Search PubMed⌕ Search

Biomedical subjects

I Jialal

Publications and source records attributed to I Jialal.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of antioxidants and fatty acids on low-density-lipoprotein oxidation.

Evidence continues to accumulate that implicates the oxidative modification of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. Numerous studies have indicated the existence of oxidized LDL in vivo. Supplementation of animals and humans with antioxidants such as alpha-tocopherol have shown promise in reducing the extent of LDL oxidation. However, another possible means of preventing LDL oxidative modification may be by reducing the amount of oxidizable polyunsaturated fatty acids in the LDL particle. Monounsaturated fatty acids have been shown to decrease the susceptibility of LDL oxidation in human studies. It remains to be seen whether saturated fatty acids can do the same. Stearic acid, found in cocoa butter, would be an ideal saturated fatty acid to test because it has a neutral effect on the plasma lipid profile.

Animals↗
PubMed1994

A critical assessment of the effects of aminoguanidine and ascorbate on the oxidative modification of LDL: evidence for interference with some assays of lipoprotein oxidation by aminoguanidine.

Several lines of evidence support a role for oxidized low density lipoprotein (LDL) in the genesis of the atherosclerotic lesion. Hence, the effect of compounds with antioxidant properties on LDL oxidation assumes great significance. Ascorbate, a potent water-soluble chain-breaking antioxidant, has been shown to inhibit LDL oxidation. Aminoguanidine (AMG) is a pharmacological inhibitor of advanced non-enzymatic glycosylation. Recently it has been suggested that aminoguanidine might have an inhibitory effect on LDL oxidation, but total lipid peroxidation assayed by conjugated diene formation was not inhibited. Thus, in this study, we compared the effect of aminoguanidine with ascorbate to obtain a better appreciation of the effect of AMG on Cu(2+)-catalyzed LDL oxidation. Oxidative modification of LDL was monitored by assaying intermediates and end products of lipid peroxidation, conjugated dienes (CD), lipid peroxides (LPO), and relative electrophoretic mobility (REM). Apolipoprotein B-100 modification (increased fluorescence, fragmentation on SDS-PAGE, and 125I-labeled LDL degradation by human macrophages) was also measured. Ascorbate (100 microM) inhibited LDL oxidation by > 95%, as evidenced by all of the selected indices. Aminoguanidine (20 mM) substantially decreased thiobarbituric acid-reactive substances (TBARS) activity and lipid peroxide formation, but only partially prevented the increase of REM (-55%), apoB fluorescence (-39%), and degradation by macrophages (-54%). Unlike ascorbate, AMG failed to preserve alpha-tocopherol in LDL, prevent apoB-100 fragmentation, or inhibit conjugated diene formation during LDL oxidation. Furthermore, incubation of AMG with already oxidized LDL resulted in a significant decrease in TBARS activity and LPO, and 26.9% decrease in the REM of LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein B-100↗
PubMed1993

Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin.

South Africans of Indian origin have a high frequency of Familial Hypercholesterolemia (FH). Fibroblasts from a South African Indian FH homozygote, D, expressed about 30% of the normal number of LDL receptors. These receptors showed defective LDL binding. Sequence and haplotype analysis revealed that D had two different mutant LDL receptor alleles: FH Durban-1 is a point mutation [asp69(GAT) to tyr(TAT)] in ligand-binding repeat 2 and FH Durban-2 is a point mutation [glu119(GAG) to lys(AAG)] in ligand-binding repeat three of the LDL receptor. Single-strand conformational polymorphism analysis, which was used in the initial detection of these mutations, was also employed for subsequent population screening assays. These mutations were not detected in any of the South African Indian FH or hypercholesterolemic patients that were screened.

Base Sequence↗
PubMed1993

Oxidized LDL and antioxidants.

Several studies have shown that the oxidative modification of low-density lipoprotein (LDL) may promote fatty-streak formation, the early lesion of atherosclerosis. Epidemiologic data suggest that decreased levels of micronutrient antioxidants are associated with an increased frequency of cardiovascular disease. Micronutrients that can act as antioxidants--ascorbic acid, alpha-tocopherol, and beta-carotene--have been shown to prevent LDL oxidation in vitro and retard the progression of atherosclerosis in animal models. In addition, supplementation of human subjects with these compounds have been shown to increase the resistance of their LDL to oxidation without producing side effects. Thus, these antioxidant micronutrients have the potential to become an additional treatment modality in the therapeutic arsenal against atherosclerosis.

Animals↗
PubMed1993

Effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on low-density lipoprotein oxidation.

BACKGROUND: Data continue to accumulate supporting a proatherogenic role for oxidized low-density lipoprotein (Ox-LDL). Antioxidant micronutrients such as ascorbate, alpha-tocopherol, and beta carotene, levels of which can be favorably manipulated by dietary measures without side effects, could be a safe approach in inhibiting LDL oxidation. In fact, in vitro studies have shown that all three antioxidants can inhibit LDL oxidation. The present study was undertaken to ascertain both the safety and antioxidant effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on LDL oxidation. METHODS AND RESULTS: The effect of combined supplementation with alpha-tocopherol (800 IU/d) plus ascorbate (1.0 g/d) and beta carotene (30 mg/d) on copper-catalyzed LDL oxidation was tested in a randomized, placebo-controlled study in two groups of 12 male subjects over a 3-month period. Blood samples for the lipoprotein profile, antioxidant levels, and LDL isolation were obtained at baseline and at 3 months. Neither placebo nor combined antioxidant therapy resulted in any side effects or exerted an adverse effect on the plasma lipoprotein profile. Compared with placebo, combined antioxidant therapy resulted in a significant increase in plasma ascorbate and lipid standardized alpha-tocopherol and beta carotene levels (2.6-, 4.1-, and 16.3-fold, respectively). At baseline, there were no significant differences in the time course curves and kinetics of LDL oxidation as evidenced by the thiobarbituric acid reacting substances (TBARS) assay and the formation of conjugated dienes. However, at 3 months, combined supplementation resulted in a twofold prolongation of the lag phase and a 40% decrease in the oxidation rate. The combined antioxidant group was also compared with a group that received 800 IU of alpha-tocopherol only. Although the combined antioxidant group had significantly higher ascorbate and beta carotene levels than the group supplemented with alpha-tocopherol alone, there were no significant differences between the two groups with respect to LDL oxidation kinetics. CONCLUSIONS: Combined supplementation with ascorbate, beta carotene, and alpha-tocopherol is not superior to high-dose alpha-tocopherol alone in inhibiting LDL oxidation. Hence, alpha-tocopherol therapy should be favored in future coronary prevention trials involving antioxidants.

Adult↗
PubMed1992

Effect of low-dose probucol therapy on LDL oxidation and the plasma lipoprotein profile in male volunteers.

The effect of 4 months of low-dose probucol treatment (250 mg/day) on LDL oxidation and on plasma-HDL cholesterol was studied in a prospective, double-blind, randomized, placebo-controlled trial involving 26 male volunteers. LDL samples isolated at baseline and at 4 months were subjected to in vitro tests of LDL oxidation, involving copper-catalyzed, time-course experiments. For the placebo group, LDL oxidation did not significantly change over the 4-month period. However, in the probucol group, LDL oxidation was significantly inhibited at 4 months, as evidenced by assays measuring conjugated diene formation, lipid peroxide production and altered electrophoretic mobility of oxidized LDL. In fact, in the probucol group the 'lag-phase' of oxidation was prolonged 2.7-fold. Neither probucol nor placebo had a significant effect on plasma HDL-cholesterol: in the probucol group HDL-cholesterol fell from 37.7 +/- 7.4 mg/dl to 34.2 +/- 8.3 mg/dl (percentage decrease -8.9), while in the placebo group plasma HDL-cholesterol levels were 42.4 +/- 8.3 mg/dl and 40.9 +/- 7.0 mg/dl at baseline and 4 months (percentage decrease -2.7). Therefore, a low dose of probucol (250 mg/day) given daily seems to afford protection against the oxidative modification of LDL, and does not appear to exert any substantial effect on the plasma lipoprotein profile.

Double-Blind Method↗
PubMed1992

Effect of dietary supplementation with alpha-tocopherol on the oxidative modification of low density lipoprotein.

Much data has accumulated supporting a proatherogenic role for oxidized low density lipoprotein (Ox-LDL). Micronutrient antioxidants such as alpha-tocopherol, the principal lipid-soluble antioxidant, assume potential significance because levels can be manipulated by dietary measures without resulting in side effects. Co-incubation of LDL in vitro with alpha-tocopherol inhibits its oxidative modification. Hence the effect of dietary supplementation with alpha-tocopherol on the time course of copper-catalyzed oxidation of LDL was tested in a randomized placebo-controlled single-blind study. Two groups of 12 male subjects were given either placebo or alpha-tocopherol (800 IU/day) for a period of 12 weeks. Alpha-tocopherol therapy did not result in any side effects or exert an adverse effect on the plasma lipid and lipoprotein profile. While the lipid standardized alpha-tocopherol levels were similar at baseline, the supplemented group had 3.3-fold and 4.4-fold higher levels compared to placebo at 6 and 12 weeks, respectively. In the 15 subjects in whom both plasma and LDL alpha-tocopherol levels were quantitated, there was a significant correlation (r = 0.79, P less than 0.0001). At baseline there were no significant differences in the time course curves of thiobarbituric acid-reacting substances (TBARS) activity or conjugated diene formation between the alpha-tocopherol and placebo groups. However, at both 6 and 12 weeks the mean levels of TBARS activity and conjugated diene formation were lower in the alpha-tocopherol group; the most significant differences were manifest at the 3-h time point. Also at both 6 and 12 weeks the mean rate of oxidation was lower in the alpha-tocopherol group.2+_

Administration, Oral↗
PubMed1991

beta-Carotene inhibits the oxidative modification of low-density lipoprotein.

Several lines of evidence indicate that oxidized LDL (Ox-LDL) may promote atherogenesis. Hence, the role of antioxidants in the prevention of LDL oxidation needs to be determined. beta-Carotene, in addition to being an efficient quencher of singlet oxygen, can also function as a radical-trapping antioxidant. Since previous studies have failed to show that beta-carotene inhibits LDL oxidation, we re-examined its effect on the oxidative modification of LDL. For these studies, LDL was oxidized in both a cell-free (2.5 microM Cu2+ in PBS) and a cellular system (human monocyte macrophages in Ham's F-10 medium). beta-Carotene inhibited the oxidative modification of LDL in both systems as evidenced by a decrease in the lipid peroxide content (thiobarbituric-acid-reacting substances activity), the negative charge of LDL (electrophoretic mobility) and the formation of conjugated dienes. By inhibiting LDL oxidation, beta-carotene substantially decreased its degradation by macrophages. beta-Carotene (2 microM) was more potent than alpha-tocopherol (40 microM) in inhibiting LDL oxidation. Thus, beta-carotene, like ascorbate and alpha-tocopherol, inhibits LDL oxidation and might have an important role in the prevention of atherosclerosis.

Antioxidants↗
PubMed1991

Pituitary function tests in black patients with pseudocyesis.

Pituitary function was evaluated in a group of 10 patients with pseudocyesis. One patient was postmenopausal; the remainder demonstrated normal basal prolactin, luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels and also normal pituitary-adrenal, pituitary-thyroid axes. Oestradiol deficiency was present in 6 patients, while 2 patients demonstrated elevated serum progesterone values, suggestive of a luteal phase. Gonadotrophin-releasing hormone administration resulted in exaggerated stimulation of LH and FSH in 4 and 2 patients, respectively. Impaired growth hormone (GH) secretion was present in 6 patients after insulin-induced hypoglycaemia and L-dopa administration. GH impairment is probably a consequence of the oestrogen deficiency that commonly occurs in this condition. It thus appears that there are aberrations in specific pituitary hormone responses after provocation in pseudocyesis.

Adult↗
PubMed1991

Coronary risk factors in newly diagnosed and previously diagnosed type 2 diabetic men with myocardial infarction.

Risk factors for coronary artery disease in 131 known non-insulin-dependent (type 2) diabetic patients is compared to that in 115 newly diagnosed type 2 diabetic subjects and in 316 non-diabetic patients. The subjects, all Indian men aged 21-60 years, represent consecutive survivors of myocardial infarction and were investigated 3-4 months after their acute episode. A group of 524 healthy Indian men aged 21-60 years were included as controls. Significant differences in parameters measured were noted when all diabetic and non-diabetic patients were compared to the control group. Diabetic patients were older than the non-diabetic patients and with significantly higher frequency of hypertension and hypertriglyceridaemia, whilst smoking and family history of coronary artery disease were elicited more frequently in the non-diabetic patients. Mean concentrations of serum total cholesterol and lipoproteins in the diabetic and non-diabetic men were similar, whereas serum triglyceride concentrations were significantly higher in the diabetic patients. Newly diagnosed and known diabetic patients did not differ with respect to the risk factors examined. Clusters of various combinations of hypertension, obesity, hypertriglyceridaemia and low HDL-cholesterol values were encountered more frequently in diabetic patients when compared to non-diabetic patients, whilst no significant differences were observed when the two groups of diabetic subjects were compared. In conclusion, this study has demonstrated that in men with myocardial infarction there are significant differences between diabetic and non-diabetic patients with respect to certain risk factors. However, newly diagnosed diabetic men have similar risk profiles to their known diabetic counterparts.

Adult↗
PubMed1991

Lipid and lipoprotein abnormalities in South African Indian men with myocardial infarction.

The Indian (Asian) population in South Africa has a high rate of coronary artery disease. Fasting serum lipid and lipoprotein levels were measured in 620 consecutive male survivors of myocardial infarction and compared with those of 524 healthy male volunteer controls, and the presence of hypercholesterolaemia and hypertriglyceridaemia in the patient group was related to other non-lipid coronary risk factors. All survivors and controls were below age 61 years. Total cholesterol, triglyceride and low-density-lipoprotein cholesterol concentrations varied significantly with age both in patient and control groups, whereas high-density-lipoprotein (HDL) cholesterol did not vary with age in either group. Using the 90th-percentile age-adjusted values of controls for total cholesterol (7.1 mmol/l) and triglyceride (3.0 mmol/l) as cut-off points, 287 (46%) survivors were hyperlipidaemic. Hypercholesterolaemia with or without associated hypertriglyceridaemia was the commonest abnormality: 125 (20%) patients showed hypercholesterolaemia without associated hypertriglyceridaemia; 73 (12%) had both hypercholesterolaemia and hypertriglyceridaemia and 89 (14%) hypertriglyceridaemia without associated hypercholesterolaemia. The frequency of hyperlipidaemia did not vary with age. HDL cholesterol levels below 0.66 mmol/l (10th percentile) were observed in 131 (22%) survivors. Obesity was significantly more frequent among hypertriglyceridaemic survivors, whilst diabetes and hypertension were seen more frequently in survivors with combined hypercholesterolaemia and hypertriglyceridaemia. No significant difference was noted in the frequency of smoking and family history of coronary artery disease in hyperlipidaemia and normolipidaemic patients.

Adult↗
PubMed1991

Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification.

Several lines of evidence indicate that the oxidative modification of low density lipoproteins (LDL) may provide an important link between plasma LDL and the genesis of the atherosclerotic lesion. Ascorbate is an important water-soluble, chain-breaking antioxidant in humans. Probucol, a lipid-soluble antioxidant drug has been shown to retard the progression of atherosclerosis. The aim of the present study was to compare the effects of probucol and physiologic levels of ascorbate on the oxidative modification of LDL in both a cell-free (2.5 microM Cu++ in phosphate-buffered saline) and cellular system (human monocyte macrophages in Ham's F-10 medium). Both ascorbate and probucol inhibited the oxidative modification of LDL in both systems to a similar degree as evidenced by the thiobarbituric acid-reacting substance activity, electrophoretic mobility, and degradation by macrophages. However, whereas co-incubation with physiologic levels of ascorbate resulted in a substantial preservation of the alpha-tocopherol, gamma-tocopherol, and beta-carotene of the LDL, probucol in concentrations ranging from 10 to 80 microM failed to protect these antioxidants. Thus, in addition to being as potent as probucol in inhibiting the oxidation of LDL, ascorbate in contrast preserves the endogenous antioxidants in the LDL.

Ascorbic Acid↗
PubMed1990

Physiologic levels of ascorbate inhibit the oxidative modification of low density lipoprotein.

Oxidatively modified low density lipoprotein (LDL) could contribute to the atherosclerotic process by its cytotoxic effect, uptake by the scavenger receptor and influence on monocyte and macrophage motility. The aim of the present study was to examine the effect of physiologic levels of alpha-tocopherol and ascorbate on Cu2(+)-induced oxidative modification of LDL. Whereas alpha-tocopherol had an inhibitory effect on the oxidative modification of LDL only for 5 h, as evidenced by the electrophoretic mobility and lipid peroxide content, ascorbate inhibited the oxidative modification of LDL for both 5 and 24 h. By inhibiting the oxidative modification of LDL, ascorbate prevented the uptake and degradation of oxidatively modified LDL by the scavenger-receptor mechanism of cultured human monocyte derived macrophages. It thus appears that in this cell-free system (2.5 microM Cu2+), ascorbate is a more potent antioxidant than alpha-tocopherol. These findings indicate that ascorbate in physiologic concentrations should inhibit the oxidate modification of LDL in vivo.

Ascorbic Acid↗
PubMed1990

Abnormalities in sex hormones are a risk factor for premature manifestation of coronary artery disease in South African Indian men.

The relation between sex hormone levels and myocardial infarction was studied in a case-control study among 117 Indian men with myocardial infarction aged 30-60 years and in 107 healthy Indian male controls. The patients and controls were further divided into subsets defined by age in decades. In the total patient population, testosterone concentration was significantly lower than in the controls (P less than 0.01), whilst oestradiol (P less than 0.0005) and the oestradiol to testosterone ratio (P less than 0.0005) were significantly higher. Multivariate stepwise logistic regression analyses demonstrated that free testosterone index, the free oestradiol index, and the oestradiol to testosterone ratio were significantly associated with myocardial infarction, and that this association was independent of age, body mass index, smoking and serum lipids. Further analyses according to age subsets revealed that compared to respective control groups, patients in the 4th decade had both significant hypotestosteronaemia and hyperoestrogenaemia, whereas in patients of the 5th decade significant differences in total and in the calculated free oestradiol index were noted, and in the 6th decade a significant difference was detected only in the free oestradiol index. Hence, we conclude that aberrations in endogenous sex hormones are significantly associated with myocardial infarction, and that this association appears to be strongest in young men and diminishes with age, suggesting that these disturbances in sex hormones may be associated with premature manifestation of coronary artery disease.

Coronary Artery Disease↗
PubMed1990

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

Adolescent↗