Administration timing and duration-dependent effects of sesamin isomers on lipid metabolism in rats.

Metabolism of lipids such as cholesterol and triglycerides has daily variations and is controlled by a circadian clock. Sesamin isomers, a mixture of sesamin and episesamin (SE), are types of lignans in sesame seed that have shown the improvement of lipid metabolism with various diseases in an animal model. We therefore tested whether the effects of SE on lipid metabolism are influenced by timing of administration. High-fat diet (HFD)-loaded rat was administered SE in the ZT13 or 14 (at the beginning of the active phase) or ZT23 or 22 (at the end of the active phase) every day for 7 or 28 days, and the effects on lipid metabolism were evaluated. The effects of SE were enhanced by duration-dependency: 28-day administration of SE strongly affected some parameters related to lipid metabolism, particularly cholesterol metabolism, as compared to 7-day administration. In particular, in 28-day administration, the analysis of serum and liver cholesterol levels revealed that SE administration decreases more effectively at the beginning of the active phase when compared to at the end of that. Furthermore, quantitative real-time polymerase chain reaction (QRT-PCR) and functional analysis indicated that suppression of cholesterol synthesis in the liver and promotion of cholesterol excretion from the liver, as well as inhibition of the functional activity and gene expression of sterol response element-binding protein 2 (Srebp2), which is a transcriptional factor and controls the gene expression involved in cholesterol-metabolism enzymes, contribute to enhancement of SE's effects at this administration timing. No significant differences were observed in triglyceride metabolism with regard to timing of SE administration. After 28-day administration of SE, administration at the beginning of the active phase only affected the expression of clock genes in the liver with phase-advance. In the pharmacokinetic study, administration time had no effect on the level of sesamin, episesamin or their metabolites in the liver after administration of SE for 28 days. The present results suggest that continuous long administration of SE at the beginning of the active phase is preferable for obtaining beneficial effects on lipid metabolism.

Effects of unilateral sinonasal surgery on sleep-disordered breathing.

Aims/objectives: To examine the effects of surgery for unilateral sinonasal lesions on sleep-disordered breathing (SDB). Material and methods: Oxygen desaturation index (3%ODI) as a marker of SDB and bilateral/unilateral nasal resistance were measured before and after surgery for 18 patients with unilateral sinonasal lesions. Various parameters were compared between those who achieved 60% or less decrease of 3%ODI and those who did not. Results: Bilateral nasal resistance as well as that of the surgical side five days after surgery was significantly lower than those of pre-operative value. Preoperative 3%ODI (times/hour) was 10.08 ± 7.32, which significantly decreased to 7.67 ± 5.79 five days after surgery. Even in unilateral patients, sinonasal surgery could reduce the bilateral nasal resistance, resulting in a decrease in 3%ODI. Age was younger and postoperative nasal resistance of the surgical side was significantly lower in the group who achieved 60% or less decrease in 3%ODI than those who did not. Conclusions and significance: SDB is influenced by even unilateral nasal obstruction. Surgery for unilateral lesion can improve the respiration during sleep as well as bilateral nasal resistance. Favorable outcome by surgery could be brought about in younger patients and those for whom sufficient improvement of nasal resistance was expected by surgery.

Mechanisms and prevention of sudden death in multiple system atrophy.

BACKGROUND: Sudden death in multiple system atrophy (MSA) usually occurs during sleep and was therefore attributed to suffocation resulting from vocal cord abductor paralysis, a characteristic laryngeal finding of MSA. This led to the use of tracheostomy and noninvasive positive pressure ventilation (NPPV) for the prevention of sudden death. However, neither method has been able to prevent sudden death, and both have occasionally precipitated treatment-related complications, including central sleep apneas and exacerbation of floppy epiglottis. Therefore, it is important to determine the mechanisms and prevention of sudden death in MSA. METHODS: We reviewed the literature on the mechanisms and prevention of sudden death in patients with MSA. RESULTS: Sudden death in MSA is hypothesized to be a consequence of disordered central respiration, suffocation caused by sputum and food, upper airway obstruction from NPPV acting on a floppy epiglottis, cardiac autonomic disturbance, or a combination of these factors. CONCLUSION: Various factors may be involved in the mechanism of sudden death in MSA. A multidisciplinary approach is needed to prevent sudden death, and this requires an organized system of several medical specialties. Neurologists require a cooperative network that includes experts in otorhinolaryngology, sleep medicine, dysphagia rehabilitation, and cardiology.

Does motor dysfunction after cerebral infarction impede the development of angina symptoms? A comparison of coronary angiographic findings in patients with and without prior cerebral infarction.

Previous studies based on coronary angiography or computed tomography coronary angiography have demonstrated a high prevalence of coronary stenosis in patients with cerebral infarction and no prior history of coronary artery disease (CAD). The purpose of the present study was to compare the coronary angiographic findings of patients with prior cerebral infarction with those of patients with no prior cerebral infarction. Consecutive patients (n = 126) who underwent a first coronary angiography for suspected CAD but had no prior history of CAD were classified into 2 groups, those with a clinical history of cerebral infarction (cerebral infarction group) and those without a clinical history of cerebral infarction (noncerebral infarction group). The incidences of diabetes mellitus, peripheral artery disease, coronary stenosis, and multivessel disease were significantly higher in the cerebral infarction group than in the noncerebral infarction group. Multiple logistic regression analysis relating to coronary stenosis identifi ed prior cerebral infarction (P = 0.0027, odds ratio = 4.414) and diabetes mellitus (P = 0.0446, odds ratio = 2.619) as explanatory factors. Thirty-four of 78 patients (44%) with coronary stenosis did not have angina symptoms. Multiple logistic regression analysis regarding the lack of angina symptoms identified motor dysfunction (modified Rankin scale ≥ 2) (P = 0.0028, odds ratio = 8.323) as an explanatory factor. The results of the present study suggest that compared with patients without cerebral infarction those with the disorder have a high prevalence of coronary stenosis, and indicate that the development of angina symptoms is influenced by the severity of motor dysfunction.

Bcl11b heterozygosity leads to age-related hearing loss and degeneration of outer hair cells of the mouse cochlea.

BCL11B/CTIP2 zinc-finger transcription factor is expressed in various types of cells in many different tissues. This study showed that BCL11B is expressed in the nucleus of the outer hair cells of the mouse cochlea, degeneration of which is known to cause deafness and presbycusis or age-related hearing loss (AHL). We tested whether or not Bcl11b heterozygosity would affect AHL in mice. Analysis of auditory brainstem responses revealed AHL in Bcl11b (+/-) heterozygous, but not wild-type, mice, which was evident as early as 3 months after birth. Histological abnormalities were observed in the outer hair cells of the Bcl11b (+/-) mice at 6 months of age with hearing loss. These results suggest that the AHL observed in Bcl11b (+/-) mice is the result of impairment of the outer hair cells and that BCL11B activity is required for the maintenance of outer hair cells and normal hearing.

Epidemiological and clinical patterns of western pacific amyotrophic lateral sclerosis (ALS) in Guam and sporadic ALS in Rochester, Minnesota, U.S.A. and Hokkaido, Japan: a comparative study.

Western Pacific amyotrophic lateral sclerosis (ALS) in Guam, so-called Guam ALS, is a neurodegenerative disease with a high incidence among the indigenous population, Chamorros, in Guam. To clarify the differences in the epidemiological and clinical features between Guam ALS and sporadic ALS, the surveys were conducted in Guam for the periods from 1980 to 1989, in Rochester, MN, USA from 1952 to 1991 and in Hokkaido, Japan from 1980 to 1989. The crude incidence rate of Guam ALS was 7.5/100,000/year, which was much higher than the rates of sporadic ALS, 2.3/100,000/year in Rochester and 0.6/100,000/year in Hokkaido, although it was markedly low as compared with that in the most frequent period between 1950-1960s. There was no remarkable change in the incidence rate either in Rochester or Hokkaido island during the above study periods. The average age of onset of Guam ALS was 56, which was more than 10 years advancement occurring in the past 40 years, although it was still younger than 68 and 58 in the sporadic ALS cases in Rochester and Hokkaido island, respectively. The average duration of the illness in Guam ALS was 36 months, which was almost the same as those in Rochester (31 months) and Hokkaido (31 months). The changing ecology and socioeconomic conditions in the past 40 years in Guam might have contributed to the drastic reduction in the environmental risk factors. However, the incidence remains high during the past decade, which suggests their genetic predisposition to Guam ALS.