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Background Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. Methods Healthy volunteers [10] were given supplementation at 4 g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. Results Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4 h = −0.5 ± 1.2 vs. −2.0 ± 1.6%, P = 0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2–4 h, and returned to baseline at 8 h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve = 220 ± 209 vs. 374 ± 216 mg/h/dL, P = 0.04) and remnant lipoprotein-cholesterol (incremental area under the curve = 21.7 ± 13.8 vs. 13.3 ± 12.9 mg/h/dL, P = 0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4 h after the cookie test. Conclusion Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state.

Residual risk of cardiovascular disease from increased small dense low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this study was to evaluate the effect of ezetimibe as an add-on to statins and supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of EPA in patients with coronary artery disease. The study population consisted of ten male patients who were concurrently receiving statins and EPA 1,800 mg/day. Serum lipids and PUFAs, including EPA and arachidonic acid, were measured in blood samples collected before ezetimibe (baseline), 4 weeks after starting 10-mg/day ezetimibe, and 4 weeks after discontinuing ezetimibe. Ezetimibe significantly decreased sdLDL-cholesterol levels after 4 weeks of treatment (baseline 35 ± 13 mg/dl; treatment 27 ± 9 mg/dl), but the levels returned to baseline after discontinuation of ezetimibe (37 ± 13 mg/dl). The concentration of EPA did not significantly change during the study. Ezetimibe shows great promise as an add-on therapy to statins to reduce sdLDL-cholesterol-related residual risk of cardiovascular disease without affecting absorption of supplemental EPA in patients with coronary artery disease.

Background Several lines of evidence suggest that atrial fibrillation (AF) may be a consequence of vascular disease. We investigated the relationship between cardio-ankle vascular index (CAVI), a new index of arterial stiffness, and the presence of paroxysmal AF (PAF). Methods and results 181 outpatients (91 patients with PAF and 90 age- and gender-matched subjects without PAF) were analysed for their sinus rhythm. The CAVI was significantly higher in patients with PAF than in subjects without PAF (9.0±1.0 vs 8.7±0.8, p

BACKGROUND No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans. METHODS AND RESULTS In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10). CONCLUSIONS In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

Background Postprandial elevation of triglyceride-rich lipoproteins impairs endothelial function, which can initiate atherosclerosis. We investigated the effects of bezafibrate on postprandial endothelial dysfunction and lipid profiles in patients with metabolic syndrome. Methods Ten patients with metabolic syndrome were treated with 400 mg/day bezafibrate or untreated for 4 weeks in a randomized crossover study. Brachial artery flow-mediated dilation (FMD) and lipid profiles were assessed during fasting and after consumption of a standardized snack. Serum triglyceride and cholesterol contents of lipoprotein fractions were analyzed by high-performance liquid chromatography. Results Postprandial FMD decreased significantly and reached its lowest value 4 h after the cookie test in both the bezafibrate and control groups, but the relative change in FMD from baseline to minimum in the bezafibrate group was significantly smaller than that in the control group (-29.0 ± 5.9 vs. -42.9 ± 6.2 %, p = 0.04). Bezafibrate significantly suppressed postprandial elevation of triglyceride (incremental area under the curve (AUC): 544 ± 65 vs. 1158 ± 283 mg h/dl, p = 0.02) and remnant lipoprotein cholesterol (incremental AUC: 27.9 ± 3.5 vs. 72.3 ± 14.1 mg h/dl, p

Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the devel- opment of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl pepti- dase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow‑mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantl y suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No signifi - cant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vilda- gliptin may be a promising antiatherogenic agent.

Adrenoleukomyeloneuropathy (ALMN) usually occurs in adulthood, it being extremely rare in childhood. We reported a quite atypical clinical case of ALMN as a variant of adrenoleukodystrophy (ALD). The onset was at 5 years 7 months and ataxia was the major symptom. His condition progressed rapidly to a vegetative state within 1 year. At the age of 11 years and 11 months he died of pneumonia and an autopsy was performed. We herein reported the neuropathological findings in this rare case. The autopsy revealed marked atrophy with diffuse demyelination and astrogliosis throughout the cerebrum, cerebellum and brainstem. Massive degeneration of the pyramidal tracts and loss of neurons were also seen in the spinal cord. The adrenal cortex showed marked atrophy with a striated cytoplasm in ballooned cells. These findings include pathological characteristics of both ALD and adrenomyeloneuropathy (AMN), suggesting ALMN. However, diffuse demyelination with gliosis in the cerebrum and cerebellum is quite atypical for ALMN. They might explain his atypical clinical course, especially the early onset of the disease with ataxia and rapid deterioration.

We investigated the prognosis of epilepsy in 54 patients with severe motor and intellectual disabilities syndrome (SMIDS). The prevalence of epilepsy was 75.7% in our institution for SMIDS. We assessed activities of daily living (ADL) of them at the onset of epilepsy and at present, according to the scores in locomotion, language, toileting, dressing and feeding. Among them, patients with uncontrolled epilepsy constituted 40.3%. ADL scores worsened in the uncontrolled group, while they improved in other cases. Early seizure control is very important in SMIDS for improving patients' quality of life.

Background Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile. Methods A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test. Results Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04). Conclusion Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.

当科で経過観察中の131例の重症心身障害 (重障) 児・者のてんかんについて予後を中心に検討を行い, 次の2つの特徴をまとめた。(1) 重障児・者のてんかんの予後においても, 一般のてんかんの予後と同様に思春期前後で発作コントロールの得られる一群がある。(2) 一方, 大部分は発作コントロールが不良である。コントロール良好な群の特徴としては (1) 基礎疾患として, 痙性両麻痺とアテトーゼの型の脳性麻痺が多い。(2) 脳障害の既往のない例が多い。(3) 発作型では全般性強直間代発作が多い。コントロール不良な群の特徴としては (1) 基礎疾患として, 重度痙性四肢麻痺の型の脳性麻痺が多い。(2) 成因として出生時・出生後要因による脳障害を有する例が多い。(3) 発作型では混合型発作, ミオクロニー発作, 脱力発作が多い。(4) てんかん分類では未決定てんかんが多い。