High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome.

OBJECTIVE: High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). PATIENTS AND MEASUREMENTS: We recruited 370 adults (18-85 years, BMI 29·3 ± 4·4 kg/m(2) , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). RESULTS: Urinary sodium was correlated with UFC (r = +0·45, P < 0·001), cortisol THM (r = +0·41, P < 0·001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0·001), THM (P < 0·001), HOMA-IR (P = 0·04), HT (81% vs 50%, P < 0·001), MetS (69% vs 41%, P < 0·001) and lower adiponectin (P = 0·003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0·878) using four clinical variables: HS intake [OR = 5·6 (CI 2·3-15·3)], HOMA-IR [OR 1·7 (1·3-2·2)] cortisol THM [OR 1·2 (1·1-1·4)] and adiponectin [OR = 0·9 (0·8-0·9)], the latter had a protective effect. CONCLUSIONS: High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.

Homocysteine, traditional risk factors and impaired renal function in coronary artery disease.

BACKGROUND: To establish whether the frequent finding of a moderate-intermediate increase in plasma total homocysteine (tHcy) causes coronary artery disease (CAD), the authors evaluated the number of coexisting major traditional risk factors, as well as the major tHcy determinants, in patients with the same degree of CAD but different tHcy levels. MATERIALS AND METHODS: The authors studied 180 patients with CAD, who were divided into three groups according to tHcy levels: 60 patients with normal tHcy, 60 patients with moderate (15-30 micromol L(-1)) and 60 patients with intermediate hyperhomocysteinaemia (30-100 micromol L(-1)). The patient groups were matched for gender, age and number of affected coronary vessels. All patients were checked for the presence of traditional risk factors for CAD (i.e. hypertension, diabetes, hyperlipidaemia, smoking habit, familial history, obesity), as well as determinants of tHcy levels. The population was subdivided into those having, or not, a substantial burden of traditional risk factors (i.e. < 4 and > or = 4, respectively). RESULTS: There was a significant trend towards a reduced number of subjects within the group with > or = 4 risk factors across increasing tHcy levels (51.7%, 37.8%, 26%, for normal, moderate, intermediate tHcy, respectively, chi2 for linear-trend = 0.006). Folate and vitamin B12 concentrations, estimated glomerular filtration rate (GFR), MTHFR 677C > T polymorphism were the major determinants of tHcy in this population. CONCLUSIONS: In patients with the same degree of CAD, those with hyperhomocysteinaemia had a reduced burden of traditional risk factors as compared with those with normal tHcy levels. Hyperhomocysteinaemia was significantly associated with an emerging non-traditional risk factor such as lower GFR.

Diagnóstico histoquímico e imunoistoquímico da enteropatia proliferativa (Lawsonia intracellularis) em suínos / Detection of swine proliferative enteropathy (Lawsonia intracellularis) in slaughtered pigs by histochemical and immunohistochemical techniques

Estudou-se a eficácia do diagnóstico macroscópico de lesões da enteropatia proliferativa suína (EPS) usando-se fragmentos de íleo de 663 suínos, coletados em abatedouros localizados em três municípios do Rio Grande do Sul. As amostras foram processadas por métodos histológicos rotineiros e coradas por uma técnica desenvolvida pela combinacão das coloracões Warthin-Starry, alcian blue e hematoxilina-eosina para deteccão simultânea de Lawsonia intracellularis e lesões associadas com EPS. Lâminas suspeitas de EPS foram submetidas à técnica de imunoistoquímica, utilizando anticorpo policlonal anti-Lawsonia intracellularis na diluicão de 1:15.000 pelo método avidina-biotina. A coloracão combinada detectou 11 casos positivos, e a imunoistoquímica, nove casos adicionais. Entre as 643 amostras consideradas negativas, 12 apresentaram desaparecimento de células caliciformes e proliferacão adenomatosa características de EPS, mas ausência de bactérias intracelulares. A eficiência do exame macroscópico para diagnóstico de EPS foi medida pela associacão entre os resultados das avaliacões macroscópicas e histológicas realizadas em 219 amostras. Embora 51 delas tenham sido consideradas macroscopicamente positivas, apenas quatro foram confirmadas pela presenca de bactérias intracelulares associadas com lesões características de EPS. Não se observou associacão entre as alteracões macroscópicas e histológicas de EPS.

Elevated plasma fibrinogen levels in patients with essential hypertension are related to vascular complications.

AIM: We investigated whether or not fibrinogen is related to the cardiovascular risk profile and complications in hypertensive subjects. METHODS: Plasma fibrinogen and laboratory tests including factor VII, homocysteine and microalbuminuria were evaluated in 127 consecutive hypertensive subjects stratified according to cardiovascular risk. Parameters were age, gender, smoking, cholesterol, diabetes, target organ damage: left ventricular hypertrophy (LVH), carotid atherosclerotic complications and retinical vessels. RESULTS: Fibrinogen levels were significantly different between patients according to risk levels (low 290+/-73, n=20, high 342+/-94 mg/dl, n=39, very high risk 350+/-72, n=29, p=0.01), hypertension grade (II-III) and organ damage. Fibrinogen was significantly higher in patients with more severe carotid atherosclerotic lesions and vascular retinal lesions (grades II-III vs 0 and I). Also in patients, matched for age and sex, without and with carotid atherosclerotic lesions, fibrinogen was significantly higher in the latter group. No significant differences were found on the basis of IVS, creatinine and microalbuminuria. In hypertensive patients, fibrinogen directly correlated with age, by multiple linear regression. In hypertensive patients with diabetes, fibrinogen was significantly higher (466+/-176 mg/dL, n=14) than in those hypertensive without diabetes (333+/-87 mg/dL, n=113, p=0.001) and in all patients there was a a significant correlation (r=0.474, p<0.001) between blood glucose and fibrinogen. CONCLUSION: Hyperfibrinogenemia is a marker of vascular damage and could be an important factor contributing to the evolution of the complications.

A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism.

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine/methionine metabolism. The most-studied C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been reported to lower enzyme activity. Whether A1298C is a risk factor for coronary artery disease, separately or in combination with C677T, and/or relative to total plasma homocysteine and folate status, is unclear to date. We evaluated this hypothesis in 470 angiographically characterized subjects, 302 with coronary artery disease, and 168 with normal coronary arteries. The frequency of the 1298C allele was 0.33 and that of combined heterozygosity 0.315. No difference was found in the frequency of the genotypes or when analyzed for combined heterozygosity between patients with coronary artery disease and normals. Independent of folate status, the 1298C allele was not associated with increased total plasma homocysteine. No additional effect of A1298C on total plasma homocysteine was observed in 148 combined heterozygotes compared with 98 heterozygotes for the C677T alone. These findings do not support a major role for the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that MTHFR genotypes may interfere with coronary artery disease risk only when an unbalanced nutritional status leads to raised total plasma homocysteine levels.

Elevated plasma levels of soluble receptors of TNF-alpha and their association with smoking and microvascular complications in young adults with type 1 diabetes.

The purposes of this study were 1) to compare soluble tumor necrosis factor-alpha receptors, which are thought to reflect the degree of TNF-alpha activation, in nondiabetic subjects and type 1 diabetic patients, and 2) to evaluate the effects of smoking and microvascular complications on soluble tumor necrosis factor-alpha receptor levels in type 1 diabetic individuals. Plasma soluble tumor necrosis factor-alpha receptor levels (R1 and R2) were measured in 50 young type 1 diabetic patients without clinical macroangiopathy and in a matched group of 20 healthy volunteers. When diabetic patients were grouped according to smoking and microvascular complication status, the groups of patients had similar values of age, sex, body mass index, blood pressure, lipids, creatinine, and glycometabolic control. Nevertheless, soluble tumor necrosis factor-alpha receptor-R1 levels but not R2 levels, were markedly elevated (P < 0.05 or less) in complicated vs. uncomplicated (2.40 +/- 0.3 vs. 1.80 +/- 0.1 ng/ml) patients and in smokers vs. nonsmokers (2.66 +/- 0.4 vs. 1.76 +/- 0.1 ng/ml). In a two-factor ANOVA, both smoking (P < 0.01) and microvascular complications (P < 0.05) were independent predictors of soluble tumor necrosis factor-alpha receptor-R1. Soluble tumor necrosis factor-alpha receptor levels of diabetic patients who did not smoke or without complications were similar to those of healthy controls. In conclusion, smoking and microvascular complications seem to exert an additive and deleterious impact on TNF-alpha activation, as reflected by levels of soluble tumor necrosis factor-alpha receptors, in young adults with type 1 diabetes.

The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin.

BACKGROUND: Iron deficiency (ID) is the main cause of hyporesponsiveness to erythropoietin in haemodialysis patients and its detection is of value since it is easily corrected by intravenous iron. Markers of iron supply to the erythron, including erythrocyte zinc protoporphyrin (Er-ZPP), percentage of hypochromic erythrocytes (Hypo), reticulocyte haemoglobin content (CHr) and soluble transferrin receptor (sTfR), may be more accurate predictors of ID than ferritin (Fer) and transferrin saturation (TSat), but relative diagnostic power and best threshold values are not yet established. METHODS: In 125 haemodialysis patients on maintenance erythropoietin, the diagnostic power of the above parameters was evaluated by ROC curve, multivariate regression, and stepwise discriminant analyses. Diagnosis of ID was based on haemoglobin response to intravenous iron (992 mg as sodium ferric gluconate complex over an 8-week period). RESULTS: Fifty-one patients were considered iron deficient (haemoglobin increase by 1.9+/-0.5 g/dl) and 74 as iron replete (haemoglobin increase by 0.4+/-0.3 g/dl). ROC curve analysis showed that all tests had discriminative ability with the following hierarchy: Hypo (area under curve W=0.930, efficiency 89.6% at cut-off >6%), CHr (W=0.798, efficiency 78.4% at cut-off < or =29 pg), sTfR (W=0.783, efficiency 72.4% at cut-off >1.5 mg/l), Er-ZPP (W=0.773, efficiency 73.0% at cut-off >52 micromol/mol haem), TSat (W=0.758, efficiency 70.4% at cut-off <19%) and ferritin (W=0.633, efficiency 64.0% at cut-off <50 ng/ml). Stepwise discriminant analysis identified Hypo as the only variable with independent diagnostic value, able to classify 87.2% of patients correctly. Additional tests did not substantially improve diagnostic efficiency of Hypo >6% alone. CONCLUSIONS: In haemodialysis patients on maintenance erythropoietin, Hypo >6% is the best currently available marker to identify those who will improve their response after intravenous iron. Cost-effectiveness suggests that this parameter should be a first-line tool to monitor iron requirements in clinical practice.

Homocysteine and atheromatous renal artery stenosis.

Hyperhomocysteinemia is an independent risk factor for vascular disease, frequently observed in patients with severe renal impairment. Hyperhomocysteinemia has never been considered as a possible risk factor in renal artery stenosis. We investigated plasma folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase (CBS) 844ins68 polymorphisms, and homocysteine levels before and after methionine (100 mg/kg) loading in 58 patients with angiographically documented renal artery stenosis and mildly impaired renal function. One hundred and two normotensive subjects with angiographically normal coronary arteries and no history or clinical or angiographic evidence of atherosclerosis in other vascular districts, were considered as a control group. Mean total homocysteine levels were significantly higher in patients than in controls (P<0.01), as was the prevalence of hyperhomocysteinemia (51.7% vs. 32.3%, P<0.05). However, MTHFR alleles and genotypes as well as CBS 844ins68 mutation frequencies were similar in the two groups, whereas a lower folate level was observed in the patients. Moreover, patients with MTHFR A/A genotype showed a poorer folate status than control subjects, suggesting that a subclinical folate deficiency may be very frequent in renal artery stenosis, regardless of C677T mutation. In conclusions, hyperhomocysteinemia is common in patients with atheromatous renal artery stenosis; a subclinical folate deficiency seems to be involved, regardless of MTHFR thermolabile or CBS insertion genotypes. Folate supplementation might be useful in the management of overall vascular risk of these patients.

Homocysteine and life-style in the elderly.

Elevated homocysteine increases the risk of vascular diseases but little information is available about this issue in the elderly. The aim of this cross-sectional study was to evaluate the relationships between homocysteinemia and gender, anthropometric, and life-style characteristics in a community-dwelling elderly population (65 men and 120 women; 67-78 years). Basal plasma homocysteine levels were determined by High Performance Liquid Chromatography (HPLC). Clinical records, and nutritional and anthropometric variables were collected in all subjects. Body composition was evaluated in all subjects by Dual energy X-ray Absorptiometry (DXA). Thirty-three percent of women and 66% of men had hyper-homocysteinemia. In women, a positive correlation was present between homocysteinemia, age, diastolic blood pressure and plasmatic creatinine, and a negative correlation between homocysteine, fiber intake and folates. In males, there was a positive correlation between plasma homocysteine, age, and body mass index. Multiple regression analysis showed that fat-free mass, cigarette smoking, fiber intake, vitamin B6 and total kcal intake accounted for 18% of homocysteine variance in males (R2 = 0.18, p<0.05). Significantly higher homocysteine values were found in women with a history of cardiovascular disease than in those without (16.6 +/- 9.4 vs 13.8 +/- 4.4 micromol/L, p<0.05). Homocysteinemia was significantly higher in elderly men compared to women (16.7 +/- 4.7 vs 15.3 +/- 7.6; p<0.05). Gender differences in homocysteine disappeared after adjusting for fat-free mass. This study confirms the age-related increase in plasma homocysteine. Life-style characteristics seem to influence significantly homocysteine levels in the elderly. Our study shows that gender effects on homocysteine may be attributed to differences in body composition.

[Proposal of a new test for the diagnosis of PROM based on the determination of hCG in the washing fluid of the posterior vaginal fornix]. / Proposta di un nuovo test per la diagnosi di PROM basato sul dosaggio della hCG nel liquido di lavaggio del fornice vaginale posteriore.

BACKGROUND: The objective of this study is to determine whether or not the measurement of hCG levels in the washing fluid of the posterior vaginal fornix is useful for the diagnosis of premature rupture of membranes. METHODS: Samples were analysed from 52 normal pregnant women, divided into three groups: 20 pregnant women without rupture of membranes, 21 patients with confirmed rupture of membranes, 11 patients with suspected rupture of membranes. In order to distinguish patients of the two groups we propose a hCG cut-off value of 100 mIU/ml. RESULTS: The analysis of our data reveals that there is no overlapping between the hCG levels of the group of pregnant women without rupture of membranes and the group of patients with confirmed rupture of membranes. CONCLUSIONS: The hCG levels in the washing fluid of the posterior vaginal fornix in our experience is a useful, very cheap and non-invasive diagnostic test of PROM.

Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes.

OBJECTIVE: The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P < 0.0001) in a dose-dependent fashion (P < 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). CONCLUSIONS: Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.

Anti-oxidant status and lipid peroxidation in patients with essential hypertension.

BACKGROUND: Lipid peroxidation and derived oxidized products are being intensively investigated, because of their potential to cause injury and their pathogenetic role in several clinically significant diseases. The view that an excess of lipid peroxidation products is present and relevant in the pathogenesis of human essential hypertension or in hypertension-induced damage has still not received definitive support. OBJECTIVE: To evaluate both the extent of lipoperoxidation in essential hypertensive patients and the status of enzymatic and non-enzymatic antioxidants that potentially are able to modulate it METHODS: We selected 105 newly diagnosed essential hypertensives among those referred to our hypertension outpatient clinic and compared them with 100 normotensive controls matched for age. Plasma malondialdehyde was measured by high-performance liquid chromatography after reaction with thiobarbituric acid, as an end product of lipid peroxidation; serum selenium (Se), plasma copper (Cu) and zinc (Zn), vitamins A and E, erythrocyte superoxide dismutase and glutathione peroxidase levels were evaluated as indices of oxidant balance. Differences between the groups were tested by Student's t test and chi2 test. RESULTS: Compared with controls, essential hypertension patients had higher malondialdehyde and glutathione peroxidase activities (P<0.05 for both) and Zn concentrations (P<0.001) and lower superoxide dismutase activities (P<0.005), vitamin A (P<0.05) and E (P<0.001) levels and Cu concentrations (P<0.005). We found no difference between Se levels of essential hypertensive and control subjects. CONCLUSIONS: Essential hypertension is associated with greater than normal lipoperoxidation and an imbalance in anti-oxidant status, suggesting that oxidative stress is important in the pathogenesis of essential hypertension or in arterial damage related to essential hypertension.

Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction.

Moderate elevation of plasma total homocysteine (tHcy) is a strong and independent risk factor for coronary artery disease (CAD). It can result from genetic or nutrient-related disturbances in the transsulfuration or remethylation pathways for Hcy metabolism. A point mutation (C677T; Ala-to-Val) in the gene encoding the 5, 10-methylenetetrahydrofolate reductase (MTHFR) has been recently reported to render the enzyme thermolabile and less active. Studies on the role of this mutation as a risk factor for CAD have given conflicting results. We studied a total of 415 subjects, 278 with angiographically documented multivessel CAD and 137 with angiographically documented normal coronary arteries. The overall frequency of the MTHFR V/V homozygous genotype was 15.7% (with 52.5% heterozygous and 31.8% normal). Subgroup analysis showed no significant differences between CAD and CAD-free subjects. A genotype/phenotype correlation study showed a marked effect of folate on the association between MTHFR genotypes and tHcy. Among individuals with folate levels below the median (11.5 nmol/L), fasting tHcy was significantly increased not only in V/V homozygotes (by 59%) but also, at intermediate values, in A/V heterozygotes (by 21% on average). Conversely, the mutation resulted neutral with respect to tHcy levels in subjects with adequate folate levels. We conclude that, in our population, the MTHFR C677T mutation is rather common, but it does not appear to be associated per se to CAD. A genetic-environmental interaction may contribute to the vascular risk by elevating tHcy when folate status is low.

Increase in circulating products of lipid peroxidation in smokers with IDDM.

OBJECTIVE: To measure plasma malondialdehyde (MDA) concentration, a product of lipid peroxidation, both in IDDM patients and in healthy control subjects and to examine whether smoking has a negative impact on the plasma MDA levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma total MDA concentration (as a thiobarbituric acid adduct by high-performance liquid chromatography) was measured in 56 young IDDM patients and in a group of 32 age-, sex-, BMI-, and smoking habit-matched healthy subjects. RESULTS: Plasma MDA concentration in IDDM patients was significantly higher than that in healthy control subjects (mean +/- SE: 0.95 +/- 0.03 vs. 0.54 +/- 0.03 mumol/l; P < 0.0001). After stratification by smoking status, it was seen that diabetic smokers had values of age, BMI, serum lipids, blood pressure, metabolic control, and diabetes duration and its chronic complications superimposable on those of their nonsmoking counterparts. Nevertheless, plasma MDA concentration was significantly higher in IDDM patients who smoked than in IDDM patients who didn't smoke (1.03 +/- 0.4 vs. 0.87 +/- 0.03 mumol/l; P = 0.002), without any sex difference with regard to MDA levels. CONCLUSIONS: These data show an increase in circulating products of lipid peroxidation in young diabetic smokers, thus further supporting the clinical importance of discouraging the initiation of smoking as well as promoting its cessation in people with IDDM.

Mechanisms involved in the in vitro modification of low density lipoprotein by human umbilical vein endothelial cells and copper ions.

In this study we evaluated the time course and mechanism of low density lipoprotein (LDL) oxidation induced by human umbilical vein endothelial cells (HUVECs), cell-free medium (CFM) and Cu2+. After incubating LDL (200 micrograms/ml) with HUVECs, CFM and Cu2+ (concentration adjusted to obtain the same degree of LDL modification as with HUVECs), the extent of LDL lipid peroxidation and apoprotein B modification was monitored at different times from 0 to 24 h. This involved evaluating the time course of LDL conjugated diene, peroxide, malonyldialdehyde (MDA), fluorescence, relative electrophoretic mobility (REM), vitamin E and monounsaturated and polyunsaturated fatty acids. After incubation with HUVECs, the LDL REM was significantly higher than that obtained in CFM (p < 0.01). When balanced for the same degree of LDL modification as obtained with HUVECs, Cu2+ gave a REM similar to that obtained with HUVECs. At the different times of incubation there was no statistical difference between conjugated diene and peroxide values after incubation with HUVECs and with CFM. The values obtained with Cu2+ were significantly higher than those obtained with HUVECs and CFM (p < 0.01). MDA and LDL fluorescence were significantly higher after exposure to HUVECs than to CFM (p < 0.01), values being similar to those obtained with Cu2+. There was no statistical difference between the values of LDL oleic, linoleic, arachidonic and eicosapentaenoic acids after incubation with HUVECs and CFM. Eicosatetraynoic acid (ETYA), a lipoxygenase inhibitor, determined dose-dependent reduction of MDA formation induced by the incubation of LDL with HUVECs; it did not affect LDL conjugated diene. ETYA did not have any effect on the MDA derived from LDL after incubation with Cu2+ or CFM. The results of this study demonstrate that, unlike Cu2+, the contribution of HUVECs to LDL modification does not involve only lipid peroxidation of the lipoprotein; it also includes intracellular radical and non-radical processes.

Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidogenesis by adrenals and gonads.

Plasma lipoproteins are a major source of cholesterol for steroid hormone synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors, which reduce both intracellular cholesterol synthesis and serum cholesterol levels, thus have a potential negative impact on steroidogenesis. In this study, we evaluated basal and maximally stimulated adrenocortical and testicular steroidogenesis in 24 hypercholesterolemic male subjects during 6-36 months of statin treatment. One group was evaluated before treatment and after 6 months of treatment. A second group, which received long term treatment, was evaluated after 24-36 months and then 2 months after treatment had been discontinued. Fourteen subjects were given simvastatin, and 12 were given pravastatin, both at the maximum therapeutic dosage of 40 mg/day. During statin therapy, serum cholesterol was lowered by about 30%. Basal serum and urinary cortisol levels as well as serum cortisol response to ACTH were not influenced by statin therapy. Basal serum testosterone and its response to hCG were also unchanged by statin treatment. In addition, steroid hormone urinary metabolites were strikingly similar when patients were given HMG-CoA reductase inhibitors and when they were not. These results indicate that maximum therapeutic doses of statins have no negative impact on adrenocortical and testicular steroidogenesis even when these glands are maximally stimulated.

The susceptibility of low-density lipoprotein to in vitro oxidation is increased in hypercholesterolemic patients.

It has been suggested that the oxidative modification of low-density lipoprotein (LDL) plays a major role in atherogenesis. We evaluated the oxidative resistance to copper-induced oxidative changes of LDL derived from patients affected by type IIa hyperlipoproteinemia compared with healthy subjects and faced the question of the importance of the antioxidants and polyunsaturated fatty acids (PUFAs) contained in LDL in determining its variability. LDL isolated from the plasmas of 25 subjects affected by familial hypercholesterolemia and 15 control subjects was oxidatively modified with Cu2+ in vitro, and the differences in LDL susceptibilities (lag and propagation phases) to lipid peroxidation were studied by measuring the changes in fluorescence intensity. LDL alpha-tocopherol and PUFAs were also measured. The lag phase was significantly lower and the propagation phase significantly higher in the type IIa patients than in control subjects (p < 0.01). The linoleic and arachidonic acids, expressed as percentage of total LDL fatty acids, were significantly higher in type IIa patients than in the control subjects (p < 0.01). There was a positive significant correlation between the LDL cholesterol and the linoleic and arachidonic acids as percentage of total LDL fatty acids (p < 0.01). Both linoleic and arachidonic acids turned out to be negatively correlated with the lag phase and positively with the propagation phase (p < 0.01). The concentration of LDL alpha-tocopherol was similar in the two groups. Therefore, type IIa patients have a greater susceptibility to LDL oxidation than control subjects. This may be due to a relative higher concentration of linoleic and arachidonic acids in LDL derived from patients with familial hypercholesterolemia.