Centrosomes with striated rootlets in rabbit zygotes

The purpose of this study was to determine if the calcium entry antagonist felodipine inhibited intimal lesion formation in hypercholesterolemic rabbits, and to determine if this was due to an effect upon monocyte and/or endothelial determinants of this interaction. Twenty-three male New Zealand White rabbits received the following treatment regimen for 10 weeks: normal chow (NP, n = 3); normal chow with felodipine infusion (NF, n = 6); 0.5% cholesterol chow (CP, n = 7); or 0.5% cholesterol chow and felodipine infusion (CF, n = 7). After 10 weeks blood was collected for biochemical measurements and mononuclear cell binding assays, and thoracic aortae were harvested for vascular reactivity studies and histomorphometry. In the animals receiving normal chow, felodipine did not significantly affect blood pressure, plasma cholesterol levels, binding studies, vascular reactivity, or structure; therefore these animals were analyzed as one group (N). Plasma cholesterol levels were significantly elevated in groups receiving the 0.5% cholesterol diet (N, 29 +/- 3 mg/dl; CP, 1221 +/- 73 mg/dl; CF, 979 +/- 108 mg/dl). High-density lipoprotein cholesterol was not different between the groups (25 +/- 4 vs 23 +/- 4 vs 27 +/- 4 mg/dl; N vs CF vs CP respectively; p = NS). Cholesterol feeding markedly augmented the adhesiveness of mononuclear cells, as demonstrated by a 250% increase in cell binding. Felodipine did not alter the adhesiveness of mononuclear cells in hypercholesterolemic animals. Cholesterol feeding significantly impaired endothelium-dependent relaxations. Endothelium-dependent relaxations were restored by felodipine treatment as reflected by the maximal responses to acetylcholine (40 +/- 7% vs 58 +/- 4% vs 67 +/- 5%; CP vs CF vs N respectively). The improvement in endothelium-dependent relaxation in the felodipine-treated animals was associated with a 2.2-fold reduction in lesion surface area of the thoracic aorta (8.2 +/- 6.3% vs 18.2 +/- 9.5%; CF vs CP; p < 0.01). Moreover, the intima/media ratio reflecting lesion thickness was substantially reduced by felodipine treatment (0.05 +/- 0.02 vs 0.20 +/- 0.07; CF vs CP; p = 0.006). Ex vivo studies revealed that felodipine inhibited the adhesiveness of vascular endothelium, but not mononuclear cells, derived from hypercholesterolemic animals. Low-dose felodipine appears to inhibit monocyte-endothelial interaction, as indicated by a reduction in the formation of lesions in hypercholesterolemic animals. This effect is not due to an alteration in adhesiveness of mononuclear cells. The salutary effect of felodipine is associated with an increase in vascular nitric oxide activity which may reduce endothelial adhesiveness.     

Outcome from treatment for spinal arteriovenous malformation

BACKGROUND: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20 years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29 mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs 49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/-4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.     

Metformin inhibits ganglionic neurotransmission in renal nerves

Intravenous administration of the antihyperglycemic agent metformin decreases arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis that metformin inhibits SNA by interrupting ganglionic neurotransmission, we compared the actions of intravenous administration of metformin and the ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats. Intravenous metformin elicited dose-dependent decreases in postganglionic renal SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7). Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory response similar to the response observed after high-dose metformin (delta renal SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal neurons were electrically stimulated in the spinal cord, before and during the peak of the sympathoinhibitory response to intravenous metformin, and the magnitude of the stimulus-evoked increases in postganglionic renal SNA were compared. Metformin dose-dependently attenuated the magnitude of the increase in postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: -23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We conclude that high-dose intravenous metformin interrupts ganglionic neurotransmission in renal nerves.     

beta-VLDL hypercholesterolemia relative to LDL hypercholesterolemia is associated with higher levels of oxidized lipoproteins and a more rapid progression of coronary atherosclerosis in rabbits

The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with beta-VLDL and LDL hypercholesterolemia was compared. In New Zealand White (NZW) rabbits on a 0.125% cholesterol diet, LDL cholesterol levels increased from 14 +/- 1 mg/dL (mean +/- SEM; n = 9) to 170 +/- 34 mg/dL (n = 10, P = .0002). On 0.5% cholesterol, LDL cholesterol levels were similar, but beta-VLDL cholesterol levels increased from 60 +/- 4 mg/dL (n = 10) to 550 +/- 75 mg/dL (n = 8; P < .0001). In Watanabe heritable hyperlipidemic (WHHL) rabbits, LDL cholesterol levels were 2.3-fold higher (n = 13; P < .0001) than in NZW rabbits on 0.5% cholesterol, whereas their beta-VLDL cholesterol levels were 3.7-fold lower (P < .0001), resulting in similar total cholesterol levels. At 2 months, mean intimal areas of lesions in the coronary arteries of NZW rabbits on 0.125% cholesterol were 0.13 +/- 0.045 mm2 (n = 4; mean +/- SEM) and were 5.8-fold, (n = 4; P = .016) and 2.0-fold (n = 6; P = NS versus 0.125% cholesterol and P = .014 versus 0.5% cholesterol) higher in NZW rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. At 5 months, mean intimal areas were 0.47 +/- 0.088 mm2 (n = 6) in NZW rabbits on 0.125% cholesterol and were 4.5-fold (n = 4; P = .0001) and 2.0-fold (n = 7; P = .012 and P = .0019) higher in rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. Levels of oxidized apoB-100 containing lipoproteins (both beta-VLDL and LDL) in the lesions correlated with mean intimal area (r = .88; n = 31; P < .0001) of those lesions and with the plasma levels of total beta-VLDL/LDL (r = .72; P < .0001). Levels of oxidized apoB-100 containing lipoproteins in the arterial wall correlate with progression of hypercholesterolemia-induced coronary atherosclerotic lesions. Plasma levels of beta-VLDL relative to similar increases in LDL result in a more pronounced accumulation of oxidized apoB-100 containing lipoproteins in the arterial wall and in the plasma and a more rapid progression of coronary atherosclerosis.     

Prevalence and profile of renovascular disease in type II diabetic patients with severe hypertension

The aim of this study was to determine the prevalence and profile of renal artery stenosis (RAS) in NIDDM population with severe hypertension. 60 consecutive NIDDM with severe HT (> or = 3 hypotensive drugs), 42 F/18 M (SR: 2.8), mean age: 66.6 +/- 6.5 years, diabetes duration: 14.1 +/- 6 years have had metabolic, ABPM and renal investigations: color duplex scan (CDS) (with renal us): n = 60, and/or arteriography: n = 17). 13 (21.5%) renal artery stenosis > or = 70%: 8 unilateral/5 bilateral were proved by arteriography. We compared classic HT (n = 47) versus renovascular HT (n = 13). There was no difference for age (years): 64.8 +/- 8 versus 70.6 +/- 6.4, HT duration (years): 11.6 +/- 6.8 versus 12.3 +/- 6. B.M.I.: 31.5 +/- 6 versus 27.6 +/- 3.3, HBA1C (%): 8.9 +/- 2.2 versus 8.8 +/- 0.9, cholesterol (mmol/L): 5.7 +/- 1.3 versus 5.5 +/- 0.6. Significant difference (p < 0.05) was noticed for S.R. (F/M): 2.9 versus 1.16, diabetes duration (years): 11.7 +/- 5 versus 16.5 +/- 8, frequency of retinopathy (%): 30 versus 61, smoking (%): 10 versus 40, triglycerides (mmol/L): 1.9 +/- 1.1 versus 2.6 +/- 1.1, and (p < 0.01) for blood pressure level (mmHg) (SBP: 142 +/- 20 vs 155 +/- 7, DBP: 81 +/- 13 vs 87 +/- 10, MBP: 103 +/- 16 vs 111 +/- 6), frequency (%) of HT escape (> or = 140/SBP, > or = 90/DBP) on ABPM: 40 versus 75 and 24 versus 40, insulin requirence (%): 36 versus 69, macroangiopathy (%): 51 versus 100 (coronaropathy: 34 vs 61, legs arteritis: 21 vs 69, carotid stenosis: 17 vs 30) and for renal function: frequency (%) of micro-macroalbuminuria: 36 versus 92 creatinaemia (mmol/L): 80 +/- 24 versus 124 +/- 44, creatinaemia clearance (mmL/min): 65 +/- 30 versus 40 +/- 12 while are found 5 renal insufficiencies (> or = 120 mmol/L). In NIDDM population with severe HT, renovascular HT is frequent (21.5%), and RAS must be evocated in unstable HT and/or renal injury with macro angiopathy, old NIDDM (> 15 years), requiring insulin. Colour duplex scan (+ renal US) mays lead to arteriography to confirm renal artery stenosis.     

Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine

OBJECTIVES: We sought to document the common mechanisms of the antiatherogenic effects of the cholesterol-lowering hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin, the dihydropyridine Ca2+ blocker amlodipine and the antioxidant vitamin E. BACKGROUND: Vitamin E, HMG-CoA reductase inhibitors and Ca2+ blockers each inhibit atherosclerosis in hypercholesterolemic animals. METHODS: New Zealand White rabbits were fed regular chow (Group A), chow with 1% cholesterol (Group B), 1% cholesterol diet plus lovastatin (Group C), 1% cholesterol diet plus vitamin E (Group D) or 1% cholesterol diet plus amlodipine (Group E) for 12 weeks. The extent of aortic atherosclerosis was measured by planimetry of the sudanophilic area. Malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured as indexes of lipid peroxidation and antioxidant activity, respectively. RESULTS: Group A rabbits showed no atherosclerosis, whereas Group B rabbits had 17.4 +/- 9.3% (mean +/- SD) of the aorta covered with atherosclerosis, and Groups C, D and E rabbits had significantly less atherosclerosis. Plasma SOD activity was lower in Group B than in Group A (6.9 +/- 1.1 vs. 12.8 +/- 1.5 U/ml, p < 0.01) and was preserved in the groups given lovastatin, vitamin E or amlodipine with a high cholesterol diet. The serum MDA level was higher in Group B rabbits than Group A rabbits (12.1 +/- 2.6 vs. 1.2 +/- 0.1 nmol/ml, p < 0.01) and increased minimally in rabbits given lovastatin, vitamin E or amlodipine with a high cholesterol diet. In in vitro experiments, both lovastatin and amlodipine preserved SOD activity and reduced the oxidizability of low density lipoproteins by rabbit leukocytes. CONCLUSIONS: This study suggests that a reduction in lipid peroxidation and preservation of SOD may be common mechanisms of antiatherosclerotic effects of lovastatin, vitamin E and amlodipine.     

Long-term ouabain administration produces hypertension in rats

Ouabain has recently been identified as an endogenous Na(+)-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 micrograms/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 micrograms/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM, 140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM, 131 +/- 5 vs 100 +/- 2 mm Hg; no RRM, 116 +/- 4 vs 98 +/- 5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39 +/- 1.17 vs 2.36 +/- 0.52 micrograms/kg, P < .05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.     

Central markers of body fat distribution are important predictors of plasma lipids in elderly men and women

We determined the contribution of body fat distribution, peak VO2, fat mass, and dietary intake to variation in plasma lipids in elderly individuals. Volunteers were a healthy cohort of older Caucasian women (n = 75, mean age +/- SD, 72 +/- 5 years) and older men (n = 101, 72 +/- 5 years). We determined fat mass from underwater weighing, fat patterning from waist circumference, as well as peripheral and truncal skinfolds, exercise capacity from peak VO2, and dietary intake from three-day food diaries. Plasma lipid levels were measured in the fasting state and included total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighted less than older men, but had higher fat mass, truncal, and peripheral skinfolds. Waist circumference and peak VO2 were lower in older women than older men. Older women had higher total cholesterol (217 +/- 31 vs. 197 +/- 30; p < 0.01), HDL-C (54 +/- 12 vs. 49 +/- 14; p < 0.05), and LDL-C (133 +/- 26 vs. 121 +/- 27; p < 0.01) when compared with older men. No gender differences were noted in fasting triglycerides. Truncal skinfolds were the best predictor of plasma lipids in older men, accounting for between 9% and 30% (r2) of the variation in plasma lipids. Similarly, in older women, central markers of fatness (i.e., waist circumference and truncal skinfolds) were the best predictors of plasma lipids (r2 = 3% to 24%). Total fat mass, peak VO2 and dietary intake were not independent predictors of plasma lipids in older men and women. Indices of central body fatness, rather than total fat mass, peak VO2 or dietary intake are stronger predictors of plasma lipids in healthy older men and women.     

Oxygen free radicals are not the main factor in experimental gentamicin nephrotoxicity

As a role for oxygen free radicals has been suggested in gentamicin (G) nephrotoxicity, we tested the hypothesis that exogenously administered glutathione (GSH), able to restore intracellular antioxidant potential, could be useful in reducing damage. Adult Sprague-Dawley rats were injected with saline (n = 30), subcutaneous (s.c.) G 100 (n = 23) and 150 mg/kg/day (n = 14), or s.c. G at the same dosages plus intraperitoneal (i.p.) GSH 1200 mg/kg/day (n = 24 and 14, respectively) for 7 days. In the G-100-day protocol, GSH-treated rats showed significantly lower renal G content (2.79 +/- 0.8 vs. 3.61 +/- 1.4 micrograms/mg prot) coupled with lower plasma urea (153 +/- 79 vs. 188 +/- 61 mg/dL) and creatinine levels (1.63 +/- 1 vs. 2.45 +/- 1 mg/dL). As to renal oxidant/antioxidant balance, local GSH was increased (0.32 +/- 0.01 vs. 0.19 +/- 0.01 microgram/mg prot) while lipid peroxidation, determined by production of thiobarbituric acid reactive substances (TBARS), was decreased (0.35 +/- 0.02 vs. 0.52 +/- 0.02 nmol/mg prot). In the G-150-mg protocol, GSH-treated rats showed no differences in renal gentamicin content or in blood urea and creatinine levels, in spite of a significantly lower renal TBARS production and a significantly higher GSH content. Urine enzyme excretion did not significantly change in GSH-treated vs. not-GSH-treated rats in both protocols. We conclude that: (a) GSH interferes with G nephrotoxicity mainly via a reduction in G uptake; (b) the oxidative renal stress is not crucial in inducing renal damage. In fact, when increased G dosages blunt the ability of GSH in reducing G uptake, no substantial protection is demonstrated.     

Effects of two low-fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free-living hypercholesterolaemic men

Diet enriched with polyunsaturated fat may increase the susceptibility of LDL to oxidation. Therefore the effects of two low-fat diets on plasma lipid peroxides in free-living mildly hypercholesterolaemic men (n = 37) were investigated in a randomized single-blind 28-week study. Composition of the diets were (1) American Heart Association (AHA) type 32/10:8:8 (indicating percentages of energy from total fat/saturated fat:monoenes:polyenes in actual diet); (2) low-fat 30/12:8:3. The subjects kept 3-day dietary records five times during the study to estimate the intake of nutrients. Plasma lipid peroxides were measured photometrically as the thiobarbituric-acid reactive substances (TBARS). Levels of serum vitamin E during the study were also determined. Mean change (+/- SD) in serum low density lipoprotein (LDL) cholesterol was similar in both groups (-0.32 +/- 0.76 vs -0.32 +/- 0.87 mmol/l) (AHA type vs low-fat). Level of TBARS decreased (P < 0.05) during the AHA type diet (-8.4 +/- 37.1%) (mean +/- SD) and increased (P = 0.228) during the low-fat diet (+8.7 +/- 27.0%) from 0 to 6 months. The mean intake of total active tocopherols was greater (14.7 +/- 3.7 mg) during the AHA type diet compared to the low-fat diet (7.8 +/- 2.1 mg). Serum vitamin E to LDL cholesterol ratio increased from 8.9 +/- 2.9 to 9.6 +/- 2.4 nmol/mmol (0 vs 6 months) (P = 0.07) during the AHA type diet and from 8.6 +/- 2.6 to 9.3 +/- 2.4 nmol/mmol (P = 0.159) during the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gender differences in intima-media permeability to low-density lipoprotein at atherosclerosis-prone aortic sites in rabbits. Lack of effect of 17 beta-estradiol

Premenopausal women are protected from coronary heart disease, and premenopausal nonhuman primates are protected from atherosclerosis, the underlying cause of coronary heart disease. Estrogen is thought to account for this protection in females, and part of this protection is independent of the effects on risk factors, including lipoprotein levels. This study considered the hypothesis that reduced intima-media permeability to low-density lipoproteins (LDL) may account for the protection from atherosclerosis and coronary heart disease in premenopausal females and that this effect might be mediated by estrogen. Intima-media permeability to LDL was determined in male and female rabbits made hypercholesterolemic by feeding them 0.5% cholesterol for 8 days. The diet of half of the female rabbits was supplemented with 17 beta-estradiol (4 mg/d) during cholesterol feeding and the preceding 4 weeks. Estrogen treatment in the female rabbits did not influence the intima-media permeability to LDL. However, intima-media permeability to LDL for branch sites of the abdominal aorta and aortic arch (regions highly susceptible to atherosclerosis) was 43% and 38% lower, respectively, in male rabbits than in female rabbits: (2.93 +/- 0.39 microL/h/g, (n = 8), vs 6.28 +/- 0.86 microL/h/g, (n = 16), P < .001, and 4.69 +/- 0.28 microL/h/g, (n = 8) vs 7.57 +/- 0.75 microL/h/g, (n = 16), P < .02). In contrast, intima-media permeability to LDL in 7 of 8 aortic sites relatively resistant to atherosclerosis did not differ between male and female rabbits. These data suggest that the protection from atherosclerosis associated with female sex and estrogen is mediated by mechanism(s) other than reduction in intima-media permeability to LDL.     

Serum lipid levels in children and teenagers from Concepción, Chile

BACKGROUND: There is a relationship between serum lipid levels in children with those of adults. Preventive measures to reduce serum lipid levels should start in childhood. AIM: To study serum lipid levels in a representative sample of children and teenagers from Concepción, Chile. SUBJECTS AND METHODS: Serum total, HDL cholesterol and triglycerides were measured in 1,286 males and 816 females from 5 to 18 years old in the city of Concepción. RESULTS: Mean total cholesterol levels were 159 +/- 30 and 162 +/- 31 mg/dl in males and females respectively. The figures for HDL cholesterol were 46 +/- 11 and 47 +/- 11 mg/dl, for LDL cholesterol were 94 +/- 27 and 96 +/- 29 mg/dl and for triglycerides were 80 +/- 35 and 87 +/- 38 mg/dl. Nine percent of males and 12% of females had a total cholesterol over 200 mg/dl. Likewise 10% of males and 11% of females had a LDL cholesterol over 130 mg/dl. CONCLUSIONS: These numbers will help to plan and perform interventions in children, in order to prevent cardiovascular diseases.     

Effect of pravastatin (10 mg/day) on progression of coronary atherosclerosis in patients with serum total cholesterol levels from 160 to 220 mg/dl and angiographically documented coronary artery disease. Coronary Artery Regression Study (CARS) Group

To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a pravastatin (10 mg/day) group (n = 45) and control group (n = 45) in a 2-year study. The proportions of patients with progression (an increase of > or = 15% in percent stenosis) and regression (a decrease of > or = 15% in percent stenosis) of coronary atherosclerosis were compared between the 2 groups. Of 90 patients, 80 (89%) had a final angiogram: the pravastatin (n = 39) and control group (n = 41). Percent changes in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels were significantly greater in the pravastatin group than in the control group (total cholesterol -11 +/- 12% vs 3 +/- 15%, p < 0.01; low-density lipoprotein cholesterol -18 +/- 16% vs 4 +/- 21%, p < 0.01; apoprotein B -5 +/- 20% vs 6 +/- 20%, p < 0.05). The proportion of patients with progression of coronary atherosclerosis was significantly smaller in the pravastatin group than in the control group (21% vs 49%, p < 0.05). The proportion of patients with disease regression did not differ in the 2 groups (3% vs 2%, p = NS). In conclusion, this study indicates that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis even in normocholesterolemic patients with established CAD.     

Determinants of the kinetics of very low-density lipoprotein apolipoprotein B-100 in non-obese men

1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.     

Predictive value of antepartum ultrasound examination for anomalies in twin gestations

RATIONALE AND OBJECTIVES: We investigated the potential of manganese (III) mesoporphyrin (Mn-mesoporphyrin) as a hepatobiliary contrast agent for magnetic resonance (MR) imaging in rabbits given VX-2 carcinoma liver implants. METHODS: Rabbits given VX-2 carcinoma liver implants (n = 8) were imaged before and after the intravenous (i.v.) administration of 0.04 mmol/kg Mn-mesoporphyrin. MR images were correlated with gross-specimen cross-sections. The distribution of Mn in various tissues following i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin was determined using atomic absorption analysis. A standard panel of serum chemistries was followed over 7 days in six rabbits following this same dose of Mn-mesoporphyrin and compared with chemistries from two control rabbits. RESULTS: I.v. administration of 0.04 mmol/kg (25 mg/kg) Mn-mesoporphyrin resulted in improvement of tumor-to-liver contrast, with enhancement of normal liver (99.7 +/- 14.7%) and the gallbladder (442 +/- 116%), but not VX-2 tumor tissue (14.8 +/- 13.9%), (n = 8, p = .05). Analysis of tissue Mn levels 100 min after i.v. Mn-mesoporphyrin injection demonstrated preferential distribution of Mn to normal liver tissue (57.8 +/- 15.3 micrograms Mn/g) compared with VX-2 tumor (4.28 +/- 1.48 micrograms Mn/g). No significant change was found in the serum chemistries of six normal rabbits over a 7-day period after the i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin. CONCLUSION: I.v. Mn-mesoporphyrin improved lesion-to-liver contrast because of preferential distribution of Mn-mesoporphyrin to normal liver parenchyma and bile.     

Risk factors for coronary atherosclerosis. Comparison between two Argentine regions

The prevalence of risk factors for coronary atherosclerosis were studied in two population samples, Northeast (Posadas, n = 498) and South (Viedma, C. Rivadavia and Cipolletti, n = 652) of 20 years and older, males and females. The diet in the Northeast (n = 102) contained more monounsaturated acids and polyunsaturated acids than the one in the South (n = 62), 9.5 +/- 4.1 vs. 8.1 +/- 3.5% TCV (Total Caloric Value) (P < 0.02) and 8.1 +/- 4.1 vs. 6.2 +/- 3.0% TCV (P < 0.001) respectively. The P/S relationship was greater in the Northeast, 1.02 +/- 0.44 vs. 0.85 +/- 0.50 (P < 0.001). Total cholesterol (TC) in the Northeast was less than in the South, in males 176 +/- 41 vs. 213 +/- 43 mg/dl (P < 0.001); CLDL (LDL cholesterol) 109 +/- 37 vs. 141 +/- 41 mg/dl (P < 0.001). The most frequent risk factors in the South vs. Northeast (males) were: TC > or = 240 mg/dl, 26.7% vs. 9.5% (P < 0.001); LDL-C > or = 160 mg/dl, 30.3% vs. 10.9% (P < 0.001); Cig > or = 10/d (equal or more than 10 cigarettes per day), 30.0% vs. 16.4% (P < 0.001). The hypertension prevalence (HTA, 160/95), in males, was higher in the Northeast than in the South, 23.7% vs. 11.5% (P < 0.001). BMI > 27 Kg/m2 was higher in the women of Northeast than in the South, 38.4% vs. 24.2% (P < 0.001). In the males of the Northeast, the combination Cig > or = 10/d and HTA, 4.1 vs 0.9% was more common; in the South Cig > or = 10/d and LDL-C > or = 160 mg/d, 8.2% vs. 1.8% (P < 0.001) was more common. The differences in the prevalence of the risk factors between the population samples indicate the need to plan the prevention of coronary atherosclerosis locally.     

Epidural anaesthesia for caesarean delivery in triple and quadruple pregnancies

BACKGROUND: Mechanical and/or hormonal factors may increase the spread of epidural anaesthesia in pregnancy, and hormonal changes are more pronounced in high-order pregnancies. However, no previous study has evaluated the dose requirements and haemodynamic effects of epidural anaesthesia for caesarean delivery in this latter situation. METHODS: The anaesthetic requirements to obtain a T4 upper sensory level were retrospectively compared in triple (n = 19) or quadruple (n = 2) pregnancies to 31 singleton pregnancies who received epidural anaesthesia for elective caesarean delivery using 2% lidocaine with 1/200,000 adrenaline. RESULTS: In high-order pregnancies, the gestational age at delivery was lower than in singleton pregnancies (34.9 +/- 1.9 weeks vs 38.2 +/- 1.1 weeks; P = 0.0001) whereas maternal body weight (76.5 +/- 8.7 kg vs 73.4 +/- 14.8 kg; NS) and lidocaine requirements (428 +/- 95 mg vs 426 +/- 98 mg; NS) were similar. Moreover, although the overall incidence of hypotension was not different (multiple pregnancy; 65% vs 58% in singletons), ephedrine (5.4 +/- 5.3 mg vs 10.7 +/- 13.8 mg; P < 0.05) and additional fluid requirements during onset of the block (4.3 +/- 1.7 mL/kg vs 5.3 +/- 2.6 mL/kg; P = 0.03) were less than in singletons. CONCLUSION: We found surprisingly similar anaesthetic requirements for epidural anaesthesia in high-order and singleton pregnancies. Mechanical factors may have played an important role. Moreover, the need for ephedrine and fluids was less in high-order pregnancies. This could be related to more pronounced physiological changes or to different physician attitudes.     

CD40 mediated activation of gingival and periodontal ligament fibroblasts

Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.