Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.

Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease.

OBJECTIVE -Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women.RESEARCH DESIGN AND METHODS -We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 Ϯ 3 years.RESULTS -Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 Ϯ 111.2 vs. 972.5 Ϯ 97.7 mol/l in men, P Ͻ 0.001; 579.8 Ϯ 95.4 vs. 930.1 Ϯ 84.2 in women, P Ͻ 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 Ϯ 2.2 vs. 2.0 Ϯ 0.7 mol/l in men, P Ͻ 0.001; 8.1 Ϯ 1.9 vs. 2.2 Ϯ 0.6 in women, P Ͻ 0.001), higher total conjugated diene (CD) levels (0.037 Ϯ 0.003 vs. 0.033 Ϯ 0.002 A.U. in men, P Ͻ 0.001), lower 246-nm CD levels (0.0032.Ϯ 0.0010 vs. 0.0070 Ϯ 0.0012 A.U. in men, P Ͻ 0.001; 0.0022 Ϯ 0.0011 vs. 0.0072 Ϯ 0.0014 A.U. in women, P Ͻ 0.001), and higher 232-nm CD levels (0.0348 Ϯ 0.0041 vs. 0.0257 Ϯ 0.0022 A.U. in men, P Ͻ 0.001; 0.0346 Ϯ 0.0031 vs. 0.0246 Ϯ 0.0074 A.U. in women, P Ͻ 0.001). Compared with diabetic men, diabetic women had lower TRAP (P Ͻ 0.01), higher ROOH levels (P Ͻ 0.01), and lower 246-nm CD levels (P Ͻ 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 Ϯ 0.3 vs. 4.3 Ϯ 0.2 mg/dl; P ϭ 0.009) with a significant difference between women and men with type 1 diabetes (2.6 Ϯ 0.3 vs. 3.9 Ϯ 0.3, respectively; P ϭ 0.009).CONCLUSIONS -Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications.

Our retrospective study confirms that morbidity and mortality rates in treatment with FDD of unruptured wide-neck or untreatable cerebral aneurysms do not differ from those reported in the largest series.

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This study shows the importance of medical nutritional therapy on glycaemic control in Type 1 diabetic subjects.

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.