High serum uric acid levels increase the risk of metabolic syndrome in elderly women: The PRO.V.A study.

BACKGROUND AND AIMS: Serum uric acid (SUA) is the end-product of purine metabolism in humans, and its levels often increase in subjects with metabolic syndrome (MetS). Despite several studies demonstrating a relationship between increased SUA levels and the prevalence of MetS, prospective data on SUA as a predictor of the incidence of MetS in the elderly are limited. Our aim was to conduct a prospective study on the association between SUA concentrations and the onset of MetS in an elderly Italian cohort. METHODS AND RESULTS: This is a cohort study (Progetto Veneto Anziani; Pro.V.A.) involving community-dwelling subjects aged ≥65 years and followed up for a mean 4.4 years. We included 1128 participants (aged 74.7 ± 7.1 years) without MetS at the baseline. Gender-specific SUA groups according to the standard deviation (SD) from the mean were considered, taking the incidence of MetS as the main outcome. The mean SUA level was significantly higher in men than in women (5.4 ± 1.2 vs. 4.5 ± 1.2 mg/dl; p < 0.0001). Over the 4.4-year follow-up, 496 individuals developed MetS. After adjusting for potential confounders, Cox's regression analysis revealed no relationship between higher baseline SUA concentrations and the incidence of MetS in men or in the sample as whole, while women with SUA levels more than 1 SD above the mean (≥5.7 mg/dl) carried a 58% higher risk (95%CI: 1.03-2.40; p = 0.03) of being newly diagnosed with MetS during the follow-up. CONCLUSION: High SUA levels significantly and independently predicted MetS in older women, but not in men, over a 4.4-year follow-up.

Impact of clinical osteoarthritis of the hip, knee and hand on self-rated health in six European countries: the European Project on OSteoArthritis.

PURPOSE: Osteoarthritis (OA) has been shown to be associated with decreased physical function, which may impact upon a person's self-rated health (SRH). Only a few studies have examined the association between OA and SRH in the general population, but to date none have used a clinical definition of OA. The objectives are: (1) To examine the cross-sectional association between clinical OA and fair-to-poor SRH in the general population; (2) To examine whether this association differs between countries; (3) To examine whether physical function is a mediator in the association between clinical OA and SRH. METHODS: Baseline data of the European Project on OSteoArthritis (EPOSA) were used, which includes pre-harmonized data from six European cohort studies (n = 2709). Clinical OA was defined according to the American College of Rheumatology criteria. SRH was assessed using one question: How is your health in general? Physical function was assessed using the Western Ontario and McMaster Universities OA Index and Australian/Canadian OA Hand Index. RESULTS: The prevalence of fair-to-poor SRH ranged from 19.8 % in the United Kingdom to 63.5 % in Italy. Although country differences in the strength of the associations were observed, clinical OA of the hip, knee and hand were significantly associated with fair-to-poor SRH in five out of six European countries. In most countries and at most sites, the association between clinical OA and fair-to-poor SRH was partly or fully mediated by physical function. CONCLUSIONS: Clinical OA at different sites was related to fair-to-poor SRH in the general population. Most associations were (partly) mediated by physical functioning, indicating that deteriorating physical function in patients with OA should be a point of attention in patient care.

Development of a method for simultaneous analysis of PCDDs, PCDFs, PCBs, PBDEs, PCNs and PAHs in Antarctic air.

The development of a unique analytical method for the determination of five classes of persistent organic pollutants (POPs) in atmospheric gas and the particle phase through gas chromatography coupled to high-resolution mass spectrometry is presented. Every step of the pre-analytical and analytical optimization process is described. Great effort was put into simplifying the traditional techniques, with reference to EPA and literature methods. Automated instruments were used for sample extraction and cleanup in order to enhance repeatability and reduce contamination risks. Unlike most common approaches, no separation of the analytes was performed before the GC analysis in order to avoid sample fractionation and to save time and materials. This allowed low instrumental and method detection limits (pg to sub-pg) to be achieved. Accuracy and precision were tested by fortifying the matrix and analysing standard reference materials (NIST SRM 1649b Urban Dust and 2585 Organic Contaminants in House Dust). The method was applied to five samples from Terra Nova Bay, Antarctica. Concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) are presented. Lighter compounds dominate the distribution and are mainly present in the gaseous phase. The observed pattern may be attributable to long-range transport. Results are in general agreement with literature data, where available.

Lipid risk factors among elderly with normal fasting glucose, impaired fasting glucose and type 2 diabetes mellitus. The Italian longitudinal study on aging.

BACKGROUND AND AIMS: Three groups of subjects were identified within a representative sample of older Italians: subjects with normal fasting glucose (NFG), with impaired fasting glucose (IFG) or with type 2 diabetes mellitus (T2D). The aim of the present study was to evaluate the relationship among plasma lipids, lipoproteins, other metabolic factors in the three groups, and their role in predicting total fatal events. METHODS AND RESULTS: 2422 subjects, aged 65-84 years, taking part into the Italian Longitudinal Study on Aging were included in the analyses. Factor analysis was conducted separately for men and women. Factor scores were used as independent variables in Cox Proportional Hazard models, to determine factors predicting death at the follow-up in NFG, IFG and T2D subjects. Four major factors were found for men ("insulin resistance", "body size", "total cholesterol", "HDL cholesterol") and four also for women ("insulin resistance", "total cholesterol", "body size", "HDL cholesterol"). For NFG and IFG men, and for both T2D men and women, the "HDL cholesterol" was a significant protective factor for total deaths (NFG men: HR = 0.79, 95% CI 0.67-0.93; IFG men: HR = 0.59, 95% CI 0.45-0.79; T2D men: HR = 0.55, 95% CI 0.34-0.89; T2D women: HR = 0.61, 95% CI 0.44-0.86). Among NFG women, the "body size" factor was also a protective factor with respect to total deaths (HR = 0.74, 95% CI 0.57-0.95). CONCLUSION: A factor including HDL Cholesterol and Apo A-I showed protection against all-cause mortality in older men, independently from the glycemia level, and in women only in those diagnosed with T2D.

Changes in total body and limb composition and muscle strength after a 6-8 weeks sojourn at extreme altitude (5000-8000 m).

AIM: Weight loss at extreme altitudes affects quantitative changes in fat-free mass (FFM), muscle mass and fat mass. No studies to date have focused on regional body composition and physical performance using reference methods after stays at extreme altitudes. The aim of this study was to investigate the changes in total and regional body composition, and muscle strength induced by the extreme altitudes. METHODS: Eight men aged 38.8±5.8 who took part in two different Italian expeditions on Mt. Everest (group A) and on Gasherbrum II (group B). Before and after the expedition all participants underwent anthropometric measurements, total and regional body composition assessment by DEXA, and handgrip and knee extensor strength measurements by dynamometry. RESULTS: The variations in body composition mainly involved FFM, with a similar loss in group A (-2.4±1.9 kg; P<0.05) and group B (-2.4±1.2 kg; P<0.05). Most of the FFM loss involved the limbs (-2.1±1.4 kg; P<0.01), and especially the upper limbs (-1.6±1.1 kg; P<0.01). The isotonic knee extensor strength declined in 6 of the 8 study participants, with a mean drop of -4.4±6.1 kg. CONCLUSIONS: In conclusion, our study evidence that extreme altitudes induce weight loss due mainly to a loss of fat-free mass in the limb.

Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. (PROgetto Veneto Anziani) study.

OBJECTIVES: To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis (CC) of the lower limbs in the elderly Italian population of the Pro.V.A. study. METHODS: Knee and pelvic basin radiographs were performed on 3099 subjects aged 65 and older, residing in the Veneto Region of Italy (Rovigo and Camposampiero areas). Two readers independently analysed the knee, coxofemoral and pubic symphysis x-rays of a consecutive sample of 1629 subjects according to Altman. Some laboratory indexes, such as serum parathyroid hormone (PTH), vitamin D (vit D), bone alkaline phosphatase (bALP), deyidroepiandrosterone (DHEA), urinary CrossLaps (XL), and inflammatory biomarkers were evaluated. Quantitative variables were summarised as mean + or - standard deviation and qualitative ones as distributions. Unpaired t-test was used to compare mean values among groups for normally distributed variables, and non-parametric Mann-Whitney test for non normal variables. RESULTS: CC was found in 169 (mean age 78.2 + or - 8.0 yrs) out of the 1629 subjects studied (10.4%). After adjusting for the sex and age structure of the target population, the prevalence was 10.0%. CC was more often observed in women than in men (M: 7.0%; F: 12.8%, p=0.0002), and increased in occurrence with age, rising from 7.8% in subjects aged 65-74 yrs, to 9.4% in those aged 75-84 yrs, and to 21.1% in subjects older than 85 yrs. The knee was the most prevalent location since it was affected in 94.1% of all the subjects with CC, in particular the right limb. Knee CC was bilateral in 71.7% of the affected patients. The occurrence of rheumatic disorders did not differ significantly between the subjects with CC and those without (rheumatoid arthritis 0.59% vs. 0.48%, p=ns). CONCLUSIONS: Although the detection of CC was limited to few joints with the knee being the most affected location, our study confirms the frequent presence of CC at different sites, in keeping with the possible role of systemic factors. Articular CC is an age-related disorder, which could partly explain the prevalence discrepancies reported by various studies. The prevalence of CC found in our survey based on standardised x-ray reading was high, suggesting that CC could be an underdiagnosed disease in the absence of radiographic investigation.

Desaturase activities and metabolic control in type 2 diabetes.

The aim of this study was to elucidate the effects of a poor glycemic control on fatty acid composition and desaturase activities in type 2 diabetic patients. Plasma phospholipid fatty acid composition and desaturase activities (estimated from fatty acid product to precursor ratios) were measured in 30 type 2 diabetic patients during poor metabolic control and after achieving a good metabolic control. Significant changes were recorded in the percentages of palmitic, stearic, dihomo-gamma-linolenic, docosatetraenoic and docosapentaenoic acid. The delta-5 desaturase activity was significantly higher with poor than with good metabolic control. The changes identified in plasma phospholipid fatty acid composition and the desaturase activity in type 2 diabetic patients go in the opposite direction to those described in similar conditions in type 1 diabetic patients and may be relevant to a better understanding of the role of metabolic control in the progression of chronic complications in type 2 diabetic patients.

Use of a low-dose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs.

BACKGROUND: Although definitive diagnosis of hypoadrenocorticism usually is made by an adrenocorticotrophic hormone (ACTH) stimulation test using 250 microg/dog of synthetic ACTH (cosyntropin/tetracosactrin), increased costs have prompted a search for less-expensive diagnostic methods. HYPOTHESIS: A low-dose ACTH stimulation test (5 microg/kg) will distinguish between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, administration of cosyntropin will not affect the results of another ACTH stimulation test performed 24 hours later. ANIMALS: Eight healthy adult dogs and 29 hospitalized dogs with suspected hypoadrenocorticism. METHODS: In this prospective study, each healthy dog received 4 ACTH stimulation tests. Dogs received either 5 microg/kg or 250 microg/dog of cosyntropin on day 1 and the alternate dose on day 2. The opposite dosing sequence was used after a 2-week washout period (days 15 and 16). Dogs with suspected Addison's disease received 2 ACTH stimulation tests, 24 hours apart, using either a dose of 5 microg/kg cosyntropin or 250 microg/dog on the 1st day and the alternate dose on the 2nd day. RESULTS: In healthy dogs, poststimulation cortisol concentrations on days 2 and 16 and days 1 and 15 were equivalent (90% confidence interval [CI]: 86.7-101.2%). In dogs with suspected Addison's disease, mean (+/-SD) cortisol responses to ACTH in the 5 microg/kg dose (16.2+/-7.7 microg/dL) and 250 microg/dog dose (15.9+/-6.3 microg/dL) were statistically equivalent (90% CI: 91.2-105.4%). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose ACTH stimulation testing distinguishes between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, the administration of 2 ACTH stimulation tests on consecutive days does not affect results of the second test.

[The future of the metabolic syndrome: certainties, open questions and discussions]. / Il futuro della sindrome metabolica tra certezze, problemi aperti e controversie.

The metabolic syndrome is a topic of hot debate among experts due to different opinions about its definition and its clinical relevance. The metabolic syndrome is identified by the presence of abnormalities of the glucose metabolism, blood pressure, fat deposition, and some plasma lipids. Several authors have attempted to find a physiopathological explanation for the association of the abnormalities in this syndrome. Recently, some aspects of the inflammation seem relevant to understand the association of visceral fat deposition, insulin-resistance and diabetes and vascular complications. From a clinical point of view this syndrome must be considered an important vascular risk factor.

Availability and use of neighborhood resources by older people with osteoarthritis: Results from the European Project on OSteoArthritis.

This study examines the availability and use of neighborhood resources in relation to clinical lower limb osteoarthritis (LLOA) in older participants from six European countries. Of the 2757 participants (65-85 years), 22.7% had LLOA. Participants with LLOA made more use of places to sit (OR=2.50; CI: 1.36-4.60 in the UK), and less use of parks and walking areas (OR=0.30; CI: 0.12-0.75 in Sweden), compared to participants without LLOA, particularly in countries with high availability of resources. The results suggest that specific features of the environment impact the use of neighborhood resources by older adults with LLOA.

Lipoprotein abnormalities in well-treated type II diabetic patients.

OBJECTIVE: To investigate lipoprotein levels and composition in well-treated type II diabetic patients. RESEARCH DESIGN AND METHODS: Cholesterol and triglyceride levels were measured in plasma, VLDL, LDL, and HDL in 120 type II diabetic patients in good to fair metabolic control (HbA1c, 7.2 +/- 1.6%) and in 30 normal control subjects. ApoAI, AII, B, CII, CIII, and E levels in plasma were also determined. RESULTS: The diabetic patients have significantly higher levels of mean plasma cholesterol (5.85 vs. 5.43 mM, P = 0.03), LDL triglycerides (0.41 vs. 0.31 mM, P = 0.003), and HDL triglycerides (0.24 vs. 0.19 mM, P = 0.02), whereas total triglycerides, VLDL cholesterol and triglycerides, LDL cholesterol, and HDL cholesterol are not significantly different from normal control subjects. ApoB (150 vs. 135 mg/dl, P = 0.02) and apoCIII (10.6 vs. 8.4 mg/dl, P = 0.01) are significantly higher in diabetic patients compared with control subjects. No significant differences are observed in all the parameters among diabetic patients treated with diet only, sulphonylurea, sulphonylurea plus biguanides, or insulin. Body weight is significantly related to VLDL lipids. The VLDL triglycerides are inversely related to the HDL cholesterol in both diabetic patients and control subjects. The VLDL triglycerides are directly related to the HDL triglycerides only in diabetic patients. No other lipid or lipoprotein parameters are significantly related to body weight or metabolic control. CONCLUSIONS: Type II diabetic patients in good to fair metabolic control are characterized by minor alterations of the plasma lipids, but LDL and HDL triglycerides, apoB, and apoCIII are increased, thus indicating that the lipoprotein composition is altered, possibly because of an abnormal triglyceride metabolism and/or lipid transfer activity.

Obesity, Muscular Strength, Muscle Composition and Physical Performance in an Elderly Population.

OBJECTIVE: To evaluate the association between BMI levels, muscular strength, muscle composition and physical performance in the elderly. DESIGN: Italians subjects from the Progetto Veneto Anziani (ProVA) study were analyzed. SETTING: The ProVa was a population study focused on chronic diseases and functional limitations in Italian subjects aged ≥65 years living in two Northeast Italian cities. PARTICIPANTS: The ProVa study included 3099 subjects. ProVa participants with unknown information on BMI or disability status were excluded. The final sample was thus represented by 1.188 men, and 1.723 women. MEASUREMENTS: Physical performance was measured with the Short Physical Performance Battery (SPPB) and leg muscular strength with dynamometry. Fat distribution and skeletal muscle composition were measured in an abdominal single-scan magnetic resonance (MRI) in a randomly selected sample of 348 subjects. Study population was stratified by BMI classes. RESULTS: An association between BMI levels and SPPB was observed. Normal weight subjects showed the best SPPB scores (8.29±0.03), with significant differences compared to underweight (7.50±0.15; p<0.001), overweight (8.12±0.02; p<0.001), class I (7.72±0.04; p<0.001), class II (6.67±0.09; p<0.001) and class III obesity (5.88±0.24; p<0.001). This pattern was not modified by adjustment for possible confounders. Compared to normal weight subjects (22.9±0.1 kg), leg muscular strength was higher in overweight (23.8±0.1; p<0.001) and in class I obesity (24.5±0.1; p<0.001), but it was reduced in class II (21.4±0.3; p<0.001) and class III (19.8±0.9; p<0.001). The association between BMI and impaired physical performance was not affected by adjustment for muscular strength. An inverse association between SPPB scores and fat infiltration in skeletal muscle was observed in patients with abdominal MRI. CONCLUSION: A poor physical performance was observed in overweight and obese elderly subjects. Leg strength was reduced only in subjects with severe obesity. Physical performance was negatively influenced by the degree of fat infiltration in skeletal muscle.

Short-term diabetic ketosis alters n-6 polyunsaturated fatty acid content in plasma phospholipids.

At present, no information is available about the possibility that acute loss of metabolic control might be able to modify fatty acid composition in IDDM patients. Therefore, the aim of this study was to determine whether a short-term period of ketosis has any effect on the composition of fatty acid of plasma phospholipids in a group of insulin-dependent diabetes mellitus (IDDM) patients. Eleven IDDM patients and nine healthy volunteers were studied. Patients were studied over a 2-day period; each 2-day period consisted of initial baseline measurements followed by a day of hyperglycemia and mild ketosis, which was promptly alleviated by insulin infusion. No significant difference in baseline percent fatty acid composition was observed between normal controls and IDDM patients. In IDDM patients, ketosis induced a significant decrease in percent arachidonic acid (20:4 n-6) content, with a significant parallel decline in n-6 total polyunsaturated fatty acids. A significant inverse correlation between the prevailing plasma glucose and the relative content of arachidonic acid in plasma phospholipids was observed (r = -0.35; P = 0.0488). A highly significant inverse correlation was observed between the change from baseline condition to ketosis of the ratio C20:4/C20:3, the product/precursor ratio for the reaction catalyzed by delta5-desaturase, and the values of hemoglobin A1c,(r = -0.855; P = 0.0015). In conclusion, short term diabetic ketosis is associated with a significant decrease in n-6 polyunsaturated fatty acid content in plasma phospholipids, especially arachidonic acid. This decrease in arachidonic acid appears to be related to the degree of metabolic derangement, whereas the influence of short-term diabetic ketosis on the ratio of C20:4 to C20:3 seems to be due to the degree of long-term metabolic control.

Effect of glyburide and omega 3 fatty acid dietary supplements on glucose and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.

Using a random crossover design, we examined the effects of glyburide for 4 wk on glucose, insulin, lipid, and lipoprotein metabolism in 10 men with non-insulin-dependent diabetes (NIDDM) receiving dietary fish-oil concentrates containing omega 3 (n-3) fatty acids (8 g/d). Compared with glyburide alone, fasting plasma glucose concentrations increased with fish oil. Although glyburide with fish oil decreased fasting glucose concentrations, they did not return to baseline. Basal insulin concentrations were unaltered by fish oil without or with glyburide; however, postprandial insulin concentrations were decreased by fish oil. Although total cholesterol and triglyceride concentrations were unchanged, very-low-density-lipoprotein cholesterol concentrations decreased and low-density-lipoprotein cholesterol rose and apolipoprotein B concentrations trended higher. Thus, glyburide only partially rectified the impaired fuel homeostasis associated with fish-oil supplements in patients with NIDDM. Therefore, we do not recommend intake of fish oil concentrates containing n-3 fatty acids in patients with NIDDM.

The effect of probucol on HDL-mediated sterol translocation and efflux from cells.

It has been suggested that the antioxidant drug probucol can prevent arterial cholesterol accumulation in part by promoting HDL-mediated cholesterol removal from cells. In this study, the effect of probucol in vitro on the interaction of HDL3 with cultured skin fibroblasts, bovine aortic endothelial cells and human monocyte-derived macrophages was tested. Treatment of cholesterol-loaded cells with up to 20 microM probucol had no effect on [3H]cholesterol efflux from plasma membranes. No effect of probucol on HDL3-mediated efflux of labeled sterol was seen after intracellular sterol was labeled either with the biosynthetic precursor [3H]mevalonolactone or after incubation with lipoprotein-associated [3H]cholesterol linoleate. Further, no effect of probucol on cell cholesterol mass efflux was observed. Thus these results demonstrate that probucol does not affect movement of sterol from different cellular radiolabeled sterol pools. Within the limitations of cell culture studies, it is suggested that the proposed antiatherogenic effect of probucol in vivo is not likely to be the result of modulation of major cellular pathways for removal of cholesterol.

Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients.

The aim of this study was to determine whether gemfibrozil-mediated decrease in very low density lipoprotein triglyceride (VLDL-TG) concentration is accompanied by an improvement in overall glucose metabolism in hypertriglyceridemic patients. We assessed this hypothesis in 7 hypertriglyceridemic without (HTG) and in 11 hypertriglyceridemic with noninsulin-dependent diabetes mellitus (NIDDM-HTG) who followed three-months treatment either with the drug or with placebo. Placebo VLDL-TG concentrations in both HTG (3.82 +/- 0.92 mmol/l (mean +/- S.D.) vs. 3.91 +/- 1.01 mmol/l) and in NIDDM-HTG (6.62 +/- 3.93 mmol/l vs. 6.84 +/- 4.16 mmol/l) were not different from baseline values, whereas gemfibrozil decreased VLDL-TG in both groups (1.84 +/- 0.56 mmol/l, P < 0.001 for HTG, and 1.93 +/- 2.68 mmol/l, P = 0.013 in NIDDM-HTG). In both groups, gemfibrozil treatment was associated with an improvement in fasting plasma glucose levels (from 5.85 +/- 0.92 mmol/l to 4.87 +/- 0.40 mmol/l in HTG, P = 0.001, and from 11.47 +/- 2.92 mmol/l to 9.56 +/- 3.41 mmol/l in NIDDM-HTG, P = 0.042). In NIDDM-HTG, gemfibrozil treatment was associated with a significantly lower 2 h-postprandial plasma glucose level (9.87 +/- 3.63 vs. 13.09 +/- 3.62, P = 0.05). A significant decrease in fasting free fatty acids (FFA) level was observed during gemfibrozil treatment in both groups, whereas in NIDDM-HTG, a significant drop of these substrates was observed in both fasting and postprandial conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced susceptibility to oxidation of low-density lipoprotein in patients with overproduction of nitric oxide (Bartter's and Gitelman's syndrome).

BACKGROUND: The oxidation of low-density lipoprotein (LDL) might play an important role in the development of atherosclerosis. OBJECTIVE: To establish whether greater than normal production of nitric oxide (NO) in vivo protects LDL from oxidation. PATIENTS AND METHODS: We studied nine subjects affected by Bartter's and Gitelman's syndrome (both characterized by greater than normal production of NO), and 10 subjects matched for age, sex and lipid levels as controls. LDL particles were isolated from plasma by density gradient ultracentrifugation. Susceptibility of LDL to oxidation was evaluated after incubation with copper sulfate solution, by measuring the formation of conjugated dienes, the thiobarbituric acid-reactive substances, and the volatile peroxidation products of n-3 (propanal) and n-6 (pentanal and hexanal) polyunsaturated fatty acids. Phospholipid fatty acid composition of LDL was determined by gas chromatography. LDL alpha-tocopherol concentrations were measured. RESULTS: Patients with Bartter's and Gitelman's syndrome had LDL particles smaller and/or denser than those of controls [Rf = 0.38 +/- 0.03 versus 0.42 +/- 0.02 (mean +/- SD), P < 0.01], which hence were assumed to be more oxidizable. The phospholipid fatty acid composition of LDL and the alpha-tocopherol concentrations did not significantly differ between patients and controls. The duration of the lag phase, which is the time preceding formation of conjugated dienes, did not differ between groups, but the lag phase times were related to urinary excretion of nitrite/nitrate from patients (r = 0.66, P < 0.05). Moreover, patient LDL had produced less thiobarbituric acid-reactive substances after 5 h (P < 0.04), and less pentanal and hexanal after 5 and 6 h (P < 0.04 and P < 0.02, respectively) than had that of controls. CONCLUSIONS: Greater than normal production of NO in vivo is associated with lower than normal susceptibility of LDL to oxidation in vitro, suggesting that NO plays a protective role in the development of atherosclerosis.

Efficacy of ciprofibrate in primary type II and IV hyperlipidemia: the Italian multicenter study.

The 127 diet-resistant primary hyperlipidemic patients received 100 mg of ciprofibrate daily for 12 weeks. In the 63 patients with type IIa hyperlipidemia and 41 patients with type IIb hyperlipidemia, serum levels of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, very-low-density lipoprotein triglycerides, and apolipoprotein (apo) B decreased significantly and levels of high-density lipoprotein cholesterol and apo A-I increased significantly. Similar changes occurred in the 23 type IV patients, except that high-density lipoprotein cholesterol levels increased significantly and apo B levels did not change. No clinically significant side effects or drug-related abnormal laboratory test results were noted. It is concluded that ciprofibrate is a safe and potent hypolipidemic agent.

Levels and physicochemical properties of lipoprotein subclasses in moderate hypertriglyceridemia.

Moderate hypertriglyceridemia is associated with several abnormalities of the plasma lipoprotein particles and it may be a risk factor for atherosclerotic vascular diseases. Plasma lipid, lipoprotein and apolipoprotein levels, as well as lipoprotein composition and physical properties, were examined by ultracentrifugation in a zonal rotor and by gradient gel electrophoresis in 14 patients with moderate hypertriglyceridemia (plasma triglycerides 4.00 +/- 0.32 mmol/l, mean +/- S.D.) and in 14 control subjects. Based on zonal ultracentrifugation hypertriglyceridemic patients have higher levels of cholesterol in all VLDL subclasses (Sf > 200, 100-200, 60-100 and 20-60), in IDL and in small and dense LDL. Both HDL2 and HDL3 cholesterol levels are reduced. The LDL flotation rate is inversely related to plasma triglyceride levels, thus indicating that the higher the plasma triglycerides the smaller and/or denser the LDL are. The triglyceride percent content of LDL2 and HDL3 is increased, while that of esterified cholesterol is reduced in hypertriglyceridemic patients. Gradient gel electrophoresis shows that the LDL peak size is lower (25.2 +/- 0.5 nm, mean +/- S.D.) in hypertriglyceridemic than in control subjects (27.1 +/- 0.4 nm; P < 0.0001). Considering both hypertriglyceridemic and control subjects the LDL peak effluent volume from the zonal rotor (which reflects the LDL flotation rate) is inversely related to the LDL peak size determined by gradient gel electrophoresis (r = -0.71; P = 0.0006) and the plasma triglyceride levels are related to LDL peak effluent volume (r = 0.74; P = 0.0002) and to LDL peak size (r = -0.95; P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients.

Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA1c) was 9.44 +/- 1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.43 +/- 0.05 vs 0.85 +/- 0.14; p < 0.05). The flotation rate LDL2, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL3, the minor component of LDL, were significantly higher (0.17 +/- 0.03 and 0.83 +/- 0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05 +/- 0.02 and 0.24 +/- 0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL2, HDL2 and HDL3, were no different in diabetic patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)