Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) and stroke are two leading causes of age-associated dementia. A rapidly growing body of evidence indicates that increased oxidative stress from reactive oxygen radicals is associated with the aging process and age-related degenerative disorders such as atherosclerosis, ischemia/reperfusion, arthritis, stroke, and neurodegenerative diseases. New evidence has also indicated that vascular lesions are a key factor in the development of AD. This idea is based on a positive correlation between AD and cardiovascular and cerebrovascular diseases such as arterio- and atherosclerosis and ischemia/reperfusion injury. In this review we consider recent evidence supporting the existence of an intimate relationship between oxidative stress and vascular lesions in the pathobiology of AD. We also consider the opportunities for therapeutic interventions based on the molecular pathways involved with these causal relationships.
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PMID:The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease. 1177 Aug 99

Cognitive functions display a progressive impairment with ageing, and this is thought to be due to the accumulation of neuronal loss or acute and/or repeated microvascular accidents. Chronic damage to the brain cortex lead to decreasing ability of elderly subjects to cope with daily events and ultimately result in loss of self-sufficiency. Since proinflammatory cytokines have been implicated both in cerebrovascular injury due to atherosclerosis and in Alzheimer's disease (AD), we investigated 70 elderly subjects with neurocognitive and functional impairment. Diagnosis was established in 54, the others were included in the "mixed" group. Sera were collected and stored at -70 degrees C until measurement of IL-1beta and TNF-alpha, performed by commercial ELISA kits. Data obtained were analysed with respect to other socio-demographic, psychoneurological and clinical variables. The results show that serum TNF-alpha was lower in mild-moderate AD compared to severe AD and dementias due to vascular disease, as well as the TNF-alpha/IL-1beta ratio. Both cytokines showed a significant relationship with age. Our study suggests that proinflammatory cytokines serum profiles seem to discriminate between mild-moderate AD and vascular or mixed forms of dementia. Furthermore, it offers new evidence of a strong implication of inflammatory mechanisms in atherosclerosis, more than in less severe AD.
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PMID:Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients. 1177 11

The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
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PMID:From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis. 1183 7

Low-grade inflammatory activity is strongly associated with age-associated diseases such as atherosclerosis, dementia, type-2 diabetes, sarcopenia, and osteoporosis and predicts mortality risk in elderly populations. The aim of the current study was to investigate if asymptomatic bacteriuria in elderly humans was associated with inflammation. Midstream clean-catch urine culture was collected from consecutive, elderly patients at admission to a department of internal medicine due to functional disability. Forty patients (age 70-91 years) were selected and included in the current study; 20 subjects had positive urine culture and 20 sex- and age-matched subjects had negative urine culture. Inclusion criteria were temperature below 37.8 degrees C, no clinical signs of infection and no current antibiotic treatment. Patients with asymptomatic bacteriuria had significantly increased levels of circulating tumor necrosis factor receptors (sTNFR-I) and a higher number of neutrophils in the blood compared to the group without bacteriuria. Thus, the present study provides some support for the hypothesis that asymptomatic urinary infections are associated with low-grade immune activity in frail, elderly humans.
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PMID:Asymptomatic bacteriuria in elderly humans is associated with increased levels of circulating TNF receptors and elevated numbers of neutrophils. 1264 Nov 28

The present report concerns the demonstration and distribution of tau-positive structures in the frontal and temporal white matter of five autopsy cases of early onset Alzheimer's disease (AD). The relationship between white matter lesions and tau positive structures was also investigated. Five early onset AD brains, which had not only unambiguous white matter lesions, but also no or rare atherosclerosis and minimal amyloid angiopathy, were examined. There were several tau-positive coiled body-like structures and many thread-like structures in the white matter, although previous reports showed only a few coiled bodies in the white matter in the AD brain. No relationship was found between the degree of each white matter lesion and number or distribution of tau-positive structures in the white matter. The results suggest that the AD brain has tau-positive structures in the white matter similar to some neurodegenarative brain diseases such as progressive supranuclear palsy, corticobasal degeneration, and dementia with grains. However, tau abnormalities may have fewer effects when they are located in white matter lesions in AD.
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PMID:Demonstration and distribution of tau-positive glial coiled body-like structures in white matter and white matter threads in early onset Alzheimer's disease. 1203 Apr 17

The plasma ACTH and cortisol levels do not change during aging. On the other hand, the plasma dehydroepiandrosterone sulfate (DHEA-S) changes remarkably during aging. Before puberty, the plasma DHEA-S level both in males and females is very low, however, it rapidly increases at puberty, and thereafter significantly decreases both linearly and age-dependently. Cytochrome P450c17 has two enzyme activities, 17-alpha-hydroxylase and 17,20-lyase. Cortisol is synthesized by 17-alpha-hydroxylase, and DHEA is synthesized by 17,20-lyase. The mechanism of dissociation of cortisol and DHEA synthesis in aging depends on another regulator of 17,20-lyase of cytochrome P450c17 such as cytochrome P450 reductase. We demonstrated significant decrease in cytochrome P450 reductase activity in bovine aged adrenal glands. We clarified the beneficial effects of DHEA as an anti-aging steroid based on both in vitro and in vivo experiments, such as the stimulatory effect of immune system, anti-diabetes mellitus, anti-atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti-osteoporosis. It is very important to identify the mechanism of action of DHEA. We clarified the conversion of DHEA to estrone by cytochrome P450 aromatase in primary cultured human osteoblasts. We indentified high affinity of DHEA binding with K(d)=6.6 nM in antigen and DHEA stimulated human T lymphocytes. We searched for the target genes that are specifically induced in activated T lymphocytes in the presence of DHEA by subtractive hybridization screening for differentially expressed transcripts. The double blind, randomized human replacement therapies utilizing DHEA are also reviewed.
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PMID:Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. 1204 59

The aim of the study was to evaluate risk factors of atherosclerosis and extra-cerebral target organ damage in patients with hypertension and vascular based mild memory disorders. A group of the study included 20 persons at age of 54-75 (8 males and 12 females) with mild vascular dementia (20-25 pts in MMSE, 22.8 +/- 1.73) with treated mild hypertension. A diagnosis of vascular dementia was confirmed in MRI by two independent experts. All examined patients presented multiinfarction changes in central nervous system as a cause of dementia. The study protocol contained present history, physical examination, 24-hour ambulatory blood pressure monitoring (ABPM), ECG, biochemical tests: total cholesterol, HDL-Ch, LDL-Ch, triglycerides, glucose, urea, creatinine plasma levels and urine test for microalbuminuria. In part of the study group (55%) echocardiography with posterior wall (PW) thickness and ejection fraction (EF) evaluation was performed. In the analysed group mean 24-hour blood pressure values were not elevated (SBP 130.8 +/- 15.8 mm Hg and DBP 77.6 +/- 9.2 mm Hg at day, respectively 121.6 +/- 17.1 mm Hg and 68.2 +/- 11.6 mm Hg at night). No significant (> 10%) nocturnal SBP decrease was observed, however DBP fall was noticed. Either total cholesterol (n < 5.2 mmol/l) or LDL-Ch (n < 3.5 mmol/l) plasma levels were increased in patients with vascular dementia and ranged respectively 5.8 +/- 0.9 and 3.7 +/- 0.9 mmol/l, HDL-Ch and triglycerides levels remained normal (respectively 1.7 +/- 0.5 and 1.5 +/- 1.1 mmol/l). Mean urea and creatinine levels were maintained in normal range (urea 5.8 +/- 1.7 mmol/l, creatinine 75.5 +/- 15.1 mumol/l). In a part of study group (35%) microalbuminuria was presented (urine albumine > 20 mg/l). In majority of patients with hypertension and vascular dementia a few risk factors co-existed. No systolic blood pressure decrease observed at night in 24-hour blood pressure monitoring, though normal mean values, can play an important role in vascular abnormalities progression.
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PMID:[Vascular dementia and systemic changes]. 1218 86

In recent years, oxidative stress has been implicated in a variety of degenerative processes, diseases, and syndromes. Some of these include atherosclerosis, myocardial infarction, stroke, and ischemia/reperfusion injury; chronic and acute inflammatory conditions such as wound healing; central nervous system disorders such as forms of familial amyotrophic lateral sclerosis (ALS) and glutathione peroxidase-linked adolescent seizures; Parkinson's disease and Alzheimer's dementia; and a variety of other age-related disorders. Among the various biochemical events associated with these conditions, emerging evidence suggests the formation of superoxide anion and expression/activity of its endogenous scavenger, superoxide dismutase (SOD), as a common denominator. This review summarizes the function of SOD under normal physiological conditions as well as its role in the cellular and molecular mechanisms underlying oxidative tissue damage and neurological abnormalities. Experimental evidence from laboratory animals that either overexpress (transgenics) or are deficient (knockouts) in antioxidant enzyme/protein levels and the genetic SOD mutations observed in some familial cases of ALS are also discussed.
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PMID:Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. 1219 1

Plasma levels of tumour necrosis factor (TNF)-alpha levels increase with age. High levels are associated with dementia and atherosclerosis in centenarians. Chlamydia pneumoniae induces the production of proinflammatory cytokines and has been related to the pathogeneses of Alzheimer's disease and cardiovascular diseases. The purpose of this study was to test the hypothesis that circulating levels of TNF-alpha represent a link between C. pneumoniae, high prevalences of dementia and cardiovascular diseases in 126 Danish centenarians. IgA antibody titres against C. pneumoniae were linearly correlated with high plasma levels of TNF-alpha in centenarians. However, both parameters were also correlated with total IgA in the blood and the association between C. pneumoniae IgA and TNF-alpha was not significant when total IgA was included in a multiple linear regression model. Accordingly, the association between C. pneumoniae-specific IgA and TNF-alpha may reflect immune activation rather than a specific antibody response. No associations were found between antibodies to C. pneumoniae and dementia or cardiovascular diseases. Although TNF-alpha is likely to be involved in the pathogenesis of atherosclerosis and dementia, the present study does not support the hypothesis that TNF-alpha represents a link between chronic C. pneumoniae infection and these disorders.
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PMID:Proinflammatory cytokines, antibodies to Chlamydia pneumoniae and age-associated diseases in Danish centenarians: is there a link? 1219 74

Post-mortem analyses suggest that atherosclerosis more often contributes to late-onset dementia than hitherto expected. We set out to further unravel the relation between atherosclerosis and cognitive impairment. We therefore tested the hypothesis that the number of cardiovascular pathologies is positively associated with cognitive impairment in elderly subjects, and that the smaller number of cardiovascular pathologies in women explains the better cognitive function of elderly women. Within the Leiden 85-plus Study, we assessed the atherosclerotic burden by counting the number of cardiovascular pathologies in the medical histories of a population-based sample of 599 subjects aged 85 years (response 87%). Significantly more men than women had a history of cardiovascular pathologies (67% compared to 59%, P<0.001). In addition, cognitive function was assessed. All subjects completed the Mini-Mental State Examination (MMSE). Cognitive speed and memory were determined with specific neuro-psychological tests in those with a MMSE-score above 18 points. There was a highly significant dose-response relationship between the number of cardiovascular pathologies and cognitive impairment for both men and women. The median MMSE-score was 26 points in subjects without cardiovascular disease and decreased to 25 points for subjects who had two or more cardiovascular pathologies (P for trend =0.003). Similar associations were found for cognitive speed but not for memory. Our data confirm that in old age atherosclerosis significantly contributes to cognitive impairment. Since treatments for atherosclerosis appear to be particularly effective in elderly people, we consider our finding of utmost clinical importance in possibly preventing cognitive impairment and late-onset dementia.
Atherosclerosis 2002 Dec
PMID:Atherosclerosis and cognitive impairment are linked in the elderly. The Leiden 85-plus Study. 1241 87


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