Effects of short-term existential group therapy for breast Cancer patients.

OBJECTIVES: Cancer patients who suffer from existential difficulties, including fear of death, isolation, or loss of human relationships, try to accept these fears by exploring the meaning of their life. In particular, early psychological intervention for patients prevents them from psychosocial maladjustment afterwards. Therefore, we have developed the Short-term Existential Group Therapy Program (Short-term EGP) for cancer patients, focusing on relief of existential or spiritual suffering and/or pain. This study aims to statistically evaluate the effects of this program on breast cancer patients within the first year after cancer diagnosis. METHODS: Thirty-one patients completed our research program. A ninety-minute therapeutic group session was held once a week for 5 weeks. We performed the above assessments three times: just before and after the intervention, as well as a month after the end of intervention. Outcome assessment included measures of spiritual well-being (SELT-M), Mental Adjustment to Cancer (MAC) and Profile of Mood States (POMS). RESULTS: The SELT-M "Overall QOL" scores were significantly increased after intervention, and these scores were maintained a month after intervention, particularly in those with high MAC "Hopelessness" scores. Subscales of the SELT-M scores were significantly increased after intervention, and these scores were maintained up to a month after intervention. CONCLUSION: Short-term EGP intervention could be effective in helping patients relieve their existential distress. Some of the treatment effects were maintained a month after the end of the intervention. In addition, Short-term EGP could be particularly effective for those patients who feel hopelessness after cancer diagnosis. TRIAL REGISTRATION: Retrospectively registered. University Hospital Medical Information Network (UMIN CTR) UMIN000040651 . Registered June 4, 2020.

Low dose of alcohol attenuates pro-atherosclerotic activity of thrombin.

BACKGROUND AND AIMS: Thrombin, the active enzyme of the coagulation system, plays a critical role in the pathogenesis of atherosclerosis. Vascular repair promoted by stromal cell-derived factor-1 is a protective process in atherosclerosis. Consumption of low amount of alcohol is believed to reduce the risk of atherosclerotic cardiovascular disease but the mechanism is unclear. This study evaluated whether alcohol can modulate the expression of stromal cell-derived factor-1 and the pro-atherosclerotic activity of thrombin. METHODS: Hepatocytes, monocytes, vascular endothelial and vascular smooth muscle cells were pre-treated with increasing concentrations of ethanol before stimulation with thrombin. The expression of cytokines, chemokines, cell adhesion molecules and epigenetic factors, including histone deacetylases and sirtuins, was evaluated. RESULTS: Thrombin stimulation significantly enhanced the expression of pro-inflammatory cytokines, chemokines and cell adhesion molecules, but significantly decreased the expression of stromal cell-derived factor-1. Pre-treatment of cells with a low dose of ethanol significantly decreased thrombin-induced production of pro-inflammatory cytokines and chemokines, and significantly increased the production of stromal cell-derived factor-1 compared to cells treated with thrombin alone. Ethanol significantly counteracted the decreased expression of histone deacetylases and sirtuins induced by thrombin. Inhibition of histone deacetylase-2 with trichostatin A or with specific siRNA abolished the stimulatory activity of low-dose ethanol on stromal cell-derived factor-1. CONCLUSIONS: Low-dose of ethanol attenuates the inflammatory response and counteracts the reduced expression of stromal cell-derived factor-1 induced by thrombin via an epigenetic mechanism, providing a potential explanation for the protective activity of low dose of alcohol in atherosclerosis.

Inhibitory effects of whisky congeners on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

Whisky is matured in oak casks. Many nonvolatile substances (whisky congeners, WC) seep from the oak cask during the maturing process. In this study, three antiallergic agents (syringaldehyde, SA; lyoniresinol, Lyo; and ellagic acid, EA) were isolated from WC. Treatment with SA, Lyo, and EA reduced the elevation of intracellular free Ca(2+) concentration ([Ca(2+)]i) and intracellular ROS production caused by FcepsilonRI activation. The inhibitions of the elevation of [Ca(2+)]i and intracellular ROS production by SA and Lyo were mainly due to the suppression of the NADPH oxidase activity and scavenging of the produced radical, respectively. On the other hand, EA inactivated spleen tyrosine kinase and led to the inhibition of the elevation of [Ca(2+)]i and intracellular ROS production. Furthermore, it was found that WC strongly inhibited IgE binding to the FcepsilonRIalpha chain, whereas SA, Lyo, and EA did not indicate this inhibitory effect. These results suggest that WC inhibits allergic reactions through multiple mechanisms. To disclose the in vivo effects of WC, SA, Lyo, and EA, these compounds were administered to type I allergic model mice, and the passive cutaneous anaphylaxis (PCA) reaction was measured. These compounds remarkably suppressed the PCA reaction. Taken together, these findings suggest that WC seemed to be beneficial to ameliorate allergic reactions.

Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men.

BACKGROUND: The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. METHODS: We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. RESULTS: The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. CONCLUSIONS: The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer.

Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype.

BACKGROUND: Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) increases the risk of UADT cancer in drinkers. METHODS: In a randomized cross-over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3-week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking. RESULTS: The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 microM in saliva vs. 2 to 5 microM in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 microM in saliva vs. 12 to 25 microM in blood), and they were 13 to 25 microM higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes. CONCLUSIONS: There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype.

Contribution of the alcohol dehydrogenase-1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men.

The less-active homozygous alcohol dehydrogenase-1B (ADH1B*1/*1) and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) increase the risk of upper aerodigestive tract cancer (UADTC) in Japanese alcoholics. We evaluated associations between ADH1B/ALDH2 genotypes and the blood and salivary ethanol/acetaldehyde levels of 80 Japanese alcoholic men in the morning when they first visited our hospital after drinking the day before. Higher levels of ethanol persisted in the blood for longer periods in ADH1B*1/*1 carriers (n = 25) than in ADH1B*2 allele carriers after adjustment for the amount and time of the preceding alcohol consumption and body weight [median (25th-75th %): 20.5 mM (15.5-52.4) vs. below detection level (