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Biomedical subjects

I Jialal

Publications and source records attributed to I Jialal.

At least 73 records · Page 4Linked to original sources
PubMed1996

RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus.

Patients with diabetes mellitus have an increased risk of premature atherosclerosis, which may be due in part to increased oxidizability of low-density lipoprotein (LDL). Numerous studies have shown that alpha-tocopherol can reduce the oxidative susceptibility of LDL in normoglycemic subjects; however, there are few studies in persons with diabetes. In addition, alpha-tocopherol may reduce the extent of protein glycation. Therefore, the objective of the present study was to assess the effect of RRR-alpha-tocopheryl acetate supplementation on LDL oxidizability and protein glycation in persons with diabetes without evidence of vascular disease. Twenty-eight persons with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) were randomly assigned to receive either placebo or 1632 mg (1200 IU) RRR-alpha-tocopherol/d, as tocopheryl acetate, for 8 wk. Plasma and LDL antioxidant concentrations and LDL oxidizability were assessed at both 0 and 8 wk. Plasma and LDL concentrations of alpha-tocopherol were significantly increased in the supplemented group only. Compared with the placebo group, the alpha-tocopherol-supplemented group had significant reductions in LDL oxidizability at 8 wk, as shown by the time-course curves of conjugated diene and lipid peroxide formation. Also, alpha-tocopherol supplementation produced a significant prolongation in the lag phases of both assays, which was evident in both the NIDDM and IDDM subgroups. However, there were no significant changes in glycated hemoglobin or in glycated plasma proteins after alpha-tocopherol supplementation. Thus, alpha-tocopherol supplementation may be beneficial in reducing LDL oxidizability in patients with diabetes.

Adult↗
PubMed1996

A practical approach to the laboratory diagnosis of dyslipidemia.

Disorders in lipoprotein metabolism (dyslipidemia) can result in premature atherosclerosis or pancreatitis. Dyslipidemias can be classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low density lipoprotein cholesterol and decreased levels of HDL cholesterol predispose to premature atherosclerosis. Triglyceride levels greater than 1,000 mg/dL increase the risk for pancreatitis. In the appraisal of the dyslipidemias, measurement of serum cholesterol, triglycerides, HDL-cholesterol and obtaining the LDL cholesterol by Friedewald equation is usually sufficient in the majority of patients. However, in some cases, such as the diagnosis of the Type III dyslipidemia and when triglycerides are > or = 400 mg/dL, ultracentrifugation is required to determine the VLDL or LDL cholesterol. Lipoprotein electrophoresis can be useful in the diagnosis of Type III dyslipidemia (broad beta band) and also to detect chylomicrons. In young subjects with coronary artery disease with a normal LDL cholesterol an apolipoprotein B-100 level may be a useful test. In children and young adults with severe hypertriglyceridemia, measurement of lipoprotein lipase activity or assaying apolipoprotein C-II levels can be useful in elucidating the cause. Also, laboratory tests are useful in excluding a secondary cause of dyslipidemia (urinalysis, plasma creatinine, TSH, glucose, protein electrophoresis, alkaline phosphatase and transaminases). Thus, laboratory investigations play an important role in the management of dyslipidemia.

Chemistry, Clinical↗
PubMed1996

Comparison of cardiac troponin I and lactate dehydrogenase isoenzymes for the late diagnosis of myocardial injury.

Cardiac troponin I (cTnI) is a highly specific marker that is elevated in the blood for several days following myocardial infarction. The lactate dehydrogenase (LD) isoenzyme 1 to isoenzyme 2 ratio (LD1/LD2) is the established marker for the late diagnosis of myocardial infarction. In this study, the sensitivity of cardiac troponin I (cTnI) and LD1/LD2 were compared as late markers of myocardial injury over a 5-day period in 36 patients admitted with a diagnosis of myocardial infarction to the coronary care unit. Over this period, the sensitivity of cTnI was significantly greater than that of LD1/LD2 (P < .05). The concurrent elevation of both cardiac markers of the five day period range from 53.1% to 79.4%. However, this low concordance was largely due to an LD1/LD2 < 1 in the presence of an increased cTnI. The average discordance over the 5-day period was 29.5%. Because cardiac troponin I (cTnI) has greater sensitivity than lactate dehydrogenase isoenzymes for delayed diagnosis of myocardial injury and is a more cost-effective test, the authors recommend it as a test of choice in this setting.

Adult↗
PubMed1996

The role of oxidized low density lipoprotein in atherogenesis.

An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerotic disease. Although the precise mechanism(s) via which LDL promotes atherogenesis remains to be elucidated, the oxidative modification of LDL may be a crucial mechanism. Several lines of evidence support a role for oxidatively modified LDL in atherogenesis. LDL can be oxidatively modified in cell-free systems by transition metals and by all the major cells of the arterial wall. Oxidatively modified LDL (Ox-LDL) is taken up by macrophage scavenger receptors, promoting cholesterol ester accumulation and foam cell formation. It also promotes atherosclerosis by recruitment and retention of monocytes in the intima, by its cytotoxicity toward endothelial cells and by stimulating monocyte adhesion to the endothelium. Several lines of evidence support the in vivo existence of Ox-LDL. The LDL of patients with atherosclerosis are more prone to oxidation; antibodies against epitopes on Ox-LDL have been positively correlated with the progression of atherosclerosis. The oxidation of LDL has been shown to be reduced by antioxidants, and in animal models, these antioxidants decrease atherosclerotic lesion formation. Thus, much evidence supports a role for oxidized LDL in atherogenesis.

Antioxidants↗
PubMed1996

Low-density lipoprotein oxidation, antioxidants, and atherosclerosis: a clinical biochemistry perspective.

Cardiovascular disease is the leading cause of mortality in westernized populations. An increased concentration of plasma low-density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Several lines of evidence support a role for oxidatively modified LDL in atherosclerosis and for its in vivo existence. Antioxidants have been shown to decrease atherosclerotic lesion formation in animal models and decrease LDL oxidation; the evaluation of LDL oxidation in vivo is therefore very important. However, there is a paucity of methods for direct measurement of LDL oxidation. Of the direct methods currently available, the preferred ones seem to be the measurement of F2-isoprostanes, autoantibodies to epitopes on oxidized LDL, and the assessment of antioxidant status. Of the indirect measures, the most uniformly accepted procedure is examining the oxidative susceptibility of isolated LDL by monitoring conjugated diene formation.

Antioxidants↗
PubMed1996

Effect of alpha-tocopherol on LDL oxidation and glycation: in vitro and in vivo studies.

Much data support a role for both low density lipoprotein (LDL) oxidation and glycation in atherogenesis. While alpha-tocopherol decreases the oxidative susceptibility of LDL, its role in decreasing LDL glycation is unclear. Hence we tested the effect of alpha-tocopherol both in vitro and in vivo on LDL oxidation and glycation. LDL was isolated after enrichment of plasma with alpha-tocopherol. This resulted in a 2-fold increase in alpha-tocopherol in LDL (AT-LDL). During a 6-day incubation of control LDL (C-LDL) and AT-LDL with 25 mM glucose, there were no significant differences in the degree of glycation on days 1, 3, and 6. Also, apoB advanced glycosylation end product levels were not significantly different between C-LDL and AT-LDL. There was a progressive increase in the susceptibility of LDL to oxidation with increasing LDL glycation as evidenced by reduced lag time of copper-catalyzed LDL oxidation. However, AT-LDL was more resistant to copper-catalyzed oxidation. Similar findings were observed when the LDLs were incubated with endothelial cells. The data from the alpha-tocopherol supplementation study confirmed our in vitro findings that alpha-tocopherol significantly decreases oxidative susceptibility of LDL, but does not affect its glycation. Therefore, while glycation increases LDL oxidative susceptibility, alpha-tocopherol decreases the oxidation of glycated LDL but not LDL glycation.

Arteriosclerosis↗
PubMed1995

Comparison of an immunoprecipitation method for direct measurement of LDL-cholesterol with beta-quantification (ultracentrifugation).

A direct LDL cholesterol assay was evaluated using immunoprecipitation (Sigma Diagnostics, St. Louis, MO) with beta-quantification obtained by ultracentrifugation. Excellent intra- and interassay coefficients of variation were obtained (< 4.5%). There was a good correlation (r = 0.88, P < .0001) between the two methods for low-density lipoprotein cholesterol (LDL-C) in 249 samples with triglyceride levels ranging from 13 mg/dL to 2,236 mg/dL and LDL cholesterol levels ranging from 28 mg/dL to 290 mg/dL. Similar correlations were seen for patients with triglyceride levels < 400 mg/dL (r = 0.89, n = 174) and > or = 400 mg/dL (r = 0.89, n = 75). However, using the Friedewald equation, there was a good correlation only in samples with triglyceride levels < 400 mg/dL. No significant differences were found between LDL-C quantitated by the direct LDL assay and beta quantification for patients with dysbetalipoproteinemia (Type III disorder). However, calculated LDL values using the Friedewald equation were found to be significantly higher when compared to beta-quantification in patients with the Type III disorder. There was a slight but significant decrease in LDL-C determined by direct LDL cholesterol assay for non-fasting versus fasting serum (4.7%) despite a strong correlation between these samples (r = 0.98, P < .0001). In addition, freezing samples for 30 days resulted in a significant decrease in levels (15.1%). Thus, this direct LDL cholesterol assay is recommended in place of beta-quantification in hypertriglyceridemic samples (TG > or = 400 mg/dL) and to monitor LDL cholesterol levels in patients with Type III dyslipidemia, because it is less time consuming, more cost-effective and can be adapted to the clinical laboratory.

Cholesterol, LDL↗
PubMed1995

The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study.

Because much data have accrued to support the concept that oxidatively modified LDL (Ox-LDL) can promote atherogenesis, the role of antioxidants in decreasing LDL oxidation has assumed great importance. High-dose alpha-tocopherol supplementation in humans decreases the susceptibility of LDL to oxidation. Hence, the aim of the present study was to ascertain the minimum dose of alpha-tocopherol that would decrease the susceptibility of LDL to oxidation. The effect of alpha-tocopherol in doses of 60, 200, 400, 800, and 1200 IU/d on copper-catalyzed LDL oxidation was tested in a randomized placebo-controlled study over 8 weeks. There were eight subjects in each group. Oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides by the thiobarbituric acid-reacting substances (TBARS) assay over an 8-hour time course at baseline and after 8 weeks of supplementation. Neither placebo nor any of the doses of alpha-tocopherol resulted in any side effects or exerted an adverse effect on the plasma lipoprotein profile. However, there was a dose-dependent increase in plasma and lipid-standardized alpha-tocopherol levels with increasing doses of alpha-tocopherol supplementation. LDL alpha-tocopherol appeared to follow a similar trend. When the time-course curves of LDL oxidation and the kinetics of LDL oxidation were examined, there was no significant effect at 8 weeks compared with baseline in the groups that received placebo or alpha-tocopherol 60 or 200 IU/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Plasma oxidizability in subjects with normal glucose tolerance, impaired glucose tolerance, and NIDDM.

OBJECTIVE: Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Studies on LDL oxidation in diabetes to date have examined LDL isolated from plasma, but have failed to evaluate the other pro- and antioxidant factors present in vivo, the balance of which could be crucial in determining the susceptibility of LDL to lipid peroxidation. RESEARCH DESIGN AND METHODS: We examined the oxidizability of plasma from Mexican-Americans in the San Antonio Heart Study. The oxidizability of plasma in 75 subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) was studied after co-incubation with a free radical initiator, 2,2'-azobis-2-amidinopropane hydrochloride (AAPH). Lipid peroxide (LPO) levels were measured by a modified fluorimetric assay. RESULTS: Baseline LPO levels (mumol/l; means +/- SE) were similar in the three glucose tolerance categories (NGT, 1.99 +/- 0.07; IGT, 1.88 +/- 0.07; NIDDM, 1.97 +/- 0.07; P = 0.521). However, after incubation with AAPH (NGT, 4.30 +/- 0.20; IGT, 4.45 +/- 0.20; NIDDM, 5.35 +/- 0.20; P = 0.003), the diabetic plasma had significantly greater amounts of LPOs compared with the other two groups. There was no significant difference in LPOs between the NGT and IGT groups. The statistical significance of increased oxidizability of the diabetic plasma persisted after exclusion of patients who smoked cigarettes (n = 15) or who had vascular disease (n = 4). CONCLUSIONS: In conclusion, this study shows that the plasma of Mexican-American subjects with NIDDM is more prone to lipid peroxidation than that of non-Hispanic whites.

Amidines↗
PubMed1995

Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and atherosclerosis.

OBJECTIVE: The oxidative modification of low density lipoprotein (LDL) may be an early step in atherogenesis. Furthermore, evidence of oxidized LDL has been found in vivo. The most persuasive evidence shows that supplementation of some animal models with antioxidants slows atherosclerosis. The purpose of this review is to examine the roles that vitamin E, vitamin C and beta-carotene may play in reducing LDL oxidation. DATA SOURCES: English language articles published since 1980, particularly from groups active in this field of research. STUDY SELECTION: In vitro, animal, and human studies on antioxidants, LDL oxidation, and atherosclerosis were selected. DATA SYNTHESIS: Vitamin E has shown the most consistent effects with regard to LDL oxidation. Beta-carotene appears to have only a mild or no effect on oxidizability. Ascorbate, although it is not lipophilic, can also reduce LDL oxidative susceptibility. CONCLUSIONS: LDL oxidizability can be reduced by antioxidant nutrients. However, more research is needed to establish their utility in the prevention of coronary artery disease.

Animals↗
PubMed1995

Effect of aging on susceptibility of low-density lipoproteins to oxidation.

According to the Adult Treatment Panel of the National Cholesterol Education Program, age is a major risk factor for heart disease. To assess the relation between age and LDL oxidizability, we studied copper-mediated LDL oxidation in 13 healthy elderly subjects (> 59 years) and 13 sex-matched healthy young controls (< 30 years). Total and LDL-cholesterol concentrations were increased in elderly subjects. The time course of copper-mediated LDL oxidation showed no significant differences between the two groups as assessed by formation of conjugated dienes, lipid peroxides, and apolipoprotein B fluorescence. Kinetics of LDL oxidation as quantified by lag time, oxidation rate, and maximal oxidation were not significantly different between the elderly and young groups. Although the concentrations of 16:0, 18:0, 18:1, 18:3, and 20:4 and total polyunsaturated fatty acids were significantly higher in the elderly group, LDL fatty acid concentrations were similar in both groups. Lipid-standardized alpha-tocopherol, beta-carotene, and ascorbate concentrations were not significantly different between the two groups. The findings of the present study suggest that in the healthy elderly, LDL oxidation may not be a crucial mediator for atherogenesis.

Adult↗
PubMed1995

Susceptibility of plasma to ferrous iron/hydrogen peroxide-mediated oxidation: demonstration of a possible Fenton reaction.

The aim of our study was to evaluate a model system by using iron in the peroxidation of plasma. Lipid peroxidation was monitored by fluorometric measurement of lipid peroxides (LPO). Plasma coincubated with Fe2+ and H2O2 had a 268% increase in plasma LPO after 1 h. The optimum concentrations were 0.42 mmol/L Fe2+ and 0.73 mol/L H2O2. Coincubation of plasma with these concentrations of Fe2+ and H2O2 separately resulted in no increase in plasma LPO. The increase in plasma LPO after oxidation with Fe2+/H2O2 was paralleled by a decrease in plasma polyunsaturated fatty acids, an increase in the relative electrophoretic mobility of low-density lipoprotein (LDL), and decreases in apolipoprotein (apo) B-100 and apo A-I immunoreactivity. In vitro oxidation of LDL and high-density lipoprotein separately with this system produced increases of LPO of 246% and 128%, respectively. LPO formation in plasma was inhibited by catalase, desferrioxamine, and mannitol, but not by superoxide dismutase. Hydroxyl radical generation with Fe2+/H2O2 was evidenced by fragmentation of deoxyribose. We conclude that the Fe2+/H2O2 system, possibly by a Fenton reaction mechanism, resulted in significant plasma oxidation. This model system may be useful for examining lipid peroxidation in clinical investigations.

Adult↗
PubMed1994

LDL modification by activated polymorphonuclear leukocytes: a cellular model of mild oxidative stress.

The purpose of this study was to determine the most potent activator of the respiratory burst of polymorphonuclear leukocytes (PMN) with respect to the oxidative modification of low density lipoprotein (LDL). Phorbol-12-myristate-13-acetate (PMA), n-formyl-methionyl-leucylphenylalanine (nFMLP), lipopolysaccharide (LPS), and opsonized zymosan (OZ) were tested. The generation of reactive oxygen species by PMN was assayed as superoxide anion production. Oxidative modification of LDL was monitored by thiobarbituric acid reactive substance (TBARS) activity, by conjugated dienes formation at 234nm and by electrophoretic mobility on agarose gel. PMA was the most potent activator of PMN, inducing a 6-fold increase in the superoxide anion production, followed by OZ (3-fold increase). PMA activation also induced the greatest modification of LDL by PMN: 700% increase of conjugated dienes formation, 222% increase of TBARS, and 70% increase in the electrophoretic mobility. The indices of oxidative modification significantly correlated with the superoxide anion generated by different activators. Also, LDL oxidation by PMN was inhibited by superoxide dismutase but not by catalase, methionine, or hydroxyl radical scavengers. Our data indicate that PMNs activated by PMA produce a mildly oxidized form of LDL by a mechanism that appears to involve the superoxide anion.

Humans↗