Sleep habits of students attending elementary schools,and junior and senior high schools in Akita prefecture

It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.     

Growth inhibitory effect of paradicsompaprika in cancer cell lines

We investigated whether components of paradicsompaprika have direct antitumor effects or inhibitory effects on cancer growth, using its water extract. We applied collagen gel droplet embedded culture drug sensitivity test (CD-DST) as a screening method, which was developed based on the characteristics of cell culture on collagen matrix. Colon adenocarcinoma cells, epithelial cells of lung cancer, and cervical cancer cells were used. Paradicsompaprika is classified as Capsiucum annume L. var. grossum of Solanaceae. It is the first of the Hungarian species that was planted in Japan. It is available as TOMA-P in Japan. TOMA-P contains abundant carotenoids including capsanthin and beta-carotene. Water extract of paradicsompaprika was added to each cell at each concentration, and the mixture was cultured for 24 h and 7 days. The inhibitory effects against lung cancer and cervical cancer were observed concentration- and time-dependently. The effect was more prominent against lung cancer. The growth of bowel cancer cells was observed after the 7-day exposure of paradicsompaprika at the concentrations below the highest concentration compared to the control. At the highest concentration, the growth inhibition was not different between the 24-h exposure and the 7-day exposure, which suggests that tumor dormancy was induced. Results of the present study suggest that the water extract of paradicsompaprika can be a candidate of a new anticancer agent. Fat soluble component of paradicsompaprika, capsanthin is regarded as an anti-promoter of cancer. Thus, paradicsompaprika possesses chemopreventive and inhibitory effects on cancer cells.     

比较有和无实时灌注成像的多巴酚丁胺负荷超声心动图在检测冠状动脉疾病中的作用

在一项初步研究中，27例胸痛患者进行了两种多巴酚丁胺负荷超声心动图检查：一种采用无造影剂的高机械指数谐波成像分析室壁运动，另一种采用静脉内注射造影剂Optison实时低机械指数灌注成像评价心肌灌注及室壁运动。而后，所有患者接受定量冠状动脉造影。两位独立的检查者都证明心肌灌注分析可提高检测的灵敏性。在21例冠状动脉明显狭窄的患者中，14例在峰值负荷时检测到心肌灌注异常，7例在标准多巴酚丁胺负荷超声心动图检出室壁运动异常。     

Developmental changes in progesterone biosynthesis and metabolism in the quail brain

We have recently demonstrated that the quail brain possesses the cholesterol side-chain cleavage enzyme (cytochrome P450scc) and 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase (3beta-HSD) and produces pregnenolone, pregnenolone sulfate and progesterone from cholesterol. To elucidate the developmental changes in progesterone biosynthesis and its metabolism in the quail brain, we examined the expression and activity of 3beta-HSD and progesterone metabolite(s) during embryonic and post-hatched ages. Both the progesterone concentration and 3beta-HSD mRNA expression in the brain were almost constant during embryonic and post-hatched ages. The conversion of pregnenolone to progesterone (net 3beta-HSD enzymatic activity) was also constant during development and at maturity. However, without radioinert progesterone, the production of progesterone was drastically reduced in the embryonic brain, indicating active progesterone metabolism at the embryonic stage. Biochemical analysis together with HPLC and TLC revealed that only the embryonic brain actively produced 5beta-dihydroprogesterone from progesterone. Thus, progesterone production may be constant during embryonic and post-hatched development and in adulthood, whereas 5beta-dihydroprogesterone may be produced actively only in embryonic life due to 5beta-reductase.     

Intraventricular administration of the neurotrophic factor midkine ameliorates hippocampal delayed neuronal death following transient forebrain ischemia in gerbils

Midkine (MK) is a growth factor with neurotrophic activities, and is expressed during the early stages of experimental cerebral infarction in rats in the zone surrounding the infarct. To evaluate in vivo activity of MK in preventing neuronal death, MK produced in yeast (Pichia pastoris) was administered into the brain ventricle immediately before occlusion of the bilateral common carotid artery of Mongolian gerbils. MK administration at the dose of 0.5-2 microg immediately before occlusion was found to ameliorate delayed neuronal death in the hippocampal CA1 region caused by transient ischemia 7 days after the insult. The hippocampal neurons of the MK-administered gerbils tended to degenerate 14 and 21 days after the insult, but their numbers remained higher than those in saline-administered controls; however, the hippocampal neurons were degenerated 28 days after the insult. MK administration at 2 h after occlusion did not ameliorate the neuronal death. These findings suggested that the therapeutic time window was narrow. The two to four times repeated administration of 2 microg MK immediately before and at 1, 2, or 3 weeks after the occlusion were not significantly different for the hippocampal neuronal death at 28 days after the insult compared with a single injection, but were significantly effective compared with vehicle administration alone. These findings suggested that the therapeutic time window was relatively narrow. The potent neuroprotective activity of MK observed in vivo suggested that MK might be useful as a therapeutic reagent for prevention of neuronal death in neurodegenerative diseases.     

Spectral analysis of electromyograms for extraocular muscles in normal and ophthalmoplegia cases.

Quantitative analysis of electromyograms (EMGs) of the extraocular muscles (EOMs), which contain fast fibers, like all skeletal muscles, but also slow fibers, was carried out in healthy subjects and a patient with external ophthalmoplegia. Interference EMGs of normal extraocular muscles demonstrated a relatively higher power spectrum in the higher frequency domain than those of the biceps brachii (BB). In the case of ophthalmoplegia, the lateral rectus (LR) and medial rectus (MR) muscles demonstrated a power spectrum with a wide ranging distribution up to 2,000 Hz in the early stage of recovery. Conservative treatment led to an improvement in the patient's ocular motility accompanied by a gradual shift of the spectrum towards lower frequencies within 265 days, during which time EMG examinations were performed four times. The results imply that the electrical activity of the slow fibers proper in the extraocular muscles affects the high frequency domain of the power spectrum and that the those fibers synchronously improve with fast fibers.     

Endothelium-fibrinolysis system interaction

The role of urokinase-type plasminogen activator (u-PA) in capillary growth was investigated using cultured bovine endothelial cells (BCE) on type I collagen gels and analyzed by morphometry for quantitative assessment of angiogenesis in vitro. BCE migrated into the gel matrix and formed capillary-like networks. The morphometrical analyses by measuring the length of tube formation enabled us to evaluate the effects of fibrinolytic proteases and several reagents. The addition of plasminogen up to 25 micrograms/ml to the gels significantly increased the extent of tube formation of BCE in a dose-dependent manner. Basic fibroblast growth factor (10 ng/ml) increased tube formation only in the presence of plasminogen. These enhancing effects on angiogenesis appeared to be related to the activation of fibrinolysis by u-PA derived from BCE, because they were suppressed by the addition of anti-u-PA IgG and anti-plasmin reagents such as aprotinin and alpha 2 anti-plasmin. Transforming growth factor beta also enhanced tube formation of BCE, but tumor necrosis factor alpha and interleukin-1 suppressed the tube formation. The quantitative assay of angiogenesis may be useful for clarifying the mechanism of neovascularization under pathological conditions.     

Localization of meso-tetra(p-sulfophenyl)porphine in murine sarcoma virus-induced tumor-bearing mice.

meso-Tetra(p-sulfophenyl)porphine (TPPS4) has been found to accumulate in the tumors of mice bearing a murine sarcoma virus-induced rhabdomyosarcoma to a greater degree than in all other tissues except for the kidney. Tumor to tissue ratios of from 3:1 (tumor to liver) to 9:1 (tumor to muscle) were observed. The uptake of TPPS4 was found to be dose dependent, and the highest tumor to tissue ratios were found 96 hours after injection. The water-soluble TPPS4 appears to be cleared through the kidneys and absolute concentrations there are reduced with increasing time after injection. These data are compared with previous studies on TPPS4 localization in Walker 256 carcinosarcoma-bearing mice. In view of this localizing ability and its relative lack of toxicity, TPPS4 seems to represent an ideal candidate for a tumor-localizing agent if high levels of the porphyrin in the kidneys can be reversed.     

Selective blockade of nicotinic acetylcholine receptors by pimobendan,a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells

Pimobendan, a Ca²⁺ sensitizer, is used clinically in the treatment of chronic heart failure. Although chronic heart failure is associated with activation of the sympathetic nervous system, it remains unknown whether pimobendan affects the function of sympathetic neurons and the adrenal medulla. Here, we report the inhibitory effects of pimobendan on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Pimobendan decreased the catecholamine secretion (IC₅₀=29.5 M) elicited by carbachol, an agonist at nicotinic acetylcholine receptors, but not that elicited by veratridine, an activator of voltage-dependent Na⁺ channels, or by high K⁺, an activator of voltage-dependent Ca²⁺ channels. Pimobendan also inhibited carbachol-induced influx of ²²Na⁺ (IC₅₀=25.9 M) and ⁴⁵Ca²⁺ (IC₅₀=26.0 M), but not veratridine-induced ²²Na⁺ influx or high K⁺-induced ⁴⁵Ca²⁺ influx. The reduction of catecholamine secretion caused by pimobendan was not overcome by increasing the concentration of carbachol. UD-CG 212, an active metabolite of pimobendan, lowered carbachol-induced catecholamine secretion with a concentration/inhibition curve similar to that of pimobendan. In experiments in situ, pimobendan suppressed both basal and carbachol-stimulated ¹⁴C-catecholamine synthesis (IC₅₀=5.3 and 4.9 M) from [¹⁴C] tyrosine [but not from l-3, 4-dihydroxyphenyl [3-¹⁴C] alanine ([¹⁴C]DOPA)], as well as tyrosine hydroxylase activity (IC₅₀=3.8 and 4.3 M). These findings suggest that pimobendan inhibits carbachol-induced catecholamines secretion and synthesis through suppression of nicotinic acetylcholine receptors.