Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent removal of refecoxib (a cyclo-oxygenase II inhibitor), a drug involved in a large prostate cancer chemoprevention trial, and the completion of recruitment for the SELECT cancer chemoprevention trial utilizing selenium and vitamin E should lead researchers to ponder a similar question in cancer chemoprevention. The question of "What agent should be utilized and what clinical trial should designed and conducted next for cancer chemoprevention?" Part I and II of this manuscript attempts to argue that statins or cholesterol-lowering drugs or heart healthy agents are the ideal next choice for a large chemoprevention trial for numerous reasons including: (1) Cardiovascular disease (CVD) has been the number one cause of death in men and women every year in the US since 1900; (2) CVD has been the number one cause of death in the major cancer chemoprevention trials; (3) CVD has been the number one or two cause of death of men and women postdiagnosis of breast, colorectal, and prostate cancer; and (4) the recent potential relationship between certain cancers and dyslipidemia needs to be investigated. What other chemoprevention agent can also boast that in the worst case scenario the number one cause of death in men and women would probably be reduced in this future cancer chemoprevention trial of statins?! The list continues to grow of cancer chemoprevention trials that will probably be either a complete hit or miss. In other words, they will or have reduced the disease of interest with virtually no potential role for reducing the number one cause of death in men and women. The time seems more than overdue for a statin and/or another cholesterol lowering or heart healthy cancer chemoprevention trial.
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PMID:Why a statin and/or another proven heart healthy agent should be utilized in the next major cancer chemoprevention trial: part II. 1561 Aug 64

Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and beta-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.
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PMID:The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. 1607 65

Diabetes mellitus has assumed epidemic proportions in most parts of the world, and it is a major source of morbidity in developed countries. In addition, in several instances, diabetes is associated with a variety of metabolic abnormalities, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and hyperglycemia. There is considerable evidence that hyperglycemia causes the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response by the endogenous antioxidants, such as vitamins C and E, catalase, glutathione, and superoxide dismutase, oxidative stress dominates, resulting in the activation of stress-sensitive intracellular signaling pathways. One of the major consequences is the generation of gene products that cause cellular damage and are ultimately responsible for the late complications of diabetes. The ability of antioxidants to protect against the effects of hyperglycemia in vitro, along with the clinical benefits often reported following antioxidant therapy, supports a causative role of oxidative stress in mediating and/or worsening these abnormalities. This review will focus on the critical assessment of the literature as it relates to the association between oxidative stress and diabetes, followed by the role of oxidative stress in the complications of type 2 diabetes mellitus. Finally, a review of the use of the antioxidant vitamin E will be provided in diabetic patients by assessing and evaluating some of the clinical trials in the literature.
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PMID:The use of vitamin E in type 2 diabetes mellitus. 1749 41

Dyslipidemia is associated with increased low-density lipoprotein (LDL) susceptibility to oxidation, a phenomenon associated with endothelial dysfunction, atherosclerosis, cell toxicity, and intrauterine growth retardation. The present study was designed to determine if women developing gestational diabetes mellitus (GDM) have both increased plasma lipids and LDL susceptibility to oxidation throughout pregnancy. We also wanted to study the effects of obesity upon these parameters. A nested case-control study was carried out in 45 women with uncomplicated pregnancies and 62 women diagnosed with GDM following the criteria of the American Diabetes Association. In all women, blood was drawn at 15, 24, and 32 weeks of gestation. Low-density lipoprotein oxidation was initiated by the addition of CuCl2, and formation of conjugated dienes was monitored. Glucose, cholesterol, triglycerides, vitamin E, estradiol, and progesterone were determined. In GDM, elevated levels of glucose, cholesterol, and triglycerides were observed when compared with the control group even in the first trimester, before the detection of diabetes. In the control group, the lag phase in the LDL oxidation was 85.3, 84.4, and 95.6 minutes at 15, 24, and 32 weeks of pregnancy, compared with 63.3, 63.4, and 74.5 minutes in the GDM group (P < .001 in the 3 periods). These differences remained when adjusted for the body mass index. In a multiple linear regression analysis, a negative correlation was observed between the lag phase and the body mass index (P < .001) and cholesterol (P < .001), whereas a positive one appeared with vitamin E (P < .05) and time of gestation (P < .001). In pregnancy, GDM increases LDL susceptibility to oxidation. Obesity and hypercholesterolemia further exacerbate this effect.
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PMID:Changes in plasma lipids and increased low-density lipoprotein susceptibility to oxidation in pregnancies complicated by gestational diabetes: consequences of obesity. 1795 Jan 4

A low cholesterol (CH)-modified poultry egg (ME Psi) containing more vitamin E, lenolenic acid, and minerals Cu and Mg but low total lipid (TL) and Zn contents than the conventional egg evaluated to reduce the severity of dyslipidemia induced by excessive Zn in the diet. The experimental data was recorded on male rats fed on normolipidemic (NL) semi-synthetic basal diet containing 20 mg Zn/kg diet in control group I, Zn supplemented dyslipidemic diet-A (Zn-DL-A) and B (Zn-DL-B) containing 40 and 80 mg Zn/kg diet in groups II and III, and ME Psi-mixed Test diet-A (Zn-DL-A + 4 ME Psi) and Test diet-B (Zn-DL-B + 4 ME Psi) in groups IIEM and IIIEM, respectively, for 180 and 90 days. Data recorded on liver and blood lipid profiles showed reduction in the concentration of TL, CH, triglycerides, and glycogen (GG) in liver consequently leading to their rise in blood serum including rise in VLDL-c and LDL-c but fall in HDL-c in groups II and III rats that reversed after ME Psi treatment resulting in rise of their levels in the liver and fall in the blood of groups IIEM and IIIEM rats, respectively. Mineral status in the liver showed a rise in Zn but fall in Cu and Mg levels in groups II and III that was reversed after ME Psi treatment resulting in fall in Zn and rise in Cu and Mg concentration in the liver of groups IIEM and IIIEM rats. Hepatopathogical studies showed reduction in the dilatation of long citernal profile of endoplasmic reticulum and increase in GG and TL granules in the cytoplasm of hepatocytes of groups IIEM and IIIEM after ME Psi treatment than those of groups II and III rats. It was concluded that the inclusion of ME Psi would be helpful in reducing dyslipidemia by correcting the ionic imbalance generated by excessive Zn intake in rats or by drugs, even in chronic diseased conditions without aggravating risk factors for heart diseases in humans that need further studies.
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PMID:Normolipidemic effect of antioxidants in low cholesterol-modified poultry eggPsi on Zn-induced dyslipidemia and liver pathology in Wistar rats. 1819 9

Objective was to assess dietary intake and physical activity in a Canadian population sample of male patients with HIV and metabolic abnormalities and to compare the data to Canadian recommendations. Sixty-five HIV-infected men with at least one feature associated with the metabolic syndrome (insulin resistance, dyslipidemia, central obesity, or lipodystrophy) were enrolled. Results from 7-day food records and activity logs were compared to the Dietary Reference Intakes and recommendations of Canada's Physical Activity Guide, respectively. Anthropometric data were also measured. Fifty-two percent of the subjects were overweight, another 15% were obese. However, energy intake (mean+/-SEM) (2153+/-99 kcal/d) was lower than the estimated requirement (2854+/-62 kcal/d; p<0.0001), and 84.5% of the patients reached the recommended minimum of 60 min of mild or 30 min of moderate daily exercise. Intake was adequate for protein, but high for fat and cholesterol in 40% of patients. No patient reached the recommendation for fiber. Intake from diet alone was suboptimal for most micronutrients. Prevalence was highest for low vitamin E (91% of patients) and magnesium (68%) intake, and high sodium intake (72%). In summary, a large proportion of HIV patients with metabolic abnormalities were overweight or obese. However, this was not associated with high energy intake, or reduced physical activity. High fat, low fiber and inadequate micronutrient intakes were prevalent.
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PMID:Dietary intake and physical activity in a Canadian population sample of male patients with HIV infection and metabolic abnormalities. 1828 80

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.
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PMID:Relationship between oxidative stress and essential hypertension. 1834 20

The oxidative stress-sensitive c-Jun-N-terminal kinase (JNK) pathway is known to be activated in diabetic condition and is involved in the progression of insulin resistance. However, the effect of antioxidants on JNK pathway and insulin resistance has not been investigated. The present study was aimed to investigate the effect of antioxidants on redox balance, insulin sensitivity, and JNK pathway in high-fat-fed rats. Male Wistar rats were divided into four groups: the control group - received a rodent chow; control+antioxidant group - fed with rodent chow supplemented with 0.2% (w/w) vitamin E, 0.3% (w/w) vitamin C, and 0.5% (w/w) alpha-lipoic acid; high-fat group - received high-fat diet; and high fat+antioxidant group - fed with high-fat diet supplemented with above antioxidants. Fat feeding to rats for 9 weeks significantly increased IRS-1 serine phoshorylation, reduced insulin-stimulated IRS-1 tyrosine phosphorylation and insulin sensitivity. High-fat diet also impaired redox balance and activated the redox-sensitive serine kinase - JNK pathway. Antioxidant supplementation along with high-fat diet preserved the free radical defense system, inhibited the activation of JNK pathway, and improved insulin signaling and insulin sensitivity. The present study shows for the first time that antioxidants inhibit JNK pathway and IRS-1 serine phosphorylation while improving insulin sensitivity in fat-fed rats. These findings implicate the beneficial effect of antioxidants in obesity-/dyslipidemia-induced insulin resistance in humans.
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PMID:Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance. 1843 58

Congenital malformations of neonates are one of the adverse effects of diabetic pregnancy which can be prevented by supplementation of vitamin E and C. The survived neonates usually are at higher risk to diabetes, hypertension, dyslipidemia and cardiovascular diseases that may possibly be prevented through antioxidants administration. In view of this information, the efficacy of modified poultry egg enriched with optimum minerals, vitamin E and omega-3 fatty acids was studied on F1-generation, which were made to survive by feeding them this modified egg to diabetic mothers of Wistar rats. The survived F1-generation displayed hyperglycemia, dyslipidemia and hypertension like their parents, evaluated after three months of the experiment. Their mineral status revealed a higher Zn and lower Cu, Mg and Mn levels in liver and kidney. Their lipid peroxidation products were however higher and the enzyme activities of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, glutathione (reduced) and glucose -6 phosphate dehydrogenase were significantly lower. In the other group of F1-generation, fed modified egg mixed diet, a significant reduction in the blood pressure, serum glucose, serum lipid profile, and the lipid peroxidation products, and a significant increase in the activities of enzymes per se with reversal of Zn, Cu, Mg and Mn levels closer to the control group were recorded. The data suggest that the modified egg can ameliorate the oxidative stress in F1-generation of diabetic rats by improving the mineral status in their body.
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PMID:Beneficial effects of modified egg* on oxidative stress in F1- generation of metabolic syndrome-X induced Wistar rat. 1937 65

Molecular mechanisms, responsible for the impaired insulin-sensitivity state due to the obesity are not fully understood in both humans and animals. The purpose of this study was to investigate the effects of castration-induced visceral obesity and the influence of two antioxidants on constituents of blood lipid profile and insulin sensitivity in New Zealand white rabbits. Twenty-six clinically healthy male New Zealand white rabbits were used in the experiment and were divided into 3 groups: first group (CI, n=7) - castrated-obese and treated with antioxidants "Immunoprotect" for 2months; second group (CO, n=7) - castrated-obese; third group (NC, n=12) - control group (non-castrated, non-obese). At the end of the follow-up period of 2months after castration an intravenous glucose tolerance test (IVGTT) was performed after a 12-h fasting period as the blood samples for determination of glucose and insulin and their kinetic parameters were obtained at 5 and 0min before and at 5, 10, 30, 60 and 120min after the infusion of the glucose. The constituents of lipid profile, triglycerides (TG), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also assessed in the overnight fasting blood samples. The body weight (BW), body mass index (BMI), amount of the visceral fat (VF) and VF/BW ratio were both measured and calculated before the IVGTT and at the end of the experimental period. All measured markers of obesity (BW, BMI, VF, VF/BW) were significantly higher in both groups of castrated rabbits than in the control group. Apart HDL-C, the plasma concentrations of all constituents of lipid profile (TG, TC, HDL-C) were the highest in CO group. There were generally no differences between CI and NC groups for the same traits. After glucose injection blood glucose concentrations and glucose and insulin kinetic parameters were considerably higher (except of glucose elimination rate) in CO rabbits than in NC ones. Castrated rabbits treated with "Immunoprotect" showed lower fasting plasma insulin and improved glucose kinetics dynamics than CO rabbits, but commensurable values of glucose and insulin kinetics parameters than NC group. The results of the current study clearly indicated that castration-induced visceral obesity affected negatively the lipid profile and insulin sensitivity and/or responsiveness. Treatment with antioxidant supplementation, consisted of d-limonene and vitamin E, improved blood lipid profile, fatty liver, glucose homeostasis and insulin sensitivity in obese rabbits. In addition, based on our results we may suggest that castrated male New Zealand white rabbits might be considered as an appropriate animal model to study various metabolic abnormalities related to visceral obesity, such as dyslipidemia and impaired insulin sensitivity.
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PMID:Effects of castration-induced visceral obesity and antioxidant treatment on lipid profile and insulin sensitivity in New Zealand white rabbits. 2054 6


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