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Biomedical subjects

M R Adams

Publications and source records attributed to M R Adams.

At least 73 records · Page 4Linked to original sources
PubMed1997

Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease.

L-Arginine is the physiological substrate for nitric oxide synthesis by the vascular endothelium. In hypercholesterolaemic rabbits, oral L-arginine reduces atheroma, improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion. The effect of oral L-arginine on endothelial physiology is unknown, however, in humans with established atherosclerosis. In a prospective, double-blind, randomised crossover trial, ten men aged 41 +/- 2 years with angiographically proven coronary atherosclerosis took L-arginine (7 g three times per day) or placebo for 3 days each, with a washout period of 10 days. After L-arginine, compared to placebo, plasma levels of arginine were increased (318 +/- 18 vs. 124 +/- 9 mumol/l, P < 0.01) and endothelium-dependent dilatation of the brachial artery (measured as the change in diameter in response to reactive hyperaemia, using external vascular ultrasound) was improved (4.7 +/- 1.1 vs. 1.8 +/- 0.7%, P < 0.04). No changes were seen in endothelium-independent dilatation of the brachial artery (measured as the change in diameter in response to sublingual nitroglycerine), blood pressure, heart rate or fasting lipid levels. Serum from six of the ten subjects after L-arginine and placebo was then added to confluent monolayers of human umbilical vein endothelial cells for 24 h, before human monocytes obtained by countercurrent centrifiguation elutriation were added and cell adhesion assessed by light microscopy. Adhesion was reduced following L-arginine compared to placebo (42 +/- 2 vs. 50 +/- 1%, P < 0.01). In young men with coronary artery disease, oral L-arginine improves endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion.

Administration, Oral↗
PubMed1997

Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C.

OBJECTIVES: This study sought to assess the effect of cigarette smoking on adhesion of human monocytes to human endothelial cells and to measure the effect of L-arginine and vitamin C supplementation on this interaction. BACKGROUND: Cigarette smoking has been associated with abnormal endothelial function and increased leukocyte adhesion to endothelium, both key early events in atherogenesis. Supplementation with both oral L-arginine (the physiologic substrate for nitric oxide) and vitamin C (an aqueous phase antioxidant) may improve endothelial function; however, their benefit in cigarette smokers is not known. METHODS: Serum was collected from eight smokers (mean [+/-SD] age 33 +/- 5 years) with no other coronary risk factors and eight age- and gender-matched lifelong nonsmokers. The serum was added to confluent monolayers of human umbilical vein endothelial cells and incubated for 24 h. Human monocytes obtained by counterflow centrifugation elutriation were then added to these monolayers for 1 h, and adhesion then was measured by light microscopy. To assess reversibility, monocyte/ endothelial cell adhesion was then measured for each subject 2 h after 2 g of oral vitamin C and 2 h after 7 g of oral L-arginine. RESULTS: In smokers compared with control subjects, monocyte/ endothelial cell adhesion was increased (46.4 +/- 4.5% vs. 27.0 +/- 5.2%, p < 0.001), endothelial expression of intercellular adhesion molecule (ICAM)-1 was increased (0.31 +/- 0.02 vs. 0.22 +/- 0.03, p = 0.004), and vitamin C levels were reduced (33.7 +/- 24.1 vs. 53.4 +/- 11.5 mumol/liter, p = 0.028). After oral L-arginine, monocyte/ endothelial cell adhesion was reduced in smokers (from 46.4 +/- 4.5% to 35.1 +/- 4.0%, p = 0.002), as was endothelial cell expression of ICAM-1 (from 0.31 +/- 0.02 to 0.27 +/- 0.01, p = 0.001). After vitamin C, there was no significant change in monocyte/ endothelial cell adhesion or ICAM-1 expression from baseline in the smokers despite an increase in vitamin C levels (to 115 +/- 7 mumol/liter). CONCLUSIONS: Cigarette smoking is associated with increased monocyte-endothelial cell adhesion when endothelial cells are exposed to serum from healthy young adults. This abnormality is acutely reversible by oral L-arginine but not by vitamin C.

Adult↗
PubMed1997

L-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules.

BACKGROUND: Monocyte adhesion to endothelial cells is a key early event in atherogenesis. Because L-arginine has been shown to reduce atheroma and to decrease monocyte-endothelial cell adhesion in an animal model of atherosclerosis, we studied the effects of L-arginine on human monocyte adhesion to human endothelial cells and endothelial expression of cell adhesion molecules. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were grown to confluence, then incubated for 24 hours with arginine-deficient media to which was added saline (control), 100 or 1000 mumol/L L-arginine, 100 mumol/L D-arginine, 100 mumol/L NG-monomethyl-L-arginine (L-NMMA), or 100 mumol/L L-arginine with 100 mumol/L L-NMMA. Human monocytes obtained by elutriation were incubated for 1 hour with HUVECs, and adhesion was measured by light microscopy. Compared with control, monocyte adhesion was reduced by L-arginine (59 +/- 10%, P = .01) and increased by L-NMMA (123 +/- 20%, P = .01). Surface expression of cell adhesion molecules by HUVECs was assessed by an ELISA under the above conditions with and without stimulation with interleukin-1 beta. Expression of ICAM-1 was reduced with both concentrations of L-arginine compared with control in both the basal (43 +/- 12%, P < .01), and stimulated (46 +/- 15%, P < .01) states, which correlated with decreased levels of mRNA. Expression of VCAM-1 was reduced only in the stimulated state and only in the presence of 1000 mumol/L L-arginine (72 +/- 24%, P = .02). CONCLUSIONS: L-Arginine reduces human monocyte adhesion to endothelial cells and decreases expression of certain endothelial cell adhesion molecules.

Arginine↗
PubMed1997

EEDQ reduces the striatal neurotensin mRNA response to haloperidol.

Haloperidol is believed to induce neurotensin/neuromedin N (NT/ N) gene expression in the dorsolateral striatum (DLST) of the rat brain via dopamine D2 receptor blockade, but is also known to interact with other receptors as well. To further characterize haloperidol's effects, rats were treated with the irreversible monoaminergic receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2 hydroxyquinolone (EEDQ). In situ hybridization was performed for NT/N mRNA. D2-like and sigma receptor autoradiography was performed using 125I-sulpride and 3H-1,3-di-o-tolylguanidine (DTG), respectively. Despite antagonism of D2 receptors, pretreatment with EEDQ failed to significantly reduce the NT/N mRNA response when given 3 days prior to the haloperidol challenge. These data suggest that the acute effects of haloperidol on NT/N mRNA expression in large part result from D2 receptor antagonism. Nonetheless, a contribution of other receptors can not be excluded.

Animals↗
PubMed1997

Arterial reactivity is enhanced in genetic males taking high dose estrogens.

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.

Adult↗
PubMed1997

Chinese adults are less susceptible than whites to age-related endothelial dysfunction.

OBJECTIVES: We sought to assess the effects of aging on the endothelial physiology of a group of Chinese adults. BACKGROUND: Several studies have documented an association between aging and progressive arterial endothelial dysfunction in white subjects. We hypothesized that age-related endothelial dysfunction, an important event in atherosclerosis, might be less marked in southern Chinese subjects, in whom the prevalence of coronary heart disease is only approximately 20% of that in industrialized countries. METHODS: We studied endothelial function in 76 healthy adults aged 16 to 70 years: 38 Chinese from a village of 3,000 people in southern China and 38 white subjects from Sydney, Australia. In each ethnic group, there were 19 younger persons (16 to 40 years) and 19 older adults (55 to 70 years). None had evidence of diabetes, hypertension or clinical vascular disease or had ever been regular cigarette smokers. With the use of high resolution external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). RESULTS: Endothelium-dependent dilation was similar in young Chinese (mean +/- SD 8.3 +/- 2.5%), young whites (7.9 +/- 2.0%) and older Chinese (6.8 +/- 2.9%), but it was significantly impaired in older whites (1.8 +/- 2.5%, p < 0.001 by analysis of variance). On multivariate analysis, older age was associated with impaired endothelium-dependent dilation (p < 0.001) (independent of the effects of serum cholesterol, gender and vessel size) in the white but not in the Chinese subjects (p = 0.83). Nitroglycerin-induced dilation was not significantly different with aging in either ethnic group. CONCLUSIONS: Endothelium-dependent dilation is similar in the arteries of healthy young Chinese and white adults. With older age, however, Chinese subjects are less susceptible to impaired endothelial function.

Adolescent↗
PubMed1997

Structural determinants of lumen narrowing after angioplasty in atherosclerotic nonhuman primates.

PURPOSE: The relationship between lumen narrowing, intimal hyperplasia, and wall remodeling after angioplasty was explored in a nonhuman primate model of atherosclerosis. METHODS: Cynomolgus monkeys (n = 37) used in long-term atherosclerosis studies underwent left iliac artery balloon injury. The uninjured right iliac artery served as a reference segment for intraanimal comparisons. One month later iliac arteries were fixed by perfusion (100 mm Hg) and removed for cross-sectional analysis to determine mean values for lumen area (LA), intimal area (IA), internal elastic lamina area (IELA), plaque burden (IA/IELA), and depth of wall injury. Values for each balloon-injured iliac artery were normalized to the contralateral uninjured iliac artery (percent of control), and linear regression analysis was performed comparing LA with IA, with IELA, and with depth of injury. Comparisons were also made between those arteries that remained dilated 1 month after balloon injury (LA > or = 140%; n = 13) and those that renarrowed (LA < or = 100%; n = 14). RESULTS: For all 37 animals, LA 1 month after balloon injury correlated well with IELA (r = 0.72; p < 0.001) but not with IA (r = 0.10; p = 0.54), suggesting that changes in artery size rather than neointimal mass determined lumen caliber. When comparing arteries that remained dilated (n = 13) with those that renarrowed (n = 14), there were no differences in depth of wall injury (injury depth: 0, no injury; 1, intima; 2, IEL; 3, media; 4, EEL; 2.1 +/- 0.3 vs 1.6 +/- 0.3; p = 0.12), neointimal accumulation (IA, 507% +/- 118% vs. 421% +/- 81% of control; p = 0.55), or plaque burden (IA/IELA, 0.39 +/- 0.04 vs 0.37 +/- 0.06; p = 0.71), respectively. However, wall size defined as IELA was significantly smaller in arteries that renarrowed than in those that remained dilated (IELA, 115% +/- 14% vs 230% +/- 19% of control; p < 0.001). CONCLUSIONS: Restenosis after angioplasty has been attributed to intimal hyperplasia, equating loss of lumen caliber with neointimal mass. The data presented herein suggest that lumen narrowing after arterial wall injury may have little to do with intimal mass per se, but rather that a change in wall caliber or wall narrowing is the cause of restenosis.

Angioplasty, Balloon↗
PubMed1997

Automatic volumetric capillary cytometry for counting white cells in white cell-reduced plateletpheresis components.

BACKGROUND: As the benefits of white cell (WBC)-reduced blood components become increasingly apparent, the need has arisen for a simple, automated WBC-counting technique that is sensitive to low WBC concentrations. Automated volumetric capillary cytometry was evaluated for its ability to quantify residual WBCs in WBC-reduced plateletpheresis components. STUDY DESIGN AND METHODS: The volumetric capillary cytometry system evaluated uses a laser to excite fluorescent dye-labeled nucleated cells. The number of nucleated cells per microliter is reported. Four studies were performed: linearity, precision of results near the value of 5 x 10(6) WBCs per unit, the limit of detection, and correlation to the Nageotte manual counting method. RESULTS: Assay values correlated to expected values (range, 0-125 WBC/microliter) with an r2 > 0.99. In the range of 5 x 10(5) WBCs per unit the CV was 8.5 percent, and concentration differences of 0.15 log10 were detectable. The limit of detection was 1.0 WBCs per microliter (95% upper confidence limit). The assay correlated to the Nageotte method with an r2 of 0.98, slope of 1.0, and y-intercept of 2.0 WBCs per microliter. Assay results were 10 to 15 percent higher than Nageotte results, in samples with values near 5 x 10(6) WBCs per unit. Technician time per sample was 2 to 3 minutes. CONCLUSION: Volumetric capillary cytometry is precise and sensitive to small differences in WBC concentration in the range of clinical interest. The device provides an efficient new method for quality assurance and control of WBC-reduced plateletpheresis products.

Blood Component Removal↗
PubMed1997

Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis.

Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.

Administration, Oral↗
PubMed1997

Androgen deprivation is associated with enhanced endothelium-dependent dilatation in adult men.

Male gender is an independent risk factor for coronary artery disease, and androgen administration has been associated with increased atherosclerosis in experimental animals. Since endothelial dysfunction is an important event in the atherogenic process, we hypothesized that androgen deprivation in adult men might be associated with enhanced arterial endothelial function. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilatation) and after nitroglycerin (an endothelium-independent dilator). We studied 30 adult males aged 40 to 70 years: 10 had had bilateral orchidectomy and/or maximal androgen blockade for > or = 6 months for treatment of prostate cancer, and all were in complete remission (group 1). Ten healthy controls (group 2) and 10 controls who had remission from nonprostate cancers (group 3) were matched for age and smoking history. Testosterone levels were lower in men in group 1 versus groups 2 or 3 (0.8 +/- 0.1 versus 19.2 +/- 8.4 or 16.1 +/- 4.9 nmol/L, P < .001). By contrast, endothelium-dependent dilatation was markedly higher in group 1 than in groups 2 or 3 (6.2 +/- 3 versus 2.7 +/- 2 or 2.0 +/- 1.9%, P < .001). The nitroglycerin response was similar in all three groups (P = .92). On multivariate analysis, increased endothelium-dependent dilatation was significantly associated with low serum testosterone levels (P = .001) but not with cholesterol levels or with a past history of malignancy (P > .25). The withdrawal of male sex hormones may be associated with enhanced endothelial function in adult men. This is consistent with a deleterious effect of physiologic levels of male sex steroids on the arterial wall.

Adult↗
PubMed1997

Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys.

Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women and inhibits progression of coronary artery atherosclerosis in monkeys. Tamoxifen is a nonsteroidal compound with mixed estrogen agonist and antagonist properties. Its antagonist activity is useful in chemotherapy of breast cancer and may have protective effects on plasma lipid concentrations, but its effects on atherogenesis have not been defined. The goal of this study was to examine the effect of tamoxifen on plasma lipids, arterial and hepatic LDL metabolism, and progression of coronary artery atherosclerosis in surgically postmenopausal female monkeys. Thirty-five monkeys were fed an atherogenic diet containing 1.3 mg.kg-1.d-1 tamoxifen (equivalent to the usual dose of 20 mg/d given to women). Thirty-one monkeys were fed the same atherogenic diet with no tamoxifen. Ten monkeys from each treatment group were fed the test diets for 12 weeks to examine the short-term effects of tamoxifen on arterial LDL metabolism. The rest of the monkeys were fed the test diets for 3 years to study the long-term effects of tamoxifen on development of atherosclerosis. In the short term, tamoxifen inhibited the rate of arterial accumulation of LDL degradation products overall (P = .03) and decreased hepatic cholesterol content (P = .003). In the long term, tamoxifen increased plasma concentrations of triglycerides (0.60 +/- 0.67 versus 0.23 +/- 0.02 mmol/L, P = .001) and reduced average LDL molecular weight (5.3 +/- 0.2 versus 4.8 +/- 0.1 g/mumol, P = 0.004) but had no effects on plasma total, LDL, or HDL cholesterol concentrations. Coronary artery atherosclerosis (intimal area, mean +/- SEM) was 0.25 +/- 0.06 mm2 in control monkeys and 0.12 +/- 0.03 mm2 in tamoxifen-treated monkeys (P = .057). We conclude that tamoxifen has antiatherogenic effects that may be modulated in part through direct effects on arterial LDL metabolism.

Animals↗
PubMed1997

Effects of short-term hormone replacement therapies on low-density lipoprotein metabolism in cynomologus monkeys.

Estrogen replacement therapy reduces the risk of coronary heart disease in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degradation and accumulation, thus indicating one mechanism by which estrogen inhibits the progression of atherosclerosis. The influence of progestins on these processes remains nuclear. The objective of this study was to determine the effects of oral estrogen (conjugated equine estrogens) and progestin (medroxyprogesterone acetate) alone or in combination on arterial LDL metabolism after 12 weeks of atherogenic stimulus. This relatively short period of treatment was chosen to determine effects on arterial LDL metabolism before substantial subendothelial macrophage accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when macrophages were present in the intima, neither estrogen nor progestin (nor their combination) had any effect on any index of arterial LDL metabolism. These results suggest that estrogen may preferentially reduce LDL metabolism in macrophages with little effect on cells of the normal artery. In contrast to arterial LDL metabolism, hepatic LDL uptake was significantly increased in animals treated with estrogen or estrogen plus progestin. Despite the increased LDL uptake by the liver, hepatic lipid content was significantly decreased by approximately 50% in both estrogen and estrogen-plus-progestin treatment compared with control and progestin-treated animals. The decrease in hepatic cholesterol content in hypothesized to be due to increased biliary secretion of cholesterol.

Animals↗
PubMed1997

Effects of contraceptive estrogen and progestin on the atherogenic potential of plasma LDLs in cynomolgus monkeys.

This study was designed to determine the effect of oral contraceptive treatment (estrogen and progestin), alone or in combination, on LDL composition and atherogenic potential in cynomolgus monkeys fed an atherogenic diet. Groups (n = 8 each) of monkeys were untreated (control) or treated with ethinyl estradiol (EE), levonorgestrel (LNG); or triphasic oral contraceptive (EE+LNG) for 1.5 years before plasma LDLs were isolated for characterization. Total plasma cholesterol concentrations were unaffected by the treatments. LDL particle size (measured as LDL molecular weight, g/mumol) was significantly smaller, in the EE (4.61 +/- 0.09) and EE+LNG (4.43 +/- 0.09) treatment groups compared with the control (4.99 +/- 0.09) or LNG (5.29 +/- 0.17) groups and contained fewer molecules of free and esterified cholesterol. Both the EE and EE+LNG groups had significantly less cholesterol and apolipoprotein B distributed in the d = 1.015 to 1.025 g/mL subfraction and correspondingly more in the d = 1.025 to 1.035 g/mL subfraction of LDL compared with the control and LNG groups. The apolipoprotein E content (molecules/particle) of LDL was significantly less in the EE (0.35 +/- 0.1) and EE+LNG (0.28 +/- 0.1) groups compared with the control (0.86 +/- 0.2) and LNG (0.99 +/- 0.2) groups, and this trend was apparent in all three LDL subfractions. The atherogenic potential of LDL was tested using an in vitro binding assay to arterial proteoglycans. Twice as much LDL bound to arterial proteoglycans in the LNG group (11.3 +/- 1.8% of total LDL cholesterol in the incubation) compared with the control (6.4 +/- 1.9%), EE (5.5 +/- 1.5%), or EE+LNG (5.2 +/- 1.2%) groups. We conclude that EE and EE+LNG treatment alters the composition of LDL toward a less atherogenic particle that is smaller and more dense, contains less cholesterol and less apolipoprotein E, and is less reactive with arterial proteoglycans compared with LNG treatment. The inclusion of EE in the triphasic oral contraceptive treatment was sufficient to negate the potentially atherogenic effects of LNG on LDL composition.

Animals↗
PubMed1997

Behaviorally elicited heart rate reactivity and atherosclerosis in ovariectomized cynomolgus monkeys (Macaca fascicularis).

It has been hypothesized that atherogenesis is accelerated among individuals who exhibit heightened cardiovascular reactions to psychologic stress. We have reported previously that the coronary atherosclerosis of cholesterol-fed, male and reproductively intact (premenopausal) female cynomolgus monkeys was exacerbated in animals that experienced the largest heart rate (HR) reactions to a fear-eliciting laboratory stressor. In this article, we report a similar relationship among 20 female monkeys that were rendered estrogen-deficient (by ovariectomy) and subsequently treated with replacement of both estrogen and progesterone. At the beginning of a 30-month study period, animals were fitted with ECG telemetry devices, and their HRs were recorded under baseline and stressed conditions. Stress HR measurements were obtained during a standard challenge involving threatened capture and physical handling of the animals. As part of a related experiment, monkeys were then ovariectomized and, for the remainder of the study, administered 17 beta-estradiol (continuously) and progesterone (cyclically) by subcutaneous Silastic implant (Dow Corning). Animals consumed a cholesterol-containing diet throughout, and HR measurements were repeated in the 24th month. At necropsy, the magnitude of animals' HR responses to stress correlated significantly with intimal area measurements in the left anterior descending and circumflex coronary arteries (r = .59 and r = .57, respectively; P < .009). This association was due to a marked exacerbation of coronary atherosclerosis in animals comprising the upper third of the reactivity distribution. Although total and HDL cholesterol concentrations also covaried with HR reactivity, the greater atherosclerosis of "high" HR reactors persisted after statistical adjustment for concomitant variability in plasma lipids. HR reactivity was unrelated to blood pressure, body weight, or social behavior.

Animals↗
PubMed1997

Plasma and LDL levels of major lipophilic antioxidants are similar in patients with advanced atherosclerosis and age-matched controls.

Oxidative modification of low-density lipoprotein (LDL), regarded an early event in atherogenesis, is associated with the depletion of the lipoprotein's antioxidants. We tested whether the levels of major lipophilic antioxidants in the blood of patients with advanced atherosclerosis are different to those in age-matched controls. On average, plasma ubiquinol-10, total coenzyme Q and coenzyme Q redox status were slightly lower whereas the levels of alpha-tocopherol were slightly higher in patients (63 +/- 11 years, n = 32) than controls (64 +/- 10 years, n = 24). However, these differences were not statistically significant (p > 0.05). The levels of antioxidants in LDL isolated from a subset of patients (n = 20) and controls (n = 15) were also indifferent, and hydroperoxides of cholesteryl esters were undetectable (detection limit 10 nM) in plasma of patients (n = 11) and controls (n = 10). The data suggests that plasma and LDL levels of lipophilic antioxidants are not depleted in patients suffering from severe atherosclerosis, and that neither parameter serves as a useful diagnostic indicator for this disease.

Aged↗
PubMed1997

A comparison of quantitative structure-activity relationships for the effect of benzoic and cinnamic acids on Listeria monocytogenes using multiple linear regression, artificial neural network and fuzzy systems.

The ability of artificial neural networks (ANN), fuzzy systems (FS) and multiple linear regression (MLR) to fit the biological activity surface describing the inhibition of Listeria monocytogenes by benzoic and cinnamic acid derivatives was compared. MLR and ANN were also compared for their ability to select the properties that best describe the biological activity of the compounds. The criteria used for comparing surface fits of all models were the coefficient of determination r2 and the standard deviation of the error, s(e). The ANN method gave a better correlation, r2 = 0.96, compared with either MLR, r2 = 0.81, or FS, r2 = 0.92, and also a lower standard error, possibly indicating non-linearity in the data. The ANN was shown to generalize better than MLR using the leave-one-out method. The ANN selection algorithm for the selection of the parameters that contributed most to the biological activity of the phenols (log K and pKa) agreed with the selected parameters of the MLR system.

Benzaldehydes↗
PubMed1996

Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.

Administration, Oral↗