Effect of L-Carnitine on Amino Acid Metabolism in Elderly Patients Undergoing Regular Hemodialysis.

INTRODUCTION: Among patients regularly undergoing hemodialysis, hypocarnitinaemia often develops as a consequence of inadequate dietary intake, reduced synthesis in the body, and considerable losses during hemodialysis. OBJECTIVES: To evaluate the effects of L-carnitine supplementation on patients with end-stage kidney disease (ESKD) who underwent hemodialysis. METHODS: Thirty-one patients with ESKD, comprising 18 men and 13 women, with a median age of 72 (range 58-89) years, who underwent regular hemodialysis received treatment with L-carnitine for 1 year. The total and free carnitine, acylcarnitine, and amino acids (AA) levels before and after L-carnitine treatment were analyzed, and the blood biochemistry results and clinical profiles of the subjects were compared before and after treatment. RESULTS: The median (interquartile range [IQR]) serum total and free carnitine and acylcarnitine levels significantly increased from 34.5 (28.2-44.3), 20.9 (15.8-27.6), and 14.1 (11.2-17.6) µmol/L, respectively to 407.4 (371.6-493.5), 270.2 (228.3-316.0), and 155.0 (136.1-168.5) µmol/L, respectively, after treatment (all p < 0.001). The median (IQR) blood valine, tyrosine, phenylalanine, and citrulline levels increased from 0.94 (0.80-1.09), 0.45 (0.39-0.55), 0.61 (0.56-0.79), and 1.04 (0.79-1.26) mg/dL, respectively to 1.24 (1.13-1.54), 0.76 (0.62-0.85), 0.90 (0.70-1.04), and 1.22 (0.92-1.39) mg/dL, respectively, following L-carnitine treatment (p < 0.001, p < 0.001, p = 0.002, and p = 0.030, respectively); however, the median (IQR) blood arginine level decreased from 0.20 (0.13-0.24) to 0.09 (0.06-0.14) mg/dL after treatment (p < 0.001). The median (IQR) percentage fractional shortening (41.5 vs. 41.9%; p = 0.012) and left ventricular ejection fraction (65.2 vs. 67.3%; p = 0.036) increased significantly following treatment. CONCLUSIONS: L-Carnitine increased the blood acylcarnitine levels, enhanced fatty acid metabolism, and affected AAs metabolism; this may be beneficial for energy production within the cardiac and skeletal muscles.

Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections.

Major outputs of the neocortex are conveyed by corticothalamic axons (CTAs), which form reciprocal connections with thalamocortical axons, and corticosubcerebral axons (CSAs) headed to more caudal parts of the nervous system. Previous findings establish that transcriptional programs define cortical neuron identity and suggest that CTAs and thalamic axons may guide each other, but the mechanisms governing CTA versus CSA pathfinding remain elusive. Here, we show that thalamocortical axons are required to guide pioneer CTAs away from a default CSA-like trajectory. This process relies on a hold in the progression of cortical axons, or waiting period, during which thalamic projections navigate toward cortical axons. At the molecular level, Sema3E/PlexinD1 signaling in pioneer cortical neurons mediates a "waiting signal" required to orchestrate the mandatory meeting with reciprocal thalamic axons. Our study reveals that temporal control of axonal progression contributes to spatial pathfinding of cortical projections and opens perspectives on brain wiring.

Dietary supplementation with arachidonic acid but not eicosapentaenoic or docosahexaenoic acids alter lipids metabolism in C57BL/6J mice.

In order to investigate the effects of dietary supplementation rich in omega 3 and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted for 1 month, food consumption of ND and n-3 PUFA were similar while it decreased in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA while increased in n-6 PUFA fed mice comparing to control group. On the other hand, there was no difference between treatments in HDL and glucose levels. Expression of leptin (ob) gene transcripts in epididymal fat were significantly elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic ob receptor A (obRa) mRNA did not changed in response to diet regimes. Transmission and scanning electron microscopy showed different degrees in fatty changes in the liver of both PUFA groups including lipid droplet infiltration and Ito cells with over accumulated lipids. In conclusion, under PUFA dietary supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups and/or different endocrine involvement. Moreover, the coincidently structural changes observed in liver of this group direct us to call for further studies to investigate the anti-obesity effect and safety of these PUFA under high supplementation condition.

The influences of method of calcium correction and the timing of blood collection on application of the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Japan.

We investigated the treatment of renal osteodystrophy (ROD) in Japan and problems concerning the K/DOQI Guidelines. The subjects were 3698 hemodialysis patients (2328 males and 1370 females) with a mean age of 61.4 years. On average, they had been on hemodialysis for 8.34 years. The serum phosphorus level was <3.5 mg/dL in 5% of the subjects, 3.5-5.5 mg/dL in 49%, 5.6-7.0 mg/dL in 33%, and >7.0 mg/dL in 13%. The serum calcium level was <8.4 mg/dL in 16% of the subjects, 8.4-9.5 mg/dL in 47%, 9.5-10.2 mg/dL in 22%, and >10.2 mg/dL in 15%. The intact PTH level was <150 pg/mL in 57%, 150-300 pg/mL in 27%, and >300 pg/mL in 16% of the patients. The first problem is that correcting Ca is not always performed in clinical fields. The uncorrected calcium level was 9.14+/-0.92 mg/dL, while the corrected calcium level [Ca = Ca + 0.8 x (4-Alb)] was 9.26+/-0.93 mg/dL (P < 0.05). The second problem is that the timing of blood collection is not described in the K/DOQI Guidelines. Subjects with a serum phosphorus level >7.0 mg/dL at 3 days after the previous dialysis were selected for assessment. In these patients, the midweek serum phosphorus level (7.13+/-0.15 mg/dL) at was significantly lower than that (8.11+/-0.15 mg/dL) at the beginning of the next week (P < 0.001). These results suggest that it is necessary to specify the timing of measurement and the method of Ca correction when guidelines for management of ROD are established in the future.

Mean corpuscular volume (MCV) and the risk of colorectal adenoma in menopausal women.

BACKGROUND/AIMS: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume is increased under these conditions. We have reported that the mean corpuscular volume was higher in patients with adenoma than without adenoma in middle-aged men. The aim of this study was to assess the association between mean corpuscular volume and risk of colorectal adenoma in menopausal women. METHODOLOGY: The subjects were 415 menopausal women who underwent both barium enema examination and total colonoscopy, and their blood samples were analyzed. The subjects were divided into two groups with or without adenoma, and were divided into four groups according to the mean corpuscular volume value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The mean corpuscular volume was higher in patients with adenoma than without adenoma (P = 0.002). As for the mean corpuscular volume value, the odds ratio (95% CI) of patients with adenoma was 1.00 (referent); (mean corpuscular volume (fl) < 90), 1.50 (0.93-2.07); (> or = 90 but < 92.5), 1.52 (0.97-2.07); (> or = 92.5 but < 95) and 2.87 (2.25-3.45); (> or = 95). CONCLUSIONS: Mean corpuscular volume > or = 95 may be used as an index of the risk for colorectal adenomas in menopausal women.