anaerobic metabolism. Functional aerobic impairment (FAI) in our study was significantly advanced in the control group and the NYHA functional class I, class II and class III groups, that is, -2.3 +/- 11.2%, +14.8 +/- 10.4%, +27.8 +/- 13.8% and +49.4 +/- 2.8%, respectively. The delta RQ values were similar among all groups; 0.29 respectively. The delta RQ values were similar among all groups; 0.29 +/- 0.06, 0.28 +/- 0.07, 0.27 +/- 0.07 and 0.29 +/- 0.09, respectively. Functional chronotropic impairment (FCI) for the same groups was -0.9 +/- 7.0%, +1.4 6.1%, +3.8 +/- 4.8% and +8.7 +/- 6.0%, and that of the class III group was significantly larger than that of the control group. Thus, in the class III congestive heart failure group, the chronotropic response to the metabolic requirement was impaired in comparison to the control group. It was concluded that the reduced chronotropic reserve was present in NYHA class III patients with old myocardial infarction, and that this mechanism might contribute to a decrease in the pump reserve of the heart, resulting in further impairment of physical capacity in these patients.

  4. Temporal Changes in Phosphatidylserine Expression and Glucose Metabolism after Myocardial Infarction: An in Vivo Imaging Study in Mice

    Directory of Open Access Journals (Sweden)

    Sebastian Lehner

    2012-11-01

    Full Text Available Positron emission tomography (PET for in vivo monitoring of phosphatidylserine externalization and glucose metabolism can potentially provide early predictors of outcome of cardioprotective therapies after myocardial infarction. We performed serial [68Ga]annexin A5 PET (annexin-PET and [18F]fluorodeoxyglucose PET (FDG-PET after myocardial infarction to determine the time of peak phosphatidylserine externalization in relation to impaired glucose metabolism in infracted tissue. Annexin- and FDG-PET recordings were obtained in female (C57BL6/N mice on days 1 to 4 after ligation of the left anterior descending (LAD artery. [68Ga]annexin A5 uptake (%ID/g in the LAD artery territory increased from 1.7 ± 1.1 on day 1 to 5.0 ± 3.3 on day 2 and then declined to 2.0 ± 1.4 on day 3 (p = .047 vs day 2 and 1.6 ± 1.4 on day 4 (p = .014 vs day 2. These results matched apoptosis rates as estimated by autoradiography and fluorescein staining. FDG uptake (%ID/g declined from 28 ± 14 on day 1 to 14 ± 3.5 on day 4 (p < .0001 vs day 1. Whereas FDG-PET revealed continuous loss of cell viability after permanent LAD artery occlusion, annexin-PET indicated peak phosphatidylserine expression at day 2, which might be the optimal time point for therapy monitoring.

  5. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  6. Clinical motivation for P-31 MRS studies on the myocardial energy metabolism of brain dead cats

    NARCIS (Netherlands)

    Bruinsma, GJBB; van Echteld, CJA

    2003-01-01

    Hemodynamic instability of the brain dead potential heart donor is an exclusion criterion for heart donation for transplantation. Based on the results of myocardial biopsies it has been reported that brain death-related catecholamine induced damage of the heart causes depletion of high-energy phosph

  7. Coronary hemodynamics and myocardial metabolism during and after pacing stress in normal humans.

    Science.gov (United States)

    Camici, P; Marraccini, P; Marzilli, M; Lorenzoni, R; Buzzigoli, G; Puntoni, R; Boni, C; Bellina, C R; Klassen, G A; L'Abbate, A

    1989-09-01

    We investigated coronary hemodynamics, myocardial utilization of circulating substrates (by coronary sinus catheterization), and overall use of oxidative fuels (by regional indirect calorimetry) in healthy adults during incremental atrial pacing (up to 159 +/- 9 beats/min), and during 25 min of recovery. Great cardiac vein flow (thermodilution) increased from 52 +/- 9 to 115 +/- 15 ml/min (P less than 0.001) with pacing; myocardial O2 uptake (301 +/- 53 to 593 +/- 71 mumol/min, P less than 0.001) and CO2 production (225 +/- 37 to 518 +/- 66 mumol/min, P less than 0.005) paralleled the pacing-induced rise in rate-pressure product (9.4 +/- 0.9 to 21.1 +/- 1.1 mmHg.beat. min-1.10(-3), P less than 0.001). During recovery, all the above variables returned to base line within 5 min, but myocardial O2 extraction remained depressed (67 +/- 2 vs. 71 +/- 3%, P less than 0.05). Circulating glucose uptake rose linearly with pacing (P less than 0.05) and remained above base line throughout recovery. By contrast, free fatty acid (FFA) uptake (10 mumol/min) did not increase with pacing and fell during recovery (P less than 0.01). Calorimetry, however, showed that net lipid oxidation exceeded FFA uptake throughout the study, whereas net carbohydrate oxidation was small at base line, rose significantly at maximal pacing (62% of myocardial energy output), and remained above base line during recovery (32% of energy output). In the basal state as well as during recovery, myocardial uptake of glucose equivalents (lactate plus glucose plus pyruvate) was in excess of carbohydrate oxidation, indicating nonoxidative disposal of these substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Protective Effect of Qiliqiangxin Capsule on Energy Metabolism and Myocardial Mitochondria in Pressure Overload Heart Failure Rats

    Directory of Open Access Journals (Sweden)

    Junfang Zhang

    2013-01-01

    Full Text Available Qiliqiangxin capsule (QL was developed under the guidance of TCM theory of collateral disease and had been shown to be effective and safe for the treatment of heart failure. The present study explored the role of and mechanism by which the herbal compounds QL act on energy metabolism, in vivo, in pressure overload heart failure. SD rats received ascending aorta constriction (TAC to establish a model of myocardial hypertrophy. The animals were treated orally for a period of six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic constriction and improved hemodynamics. This effect was linked to the expression levels of the signaling factors in connection with upregulated energy and the regulation of glucose and lipid substrate metabolism and with a decrease in metabolic intermediate products and the protection of mitochondrial function. It is concluded that QL may regulate the glycolipid substrate metabolism by activating AMPK/PGC-1α axis and reduce the accumulation of free fatty acids and lactic acid, to protect cardiac myocytes and mitochondrial function.

  9. Effect of Shen-Fu Injection Pretreatment to Myocardial Metabolism During Untreated Ventricular Fibrillation in a Porcine Model

    Institute of Scientific and Technical Information of China (English)

    Wei Yuan; Jun-Yuan Wu; Guo-Xing Wang; Qian Zhang; Chun-Sheng Li

    2015-01-01

    Background: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation.We hypothesized that SFI may also have an influence on myocardial metabolism during ventricular fibrillation (VF).In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardium.Methods: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group).Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection;the SA group received an equal amount of sodium chloride solution.The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF.Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na+-K+-ATPase and Ca2+-ATPase enzyme activities were measured after untreated VF.Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals.Results: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group.Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group.In both the SA and SFI groups, the levels of dopamine, norepinephrine, and epinephrine increased significantly.There were no statistical differences between the two groups.The content ofATP, ADP, and phosphocreatine in the SFI group was higher than those in the SA group.The activity of LV Na+-K+-ATPase was significantly higher in the SFI group than in the SA group.Amplitude mean spectrum area (AMSA) was significantly lower in the SA and

  10. Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model.

    Science.gov (United States)

    Kajimoto, Masaki; Ledee, Dolena R; Olson, Aaron K; Isern, Nancy G; Des Rosiers, Christine; Portman, Michael A

    2015-10-01

    Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Odd-numbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant β-oxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Fifteen male Yorkshire pigs (26-45 days old) with 8-h ECMO received either normal saline, heptanoate (odd-numbered MCFA), or octanoate (even-numbered MCFA) at 2.3 μmol·kg body wt(-1)·min(-1) as MCFAs systemically during ECMO (n = 5/group). The 13-carbon ((13)C)-labeled substrates ([2-(13)C]lactate, [5,6,7-(13)C3]heptanoate, and [U-(13)C6]leucine) were systemically infused as metabolic markers for the final 60 min before left ventricular tissue extraction. Extracted tissues were analyzed for the (13)C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]-to-[ADP] ratio compared with other groups. Unexpectedly, octanoate and heptanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC compared with control. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in protein synthesis rate. In conclusion, octanoate provides energetic advantages to the heart over heptanoate.

  11. Differential Effects Of Octanoate And Heptanoate On Myocardial Metabolism During Extracorporeal Membrane Oxygenation In An Infant Swine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Ledee, Dolena R.; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2015-10-01

    Background: Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Oddnumbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant betaoxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Methods: Fifteen male Yorkshire pigs (26-45 days old) with 8-hour ECMO were received either normal saline, heptanoate (odd-numbered MCFA) or octanoate (even-numbered MCFA) at 2.3 μmol/kg body wt/min as MCFAs systemically during ECMO (n = 5 per group). The 13-Carbon (13C)-labeled substrates ([2-13C]lactate, [5,6,7-13C3]heptanoate and [U-13C6]leucine) were systemically infused as metabolic markers for the final 60 minutes before left ventricular tissue extraction. Extracted tissues were analyzed for the 13C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Results: Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]/[ADP] ratio compared with other http://mc.manuscriptcentral.com/jpen Journal of Parenteral and Enteral Nutrition For Peer Review groups. Unexpectedly, octanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC as well as heptanoate. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in fractional protein synthesis rate. Conclusion: Octanoate provides energetic advantages to the heart over heptanoate, while preserving protein synthesis.

  12. Nut consumption and age-related disease.

    Science.gov (United States)

    Grosso, G; Estruch, R

    2016-02-01

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

  13. Dehydroepiandrosterone and age-related cognitive decline.

    Science.gov (United States)

    Sorwell, Krystina G; Urbanski, Henryk F

    2010-03-01

    In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

  14. Animal models of age related macular degeneration.

    Science.gov (United States)

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

    2012-08-01

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

  15. Impaired myocardial blood flow reserve in subjects with metabolic syndrome analyzed using positron emission tomography and N-13 labeled ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Teragawa, Hiroki; Kihara, Yasuki [Hiroshima University Graduate School of Biomedical Sciences, Department of Cardiovascular Medicine, Hiroshima (Japan); Morita, Koichi; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Shishido, Hiroki; Otsuka, Nobuaki; Hirokawa, Yutaka [Hiroshima Heiwa Clinic, Hiroshima (Japan); Chayama, Kazuaki [Hiroshima University Graduate School of Biomedical Sciences, Department of Molecular Science and Medicine, Hiroshima (Japan)

    2010-02-15

    Coronary vasomotor response might be impaired in metabolic syndrome (MS); however, the precise abnormality has not been elucidated. The aim of this study was to assess coronary-vasomotor response in MS subjects using N-13 labeled ammonia and positron emission tomography. Myocardial blood flow (MBF) was measured at rest and during adenosine infusion in MS subjects (n = 13, MS group) with no definite evidence of heart disease and in subjects without MS (n = 14, non-MS group). Coronary vascular resistance (CVR) was calculated by dividing the mean aortic blood pressure by MBF. Myocardial blood flow reserve (MFR) was calculated as the ratio of the MBF during adenosine infusion to that during rest. Blood chemical parameters were measured to evaluate their relationship with MFR. During adenosine infusion, MBF was lower (p = 0.0085) and CVR higher (p = 0.0128) in the MS group than in the non-MS group and MFR was significantly lower in the MS group than in the non-MS group (2.13 {+-} 0.99 vs. 3.38 {+-} 0.95, p = 0.0027). Multivariate analysis demonstrated that the homeostasis model assessment-insulin resistance (p < 0.05) and the presence of hypertension (p < 0.05) were independent determinants of MFR. The results indicate that MFR was impaired in MS subjects, suggesting that an abnormal coronary microvascular response occurred in these subjects. This abnormality may have been partially due to insulin resistance and hypertension. (orig.)

  16. Persistent abnormal coronary flow reserve in association with abnormal glucose metabolism affects prognosis in acute myocardial infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2011-01-01

    Objectives: To evaluate changes in coronary flow reserve (CFR) over time after acute myocardial infarction (AMI) in relation to left ventricular (LV) function and glucometabolic state and prognostic implication of abnormal CFR. Methods: 154 patients with first time AMI had a comprehensive...... baseline CFR (P = 0.004), S' (P = 0.045) and abnormal glucose metabolism (P = 0.001) were predictors of a decreased CFR at 3 months of follow-up. In multivariate analyses abnormal glucose metabolism (OR: 5.3; 95%CI: 1.9-14.4; P = 0.001) remained a predictor of decreased CFR at follow-up, furthermore...... baseline CFR (OR: 0.5; 95%CI: 0.25-0.94; P = 0.032) and S' (OR: 0.67; 95% CI: 0.47-0.94; P = 0.021) was predictors of decreased CFR. Finally, CFR was associated with a lower risk of cardiac events in patients with normal glucose metabolism (HR: 0.64; 95% CI: 0.22-1.9; P = 0.42) than in patients...

  17. Myocardial oxidative metabolism is increased due to haemodynamic overload in patients with aortic valve stenosis: assessment using {sup 11}C-acetate positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Naya, Masanao; Chiba, Satoru; Iwano, Hiroyuki; Yamada, Satoshi; Tsutsui, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Cardiovascular Medicine, Sapporo (Japan); Katoh, Chietsugu [Hokkaido University Graduate School of Medicine, Department of Health Science, Sapporo (Japan); Manabe, Osamu; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan); Yoshinaga, Keiichiro [Hokkaido University Graduate School of Medicine, Department of Molecular Imaging, Sapporo (Japan); Matsui, Yoshiro [Hokkaido University Graduate School of Medicine, Department of Cardiovascular Surgery, Sapporo (Japan)

    2010-12-15

    The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS. Myocardial {sup 11}C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR. Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068 {+-} 0.014 vs 0.048 {+-} 0.007/min, p < 0.01). Kmono was significantly correlated with age (r = 0.58, p < 0.01), left ventricular (LV) mass index (r = 0.61, p < 0.01) and estimated systolic LV pressure (r = 0.81, p < 0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono ({beta} = 0.93, p < 0.01). After AVR, Kmono (from 0.075 {+-} 0.012 to 0.061 {+-} 0.014/min, p = 0.043) and LV mass index (from 183 {+-} 49 to 124 {+-} 41 g/ml{sup 2}, p = 0.043) were significantly decreased despite no significant changes in rate-pressure product. Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV. (orig.)

  18. Influence of recombinant human brain natriuretic peptide on myocardial enzymes, serum cardiac function indexes and oxygen metabolism of patients with open heart surgery with cardiopulmonary bypass

    Institute of Scientific and Technical Information of China (English)

    Shu-Tian Song; Ming Yang; Kun-Peng Li; Juan Xu; Chuan-Ming Bai; Ji-Wu Zhou

    2016-01-01

    Objective:To investigate and analyze the influence of recombinant human brain natriuretic peptide on myocardial enzymes, serum cardiac function indexes and oxygen metabolism of patients with open heart surgery with cardiopulmonary bypass.Methods:A total of 42 patients with open heart surgery with cardiopulmonary bypass during the period of June 2014 to January 2016 were randomly divided into the control group of 21 cases and the observation group of 21 cases. The control group was treated with routine postoperative treatment, and the observation group was treated with recombinant human brain natriuretic peptide on the basic treatment of control group, then the myocardial enzymes, serum cardiac function indexes and oxygen metabolism indexes of the two groups before the surgery and at 2 h, 12 h and 24 h after the surgery were respectively detected and compared.Results: There were no significant difference in myocardial enzymes, serum cardiac function indexes and oxygen metabolism indexes between two groups before the surgery (allP>0.05), while the myocardial enzymes and serum cardiac function indexes of the observation group at 2 h ,12 h and 24 h after the surgery were all significantly lower than those of control group, the oxygen metabolism indexes were significantly better than the levels of control group (allP<0.05).Conclusions:The recombinant human brain natriuretic peptide can effectively improve the myocardial enzymes, serum cardiac function indexes and oxygen metabolism state of patients with open heart surgery with cardiopulmonary bypass, and it has application value for the patients with the surgery is higher.

  19. Global Metabolic Profiling of Plasma Shows that Three-Year Mild-Caloric Restriction Lessens an Age-Related Increase in Sphingomyelin and Reduces L-leucine and L-phenylalanine in Overweight and Obese Subjects.

    Science.gov (United States)

    Kim, Minjoo; Lee, Sang-Hyun; Lee, Jong Ho

    2016-12-01

    The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 40-59 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (Δ) in BMI positively correlated with the ΔTG, ΔHOMA-IR, ΔL-leucine, and ΔSM (d18:0/16:1). The ΔHOMA-IR positively correlated with ΔTG, ΔL-leucine, ΔL-phenylalanine, and ΔSM (d18:0/16:1). The weight loss resulting from three-year mild-caloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).

  20. Immunosenescence of the CD8(+) T cell compartment is associated with HIV-infection, but only weakly reflects age-related processes of adipose tissue, metabolism, and muscle in antiretroviral therapy-treated HIV-infected patients and controls

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Langkilde, Anne; Haupt, Thomas Huneck

    2015-01-01

    -related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA...... differentiated and mature CD8 (+) T cell phenotypes. PD-1 and KLRG1 expression did not differ between HIV(+) and Controls, but depended on differentiation and maturation stages of the cells. CD8 (+) T cell maturation was associated with age. KLRG1 expression was associated with age, metabolic syndrome, visceral...

  1. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular diseas

  2. Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris.

    Science.gov (United States)

    Rousseau, M F; Vincent, M F; Cheron, P; van den Berghe, G; Charlier, A A; Pouleur, H

    1985-01-01

    The effects of intravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. After nicardipine, coronary blood flow and oxygen content in the coronary sinus increased significantly. The indices of inotropic state increased slightly, and the rate of isovolumic LV pressure fall improved. Myocardial oxygen consumption was unchanged despite the significant reduction in pressure-rate product, but LV lactate uptake increased, particularly during the cold pressor test. When nicardipine was administered after propranolol, the indices of inotropic state were unaffected. The lack of direct effect of nicardipine on LV inotropic state was further confirmed by intracoronary injection of 0.1 and 0.2 mg in a separate group of 10 patients. It is concluded that the nicardipine-induced coronary dilatation seems to improve perfusion and aerobic metabolism in areas with chronic ischaemia, resulting in reduced lactate production and augmented oxygen consumption.

  3. Effects of nicardipine and nisoldipine on myocardial metabolism, coronary blood flow and oxygen supply in angina pectoris.

    Science.gov (United States)

    Rousseau, M F; Vincent, M F; Van Hoof, F; Van den Berghe, G; Charlier, A A; Pouleur, H

    1984-12-01

    The effects of the calcium antagonists nicardipine and nisoldipine on left ventricular (LV) metabolism were analyzed in 32 patients with angina pectoris. Measurements were made at a fixed heart rate under the basal state and during a cold pressor test (CPT). After administration of the drugs, coronary blood flow increased significantly and the mean aortic pressure decreased by 10% (p less than 0.01) in the basal state and by 11% (p less than 0.01) during CPT. Despite the reduction in pressure-rate product, myocardial oxygen consumption was unchanged in the basal state (18 +/- 4 vs 19 +/- 4 ml/min, difference not significant) and during CPT (21 +/- 5 vs 21 +/- 5 ml/min, difference not significant); this discrepancy between a reduced pressure-rate product and an unchanged oxygen consumption was also noted when nicardipine was given after propranolol (0.1 mg/kg; 12 patients). Both agents also increased LV lactate uptake, particularly during CPT (+13 mumol/min, p less than 0.05 vs control CPT) and reduced LV glutamine production. In 10 patients in whom 14C-lactate was infused, the chemical LV lactate extraction ratio increased more than the 14C-lactate extraction ratio after administration of the drugs, indicating a reduction in LV lactate production. The data are consistent with the hypothesis that nicardipine and nisoldipine improve perfusion and aerobic metabolism in chronically ischemic areas, resulting in an augmented oxygen consumption and in a reduced lactate production.

  4. Mitochondrial sirtuins as therapeutic targets for age-related disorders.

    Science.gov (United States)

    Shih, Jennifer; Donmez, Gizem

    2013-03-01

    Sirtuins are a class of histone deacetylases that have a wide range of regulatory roles in the cell. Three sirtuins, SIRT3 to SIRT5, localize to and function within the mitochondria. Mitochondrial dysfunction is thought to be the underlying mechanism of several age-related diseases, such as metabolic syndrome, cancer, and neurodegeneration. This review examines current evidence that mitochondrial sirtuins are involved in regulating mitochondrial function and pathogenesis.

  5. Distinct properties and metabolic mechanisms of postresuscitation myocardial injuries in ventricular fibrillation cardiac arrest versus asphyxiation cardiac arrest in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Wu Caijun; Li Chunsheng; Zhang Yi; Yang Jun

    2014-01-01

    Background The two most prevalent causes of sudden cardiac death are ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA).Profound postresuscitation myocardial dysfunction has been demonstrated in both VFCA and ACA animal models.Our study aimed to characterize the two porcine models of cardiac arrest and postresuscitation myocardial metabolism dysfunction.Methods Thirty-two pigs were randomized into two groups.The VFCA group (n=16) were subject to programmed electrical stimulation and the ACA group (n=16) underwent endotracheal tube clamping to induce cardiac arrest (CA).Once induced,CA remained untreated for a period of 8 minutes.Two minutes following initiation of cardiopulmonary resuscitation (CPR),defibrillation was attempted until return of spontaneous circulation (ROSC) was achieved or animals died.To assess myocardial metabolism,18F-FluoroDeoxyGlucose Positron Emission Tomography was performed at baseline and 4 hours after ROSC.Results ROSC was 100% successful in VFCA and 50% successful in ACA.VFCA had better mean arterial pressure and cardiac output after ROSC than ACA.Arterial blood gas analysis indicated more detrimental metabolic disturbances in ACA compared with VFCA after ROSC (ROSC 0.5 hours,pH:7.01±0.06 vs.7.21±0.03,P<0.01; HCO3-:(15.83±2.31 vs.20.11±1.83) mmol/L,P<0.01; lactate:(16.22±1.76 vs.5.84±1.44) mmol/L,P<0.01).Myocardial metabolism imaging using Positron Emission Tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA at 4 hours after ROSC (the maximum standardized uptake value of the whole left ventricular:1.00±0.17 vs.1.93±0.27,P<0.01).Lower contents of myocardial energy metabolism enzymes (Na+-K+-ATPase enzyme activity,Ca2+-ATPase enzyme activity,superoxide dismutase and phosphodiesterase) were found in ACA relative to VFCA.Conclusions Compared with VFCA,ACA causes more severe myocardium injury and metabolism hindrance,therefore they

  6. Pathophysiology of age-related hearing loss (peripheral and central).

    Science.gov (United States)

    Lee, Kyu-Yup

    2013-09-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Extrinsic factors include noise, ototoxic medication and diet. However, presbycusis may not be related to the intrinsic and extrinsic factors separately. Presbycusis affects not only the physical, cognitive and emotional activities of patients, but also their social functioning. As a result, patients' quality of life deteriorates, compounded by various symptoms including depression, social isolation and lower self-esteem. Presbycusis is classified into six categories, as based on results of audiometric tests and temporal bone pathology, established by Schuknecht (1993): sensory, neural, metabolic or strial, cochlear conductive, mixed and indeterminate types. Among these, metabolic presbycusis is the mainstay of presbycusis types. Age-related changes also develop in the central hearing system. Functional decline of the central auditory system, caused by aging, reduces speech-understanding in noisy background and increase temporal processing deficits in gap-detection measures. This study reviews the literature on the age-related hearing loss.

  7. Genes, inflammation, and age-related diseases

    OpenAIRE

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying gen...

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

    Science.gov (United States)

    2017-01-12

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

  9. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  10. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  11. Age-related changes in triathlon performances.

    Science.gov (United States)

    Lepers, R; Sultana, F; Bernard, T; Hausswirth, C; Brisswalter, J

    2010-04-01

    The aim of this study was two-fold: i) to analyse age-related declines in swimming, cycling, and running performances for Olympic and Ironman triathlons, and ii) to compare age-related changes in these three disciplines between the Olympic and Ironman triathlons. Swimming, cycling, running and total time performances of the top 10 males between 20 and 70 years of age (in 5 years intervals) were analysed for two consecutive world championships (2006 and 2007) for Olympic and Ironman distances. There was a lesser age-related decline in cycling performance (ptriathlon in cycling (>55 years) and running (>50 years), respectively. In contrast, an age-related decline in swimming performance seemed independent of triathlon distance. The age-related decline in triathlon performance is specific to the discipline, with cycling showing less declines in performance with age than swimming and running. The magnitude of the declines in cycling and running performance at Ironman distance is greater than at Olympic distance, suggesting that task duration exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  12. L-propionylcarnitine does not affect myocardial metabolic or functional response to chronotropic and inotropic stimulation after repetitive ischemia in anesthetized pigs.

    Science.gov (United States)

    Duncker, D J; Sassen, L M; Bartels, G L; van Meegen, J R; McFalls, E O; Krams, R; Bezstarosti, K; Lamers, J M; Verdouw, P D

    1993-09-01

    In postischemic myocardium, fatty acid oxidation may be deficient owing to depletion of carnitine and citric acid cycle intermediates and fatty acylCoA-induced inhibition of adenine nucleotide translocase. During postischemic stress, the impairment of the fatty acid oxidation may become more apparent. We therefore investigated in open-chest anesthetized pigs the effect of L-propionylcarnitine [100 mg/kg per day orally (p.o.) for 3 days and 50 mg/kg intravenously (i.v.) 2 h before the first occlusion; n = 13] on myocardial function and metabolism of postischemic (two cycles of 10-min occlusion each followed by 30-min reperfusion) myocardium under resting conditions and during chronotropic and inotropic stimulation with dobutamine. Myocardial levels of free carnitine were higher after pretreatment (5.7 +/- 1.4 vs. 4.0 +/- 1.3 mumol/g protein, p Propionylcarnitine-treated animals displayed slightly better postischemic recovery of systolic SS than did control animals; to 39 and 28% (p = 0.056) of baseline, respectively, probably owing to a reduction in arterial blood pressure (BP), because L-propionylcarnitine prevented the increase in systemic vascular resistance produced by ischemia-reperfusion. L-Propionylcarnitine did not affect myocardial metabolic and contractile functional responses to chronotropic and inotropic stimulation. In a model of repetitive myocardial ischemia, L-propionylcarnitine prevents systemic vasoconstriction in response to ischemia and reperfusion and, probably as a result of the lower afterload, slightly ameliorates postischemic hypofunction, but loss of carnitine apparently does not play a role in myocardial hypofunction after brief repetitive ischemia and reperfusion in pigs.

  13. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  14. [Pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  15. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    DEFF Research Database (Denmark)

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E

    2009-01-01

    tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend)

  16. Folate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

    Aging is associated with increased risk of cardiovascular and neurodegenerative disorders and an increase in their risk factors, such as decreased concentrations of folate and increased concentrations of homocysteine. The association of folate and homocysteine with age-related disease and, most impo

  17. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  18. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

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

  19. Cardioselective Dominant-negative Thyroid Hormone Receptor (Δ337T) Modulates Myocardial Metabolism and Contractile Dfficiency

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Olson, Aaron; Ge, Ming; Ning, Xue-Han; Buroker, Norman E.; Chung, Youngran; Jue, Thomas; Portman, Michael A.

    2008-06-03

    Dominant- negative thyroid hormone receptors (TRs) show elevated expression relative to ligand-binding TRs during cardiac hypertrophy. We tested the hypothesis that overexpression of a dominant-negative TR alters cardiac metabolism and contractile efficiency (CE). We used mice expressing the cardioselective dominant-negative TRβ1 mutation Δ337T. Isolated working Δ337T hearts and nontransgenic control (Con) hearts were perfused with 13C-labeled free fatty acids (FFA), acetoacetate (ACAC), lactate, and glucose at physiological concentrations for 30 min. 13C NMR spectroscopy and isotopomer analyses were used to determine substrate flux and fractional contributions (Fc) of acetyl-CoA to the citric acid cycle (CAC). Δ337T hearts exhibited rate depression but higher developed pressure and CE, defined as work per oxygen consumption (MV˙ O2). Unlabeled substrate Fc from endogenous sources was higher in Δ337T, but ACAC Fc was lower. Fluxes through CAC, lactate, ACAC, and FFA were reduced in Δ337T. CE and Fc differences were reversed by pacing Δ337T to Con rates, accompanied by an increase in FFA Fc. Δ337T hearts lacked the ability to increase MV˙ O2. Decreases in protein expression for glucose transporter-4 and hexokinase-2 and increases in pyruvate dehydrogenase kinase-2 and -4 suggest that these hearts are unable to increase carbohydrate oxidation in response to stress. These data show that Δ337T alters the metabolic phenotype in murine heart by reducing substrate flux for multiple pathways. Some of these changes are heart rate dependent, indicating that the substrate shift may represent an accommodation to altered contractile protein kinetics, which can be disrupted by pacing stress.

  20. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  1. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra;

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  2. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  3. Depression in Age-Related Macular Degeneration

    OpenAIRE

    Casten,Robin; Rovner,Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depressio...

  4. Evaluation of Age-Related Hearing Loss

    OpenAIRE

    2013-01-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide imp...

  5. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  6. Abnormalities in myocardial contractility, metabolism and perfusion reserve in non-stenotic coronary segments in heart failure patients

    NARCIS (Netherlands)

    van den Heuvel, AFM; Bax, JJ; Blanksma, PK; Vaalburg, W; Crijns, HJGM; van Veldhuisen, DJ

    2002-01-01

    Objective: Myocardial blood flow (MBF) reserve is impaired in congestive heart failure (CHF), while fluorine-18-deoxyglucose ((18)FDG) uptake is relatively preserved. To determine whether this mismatch could be interpreted as ischemia, we performed dobutamine stress echocardiography (DSE). Methods:

  7. Carbohydrate and lipid metabolism indices dynamic in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity in 6 months and 1 year after myocardial revascularization

    Directory of Open Access Journals (Sweden)

    P. P. Kravchun

    2016-11-01

    Full Text Available Nowadays conservative therapy and reperfusion techniques, which include thrombolytic therapy and percutaneous coronary intervention considered as the main strategies for the acute coronary syndrome treatment. Aim. To assess carbohydrate and lipid metabolism in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity in 6 months and 1 year after myocardial revascularization. Methods and results. 58 patients who underwent thrombolytic therapy and 32 patients who underwent percutaneous coronary intervention were examined. Glucose level was determined by glucose oxidation method, insulin – by ELISA and lipid profile – according to the standard biochemical methods. It was established that in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity positive effect was defined in carbohydrate and lipid metabolism by reducing of serum glucose level, insulin, total cholesterol, low and very low-density lipoproteins, triglycerides and increasing of high density lipoproteins, cholesterol in 6 months and 1 year after reperfusion therapy. Significant differences in carbohydrate and lipid metabolism in the examined patients, depending on the type of reperfusion therapy, have not been detected in 6 months and 1 year after revascularization. Conclusion. Comparative analysis of different methods of myocardial revascularization did not show any advantages of them.

  8. 曲美他嗪优化心肌代谢的研究进展%Research Progress of Trimetazidine on Optimizing Myocardial Metabolism

    Institute of Scientific and Technical Information of China (English)

    张莹(综述); 史大卓(审校)

    2015-01-01

    心肌能量代谢是影响冠心病患者心功能的重要因素。曲美他嗪作为调节心肌能量代谢药物,通过降低游离脂肪酸的氧化速率,减轻线粒体内钙聚积,使心肌细胞内氧自由基产生减少,发挥线粒体保护、抗氧化应激等多方面的药理作用,从而发挥对心肌的保护作用,维持ATP的产生和缺血心肌细胞的能量代谢及收缩功能。临床广泛应用于心绞痛、心力衰竭、心肌梗死、糖尿病合并冠心病及经皮冠状动脉介入围术期等的治疗。%Myocardial energy metabolism is an important factor that affects the heart function in patients with coronary heart disease.Trimetazidine,as a myocardial metabolism regulating agent,through lowering the oxidation speed of free fatty acids ,reducing the mitochondrial calcium accumulation and decreasing the genera-tion of oxyradical, plays the pharmacological effects of anti-oxidative stress and mitochondria protection to achieve the purpose of protecting the myocardium,to maintain the ATP generation and the energy metabolism and contractile function of ischemic cardiac muscle cells ,which is widely applied in the treatment of angina , heart failure,myocardial infarction and peri-operation period of percutaneous coronary intervention in clinical .

  9. Evaluation of age-related hearing loss.

    Science.gov (United States)

    Kim, Tae Su; Chung, Jong Woo

    2013-09-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide improved communication ability to users. But, simple auditory rehabilitation is ineffective in managing the central auditory processing disorder and the psychosocial problem of presbycusis. The evaluation of central auditory processing disorder and psychosocial disorder in presbycusis should not be overlooked while providing auditory rehabilitation.

  10. Age-related perspectives and emotion processing.

    Science.gov (United States)

    Lynchard, Nicholas A; Radvansky, Gabriel A

    2012-12-01

    Emotion is processed differently in younger and older adults. Older adults show a positivity effect, whereas younger adults show a negativity effect. Socioemotional selectivity theory suggests that these effects can be elicited in any age group when age-related perspectives are manipulated. To examine this, younger and older adults were oriented to actual and age-contrasting possible selves. Emotion activations were assessed using lexical decision. In line with socioemotional selectivity theory, shifts in emotion orientation varied according to perspective, with both younger and older adults showing a negativity effect when a younger adult perspective was taken and a positivity effect when an older adult perspective was taken.

  11. [Age-related macular degeneration (AMD)].

    Science.gov (United States)

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  12. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Toft, Ulla; Linneberg, Allan;

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD....

  13. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2014-01-01

    Full Text Available This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R. At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7% and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

  14. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    Science.gov (United States)

    Di Filippo, C.; Rossi, C.; Ferraro, B.; Maisto, R.; De Angelis, A.; Ferraraccio, F.; Rotondo, A.; D'Amico, M.

    2014-01-01

    This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF) rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R). At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg) reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7%) and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R. PMID:25110402

  15. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

    Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

  16. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  17. Early Detection of Regional and Global Left Ventricular Myocardial Function Using Strain and Strain-rate Imaging in Patients with Metabolic Syndrome

    Institute of Scientific and Technical Information of China (English)

    Qin Wang; Qi-Wei Sun; Dan Wu; Ming-Wu Yang; Rong-Juan Li; Bo Jiang; Jiao Yang

    2015-01-01

    Background:Strain and strain-rate imaging (SRI) have been found clinically useful in the assessment of cardiac systolic and diastolic function as well as providing new insights in deciphering cardiac physiology and mechanics in cardiomyopathies,and identifying early subclinical changes in various pathologies.The aim of this study was to evaluate the regional and global left ventricular (LV) myocardial function in metabolic syndrome (MS) with SRI so that we can provide more myocardial small lesions in patients with MS,which is robust and reliable basis for early detection of LV function.Methods:Thirty-nine adults with MS were enrolled in the study.There was a control group of 39 healthy adults.In addition to classic echocardiographic assessment of LV global functional changes,SRI was used to evaluate regional and global LV function.Including:Peak systolic strain (S),peak systolic strain-rate (SR-s),peak diastolic strain-rate (SR-e).Results:There were no statistically significant differences between MS and controls in all traditional parameters of LV systolic function.On the other hand,significant differences were observed between MS and the control group in most of the parameters of S,SR-s,SR-e in regional LV function.Multiple stepwise regression analyses revealed that S and SR significantly were negatively correlated with blood pressure,waist circumference,fasting plasma glucose,uric acid,suggesting that risk factories were relevant to regional systolic dysfunction.Conclusion:In MS with normal LV ejection fraction,there was regional myocardial dysfunction,risk factors contributed to the impairment of systolic and diastolic function of the regional myocardium.Assessment of myocardial function using SRI could be more accurate in MS patient evaluation than conventional echocardiography alone.

  18. Early Detection of Regional and Global Left Ventricular Myocardial Function Using Strain and Strain-rate Imaging in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Qin Wang

    2015-01-01

    Full Text Available Background: Strain and strain-rate imaging (SRI have been found clinically useful in the assessment of cardiac systolic and diastolic function as well as providing new insights in deciphering cardiac physiology and mechanics in cardiomyopathies, and identifying early subclinical changes in various pathologies. The aim of this study was to evaluate the regional and global left ventricular (LV myocardial function in metabolic syndrome (MS with SRI so that we can provide more myocardial small lesions in patients with MS, which is robust and reliable basis for early detection of LV function. Methods: Thirty-nine adults with MS were enrolled in the study. There was a control group of 39 healthy adults. In addition to classic echocardiographic assessment of LV global functional changes, SRI was used to evaluate regional and global LV function. Including: Peak systolic strain (S, peak systolic strain-rate (SR-s, peak diastolic strain-rate (SR-e. Results: There were no statistically significant differences between MS and controls in all traditional parameters of LV systolic function. On the other hand, significant differences were observed between MS and the control group in most of the parameters of S, SR-s, SR-e in regional LV function. Multiple stepwise regression analyses revealed that S and SR significantly were negatively correlated with blood pressure, waist circumference, fasting plasma glucose, uric acid, suggesting that risk factories were relevant to regional systolic dysfunction. Conclusion: In MS with normal LV ejection fraction, there was regional myocardial dysfunction, risk factors contributed to the impairment of systolic and diastolic function of the regional myocardium. Assessment of myocardial function using SRI could be more accurate in MS patient evaluation than conventional echocardiography alone.

  19. 代谢综合征/心肌梗死大鼠模型的建立%Establishment of a rat model of myocardial infarction with metabolism syndrome

    Institute of Scientific and Technical Information of China (English)

    朱冰坡; 范利; 曹剑; 刘霖; 王浩; 李健

    2012-01-01

    背景:代谢综合征合并急性心肌梗死是目前临床研究的热点问题之一,但现今有关代谢综合征合并急性心肌梗死动物模型的报告罕见报道.目的:建立代谢综合征/左前降支心肌梗死大鼠模型.方法:将雄性SD大鼠给予高果糖饮食,喂养时间8周,建立代谢综合征模型.再将此模型大鼠结扎左冠状动脉前降支深部建立代谢综合征/心肌梗死大鼠模型.结果与结论:采用高果糖喂养后的大鼠出现了高血压、高三酰甘油以及胰岛素抵抗现象(P < 0.05).代谢综合征/心肌梗死大鼠模型建模成功率为70%;组织切片可见大量心肌细胞坏死,瘢痕形成;超声心动图显示代谢综合征/心肌梗死模型大鼠左室舒张末内径和收缩末内径显著增加(P < 0.05),射血分数和缩短分数显著减少(P < 0.05),有创血流动力学检查提示代谢综合征/心肌梗死大鼠左室收缩压、左心室压最大上升速率和左心室压最大下降速率均下降(P < 0.05),而左室舒张末期压和心率升高(P < 0.05).结果证实,采用高果糖喂养可以制作可靠的大鼠代谢综合征模型;采用结扎左前降支方法能成功建立代谢综合征大鼠的心肌梗死模型.%BACKGROUND: Metabolic syndrome associated with acute myocardial infarction is currently a hot topic of clinical research, but to date there are few animal models of metabolic syndrome with acute myocardial infarction. OBJECTIVE: To establish a rat model of metabolism syndrome associated with myocardial infarction in left anterior descending artery. METHODS: Male SD rats were fed with high-fructose diet for 8 weeks to establish metabolism syndrome model. The left anterior descending artery of the model rats was ligaturing to construct a rat model of metabolic syndrome with acute myocardial infarction. RESULTS AND CONCLUSION: Rats developed hypertension, hypertriglyceridemia and insulin resistance after fed with high-fructose diet (P < 0.05). The

  20. Influence of high energy phosphate metabolism in postischemic myocardial dysfunction using magnetic resonance spectroscopy; Influencia dos fosfatos de alta energia na funcao ventricular em pacientes com infarto do miocardio avaliada pela resonancia magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Kalil Filho, Roberto [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital das Clinicas

    1998-05-01

    The recovery of left ventricular function after reperfusion is delayed in general by several hours, days or weeks and this phenomenon is known as myocardial stunning. One of the theories to explain the pathogenesis of this postischemic myocardial dysfunction is the production of not enough energy by mitochondria, leading to decreased adenosine-triphosphate (ATP) levels. We evaluated the influence of high energy phosphate metabolism in postischemic myocardial dysfunction, using magnetic resonance spectroscopy in patients with acute anterior wall myocardial infarction, successfully reperfused, within the first six hours from the onset of the symptoms. Twenty-nine patients were studied in the acute phase (on average four days after the onset of myocardial infarction) and 21 repeated the examination in the follow-up phase (average 39 days). Regional left ventricular function was evaluated by cine-resonance and high energy phosphate metabolism by phosphorus-31 spectroscopy, using the phosphocreatine {beta} ATP (P Cr/{beta}ATP) ratio. The existence of myocardial stunning was suggested by the improvement of the related regional contractility during the follow-up. The contractility improved in the septal wall from 2.46{+-} 0.68 to 1.54 {+-} 0.78 (p<0.001), in the anteroseptal wall from 2.0 {+-} 0.89 to 1.40 {+-} 0.75 (p<0.001) and in the anterior wall from 2.37 {+-} 0.71 to 1.41 {+-} 0.59 (p<0.001). The P Cr/{beta}ATP ratio did not change from acute to follow-up phase (1.51 {+-} 0.17 vs. 1.53 {+-} 0.17; p = 0.6). This study suggests that decreased high energy phosphate metabolism after reperfusion does not have an important role in the genesis of the myocardial stunning in patients with acute anterior wall myocardial infarction. (author) 25 refs., 9 figs., 1 tab.

  1. [Treatment options for age-related infertility].

    Science.gov (United States)

    Belaisch-Allart, Joëlle

    2010-06-20

    There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive.

  2. Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-{sup 11}C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Kagaya, Yutaka; Chida, Masanobu; Namiuchi, Shigeto; Takeda, Morihiko; Yamane, Yuriko; Otani, Hiroki; Watanabe, Jun; Fukuchi, Mitsumasa; Shirato, Kunio [Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Imahori, Yoshio [Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto (Japan); Fujii, Ryou [Cyclotron Unit, Nishijin Hospital, Kyoto (Japan); Tezuka, Fumiaki [Department of Pathology, National Sendai Hospital, Sendai (Japan); Ido, Tatsuo [Cyclotron and Radioisotope Center, Tohoku University, Sendai (Japan)

    2002-11-01

    We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-{sup 11}C]-butyryl-2-palmitoyl-rac-glycerol ({sup 11}C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of {sup 11}C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with {sup 11}C-DAG after 3 or 10weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the {sup 11}C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The {sup 11}C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the {sup 11}C

  3. Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study.

    Science.gov (United States)

    Chagoya de Sánchez, V; Hernández-Muñoz, R; López-Barrera, F; Yañez, L; Vidrio, S; Suárez, J; Cota-Garza, M D; Aranda-Fraustro, A; Cruz, D

    1997-12-01

    Acute myocardial infarction is the second cause of mortality in most countries, therefore, it is important to know the evolution and sequence of the physiological and biochemical changes involved in this pathology. This study attempts to integrate these changes and to correlate them in a long-term model (96 h) of isoproterenol-induced myocardial cell damage in the rat. We achieved an infarct-like damage in the apex region of the left ventricle, occurring 12-24 h after isoproterenol administration. The lesion was defined by histological criteria, continuous telemetric ECG recordings, and the increase in serum marker enzymes, specific for myocardial damage. A distinction is made among preinfarction, infarction, and postinfarction. Three minutes after drug administration, there was a 60% increase in heart rate and a lowering of blood pressure, resulting possibly in a functional ischemia. Ultrastructural changes and mitochondrial swelling were evident from the first hour of treatment, but functional alterations in isolated mitochondria, such as decreases in oxygen consumption, respiratory quotient, ATP synthesis, and membrane potential, were noticed only 6 h after drug administration and lasted until 72 h later. Mitochondrial proteins decreased after 3 h of treatment, reaching almost a 50% diminution, which was maintained during the whole study. An energy imbalance, reflected by a decrease in energy charge and in the creatine phosphate/creatine ratio, was observed after 30 min of treatment; however, ATP and total adenine nucleotides diminished clearly only after 3 h of treatment. All these alterations reached a maximum at the onset of infarction and were accompanied by damage to the myocardial function, drastically decreasing left ventricular pressure and shortening the atrioventricular interval. During postinfarction, a partial recovery of energy charge, creatine phosphate/creatine ratio, membrane potential, and myocardial function occurred, but not of mitochondrial

  4. Sarcopenia and Age-Related Endocrine Function

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2012-01-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

  5. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

    Aging is a natural consequence of a society developing process. Although many adults retain good hearing as they aging, hearing loss related with age-presbycusis which can vary in severity from mild to substantial is common among elderly persons. There are a number of pathophysiological processes underlying age-related changes in the auditory system as well as in the central nervous systems. Many studies have been dedicated to the illustration of risk factors accumulating presbycusis such as heritability, environment factors, medical conditions, free radical (reactive oxygen species, ROS) and damage of mitochondrial DNA. Left untreated, presbycusis can not only lead sufferers to reduced quality of life, isolation, dependence and frustration, but also affect the healthy people around. These can be partly corrected using hearing aids, but it is not enough, more and more strategies of treatment based on the findings associating with presbycusis should be added rather than using single hearing aids. We review here the pathophysiology; heritability, susceptibility genes and other risk factors including environmental, medical, especially free radical (ROS) and damage of mitochondrial DNA; and some strategies of treatment, as well as promising rehabilitations associating with presbycusis.

  6. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  7. Age-related differences in walking stability.

    Science.gov (United States)

    Menz, Hylton B; Lord, Stephen R; Fitzpatrick, Richard C

    2003-03-01

    a large proportion of falls in older people occur when walking; however the mechanisms underlying impaired balance during gait are poorly understood. to evaluate acceleration patterns at the head and pelvis in young and older subjects when walking on a level and an irregular walking surface, in order to develop an understanding of how ageing affects postural responses to challenging walking conditions. temporo-spatial gait parameters and variables derived from acceleration signals were recorded in 30 young people aged 22-39 years (mean 29.0, SD 4.3), and 30 older people with a low risk of falling aged 75-85 years (mean 79.0, SD 3.0) while walking on a level and an irregular walking surface. Subjects also underwent tests of vision, sensation, strength, reaction time and balance. older subjects exhibited a more conservative gait pattern, characterised by reduced velocity, shorter step length and increased step timing variability. These differences were particularly pronounced when walking on the irregular surface. The magnitude of accelerations at the head and pelvis were generally smaller in older subjects; however the smoothness of the acceleration signals did not differ between the two groups. Older subjects performed worse on tests of vision, peripheral sensation, strength, reaction time and balance. the adoption of a more conservative basic gait pattern by older people with a low risk of falling reduces the magnitude of accelerations experienced by the head and pelvis when walking, which is likely to be a compensatory strategy to maintain balance in the presence of age-related deficits in physiological function, particularly reduced lower limb strength.

  8. The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Schuetz, Matthias; Karanikas, Georgios [Vienna General Hospital/Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Khazen, Cesar [Vienna General Hospital/ Medical University of Vienna, Department of Cardiothoracic Surgery, Vienna (Austria); Wolzt, Michael [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Vienna General Hospital/ Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria)

    2012-03-15

    Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO{sub 2}) in patients with chronic heart failure using {sup 11}C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. {sup 11}C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO{sub 2} and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 {+-} 0.18 ml min{sup -1} g{sup -1} with the device off and 0.80 {+-} 0.15 ml min{sup -1} g{sup -1} with the device on (p = 0.818), MVO{sub 2} was 6.81 {+-} 1.69 ml/min/100 g with the device off and 7.15 {+-} 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 {+-} 1.14 mmHg ml/m{sup 2} with the device off and 5.21 {+-} 1.36 mmHg ml/m{sup 2} with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO{sub 2} and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO{sub 2}, even under stress conditions. (orig.)

  9. Comparative Analysis of Changes of Myocardial Angiogenesis and Energy Metabolism in Postinfarction and Diabetic Damage of Rat Heart

    Directory of Open Access Journals (Sweden)

    Sergey A. Afanasiev

    2014-01-01

    Full Text Available Comparative study of changes in myocardial activity of lactate dehydrogenase (LDH, succinate dehydrogenase (SDH, and capillary density distribution in the experimental models of diabetic and postinfarction damage of rat heart was performed. Data showed that decrease in LDH and SDH activities was observed in both pathologies which can suggest abnormal processes of glycolysis and oxidative phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined pathologies was comparative with the corresponding values of these parameters in control group. The authors hypothesize that these differences can be caused by specifics of myocardial vascularization. The results of the study showed that an increase in capillary density was found in all groups of rats with pathologies compared with control group. However, no significant differences in the intensity of angiogenesis processes were found between groups with pathologies.

  10. Plasma Metabolic Profile Determination in Young ST-segment Elevation Myocardial Infarction Patients with Ischemia and Reperfusion: Ultra-performance Liquid Chromatography and Mass Spectrometry for Pathway Analysis

    Institute of Scientific and Technical Information of China (English)

    Lei Huang; Tong Li; Ying-Wu Liu; Lei Zhang; Zhi-Huan Dong; Shu-Ye Liu; Ying-Tang Gao

    2016-01-01

    Background:This study was to establish a disease differentiation model for ST-segment elevation myocardial infarction (STEMI) youth patients experiencing ischemia and reperfusion via ultra-performance liquid chromatography and mass spectrometry (UPLC/MS) platform,which searches for closely related characteristic metabolites and metabolic pathways to evaluate their predictive value in the prognosis after discharge.Methods:Forty-seven consecutive STEMI patients (23 patients under 45 years of age,referred to here as "youth," and 24 "elderly" patients) and 48 healthy control group members (24 youth,24 elderly) were registered prospectively.The youth patients were required to provide a second blood draw during a follow-up visit one year after morbidity (n =22,one lost).Characteristic metabolites and relative metabolic pathways were screened via UPLC/MS platform base on the Kyoto encyclopedia of genes and genomes (KEGG) and Human Metabolome Database.Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of characteristic metabolites in the prognosis after discharge.Results:We successfully established an orthogonal partial least squares discriminated analysis model (R2X =71.2%,R2Y =79.6%,and Q2 =55.9%) and screened out 24 ions; the sphingolipid metabolism pathway showed the most drastic change.The ROC curve analysis showed that ceramide [Cer(d18:0/16:0),Cer(t18:0/12:0)] and sphinganine in the sphingolipid pathway have high sensitivity and specificity on the prognosis related to major adverse cardiovascular events after youth patients were discharged.The area under curve (AUC) was 0.671,0.750,and 0.711,respectively.A follow-up validation one year after morbidity showed corresponding AUC of 0.778,0.833,and 0.806.Conclusions:By analyzing the plasma metabolism of myocardial infarction patients,we successfully established a model that can distinguish two different factors simultaneously:pathological conditions and age

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

    Science.gov (United States)

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

    2015-10-01

    Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  12. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  13. Cardiorespiratory fitness modifies the relationship between myocardial function and cerebral blood flow in older adults.

    Science.gov (United States)

    Johnson, Nathan F; Gold, Brian T; Bailey, Alison L; Clasey, Jody L; Hakun, Jonathan G; White, Matthew; Long, Doug E; Powell, David K

    2016-05-01

    A growing body of evidence indicates that cardiorespiratory fitness attenuates some age-related cerebral declines. However, little is known about the role that myocardial function plays in this relationship. Brain regions with high resting metabolic rates, such as the default mode network (DMN), may be especially vulnerable to age-related declines in myocardial functions affecting cerebral blood flow (CBF). This study explored the relationship between a measure of myocardial mechanics, global longitudinal strain (GLS), and CBF to the DMN. In addition, we explored how cardiorespiratory affects this relationship. Participants were 30 older adults between the ages of 59 and 69 (mean age=63.73years, SD=2.8). Results indicated that superior cardiorespiratory fitness and myocardial mechanics were positively associated with DMN CBF. Moreover, results of a mediation analysis revealed that the relationship between GLS and DMN CBF was accounted for by individual differences in fitness. Findings suggest that benefits of healthy heart function to brain function are modified by fitness.

  14. Alterations in myocardial metabolism and function at rest in stable angina pectoris: relations with the amount of exercise-induced thallium-201 perfusion defect

    Energy Technology Data Exchange (ETDEWEB)

    De Kock, M.; Melin, J.A.; Pouleur, H.; Rousseau, M.F.

    1986-01-01

    The relation between the amount of exercise-induced ischemia and alterations in left ventricular (LV) function and metabolism at rest was studied in 18 coronary patients with stable angina pectoris. An ischemic defect area score was computed from quantitative exercise thallium-201 (Tl-201) scintigraphy; this estimation of the amount of ischemic myocardium was used to classify the patients in group I (n = 8; score less than 15%, mean 6.7 +/- 2.5%) and II (n = 10; score greater than 15%; mean 27.2 +/- 8.9%). Hemodynamics and metabolism were studied in basal state. No patient had anginal pain during the study, and the extent of angiographic coronary artery disease (CAD) was comparable in the two groups. Heart rate, aortic pressure, coronary blood flow, and myocardial oxygen uptake were also similar in both groups. However, ejection fraction was reduced in group II (51 +/- 13 vs 63 +/- 5%; p less than 0.01) and LV relaxation was impaired as shown by the increase in time-constant of isovolumic pressure fall (55 +/- 16 vs 44 +/- 6 ms in group I; p less than 0.05); the LV end-diastolic pressure was also increased in group II (19 +/- 8 vs 10 +/- 4 mmHg in group l; p less than 0.05). Furthermore, in group II, myocardial lactate uptake was reduced (4 +/- 19 vs 30 +/- 29 mumole/min in group I; p less than 0.01) and the productions of alanine and glutamine were augmented (-7.5 +/- 4.4 vs -4.6 +/- 1.6 mumole/min in group I; p less than 0.05).

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

    Science.gov (United States)

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

    2013-01-01

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

  16. Metabolism

    Science.gov (United States)

    ... Surgery? Choosing the Right Sport for You Shyness Metabolism KidsHealth > For Teens > Metabolism Print A A A ... food through a process called metabolism. What Is Metabolism? Metabolism (pronounced: meh-TAB-uh-lih-zem) is ...

  17. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Oezcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancr

  18. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Oezcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancr

  19. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    NARCIS (Netherlands)

    Rahimi, M.; Vinciguerra, M.; Daghighi, M.; Ozcan, B.; Akbarkhanzadeh, V.; Sheedfar, F.; Amini, M.; Mazza, T.; Pazienza, V.; Motazacker, M.M.; Mahmoudi, M.; Rooij, F.W. De; Sijbrands, E.; Peppelenbosch, M.P.; Rezaee, F.

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancr

  20. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    M. Rahimi (Mehran); M. Vinciguerra (Manlio); M. Daghighi (Mojtaba); B. Özcan (Behiye); V. Akbarkhanzadeh (Vishtaseb); F. Sheedfar (Fareeba); M. Amini (Marzyeh); T. Mazza (Tommaso); V. Pazienza (Valerio); M.M. Motazacker (Mohammad); T. Mahmoudi (Tokameh); F.W.M. de Rooij (Felix); E.J.G. Sijbrands (Eric); M.P. Peppelenbosch (Maikel); F. Rezaee (Farhad)

    2015-01-01

    textabstractDespite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (A

  1. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  2. Phase 3 study of. beta. -methyl-p-( sup 123 I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating fatty acid metabolism; A multi-center trial

    Energy Technology Data Exchange (ETDEWEB)

    Torizuka, Kanji (Fukui Medical School, Matsuoka (Japan)); Yonekura, Yoshiharu; Nishimura, Tsunehiko; Ohtake, Tohru; Bunko, Hisashi; Tamaki, Nagara; Uehara, Toshiisa

    1992-04-01

    A multi-center trial of {beta}-methyl-p-({sup 123}I)-iodophenyl-pentadecanoic acid ({sup 123}I-BMIPP) was performed to assess its clinical usefulness in the evaluation of myocardial fatty acid metabolism in 587 patients with various heart diseases. {sup 123}I-BMIPP showed relatively decreased uptake compared with {sup 201}Tl in the myocardial lesions of 62% of patients with ischemic heart disease (IHD), 39% of those with cardiomyopathy and 32% of those with other heart diseases. In case of myocardial infarction, less uptake of {sup 123}I-BMIPP (Type B) than {sup 201}Tl was more frequently seen in patients with successful recanalization than in those without recanalization. The patients with matched distribution of the two tracers (Type E) increased in the direct proportion to the interval between the onset of myocardial infarction and the radionuclide studies. The uptake of {sup 123}I-BMIPP correlated well with myocardial viability evaluated by {sup 201}Tl exercise-redistribution studies. Type B was frequently seen in the areas with {sup 201}Tl redistribution, while Type E was seen in the fixed defect areas. In the other heart diseases studied, Type E was observed in approximately 60% of patients with dilated or secondary cardiomyopathies. Type B was seen in about 45% of patients with valvular heart diseases and myocarditis. Various types of mismatch between the two tracers were demonstrated in hypertrophic cardiomyopathy and hypertensive heart disease. It is concluded that {sup 123}I-BMIPP is a safe and useful agent for the diagnosis of various heart diseases, since it reflects myocardial fatty acid metabolism. (author)

  3. Oxidative modification of proteins: age-related changes.

    Science.gov (United States)

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  4. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... Resources (3 links) BrightFocus Foundation: Macular Degeneration Treatment Macular Degeneration Partnership: Low Vision Rehabilitation Prevent Blindness America: Age-Related Macular Degeneration (AMD) ...

  5. Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

    Institute of Scientific and Technical Information of China (English)

    Fang-Fang WANG; Bao-Xia CHEN; Hai-Yi YU; Lin MI; Zi-Jian LI; Wei GAO

    2016-01-01

    BackgroundGrowth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF.MethodsThe study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group,n= 50), old MI patients without HF (OMI group,n = 56), old MI patients with HF (OMI-HF group,n= 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay.ResultsThe plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P< 0.001). The indi-cators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02μg/Lvs. 2.08 ± 0.95μg/L, 22.2 ± 6.6μg/Lvs. 16.7 ± 5.1μg/L and 13.2 ± 7.9μg/Lvs. 6.4 ± 2.1μg/L, respectively;P< 0.01). GDF-15 positively cor-related with ICTP and PIIINP (r = 0.302,P< 0.001 andr= 0.206,P= 0.006, respectively). GDF-15 positively correlated to the echocardio-graphic diastolic indicators E/Em and left atrial pressure (r= 0.349 and r= 0.358, respectively;P< 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r=-0.623 and r=-0.365, respectively;P< 0.01).ConclusionPlasma GDF-15 is associated with the indicators of type I and III collagen

  6. Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand.

    Science.gov (United States)

    Hauton, David; Al-Shammari, Abdullah; Gaffney, Eamonn A; Egginton, Stuart

    2015-01-01

    Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve

  7. Maternal hypoxia decreases capillary supply and increases metabolic inefficiency leading to divergence in myocardial oxygen supply and demand.

    Directory of Open Access Journals (Sweden)

    David Hauton

    Full Text Available Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO2=0.12 at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. 14C-labelled glucose and 3H-palmitate were provided as substrates and metabolism quantified from recovery of 14CO2 and 3H2O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05, despite recording a 2-fold increase in glucose oxidation (P<0.01 and 2.5-fold increase (P<0.01 in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01 and suppressed palmitate oxidation (P<0.05, suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01, although pyruvate dehydrogenase sensitivity to insulin was lost (NS, while citrate synthase activity declined by 30% (P<0.001 and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001. Calculated metabolic efficiency decreased 4-fold (P<0.01 for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to

  8.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  9. Effect of Salvianolic Acid b and Paeonol on Blood Lipid Metabolism and Hemorrheology in Myocardial Ischemia Rabbits Induced by Pituitruin

    Science.gov (United States)

    Yang, Qian; Wang, Siwang; Xie, Yanhua; Wang, Jianbo; Li, Hua; Zhou, Xuanxuan; Liu, Wenbo

    2010-01-01

    The purpose of this study was to determine the therapeutic effect of salvianolic acid b and paeonol on coronary disease. The ischemia myocardial animal model is induced by administering pituitrin (20 μg·kg−1) intravenously via the abdominal vein. A combination of salvianolic acid b and paeonol (CSAP) (5, 10 and 15 mg/kg BW) was administrated to experimental rabbits. Biochemical indices were evaluated during six weeks of intervention. We found that the compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW) can markedly and dose-dependently reduce fibrinogen and malonaldehyde levels, increase the HDL level, improve blood viscosity and plasma viscosity in rabbits. In addition, the medicine can still reduce the ratio of NO/ET and the contents of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in a dose-dependent manner. This study demonstrates that compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW) can improve the blood hemorrheology, decrease oxidative injury and repair the function of blood vessel endothelium, and subsequently prevent the development of Coronary disease. PMID:21152295

  10. Effect of Salvianolic Acid b and Paeonol on Blood Lipid Metabolism and Hemorrheology in Myocardial Ischemia Rabbits Induced by Pituitruin

    Directory of Open Access Journals (Sweden)

    Qian Yang

    2010-09-01

    Full Text Available The purpose of this study was to determine the therapeutic effect of salvianolic acid b and paeonol on coronary disease. The ischemia myocardial animal model is induced by administering pituitrin (20 μg·kg−1 intravenously via the abdominal vein. A combination of salvianolic acid b and paeonol (CSAP (5, 10 and 15 mg/kg BW was administrated to experimental rabbits. Biochemical indices were evaluated during six weeks of intervention. We found that the compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW can markedly and dose-dependently reduce fibrinogen and malonaldehyde levels, increase the HDL level, improve blood viscosity and plasma viscosity in rabbits. In addition, the medicine can still reduce the ratio of NO/ET and the contents of lactate dehydrogenase (LDH and creatine phosphokinase (CPK in a dose-dependent manner. This study demonstrates that compound of salvianolic acid b and paeonol (5, 10 and 15 mg/kg BW can improve the blood hemorrheology, decrease oxidative injury and repair the function of blood vessel endothelium, and subsequently prevent the development of Coronary disease.

  11. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine

    2014-01-01

    -significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes...

  12. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  13. Age-related intramyocardial patterns in healthy subjects evaluated with Doppler tissue imaging.

    Science.gov (United States)

    Pérez-David, Esther; García-Fernández, Miguel A; Ledesma, Maria Jesús; Malpica, Norberto; López Fernández, Teresa; Santos, Andrés; Moreno, Mar; Antoranz, José C; Bermejo, Javier; Desco, Manuel

    2005-06-01

    The aim of this study is to analyse spatial distribution of myocardial velocities (MV) and myocardial velocity gradient (MVG) with color M-mode Doppler tissue imaging (DTI) and to analyse the influence of age in such parameters. A prospective study including 66 healthy volunteers was carried out with color M-mode DTI. Postprocessing of images was performed using proprietary software allowing the division of the myocardial wall into subendocardium, mesocardium and subepicardium. MV corresponding to the three layers and MVG time curves were obtained and systolic, early diastolic and late diastolic peak values were identified. MV were highest in subendocardium in systole, protodiastole and telediastole compared to external layers. Protodiastolic peak MV decreased in all layers with age, but with a higher impact in the subendocardium (r = 0.72, b = 0.136 (IC 95% 0.107-0.164), p = 0.0005). Older age resulted in larger telediastolic peak MV, without significant differences among layers. Linear correlation between protodiastolic peak mitral flow and peak protodiastolic velocity was higher in endocardium than in other layers (r = 0.79, p = 0.0005). Color M-mode DTI multilayer analysis showed that endocardium is more susceptible to age-related changes involving diastolic function. This dependency on age should be considered when assessing MV in other clinical settings.

  14. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  15. Assessment of myocardial metabolic rate of glucose by means of Bayesian ICA and Markov Chain Monte Carlo methods in small animal PET imaging

    Science.gov (United States)

    Berradja, Khadidja; Boughanmi, Nabil

    2016-09-01

    In dynamic cardiac PET FDG studies the assessment of myocardial metabolic rate of glucose (MMRG) requires the knowledge of the blood input function (IF). IF can be obtained by manual or automatic blood sampling and cross calibrated with PET. These procedures are cumbersome, invasive and generate uncertainties. The IF is contaminated by spillover of radioactivity from the adjacent myocardium and this could cause important error in the estimated MMRG. In this study, we show that the IF can be extracted from the images in a rat heart study with 18F-fluorodeoxyglucose (18F-FDG) by means of Independent Component Analysis (ICA) based on Bayesian theory and Markov Chain Monte Carlo (MCMC) sampling method (BICA). Images of the heart from rats were acquired with the Sherbrooke small animal PET scanner. A region of interest (ROI) was drawn around the rat image and decomposed into blood and tissue using BICA. The Statistical study showed that there is a significant difference (p < 0.05) between MMRG obtained with IF extracted by BICA with respect to IF extracted from measured images corrupted with spillover.

  16. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  17. Age-related loss of orexin/hypocretin neurons

    Science.gov (United States)

    Kessler, Brice A.; Stanley, Emily M.; Frederick-Duus, Danielle; Fadel, Jim

    2011-01-01

    Aging is associated with many physiological alterations—such as changes in sleep patterns, metabolism and food intake—suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3–4 months) and old (26–28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances. PMID:21262323

  18. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bruce eCrosson

    2015-05-01

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

  1. Myocardial disease

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970309 Myocardial injury of Keshan disease andapoptosis. ZHONG Xuekuan(钟学宽), et al. KeshanDis Instit, Harbin Med Univ, Harbin, 150086. Chin JEndemiol 1997, 16(2): 81-82. Objective: To discuss the relationship between my-ocardial injury Of Keshan disease and apoptosis. Meth-

  2. Myocardial metabolism of {sup 123}I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Ryohei; Fujita, Masatoshi; Kambara, Naoshige; Ohba, Muneo; Tadamura, Eiji; Kimura, Takeshi; Kita, Toru [Kyoto University Graduate School of Medicine, Department of Cardiovascular Medicine, and Nuclear Medicine, Kyoto (Japan); Nohara, Ryuji [The Tazuke Kofukai Medical Research Institute, Department of Cardiology, Kitano Hospital, Osaka (Japan); Hirai, Taku [Kinki University School of Medicine, Department of Cardiology, Nara Hospital, Nara (Japan); Fujibayashi, Yasuhisa [Fukui Medical University, Molecular Imaging, Biomedical Imaging Research Center, Fukui (Japan)

    2005-01-01

    {sup 123}I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ({sup 123}I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of {sup 123}I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake. Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6). Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48{+-}19% vs 66{+-}14%, p<0.05) and its subsequent retention (73{+-}13% vs 85{+-}8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0{+-}20.0% to 15.8{+-}9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3{+-}21.9% to 71.3{+-}10.1%, p<0.05). These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight

  3. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases.

    Science.gov (United States)

    Knutson, Mitchell D; Leeuwenburgh, Christiaan

    2008-10-01

    Studies show that the plant polyphenol resveratrol can extend the life span of yeast, worms, flies, and fish. It also mitigates the metabolic dysfunction of mice fed high-fat diets. Resveratrol appears to mediate these effects partly by activating SIRT1, a deacetylase enzyme that regulates the activity of several transcriptional factors and enzymes responsive to nutrient availability. However, few foods contain resveratrol and humans metabolize it extensively, resulting in very low systemic bioavailability. Substantial research effort now focuses on identifying and testing more bioavailable and potent activators of SIRT1 for use as pharmacologic interventions in aging and age-related disorders.

  4. Slowing down: age-related neurobiological predictors of processing speed

    Directory of Open Access Journals (Sweden)

    Mark A Eckert

    2011-03-01

    Full Text Available Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-relatedcognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed - dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging.

  5. New Clues to Age-Related Hearing Loss

    Science.gov (United States)

    ... fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a harder time processing ... conversation, many older people chalk it up to hearing loss. But a new, small study finds that the ...

  6. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  7. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  8. Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis

    Directory of Open Access Journals (Sweden)

    Yunpeng Qi

    2013-01-01

    Full Text Available Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD has been clinically used for treatment of myocardial ischemia (MI for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

  9. Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis.

    Science.gov (United States)

    Qi, Yunpeng; Gu, Haiwei; Song, Yunlong; Dong, Xin; Liu, Aijun; Lou, Ziyang; Fan, Guorong; Chai, Yifeng

    2013-01-01

    Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD) has been clinically used for treatment of myocardial ischemia (MI) for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

  10. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  11. Oxidative stress, innate immunity, and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE. These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD or choroidal neovascularization (CNV, or wet AMD. Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory

  12. Oxidative stress, innate immunity, and age-related macular degeneration.

    Science.gov (United States)

    Shaw, Peter X; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  13. Product of heart rate and first heart sound amplitude as an index of myocardial metabolic stress during graded exercise.

    Science.gov (United States)

    Tanaka, Hiroaki; Matsuda, Takuro; Tobina, Takuro; Yamada, Yousuke; Yamagishi, Tamiharu; Sakai, Hideaki; Obara, Shigeru; Higaki, Yasuki; Kiyonaga, Akira; Brubaker, Peter H

    2013-01-01

    The double product (DP) breakpoint of heart rate (HR) and systolic blood pressure has been identified as coincident with anaerobic threshold (AT), but there are no simple methods for measuring cardiac metabolic stress (CMS) during an exercise test. It was hypothesized that the DP of HR and the amplitude of the first heart sound (AHS1) (DP-AHS1) would reflect CMS, and thus, the breakpoint in the DP-AHS1 (DPBP-AHS1) could be an alternative method for determining AT. Subjects (age range, 18-73 years) were recruited to perform a graded exercise test on a cycle ergometer with continuous monitoring of DP-AHS1, with left ventricular pressure (LVP; experiment 1, Ex1), plasma catecholamine and blood lactate (experiment 2, Ex2) and gas exchange (experiment 3, Ex3). Ex1: in all subjects there was a strong correlation between AHS1 and LVdP/dtmax (r=0.94-0.98), and between the DP-AHS1 and the triple product of HR, LVdP/dtmax, and max LVP (r=0.98-0.99). Ex2: DP-AHS1 was strongly correlated with adrenaline (r=0.97-1.00) and lactate (r=0.96-1.00) levels in all subjects. Ex3: there was a strong correlation between DPBP-AHS1, AT and maximum oxygen consumption. The present simple measure of DP-AHS1 can reflect plasma adrenaline and lactate levels during graded exercise testing. Further, DPBP-AHS1 is a surrogate marker of AT and a good index of functional aerobic capacity.

  14. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  15. Pharmacogenetics and nutritional supplementation in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hampton BM

    2015-05-01

    Full Text Available Blake M Hampton, Jaclyn L Kovach, Stephen G Schwartz Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: The Age-Related Eye Disease Study (AREDS recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available. Keywords: Age-Related Eye Disease Study (AREDS, age-related macular degeneration, age-related maculopathy susceptibility 2 (ARMS2, complement factor H (CFH, pharmacogenetics, randomized clinical trial (RCT

  16. Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  17. Age-related macular degeneration: current treatment and future options.

    Science.gov (United States)

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  18. Mouse models of age-related mitochondrial neurosensory hearing loss.

    Science.gov (United States)

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Age-related changes in task related functional network connectivity.

    Directory of Open Access Journals (Sweden)

    Jason Steffener

    Full Text Available Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.

  20. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  1. An epigenetic hypothesis of aging-related cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Marsha R Penner

    2010-03-01

    Full Text Available This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

  2. [Impact of thymic function in age-related immune deterioration].

    Science.gov (United States)

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  3. A Context for Teaching Aging-Related Public Policy.

    Science.gov (United States)

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  4. Age-related differences in women's foot shape

    NARCIS (Netherlands)

    Ansuategui Echeita, Jone; Hijmans, Juha M.; Smits, Sharon; Van der Woude, Lucas H. V.; Postema, Klaas

    2016-01-01

    Purpose: Describe age-related differences in women's foot shape using a wide range of measurements and ages. Study design: Cross-sectional, observational study. Main outcome measurements: Six foot-shape measurements of each foot: foot lengths, ball widths, ball circumferences, low instep circumferen

  5. Oxidation stress role in age-related cataractogenesis

    Directory of Open Access Journals (Sweden)

    Žorić Lepša

    2010-01-01

    Full Text Available Introduction. Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress. Oxidation stress and its form caused by ultraviolet light-photo-oxidative stress - are considered to be crucial in the etiopatho­genesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens posses a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  6. [Oxidation stress role in age-related cataractogenesis].

    Science.gov (United States)

    Zorić, Lepsa; Colak, Emina; Canadanović, Vladimir; Kosanović-Jaković, Natalija; Kisić, Bojana

    2010-01-01

    Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress and its form caused by ultraviolet light- photo-oxidative stress--are considered to be crucial in the etiopathogenesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens possess a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  7. Age-related decrements in cycling and running perfor- mance

    African Journals Online (AJOL)

    Enrique

    while exercise can reduce the rate of decline in age-related exercise capacity ... a gradual increase in degenerative changes in both type I and type II fibres ..... ery of vertical jump height and heart rate vs. running speed after a 90 km foot race.

  8. The Experience of Age-Related Macular Degeneration

    Science.gov (United States)

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  9. Age-Related Differences in Worry and Related Processes

    Science.gov (United States)

    Basevitz, Paul; Pushkar, Dolores; Chaikelson, June; Conway, Michael; Dalton, Connie

    2008-01-01

    This study investigated the hypothesis that older adults would show age-related reductions in the tendency to worry in both their retrospective accounts and through cross-sectional age comparisons with a sample of younger adults. We also sought to determine whether age differences would be evident in psychological processes associated with a…

  10. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

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

  11. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved...

  12. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  13. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  14. Age-related differences in Second Language Acquisition

    Institute of Scientific and Technical Information of China (English)

    严爽

    2016-01-01

    There are many factors affecting second language acquisition such as motivation, personality, intelligence, ap-titude, learning styles and so on. This paper focuses on one crucial factor-age. The author tries to explore the age-related differences among second language learners. The main reasons behind the differences and the implications are also discussed.

  15. Age-related maculopathy: A genetic and epidemiological approach

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline)

    2000-01-01

    textabstractIn the 19th century, age-related maculopathy (ARM) was described for the first time as an agerelated abnormality of the macula lutea. ARM consists of a variety of clinical signs, from the early stages with soft distinct drusen, indistinct drusen and pigment alterations up to the late st

  16. Effect of isoproterenol on myocardial perfusion, function, energy metabolism and nitric oxide pathway in the rat heart - a longitudinal MR study.

    Science.gov (United States)

    Desrois, Martine; Kober, Frank; Lan, Carole; Dalmasso, Christiane; Cole, Mark; Clarke, Kieran; Cozzone, Patrick J; Bernard, Monique

    2014-05-01

    The chronic administration of the β-adrenoreceptor agonist isoproterenol (IsoP) is used in animals to study the mechanisms of cardiac hypertrophy and failure associated with a sustained increase in circulating catecholamines. Time-dependent changes in myocardial blood flow (MBF), morphological and functional parameters were assessed in rats in vivo using multimodal cardiac MRI. Energy metabolism, oxidative stress and the nitric oxide (NO) pathway were evaluated in isolated perfused rat hearts following 7 days of treatment. Male Wistar rats were infused for 7 days with IsoP or vehicle using osmotic pumps. Cine-MRI and arterial spin labeling were used to determine left ventricular morphology, function and MBF at days 1, 2 and 7 after pump implantation. Isolated hearts were then perfused, and high-energy phosphate compounds and intracellular pH were followed using ³¹P MRS with simultaneous measurement of contractile function. Total creatine and malondialdehyde (MDA) contents were measured by high-performance liquid chromatography. The NO pathway was evaluated by NO synthase isoform expression and total nitrate concentration (NO(x)). In IsoP-treated rats, left ventricular mass was increased at day 1 and maintained. Wall thickness was increased with a peak at day 2 and a tendency to return to baseline values at day 7. MBF was markedly increased at day 1 and returned to normal values between days 1 and 2. The rate-pressure product and phosphocreatine/adenosine triphosphate ratio in perfused hearts were reduced. MDA, endothelial NO synthase expression and NO(x) were increased. Sustained high cardiac function and normal MBF after 24 h of IsoP infusion indicate imbalance between functional demand and blood flow, leading to morphological changes. After 1 week, cardiac hypertrophy and decreased function were associated with impaired phosphocreatine, increased oxidative stress and up-regulation of the NO pathway. These results provide supplemental information on the

  17. Lipids, lipid genes, and incident age-related macular degeneration: The three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    R. Klein (Ronald); C.E. Myers (Chelsea); G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); X. Gao (Xiaoyi); P.T.V.M. de Jong (Paulus); T.A. Sivakumaran (Theru); G. Burlutsky (George); R. McKean-Cowdin (Roberta); A. Hofman (Albert); S.K. Iyengar (Sudha); K.E. Lee (Kristine); B.H.Ch. Stricker (Bruno); J.R. Vingerling (Hans); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline); J.J. Wang (Jie Jin)

    2014-01-01

    textabstractPurpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES),

  18. Lipids, lipid genes, and incident age-related macular degeneration : the three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

    PURPOSE: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). DESIGN: Meta-analysis. METHODS: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue

  19. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

    Directory of Open Access Journals (Sweden)

    Vasieva Olga

    2011-01-01

    Full Text Available Abstract Background The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes, for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. Results The main patterns discovered by the classification methods are as follows: (a the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO annotations; (c GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d interaction with the XRCC5 (Ku80 protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. Conclusions The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  20. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

    Directory of Open Access Journals (Sweden)

    Chunhu Gu

    Full Text Available Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1 is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo and aged (22-24 mo mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2, SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P<0.05. Exogenous toxic aldehydes (4-HNE exposure in isolated cardiomyocyte verified that aldehyde-induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse hypoxia/reoxygenation (H/R injury, which could all be rescued by Alda-1 (ALDH2 activator (all P<0.05. However, SIRT1 inhibitor blocked the protective effect of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher carbonylation but lower activity of SIRT1 in aged hearts than that seen in young hearts (P<0.05. The application of Alda-1 significantly reduced the carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury in aged hearts, but failed to protect Sirt1(+/- knockout mice against myocardial I/R injury. This was verified by Alda-1 treatment improved postischemic contractile function recovery in ex vivo perfused aged but not in Sirt1(+/- hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These results provide a new insight that impaired cardiac SIRT1 activity by carbonyl stress plays a critical role in the increased susceptibility of aged heart to I/R injury. ALDH2 activation can restore this aging-related myocardial ischemic intolerance.

  1. Stem Cell Transplantation Improves Aging-Related Diseases

    Directory of Open Access Journals (Sweden)

    Susumu eIkehara

    2014-05-01

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

  2. Ageism, age relations, and garment industry work in Montreal.

    Science.gov (United States)

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  3. Mitochondrial aging and age-related dysfunction of mitochondria.

    Science.gov (United States)

    Chistiakov, Dimitry A; Sobenin, Igor A; Revin, Victor V; Orekhov, Alexander N; Bobryshev, Yuri V

    2014-01-01

    Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

  4. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  5. Mechanisms of age-related macular degeneration and therapeutic opportunities.

    Science.gov (United States)

    van Lookeren Campagne, Menno; LeCouter, Jennifer; Yaspan, Brian L; Ye, Weilan

    2014-01-01

    As the age of the population increases in many nations, age-related degenerative diseases pose significant socioeconomic challenges. One of the key degenerative diseases that compromise quality of life is age-related macular degeneration (AMD). AMD is a multi-faceted condition that affects the central retina, which ultimately leads to blindness in millions of people worldwide. The pathophysiology and risk factors for AMD are complex, and the symptoms manifest in multiple related but distinct forms. The ability to develop effective treatments for AMD will depend on a thorough understanding of the underlying pathophysiology, risk factors, and driver molecular pathways, as well as the ability to develop useful animal models. This review provides an overview of the aforementioned aspects in AMD.

  6. Smoking and Age-Related Macular Degeneration: Review and Update

    Science.gov (United States)

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  7. The role of epigenetics in age-related macular degeneration

    OpenAIRE

    Gemenetzi, M; Lotery, A.J.

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research fo...

  8. Binocular Refraction in Patients with Age-Related Macular Degeneration

    OpenAIRE

    Skrbek, Matěj

    2013-01-01

    We’ve been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used ...

  9. Vitreomacular traction and age-related macular degeneration.

    Science.gov (United States)

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  10. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Shan Duan; Haraldur Sigurdsson; Hjorvar Petursson; Zhenglin Yang; Yu Zhao; Bernstein, Paul S.; Jian Ge; Fridbert Jonasson; Einar Stefansson; Gudleif Helgadottir; Norman A Zabriskie; Thorlakur Jonsson; Asgeir Björnsson; Theodora Thorlacius

    2005-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in t...

  11. Stereotactic radiotherapy in neovascular age-related macular degeneration

    OpenAIRE

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

  12. The Burden of Age-Related Macular Degeneration

    OpenAIRE

    Jordana K. Schmier; Mechelle L. Jones; Halpern, Michael T.

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, bo...

  13. An Immunologic Study on Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted...

  14. Present and Possible Therapies for Age-Related Macular Degeneration

    OpenAIRE

    Muhammad Khan; Ketan Agarwal; Mohamed Loutfi; Ahmed Kamal

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment ...

  15. Smoking and Age-Related Macular Degeneration: Review and Update

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  16. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  17. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  18. Results of submacular surgery in age-related macula degeneration

    OpenAIRE

    Laue, Jessica

    2010-01-01

    Due to a disruption of barrier function of the membrane Bruch and a change of the phagocities retinal pigment epithelial (rpe), exists possibility for progress of pathologist invasion of new vessels from the choroidea under the retina. On the position of the macula it will cause quick loss of central visual acuity. The most frequent cause for a choroidal neovascular membrane (CNV) is age-related macula degeneration (AMD); further causes are based on idiopathic or postinflammable reasons. ...

  19. Age-related expression profile of the SLC27A1 gene in chicken tissues.

    Science.gov (United States)

    Wang, Yan; Zhu, Qing; Zhao, Xiao-Ling; Yao, Yong-Gang; Liu, Yi-Ping

    2011-11-01

    The solute carrier family 27 (SLC27, also known as fatty acid transport proteins [FATPs]) plays important biological roles in cells. However, there is no report about the expression profile of SLC27 member in chicken. In this study, we quantified the expression of SLC27A1 (FATP1) mRNA in a mountainous black-boned chicken breed (MB) and a commercial meat type chicken breed (S01), to discern the tissue and age-related specific expression pattern and their potential involvement in fat deposition and muscle fatty acid metabolism. Real-time quantitative PCR assays were developed for accurate measurement of SLC27A1 mRNA levels in different tissues from chicken with different ages (0-12 weeks). Expression of SLC27A1 mRNA was detected in all tissues examined. There was a significantly age-related change of the SLC27A1 mRNAs in heart, breast muscle (BMW), leg muscle (LMW), liver, and abdominal fat (AF) tissues (P chicken had a higher expression of the SLC27A1 mRNA in breast muscle, subcutaneous fat, and heart tissues than the MB chicken. Our results showed that the expression of SLC27A1 mRNA in chicken tissues exhibits specific developmental changes and age-related patterns.

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Age-related differences in working memory updating components.

    Science.gov (United States)

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.

  2. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  3. Myocardial disease

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920666 Immunocytochemical study ofCuZn superoxide dismutase in the myocardi-um of normal subjects and patients ofrheumatic heart disease.ZHENG Yi(郑毅),et al. Dept Intern Med, Navy General Hosp,PLA, Beijing. 100037. Natl Med J China 1992;72(4): 225-227. By using the methods of immunocytochemistry

  4. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  5. [An approach for comparative quantification of myocardial blood flow (O-15-H2O-PET), perfusion (Tc-99m-tetrofosmin-SPECT) and metabolism (F-18-FDG-PET)].

    Science.gov (United States)

    Schäfer, W M; Nowak, B; Kaiser, H J; Block, S; Koch, K C; vom Dahl, J; Büll, U

    2001-10-01

    In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin SPECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All data sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, midventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (> 70% TT-SPECT) were used for comparative quantification. First and second mean global MBF values were 0.85 ml x min-1 x g-1 and 0.84 ml x min-1 x g-1, respectively, with a repeatability coefficient of 0.30 ml x min-1 x g-1. After sectorization mean MBF_micr was between 0.58 ml x min-1 x ml-1 and 0.68 ml x min-1 x ml-1 in well perfused areas. Corresponding TT-SPECT values ranged from 83% to 91%, and FDG-PET values from 91% to 103%. All procedures yielded higher values for the lateral than the septal regions. Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.

  6. The role of epigenetics in age-related macular degeneration.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  7. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  8. Future Therapies of Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

  9. Preventing depression in age-related macular degeneration.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E; Tasman, William S

    2007-08-01

    Age-related macular degeneration is a prevalent disease of aging that may cause irreversible vision loss, disability, and depression. The latter is rarely recognized or treated in ophthalmologic settings. To determine whether problem-solving treatment can prevent depressive disorders in patients with recent vision loss. Randomized, controlled trial. Outpatient ophthalmology offices in Philadelphia, Pennsylvania. Two hundred six patients aged 65 years or older with recent diagnoses of neovascular age-related macular degeneration in one eye and pre-existing age-related macular degeneration in the fellow eye. Patients were randomly assigned to problem-solving treatment (n = 105) or usual care (n = 101). Problem-solving treatment therapists delivered 6 sessions during 8 weeks in subjects' homes. Outcomes were assessed at 2 months for short-term effects and 6 months for maintenance effects. These included DSM-IV-defined diagnoses of depressive disorders, National Eye Institute Vision Function Questionnaire-17 scores, and rates of relinquishing valued activities. The 2-month incidence rate of depressive disorders in problem-solving-treated subjects was significantly lower than controls (11.6% vs 23.2%, respectively; odds ratio, 0.39; 95% confidence interval, 0.17-0.92; P = .03). Problem-solving treatment also reduced the odds of relinquishing a valued activity (odds ratio, 0.48; 95% confidence interval, 0.25-0.96; P = .04). This effect mediated the relationship between treatment group and depression. By 6 months, most earlier observed benefits had diminished, though problem-solving treatment subjects were less likely to suffer persistent depression (chi2(1,3) = 8.46; P = .04). Problem-solving treatment prevented depressive disorders and loss of valued activities in patients with age-related macular degeneration as a short-term treatment, but these benefits were not maintained over time. Booster or rescue treatments may be necessary to sustain problem-solving treatment

  10. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  11. Stem cell treatment for age-related neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nurković J.

    2015-01-01

    Full Text Available The belief in the inability of neurogenesis, that is the inability to create new neurons after embryonic and early postnatal development of the central nervous system, was rejected in the mid-nineties, when the existence of neurogenesis in restricted areas of CNS adult mammals, including humans, was discovered.Transplantation of stem cells or their derivatives into respective tissues or organs is considered as one of the most promising remedies for many incurable diseases.In this review, we summarized current knowledge and present and future perspectives andchallenges regarding stem cells treatment for Parkinson's and Alzheimer's disease, as the most common age-related neurodegenerative diseases.

  12. Vision rehabilitation of persons with age related macular degeneration.

    Science.gov (United States)

    Siemsen, Dennis W; Brown, William L

    2011-05-01

    As the population of the United States ages, there is an increase in the number of persons with age related macular degeneration (ARMD). Even as new prevention and treatment techniques are developed, the vision loss associated with ARMD may lead to loss of independence and quality of life. Low vision is a rehabilitative process designed to improve visual function and restore independence. This paper is a review of the current research related to low vision in the areas of magnification, contrast and illumination, reading, training, driving and outcomes assessment.

  13. Binocular refraction in patients with age-related macular degeneration.

    Science.gov (United States)

    Skrbek, Matej

    2013-04-01

    We've been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used to prismatic correction was spontaneous and non-problematic. Based on these results we expect to find possibly the most effective rehabilitation of vision in patients suffering from ARMD.

  14. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies.

  15. Nutritional Modulation of Age-Related Macular Degeneration

    OpenAIRE

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 20...

  16. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  17. The age-related advancement of arterial disease measured by Doppler ultrasound diastolic flow analysis.

    Science.gov (United States)

    Terenzi, T; Gallagher, D; DeMeersman, R; Beadle, E; Muller, D

    1993-10-01

    To quantify by A-mode Doppler sonography the age-related progression of arterial disease so that age dependent normal values may be established for the screening Doppler peripheral arterial exam. Arterial distensibility was assessed by A-mode Doppler diastolic flow analysis as a measure of atherogenesis. These values will increase the sensitivity and decrease the incidence of false-positive results when the Doppler exam is utilized to differentially diagnosis vascular and sciatic neurogenic claudication. The relationship between age and results from the standard ankle/arm index ultrasound pneumatic cuff examination was also analyzed. A two by three analysis of variance with orthogonal Helmert contrast codes and simple linear regression analysis was utilized for this cross-sectionally designed investigation. The dependent measures of diastolic flow analysis and ankle/arm pressure index were obtained within three nested successively increasing age groups. Chiropractic office. Studied were a total of 90 sedentary nonsmoking subjects, aged 23-79 yr, all of whom had normally accepted levels of serum glucose, cholesterol and blood pressure. Subjects were screened for evidence of aortic coarctation, myocardial infarction, tachyarrhythmia, aortic valve stenosis, mitral prolapse, hypertension, hypercholesterolemia, diabetes and peripheral occlusive arterial disease. Anthropometric measurements and percent body fat were obtained. A predictive oxygen consumption bike ergometer test was performed to obtain aerobic capacity. The commonly utilized standard ankle/arm index ultrasound pneumatic cuff examination and arterial diastolic flow analysis were performed with A-mode Doppler ultrasound on all subjects. These results demonstrate that a significant inverse linear relationship exists between aging and arterial compliance (p < .0001) in our population. Diastolic flow analysis had a greater sensitivity to arterial disease than the standard ankle/arm index ultrasound pneumatic

  18. Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging.

    Science.gov (United States)

    Han, Meng; Giese, Guenter; Schmitz-Valckenberg, Steffen; Bindewald-Wittich, Almut; Holz, Frank G; Yu, Jiayi; Bille, Josef F; Niemz, Markolf H

    2007-01-01

    The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

  19. Myocardial ATP catabolism and its pharmacological prevention

    NARCIS (Netherlands)

    T. Huizer (Tom)

    1991-01-01

    textabstractThis thesis deals with high-energy phosphate metabolism during myocardial ischemia. describes the effects of some pharmacological interventions on the energy metabolism of ischemic myocardium. The chapters of this thesis are based on 11 published papers, added as appendices.

  20. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    Full Text Available BACKGROUND: Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms. METHODS AND FINDINGS: Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice. CONCLUSIONS: Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  1. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  2. Exploring age-related brain degeneration in meditation practitioners.

    Science.gov (United States)

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  3. Relationship between Aging-Related Skin Dryness and Aquaporins

    Directory of Open Access Journals (Sweden)

    Nobutomo Ikarashi

    2017-07-01

    Full Text Available Skin function deteriorates with aging, and the dermal water content decreases. In this study, we have analyzed the mechanism of aging-related skin dryness focusing on aquaporins (AQPs, which are the water channels. Mice aged 3 and 20 months were designated as young and aged mice, respectively, to be used in the experiments. No differences were observed in transepidermal water loss between the young mice and aged mice. However, the dermal water content in aged mice was significantly lower than that in young mice, thus showing skin dryness. The expression of AQP1, AQP3, AQP4, AQP7, and AQP9 was observed in the skin. All the mRNA expression levels of these AQPs were significantly lower in aged mice. For AQP3, which was expressed dominantly in the skin, the protein level was lower in aged mice than in young mice. The results of the study showed that the expression level of AQPs in the skin decreased with aging, suggesting the possibility that this was one of the causes of skin dryness. New targets for the prevention and treatment of aging-related skin dryness are expected to be proposed when the substance that increases the expression of AQP3 is found.

  4. Age-related vascular gene expression profiling in mice.

    Science.gov (United States)

    Rammos, Christos; Hendgen-Cotta, Ulrike B; Deenen, Rene; Pohl, Julia; Stock, Pia; Hinzmann, Christian; Kelm, Malte; Rassaf, Tienush

    2014-01-01

    Increasing age involves a number of detrimental changes in the cardiovascular system and particularly on the large arteries. It deteriorates vascular integrity and leads to increased vascular stiffness entailing hypertension with increased cardiovascular morbidity and mortality. The consequences of continuous oxidative stress and damages to biomolecules include altered gene expression, genomic instability, mutations, loss of cell division and cellular responses to increased stress. Many studies have been performed in aged C57BL/6 mice; however, analyses of the age-related changes that occur at a gene expression level and transcriptional profile in vascular tissue have not been elucidated in depth. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of adult and old mice, in which age-related vascular dysfunction was confirmed by increased stiffness and associated systolic hypertension. Our results highlight differentially expressed genes overrepresented in Gene Ontology categories. Molecular interaction and reaction pathways involved in vascular functions and disease, within the transforming growth factor-beta (TGF-β) pathway, the renin-angiotensin system and the detoxification systems are displayed. Our results provide insight to an altered gene expression profile related to age, thus offering useful clues to counteract or prevent vascular aging and its detrimental consequences. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. [Age-related macular degeneration: paradigm shift from recent findings].

    Science.gov (United States)

    Yanagi, Yasuo

    2015-03-01

    This review describes recent advances in age-related macular degeneration (AMD), based mainly on our own research findings. First, we investigated the effect of choroidal abnormality and found that choroidal hyperpermeability was observed more often in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD; however, even in eyes with typical AMD, substantial proportion of eyes showed hyperpermeability. Exudative AMD eyes with choroidal hyperpermeability showed thickened choroid more widely than previously demonstrated, and there were more frequent abnormalities with fundus autofluorescence examination. Thus, rather than classifying exudative AMD into PCV and typical AMD, AMD classification by choroidal hyperpermeability may be useful in illustrating the difference of certain clinical characteristics. Second, we investigated the importance of vitreomacular adhesion in the treatment outcome of exudative AMD. The currently prevailing hypothesis is that premacular VEGF concentration is lower in eyes with posterior vitreous detachment (PVD) than in eyes without PVD, thus leading to good treatment outcomes; however, in the current study, we showed that not only VEGF but also anti-angiogenic factor, interferon-inducible protein 10 (IP-10), is affected according to PVD. These results suggest that the effect of PVD on the intraocular environment is more complicated than previously thought, and may have diverse functions. Last, we explained the mechanism of AMD progression based mainly on our basic research. Our research showed that age-related decline of autophagic activity may, at least partly, contribute to the precursor lesion of AMD.

  6. Mitochondrial theory of aging in human age-related sarcopenia.

    Science.gov (United States)

    Parise, Gianni; De Lisio, Michael

    2010-01-01

    Understanding age-related sarcopenia and, more importantly, devising counterstrategies require an intimate knowledge of the underlying mechanism(s) of sarcopenia. The mitochondrial theory of aging (MTA) has been a leading theory on aging for the last decade; however, there is relatively little information from human tissue to support or rebut the involvement of the MTA in aging skeletal muscle. It is believed that mitochondria may contribute to sarcopenia in a stochastic fashion where regions of fibers containing dysfunctional mitochondria are forced to atrophy. Resistance exercise, a known hypertrophic stimulus, has been shown to improve the mitochondrial phenotype of aged skeletal muscle. Furthermore, activation of skeletal muscle stem cells by resistance exercise may attenuate sarcopenia in two ways. First by inducing nuclear addition to postmitotic fibers, and, second, by increasing the proportion of functional mitochondria donated by muscle stem cells in a process termed 'gene shifting'. In this chapter we review the evidence supporting the MTA, the potential to attenuate the MTA with a known hypertrophic stimuli and explore the role of muscle stem cells in gene shifting to determine the connection between mitochondrial dysfunction and age-related sarcopenia. Copyright © 2010 S. Karger AG, Basel.

  7. Age-related changes to the production of linguistic prosody

    Science.gov (United States)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  8. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  9. Nitroxide Pharmaceutical Development for Aging-Related Degeneration & Disease

    Directory of Open Access Journals (Sweden)

    Jacob A. Zarling

    2015-11-01

    Full Text Available Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP, Tempol Hydroxylamine (TP-H, and TP-H prodrug (OT-551 are evaluated in (1 nonsmokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2 elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3 elderly smoker or nonsmoker Age-related Macular Degeneration (AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and reducing low luminance deficit and night vision loss in dry AMD smokers and non-smoker patients. Topical, oral or injectable drug formulations are discussed.

  10. KCNQ channels regulate age-related memory impairment.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  11. METABOLISM

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective: To determine the allele frequencies of genetic variants 373 Ala→Pro and 451 Arg→Gln of cholesteryl ester transfer protein (CETP) and to explore their potential impacts on serum lipid metabolism. Methods: The genotypes in CETP codon 373 and 451 in 91 German healthy students and 409 an-

  12. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  13. The dopamine D3 receptor knockout mouse mimics aging-related changes in autonomic function and cardiac fibrosis.

    Directory of Open Access Journals (Sweden)

    Tracy L Johnson

    Full Text Available Blood pressure increases with age, and dysfunction of the dopamine D3 receptor has been implicated in the pathogenesis of hypertension. To evaluate the role of the D3 receptor in aging-related hypertension, we assessed cardiac structure and function in differently aged (2 mo, 1 yr, 2 yr wild type (WT and young (2 mo D3 receptor knockout mice (D3KO. In WT, systolic and diastolic blood pressures and rate-pressure product (RPP significantly increased with age, while heart rate significantly decreased. Blood pressure values, heart rate and RPP of young D3KO were significantly elevated over age-matched WT, but similar to those of the 2 yr old WT. Echocardiography revealed that the functional measurements of ejection fraction and fractional shortening decreased significantly with age in WT and that they were significantly smaller in D3KO compared to young WT. Despite this functional change however, cardiac morphology remained similar between the age-matched WT and D3KO. Additional morphometric analyses confirmed an aging-related increase in left ventricle (LV and myocyte cross-sectional areas in WT, but found no difference between age-matched young WT and D3KO. In contrast, interstitial fibrosis, which increased with age in WT, was significantly elevated in the D3KO over age-matched WT, and similar to 2 yr old WT. Western analyses of myocardial homogenates revealed significantly increased levels of pro- and mature collagen type I in young D3KO. Column zymography revealed that activities of myocardial MMP-2 and MMP-9 increased with age in WTs, but in D3KO, only MMP-9 activity was significantly increased over age-matched WTs. Our data provide evidence that the dopamine D3 receptor has a critical role in the emergence of aging-related cardiac fibrosis, remodeling, and dysfunction.

  14. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice.

    Science.gov (United States)

    Stout, Michael B; Tchkonia, Tamara; Pirtskhalava, Tamar; Palmer, Allyson K; List, Edward O; Berryman, Darlene E; Lubbers, Ellen R; Escande, Carlos; Spong, Adam; Masternak, Michal M; Oberg, Ann L; LeBrasseur, Nathan K; Miller, Richard A; Kopchick, John J; Bartke, Andrzej; Kirkland, James L

    2014-07-01

    The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible.

  15. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice

    Science.gov (United States)

    Pirtskhalava, Tamar; Palmer, Allyson K.; List, Edward O.; Berryman, Darlene E.; Lubbers, Ellen R.; Escande, Carlos; Spong, Adam; Masternak, Michal M.; Oberg, Ann L.; LeBrasseur, Nathan K.; Miller, Richard A.; Kopchick, John J.; Bartke, Andrzej; Kirkland, James L.

    2014-01-01

    The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible. PMID:25063774

  16. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    Science.gov (United States)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  17. Effect of Ligustrazine and Shenmai Injection on ATPase and free radical metabolism in the aged rats with myocardial injury after brain ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the protecitve mechanism of Ligustrazine (LT), Shenmai Parenteral Injection (SPI), combination of Ligustrazine and Shenmai Parenteral Injection (LSP) to myocardial injury after brain ischemia-reperfusion in aged rats from the change in ATPase and free radical in order to provide theoretical basic for prevention and cure of cerebral infarction. METHODS: Aged rats (more than 20 months) were divided into model group, control group, Nimotop group, LT group, SPI group and LSP group. We measured the following items in aged rats with 60 min of reperfusion after 30 min of brain ischemia: the content of MDA, the activities of superoxide dismutase (SOD), lactic dehydrrogenase (LDH), creatine phosphokinase (CPK), ATPase. RESUTLS: The CPK and LDH activities in the model rats increased obviously. The serum CPK activity in the LSP group, the LT group, nimotop group was lower than those in the model group obviously. The serum LDH activities in LT group and SPI group were obviously lower compared with those in the model group. The activity of Na+-K+-ATPase and Ca2+-ATPase in model group was decreased. Contrast to the model group, the activity of Na+-K+-ATPase in LSP group, Nimotop group, LT group and the activities of Ca2+-ATPase in the LSP group were higher. The serum MDA/SOD ratio was larger than that in the control group. The decrease in myocardial SOD activity and the increase in the MDA level, MDA/SOD ratio in the model group showed significant difference compared with that in the control. The MDA level in the LSP group was lower than that in the model group. The increase in myocardial SOD activity and decrease in MDA, MDA/SOD ratio were obvious in the LSP group compared with the model group. CONCLUSION: The myocardial injury after brain ischemia-reperfusion in aged rats was related to the decrease in the activity of Na+-K+-ATPase and injury of free radical. LT, SPI, LSP and Nimotop could prevent this inury. Nimotop and LT could enhanced the

  18. Validation of {sup 99m}Tc-labeled '4+1' fatty acids for myocardial metabolism and flow imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mirtschink, Peter [Institute of Physiology, Technical University Dresden, 01307 Dresden (Germany)], E-mail: peter_mirtschink@web.de; Stehr, Sebastian N. [Department of Anesthesiology, Technical University Dresden, 01307 Dresden (Germany); Walther, Martin; Pietzsch, Jens; Bergmann, Ralf; Pietzsch, Hans-Juergen [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, 01314 Dresden (Germany); Weichsel, Johannes; Pexa, Annette; Dieterich, Peter [Institute of Physiology, Technical University Dresden, 01307 Dresden (Germany); Wunderlich, Gerd [Department of Nuclear Medicine, Technical University Dresden, 01307 Dresden (Germany); Binas, Bert [Department of Veterinary Pathobiology, Texas A and M University, College Station, TX 77843 (United States); Kropp, Joachim [Department of Nuclear Medicine Carl-Thiem Hospital Cottbus, 03048 Cottbus (Germany); Deussen, Andreas [Institute of Physiology, Technical University Dresden, 01307 Dresden (Germany)

    2009-10-15

    Introduction: {sup 13}C, {sup 18}F and {sup 123}I fatty acids (FA) are used for myocardial imaging. Recently, our group showed that [{sup 99m}Tc]-labeled '4+1' FA are extracted into the rat and guinea pig myocardium. The present study evaluates determinants of myocardial uptake and whole body biodistribution of these FA derivatives. Methods: Studies were performed with isolated perfused hearts of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with a FAT/CD36 deficiency, as well as with heart type FA binding protein knockout mice (H-FABP){sup -/-} and H-FABP{sup +/+}. Eight 4+1-{sup 99m}Tc-FA were applied for 3 min followed by 1-min washout. A mathematical model was used to analyze FA dynamics and binding to proteins. Whole-body distribution was studied in rats with and without Tween 80. In vitro fractionation studies with [{sup 99m}Tc]-FA assessed red blood cell uptake as well as association with plasma lipoproteins very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Results: Myocardial extraction was 19.0-33.0% of the infused dose in isolated WKY and 15.2-26.4% in SHR hearts. However, H-FABP{sup -/-} showed a marked reduction of tracer extraction [2.8{+-}0.6%ID (percent injected dose) vs. 17{+-}2%ID P<.001]. Uptake in red blood cells (<1.2%ID) and incorporation into lipoproteins were negligible. Incubation of {sup 99m}Tc-FA with albumin reduced ventricular extraction (P<.001) into the range of established iodinated FA tracers. polyoxyethylene(20) sorbitan monooleate improved the heart-to-liver ratio in the biodistribution studies. Conclusions: Myocardial uptake of [{sup 99m}Tc]-FA 4+1 derivatives is dependent on H-FABP. These substances may therefore provide a new tool to specifically assess regional myocardial changes of H-FABP.

  19. Age-related changes in cardiovascular performance in mitral regurgitation: analysis of 61 patients.

    Science.gov (United States)

    Clancy, K F; Iskandrian, A S; Hakki, A H; Nestico, P; DePace, N L

    1985-03-01

    This study examines the cardiovascular performance in relation to age in 61 patients with moderate or severe chronic mitral regurgitation (MR). Coronary artery disease (CAD) (50% or more diameter narrowing of one or more major coronary arteries) was present in 20 patients (33%). Patients less than 60 years (n = 33) had lower pulmonary artery pressure, systolic arterial pressure, left ventricular (LV) end-diastolic pressure, and pulmonary artery wedge pressure than the patients greater than or equal to 60 years (n = 28) (p less than 0.05). In the 41 patients without associated CAD, the LV end-diastolic pressure and systemic arterial pressure were higher in patients greater than or equal to 60 years (n = 14) than patients less than 60 years (n = 27) (p less than 0.05). The LV end-diastolic pressure showed an age-related increase in the presence or absence of CAD. Thus, older patients with MR have higher LV end-diastolic pressure, probably because of an increase in myocardial stiffness.

  20. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... stem cells (MSCs) that are present in the bone marrow and are able to differentiate into cell types such as osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like cells. Because of the ease of their isolation and their extensive differentiation potential, MSCs are among the first...

  1. The Neural Consequences of Age-Related Hearing Loss.

    Science.gov (United States)

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.

  2. [Future methods of treatment in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.

  3. Wearable diagnostic system for age-related macular degeneration.

    Science.gov (United States)

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  4. AMO Teledioptric System for age-related macular degeneration

    Science.gov (United States)

    Chou, Jim-Son; Ting, Albert C.

    1994-05-01

    A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

  5. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  6. Redox control of senescence and age-related disease

    Directory of Open Access Journals (Sweden)

    Akshaya Chandrasekaran

    2017-04-01

    Full Text Available The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology.

  7. Metalloproteinases and metalloproteinase inhibitors in age-related diseases.

    Science.gov (United States)

    Gargiulo, Simona; Gamba, Paola; Poli, Giuseppe; Leonarduzzi, Gabriella

    2014-01-01

    Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS). This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

  8. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

    Full Text Available Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  9. The genetics of age-related macular degeneration.

    Science.gov (United States)

    Guymer, Robyn

    2001-07-01

    AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.

  10. Age-related differences in attentional bias for emotional faces.

    Science.gov (United States)

    Tomaszczyk, Jennifer C; Fernandes, Myra A

    2014-01-01

    Past research suggests an aging-related positivity effect in orienting to faces. However, these studies have eschewed direct comparison of orienting when positive and negative faces are presented simultaneously, thereby potentially underestimating the degree to which emotional valence influences such effects. In the current study younger and older adults viewed face pairs for 1000 ms, and upon face-pair offset indicated the location of a dot that appeared in the former location of one of the faces, to assess attentional orienting. When shown negative-neutral pairs, both age groups were biased to attend to negative faces, but when shown positive-negative pairs only younger adults showed a bias toward negative; older adults showed a lack of orienting toward either emotional face. Results suggest younger adults have a negativity bias in attention orienting regardless of the valence of nearby stimuli, whereas older adults show an absence of this bias when positive information is present.

  11. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  12. [Etiology and pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Herrmann, P; Holz, F G; Charbel Issa, P

    2013-04-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in Germany. Due to the demographic development a further increase of affected patients is to be expected. Improved understanding of AMD pathogenesis resulted from the molecular biological approaches in recent years and showed an association of genetic factors with AMD. The complement factor H gene and the second high-risk locus ARMS2 in particular were found to contribute a significant risk for development of the disease. Ageing and environmental factors, such as smoking, modulate the individual genetic risk profile. A detailed understanding of the complex AMD pathogenesis is also relevant in ophthalmological practice to understand new treatment strategies. In this review we aim to give an overview of the interplay of ageing, external environmental factors and genetic risk variants leading to AMD.

  13. Age-related differences in arithmetic strategy sequential effects.

    Science.gov (United States)

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  14. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    Visual selection of illusory ‘Kanizsa’ figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form – an instance of ‘global precedence’ in visual processing....... Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global....... Electrophysiologically, this effect was accompanied by an early (150-225 ms) ‘positivity posterior contralateral’ (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing...

  15. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith;

    2015-01-01

    , a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5 mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard...... for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.......OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  16. Myocardial Infarction Type 2 and Myocardial Injury

    DEFF Research Database (Denmark)

    Sandoval, Yader; Thygesen, Kristian

    2017-01-01

    BACKGROUND: The development and implementation of sensitive and high-sensitivity cardiac troponin assays has not only expedited the early ruling in and ruling out of acute myocardial infarction, but has also contributed to the identification of patients at risk for myocardial injury with necrosis......, as confirmed by the presence of cardiac troponin concentrations above the 99th percentile. Myocardial injury with necrosis may occur either in the presence of overt ischemia from myocardial infarction, or in the absence of overt ischemia from myocardial injury accompanying other conditions. Myocardial...... infarction type 2 (T2MI) has been a focus of attention; conceptually T2MI occurs in a clinical setting with overt myocardial ischemia where a condition other than an acute atherothrombotic event is the major contributor to a significant imbalance between myocardial oxygen supply and/or demand. Much debate...

  17. Serum 25-hydroxyvitamin D and Age-Related Cataract.

    Science.gov (United States)

    Park, Sangshin; Choi, Nam-Kyong

    2017-10-01

    Cataract and insufficient vitamin D intake are both increasing worldwide concerns, yet little is known about the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and age-related cataract. We performed this study to determine the association between serum 25(OH)D levels and age-related cataract in adults. Study participants comprised 16,086 adults aged 40 years or older who had never been diagnosed with or undergone surgery for cataract using Korean National Health and Nutrition Examination Survey data from 2008 to 2012. Participants were assessed to have cataract when diagnosed with cortical, nuclear, anterior subcapsular, posterior subcapsular, or mixed cataract. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the magnitude and significance of the association between serum 25(OH)D levels and cataract in multivariable logistic regression models. The OR for nuclear cataract with the highest quintile of serum 25(OH)D levels was 0.86 (95% CI 0.75-0.99) compared to the lowest quintile. A linear trend across quintiles was significant. Natural log-transformed serum 25(OH)D levels were also significantly associated with nuclear cataract (OR 0.84, 95% CI 0.75-0.95). The opulation-attributable fraction of nuclear cataract due to serum 25(OH)D insufficiency (D levels were inversely associated with the risk of nuclear cataract. Prospective studies investigating the effects of serum 25(OH)D levels on the development of nuclear cataract are needed to confirm our findings.

  18. Nutritional modulation of age-related macular degeneration.

    Science.gov (United States)

    Weikel, Karen A; Chiu, Chung-Jung; Taylor, Allen

    2012-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.

  19. Inflammation and its role in age-related macular degeneration.

    Science.gov (United States)

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.

  20. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  1. Stem cell therapies in age-related neurodegenerative diseases and stroke.

    Science.gov (United States)

    Wang, Yuan; Ji, Xunming; Leak, Rehana K; Chen, Fenghua; Cao, Guodong

    2017-03-01

    Aging, a complex process associated with various structural, functional and metabolic changes in the brain, is an important risk factor for neurodegenerative diseases and stroke. These diseases share similar neuropathological changes, such as the formation of misfolded proteins, oxidative stress, loss of neurons and synapses, dysfunction of the neurovascular unit (NVU), reduction of self-repair capacity, and motor and/or cognitive deficiencies. In addition to gray matter dysfunction, the plasticity and repair capacity of white matter also decrease with aging and contribute to neurodegenerative diseases. Aging not only renders patients more susceptible to these disorders, but also attenuates their self-repair capabilities. In addition, low drug responsiveness and intolerable side effects are major challenges in the prevention and treatment of senile diseases. Thus, stem cell therapies-characterized by cellular plasticity and the ability to self-renew-may be a promising strategy for aging-related brain disorders. Here, we review the common pathophysiological changes, treatments, and the promises and limitations of stem cell therapies in age-related neurodegenerative diseases and stroke. Published by Elsevier B.V.

  2. Role of cancer stem cells in age-related rise in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Pratima; Nangia-Makker; Yingjie; Yu; Adhip; PN; Majumdar

    2015-01-01

    Colorectal cancer(CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells(CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of(1) CSC;(2) epigenetic and genetic mechanisms giving rise to CSCs;(3) markers of CSC;(4) characteristics; and(5) age-related increase in CSC in the colonic crypt.

  3. Role of cancer stem cells in age-related rise in colorectal cancer

    Science.gov (United States)

    Nangia-Makker, Pratima; Yu, Yingjie; Majumdar, Adhip PN

    2015-01-01

    Colorectal cancer (CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells (CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of (1) CSC; (2) epigenetic and genetic mechanisms giving rise to CSCs; (3) markers of CSC; (4) characteristics; and (5) age-related increase in CSC in the colonic crypt. PMID:26600965

  4. Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway.

    Science.gov (United States)

    Kim, Mi Kyung; Chung, Sang Woon; Kim, Dae Hyun; Kim, Ji Min; Lee, Eun Kyeong; Kim, Ji Young; Ha, Young Mi; Kim, Yun Hee; No, Jae-Kyung; Chung, Hye Sun; Park, Kun-Young; Rhee, Sook Hee; Choi, Jae Sue; Yu, Byung Pal; Yokozawa, Takako; Kim, Young Jin; Chung, Hae Young

    2010-06-01

    Zingerone, a major component found in ginger root, has been known as anti-mutagenic and anti-carcinogenic activities that are often associated with its anti-oxidative and anti-inflammatory activities. In recent studies, we examined molecular mechanism of zingerone treatment on pro-inflammatory NF-kappaB activation via the redox-related NIK/IKK and MAPK pathways. Action mechanism of zingerone on NF-kappaB signaling was investigated in aged rat kidney and endothelial cells. The results showed that zingerone had not only the antioxidant effect by constitutive suppression of ROS, but also anti-inflammatory effects by suppression of nuclear factor (NF)-kappaB activation in aged rat. In addition, zingerone treatment suppressed gene activation of pro-inflammatory enzymes, COX-2 and iNOS, which were upregulated with aging through NF-kappaB activation and IKK/MAPK signaling pathway. These experiments strongly indicate that zingerone treatment exerts a beneficial efficacy by suppressing both oxidative stress and age-related inflammation through the modulation of several key pro-inflammatory genes and transcription factors. Thus, the significance of our findings is that the zingerone treatment may provide some preventive measure against chronic inflammatory conditions that underlie many age-related inflammatory diseases, such as metabolic syndrome, cardiovascular disease, dementia, arthritis, diabetes, osteoprosis, and cancers.

  5. Research Progress of Chinese Medicine in Inhibiting Myocardial Fatty Acid Metabolism%中医药抑制心脏脂肪酸代谢的研究进展

    Institute of Scientific and Technical Information of China (English)

    王通; 李彬; 朱明军; 王永霞; 高原; 谢世阳; 谢航; 郝轩轩

    2016-01-01

    慢性心力衰竭(CHF)是一种由各种心脏疾病导致心功能不全的复杂临床症候群,是各种心脏疾患的终末状态。能量代谢障碍是心衰的原因,也可作为心衰的继发后果。21世纪,以心肌代谢重构为靶点的心肌代谢疗法成为治疗热点,也是治疗理念的一大转变,针对慢性心力衰竭,中医药在控制症状﹑改善预后﹑减少西药毒副反应﹑调整病人机体的免疫功能﹑减少心衰复发和提高病人生活质量等方面具有独特的疗效优势,因此,慢性心衰是心血管领域中医药防治的优势病种,以抑制心脏脂肪酸代谢为切入点,开展中医药调控心肌能量代谢防治慢性心力衰竭具有广阔前景和应用价值。%Chronic heart failure(CHF)is a complex clinical symptom group,which is caused by various heart diseases,and is the end of al kinds of heart diseases.Energy metabolism disorders can be used as the cause of heart failure,but also as a secondary conse-quence of heart failure.In twenty first century,myocardial metabolic therapy,which is the target of myocardial metabolism,has be-come a hot spot for treatment,but also a major change in the concept of treatment,in chronic heart failure,Chinese medicine to con-trol symptoms,improve the prognosis and reduce the drug adverse reaction,adjust the body of the patient's immune function,reduce the recurrence of heart failure,improve the quality of life of patients and has unique advantages in efficacy.CHF is the dominant dis-eases of cardiovascular field of prevention and treatment of Chinese medicine,to inhibit the metabolism of fatty acids as starting point and has a broad prospect and application value to carry out Chinese medicine in regulation of myocardial energy metabolism in pre-vention and treatment of chronic heart failure.

  6. Progress on retinal image analysis for age related macular degeneration.

    Science.gov (United States)

    Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ∼1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which

  7. Age-related macular degeneration: beyond anti-angiogenesis.

    Science.gov (United States)

    Kent, David L

    2014-01-06

    Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate

  8. The energy-redox axis in aging and age-related neurodegeneration.

    Science.gov (United States)

    Yap, Li-Peng; Garcia, Jerome V; Han, Derick; Cadenas, Enrique

    2009-11-30

    Decrease in mitochondrial energy-transducing capacity is a feature of the aging process that accompanies redox alterations, such as increased generation of mitochondrial oxidants, altered GSH status, and increased protein oxidation. The decrease in mitochondrial energy-transducing capacity and altered redox status should be viewed as a concerted process that embodies the mitochondrial energy-redox axis and is linked through various mechanisms including: (a) an inter-convertible reducing equivalents pool (i.e., NAD(P)(+)/NAD(P)H) and (b) redox-mediated protein post-translational modifications involved in energy metabolism. The energy-redox axis provides the rationale for therapeutic approaches targeted to each or both component(s) of the axis that effectively preserves or improve mitochondrial function and that have implications for aging and age-related neurodegenerative disorders.

  9. Classifying human audiometric phenotypes of age-related hearing loss from animal models.

    Science.gov (United States)

    Dubno, Judy R; Eckert, Mark A; Lee, Fu-Shing; Matthews, Lois J; Schmiedt, Richard A

    2013-10-01

    Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations ("audiometric phenotypes"). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for "exemplars" (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.

  10. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    Science.gov (United States)

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  11. Myocardial Bridge

    Science.gov (United States)

    ... Kawasaki Disease Long Q-T Syndrome Marfan Syndrome Metabolic Syndrome Mitral Valve Prolapse Myocarditis Obstructive Sleep Apnea Pericarditis Peripheral Vascular Disease Rheumatic Fever Sick Sinus Syndrome Silent Ischemia Stroke Sudden ...

  12. Age-related neuroinflammatory changes negatively impact on neuronal function

    Directory of Open Access Journals (Sweden)

    Marina A Lynch

    2010-01-01

    Full Text Available Neuroinflammatory changes, characterized by an increase in microglial activation and often accompanied by upregulation of inflammatory cytokines like interleukin-1β (IL-1β, are common to many, if not all, neurodegenerative diseases. Similar, though less dramatic neuroinflammatory changes are also known to occur with age. Among the consequences of these changes is an impairment in synaptic function and the evidence suggests that inflammatory cytokines may be the primary contributory factor responsible for the deficits in synaptic plasticity which have been identified in aged rodents. Specifically a decrease in the ability of aged rats to sustain long-term potentiation (LTP in perforant path-granule cells of the hippocampus is associated with increased microglial activation. This review considers the evidence which suggests a causal relationship between these changes and the factors which contribute to the age-related microglial activation, and reflects on data which demonstrate that agents which inhibit microglial activation also improve ability of rats to sustain LTP.

  13. Treatment of neovascular age-related macular degeneration: Current therapies

    Directory of Open Access Journals (Sweden)

    Albert J Augustin

    2009-01-01

    Full Text Available Albert J Augustin, Stefan Scholl, Janna KirchhofDepartment of Ophthalmology, Klinikum Karlsruhe, GermanyAbstract: Choroidal neovascularization (CNV secondary to age-related macular degeneration (AMD is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition.Keywords: wet AMD, neovascularization, PDT, steroids, anti-angiogenesis

  14. Effect of NCAM on aged-related deterioration in vision.

    Science.gov (United States)

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging.

  15. Sunlight exposure, antioxidants, and age-related macular degeneration.

    Science.gov (United States)

    Fletcher, Astrid E; Bentham, Graham C; Agnew, Maureen; Young, Ian S; Augood, Cristina; Chakravarthy, Usha; de Jong, Paulus T V M; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vingerling, Johannes R; Vioque, Jesus

    2008-10-01

    To examine the association of sunlight exposure and antioxidant level with age-related macular degeneration (AMD). Four thousand seven hundred fifty-three participants aged 65 years or older in the European Eye Study underwent fundus photography, were interviewed for adult lifetime sunlight exposure, and gave blood for antioxidant analysis. Blue light exposure was estimated by combining meteorologic and questionnaire data. Data on sunlight exposure and antioxidants were available in 101 individuals with neovascular AMD, 2182 with early AMD, and 2117 controls. No association was found between blue light exposure and neovascular or early AMD. Significant associations were found between blue light exposure and neovascular AMD in individuals in the quartile of lowest antioxidant level-vitamin C, zeaxanthin, vitamin E, and dietary zinc-with an odds ratio of about 1.4 for 1 standard deviation unit increase in blue light exposure. Higher odds ratios for blue light were observed with combined low antioxidant levels, especially vitamin C, zeaxanthin, and vitamin E (odds ratio, 3.7; 95% confidence interval, 1.6-8.9), which were also associated with early stages of AMD. Although it is not possible to establish causality between sunlight exposure and neovascular AMD, our results suggest that people in the general population should use ocular protection and follow dietary recommendations for the key antioxidant nutrients.

  16. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  17. Age-Related Changes in Trabecular Meshwork Imaging

    Directory of Open Access Journals (Sweden)

    Mark E. Gold

    2013-01-01

    Full Text Available Purpose. To evaluate the normal aging effects on trabecular meshwork (TM parameters using Fourier domain anterior segment optical coherence tomography (ASOCT images. Patients and Methods. One eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18–40, 41–60, and 61–80. Measurements were compared using stepwise regression analysis. Results. The average TM parameters were 0.0487 (±0.0092 mm2 for TM area, 0.5502 (±0.1033 mm for TM length, 0.1623 (±0.341 mm2 for TM interface shadow area, and 0.7755 (±0.1574 mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length to 0.82 (TM area. TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters. Conclusion. Although the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function.

  18. Age-related hearing loss increases cross-modal distractibility.

    Science.gov (United States)

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  19. Age-related changes in the efficacy of crystalloid cardioplegia.

    Science.gov (United States)

    Magovern, J A; Pae, W E; Waldhausen, J A

    1991-09-01

    Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10 degrees C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means +/- standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 +/- 8.2 and 66.2 +/- 7.7%) than in the 6- and 8-week hearts (93.0 +/- 6.4 and 97.6 +/- 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations.

  20. eNOS-uncoupling in age-related erectile dysfunction

    Science.gov (United States)

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  1. Imaging polarimetry in age-related macular degeneration.

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2008-06-01

    To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques--scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)--and investigate how they complement each other. The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD.

  2. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

    Full Text Available The positivity effect refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather & Carstensen, 2005 scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision-making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people.

  3. Fundus Autofluorescence in Age-related Macular Degeneration

    Science.gov (United States)

    Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  4. Age-Related Deficits in Conjunctive Representation of Complex Objects

    Science.gov (United States)

    Scheerer, Nichole; Marrone, Diano F.

    2014-01-01

    Although some evidence is consistent with the notion that distinct cortical systems support memory and perception, mounting evidence supports a representational-hierarchical view of cognition, which posits that distinctions lie in simple feature representations versus more complex conjunctive representations of many stimulus features simultaneously. Thus, typical memory tasks engage different regions from typical perception tasks because they inherently test information on opposing ends of this continuum. Memory deficits are reliably reported with age, but the tasks used to make these conclusions predominantly rely on conjunctive representations. To test the extent to which age-related deficits may be accounted for by perceptual processing, this study investigated discriminations involving conjunctive representations in older adults. Results show that adults aged 50 to 77 are impaired, relative to their younger counterparts, on discriminations requiring feature conjunctions, but not simple feature representations. These findings support recent data showing an agerelated decline in the ability to form conjunctive representations. Furthermore, these data suggest that some ‘mnemonic’ deficits associated with age may in fact be the result of deficits in perception rather than memory. PMID:25308561

  5. Stereotactic radiotherapy in neovascular age-related macular degeneration

    Science.gov (United States)

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  6. Activity loss and depression in age-related macular degeneration.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J

    2002-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of severe vision loss in older persons and is associated with high rates of disability and depression. The authors evaluated 51 patients with bilateral AMD to investigate the interrelationships of disease severity, disability, and depression and focused on loss of valued activities as an emblematic disabling consequence of AMD. They characterized depression by the Center for Epidemiologic Studies-Depression (CES-D) score, a syndromal state based on the CES-D, and as a level of distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%) had loss of a valued, discretionary activity. They had worse visual acuity and more depressive symptoms and were represented in higher IAS levels than other subjects. Visual acuity was significantly correlated with IAS levels, but not with CES-D scores or syndromal depression. A regression model demonstrated that activity loss mediated the relationship between visual acuity and IAS level. Affective distress occurs in AMD, largely to the extent that valued activities are relinquished because of vision loss. IAS levels best illuminated this relationship, suggesting the value of this dimension of affective functioning in studies of the consequences of chronic disease.

  7. Age-related changes in skin topography and microcirculation.

    Science.gov (United States)

    Li, Li; Mac-Mary, Sophie; Marsaut, David; Sainthillier, Jean Marie; Nouveau, Stéphanie; Gharbi, Tijani; de Lacharriere, Olivier; Humbert, Philippe

    2006-03-01

    Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

  8. The Chromospheric Activity-Age Relation for M Dwarf Stars

    Science.gov (United States)

    Silvestri, N. M.; Oswalt, T. D.; Hawley, S. L.

    2000-12-01

    We present preliminary results from our study in which we use moderate resolution spectroscopy to determine the correlation between the chromospheric activity and age of M dwarf stars in wide binary systems. We have observed ~50 M dwarf stars from our sample with the Apache Point Observatory 3.5-m telescope. We measure the ratio of Hα luminosity to the bolometric luminosity (LHα /Lbol) of the M dwarf---a measure of activity that is proven to correlate well with age. This project is unique in that it will extend the chromospheric activity-age relation of low-mass main sequence stars beyond the ages provided by cluster methods. The ages so determined are also independent of the uncertainties in cluster age determinations. The technique has the potential to improve by at least a factor of two the precision and the range over which ages can currently be determined for main sequence stars. Work on this project is supported by the NASA Graduate Student Researchers Program grant NGT-50290 (N.M.S.).

  9. Imaging Polarimetry in Age-Related Macular Degeneration

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2010-01-01

    PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

  10. Nitroxide pharmaceutical development for age-related degeneration and disease.

    Science.gov (United States)

    Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.

  11. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  12. Mechanism of inflammation in age-related macular degeneration.

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  13. Breed- and age-related differences in canine mammary tumors.

    Science.gov (United States)

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  14. Impact of Endothelial Progenitor Cells on Myocardial Enzyme and Energy Metabolism of Patients with Heart Failure after Myocardial Infarction%内皮祖细胞治疗心肌梗死后心力衰竭患者心肌酶及能量代谢的改变

    Institute of Scientific and Technical Information of China (English)

    赵子粼; 罗建春; 黄梁艳; 覃善都; 郑学鸥; 许顶立

    2012-01-01

    目的 应用粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)动员内皮祖细胞(endothelial progenitor cells,EPCs)治疗心肌梗死后心力衰竭患者,研究其对心肌组织中超氧化物歧化酶(superoxide dismutase,SOD)活性、脂质过氧化物(lipid peroxidation,LPO)、丙二醛(malondialdehyde,MDA)及心肌能量代谢的影响.方法 选取38例心肌梗死患者,入院后均接受心肌梗死的常规治疗,随机分成治疗组和对照组.治疗组除常规治疗外还给予动员剂G-CSF(450 μg/d)皮下注射,连续注射5天.检测两组治疗前、治疗后第3、7、14、28天外周血EPCs数量;于治疗前、治疗后1个月检测两组SOD、LPO、MDA含量,并行心脏超声检测左心室射血分数(left ventricular ejection fraction,LVEF)等左心室心功能指标,应用相关公式计算左心室收缩末圆周室壁应力(circumferential end-systolic wall stress,cESS)、心肌能量消耗(myocardial energy expenditure,MEE).结果 治疗组的EPCs数量较治疗前及对照组增加明显,于第7天达到峰值,增加有统计学意义(P<0.01);两组患者治疗后心肌能量代谢均好转,心肌组织中SOD活性提高,LPO、MDA生成减少,LVEF升高,cESS下降,MEE水平降低,心功能得到改善,治疗组改善优于对照组,差异有统计学意义(P<0.05).结论 应用G-CSF动员EPCs治疗心肌梗死后心力衰竭患者,EPCs具有保护缺血心肌,增强SOD活性,抑制LPO、MDA的生成,降低心肌耗氧,有效改善心脏功能的作用.%Objective To study the changes of myocardial enzyme and energy metabolism in patients with heart failure after myocardial infarction treated by granulocyte colony stimulating factor. Methods A total of 38 patients with myocardial infarction were randomly divided into treatment group and control group. All patients received conventional treatment (medication and interventional therapy), and treatment group underwent additional G-CSF mobilization

  15. Detection of myocardial metabolic abnormalities by 18F-FDG PET/CT and corresponding pathological changes in beagles with local heart irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Rul [Nursing College of Shanxi Medical University, Taiyuan (China); Song, Jianbo; Wu, Zhi Fang; Liu, Jian Zhang; Hao, Xin Zhong; Li, Sijin [Dept. of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan (China); Guo, Min [Dept. of Cardiology, First Hospital of Shanxi Medical University, Taiyuan (China); Li, Jianguo [Dept. of Radiological and Environmental Medicine, China Institute for Radiation Protection, Taiyuan (China)

    2015-08-15

    To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings. The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy. Using the 12H-F protocol, the average INRs were 1.18 ± 0.10 and 1.41 ± 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 ± 0.15 and 2.54 ± 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles. High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.

  16. Age-related distance esotropia: Clinical features and therapeutic outcomes.

    Science.gov (United States)

    Gómez de Liaño Sánchez, P; Olavarri González, G; Merino Sanz, P; Escribano Villafruela, J C

    2016-12-01

    To describe the clinical characteristics and surgical outcomes of a group of patients with age-related distance esotropia (ARDE). A retrospective study was conducted on a consecutive case series of 16 adult patients diagnosed with ARDE between 2008 and 2015. The clinical features evaluated included mean age and gender, primary position deviations at distance and near, measured in prism dioptres (pd), treatment offered in each case, and post-surgical deviations. Ductions and versions were full, with no evidence of lateral rectus paresis. None of these patients had any obvious underlying neurological disorder, such as, high myopia or thyroid disease. A good result is considered to be the disappearance of diplopia in all positions of gaze. A total of 16 patients (11 females [68.8%]) were identified. The mean age at diagnosis was 78.19±6.77 years. The mean initial esodeviation was 2.25±3.08 pd at near (-4 to +8 pd) and 9.5±4.18 pd at distance (2 to 18 pd). Treatment was not necessary in 5 cases because the symptoms were intermittent or well-tolerated. Of the 11 patients with symptoms, one was corrected with an external base therapeutic prism. Botulinum toxin was administered in another patient, without satisfactory results. Unilateral medial rectus muscle recession was performed on one patient, and unilateral lateral rectus plication on 7 patients, indicating prisms before surgery. One patient refused surgery despite continuous diplopia in far vision. After a mean follow-up of 16.5 months, all operated patients were asymptomatic. Not all patients with ARDE require treatment, as the tolerance to diplopia varies from one subject to another. Both medial rectus weakening and lateral rectus strengthening provides excellent results. Crown Copyright © 2016. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

    Science.gov (United States)

    Ruiz Ramos, J; Pascual-Camps, I; Cuéllar-Monreal, M J; Dolz-Marco, R; Fenoll, M A; Font-Noguera, I; Poveda-Andrés, J L; Gallego-Pinazo, R

    2015-12-01

    The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  19. Age-related differences in perceptuomotor procedural learning in children.

    Science.gov (United States)

    Lejeune, Caroline; Catale, Corinne; Schmitz, Xavier; Quertemont, Etienne; Meulemans, Thierry

    2013-10-01

    Procedural learning is generally considered to proceed in a series of phases, with cognitive resources playing an important role during the initial step. From a developmental perspective, little is known about the development of procedural learning or the role played by explicit cognitive processes during learning. The main objectives of this study were (a) to determine whether procedural learning performance improves with age by comparing groups of 7-year-old children, 10-year-old children, and adults and (b) to investigate the role played by executive functions during the acquisition in these three age groups. The 76 participants were assessed on a computerized adaptation of the mirror tracing paradigm. Results revealed that the youngest children had more difficulty in adapting to the task (they were slower and committed more errors at the beginning of the learning process) than 10-year-olds, but despite this age effect observed at the outset, all children improved performance across trials and transferred their skill to a different figure as well as adults. Correlational analyses showed that inhibition abilities play a key role in the performance of 10-year-olds and adults at the beginning of the learning but not in that of 7-year-olds. Overall, our results suggest that the age-related differences observed in our procedural learning task are at least partly due to the differential involvement of inhibition abilities, which may facilitate learning (so long as they are sufficiently developed) during the initial steps of the learning process; however, they would not be a necessary condition for skill learning to occur. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

    Science.gov (United States)

    Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  1. Age-related decline in global form suppression.

    Science.gov (United States)

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution.

  2. The burden of age-related macular degeneration.

    Science.gov (United States)

    Schmier, Jordana K; Jones, Mechelle L; Halpern, Michael T

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

  3. Static and flicker perimetry in age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Wu, Zhichao; Ayton, Lauren N; Makeyeva, Galina; Aung, Khin-Zaw; Varsamidis, Mary; Robman, Luba; Vingrys, Algis J; Guymer, Robyn H

    2013-05-01

    The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] static and flicker] static and flicker sensitivities compared to normal eyes. Static (β-coefficient -1.59, 95% confidence interval [CI] -4.78-1.60) and flicker (β-coefficient -1.29, 95% CI -4.66-2.08) sensitivities declined at a similar rate in eyes that showed clinical signs of progression. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 μm are present, but before the development of late AMD.

  4. Systemic complement activation in age-related macular degeneration.

    Science.gov (United States)

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (pAMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  5. Age related macular degeneration and drusen: neuroinflammation in the retina.

    Science.gov (United States)

    Buschini, Elisa; Piras, Antonio; Nuzzi, Raffaele; Vercelli, Alessandro

    2011-09-15

    Inflammation protects from dangerous stimuli, restoring normal tissue homeostasis. Inflammatory response in the nervous system ("neuroinflammation") has distinct features, which are shared in several diseases. The retina is an immune-privileged site, and the tight balance of immune reaction can be disrupted and lead to age-related macular disease (AMD) and to its peculiar sign, the druse. Excessive activation of inflammatory and immunological cascade with subsequent induction of damage, persistent activation of resident immune cells, accumulation of byproducts that exceeds the normal capacity of clearance giving origin to a chronic local inflammation, alterations in the activation of the complement system, infiltration of macrophages, T-lymphocytes and mast-cells from the bloodstream, participate in the mechanisms which originate the drusen. In addition, aging of the retina and AMD involve also para-inflammation, by which immune cells react to persistent stressful stimuli generating low-grade inflammation, aimed at restoring function and maintaining tissue homeostasis by varying the set point in relation to the new altered conditions. This mechanism is also seen in the normal aging retina, but, in the presence of noxious stimuli as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy may provide new insights to understand AMD pathology, due to its contribution in the removal of defective proteins. Therefore, the AMD retina can represent a valuable model to study neuroinflammation, its mechanisms and therapy in a restricted and controllable environment. Targeting these pathways could represent a new way to treat and prevent both exudative and dry forms of AMD.

  6. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  7. Protective effect of xanthohumol against age-related brain damage.

    Science.gov (United States)

    Rancán, Lisa; Paredes, Sergio D; García, Irene; Muñoz, Pedro; García, Cruz; López de Hontanar, Guzmán; de la Fuente, Mónica; Vara, Elena; Tresguerres, Jesús A F

    2017-07-27

    It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg(-1) day(-1) or 5 mg kg(-1) day(-1) xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg(-1) day(-1) xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Wet age related macular degeneration management and follow-up.

    Science.gov (United States)

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  9. The Effect of Atorvastatin on Myocardial Energy Metabolism in Rabbits with Hypercholesterolemia%阿托伐他汀对高胆固醇兔心肌线粒体能量代谢的影响

    Institute of Scientific and Technical Information of China (English)

    曲润波; 鹿育萨; 龚飞宇

    2012-01-01

    Aim To observe the intervention of atorvastatin on myocardial energy metabolism in rabbits with hypercholesterolemia. Methods Twenty-four male New Zealand white rabbits were randomly divided into three groups: control group, cholesterol group, atorvastatin treated group fed with cholesterol. After feeding for 6 weeks, the empty stomach blood preparation through ear marginal vein were collected, the levels of serum total cholesterol were determined; the myocardium was taken to observe its ultrastruetures by electron microscopy; High-performance liquid chromatography (HPLC) was used to measure myocardial mitochondria ATP and CoQ10; Ultraviolet spectrophotomtry was used to measure the activities of SDH and CCO. Results In cholesterol group there were myocardial fibers derangement, part of the fracture,dissolution,mitochondria swelling,crest disturbance,fuzzy, and Comparing with control group,the activities of SDH and CCO were significantly decreased, the content of myocardial mitochondria ATP and CoQ10 was significantly decreased (P 0. 05). Conclusions Atorvastatin may reduce structure damage of myocardial mitochondri-al cause by hypercholesterolemia,increase the activities of SDH and CCO,thereby improve the oxidative phosphorylation capacity of mitochondrial.%目的 探讨阿托伐他汀对高胆固醇血症兔心肌能量代谢的干预作用.方法 24只健康雄性新西兰兔随机分成正常对照组、高胆固醇组和阿托伐他汀组(予高胆固醇饮食并给与阿托伐他汀处理).喂养6周后,经兔耳缘静脉取空腹血标本测血清总胆固醇的浓度;取心肌组织,电镜观察心肌及线粒体超微结构改变;用高效液相色谱法测心肌线粒体ATP和辅酶Q10含量;用紫外分光光度法测线粒体呼吸链复合物Ⅱ、Ⅳ的活性.结果 高胆固醇组心肌纤维排列紊乱,部分断裂、溶解,线粒体肿胀,嵴紊乱、模糊,与正常对照组比较,线粒体呼吸链复合物Ⅱ、Ⅳ活

  10. 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients.

    Directory of Open Access Journals (Sweden)

    Zhiyong Du

    Full Text Available OBJECTIVE: Elevated myocardial energy expenditure (MEE is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. METHODS: A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. RESULTS: The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05. CONCLUSIONS: These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.

  11. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

    Science.gov (United States)

    Selker, Harry P; Udelson, James E; Massaro, Joseph M; Ruthazer, Robin; D'Agostino, Ralph B; Griffith, John L; Sheehan, Patricia R; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M; Atkins, James M; Aufderheide, Tom P; Sayah, Assaad J; Pirrallo, Ronald G; Levy, Michael K; Richards, Michael E; Braude, Darren A; Doyle, Delanor D; Frascone, Ralph J; Kosiak, Donald J; Leaming, James M; Van Gelder, Carin M; Walter, Gert-Paul; Wayne, Marvin A; Woolard, Robert H; Beshansky, Joni R

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

  12. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  13. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Science.gov (United States)

    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  14. The Rationale for Delaying Aging and the Prevention of Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Nir Barzilai

    2012-10-01

    Full Text Available [Excerpt] We offer a different approach to delaying or preventing age-related diseases. To understand the necessity for a new approach we have plotted the mortality rates in Israelis in relation to specific age groups and diseases. With the common phenomenon of aging of Western populations it is of utmost importance to follow time-dependent and age-dependent mortality patterns to predict future needs of Western health systems. Age-specific, gender-specific, and cause-of-death-specific mortality rates were extracted from the statistical abstract of Israel1 and include data for the period of 1975–2010; these are presented in Figure 1, separately for men (A and women (B. Detailed age-specific causes of death data were available for the year 2009. Data presented were restricted to 5-year age groups starting at age 50, and for cause-specific mortality to the following age groups: 45–54, 55–64, 65–74, 75–84, and 85+. Causes of mortality were separated into malignant diseases, acute myocardial infarction, other ischemic heart diseases, other forms of heart diseases, cerebrovascular disease, diabetes mellitus, respiratory diseases, diseases of kidney, infectious diseases, all external causes, signs/symptoms and ill-defined conditions, and all other diseases. Figure 1 is similar to the one posted on the National Institute of Aging website and similar to data across the industrial world. The striking feature of this graph is that aging is a major log scale risk for most diseases, including the major killers: heart disease, cancer, diabetes, and Alzheimer’s. For example, while aging is a 100-fold risk for cardiovascular disease (CVD according to Figure 1, hypercholesterolemia is known to carry only a three-fold risk for CVD. For each of the mentioned diseases, aging is a log risk greater than the most important known risk factor for that disease.

  15. The ERCC6 gene and age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Dominique C Baas

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS reported an association between AMD and a single nucleotide polymorphism (SNP (rs3793784 in the ERCC6 (NM_000124 gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS. Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. METHODOLOGY/PRINCIPAL FINDINGS: Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls. We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study, but this was not replicated in two non-European studies (AREDS, Columbia University. In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018. CONCLUSIONS/SIGNIFICANCE: Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.

  16. Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.

    Science.gov (United States)

    Kobayashi, Keiji; Nojiri, Hidetoshi; Saita, Yoshitomo; Morikawa, Daichi; Ozawa, Yusuke; Watanabe, Kenji; Koike, Masato; Asou, Yoshinori; Shirasawa, Takuji; Yokote, Koutaro; Kaneko, Kazuo; Shimizu, Takahiko

    2015-03-16

    Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to bone tissue. The number of living osteocytes and canalicular networks declines in an age-dependent manner. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated mice lacking mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Like an aged bone, Sod2 depletion in the osteocytes positively enhanced the production of cellular superoxide in vivo. A bone morphological analysis demonstrated that the Sod2-deficient femurs showed remarkable bone loss in an age-dependent manner. Interestingly, Sod2 loss induced markedly disorganized osteocytic canalicular networks and decreased the number of live osteocytes. Furthermore, Sod2 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-κB ligand (RANKL). In vitro experiments also revealed that treatment with paraquat, a superoxide inducer in mitochondria, promoted the RANKL expression via, in part, ERK phosphorylation. These findings demonstrate that the mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age-related bone loss due to the impairment of canalicular networks and bone metabolism via the deregulation of the sclerostin and RANKL expression.

  17. Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Zinkernagel, Martin S.; Zysset-Burri, Denise C.; Keller, Irene; Berger, Lieselotte E.; Leichtle, Alexander B.; Largiadèr, Carlo R.; Fiedler, Georg M.; Wolf, Sebastian

    2017-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient’s intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions. PMID:28094305

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

    Science.gov (United States)

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

    2014-07-01

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

  19. Influence of Age-Related Versus Non-Age-Related Renal Dysfunctionon Survival in Patients with Left Ventricular Dysfunction

    Science.gov (United States)

    Testani, Jeffrey M.; Brisco, Meredith A.; Han, Gang; Laur, Olga; Kula, Alexander J.; Cheng, Susan J.; Tang, W. H. Wilson; Parikh, Chirag R.

    2013-01-01

    Normal aging results in a predictable decline in glomerular filtration rate (GFR) and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age related declines in estimated GFR (eGFR) carry the same prognostic importance as disease attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337). The primary analysis focused on determining if the eGFR mortality relationship differed by the extent the eGFR was consistent with normal ageing. Mean eGFR was 65.7 ± 19.0ml/min/1.73m2. Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73m2 per year (95% CI 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted HR=1.0 per 10 ml/min/1.73m2, 95% CI 0.97–1.1, p=0.53) whereas a disease attributable decrease in eGFR above the median carried significant risk (adjusted HR=2.8, 95% CI 1.6–4.7, p<0.001). In conclusion, in the setting of LV dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID:24216124

  20. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Lipoprotein lipase gene variants: Association with acute myocardial infarction and lipid profiles. ... Therefore, genes involved in lipid and lipoprotein metabolism pathways such as lipoprotein lipase (LPL), are proper candidates ... Article Metrics.

  1. 14-year incidence, progression, and visual morbidity of age-related maculopathy

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Nielsen, Niels V; Vinding, Troels;

    2005-01-01

    To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss.......To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss....

  2. Age-related changes in fasting plasma cortisol in rhesus monkeys: implications of individual differences for pathological consequences.

    Science.gov (United States)

    Erwin, Joseph M; Tigno, Xenia T; Gerzanich, Georgielle; Hansen, Barbara C

    2004-05-01

    Elevated cortisol may damage receptor neurons involved in responses to stress, leading to progressive metabolic dysregulation and age-related increases in cortisol; however, documentation of rising cortisol with age in humans has been inconsistent. Here we report fasting cortisol values from rhesus monkeys maintained for obesity, diabetes, and aging research. A modest correlation (r =.20) between age and cortisol was found for 138 rhesus monkeys (aged 4-40 years) and (r =.16) for 30 males for whom at least 10 years of longitudinal data were available. Subgroups of ad libitum-fed and weight-stabilized animals also exhibited significant positive relationships between age and cortisol (r =.14-.37). Individual regression analyses revealed both significant increases (r =.29-.85) and decreases (r = -.47 to -.66) in cortisol relative to age. Unexpectedly, significant age-related increases occurred in 77% of healthy primates, but only 33% of diabetic primates, while significant declines occurred only in diabetics.

  3. Vision rehabilitation for age-related macular degeneration.

    Science.gov (United States)

    Park, W

    1999-01-01

    Though the numbers of patients with ARMD are high, associated referrals for vision rehabilitation are not. Practitioners need to refer patients with age-related maculopathy when medical and surgical treatment are no longer possible, and patients need to be educated to that fact. The impact of improving activities of daily living may be monumental and benefits society as a whole. People who are visually impaired are often ill-prepared to deal with the substantial adjustment involved, further stressing their entire support system. It may not be safe for visual and systemic reasons for older adults to cook, clean, and maintain their home. Poor vision contributes to the already increased risk of falls and subsequent fractures in these patients. Individuals who may have already been told they can no longer drive now face the possibility of being unable to live in their houses. Their independence may be threatened dramatically and abruptly. All these circumstances contribute to anxiety and depression. Patients with ARMD need to be educated about their disease process (teaching that can never be assumed to have been initiated). They need to be educated that they will not go completely blind and that, with assistance, they can accomplish a great deal. With today's technology, it is not difficult to help visually impaired individuals with ARMD, unless they are not referred or lack motivation. The primary complaint of an individual with ARMD is recognition of central detail. This affects all activities of daily living, and patient performance is subject to the duration and severity of the disease (including the size, density, and location of the central scotoma) and to their understanding of the disease. Rubin and coworkers, found that slow reading performance of patients with a dense central scotoma might reflect inherent limitations of peripheral retina for complex visual tasks. ARMD in most cases lends itself to magnification that enlarges the object beyond the blind spot

  4. Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.

    Directory of Open Access Journals (Sweden)

    Tamuno Alfred

    Full Text Available The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP rs1260326 (P446L in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.As part of the Healthy Ageing across the Life Course (HALCyon collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI, blood lipid levels, lung function, and cognitive and physical capability.We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score= -0.04, p-value=0.0001, n=16,251. Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.

  5. Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4.

    Science.gov (United States)

    Sanguino, Elena; Roglans, Nuria; Alegret, Marta; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C

    2005-08-01

    Old rats are resistant to fibrate-induced hypolipidemia owing to a reduction in hepatic peroxisome proliferator-activated receptor alpha (PPARalpha). We tested whether the age-related decrease in PPARalpha is prevented by atorvastatin (ATV), a hypolipidemic statin. We determined the activity and expression of Liver X receptor alpha (LXRalpha) and PPARalpha in the liver of 18-month-old rats treated with 10 mg kg(-1) of ATV for 21 days. We measured fatty acid oxidation (FAO), the expression of PPARalpha-target genes, liver triglyceride (TG) and cholesteryl ester (CE) contents and plasma concentrations of TG, cholesterol, glucose, nonesterified fatty acids (NEFA), insulin and leptin. While old female rats were practically unresponsive, ATV-treated old males showed lower liver TG (-41%) and CE (-48%), and plasma TG (-35%), glucose (-18%) and NEFA (-39%). Age-related alterations in LXRalpha expression and binding activity were reverted in ATV-treated old males. These changes were related to an increase in hepatic FAO (1.2-fold), and PPARalpha mRNA (2.2-fold), PPARalpha protein (1.6-fold), and PPARalpha-binding activity. Hepatic nuclear factor-4 (HNF-4) and chicken ovalbumin upstream-transcription factor-II participate in the transcriptional regulation of the PPARalpha gene, while peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) behaves as a PPAR coactivator. Ageing reduced the hepatic content of HNF-4 (74%) and PGC-1 (77%) exclusively in male rats. ATV administration to old males enhanced the hepatic expression and binding activity (two-fold) of HNF-4. ATV-induced changes in hepatic HNF-4 and PPARalpha may be responsible for the improvement of the lipid metabolic phenotype produced by ATV administration to senescent male rats.

  6. REM-PCL对体外循环犬心肌能量代谢的影响%Effect of REM-PCL on myocardial energy metabolism in dogs during cardiopulmonary bypass

    Institute of Scientific and Technical Information of China (English)

    方华; 杨淼; 张伟晶; 章建平; 张竞超; 章放香

    2015-01-01

    Objective To observe the effect of REM-PCL on myocardial energy metabolism in dogs during cardiopulmonary bypass.Methods Used CPB myocardial ischemia reperfusion model, 12 dogs were randomly divided into REM-PCL group (group RP,n=6) and control group (group C,n=6). RP group and C group respectively were given intravenous injection of 0.2mg/kg REM-PCL and normal saline before the driving of the rotary machine. Before the driving of the rotary machine, at 60 minutes of ischemia,and after 60 minutes reperfusion, myocardial mitochondrial swelling degree (MSD), malondialdehyde (MDA) content, adenylate (ATP, AMP, ADP, EC, TAN), reactive oxygen species (ROS) and total antioxidative capacity (T-AOC) were respectively determined. Before the driving of the rotary machine, at 60 minutes of ischemia,and after 60 minutes reperfusion, Mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) were measured. ResultsAfter ischemia, MDA, MSD and ROS of two groups were increased, and TAN, EC, T-AOC and ATP content were decreased(P<0.01). At 60 minutes of ischemia and reperfusion for 60 minutes, MDA, MSD and ROS of the RP group were significantly lower than those of C group (P<0.01), TAN, EC, T-AOC and ATP contents of the RP group were significantly higher than those of C group(P<0.01).At reperfusion for 30 minutes and 60 minutes, MAP, CO and HR of the RP group recovered more rapidly than those of group C (P<0.01).Conclusion Through the protection of myocardial mitochondrial structure and improve myocardial energy metabolism, REM-PCL can reduce myocardial ischemia reperfusion injury.%目的:观察犬体外循环(CPB)中REM-PCL对心肌能量代谢的影响。方法采用CPB心肌缺血再灌注模型,12只犬随机分为REM-PCL组(RP组,n=6)和对照组(C组,n=6)。RP组和C组分别于转机前静脉注射0.2mg/kg REM-PCL及等量生理盐水。分别于转机前、缺血60min和再灌注60min时,测定心肌线粒体肿胀度(MSD)、丙二醛

  7. Nitrogen-13-labeled ammonia for myocardial imaging

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, W.F.; Fill, H.R.; Harper, P.V.

    1977-01-01

    Cyclotron-produced nitrogen-13 (half-life 10 min), as labeled ammonia (/sup 13/NH/sub 4//sup +/), has been evaluated as a myocardial perfusion imaging agent. The regional myocardial uptake of /sup 13/NH/sub 4//sup +/ has been shown to be proportional to regional tissue perfusion in animal studies. Intravenously administered /sup 13/NH/sub 4//sup +/ is rapidly cleared from the circulation, being extracted by the liver (15 percent), lungs, myocardium (2 percent--4 percent), brain, kidney, and bladder. Myocardial ammonia is metabolized mainly to glutamine via the glutamine synthetase pathway. Pulmonary uptake is substantial, but usually transient, except in smokers where clearance may be delayed. The positron annihilation irradiation (511 keV) of /sup 13/N may be imaged with a scintillation camera, using either a specially designed tungsten collimator or a pinhole collimator. After early technical problems with collimation and the production method of /sup 13/NH/sub 4//sup +/ were overcome, reproducible high quality myocardial images were consistently obtained. The normal myocardial image was established to be of a homogeneous ''doughnut'' configuration. Imaging studies performed in patients with varying manifestations of ischemic and valvular heart disease showed a high incidence of localized perfusion defects, especially in patients with acute myocardial infarction. Sequential studies at short intervals in patients with acute infarction showed correlation between alterations in regional perfusion and the clinical course of the patient. It is concluded that myocardial imaging with /sup 13/NH/sub 4//sup +/ and a scintillation camera provides a valid and noninvasive means of assessing regional myocardial perfusion. This method is especially suitable for sequential studies of acute cardiac patients at short intervals. Coincidence imaging of the 511 keV annihilation irradiation provides a tomographic and potentially quantitative assessment of the

  8. Age-related mortality, clinical heart failure, and ventricular fibrillation in 4259 Danish patients after acute myocardial infarction

    DEFF Research Database (Denmark)

    Rask-Madsen, C; Jensen, G; Køber, L

    1997-01-01

    % for patients less than or = 80 years old. Two thirds of patients > or = 80 years old had heart failure, and cardiogenic shock was twice as common in this age group than in patients 60-69 years. Heart failure was a strong independent risk......, factor for post-discharge mortality, particularly in the oldest age groups. Four out of eight patients > or = 80 years survived one year if discharged alive after experiencing in-hospital ventricular fibrillation. CONCLUSION: The life-saving potential of preventing or treating heart failure seems...... considerable even in the oldest patient groups. Patients > or = 80 years old who survive in-hospital ventricular fibrillation have an acceptable prognosis 1 year post-discharge....

  9. Mouse model of SCN5A-linked hereditary Lenegre's disease - Age-related conduction slowing and myocardial fibrosis

    NARCIS (Netherlands)

    Royer, A; van Veen, TAB; Le Bouter, S; Marionneau, C; Griol-Charhbili, [No Value; Leoni, AL; Steenman, M; van Rijen, HVM; Demolombe, S; Goddard, CA; Richer, C; Escoubet, B; Jarry-Guichard, T; Colledge, WH; Gros, D; de Bakker, JMT; Grace, AA; Escande, D; Charpentier, F

    2005-01-01

    Background-We have previously linked hereditary progressive cardiac conduction defect (hereditary Lenegre's disease) to a loss-of-function mutation in the gene encoding the main cardiac Na+ channel, SCN5A. In the present study, we investigated heterozygous Scn5a-knockout mice (Scn5a(+/-) mice) as a

  10. Myocardial infarction 1979-1988 in Denmark: secular trends in age-related incidence, in-hospital mortality and complications

    DEFF Research Database (Denmark)

    Hildebrandt, P; Jensen, G; Køber, L;

    1994-01-01

    All admissions to a coronary care unit (CCU) in Copenhagen County were prospectively registered over a 10-year period, from 1979 to 1988, i.e. after the introduction of CCUs but before the era of intervention with thrombolytic or prophylactic medical treatment. The catchment area remained nearly...

  11. [Age-related characteristics of experimental hypothyroidism in rats].

    Science.gov (United States)

    Hromakova, I A; Zil'berman, S Ts; Konovalenko, O O

    2002-01-01

    The rate of both the synthesis of liver and plasma proteins and RNA-1 and RNA-2 polymerase activities in liver were studied in rats of various ages at experimental hypothyroidism. There has been marked more significant decrease in plasma protein synthesis with age. Both the rate of liver and plasma protein synthesis have been shown to be reduced at experimental hypothyroidism but synthesis of plasma proteins was inhibited to a greater extent. Considerable changes were observed neither in liver and plasma protein synthesis nor in the balance between these two groups of the protein synthesis in old rats. RNA-1 and RNA-2 polymerase activities decreased at hypothyroidism. At all ages the activity of bound enzymes decreased to a larger extent as compared to free forms. The activity of RNA-polymerase 2 was more inhibited than that of RNA-polymerase 1. Reducing protein- and RNA-synthetic processes in the liver with age correlated with the peculiarities of the carbohydrate metabolism: in those young animals with an impaired glucose tolerance the inhibitory effect of hypothyroidism on the intensity of protein and RNA synthesis was more potent as compared to old animals.

  12. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne Elisabeth

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...... and supply of oxygen in the myocardium. However, no specific criteria for type 2 myocardial infarction have been established....

  13. Lack of Acid Sphingomyelinase Induces Age-Related Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Bill X Wu

    Full Text Available Mutations of acid sphingomyelinase (ASMase cause Niemann-Pick diseases type A and B, which are fatal inherited lipid lysosomal storage diseases, characterized with visceral organ abnormalities and neurodegeneration. However, the effects of suppressing retinal ASMase expression are not understood. The goal of this study was to determine if the disruption of ASMase expression impacts the retinal structure and function in the mouse, and begin to investigate the mechanisms underlying these abnormalities.Acid sphingomyelinase knockout (ASMase KO mice were utilized to study the roles of this sphingolipid metabolizing enzyme in the retina. Electroretinogram and morphometric analysis were used to assess the retinal function and structure at various ages. Sphingolipid profile was determined by liquid chromatography-mass spectrometry. Western blots evaluated the level of the autophagy marker LC3-II.When compared to control animals, ASMase KO mice exhibited significant age-dependent reduction in ERG a- and b-wave amplitudes. Associated with these functional deficits, morphometric analysis revealed progressive thinning of retinal layers; however, the most prominent degeneration was observed in the photoreceptor and outer nuclear layer. Additional analyses of ASMase KO mice revealed early reduction in ERG c-wave amplitudes and increased lipofuscin accumulation in the retinal pigment epithelium (RPE. Sphingolipid analyses showed abnormal accumulation of sphingomyelin and sphingosine in ASMase KO retinas. Western blot analyses showed a higher level of the autophagosome marker LC3-II.These studies demonstrate that ASMase is necessary for the maintenance of normal retinal structure and function. The early outer retinal dysfunction, outer segment degeneration, accumulation of lipofuscin and autophagosome markers provide evidence that disruption of lysosomal function contributes to the age-dependent retinal degeneration exhibited by ASMase KO mice.

  14. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  15. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  16. Mineral Metabolism Markers Are Associated with Myocardial Infarction and Hemorrhagic Stroke but Not Ischemic Stroke in Hemodialysis Patients: A Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Miho Tagawa

    Full Text Available The associations between phosphate, calcium, and intact parathyroid hormone (PTH levels and composite cardiovascular end points have been studied. This study examined the associations of these markers with myocardial infarction (MI and stroke separately.This is a longitudinal study on 65,849 hemodialysis patients from the Japan Renal Data Registry. Patients with prior events at baseline were excluded. Predictors were phosphate, albumin-corrected calcium, intact PTH, and calcium times phosphate product levels. Outcome was the first episode of MI or stroke during a 1-year observation period. Data were analyzed using multiple logistic regression analyses, adjusted for potential confounders.There were 1,048, 651, and 2,089 events of incident MI, hemorrhagic, and ischemic stroke, respectively. Incident MI was associated with phosphate levels ≥6.5 mg/dL (odds ratio 1.49; confidence interval 1.23-1.80 compared with phosphate levels of 4.7-5.4 mg/dL and intact PTH levels>500 pg/mL (1.35; 1.03-1.79 compared with intact PTH levels of 151-300 pg/mL. Higher albumin-corrected calcium level was positively associated with MI (p = 0.04 by trend analysis. Hemorrhagic stroke was associated only with intact PTH levels>500 pg/mL (1.54; 1.10-2.17. Incident ischemic stroke had no association with phosphate, calcium, or intact PTH levels. The association of calcium times phosphate product with outcomes was essentially the same pattern as that of phosphate and outcomes.MI was associated with phosphate, calcium, and intact PTH levels, whereas hemorrhagic stroke was associated only with intact PTH. Ischemic stroke was not associated with any of them. The potential distinct beneficial effect on MI and stroke by managing bone and mineral disease should be investigated in future studies.

  17. Cardiac function, perfusion, metabolism and innervation following autologous stem cell therapy for acute ST-elevation myocardial infarction. A FINCELL-INSIGHT sub-study with PET and MRI

    Directory of Open Access Journals (Sweden)

    Maija T. Mäki

    2012-01-01

    Full Text Available Purpose: Beneficial mechanisms of bone marrow cell (BMC therapy for acute ST-segment elevation myocardial infarct (STEMI are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 hours after symptoms for STEMI were randomized for BMC therapy (2.9 x 106 CD34+ cells or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7-12 days after therapies and repeated after six months, and images were analyzed at a central core laboratory. Results: In BMC treated patients, there was a decrease in [11C]-HED defect size (-4.9±4.0% vs. -1.6±2.2%, p=0.08 and an increase in [18F]-FDG uptake in the infarct area at risk (0.06±0.09 vs. -0.05±0.16, p=0.07 compared to controls, as well as less left ventricular dilatation (-4.4±13.3 mL/m2 vs. 8.0±16.7 mL/m2, p=0.12 at six-months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (-0.09±0.17 vs. 0.10±0.17, p=0.03 and infarct size (0.4±4.2 g vs. -5.1±5.9 g, p=0.047, and no effect was observed on ejection fraction (EF (p=0.37. Conclusions: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct related myocardium and also a trend of less ventricular dilatation in the BMC treated group compared to placebo. However, no consistently better outcome was observed in the BMC treated group compared to placebo.

  18. Age-related normal uptake of {sup 99m}Tc-MDP in the lower spine

    Energy Technology Data Exchange (ETDEWEB)

    Sundkvist, G.M.G. [Dept. of Clinical Physiology, Centralsjukhuset, Kristianstad (Sweden); Lilja, B. [Dept. of Clinical Physiology, Universitetssjukhuset MAS, Malmoe (Sweden); Mattsson, S. [Dept. of Radiation Physics, Universitetssjukhuset MAS, Malmoe (Sweden)

    1997-03-01

    Aim: The uptake of {sup 99m}Tc-MDP in the lower spine was quantified in connection with ordinary bone scintigraphy. Methods: Fifty-seven women and seventy-two men (aged 20-69 y), with no signs of metabolic or malignant disease and no history of back pain or atraumatic fractures, were included in the study. Results: The women showed an increase in {sup 99m}Tc-MDP uptake from the age of 20 y to about 45 y with a decrease from the time of menopause. In contrast to women, the uptake in men showed a slight decrease from the age of 20 y to about 50 y and thereafter a more marked decrease was seen. The major difference between men and women is the high premenopausal uptake in the female skeleton. Conclusion: An understanding of age-related changes in {sup 99m}Tc-MDP uptake, which are indices of the skeletal metabolism, is of importance especially in prevention and treatment of osteoporosis, a common disorder in postmenopausal women. (orig.) [Deutsch] Ziel: In Verbindung mit einer routinemaessigen Skelettszintigraphie wurde die Speicherung von {sup 99m}Tc-MDP in der unteren Wirbelsaeule quantifiziert. Methoden: 57 Frauen und 22 Maenner (Alter von 20-69 Jahren) ohne metabolische oder boesartige Erkrankungen sowie ohne Rueckenschmerzen oder Wirbelsinterungen wurden in die Studien aufgenommen. Ergebnisse: Bei Frauen zeigte sich ein Anstieg der {sup 99m}Tc-MDP-Speicherung zwischen den Altersabschnitten 20 bis 45 Jahre und dann ein Abfall waehrend der Menopause. Im Gegensatz hierzu zeigte sich bei Maennern ein leichter Abfall der Speicherung vom 20. bis 50. Lebensjahr und danach eine noch staerkere Abnahme. Der Hauptunterschied zwischen den Geschlechtern ist die relativ hohe Speicherung im weiblichen Skelett praemenopausal. Schlussfolgerung: Das Verstaendnis der Altersbeziehungen der {sup 99m}Tc-MDP-Speicherung als Indikator des Knochenstoffwechsels ist fuer Praevention und Behandlung der postmenopausalen Osteoporose wichtig. (orig.)

  19. Running for exercise mitigates age-related deterioration of walking economy.

    Science.gov (United States)

    Ortega, Justus D; Beck, Owen N; Roby, Jaclyn M; Turney, Aria L; Kram, Rodger

    2014-01-01

    Impaired walking performance is a key predictor of morbidity among older adults. A distinctive characteristic of impaired walking performance among older adults is a greater metabolic cost (worse economy) compared to young adults. However, older adults who consistently run have been shown to retain a similar running economy as young runners. Unfortunately, those running studies did not measure the metabolic cost of walking. Thus, it is unclear if running exercise can prevent the deterioration of walking economy. To determine if and how regular walking vs. running exercise affects the economy of locomotion in older adults. 15 older adults (69 ± 3 years) who walk ≥ 30 min, 3x/week for exercise, "walkers" and 15 older adults (69 ± 5 years) who run ≥ 30 min, 3x/week, "runners" walked on a force-instrumented treadmill at three speeds (0.75, 1.25, and 1.75 m/s). We determined walking economy using expired gas analysis and walking mechanics via ground reaction forces during the last 2 minutes of each 5 minute trial. We compared walking economy between the two groups and to non-aerobically trained young and older adults from a prior study. Older runners had a 7-10% better walking economy than older walkers over the range of speeds tested (p = .016) and had walking economy similar to young sedentary adults over a similar range of speeds (p =  .237). We found no substantial biomechanical differences between older walkers and runners. In contrast to older runners, older walkers had similar walking economy as older sedentary adults (p =  .461) and ∼ 26% worse walking economy than young adults (peconomy whereas walking for exercise appears to have minimal effect on the age-related deterioration in walking economy.

  20. Structural and molecular changes in the aging choroid: implications for age-related macular degeneration.

    Science.gov (United States)

    Chirco, K R; Sohn, E H; Stone, E M; Tucker, B A; Mullins, R F

    2017-01-01

    Age-related macular degeneration (AMD) is a devastating disease-causing vision loss in millions of people around the world. In advanced stages of disease, death of photoreceptor cells, retinal pigment epithelial cells, and choroidal endothelial cells (CECs) are common. Loss of endothelial cells of the choriocapillaris is one of the earliest detectable events in AMD, and, because the outer retina relies on the choriocapillaris for metabolic support, this loss may be the trigger for progression to more advanced stages. Here we highlight evidence for loss of CECs, including changes to vascular density within the choriocapillaris, altered abundance of CEC markers, and changes to overall thickness of the choroid. Furthermore, we review the key components and functions of the choroid, as well as Bruch's membrane, both of which are vital for healthy vision. We discuss changes to the structure and molecular composition of these tissues, many of which develop with age and may contribute to AMD pathogenesis. For example, a crucial event that occurs in the aging choriocapillaris is accumulation of the membrane attack complex, which may result in complement-mediated CEC lysis, and may be a primary cause for AMD-associated choriocapillaris degeneration. The actions of elevated monomeric C-reactive protein in the choriocapillaris in at-risk individuals may also contribute to the inflammatory environment in the choroid and promote disease progression. Finally, we discuss the progress that has been made in the development of AMD therapies, with a focus on cell replacement.

  1. The determination of genetic markers of age-related cancer pathologies in populations from Kazakhstan

    Directory of Open Access Journals (Sweden)

    Leyla Bulatovna Djansugurova

    2013-05-01

    Full Text Available Aging associates with a variety of pathological conditions such as cancer, cardiovascular, neurodegenerative, autoimmune diseases, and metabolic disorders. The oncogenic alterations overlap frequently with the genes linked to aging. Here, we show that several aging related genes may serve as the genetic risk factors for cervical and esophagus cancers. In our study, we analyzed samples obtained from 115 patients with esophageal and 207 patients with cervical cancer. The control groups were selected to match the ethnicity and age of cancer patients. We examined the genes involved in the processes of xenobiotics detoxification (GSTM1 and GSTT1, DNA repair (XRCC1 and XRCC3, and cell cycle regulation and apoptosis (CCND1 and TP53. Our study revealed that deletions of GSTT1 and GSTM1 genes or the distinct point mutations of XRCC1 gene are associated with cervical and esophageal cancers. These results will lead to development of screening for detection of individuals susceptible to esophageal and cervical cancers. Introduction of the screening programs will allow the early and effective preventive measures that will reduce cancer incidence and mortality in Kazakhstan.

  2. Selected biomarkers of age-related diseases in older subjects with different nutrition.

    Science.gov (United States)

    Krajcovicova-Kudlackova, M; Babinska, K; Blazicek, P; Valachovicova, M; Spustova, V; Mislanova, C; Paukova, V

    2011-01-01

    The nutritionists introduce on the base of epidemiological and clinical studies that appropriately planned vegetarian diets are healthful, and may provide health benefits in the prevention and treatment of certain diseases. Aging belongs to the main risks of cardiovascular disease. Markers of age-related diseases (cardiovascular, metabolic syndrome, diabetes) were assessed in two nutritional groups of older apparently healthy non-obese non-smoking women aged 60-70 years, 45 vegetarians (lacto-ovo-vegetarians and semi-vegetarians) and 38 non-vegetarians (control group on a traditional mixed diet, general population). Vegetarian values of total cholesterol, LDL-cholesterol, triacylglycerols, C-reactive protein, glucose, insulin and insulin resistance are significantly reduced. Non-vegetarian average values of total cholesterol, LDL-cholesterol and C-reactive protein are risk. Vegetarians have a better antioxidative status (significantly increased vitamin C, lipid-standardized vitamine E and beta-carotene plasma concentrations). Favourable values of cardiovascular risk markers in older vegetarian women document a beneficial effect of vegetarian nutrition in prevention of this disease as well as the vegetarian diet can be an additional factor in therapy. Vegetarians suffer from mild hyperhomocysteinemia; it is due to the lower vitamin B12 concentration. Vitamin B12 supplements are inevitable for the hyperhomocysteinemia prevention (Tab. 2, Ref. 26).

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

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

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

  4. The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Yafeng Wang

    2016-10-01

    Full Text Available Lipid metabolism may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR, 1.18; 95% confidence interval (CI, 1.01 to 1.35; I2 = 53.8%; p = 0.007. High levels of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and triglycerides (TG were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05. The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05. The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions.

  5. Relationships Among Factors Relevant to Abdominal Fat and Age-Related Hearing Loss.

    Science.gov (United States)

    Lee, Young; Park, Mina

    2017-05-11

    Metabolic syndrome is related with abdominal fat and with age-related hearing loss (ARHL). In this study, we evaluated the association between a variety of factors relevant to abdominal fat (FRAs) and hearing thresholds. We reviewed retrospectively the medical records of 2,602 subjects aged over 40 years with symmetrical sensorineural hearing loss who underwent abdominal fat computed tomography (CT) scans. Univariate and multivariate linear regression analyses were used to demonstrate the association between each FRA and hearing thresholds at low and high frequencies. Four of 5 FRAs were associated with hearing thresholds at high frequencies in males. All FRAs examined showed a relationship with hearing thresholds at low frequencies in females. Diabetes mellitus (DM) among clinical factors and visceral adipose tissue (VAT) among the 5 FRAs were the most reflective of hearing thresholds in both males and females. We found that FRAs were associated with hearing loss with frequency specific characteristics according to sex and reinforced that DM and VAT is particularly an important role for hearing.

  6. Age-related synaptic loss of the medial olivocochlear efferent innervation

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    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  7. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    Science.gov (United States)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  8. Oxidative stress, redox signalling and endothelial dysfunction in ageing-related neurodegenerative diseases: a role of NADPH oxidase 2.

    Science.gov (United States)

    Cahill-Smith, Sarah; Li, Jian-Mei

    2014-09-01

    Chronic oxidative stress and oxidative damage of the cerebral microvasculature and brain cells has become one of the most convincing theories in neurodegenerative pathology. Controlled oxidative metabolism and redox signalling in the central nervous system are crucial for maintaining brain function; however, excessive production of reactive oxygen species and enhanced redox signalling damage neurons. While several enzymes and metabolic processes can generate intracellular reactive oxygen species in the brain, recently an O2−-generating enzyme, NADPH oxidase 2 (Nox2), has emerged as a major source of oxidative stress in ageing-related vascular endothelial dysfunction and neurodegenerative diseases. The currently available inhibitors of Nox2 are not specific, and general antioxidant therapy is not effective in the clinic; therefore, insights into the mechanism of Nox2 activation and its signalling pathways are needed for the discovery of novel drug targets to prevent or treat these neurodegenerative diseases. This review summarizes the recent developments in understanding the mechanisms of Nox2 activation and redox-sensitive signalling pathways and biomarkers involved in the pathophysiology of the most common neurodegenerative diseases, such as ageing-related mild cognitive impairment, Alzheimer's disease and Parkinson's disease.

  9. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

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    Audrey Cougnard-Grégoire

    Full Text Available BACKGROUND: Lipid metabolism and particularly high-density lipoprotein (HDL may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. METHODS: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France. AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes; large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247; late AMD (n = 40, 61. Associations of AMD with plasma lipids (HDL, total cholesterol (TC, Low-density lipoprotein (LDL, and triglycerides (TG were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. RESULTS: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261, higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002 and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003. Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45. No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. CONCLUSIONS: This study suggests that elderly patients with high HDL

  10. Myocardial triglycerides : magnetic resonance spectroscopy in health and diabetes

    NARCIS (Netherlands)

    Hammer, Sebastiaan

    2008-01-01

    In this thesis we focused on the functional and metabolic consequences of myocardial triglyceride (TG) accumulation in healthy subjects and in patients with diabetes mellitus. Ectopic accumulation of TGs is associated with organ dysfunction in metabolic disease in experimental animal studies. These

  11. Myocardial triglycerides : magnetic resonance spectroscopy in health and diabetes

    NARCIS (Netherlands)

    Hammer, Sebastiaan

    2008-01-01

    In this thesis we focused on the functional and metabolic consequences of myocardial triglyceride (TG) accumulation in healthy subjects and in patients with diabetes mellitus. Ectopic accumulation of TGs is associated with organ dysfunction in metabolic disease in experimental animal studies. These

  12. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    Science.gov (United States)

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  13. Quality of Life and Health Economic Assessments of Age-Related Macular Degeneration

    OpenAIRE

    Covert, D.; Berdeaux, G; Mitchell, J; Bradley, Clare; Barnes, R.

    2007-01-01

    In this article, we review measures of patient-reported outcomes that can show whether a treatment for age-related macular degeneration also provides patient-perceived benefits. In addition, we look at health economic measurements currently being used to develop cost-effectiveness models for age-related macular degeneration.

  14. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  15. Comparative study of oxidative stress in individuals with and without age related hearing loss

    Directory of Open Access Journals (Sweden)

    Vineeth VK

    2015-08-01

    Conclusion: We found an association between the level of Glutathione and Super Oxide Dismutase in age related hearing loss. Thus the serum Glutathione and Super Oxide Dismutase level can be used as a biomarker for the assessment of age related hearing loss. [Int J Res Med Sci 2015; 3(8.000: 2020-2023

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

    Science.gov (United States)

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

  17. INFLAMMATORY REACTIONS IN EXPERIMENTAL MYOCARDIAL DAMAGE

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    L. D. Khidirova

    2015-12-01

    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  18. Age-related differences in memory after attending to distinctiveness or similarity during learning.

    Science.gov (United States)

    Carr, Valerie A; Castel, Alan D; Knowlton, Barbara J

    2015-01-01

    Episodic memory is vulnerable to age-related change, with older adults demonstrating both impairments in retrieving contextual details and susceptibility to interference among similar events. Such impairments may be due in part to an age-related decline in the ability to encode distinct memory representations. Recent research has examined how manipulating stimulus properties to emphasize distinctiveness can reduce age-related deficits in memory. However, few studies have addressed whether learning strategies that differentially encourage distinctiveness processing attenuate age-related differences in episodic memory. In the present study, participants engaged in two incidental encoding tasks emphasizing either distinctiveness or similarity processing. Results demonstrated higher rates of recollection for stimuli studied under the distinctiveness task than the similarity task in younger but not older adults. These findings suggest a declining capacity for distinctiveness processing to benefit memory in older adults, and raise the possibility that strategies that enhance gist-based encoding may attenuate age-related memory deficits.

  19. New approaches and potential treatments for dry age-related macular degeneration.

    Science.gov (United States)

    Damico, Francisco Max; Gasparin, Fabio; Scolari, Mariana Ramos; Pedral, Lycia Sampaio; Takahashi, Beatriz Sayuri

    2012-01-01

    Emerging treatments for dry age-related macular degeneration (AMD) and geographic atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification) and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS) formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  20. Mechanism of reduced myocardial glucose utilization during acute hypertriglyceridemia in rats.

    Science.gov (United States)

    Ménard, Sébastien L; Ci, Xiuli; Frisch, Frédérique; Normand-Lauzière, François; Cadorette, Jules; Ouellet, René; Van Lier, Johannes E; Bénard, François; Bentourkia, M'hamed; Lecomte, Roger; Carpentier, André C

    2009-01-01

    The purpose of the research is to study the effect of acute inhibition of intravascular lipolysis on myocardial substrate selection during hypertriglyceridemia using in vivo radiotracer analysis and positron emission tomography. We induced acute hypertriglyceridemia in vivo using an intravenous infusion of Intralipid 20% (IL) without and with acute inhibition of fatty acid delivery from circulating triglycerides with injection of Triton WR-1339 (TRI) during a euglycemic-hyperinsulinemic clamp in Wistar rats. We determined the effect of TRI on myocardial uptake of circulating triglycerides and free fatty acids using intravenous injection of [(3)H]-triolein and [(14)C]-bromopalmitate, respectively. Myocardial blood flow, oxidative metabolism, and metabolic rate of glucose (MMRG) were determined using micro-positron emission tomography (microPET) with [(13)N]-ammonia, [(11)C]-acetate, and 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG). TRI reduced myocardial incorporation of [(3)H]-triolein but not [(14)C]-bromopalmitate showing that it selectively reduces myocardial fatty acid delivery from circulating triglycerides but not from free fatty acids. IL reduced myocardial blood flow and MMRG by 37% and 56%, respectively, but did not affect myocardial oxidative metabolism. TRI did not abolish the effect of IL on myocardial blood flow and MMRG. Hypertriglyceridemia acutely reduces myocardial blood flow and MMRG in rats, but this effect is not explained by increased myocardial fatty acid delivery through intravascular triglyceride lipolysis.

  1. Age-related changes assessed by peripheral QCT in healthy Italian women

    Energy Technology Data Exchange (ETDEWEB)

    Guglielmi, G.; Serio, A. de; Cammisa, M. [Scientific Institute Hospital ' ' Casa Sollievo della Sofferenza' ' , San Giovanni Rotondo (Italy). Dept. of Radiology; Fusilli, S. [Scientific Institute Hospital ' ' Casa Sollievo della Sofferenza' ' , San Giovanni Rotondo (Italy). Dept. of Clinical Pathology; Scillitani, A.; Chiodini, I.; Torlontano, M. [Scientific Institute Hospital ' ' Casa Sollievo della Sofferenza' ' , San Giovanni Rotondo (Italy). Division of Endocrinology

    2000-04-01

    The purpose of this study was to describe the normal cross-sectional pattern of radial bone loss associated with aging in healthy women and to generate a normative database using peripheral quantitative computed tomography (pQCT). Subjects with suspected conditions affecting bone metabolism or receiving any drugs affecting bone mineralization were excluded. The trabecular bone mineral density (BMD) and the total bone density of the ultradistal radius at the nondominant forearm was measured using the Norland-Stratec XCT-960 pQCT scanner in 386 healthy pre-, peri-, and postmenopausal females aged 15-81 years. The long-term in vivo precision error was 1.6% CV (coefficient of variation) for trabecular and 0.8% CV for total BMD measurements. The highest value of trabecular and total BMD measured was observed at the age group 15-39 years. Beyond these ages both trabecular and total BMD showed a linear decline with aging, decreasing by an overall slope of -1.28 and -0.55 mg/cm{sup 3} per year for total and trabecular BMD measurements, respectively. The test of parallelism between the regression slopes of the peri- and postmenopausal women showed a statistically significant difference for total BMD measurement (p=0.003). Measurement of total and trabecular BMD was not influenced by weight, height or body mass index, but it was correlated with natural logarithm of years since menopause. We conclude that pQCT of the ultradistal radius is a precise method for measuring the true volumetric BMD and for detecting age-related bone loss in the trabecular and total bone of female subjects encompassing the adult age range and menopausal status. (orig.)

  2. Age-related changes in functional connectivity of cerebellar PlV: a FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Yoon, Eun Jin; Bang, Seong Ae; Park, Hyun Soo; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    The cerebellum is known to have strong connection with cerebral cortex, and it shows the greatest mean shrinkage with aging. Changes in functional connectivity between cerebellum and cortical and subcortical cerebral areas possibly occur in normal aging. In this study, we tested changes of interregional connection between cerebellar posterior inferior vermis (PIV) and cerebrum in healthy subjects divided in three classes of age group (young: 20-30, middle age: 40-50, elderly: over 60 years) using FDG PET. 211 healthy subjects (age, 20-82 y; 134 female) were studied with resting-state brain glucose utilization measured by FDG-PET, cerebellar PIV activity after count-normalization to the whole gray matter mean count was extracted. Using PIV count as a 'seed', the maps of cross-correlation coefficients were computed by measuring the correlation between 'seed' and all the other brain voxels (P < 0.001 uncorrected, k = 100). Across all age groups, positive correlations of metabolic activity in the cerebellar PIV showed in cerebellum itself and bilateral thalamus. An extended positive correlation in cuneus which is served for visual information processing was observed in middle aged and elderly group differently from the young group. Also, in elderly group, this correlation was observed in the frontal areas such as right orbital and precentral gyri. Negative correlation implicating mutual inhibition between the areas was also founded in prefrontal and cingulate cortices and temporoparietal association areas. Comparing with the young group, in theses areas, enlarged negative correlations was founded with aging. We identified age related changes in cerebrocerebellar communication loop which reflect changes in local neuroplasticity in the normal aging brain. Present result may have implication for understanding the functional decline of cerebellum related cognitive ability as well as the deficit of motor coordination in normal aging and its compensation

  3. [New possibilities in the pharmacologic prevention of age-related macular degeneration].

    Science.gov (United States)

    Fischer, Tamás

    2008-01-20

    The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into consideration all possible side effects--ACE-inhibitor and/or AR blocker and statin and aspirin treatment, and trimetazidine as adjuvant medicine 1. those without maculopathy but being above the age of 50 and having risk factors inducing endothelial dysfunction; 2. those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3. those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory to

  4. Acute myocardial infarction and renal failure following naphtha ingestion.

    Science.gov (United States)

    Roberge, R J; Crippen, D R; Jayadevappa, D; Kosek, T L

    2001-10-01

    We present a case of a non-Q wave myocardial infarction and acute renal failure following an ingestion of naphtha, a petroleum distillate composed primarily of hydrocarbons. The patient's renal, metabolic, and cardiac status improved over several days with aggressive volume replacement and bicarbonate therapy. Acute cardiotoxic effects of hydrocarbon exposure generally manifest as dysrhythmias, secondary to myocardial sensitization to circulating catecholamines, or, possibly, coronary vasospasm. Ischemia from associated hypotension or direct myocardial toxicity are other potential causes of naphtha-related cardiac injury.

  5. PERIOPERATIVE MYOCARDIAL INFRACTION

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    Ravindra S

    2015-10-01

    Full Text Available Perioperative myocardial ischaemia and infarction (PMI is a major cause of short and long term morbidity and mortality in the surgical population. It is estimated that more than one half of postoperative deaths are caused by cardiac events, most of which are ischaemic in origin. Over 50,000 patients each year sustain a perioperative MI . Thus prevention of a PMI is important to improve overall postoperative outcome. Myocardial ischaemia is a dual state composed of inadequate myocardial oxygenation and accu mulation of anaerobic metabolites and occurs when myocardial oxygen demand exceeds the supply. Myocardial infarction is defined as the death of myocardial myocytes due to prolonged ischaemia. In patients with, or at risk of coronary artery disease (CAD, t he reported incidence of perioperative myocardial ischaemia is 20 - 63%. Various studies have shown that postoperative myocardial ischaemia was consistently found to occur considerably more often than preoperative and intraoperative ischaemia ( R atio approxim ately 3:1 and 5:1 respectively. As more and more patients coming for non - cardiac surgeries who have already undergone coronary intervention such as balloon angioplasty, stenting or CABG, we as anaesthesiologists should have thorough knowledge of the perio perative implications of the same in a day to day practice. Secondly, as the geriatric population is increasing there are more chances of encountering patients with known or unknown ischaemic heart disease both on an emergency and elective basis.

  6. Age-related variations of visuo-motor adaptation beyond explicit knowledge

    Directory of Open Access Journals (Sweden)

    Herbert eHeuer

    2014-07-01

    Full Text Available Visuo-motor adaptation suffers at older working age. The age-related decline of behavioural adjustments is accompanied by reduced explicit knowledge of the visuo-motor transformation. It disappears when explicit knowledge is kept constant across the age range, except for particularly high levels of explicit knowledge. According to these findings, at older adult age both the acquisition of explicit knowledge and its application for strategic corrections become poorer. Recently it has been posited that visuo-motor adaptation can involve model-free reinforcement mechanisms of learning in addition to model-based mechanisms. We tested whether age-related declines of reinforcement learning can also contribute to the age-related changes of visuo-motor adaptation. Therefore we enhanced the contribution of reinforcement learning to visuo-motor adaptation by way of introducing salient markers of success and failure during practice. With such modified practice conditions, there were residual age-related variations of behavioural adjustments at all levels of explicit knowledge, even when explicit knowledge was absent. The residual age-related variations were observed for practiced target directions only, but not for new target directions. These findings are consistent with an age-related decline of model-free reinforcement learning as a third factor in the age-related decline of visuo-motor adaptation. Under practice conditions, which spur model-free reward-based learning, this factor adds to the decrements of the acquisition of explicit knowledge and its use for strategic corrections.

  7. Clinical significance of determination of myocardial enzymes in pregnant women with metabolic syndrome%心肌酶谱测定对妊娠期代谢综合征的临床意义

    Institute of Scientific and Technical Information of China (English)

    姚保芬

    2011-01-01

    To investigate the clinical significance of the serum troponin and myocardial enzymes in pregnant women with metabolic syndrome. Methods Two study groups included 37 cases of pregnancy-induced hypertension syndrome and 45 cases of gestationaldiabetes respectively. The control group included 28 cases of healthy prepartal women. Fasting blood glucose in late pregnancy, fasting insulin, weight, blood lipid, nyocardial enzymes and troponin of them were detected. Results The fasting insulin, weight gain in pregnancy, triglyceride and body mass index ( BMI ) of the pregnancy-induced hypertension group were significantly higher than those of the control group ( t was 3.16, 3.52, 2.56 and 2.73 respectively, P < 0.05 ). The fasting glucose, fasting insulin, weight gain in pregnancy,triglyceride, insulin resistance index and BMI of gestational diabetes group were significantly different from those of the control group ( t was 2.53, 2.65, 2.74, 3.61, 2.58 and 3.18 respectively, P < 0.05 ). The concentration of CK, CKMB, HBDH, LDH and the positive number of troponin were significantly different among three groups ( F was 19.61, 19.56, 21.37 and 22.68 respectively, X2= 7.46, P <0.05 ). Conclusion The degree of nyocardial function of pregnant women with metabolic syndrome is positively crrrelated with the severity of metabolic syndrome.%目的 探讨妊娠期代谢综合征孕妇血清肌钙蛋白和心肌酶改变的临床意义.方法 以收治的妊娠期高血压疾病37例和妊娠期糖尿病45例为研究组,以健康待产孕妇28例为对照组,测定其孕晚期空腹血糖、空腹胰岛素、体重、血脂、心肌酶谱和肌钙蛋白.结果 妊娠期高血压疾病组空腹胰岛素、孕期体重增加值、甘油三酯及孕晚期BMI显著高于对照组(t值分别为3.16、3.52、2.56、2.73,均P<0.05);妊娠期糖尿病组空腹血糖、空腹胰岛素、孕期体重增加值、甘油三酯、胰岛素抵抗指数及孕晚期身体质量指数与对

  8. The association between plasma 25-hydroxyvitamin D and subgroups in age-related macular degeneration: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Amardeep Singh

    Full Text Available OBJECTIVES: To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD, and in patients in Clinical Age-Related Maculopathy Staging (CARMS group 5 with or without subretinal fibrosis. METHODS: This single-center cross-sectional study included 178 participants during a period of 20 months. Ninety-five patients belonged to CARMS 5; twelve belonged to CARMS 4; twenty-two belonged to CARMS 2 or 3; and 49 individuals did not have AMD (CARMS 1. Following a structured interview, a detailed bilateral retinal examination was performed and participants were allocated to their respective subgroups in accordance with the Clinical Age-Related Maculopathy Staging system. Plasma 25-hydroxyvitamin D2 and D3 were analyzed using liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from leukocytes and genotyped for single nucleotide polymorphisms (SNPs in the vitamin D metabolism. Differences in plasma 25-hydroxyvitamin D were determined in the subgroups as well as between patients in CARMS 5 with or without subretinal fibrosis. RESULTS: Plasma 25-hydroxyvitamin D was comparable in patients across CARMS groups 1 to 5 (p = 0.83. In CARMS 5, the presence of subretinal fibrosis was associated with significantly lower concentrations of 25-hydroxyvitamin D as compared to the absence of subretinal fibrosis (47.2 versus 75.6 nmol/L, p<0.001. Patients in CARMS 5 with subretinal fibrosis were more likely to have insufficient levels of 25-hydroxyvitamin D compared to patients without subretinal fibrosis (p = 0.006. No association was found between the SNPs rs10877012, rs2228570, rs4588, or rs7041 and AMD subgroups or plasma 25-hydroxyvitamin levels. CONCLUSIONS: This study suggests that the presence of subretinal fibrosis in patients belonging to CARMS 5 may be associated with a poor vitamin D status. Our observations warrant further investigation into the role of vitamin D in the

  9. The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis.

    Directory of Open Access Journals (Sweden)

    Xingjun Fan

    Full Text Available Age-related nuclear cataracts are associated with progressive post-synthetic modifications of crystallins from various physical chemical and metabolic insults, of which oxidative stress is a major factor. The latter is normally suppressed by high concentrations of glutathione (GSH, which however are very low in the nucleus of the old lens. Here we generated a mouse model of oxidant stress by knocking out glutathione synthesis in the mouse in the hope of recapitulating some of the changes observed in human age-related nuclear cataract (ARNC. A floxed Gclc mouse was generated and crossed with a transgenic mouse expressing Cre in the lens to generate the LEGSKO mouse in which de novo GSH synthesis was completely abolished in the lens. Lens GSH levels were reduced up to 60% in homozygous LEGSKO mice, and a decreasing GSH gradient was noticed from cortical to nuclear region at 4 months of age. Oxidation of crystallin methionine and sulfhydryls into sulfoxides was dramatically increased, but methylglyoxal hydroimidazolones levels that are GSH/glyoxalase dependent were surprisingly normal. Homozygous LEGSKO mice developed nuclear opacities starting at 4 months that progressed into severe nuclear cataract by 9 months. We conclude that the LEGSKO mouse lens mimics several features of human ARNC and is thus expected to be a useful model for the development of anti-cataract agents.

  10. Inhibition of Age-Related Cytokines Production by ATGL: A Mechanism Linked to the Anti-Inflammatory Effect of Resveratrol

    Directory of Open Access Journals (Sweden)

    Daniele Lettieri Barbato

    2014-01-01

    Full Text Available Ageing is characterized by the expansion and the decreased vascularization of visceral adipose tissue (vAT, disruption of metabolic activities, and decline of the function of the immune system, leading to chronic inflammatory states. We previously demonstrated that, in vAT of mice at early state of ageing, adipocytes mount a stress resistance response consisting in the upregulation of ATGL, which is functional in restraining the production of inflammatory cytokines. Here, we found that, in the late phase of ageing, such an adaptive response is impaired. In particular, 24-months-old mice and aged 3T3-L1 adipocytes display affected expression of ATGL and its downstream PPARα-mediated lipid signalling pathway, leading to upregulation of TNFα and IL-6 production. We show that the natural polyphenol compound resveratrol (RSV efficiently suppresses the expression of TNFα and IL-6 in an ATGL/PPARα dependent manner. Actually, adipocytes downregulating ATGL do not show a restored PPARα expression and display elevated cytokines production. Overall the results obtained highlight a crucial function of ATGL in inhibiting age-related inflammation and reinforce the idea that RSV could represent a valid natural compound to limit the onset and/or the exacerbation of the age-related inflammatory states.

  11. Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1

    Science.gov (United States)

    Ma, Cao; Pi, Chenchen; Yang, Yue; Lin, Lin; Shi, Yingai; Li, Yan; Li, Yulin; He, Xu

    2017-01-01

    Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases. PMID:28125705

  12. Progress and perspectives on the role of RPE cell inflammatory responses in the development of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Suofu Qin

    2008-12-01

    Full Text Available Suofu Qin, Gerard A RodriguesRetinal Disease Research, Department of Biological Sciences, Allergan, Inc., Irvine, CA, USAAbstract: Age-related macular degeneration (AMD is the leading cause of blindness in developed countries. The etiology of AMD remains poorly understood and no treatment is currently available for the atrophic form of AMD. Atrophic AMD has been proposed to involve abnormalities of the retinal pigment epithelium (RPE, which lies beneath the photoreceptor cells and normally provides critical metabolic support to these light-sensing cells. Cumulative oxidative stress and local inflammation are thought to represent pathological processes involved in the etiology of atrophic AMD. Studies of tissue culture and animal models reveal that oxidative stress-induced injury to the RPE results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration in turn causes a progressive degeneration of photoreceptors, leading to the irreversible loss of vision. This review describes some of the potential major molecular and cellular events contributing to RPE death and inflammatory responses. In addition, potential target areas for therapeutic intervention will be discussed and new experimental therapeutic strategies for atrophic AMD will be presented.Keywords: age-related macular degeneration, danger signals, complement, inflammation, retinal pigment epithelial cells

  13. Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study

    NARCIS (Netherlands)

    R. van Leeuwen (Redmer); M.K. Ikram (Kamran); J.R. Vingerling (Hans); J.C.M. Witteman (Jacqueline); P.T.V.M. de Jong (Paulus); A. Hofman (Albert)

    2003-01-01

    textabstractPURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlan

  14. Age-related differentiations of Th1/Th2 cytokines in newborn infants

    Directory of Open Access Journals (Sweden)

    Efthimia Protonotariou

    2004-01-01

    Full Text Available OBJECTIVE: To evaluate age-related differentiation of immune response in newborns by measuring serum concentrations of interleukin-2 (IL-2, interleukin-4 (IL-4 and interferon-γ (IFN-γ during the perinatal period.

  15. Validation of anti-aging drugs by treating age-related diseases.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  16. Validation of anti-aging drugs by treating age-related diseases

    Science.gov (United States)

    Blagosklonny, Mikhail V.

    2009-01-01

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities. PMID:20157517

  17. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo;

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  18. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    Science.gov (United States)

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  19. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    Science.gov (United States)

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  20. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    OpenAIRE

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rat...

  1. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Larsen, Michael; Munch, Inger Christine

    2012-01-01

    To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.......To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older....

  2. Update on Clinical Trials in Dry Age-related Macular Degeneration

    OpenAIRE

    Ibrahim Taskintuna; M.E. A. Abdalla Elsayed; Patrik Schatz

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age.related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age.Related Eye Disease Study 2 (AREDS2), implantable miniatu...

  3. AGE-RELATED MACULAR DEGENERATION: CURRENT ASPECTS OF PATHOGENESIS AND TREATMENT

    Institute of Scientific and Technical Information of China (English)

    H; P; Heidenkummer

    1991-01-01

    About 1.1 million people are estimated to have age-related macular degeneration in West Germany. Anatomical aspects of the normal macula and physiological ageing processes in the retina will be discribed including alterations in the choroid, in Bruch's membrane, the pigment epithelium and the sensory retina. Risk factors for the development of age-related macular degeneration are age per se, perhaps ethnologic characteristics, ocular characteristics, and perhaps environmental factors. The histopathology...

  4. Comparison of life quality scores of ranibizumab-treated patients with age-related macular degeneration

    OpenAIRE

    Saadet Arslan; Merih Soylu; ilter Varinli

    2016-01-01

    Purpose: To evaluate the visual acuity, fluorescein angiography, optic coherence tomography and life quality of patients diagnosed with exudative age-related macular degeneration and administered with intravitreal Ranibizumab injection. Material and Methods: This study included of 48 different patients who were diagnosed as exudative age-related macular degeneration and administered with ranibizumab injection. In this study, demographic characteristics, pre- and post-injection corrected v...

  5. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

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

    Science.gov (United States)

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

    2012-02-01

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

  7. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes

    Directory of Open Access Journals (Sweden)

    Biswas Jyotirmay

    2002-01-01

    Full Text Available PURPOSE: Age-related macular degeneration (ARMD is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, and the macula. Six sections, 6 microns thick, were cut from three levels in the macula at a distance of 140 microns. These were stained with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains. The presence of basal laminar deposits, drusen and thickening and calcification of Bruch′s membrane in the macula were assessed at 400 x magnification using a modified version of Sark′s classification. RESULTS: Twenty-four donor eyes (48% had some form of age-related macular change. These included basal laminar deposits, hard drusen, soft drusen, extensive retinal pigment epithelium atrophy of the macula, and disciform degeneration of macula. A combination of changes was often seen. Age-related changes were more common in the seventh and eighth decade. CONCLUSION: Our study shows that histological changes characteristic of the early stages of age-related macular degeneration are fairly common in the Indian population. However, advanced macular changes are significantly rare.

  8. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    Science.gov (United States)

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes.

  9. SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin

    Directory of Open Access Journals (Sweden)

    Huiqiang eChen

    2014-06-01

    Full Text Available Age-related mesenchymal stem cells (MSCs senescence, which impairs its tissue repair capacity in vivo and hence compromises the effects of MSCs-based therapy in clinical applications, is closely related to aging and aging-related diseases. Here, we demonstrated the effect of SIRT1, a NAD+-dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in young MSCs induces cellular senescence and inhibits cellular proliferation ability whereas overexpression of SIRT1 in aged MSCs reversed the cellular senescence and regained its proliferation capacity, suggesting that SIRT1 could modulate age-induced MSCs senescence. Aging-related proteins, P16 and P21, might be involved in SIRT1-mediated anti-aging effect on MSCs. SIRT1 could positively modulate age-related DNA damage in MSCs. In addition, SIRT1 could induce telomerase reverse transcriptase (TERT expression and consequently enhance telomerase activity, however, no significant change was observed in telomere length. Moreover, SIRT1 could positively regulate TPP1, an important member of telomere shelterin, expression. Together, these results demonstrate that SIRT1 dampens age-related MSCs senescence, which was correlated with the up-regulation of TPP1 expression, telomerase activity and down-regulation of DNA damage.

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

    Science.gov (United States)

    Machalińska, Anna

    2013-01-01

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

  11. Modeling age-related changes in muscle-tendon dynamics during cyclical contractions in the rat gastrocnemius.

    Science.gov (United States)

    Danos, Nicole; Holt, Natalie C; Sawicki, Gregory S; Azizi, Emanuel

    2016-10-01

    Efficient muscle-tendon performance during cyclical tasks is dependent on both active and passive mechanical tissue properties. Here we examine whether age-related changes in the properties of muscle-tendon units (MTUs) compromise their ability to do work and utilize elastic energy storage. We empirically quantified passive and active properties of the medial gastrocnemius muscle and material properties of the Achilles tendon in young (∼6 mo) and old (∼32 mo) rats. We then used these properties in computer simulations of a Hill-type muscle model operating in series with a Hookean spring. The modeled MTU was driven through sinusoidal length changes and activated at a phase that optimized muscle-tendon tuning to assess the relative contributions of active and passive elements to the force and work in each cycle. In physiologically realistic simulations where young and old MTUs started at similar passive forces and developed similar active forces, the capacity of old MTUs to store elastic energy and produce positive work was compromised. These results suggest that the observed increase in the metabolic cost of locomotion with aging may be in part due to the recruitment of additional muscles to compensate for the reduced work at the primary MTU. Furthermore, the age-related increases in passive stiffness coupled with a reduced active force capacity in the muscle can lead to shifts in the force-length and force-velocity operating range that may significantly impact mechanical and metabolic performance. Our study emphasizes the importance of the interplay between muscle and tendon mechanical properties in shaping MTU performance during cyclical contractions. Copyright © 2016 the American Physiological Society.

  12. Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration

    Directory of Open Access Journals (Sweden)

    Pavlo eKyryakov

    2012-07-01

    Full Text Available The nonreducing disaccharide trehalose has been long considered only as a reserve carbohydrate. However, recent studies in yeast suggested that this osmolyte can protect cells and cellular proteins from oxidative damage elicited by exogenously added reactive oxygen species (ROS. Trehalose has been also shown to affect stability, folding and aggregation of bacterial and firefly proteins heterologously expressed in heat-shocked yeast cells. Our recent investigation of how a lifespan-extending caloric restriction (CR diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact 1 the age-related dynamics of changes in trehalose concentration; 2 yeast chronological lifespan under CR conditions; 3 the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and 4 the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility and aggregation throughout lifespan.

  13. Prevalence and Incidence of Myocardial Infarction and Cerebrovascular Accident in Ageing Persons with Intellectual Disability

    Science.gov (United States)

    Jansen, J.; Rozeboom, W.; Penning, C.; Evenhuis, H. M.

    2013-01-01

    Background: Epidemiological information on age-related cardiovascular disease in people with intellectual disability (ID) is scarce and inconclusive. We compared prevalence and incidence of cerebrovascular accident and myocardial infarction over age 50 in a residential population with ID to that in a general practice population. Method: Lifetime…

  14. Prevalence and Incidence of Myocardial Infarction and Cerebrovascular Accident in Ageing Persons with Intellectual Disability

    Science.gov (United States)

    Jansen, J.; Rozeboom, W.; Penning, C.; Evenhuis, H. M.

    2013-01-01

    Background: Epidemiological information on age-related cardiovascular disease in people with intellectual disability (ID) is scarce and inconclusive. We compared prevalence and incidence of cerebrovascular accident and myocardial infarction over age 50 in a residential population with ID to that in a general practice population. Method: Lifetime…

  15. Effect of drug treatment and selective percutaneous coronary intervention on myocardial collagen metabolism in patients with ST-elevation myocardial infarction%药物与择期经皮冠状动脉介入治疗对ST段抬高心肌梗死后心脏胶原代谢的影响

    Institute of Scientific and Technical Information of China (English)

    张雪松; 黄广勇; 高航

    2010-01-01

    changes of myocardial collagen metabolism. Methods Forty-one patients with STEMI were divided into drug treatment group (22 cases) and selective percutaneous coronary intervention (PCI) group (19 cases). Meanwhile,47 healthy controls were included in control group. The levels of serum carboxy terminal propeptide of type Ⅰ procollagen (PⅠCP), precollagen Ⅲ ( PC Ⅲ ), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by enzyme-linked immunosorbent assay at the 3rd ,6th, 12th, 18th month after STEMI,and compared with those in control group. Results The level of P Ⅰ CP in selective PCI group was significantly lower than that in drug treatment group at the 3rd, 6th month [( 15.08 ± 3.37 ) μ g/L vs. ( 19.78 ± 2.22 ) μ g/L, (23.88 ± 3.33 ) μg/Lvs. ( 30.00 ± 3.14) μ g/L, P < 0.05], but there was no significant difference at the 12th and 18th month (P >0.05 ). The level of serum PC Ⅲ in selective PCI group was significantly lower than that in drug treatment group at the 3rd month [(50.70 ±4.83) ng/L vs. (59.91 ±4.64) ng/L,P <0.05],and there was no significant difference at others times between drug treatment group and selective PCI group. There was no significant difference in P Ⅰ CP/PC Ⅲ between drug treatment group and selective PCI group in all times(P >0.05). Compared with those in control group,the levels of serum MMP-1 in all times were significantly decreased in drug treatment group and selective PCI group(P < 0.05 ), but there was no significant difference between drug treatment group and selective PCI group at same times (P > 0.05). The level of serum TIMP-1was significantly higher in selective PCI group than that in drug treatment group at the 3rd and 6th month [(61.89 ± 11.44) μg/L vs. (52.23 ±4.97)μg/L, (62.85 ±6.31) μg/L vs. (52.97 ±6.43)μg/L,P<0.05] ,and there was no significant difference in TIMP-1 between drug treatment group and selective PCI group in other times (P

  16. Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs

    NARCIS (Netherlands)

    Bartelds, B; Gratama, JWC; Knoester, H; Takens, J; Smid, GB; Aarnoudse, JG; Heymans, HSA; Kuipers, JRG

    1998-01-01

    No information is available on perinatal changes in myocardial metabolism in vivo. We measured myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in chronically instrumented fetal, newborn (1-4 days), and juvenile (7 wk) lambs, by measuring aorta-coronary sinus concentration

  17. [Depression and myocardial infaction].

    Science.gov (United States)

    Testuz, A

    2009-03-04

    Several works show an association between depression and the occurence of a first myocardial infarction. Depression after myocardial infarction seems to be a marker of poorer outcome, regardless of other risk factors or severity of the myocardial infarction. Dysautonomia and alteration of platelet activation are a few physiopathological changes shared by both affections, through which they might be related. Treatment of depression is not associated with better cardiovascular outcome, but selective serotonin reuptake inhibitors have been shown safe and efficient among patients with coronary heart disease. Cognitivo-comportemental approach and cardiovascular rehabilitation program after myocardial infarction also play a role in improving quality of life of the depressed patient with coronary heart disease.

  18. Attenuating age-related learning deficits: emotional valenced feedback interacts with task complexity.

    Science.gov (United States)

    Gorlick, Marissa A; Giguère, Gyslain; Glass, Brian D; Nix, Brittany N; Mather, Mara; Maddox, W Todd

    2013-04-01

    Previous research reveals that older adults sometimes show enhanced processing of emotionally positive stimuli relative to negative stimuli, but that this positivity bias reverses to become a negativity bias when cognitive control resources are less available. In this study, we test the hypothesis that emotionally positive feedback will attenuate well-established age-related deficits in rule learning whereas emotionally negative feedback will amplify age deficits-but that this pattern will reverse when the task involves a high cognitive load. Experiment 1 used emotional face feedback and revealed an interaction among age, valence of the feedback, and task load. When the task placed minimal load on cognitive control resources, happy-face feedback attenuated age-related deficits in initial rule learning and angry-face feedback led to age-related deficits in initial rule learning and set shifting. However, when the task placed a high load on cognitive control resources, we found that angry-face feedback attenuated age-related deficits in initial rule learning and set shifting whereas happy-face feedback led to age-related deficits in initial rule learning and set shifting. Experiment 2 used less emotional point feedback and revealed age-related deficits in initial rule learning and set shifting under low and high cognitive load for point-gain and point-loss conditions. The research presented here demonstrates that emotional feedback can attenuate age-related learning deficits-but only positive feedback for tasks with a low cognitive load and negative feedback for tasks with high cognitive load. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  19. Metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

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

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

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

  1. Genetics and age-related macular degeneration: a practical review for the clinician

    Directory of Open Access Journals (Sweden)

    Schwartz SG

    2016-07-01

    Full Text Available Stephen G Schwartz,1 Blake M Hampton,1 Jaclyn L Kovach,1 Milam A Brantley Jr2 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH and age-related maculopathy susceptibility 2 (ARMS2. There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients. Keywords: age-related macular degeneration, age-related maculopathy susceptibility 2, ARMS2, complement factor H, CFH, pharmacogenetics, vascular endothelial growth factor

  2. The potential preventive effects of vitamins for cataract and age-related macular degeneration.

    Science.gov (United States)

    Jacques, P F

    1999-05-01

    Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

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

  5. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    Science.gov (United States)

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  6. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    Energy Technology Data Exchange (ETDEWEB)

    Gehl, A.C.; Hagen, E.W. [Oak Ridge National Lab., TN (United States)

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns.