Search

The reported incidence of adverse events (AEs) in endoscopic retrograde cholangiopancreatography (ERCP) varies between 2.5% and 14%. The aim of this study was to evaluate the incidence and severity of AEs in biliary ERCP and to specify the risk factors and preventive measures for post-ERCP pancreatitis (PEP).Patients with biliary disease with intact papilla were prospectively enrolled at 36 hospitals between April 2017 and March 2018. The primary outcomes were the incidence and severity of AEs.A total of 16,032 ERCP procedures were performed at the 36 hospitals during the study period and 3739 patients were enrolled. The overall incidence of AEs was 10.1% and ERCP-related mortality was 0.08%. PEP developed in 258 cases (6.9%), bleeding in 33 (0.9%), instrumental AEs in 17 (0.5%), infections in 37 (1.0%), cardiovascular AEs in eight (0.2%), pulmonary AEs in eight (0.2%), drug reaction AE in one (0.03%), pain in 15 (0.4%), and other AEs in 15 (0.4%). Multivariable analysis showed significant risk factors for PEP were: female of younger age, pancreatic guidewire-assisted biliary cannulation, temporary guidewire insertion into the pancreatic duct, total procedure time60 min, and post-ERCP administration of non-steroidal anti-inflammatory drugs. Effective preventive measures were prophylactic pancreatic stenting (PPS) and epinephrine spraying onto the papilla.In patients with intact papilla who underwent biliary ERCP, the incidence of AEs was 10.1% and the mortality was 0.08%. PPS and epinephrine spraying may prevent PEP.This study was registered in the University Hospital Medical Information Network (UMIN000024820).

Aim We aimed to clarify whether snacking habits decrease the risk of all-cause mortality in an older Japanese population. Methods The study participants were 64- or 65-year-old community-dwelling residents recruited each survey year from 1996 through 2005. Data on the frequency of snacking and other lifestyle factors were obtained during the baseline survey using self-administered questionnaires, and the participants were followed up annually until the end of 2017. In total, 2943 participants (1484 men and 1459 women) were eligible. All-cause mortality was compared among participants grouped by frequency of snacking (no snacking, one to four times/week, or every day). Results The number of deaths recorded over the study period of 43 204 person-years was 357 (24.1%) for men and 173 (11.9%) for women. The mean +/- standard deviations for the follow-up period were 14.2 +/- 4.9 years in men and 15.2 +/- 4.5 years in women. Cox proportional hazard regression analyses showed that after adjusting for potential confounding factors, the hazard ratios for women were 0.64 (95% confidence interval [CI], 0.43-0.94) in the group that had a habit of snacking one to four times/week, and 0.93 (95% CI 0.63-1.36) in the group that had a habit of snacking every day compared with those in the no snacking group. These associations were not observed among men. Conclusions A moderate frequency of snacking slightly decreases the risk of all-cause mortality among women. Our findings might be useful for improving the nutrition statuses in older female adults. Geriatr Gerontol Int center dot center dot; center dot center dot: center dot center dot-center dot center dot Geriatr Gerontol Int 2021; center dot center dot: center dot center dot-center dot center dot.

Aim We aimed to investigate prehospital factors associated with difficulty in hospital acceptance among elderly emergency patients. Methods We reviewed ambulance records in Osaka City from January 2013 through December 2014, and enrolled all elderly emergency patients aged ≥65 years who were transported by on-scene emergency medical service personnel to a hospital that the personnel had selected. The definition of difficulty in hospital acceptance was to the requirement for ≥4 phone calls to hospitals by emergency medical service personnel before receiving a decision from the destination hospitals. Prehospital factors associated with difficulty in hospital acceptance were examined through logistic regression analysis. Results During the study period, 72 105 elderly patients were included, and 13 332 patients (18.5%) experienced difficulty in hospital acceptance. In the simple linear regression model, hospital selection time increased significantly with an increasing number of phone calls (R2 = 0.774). In the multivariable analysis, older age (P for trend

Aim Although the prolongation of the time between injury and hospital arrival of traffic accident patients can influence their prognosis, factors associated with the difficulty in hospital acceptance of these patients have not been sufficiently evaluated in Japan. Methods We retrospectively analyzed the population-based ambulance records of all traffic accident patients for whom the Osaka Municipal Fire Department (Osaka City, Japan) dispatched an ambulance in 2013. We defined “cases with difficulty in hospital acceptance” as cases that required ≥4 calls by emergency medical service personnel at the scene before receiving hospital acceptance. We included patient characteristics (age, sex, coma status, and trauma severity judged by emergency medical service personnel), time factors (day/night or weekday/holiday and weekends), and accident location for multivariable logistic regression analysis to assess factors associated with the difficulty in hospital acceptance. Results Among 13,427 traffic accident patients, 2,033 (15.1%) were cases with difficulty in hospital acceptance. Pediatric patients (adjusted odds ratio [OR], 1.265; 95% confidence interval [CI], 1.060–1.509), male sex (adjusted OR, 1.260; 95% CI, 1.135–1.398), moderate-grade trauma (adjusted OR, 2.241; 95% CI, 1.972–2.547), severe-grade trauma (adjusted OR, 2.057; 95% CI, 1.249–3.388), holidays and weekends (adjusted OR, 1.702; 95% CI, 1.539–1.882), and night-time (adjusted OR, 2.720; 95% CI, 2.443–3.027) were positively associated with difficulty in hospital acceptance. Conclusions Using population-based ambulance records from a large urban community in Japan, we showed that the difficulty in hospital acceptance of patients at the scene of traffic accidents was positively associated with several prehospital factors.

For the realization of the smart community, the Internet of Things IoT and sensor technology in the millimeter-wave band is necessary. The development of these technologies requires accurate spectrum analysis in the frequency domain over 100 GHz. A tunable preselection filter is a key device in building such a spectrum analyzer. In this paper, we propose use of a ridge waveguide to achieve frequency tuning over a wider bandwidth. In addition, we demonstrate an example design and prototype for a filter with a relative bandwidth of 38% 75 GHz to 110 GHz and 32% 78.1 GHz to 107.5 GHz, respectively.

AIM: To investigate the association between falls and self-reported depressive symptoms or visual impairment among young-old adults. METHODS: A total of 1904 participants (986 men and 918 women) aged 64 years from the New Integrated Suburban Seniority Investigation Project from 1996 to 2005, an age-specific cohort study in Nisshin, Japan, took part in the present study. Depressive symptoms were evaluated using the Geriatric Depression Scale. Visual impairment was assessed using a self-administered questionnaire. The outcome variable was self-reported injurious falls at the age of 70 years. Multivariate odds ratios (OR) and 95% confidence intervals (CI) of depressive symptoms and visual impairment for the incidence of falls were calculated using logistic regression models and adjusted for possible confounding factors. RESULTS: Overall, 77 (7.8%) men and 126 (13.7%) women reported falls within the past 1 year at age 70 years. Among women, depressive symptoms and visual impairment were significantly associated with falls after adjusting for potential confounders (OR 1.70, 95% CI 1.09-2.62; OR 2.34, 95% CI 1.45-3.71, respectively), but not among men. Women with both conditions had a significantly increased risk of falls after adjusting for potential confounders (OR 3.50, 95% CI 1.65-7.13) compared with those with neither condition; the association was not significant among men. CONCLUSIONS: Depressive symptoms and visual impairment at age 64 years were significantly associated with an increased risk of falls at age 70 years in Japanese women but not in men. The combination of the two symptoms had an even greater association with fall risk. Geriatr Gerontol Int 2015; ●●: ●●-●●. Language: en

Background In Japan, 5000–300 000 persons contracted measles every year until 2001. The measles/rubella-combined (MR) vaccination at age 17–18 years (phase 4 MR vaccination: MR-IV) was launched in 2008 in Japan as a measles–rubella catch-up campaign. A serological assessment of this campaign has not been thoroughly performed. Methods Titers of anti-measles and anti-rubella immunoglobulin G antibodies, and past medical history including measles and rubella vaccination and infection were obtained from first-year university students in 2008 and 2009, and the immune status against measles and rubella was compared between students at the target MR-IV age (the target age group) and those 1 year older than the target age (non-target age group). Results A total of 186 students were in the target age group and 146 were in the non-target age group. The proportion of students with a history of measles and rubella infection was not significantly different between the two groups (8.8% vs. 6.3%, P = 0.41 and 11.0% vs. 9.9%, P = 0.75, respectively). A history of two or more measles and rubella vaccinations was significantly more frequent in the target age group (85.2% and 54.9%, respectively) than in the non-target age group (20.8% and 13.2%, respectively; both P < 0.001). Prevalence of seropositivity for measles and for rubella was also higher in the target age group (98.9% and 97.8%, respectively) than in the non-target age group (91.0% and 87.5%, respectively; both P < 0.001). Conclusions The MR-IV catch-up campaign helped achieve herd immunity and will contribute to the elimination of measles and rubella.

Results: During the study period, 8,596 patients with acute myocardial infarction without arrest and 9,283 out-of-hospital cardiac arrests of cardiac origin were registered. The hospital arrival time (from patient’s call until hospital arrival) increased along with the increasing number of phone calls to hospitals from ambulances for patients with acute myocardial infarction (from 23.2 min with one phone call to 39.7 min with ≥5 phone calls; P for trend

Objectives It is unclear how much the length of a cardiopulmonary resuscitation (CPR) training program can be reduced without ruining its effectiveness. The authors aimed to compare CPR skills 6 months and 1 year after training between shortened chest compression–only CPR training and conventional CPR training. Methods Participants were randomly assigned to either the compression-only CPR group, which underwent a 45-minute training program consisting of chest compressions and automated external defibrillator (AED) use with personal training manikins, or the conventional CPR group, which underwent a 180-minute training program with chest compressions, rescue breathing, and AED use. Participants' resuscitation skills were evaluated 6 months and 1 year after the training. The primary outcome measure was the proportion of appropriate chest compressions 1 year after the training. Results A total of 146 persons were enrolled, and 63 (87.5%) in the compression-only CPR group and 56 (75.7%) in the conventional CPR group completed the 1-year evaluation. The compression-only CPR group was superior to the conventional CPR group regarding the proportion of appropriate chest compression (mean ± SD = 59.8% ± 40.0% vs. 46.3% ± 28.6%; p = 0.036) and the number of appropriate chest compressions (mean ± SD = 119.5 ± 80.0 vs. 77.2 ± 47.8; p = 0.001). Time without chest compression in the compression-only CPR group was significantly shorter than that in the conventional CPR group (mean ± SD = 11.8 ± 21.1 seconds vs. 52.9 ± 14.9 seconds; p

Objectives To determine whether the number of teeth lost can predict the risk of subsequent hip fracture. Methods We followed up 9992 male Japanese dentists aged 50 years or more (mean age ± standard deviation [SD], 61.1 ± 9.6 years) for incidence of hip fracture. From 2001 through 2006, they completed a baseline questionnaire on lifestyle and health factors including the number of teeth lost (excluding third molars). Incidence rate ratios (IRRs) were estimated by fitting proportional hazard models. Results During the mean follow-up period of 6.0 years, 20 new cases of hip fracture occurred. Participants who had lost 15 or more teeth at baseline were at a significantly increased risk of hip fracture: the multivariate-adjusted IRRs were 4.1 (95% confidence interval [CI], 1.2–14.2) for loss of 15–27 teeth and 4.5 (1.1–18.0) for edentulousness relative to loss of 0–14 teeth (trend P, 0.028). Overall, the risk of hip fracture was weakly associated with the number of teeth lost: the IRR per tooth was 1.06 (95% CI, 1.01–1.12). Conclusions Tooth loss was slightly associated with a higher risk of subsequent hip fracture. The number of teeth lost might be informative in predicting this risk.

Wakai K, Naito M, Naito T, Kojima M, Nakagaki H, Umemura O, Yokota M, Hanada N, Kawamura T. Tooth loss and intakes of nutrients and foods: a nationwide survey of Japanese dentists. Community Dent Oral Epidemiol 2010; 38: 43–49. © 2009 John Wiley & Sons A/S Abstract – Objectives: To clarify the association of tooth loss with dietary intakes among dentists, for whom sufficient dental care is available. Methods: We analyzed the data from 20 366 Japanese dentists (mean age ± SD, 52.2 ± 12.1 years; women 8.0%) who participated in a nationwide cohort study from 2001 to 2006. The baseline questionnaire included a validated food-frequency questionnaire to estimate intakes of foods and nutrients. We computed the geometric means of daily intakes by the number of teeth, adjusting for age, sex, smoking, physical activity, and history of diabetes. Results: The mean intakes of some key nutrients and food groups, such as carotene, vitamins A and C, milk and dairy products, and vegetables including green-yellow vegetables, decreased with the increasing number of teeth lost (P for trend

Background and purpose: To estimate the diagnostic accuracy of cardiac 123I-metaiodobenzylguanidine (MIBG) scintigram for detection of Parkinson disease. Methods: A cross-sectional study with index test of MIBG scintigram and reference standard of U.K. Parkinson’s Disease Brain Bank Criteria was performed in 403 patients. Ratio of cardiac-to-mediastinum MIBG accumulation was determined at 20 min (early H/M) and 4 h (late H/M). Area under the receiver-operator characteristic (ROC) curve, sensitivity and specificity in detecting Parkinson disease were analyzed. Accuracy was analyzed in a subgroup of patients with disease duration of 3 years or less. Results: Area under the ROC curve was 0.89 using either early or late H/M as a diagnostic marker (95% CI 0.85–0.92 for early H/M and 0.86–0.93 for late H/M). Sensitivity and specificity were 81.3% (76.1–85.8%) and 85.0% (77.7–90.6%) for early H/M and 84.3% (79.3–88.4%) and 89.5% (83.01–94.1%) for late H/M. In the subgroup with duration of 3 years or less, the ROC curve area, sensitivity, and specificity were 0.86 (0.79–0.92), 76.0% (64.8–85.1%), and 83.9% (71.7–92.4%) for early H/M and 0.85 (0.78–0.92), 73.3% (61.9–82.9%), and 87.5% (75.9–94.8%) for late H/M. Conclusion: Although diagnostic accuracy of cardiac MIBG scintigram is high, it is limited because of insufficient sensitivity in patients with short duration.

Objective To elucidate epidemiologic and clinical manifestations of Japanese patients with giant cell arteritis (GCA), the first nationwide survey for GCA was conducted in 1998 in Japan. Methods The first questionnaire on GCA for patients treated in 1997 was sent to 10,717 medical departments in Japan. A total of 177 patients were reported. Among the 177 patients, 66 GCA patients with detailed clinical and epidemiologic features on second survey were analyzed. Results Prevalence in patients 50 years of age and older in 1997 was 1.47 per 100,000 population in Japan. The average age at onset was 71.5 years old. The male:female ratio was 1:1.7. The association with permanent and complete visual loss (6.5%), jaw claudication (15.2%), and polymyalgia rheumatica (PMR) (30.3%) were low in frequency compared with those reported from other countries. All patients were treated with corticosteroids. Only 3 (4.5%) patients were reported as deceased due to other causes. Conclusion The prevalence of GCA in Japan was revealed to be extremely low compared with other countries. Clinical findings of permanent and complete visual loss, jaw claudication, and PMR were infrequent among Japanese patients with GCA.

To examine whether simple beta-carbolines induce parkinsonian-like symptoms in vivo via N-methylation, the simple beta-carbolines norharman (NH), 2-mono-N-methylated norharmanium cation (2-MeNH+), and 9-mono-N'-methylnorharman (9-MeNH) were systematically administered to C57BL/6 mice for 7 days. These substances induced bradykinesia with reduction of locomotion activity. NH or 2-MeNH+ decreased dopamine (DA) contents to 50-70% of values in controls in the striatum and midbrain. 9-MeNH potently decreased not only DA but also serotonin content in various regions. Immunohistochemical examination revealed that the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta of NH- and 9-MeNH-treated mice were diminished to 76 and 66% of values in control mice, respectively. The formation of a toxic metabolite, 2,9-di-N,N'-methylated norharmanium cation (2,9-Me2NH+), was 14 and eight times higher in the brain of mice receiving 9-MeNH than that in NH- and 2-MeNH+-treated mice, respectively. In cultured mesencephalic cells from rat embryo, 2,9-Me2NH+ selectively killed TH-positive neurons only at a lower dose but was toxic to all neurons at higher doses. Thus, the excess formation of 2,9-Me2NH+ would induce nonspecific neurotoxicity. These results indicated that 9-indole nitrogen methylation should be the limiting step in the development of the toxicity. NH, a selective dopaminergic toxin precursor, is sequentially methylated to form 2,9-Me2NH+, which could be an underlying factor in idiopathic Parkinson's disease.

The co-existence of an endometrioid adenocarcinoma with an ovarian yolk sac tumor is very rare. Only eight cases have been reported in the English language literature. A 54-year-old postmenopausal woman with a 6-month history of progressive abdominal distension was seen at our hospital. MR imaging revealed a large cyst with a solid intramural node. Serum alpha-fetoprotein and CA125 levels were 13143 ng/ml and 170 U/ml, respectively. At laparotomy, a large tumor approximately 20 cm in diameter was found to occupy the abdominal cavity, adhering to the swollen appendix and part of the omentum. Microscopically, foci of endometrioid adenocarcinoma together with a yolk sac tumor component were observed within a large endometriotic cyst. Since the tumor was clinically staged 1c, the patient was given 500 mg of intraperitoneal carboplatin postoperatively, followed by five courses of combination chemotherapy consisting of cisplatin, etoposide and peplomycin at 4-week intervals. The levels of both serum alpha-fetoprotein and CA 125 decreased gradually to normal ranges and remained normal at the most recent follow-up on 29 December, 2001. In contrast to a very poor prognosis of this tumor in previously reported cases, our patient showed no sign of recurrence during a 21-month follow-up period.

To determine the possible associations of medical status and physical fitness with periodontal disease, a cross-sectional study was conducted. The subjects were 517 males and 113 females aged 23 to 83 years who participated in a multiphasic health test at the Aichi Prefectural Center of Health Care, Japan, from 1992 to 1997. Their periodontal status was assessed by means of the CPITN scoring system. To assess the strength of associations between the examined factors and the score, odds ratios were computed using ordinal logistic models. Conventional risk factors such as old age, smoking habits, and higher fasting plasma glucose and simplified debris index increased the risk of periodontal disease. Hypertension, hematuria, leucocytosis or thrombocytosis, positive C-reactive protein and higher serum alkaline phosphatase were positively associated with the score, whereas higher serum high-density lipoprotein cholesterol was related to a lower risk. Poor physical fitness affecting aerobic capacity, foot balance and reaction was associated with a higher CPITN score. These associations were independent of the conventional risk factors. Although these new potential risk factors should be further investigated for their causal relationship, our findings suggested a close relationship of oral health to medical status and physical fitness.

Summary Aim To investigate the influence of glucose and the efficacy of two different aldose reductase (AR) inhibitors, epalrestat and SNK-860, on the polyol pathway and myo-inositol metabolism in human neutrophils. Methods We incubated neutrophils with various concentrations of glucose and AR inhibitors. The neutrophils from healthy volunteers were incubated in the media containing 5–40 mmol/l glucose with or without an AR inhibitor. The sorbitol and myo-inositol contents, and myo-inositol uptake were measured by high performance liquid chromatography and radio isotope technique with 2-[3H]-myo-inositol. Results After 2 h incubation, the sorbitol content increased with rising extracellular glucose concentrations, while the myo-inositol content decreased. Both AR inhibitors reduced the sorbitol content in neutrophils exposed to 40 mmol/l glucose medium. A 70% fall in the myo-inositol content in neutrophils exposed to 40 mmol/l glucose medium was attenuated ≈ 40% by the addition of AR inhibitors. myo-Inositol uptake into neutrophils was inhibited by high glucose. AR inhibitors significantly ameliorated the decrease in myo-inositol uptake, but did not completely normalize it. Conclusions Our present in vitro studies showed that the glucose-induced metabolic alterations in human neutrophils were similar to those in tissues prone to diabetic complications, and that AR inhibitors effectively corrected glucose-induced imbalances of the polyol pathway and myo-inositol uptake in neutrophils. In addition, our study suggests that glucose-induced metabolic alterations may result in the neutrophil dysfunction and that an AR inhibitor may be capable ameliorating it. Diabet. Med. 16, 67–73 (1999)

We previously reported that mesencephalic dopaminergic neurons are resistant to cytotoxicity induced by nitric oxide (NO). This study investigated the intracellular mechanism that protects dopaminergic neurons against NO toxicity in rat mesencephalic cultures. Peroxynitrite anion, an active metabolite of NO, caused significant cytotoxic effects against dopaminergic and nondopaminergic neurons, but NO caused cytotoxic effects restricted to nondopaminergic neurons. In addition, we studied the effects of ascorbate, an anti-oxidant, on NO-induced neurotoxicity against dopaminergic neurons and found that coadministration of ascorbate failed to affect resistance against NO-induced neurotoxicity. These findings suggest that the protecting mechanism from NO neurotoxicity in dopaminergic neurons is based on inhibition of conversion of NO to peroxynitrite anion, is independent of the NO redox state, and is possibly due to suppression of superoxide anion production. Furthermore, we investigated NO-induced neurotoxicity with or without pretreatment with sublethal doses of methylphenylpyridium ion (MPP+). Following pretreatment with 1 microM MPP+, which did not show significant cytotoxic effects against dopaminergic neurons, NO demonstrated significant cytotoxicity. Therefore, MPP+ may inhibit the protecting systems from NO neurotoxicity in dopaminergic neurons.

Parkinson's disease is characterized by dopaminergic neuronal degeneration, but its pathogenic mechanism is still unknown. In the dopaminergic neurons, oxygen radicals such as hydrogen peroxide are released through dopamine oxidation. Many factors are involved in radical formation, but glutamate and nitric oxide (NO) are the major effectors of the radical-induced neurotoxicity mediated primarily through calcium influx. In the cultured embryonic rat mesencephalon, we investigated the dopaminergic and non-dopaminergic neuronal death induced by glutamate and by NO-generating agents. Although glutamate had a neurotoxic effect on both dopaminergic and non-dopaminergic neurons, it showed slightly greater effect in the dopaminergic neurons. In contrast to glutamate, NO-generating agents (S-nitrosocysteine and sodium nitroprusside) showed neurotoxic effects restricted exclusively to non-dopaminergic neurons. Although No-nitro-L-arginine, an NO synthase inhibitor, had no significant effect on the glutamate-induced cytotoxicity in dopaminergic neurons, it had a significant antagonistic effect on that in non-dopaminergic neurons. These findings indicate the presence of two different mechanisms of glutamate-induced neuronal death, one being neurotoxicity not mediated by NO, found in dopaminergic neurons, and the other being that mediated via NO, found in non-dopaminergic neurons. © 1996 Wiley-Liss, Inc.

Parkinson's disease is characterized by chronic progression of dopaminergic neuronal death, the mechanism of which is still unknown. Although methyl-4-phenylpyridium ion (MPP+) or MPP+-like substance, that can reduce mitochondrial complex I activity, is supposed to be a causative agent for Parkinson's disease, it is difficult to explain the chronic neuronal degeneration for years. It is important to identify other putative agents capable of causing chronic cell death besides MPP+. We hypothesized that treatment with small doses of MPP+, not causing severe damage to dopaminergic neurons but merely reducing the activity of mitochondrial complex I, can be a model of Parkinson's disease, and that glutamate can be a putative agent causing chronic neuronal degeneration. Using primary culture of the rat mesencephalon, we investigated glutamate-induced cytotoxicity against dopaminergic and non-dopaminergic neurons with or without the pretreatment with MPP+. Brief exposure to glutamate showed similar cytotoxicity against both dopaminergic and non-dopaminergic neurons. An N-methyl-D-aspartate receptor antagonist completely blocked the glutamate-induced cytotoxicity against both dopaminergic and non-dopaminergic neurons. In the dopaminergic neurons, MPP+ caused cytotoxicity that was not blocked by co-administration of MK-801. After pretreatment with small doses of MPP+, sub-lethal doses of glutamate caused severe cell damage restricted to dopaminergic neurons, suggesting that MPP+ potentiates the glutamate-induced cytotoxicity only against dopaminergic neurons. As glutamate is putatively capable of causing cytotoxicity against dopaminergic neurons, the present findings might be important in considering the pathogenesis of dopaminergic neuronal degeneration and a possible therapeutic application of glutamate receptor antagonists in Parkinson's disease. © 1996 Wiley-Liss, Inc.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawa tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95% confidence intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26-2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68), respectively. These findings suggest a protective effect of tea consumption against lung cancer in humans.

Silylation of allylic acetates (1) using organodisilanes (2) was carried out in the presence of a catalytic amount of Pd(DBA)2−LiCl at 100 °C. The silylation proceeded smoothly without β-hydrogen elimination of a resulting (π-allyl)palladium intermediate. The added chloride salt such as LiCl or NaCl was indispensable for the catalytic activity. On the other hand, remarkable improvement of the silylation was realized by employing allylic trifluoroacetates (4) in place of the acetates (1) as the substrates. The silylation proceeded even at room temperature, and the added chloride salts was not necessary as the catalyst component. In the silylation, transmetalation of the disilanes (2) with (η3-allyl)palladium intermediate (7) might be a critical step in the catalytic cycle. Model reactions for the transmetalation were carried out.

Two series of dehydroannulenes fused with bicyclo[2.2.2]octene (BCO) units were synthesized either by an oxidative coupling with copper(I) under air or by a palladium−copper-catalyzed coupling. The first series of dehydroannulenes consisted of tetradehydro[12]annulene (12), hexadehydro[18]annulene (13), octadehydro[24]annulene (14), and decadehydro[30]annulene (15), which all have the BCO units connected by the butadiyne linkage. The second consisted of tridehydro[12]annulene (16) and tetradehydro[16]annulene (17), which have the BCO units connected by the acetylene bond. The molecular structures of the relatively stable annulenes 13 and 17 were determined by X-ray crystallography, which showed that 13 has a planar π-system, whereas 17 has a tub structure like cyclooctatetraene. The 1H NMR signal for the bridgehead proton of the BCO units is a good measure for the ring current effect. This signal clearly indicated the presence of diatropicity in [18]annulene 13 and paratropicity in [12]annulenes 12 and 16...

Allylic carbonates are cyanated in high yields to β,γ-unsaturated carbonitriles using trimethylsilyl cyanide in the presence of a catalytic amount (5 mol %) of Pd(PPh3)4 in THF under reflux. In the reaction, cinnnamyl methyl carbonate affords cinnamyl cyanide in 98% yield. Allylic acetates also provide the corresponding carbonitriles, but often in lower yields. The cyanations of several cis- and trans-alicyclic substrates proceed cleanly (stereoselectivity > 99%) with overall retention. Characterization and reaction of palladium complexes relevant to the present catalysis indicate that transmetalation of an η3-allyl palladium complex with trimethylsilyl cyanide is facile, while the resulting cyano(η3-allyl)palladium complexes afford the corresponding allylic cyanides only when excess trimethylsilyl cyanide is present. Stereochemistry of the product indicates that the CN attacks the η3-allyl moieties from the palladium side.

Acylation of allylic esters (2) with acylsilanes (1) in the presence of a catalytic amount (5 mol %) of a palladium complex is reported. The reaction proceeds selectively to afford β,γ-unsaturated ketones (3) in high yields. [Pd(η3-C6H5CHCHCH2)(CF3COO)]2 (4a) showed the best catalytic activity. After the reaction, formation of CF3COOSiMe3 (5a) was confirmed by 29Si NMR measurement of the resulting reaction mixture, indicating the trimethylsilyl moiety effectively traps the CF3COO leaving group from 2. The leaving group of the allylic esters affects the reaction considerably: allylic trifluoroacetate gave the best result, while the corresponding acetates and trichloroacetates did not afford any acylation products at all. Stoichiometric reaction of 4a with 1 gave acylation product 3 with a formation of 5a and Pd(0), whereas no acylation reaction took place with the corresponding acetate complex [Pd(η3-C6H5CHCHCH2)(CH3COO)]2 (4b). A DFT calculation suggests that interaction of high-lying HOMO of 1 and low-l...

1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.

A catalytic system consisting of vanadium oxyacetylacetonate [VO(acac)(2)] and 3 A molecular sieves (MS3A) in acetonitrile works effectively for the aerobic oxidation of propargylic alcohols [R(1)CH(OH)Ctbd1;CR(2)] to the corresponding carbonyl compounds under an atmospheric pressure of molecular oxygen. Although the reactivity of alpha-acetylenic alkanols (R(1) = alkyl) is lower compared to that of the alcohols of R(1) = aryl, alkenyl, and alkynyl, the use of VO(hfac)(2) as a catalyst and the addition of hexafluoroacetylacetone improve the product yield in these cases. A catalytic cycle involving a vanadium(V) alcoholate species and beta-hydrogen elimination from it has been proposed for this oxidation.

An equimolar mixture of propargylic carbonate (1) and trimethylsilyl cyanide (2) in THF under reflux affords cyanoallene (3) in the presence of a catalytic amount (5 mol %) of Pd(PPh3)4. In the reaction, the trimethylsilyl moiety of 2 effectively traps the leaving group of 1. The use of 2 in excess (6 equiv) provides dicyanated products (7 or 8) in high yields.

Although increased protein kinase C (PKC) activity has been invoked in the pathogenesis of diabetic retinopathy, nephropathy and macroangiopathy, the role of PKC in neuropathy remains unclear. We reported that total PKC activity in sciatic nerves of STZ-induced diabetic rats was not altered compared with that of normal rats, and that PKC-β inhibitor, LY-333531 (LY) ameliorated neural dysfunction and reduced endoneurial blood flow without affecting PKC activity, suggesting that this effect of LY would be mediated through its action on endoneurial microvasculature. In this study, effect of LY on diabetic neuropathy was investigated in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of type 2 diabetes. Three-month-old male OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats as normal control rats were divided into 5 groups as follows: 1) LETO control, 2) OLETF control, 3) LY (1 mg/kg/day)-treated OLETF, 4) sucrose-fed OLETF, and 5) sucrose-fed OLETF treated with LY. After 21-month treatment, motor nerve conduction velocity (MNCV) in tail nerves, sciatic nerve blood flow (SNBF) and protein expression of phosphorylated PKC in sciatic nerves were measured. 1) MNCV: OLETF rats demonstrated a significant delay in MNCV, which was enhanced by sucrose feeding, and these deficits were prevented by LY. 2) SNBF: reduced SNBF in OLETF and sucrose-fed OLETF rats was ameliorated by LY. 3) PKC: phosphorylated PKC expression was decreased in OLETF rats, which was more prominent in sucrose-fed OLETF rats. Treatment with LY increased phosphorylated PKC expression in both groups of OLETF rats. These observations suggest that diabetes with long duration and poor glycemic control decreases phosphorylated PKC in nerve tissues, which would contribute to the development of diabetic neuropathy, and that PKC-β inhibition would be beneficial for the prevention of this neuropathy.

The 2,4,6-trichlorophenoxo–hexamethylphosphoramide(HMPA)–copper(II) complex was isolated by the reaction of copper(II) chloride with 2,4,6-trichlorophenol, sodium methoxide, and HMPA in methanol solvent under an atmosphere of nitrogen. This complex has the composition of Cu·HMPA·2(C6H2Cl3O). The molecular weight determination was consistent with the copper(II) complex of binuclear structure. The infrared, electronic, and ESR spectra and magnetic susceptibility of the copper(II) complex are discussed in relation to its structure. Decomposition of the copper(II) complex in refluxing benzene yielded poly(dichlorophenylene oxide), coupling product of the 2,4,6-trichlorophenoxo ligand of the copper(II) complex. Electron spin resonance (ESR) measurements on the copper(II) complex in the solid state in a degassed sealed tube at 120 ± 5°C indicated that the phenoxy radical was generated during the period of decomposition and the intensity of the ESR spectra based on copper(II) ion decreased with the measurement time. From these ESR spectra, a possible initial step involving one electron transfer of the decomposition of the 2,4,6-trichlorophenoxo–HNPA–copper(II) complex is discussed.