9H-xanthene-2,7-diols as antioxidants for autoxidation of linoleic acid

The antioxidant activities of 9H-xanthene-2,7-diols and α-tocopherol were studied during the oxidation of linoleic acid in a homogeneous solution and in an aqueous micelle dispersion. The antioxidant activities of 9H-xanthene-2,7-diols for both systems were 1.0–2.4 times greater relative to α-tocopherol. In addition, the 1,3,4,5,6,8-hexamethylxanthene-2,7-diol showed less cytotoxicity toward human fibroblasts than did 2,6-di-t-butyl-4-methylphenol.     

Factors affecting the nocturnal decrease in blood pressure: a community-based study in Ohasama

OBJECTIVE: To investigate factors affecting the nocturnal decrease in blood pressure. DESIGN: A cross-sectional study of 823 community-based untreated subjects aged > 20 years. Screening and ambulatory blood pressures were measured and the effects of age and the ambulatory blood pressure on the nocturnal decrease were examined. RESULTS: The magnitude of the decrease and the percentage decrease in the nocturnal blood pressure increased with increasing daytime ambulatory blood pressure and decreased with increasing night-time ambulatory blood pressure. Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels in hypertensives were still higher than those in normotensive subjects. The magnitude decreased with increasing age for men but not for women, whereas the percentage decrease decreased with increasing age both for men and for women. The SD of the 24 h blood pressure correlated strongly to the magnitude of the nocturnal decrease (systolic blood pressure r = 0.62, P < 0.0001; diastolic blood pressure r = 0.52, P < 0.0001), suggesting that the SD of the 24 h blood pressure is representative of the nocturnal decrease. A minimal nocturnal decrease was observed frequently in elderly normotensive men but infrequently in hypertensive individuals from the general population. A marked nocturnal decrease was observed frequently in hypertensive women aged > 70 years. CONCLUSION: Although the magnitude of the nocturnal decrease in blood pressure increased with increasing daytime blood pressure, the nocturnal blood pressure levels increased with increasing daytime ambulatory blood pressure. Therefore, the blood pressure in hypertensive subjects should essentially be lowered throughout the 24 h period. A marked nocturnal decrease in blood pressure in some elderly hypertensive women was observed without treatment. The nocturnal blood pressure levels of such subjects should be considered during treatment.     

Inhibition of malonaldehyde formation from lipids by an isoflavonoid isolated from young green barley leaves

The inhibitory effect of 2″-O-glycosylisovitexin (2″-O-GIV), isolated from young green barley leaves, on malonaldehyde (MA) formation from lipids was determined by gas chromatography. Two μmol of 2″-O-GIV inhibited MA formation from 0.2 mmol of squalene by almost 100% upon ultraviolet (UV) irradiation. Only 1 μmol of 2″-O-GIV inhibited 90% of MA formation from 0.2 mmol of ethyl linoleate upon UV irradiation. The effective quantities of 2″-O-GIV were much lower than those of either butylated hydroxytoluene or α-tocopherol. When ethyl linoleate, ethyl linolenate and ethyl arachidonate were oxidized by Fenton’s reagent in the presence of 2″-O-GIV or α-tocopherol, both compounds showed similar activity toward MA formation. Both compounds gave maximum inhibition at doses of 0.1–0.3 μmol for ethyl linoleate, 0.1–0.5 μmol for ethyl linolenate and 0.1–0.5 μmol for ethyl arachidonate.     

Distal sensory axonopathy after sarin intoxication

A 51-year-old man inhaled sarin during a terrorist attack on the Tokyo subway system and died 15 months later. Neuropathologic examination revealed marked nerve fiber decrease in the sural nerve, moderate nerve fiber loss in the sciatic nerve, and unremarkable dorsal root ganglia, dorsal roots, and posterior column of the spinal cord. This pathology is consistent with dying-back degeneration of the peripheral nervous system and could represent a late sequela of sarin intoxication.     

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.     

Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides in male volunteers

STUDY OBJECTIVES: To test the effect of stellate ganglion block on tympanic membrane temperatures. DESIGN: Prospective, observational study. SETTING: Department of Anesthesia, Yamanashi Medical University, Yamanashi, Japan. SUBJECTS: 7 healthy male volunteers. INTERVENTIONS: Stellate ganglion block, 6 ml of 1% mepivacaine hydrochloride, was administered. MEASUREMENTS AND MAIN RESULTS: Application of temperature probes (right and left tympanic membranes, eight adhesive right skin-surface temperatures at the chest, upper arm, digital fingertip, lateral calf, thigh, and great toe) was followed by a 30-minute control period. Temperatures were recorded every 15 minutes for 30 minutes before stellate ganglion block and every 5 minutes for 40 minutes after the block. The right tympanic membrane temperature increased slightly but not significantly compared with the left tympanic membrane temperature 10 minutes after stellate ganglion block and subsequently. Right skin-surface temperature gradients at the upper limb decreased slightly but not significantly after stellate ganglion block. Similarly, right skin-surface temperature gradients at the lower limb decreased slightly but not significantly after stellate ganglion block. CONCLUSIONS: Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides.     

Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein

We have cloned a cDNA for a novel human homolog of the Drosophila discs large (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig). Northern blot analysis revealed that the gene is highly expressed in neuronal and endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE-dlg antibody showed that the protein tended to be expressed in non-proliferating cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of the heart muscles, and the prickle and functional layer cells of the esophageal epithelium. Proliferative cells, including various cultured cancer cell lines and basal cells in the esophageal epithelium, showed little expression of the NE-dlg protein. In addition, yeast two-hybrid screening and in vitro binding assays revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC tumor suppressor protein. These data suggest that NE-dlg negatively regulates cell proliferation through its interaction with the APC protein.     

Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial

OBJECTIVES: The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. METHODS: One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. RESULTS: Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p = 0.001). Minimal lumen diameter was 1.49 +/- 0.75 mm (mean +/- SD) in the probucol group and 1.13 +/- 0.65 mm in the control group (p = 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p = 0.009). The late loss was 0.37 +/- 0.69 mm in the probucol group and 0.60 +/- 0.62 mm in the control group (p = 0.13). The loss/gain ratio was 0.32 +/- 0.74 in the probucol group and 0.56 +/- 0.81 in the control group (p = 0.059). Net gain was greater in the probucol group than in the control group (0.77 +/- 0.70 vs. 0.48 +/- 0.59 mm, p = 0.053). CONCLUSIONS: Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.     

Application of extremely low viscosity methylcellulose (MC) for pellet film coating

OBJECTIVE: The American Diabetes Association has recommended that pregnant women with low-risk factors need not be tested for gestational diabetes mellitus (GDM). The aim of this study was to determine the prevalence of GDM in women with low-risk factors and to see if the pregnancy outcomes of women with GDM from a low-risk group were different from the outcomes of other women with GDM. RESEARCH DESION AND METHODS: Over an 18-month period, all pregnant women were offered a test for GDM using a 75-g glucose tolerance test at the beginning of the 3rd trimester. GDM was diagnosed if the 2-h glucose level was > or =8.0 mmol/l. The prevalence of GDM was determined in women with defined low-risk factors (Caucasian ethnic origin, age <25 years, and BMI <25 kg/m2). The pregnancy outcomes of women with GDM from a low-risk group were compared with those of other women with GDM. RESULTS: From a tested population of 2,907 women, 573 were identified as coming from a low-risk group. The prevalence of GDM in this low-risk group was 2.8%. The pregnancy outcomes of women with GDM from a low-risk group were no different from the pregnancy outcomes of other women with GDM, with respect to frequency of insulin use, units of insulin per day, morbidity, emergency caesarian section, and the percentage of both large- and small-for-gestational-age babies. In our population, if low-risk women were excluded, 80% of women would still require testing and nearly 10% of all cases of GDM would be missed. CONCLUSIONS: Women from a low-risk group have a 2.8% prevalence rate of GDM. The pregnancy outcomes of women with GDM from a low-risk group are similar to the outcomes of other women with GDM. Concerning the use of the 75-g glucose tolerance test in pregnancy, the recommendation not to test women from a low-risk group requires further evaluation in different populations before it can be endorsed.     

Synthesis of nucleosides having unusual branched sugars as potential antiviral agents

Enantiomerically pure novel nucleosides having unusual branched sugars were synthesized in a stereospecific manner from a common chiral pool of (S, S)-1,4-bis(benzyloxy)-2,3-epoxybutane and evaluated for antiviral activity.