Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Through a variety of different mechanisms, it appears that survivors of childhood acute lymphoblastic leukemia have an increased prevalence of several cardiovascular risk factors and thus are at increased risk for developing cardiovascular disease. The aim of this paper is to describe the current understanding of particular risk factors, including obesity, physical inactivity, dyslipidemia, insulin resistance, and metabolic syndrome, that may contribute to cardiovascular disease in survivors of childhood ALL. The potential roles of different cancer therapies in the development of these risk factors are discussed. In addition, two other late effects that may affect cardiovascular health are discussed: late-onset anthracycline-induced left ventricular dysfunction and methotrexate-mediated elevations of homocysteine during therapy with the potential for endothelial dysfunction. Lastly, areas needing further investigation to elucidate these risks are highlighted.
 ...
PMID:Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of cardiovascular disease? 1806 58

Chronic sub-clinical inflammation observed in hypertension plays a prominent role in the progression of atherosclerosis. Accumulating evidence suggests that homocysteine (Hcy) can cause inflammation. The aim of this study was to compare the predictive utility of Hcy and lipid measures as determinants of inflammation in hypertensive patients. We studied a group of 100 patients (45.0+/-12.2 years old) with essential hypertension and a control group of 40 healthy volunteers (44.0+/-8.7 years old). We found that plasma total Hcy (tHcy), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP) were significantly higher in hypertensive patients compared with the control group. The subgroup of hypertensive patients with obesity had higher levels of TNF-alpha (p<0.001), IL-6 (p<0.01), and tHcy (p=0.063), compared with the subgroup of hypertensive patients without obesity. The subgroup of patients with a history of myocardial infarction or stroke had significantly higher levels of tHcy, TNF-alpha, IL-6, and CRP compared to patients with a negative history of vascular events. In the group of hypertensive patients, a strong positive correlation between tHcy and TNF-alpha was observed (r=0.48; p<0.001). In contrast, no correlation was observed between TNF-alpha and any of the lipid measures. In multivariate regression analysis tHcy, but not lipids, was an independent predictor of TNF-alpha. In conclusion, our findings show that plasma tHcy is a determinant of TNF-alpha in hypertension and that obesity or a history of vascular events aggravates inflammation in patients with hypertension. A positive correlation between Hcy and TNF-alpha suggests a mechanism underlying the pro-atherogenic properties of Hcy.
 ...
PMID:Plasma homocysteine is a determinant of tissue necrosis factor-alpha in hypertensive patients. 1809 92

Increased intima-media thickness (IMT) and pulse wave velocity (PWV) are noninvasive markers of early arterial wall alteration and are more widely used in adult clinical research. We investigated whether IMT and PWV are useful predictors of cardiovascular risk in hypertensive adolescents. Fifteen hypertensive adolescents (13-18 yr old, systolic BP > or = 140 mmHg, diastolic BP > or = 90 mmHg) and seventeen normotensive subjects were included. Height, weight, obesity index, body mass index (BMI), and fat distribution were obtained from each group. Serum lipid, insulin, vitamine B12, folate, renin, aldosterone, angiotensin-converting enzyme (ACE), and homocysteine levels were compared. The carotid IMT and PWV were measured. Arterial wall compliance and distensibility were calculated with the equation. High systolic blood pressure significantly correlated with height, weight, BMI, obesity index, arm circumference, fat mass, and fat distribution. Hypertensive adolescents had significantly greater cIMT (carotid intima-media thickness) and lower elastic properties such as cross-sectional compliance and distensibility of the carotid artery. The carotid IMT significantly correlated with brachial-ankle PWV. In conclusion, the measurement of carotid IMT and brachial-ankle PWV might be useful to predict the development of atherosclerosis in hypertensive adolescents.
 ...
PMID:Intima-media thickness and pulse wave velocity in hypertensive adolescents. 1830 96

Obesity is associated with atherosclerotic risk factors, including reduced blood flow, endothelial dysfunction, lipid disorders and hyperinsulinemia. In recent years, several studies have demonstrated that elevated homocysteine is a risk factor for atherosclerosis. This study was aimed at determining whether any relationship between plasma viscosity and homocysteine levels in patients with normo and hyperinsulinemic obese patients. Obese women (n=75) and healthy, age-matched non-obese women (n=70) was included in our study. Plasma viscosity, tHcy, insulin level, total-C, LDL-C, HDL-C, triglyceride and glucose level were significantly higher in obese subjects than in non-obese subjects. Obese subjects were also divided into two groups, according to the basal insulin levels as normo and hyper insulinemic. Hyperinsulinemic obese subjects had significantly higher PV level compared with normoinsulinemic subjects. When correlation analyses were performed normoinsulinemic obese subjects, significant correlations were found between PV and total-C (r: 0.776) and insulin level (r: 0.752), BMI (r: 0.580), HOMA-IR (r: 0.510). PV was positively correlated with total-C (r: 0.485), insulin level (r: 0.624), BMI (r: 0.624) and HOMA-IR ratio (r: 0.707), in hyperinsulinemic obese subjects. Hcy was positively correlated BMI in both groups. In conclusion that, it is point out that elevated homocysteine and increased PV are two factors that may act separately and probably do not affect each other.
 ...
PMID:Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese female subjects. 1833 77

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.
 ...
PMID:Relationship between oxidative stress and essential hypertension. 1834 20

The cholesteryl ester transfer protein (CETP) gene has been associated with a variety of phenotypes, including HDL-cholesterol levels and, more sporadically, with cardiovascular disease, obesity, and extreme longevity. Alterations of CETP activity levels can be caused by single-base polymorphisms as well as by alternative splicing. In addition to the previously characterized alternative splicing that skips exon 9, we found additional minor variants and characterized the activity of the resultant proteins. The novel variants skipped exon 9 sequences and inserted one of two in-frame exons from Alu-derived intronic sequences. None of the alternatively spliced variants are efficiently secreted, and coexpression of them inhibits wild-type CETP secretion. Expression of the alternative spliced variants causes an induction of genes linked to the endoplasmic reticulum (ER) stress response, including the neighboring HERPUD1 (homocysteine- and ER stress-inducible protein, ubiquitin-like domain-containing) gene. Unexpectedly, even though wild-type CETP is secreted much more efficiently than spliced variants, it induces the same degree of stress response as spliced variants, whereas a control secreted protein does not. CETP plays a complex role in modulating ER stress, with its expression inducing the response and its cholesteryl ester transfer activity and differential splicing modulating the response in other ways.
 ...
PMID:Expression of CETP and of splice variants induces the same level of ER stress despite secretion efficiency differences. 1850 95

Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease.
 ...
PMID:Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. 1859 Mar 47

Leptin is an important circulating signal for inhibiting food intake and body weight gain. In recent years, "leptin resistance" has been considered to be one of the main causes of obesity. However, the detailed mechanisms of leptin resistance are poorly understood. Increasing evidence has suggested that stress signals, which impair endoplasmic reticulum (ER) function, lead to an accumulation of unfolded proteins, which results in ER stress. In the present study, we hypothesized that ER stress is involved in leptin resistance. Tunicamycin, thapsigargin, or brefeldin A was used to induce ER stress. The activation status of leptin signals was measured by Western blotting analysis using a phospho-(Tyr705) signal transducer and activator of transcription 3 (STAT3) antibody. We observed that ER stress markedly inhibited leptin-induced STAT3 phosphorylation. In contrast, ER stress did not affect leptin-induced c-Jun NH(2)-terminal kinase activation. These results suggest that ER stress induces leptin resistance. ER stress-induced leptin resistance was mediated through protein tyrosine phosphatase 1B but not through suppressors of cytokine signaling 3. It is noteworthy that a chemical chaperone, which could improve the protein-folding capacity, reversed ER stress-induced leptin resistance. Moreover, homocysteine, which induces ER stress, caused leptin resistance both in vitro and in vivo. Together, these findings suggest that the pathological mechanism of leptin resistance is derived from ER stress.
 ...
PMID:Endoplasmic reticulum stress induces leptin resistance. 1875 73

The vasculature plays a crucial role in inflammation, angiogenesis, and atherosclerosis associated with the pathogenesis of inflammatory rheumatic diseases, hence the term 'vascular rheumatology'. The endothelium lining the blood vessels becomes activated during the inflammatory process, resulting in the production of several mediators, the expression of endothelial adhesion molecules, and increased vascular permeability (leakage). All of this enables the extravasation of inflammatory cells into the interstitial matrix. The endothelial adhesion and transendothelial migration of leukocytes is a well-regulated sequence of events that involves many adhesion molecules and chemokines. Primarily selectins, integrins, and members of the immunoglobulin family of adhesion receptors are involved in leukocyte 'tethering', 'rolling', activation, and transmigration. There is a perpetuation of angiogenesis, the formation of new capillaries from pre-existing vessels, as well as that of vasculogenesis, the generation of new blood vessels in arthritis and connective tissue diseases. Several soluble and cell-bound angiogenic mediators produced mainly by monocytes/macrophages and endothelial cells stimulate neovascularization. On the other hand, endogenous angiogenesis inhibitors and exogenously administered angiostatic compounds may downregulate the process of capillary formation. Rheumatoid arthritis as well as systemic lupus erythematosus, scleroderma, the antiphospholipid syndrome, and systemic vasculitides have been associated with accelerated atherosclerosis and high cardiovascular risk leading to increased mortality. Apart from traditional risk factors such as smoking, obesity, hypertension, dyslipidemia, and diabetes, inflammatory risk factors, including C-reactive protein, homocysteine, folate deficiency, lipoprotein (a), anti-phospholipid antibodies, antibodies to oxidized low-density lipoprotein, and heat shock proteins, are all involved in atherosclerosis underlying inflammatory rheumatic diseases. Targeting of adhesion molecules, chemokines, and angiogenesis by administering nonspecific immunosuppressive drugs as well as monoclonal antibodies or small molecular compounds inhibiting the action of a single mediator may control inflammation and prevent tissue destruction. Vasoprotective agents may help to prevent premature atherosclerosis and cardiovascular disease.
 ...
PMID:Vascular involvement in rheumatic diseases: 'vascular rheumatology'. 1894 76

A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.
 ...
PMID:[Chronic renal disease as cardiovascular risk factor]. 1899 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>