Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

Background: Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles.

Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins.

Background: There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks.

Methods: Lipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets.

Efficacy and safety of sitagliptin for the treatment of diabetes mellitus complicated by chronic liver injury.

Aim: To investigate the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, sitagliptin, for treating diabetes mellitus complicated by chronic liver injury.

Methods: Sitagliptin was administered for 13.7 ± 10.

A Case of Rathke's Cleft Cyst Associated with Transient Central Adrenal Insufficiency and Masked Diabetes Insipidus.

A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm.

Well-defined iron complexes as efficient catalysts for "green" atom-transfer radical polymerization of styrene, methyl methacrylate, and butyl acrylate with low catalyst loadings and catalyst recycling.

Environmentally friendly iron(II) catalysts for atom-transfer radical polymerization (ATRP) were synthesized by careful selection of the nitrogen substituents of N,N,N-trialkylated-1,4,9-triazacyclononane (R3 TACN) ligands. Two types of structures were confirmed by crystallography: "[(R3 TACN)FeX2 ]" complexes with relatively small R groups have ionic and dinuclear structures including a [(R3 TACN)Fe(μ-X)3 Fe(R3 TACN)](+) moiety, whereas those with more bulky R groups are neutral and mononuclear. The twelve [(R3 TACN)FeX2 ]n complexes that were synthesized were subjected to bulk ATRP of styrene, methyl methacrylate (MMA), and butyl acrylate (BA).

Lowering LDL cholesterol, but not raising LDL receptor activity, by ezetimibe.

Background: Ezetimibe, an inhibitor of intestinal cholesterol absorption, is effective in lowering serum low-density lipoprotein (LDL) cholesterol with or without coadministration of statin. Ezetimibe-plus-statin therapy enhances LDL receptor activity, but it is still unclear whether ezetimibe alone enhances LDL receptor activity, resulting in LDL cholesterol decrease.

Objective: We investigated whether ezetimibe lowers serum LDL cholesterol by raising LDL receptor activity in humans.

RESEARCH (Recognized effect of Statin and ezetimibe therapy for achieving LDL-C Goal), a randomized, doctor-oriented, multicenter trial to compare the effects of higher-dose statin versus ezetimibe-plus-statin on the serum LDL-C concentration of Japanese type-2 diabetes patients design and rationale.

Aims: Hypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses. No second-step strategy is established, however, for cases where strong statins fail to bring cholesterol down to target levels. In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia.

Statin-induced Ca(2+) release was increased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment.

Aim: Statins are effective in lowering cholesterol levels, but cause fatal rhabdomyolysis in susceptible individuals. Because it has been hypothesized that muscle damage could result from alterations in Ca(2+) homeostasis in muscle cells, we tested whether measuring statin-induced changes in intracellular calcium ([Ca(2+)](i)) is useful for predicting susceptibility to statin-muscle damage, using human CD19+ primary B lymphocytes.

Methods: Statin-induced alterations in [Ca(2+)](i) were studied using the human THP-1 cell line and CD19+ primary B lymphocytes.

Circulating levels of ganglioside GM3 in metabolic syndrome: A pilot study.

Background: Insulin resistance is a characteristic feature of metabolic syndrome. Ganglioside GM3 [α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-ceramide] may impair insulin sensitivity in adipose tissue. We investigated the relationship between serum GM3 levels and adiposity indices, as well as between serum GM3 levels and metabolic risk variables.

Distribution of dolichol in the serum and relationships between serum dolichol levels and various laboratory test values.

We examined the correlations between serum dolichol levels and laboratory test parameters in patients affected by disease, as well as the distribution of dolichol in sera from patients with hyperbetalipoproteinemia and hyperalphalipoproteinemia. Serum dolichol was evaluated by a reverse-phase HPLC method. After centrifugation, the serum dolichol found in healthy controls was mainly associated with medium-sized particles of the high-density lipoprotein (HDL) fraction.

Bromocriptine-responsive Cushing's disease; clinical and biochemical remission accompanied by amelioration of impaired ocular movement.

A 73-year-old woman presented with disturbance of right eyelid opening with ptosis and impairment of right ocular movement, and later was found to have Cushingoid features. Endocrine examinations revealed that plasma ACTH and cortisol levels were elevated, lack of circadian rhythm, resistant to low-doses (0.5, 1, 2 mg) and high-dose (8 mg) dexamethasone, and responsive to CRH and DDAVP.

Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma.

Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its detailed mechanism remains elusive. The present study was designed to determine whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative modification was investigated by a method using 2,2'-azobis or Cu2+.

Enhanced susceptibility of LDL to oxidative modification in a CTX patient:- role of chenodeoxycholic acid in xanthoma formation.

Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease, causing multiple xanthomas in tendons and the brain. The underlying biochemical defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of chenodeoxycholic acid (CDCA). It has been reported that administration of CDCA to CTX patients improves neurological disorders and xanthomas of the Achilles tendon.

Modulation of HDL metabolism by probucol in complete cholesteryl ester transfer protein deficiency.

Probucol, an antioxidative and hypolipidemic agent, has been postulated to increase reverse cholesterol transport by enhancing cholesteryl ester transfer protein (CETP) activity. However, its clinical implication in CETP deficient patients has not been fully defined. To characterize the effects of probucol in the absence of CETP, we evaluated the changes in lipid profile, lipid peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient patients, caused by treatment with probucol.

Nickel(0)-mediated sequential addition of carbon dioxide and aryl aldehydes into terminal allenes.

[reaction: see text] Nickel-mediated sequential addition of carbon dioxide and aryl aldehydes into terminal allenes is reported. The reaction proceeded in a diastereoselective manner to afford alpha-methylene-gamma-hydroxy carboxylic acids, which allowed stereoselective preparation of cis-beta, gamma-disubstituted alpha-methylene-gamma-lactones.

Human plasma platelet-activating factor acetylhydrolase binds to all the murine lipoproteins, conferring protection against oxidative stress.

Objective: Plasma platelet-activating factor (PAF) acetylhydrolase (AH) is an enzyme bound with lipoproteins that degrades not only PAF but also PAF-like oxidized phospholipids that are proposed to promote atherosclerosis. In this study, we investigated the distribution of PAF-AH protein among lipoprotein classes by using adenovirus-mediated gene transfer in mice, and we examined its effects on lipoprotein oxidation and foam cell formation of macrophages.

Methods And Results: Adenovirus-mediated overexpression of PAF-AH in mice resulted in a 76- to 140-fold increase in plasma PAF-AH activity.

Ascorbic acid augments cytotoxicity induced by oxidized low-density lipoprotein.

Although ascorbic acid (ASA) is known as a water-soluble antioxidant, we found that it accelerated the cytotoxicity induced by oxidized low-density lipoprotein (OxLDL) in vitro. This suggests that ASA may enhance the oxidation of LDL to augment the atherogenic activities of OxLDL under certain conditions. Thus, this study was designed to investigate the underlying mechanism that ASA enhances OxLDL-induced cytotoxicity.

Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of CHD.

We evaluated a 69-year-old Japanese woman with apolipoprotein (apo) A-I deficiency, high levels of low-density lipoprotein (LDL)-cholesterol, hypertension and impaired glucose tolerance. The patient had corneal opacity, but neither xanthomas, xanthelasma, nor tonsillar hypertrophy. She was not symptomatic for coronary heart disease (CHD), and had normal electrocardiograms at rest and exercise using a cycle ergometer.