Search

Chronic alcohol consumption can cause dysbiosis, but it is difficult to determine the effect of alcohol on the structure and activity of gastrointestinal tract microbiota. We therefore designed a noninvasive hydrogen breath test (HBT) to investigate the alteration in the chemical profile of gut microbiota in ethanol-fed rats. Thirteen F344/DuCri rats were fed on a commercial mash food with 16% ethanol solution drinking fluid from 4 weeks of age. HBTs were carried out on six 8-week-old and seven 24-week-old ethanol-fed rats. As controls, HBTs were carried out on sixteen 8-week-old, six 24-week-old, and five 48-week-old male rats. Six 24-week- old male rats were examined twice at 1-week intervals. HBTs were performed after fasting for 24 hr. Rats were orally administrated 4 mL/kg of 65% lactulose solution and housed in an animal chamber. The expired air was collected in a breath-sampling bag at 10-min intervals for 180 min. The hydrogen (H2) and methane (CH4) levels in the breath sample were measured using a breath analyzer and were expressed.as parts- per million (ppm). Elevated H2 and CH4 levels were more frequent in male rats. Maximal values of H2 and CH4 were highest in 8-week- old rats, followed by 48-week-old and 24-week-old rats. No ethanol-fed rat exhaled more than 2 ppm of H2 or CH4 until 180 min after the oral administration of lactulose, unlike the controls. This alteration was more obvious than that of aging or gender differentiation. We conclude that there is a close association between chronic ethanol consumption and H2 and CH4 production. An asymptomatic heavy drinker might have dysbiosis that involves gut microbiota with lower fermentation performance.

Vascular function is regulated by a balance of vasoconstriction and vasorelaxation. Disorder in this balance due to alcohol consumption causes various clinical conditions. In this review, we discuss the effects of acute and chronic ethanol consumption on vascular responses, including vasoconstriction, endothelium-dependent vasorelaxation, and nerve-mediated vasorelaxation. Acute ethanol administration induces vasoconstriction in ethanol-naive animals in vitro. Furthermore, ethanol can both potentiate and suppress agonist-induced Ca(2+)-dependent vasoconstriction. Moreover, ethanol augments Ca(2+)-independent vasoconstriction by increasing Ca2+ sensitivity. Endothelium-dependent relaxation is mediated by the nitric oxide (NO) pathway and the endothelium-derived hyperpolarizing factor (EDHF) pathway. Acute ethanol treatment inhibits both NO- and EDHF-mediated relaxation. Furthermore, acute ethanol ingestion can also potentiate and suppress calcitonin gene-related peptide (CGRP)-induced nerve-mediated relaxation. These opposing effects may be due to differences in species or vascular beds. Thus, acute ethanol treatment decreases vasorelaxation, thereby shifting the contraction-relaxation balance towards contraction. Combined, these effects are one mechanism by which acute heavy alcohol consumption causes circulatory disturbances such as vasospasms or ischemic heart disease. In contrast, chronic low-dose ethanol has no effect on vasoconstriction, whereas chronic high-dose ethanol increases vasoconstriction. Additionally, chronic ethanol intake has diminished, unchanged, and even increased effects on nerve-mediated relaxation; therefore, conclusions on these effects are not possible at present. Interestingly, chronic low-dose ethanol administration enhanced endothelium-dependent relaxation; however, higher doses inhibited these responses. Therefore, regular or light-to-moderate alcohol intake increases vasorelaxation and may suppress elevated blood pressure, whereas chronic heavy alcohol consumption may raise blood pressure, causing various clinical conditions.

In the present study, we measured breath alcohol concentration(BAC)after the administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and examined the safety of OTX outpatient administration. Twenty breast cancer patients who received OTX chemotherapy at our outpatient facility were included. The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60 mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30 minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash or drunkenness due to alcohol were observed. BAC was detected in 10 cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than 0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after 30 minutes. Our results suggest that the effects of alcohol are alleviated 60 minutes after infusion and that patients receiving OTX could return home safely.

Ethanol has a variety of action on neuronal functions, though its mechanism of action remains uncertain. Previous investigations have demonstrated functional alteration of neurotransmitter receptors and ion channels by ethanol at its concentration observed in the blood of alcoholics. Our recent studies have shown that chronic ethanol treatment up-regulates high voltage-gated L-type calcium channels and ryanodine receptors, both of which regulate intracellular Ca2+ concentration, and that the up-regulation of these calcium channels participates in behavioral changes including the rewarding effect. Among inositol 1,4,5-trisphosphate receptors (IP3Rs) classified into three different subtypes (type 1 (IP3R-1), type 2, and type 3 IP3Rs) with distinct physiological properties, IP3R-1 is the major neuronal member in the central nervous system, predominantly enriched in cerebellar Purkinje cells and abundant in neurons in the cerebral cortex. Although the most important result of IP3R channel functions is the change in intracellular Ca2+ concentration and phosphorylation of IP3Rs, there are few available data on ethanol effect on IP3Rs. In this report, we demonstrate the functional relationship between ethanol-induced rewarding effect and IP3R-1 expression and regulatory mechanisms of IP3R-1 expression after chronic ethanol exposure, especially focusing on Ca(2+)-related signal transduction pathways via dopamine D1 receptors using mouse cerebral cortical neurons.

From 1998 to 2000, UOEH Hospital identified a problem with bronchoscopes which were contaminated with mycobacteria. While conducting research into the problem, we found an extensive amount of nontuberculous mycobacteria (NTM) in wet areas. In this study, we collected a total of 114 samples to screen wet areas such as drains and taps in our hospital and in standard residences. We used the Ziehl-Neelsen staining method and specific PCR for mycobacteria. As a result, mycobacteria were detected in 96% (27/28) of hospital samples and 40% (34/86) of standard residential samples. Next, we tried to isolate mycobacteria. Eleven isolates from hospital samples and 24 isolates in standard residential samples were isolated through cultivation. Seventeen isolates of Mycobacterium gordonae were isolated. Four isolates of M avium were isolated exclusively in hospital samples. Three isolates of M. avium were resistant to 8 antimicrobial agents, including antituberculous agents. Two hospital isolates survived in phagocytes. Although 80% ethanol solution was effective in all 13 tested isolates, it was not effective in decontaminating the one drain we tested. After brushing the drain with 80% ethanol solution, mycobacteria were not detected for 3 months. This indicated to us that brushing with 80% ethanol solution was an effective procedure for eradicating mycobacteria.

Alcohol consumption impairs Th1-mediated cellular immune responses and enhances serum IgE levels. It has been reported that the elevated IgE levels are associated with a Th2 polarization response, but the mechanisms for enhancing Th2 polarization by the ethanol treatment remain to be elucidated. The aim of this review is to present and discuss the mechanism of Th2 polarization response by alcohol. IL-12 production by APCs such as monocytes, macrophages, and dendritic cells (DCs) preferentially leads to Th1 polarization. Acute ethanol consumption results in a significant decrease in IL-12 production in LPS-stimulated DCs and a CD40/CD40L interaction between CD40 on the DCs and CD40 ligand expressed on activated T cells. This suggests that Th2 polarization by ethanol is caused by impaired IL-12 production from APCs. In contrast, the induction of IL-10 by LPS is enhanced by ethanol treatment, suggesting that elevated IL-10 may play a role in ethanol-induced suppression of IL-12. However, ethanol inhibited IL-12 production in LPS-stimulated DCs devoid of IL-10 (IL-10/DC), suggesting that down-regulation of IL-12 by ethanol is independent of the IL-10 levels. Furthermore, several studies report that PGE2, cAMP and linolic acid, and endogenous lipid mediators released in inflammatory conditions, also inhibit IL-12 production. These inhibitory effects are similar to the IL-12 inhibition by ethanol. In addition, increase in the levels of these lipid mediators is induced by ethanol treatment. Alternatively, cytokine signaling studies indicate that IL-12 production by DCs is negatively regulated by PI3K and GSK-3, but positively regulated by p38 MAPK, mTOR, and NF-kappa B. Thus, it seems possible that ethanol may interact on the upstream of IL-12 producing a signal pathway. In fact, ethanol alters the stability of cell membrane, and suppresses clustering of TLR4 and recruitment of signaling molecules into lipid rafts, where it associates with the Ser/Thr kinase and the adaptor proteins, and forms a signaling complex. Down-regulation of lipid raft signaling is results in the impaired IL-12 production leading to the Th1 polarization, and causes CD4+ T cells to differentiation toward the Th2 lineage.

Vascular tone is controlled by endothelium and nerves innervating blood vessels. Endothelium releases various substances such as PGI2 (Prostacyclin), NO (nitric oxide), TXA2 (thromboxane A2) and ET-1 (endothelin-1). It is well documented that ethanol affects vascular responses mediated by these substances. On the other hand, peripheral vascular tone is also regulated not only by sympathetic adrenergic nerves but also by nonadrenergic noncholinergic (NANC) nerves. NANC nerves include NO nerves and sensory nerves which release calcitonin gene-related peptide (CGRP) and nerve-mediated hyperpolarizing factor (NDHF). However, effect of ethanol on nerve-mediated vascular responses remains poorly understood. Therefore, this review summarizes the effect of ethanol on the sympathetic adrenergic nerve-mediated vasoconstriction and the sensory nerve-mediated vasorelaxation.

Recent clinical neuroimaging studies have suggested the morphological brain changes occur and progress in the course of alcoholism and depression. The abnormality of neurogenesis has emerged as a potential epidemiological mechanism of these diseases. Previously, we have indicated the low dose of ethanol that could not influence on the survival of neurons and neural stem cell (NSC) suppress differentiation to neurons but glias through activation of neuron-restrictive silencing factor/repressor element-1 silencing transcription factor (NRSF/REST). We revealed the endoplasmic reticulum function and trophic factor signaling change implicated in this mechanism of ethanol action on NSC differentiation change. The analysis of potentials of psychotropic drugs on the ethanol-induced NSC function change may reveal the possible biological way of neural network impairment and its repair. Furthermore, the approach of using stem cells such as intravenous NSC transplantation can be a useful method to clarify the neural network reconstruction damaged by ethanol. The importance of interactive analysis of in vitro to in vivo should be documented for the pathophysiological understanding and new therapy development against alcohol-induced brain damage.

Purpose: To evaluate the effect of disinfectant against human adenovirus (HAdV) using a real-time polymerase chain reaction method., Methods: Ethanol, povidone-iodine, and sodium hypochlorite were mixed with HAdV-3, -4, -8, -19, and -37. A diluted mixed solution was infected with A549 cells for six days and then the number of HAdV DNA copies was counted. A reduction in the number of HAdV DNA copyies by 4 log was considered as virucidal activity., Results: Ethanol at 80% concentration was effective against all serotypes after ten minutes, but 70% and 40% concentrations of ethanol were ineffective against all serotypes. Povidone-iodine at 0.2% concentration was effective against HAdV-3, -4, -19, and -37 after one minute, and against HAdV-8 after three minutes. Sodium hypochlorite (0.1% concentration) was effective against all serotypes after 15 seconds., Conclusion: While all disinfectants were effective against HAdV, the effective concentration percentages and the times required were different, which indicates the importance of deliberating on the concentration, application time and location to apply the disinfectant, and what equipment to use for application.

Hand washing is the most fundamental method for preventing infection. Currently, hand washing with an alcohol-based handrub is the international gold standard method. However, in our study we found many samples of ineffective hand washing using an alcohol-based handrub. The rates of ineffective samples were 10.4% (5/48) in 2004 and 34.3% (12/35) in 2005. We examined the morphology by Gram staining and biochemical properties of the bacteria which remained after hand washing in 2005. Their colonies were divided into 3 groups (round colonies, irregular-shaped and diffusive colonies). The round colonies were considered Staphylococcus spp., and the irregular-shaped colonies or diffusive colonies were considered Gram-positive spore-forming bacteria. In the 12 ineffective hand washing samples (more than the same number of bacteria colonies as before hand washing, or > or = 300), there were 3 samples considered to be the result of the survival of Staphylococcus spp., and 9 samples considered to be the result of the survival of Gram-positive spore-forming bacteria including Bacillus cereus. Based on these results, we should take careful measures, such as wearing sterile gloves if necessary. We should never be overconfident regarding the effect of hand washing.

Morbidity and mortality rates of ARDS (acute respiratory distress syndrome) are high in patients with a history of chronic alcohol abuse. In addition to susceptibility to lung infection, alteration of local cellular functions in the lung has recently been proposed as a new mechanism of exacerbation of ARDS in patients with a history of chronic alcohol abuse. Clinical studies and studies using animal experiments have shown that a decrease in lung glutathione levels is associated with exacerbation of ARDS in chronic alcohol abuse. In the alcoholic lung, depletion of glutathione increases oxidative stress derived from activated neutrophils, resulting in decreased surfactant production, apoptosis and increased permeability of alveolar epithelial type II cells, in which TGF-beta1 may be involved. Acetoaldehyde has been suggested to be involved in the mechanism of exacerbation of ARDS by inducing lung remodeling through stimulation of fibronectin expression following nicotinic acetylcholine receptor stimulation and CREB activation in chronic alcohol abuse. More recently, antagonists of angiotensin II type-1 receptor (AT1 receptor) have been shown to prevent glutathione depletion, increase in TGF-beta1 expression and lung edema in endotoxemic rats with chronic alcohol administration. On the other hand, macrophage-derived prostaglandin E2 plays a protective role at an initial phase of ARDS by inhibiting cytokine production by macrophages and extravascular invasion of activated neutrophils. Our recent studies have shown that LPS-induced COX-2 expression and subsequent prostaglandin E2 production in rat alveolar macrophages are inhibited by ethanol incubation in vitro and ethanol administration in vivo. Only a decade has passed since alcohol abuse was demonstrated to be associated with increased mortality of ARDS and future studies are needed to clarify the mechanism underlying alcohol-induced exacerbation of ARDS.

We previously reported that a loss of contraction in the mucosal tissue of the palate arch is effectively induced by ethanol injections of moderate concentration and dosage. The present study was performed to obtain more information on how such ethanol injections induce contraction loss in mucosa tissue. Guinea pigs of both sexes were used in this study. The left arch of the palate mucosa was injected with 2 microliters of 70% ethanol and used as the experimental group. The right arch of the palate mucosa of the same animal was injected with saline and used as a control. One, three, five, eight, 10, 30, 50, and 90 days after injection, the mucosal tissues that received the injection were resected under anesthesia and processed for light microscopy using standard procedures. One day after the ethanol injection, severe coagulative degeneration of the mucosal tissue of the palate was seen. However, the damaged area was strictly restricted to the arch of the palate. Coagulative degeneration of the tissue peaked three days after the injection. Thereafter, the mucosal epithelial and mucosal connective tissues regenerated, and the damaged mucosal tissue quickly began to repair. An apparent cicatricial contraction loss was observed 10 days after the ethanol injection, along with the progression of fibrotic changes in the submucosal connective tissue of the arch of the palate. The regenerative action of the mucosal arch of the palate abated 30 days after the ethanol injection, and the reduced mucosal tissue appeared to have become denser as a result of an increase in dense fibrous connective tissue in the submucosal layer. No cell malignancies were seen throughout the entire 90-day observation period. In conclusion, cicatricial contraction loss of the mucosal arch of the palate resulting from the injection of an appropriate concentration and dosage of ethanol leads to the regeneration of the mucosal epithelium and fibrotic changes in the submucosa. The ethanol injection described here seems to be extremely safe, since it exerted no malignant effects on the cells and tissues either morphologically or functionally.

Gut-derived endotoxin plays an important role in alcoholic liver injury. Intestinal sterilization with antibiotics (polymyxin B and neomycin) or inactivation of Kupffer cells with gadolinium chloride can prevent early alcohol-induced liver injury in the Tsukamoto-French model. Although short-term administration of alcohol enhances endotoxin hepatotoxicity, a majority of studies report that short-term ethanol inactivates Kupffer cells. It is therefore paradoxical that Kupffer cells are involved in alcoholic liver injury based on in vivo data with gadolinium chloride and antibiotics, yet ethanol blunts activation of isolated Kupffer cells. Accordingly, this review focuses on understanding this paradox by studying the temporal effect of ethanol in vivo on the response of subsequently isolated Kupffer cells. Mice were given ethanol intragastrically, and LPS was injected later. One hour after ethanol treatment, serum transaminases after LPS were 60% of control, while ethanol increased these parameters about 3-fold 21 hours after ethanol. Pretreatment with antibiotics blocked these effects of ethanol. Two hours after ethanol administration, the LPS-induced increases in intracellular calcium concentration and TNF alpha release by Kupffer cells was diminished by 50% of control, and these parameters were reciprocally enhanced two-fold at 24 hours. Sterilization of the gut with antibiotics blocked both effects of ethanol on intracellular calcium concentration and TNF alpha release. Twenty-four hours after ethanol, CD14 in Kupffer cells was elevated to about five-fold. In Kupffer cells from mice treated with ethanol 1 hour earlier, IRAK expression and activity and NF kappa B were decreased to 50-60% of control. In contrast, in Kupffer cells from mice treated with ethanol 21 hours earlier, LPS-induced TNF alpha production, expression and activity of IRAK were increased 1.5-fold over controls, while NF kappa B activation was elevated 3-fold. Kupffer cells isolated from rodents early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. In conclusion, acute ethanol alters the expression of endotoxin receptors and intracellular signaling molecules, and causes both tolerance and sensitization of Kupffer cells to endotoxin. It is postulated that tolerance of Kupffer cells contributes to the impairment of innate immune system in alcoholism, while sensitization to endotoxin enhances progression of alcoholic liver injury.

The dimorphic transition from yeast to pseudohyphae in the petroleum-assimilating yeast Candida tropicalis occurs following the addition of ethanol to glucose semi-defined medium. Subtractive gene cloning was performed on the cDNA from the yeast-growing control culture and on that from the ethanol-supplemented one (the ethanol culture). A homologue of Schizosaccharomyces pombe nmt1+ or Saccharomyces cerevisiae THI5 was isolated from the cDNA fraction as a preferentially expressed gene for the ethanol culture. This homologue was tentatively called Ctnmt1+, since exogenous thiamine repressed its expression in C. tropicalis growth media. The ethanol culture showed a biphasic pattern of growth phases and the expression of Ctnmt1+ occurred at the first growth phase. The supplementation of thiamine to the ethanol culture at the first phase was followed by repression of Ctnmt1+ expression and also delay of pseudohyphal growth: filamentous growth was inhibited and chains of yeast cells were formed. A Ctnmt1+ disruptant of this organism did not show thiamine auxotrophy and produced pseudohyphal filaments even in the control culture. The supplementation of oxythiamine, an analog of thiamine, to the control culture was followed by the appearance of pseudohyphal filaments, indicating the participation of thiamine during the process of pseudohyphal growth in this organism.

We have investigated the effects of single administration of methamphetamine (MAP) (1.0 mg/kg, i.p.), and of combined administration of ethanol (EtOH) (2.0 g/kg, i.v.) and MAP (1.0 mg/kg, i.p.) on striatal extracellular dopamine (DA) and serotonin (5-HT) levels in chronic alcohol treated rats using a brain-microdialysis method. We used two different lines of rats with high and low alcohol preferences, (high alcohol preference rat (HAP) and low alcohol preference rat (LAP), respectively), which were chronically fed an alcohol containing liquid diet for 6 to 8 weeks. The percent change in DA and 5-HT in striatum following single administration of MAP was significantly higher in control-fed LAP than HAP. However, in the alcohol-fed group, the percent changes in DA and 5-HT were significantly elevated in the alcohol-fed HAP compared to LAP. There were no significant increases in striatal extracellular DA and 5-HT in alcohol-fed LAP. In combined administration of MAP and EtOH, extracellular DA and 5-HT levels increased slightly following EtOH administration in chronic alcohol-fed rats, especially in HAP. Dramatic increases of DA and 5-HT levels were observed in alcohol-fed HAP following EtOH and MAP administration. The percent change in DA and 5-HT in alcohol-fed HAP was further elevated to 4667.7 +/- 1095.5% and 3116.9 +/- 1162.7% of the maximal change, respectively. These percent changes ware higher than that observed with a single administration of MAP. Meanwhile, LAP were less sensitive to the influence of chronic EtOH administration and to single administration of MAP. These results demonstrate that a chronic treatment of EtOH enhances the sensitivity to MAP in a high alcohol preference rat line, when two drugs were administrated simultaneously, and that a significant difference of responsiveness to abused drugs was indicated between these two lines. It is necessary to consider the alcohol preference when investigating the interaction of alcohol and/or other abused drugs.

It has long been postulated that an interaction between ethanol and stress may play an important role in the etiology of alcoholism. In the present review, we focused on an interaction between ethanol and stress in the mechanism of psychological dependence on ethanol. Ethanol with conditioned fear stress (CFS), but not without the stress, induced a significant place preference. These results suggest that psychological stress may play an important role in the rewarding effect of ethanol. It has been hypothesized that activation of the mesolimbic dopamine system mediated by the endogenous opioid system may be particularly important in the rewarding mechanism of ethanol. It appeared that mu- and delta-opioid receptors might play critical roles in the development of the rewarding effect of ethanol under the stress. Under psychological stress, the rewarding effect of ethanol through the activation of mu- and/or delta-opioid receptors was found to results the activation of dopamine D1 and/or D2 receptors. Additionally, a subtype of serotonin (5-HT) receptors, 5-HT3 receptor, was shown to be involved in the rewarding mechanism of ethanol through the activation of mu- and delta-opioid receptors. In conclusion, psychological stress may be an important factor in the development of the rewarding effect of ethanol and may potentiate the rewarding mechanism. 5-HT3 receptor, is likely to be involved in the rewarding mechanism of ethanol under stress. Dopamine D1 and D2 receptors may also be implicated in the rewarding mechanism of ethanol under stress.

NC/Nga mouse is well known as a mouse model for atopic dermatitis. In general, when NC/Nga mouse are raised under specific pathogen free (SPF) conditions no skin lesions are detected, but when under non-filtrated (conventional) condition, atopic dermatitis like skin lesions appear spontaneously. However, this dermatitis develops in 70-90% of mice (not 100%), which makes it difficult to perform reproducible experiments every time. This study was performed under SPF conditions, using the four solutions (2% SDS, 4% SDS, ethanol, acetone/ether) to destroy the skin barrier function, and thereafter, applying the extracted solution of mite: Dermatophagoides pteronyssinus, which is a very popular antigen in pathogenesis of human atopic dermatitis. The extracted solution of mite was applied repeatedly on the NC/Nga mice with a pretreatment of barrier destroying solution and after 8 weeks the mice developed severe dermatitis (clinical skin condition score of 7-10.2 points) with marked elevation of plasma IgE level, whereas mice coated only with the barrier destroying solution showed weak skin lesion with no elevation of plasma IgE level. BALB/c mice, which are employed as control, showed weak skin lesion (clinical skin condition score of 0-3.8 points) and slight elevation of plasma IgE level after repeated application of the extracted solution of mite with a pretreatment of the barrier destroying solution, whereas mice coated only with the barrier destroying solution showed weak skin lesion and the no elevation of plasma IgE level was observed. In this study, using several solutions to disturb the skin barrier function before applying the antigen, we have found a suitable condition and types of solutions in inducing dermatitis in NC/Nga mice.

Mycobacteria are being isolated with increasing frequency from automated bronchoscope disinfection machines. This has led to misdiagnosis and nosocomial infections. In this study, we isolated Mycobacterium chelonae from a bronchoscope disinfection machine and found one strain to be resistant to 2% glutaraldehyde and sensitive to 70% ethanol. Since we began cleaning the sink of the machine with 70% ethanol, no mycobacteria has been seen throughout the machine.

We studied about influence of alcohol preference and of simultaneously administered ethanol (EtOH) on the effect of methamphetamine (MA) on the central nervous system neurochemically and behavioral pharmacologically using two strains of rat with high or low preference for alcohol (HAP and LAP). In the neurochemical study, we determined dopamine (DA) and serotonin (5-HT) level in striatum and nucleus accumbens (N.Acc) by means of brain microdialysis after administration of MA 1 mg/kg alone (LAP-MA group, HAP-MA group) or EtOH 2 g/kg + MA 1 mg/kg (LAP-EtOH/MA group, HAP-EtOH/MA group) every 20 minutes for 10 sessions. In the behavioral pharmacological study, we observed rat's behavior in the open field and performed scoring according to Locomotion-Stereotypy (L-S) rating scale by Ellinwood every five minutes, and counted locomotion and rearing by means of infrared beam cutting every 20 minutes after administration of MA 1 mg/kg alone (LAP-MA group, HAP-MA group) or EtOH 2 g/kg + MA 1 mg/kg (LAP-EtOH/MA group, HAP-EtOH/MA group). When MA was given alone, HAP rat showed no significant difference in locomotion, rearing and L-S score compared to LAP rat, although HAP rat showed significantly lower elevation of DA and 5-HT in both striatum and N.Acc. When EtOH was simultaneously administered with MA, in LAP rat, DA and 5-HT elevation in the striatum and N.Acc showed no significant differences between LAP-EtOH/MA group and LAP-MA group. Locomotion and rearing reduced and L-S score temporarily reduced significantly in LAP-EtOH/MA group compared to LAP-MA group. However in HAP rat, HAP-EtOH/MA group showed significantly higher DA and 5-HT elevation in both striatum and N.Acc, and also showed significantly higher L-S score and higher locomotion count compared to HAP-MA group. Our results indicate that effect of MA may be influenced by alcohol preference, and that simultaneous administration of EtOH emphasizes the effect of MA on central nervous system in rat with high alcohol preference.

Purpose: The effect of the consumption of ethanol on the circulation of the optic nerve head (ONH) in the human eye in the acute phase and its mechanism were studied., Methods: Eleven volunteers drank a bottle of beer (633 ml) with or without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood flow velocity, was measured in the temporal site of the ONH. NB, blood pressure (BP) and pulse rate (PR) were measured before, immediately after, and every 15 minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma ethanol concentration were measured before, and 30 and 90 minutes after consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also performed., Results: NB in the ONH increased significantly from 15 to 45 minutes after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP was lowered at 90 minutes after consumption, but it was not significant. Mean BP was lowered significantly after 60 minutes. PR and ocular perfusion pressure did not change. A significant correlation was found between plasma ethanol concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was significantly larger from 15 to 45 minutes after consumption than in the proficient group., Conclusion: It appeared that the consumption of ethanol can increase the blood flow in the human ONH in the acute phase through decreased resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.

There are few reports regarding the effects of benzene and ethanol being administered simultaneously. In our experiments with 4 groups (controls, ethanol, benzene and ethanol plus benzene) Wistar male rats were treated with ethanol (20%) for 5 weeks, and then exposed to benzene (0.26 g/kg) for 5 days per week for 3 weeks. We also investigated the effects of benzene on the body weight, organ weight, peripheral hematology and hepatic drug metabolizing enzymes in the ethanol administrated rats. The liver weight increased significantly, but spleen weight decreased significantly in the benzene exposed group. Hematological examination showed a decrease of leukocyte in the two groups of benzene and ethanol plus benzene in comparison with the controls, but an effect promoted by ethanol was not found. Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) values were not significantly different in the exposure groups when compared with the controls. The contents of microsomal cytochrome P450 in all the exposed groups showed a tendency to increase, but they were not significantly different in comparison with the controls. On the other hand, hepatic glutathione S-transferase activity in the exposed groups increased significantly.

We investigated the effects of different concentrations of ethanol on contraction of gallbladder isolated from guinea pig. Ethanol at 25 mM significantly inhibited the contraction induced by histamine, but not those by KCl and acetylcholine. A higher concentration (100 mM) of ethanol inhibited both histamine-, acetylcholine- and KCl- induced contractions. The inhibitory effect of the lower concentration (25 mM) of ethanol was not observed in the presence of verapamil, an antagonist of L-type Ca2+ channel or staurosporine, a selective inhibitor of protein kinase C. Verapamil and staurosporine significantly inhibited both histamine- and acetylcholine-induced contractile responses: the inhibitory effect was more potent for the histamine contraction. Our recent study has demonstrated that contraction caused by protein kinase C activation is completely dependent on Ca2+ influx through the L-type Ca2+ channel in gallbladder smooth muscle of guinea pig. Therefore, the difference in 25 mM ethanol effect on histamine- and acetylcholine-induced contractions may be due to different degree of involvement of protein kinase C activation in the agonist-induced contraction. On the other hands, the higher concentration (100 mM) of ethanol inhibits the common pathway of contraction in gallbladder smooth muscle cells.

Reports on effects of ethanol intake on the kidneys and bones are few. Circulation of blood through the kidneys is large in amount; kidney takes water-soluble exogenous substances and their metabolites in from the blood and accumulates them in the cells and interstitial tissues; in addition kidney plays important roles in producing substances that activate a living body and associating with their functions. The author let male and female ICR mice take 16% ethanol (Sake) ad lib for 472 days beginning at the age of 38 days. Observations were carried out on renal tissues and other organs which have some connection with the renal function. These included bones (femur, knee joint, tibia), muscle (gastrocnemius), 1 alpha, 25(OH)2D3 and erythropoietin (EPO). The results were as follows: Renal tissue observations: Significantly more cases of appearances of basophilic renal tubular, swelling of tubular epithelial cells and urinary casts in tubular lumens, PAS positive deposits in glomerulus, and atrophy of glomerulus were seen in the ethanol groups than in a group used as the control. These occurrences were significantly clear and intensive relative to those in the control. Findings in gastrocnemius: Significantly large number of muscle atrophy, random variation of fiber size and multinucleated fibers were seen. Observations on bones based upon soft X-ray pictures: Bone atrophy, thinning of bone trabeculae, thinning of bone cortex, and porosity of bone cortex were disclosed significantly more than the control. Values of 1 alpha, 25(OH)2D3 and EPO were significantly high increased in the ethanol groups relative to the control. Through the above-mentioned results, it has been supposed that ethanol intake affects kidney tissues and consequently affects bones and muscles.

The authors attempted to clarify the histological changes of superior cervical ganglion (SCG) cells in chronological order. Adult rat SCGs were injected with ethyl alcohol and were examined under light microscopy after fixation and histological processes. All neurons showed the so-called coagulation necrosis. Inflammatory reactions characterized by cellular invasion were delayed in contrast to ethyl alcohol exposure from outside of the ganglion capsule.

Research on the interaction of ethanol and stress with experimental animals are briefly reviewed. There might be the two aspects of the interaction of stress and ethanol, i.e., how stress affects ethanol ingestion and response to ethanol, and how ethanol modifies stress response. In general, stress increases ingestion of ethanol in animals exposed to various stresses including electric shock, immobilization and psychological or emotional stresses, wherein the psychological or emotional factors were predominantly involved. However, in most cases, ethanol ingestion is increased after release from stress not during exposure to stress. A variety of stressful stimuli caused marked increases in the neurotransmitter release in many brain regions. Immobilization stress increased noradrenaline release in the extended brain regions in rats. These increases were significantly attenuated by pretreatment with ethanol in the rat amygdala and locus coeruleus, but not in the hypothalamus, although ethanol by itself increased noradrenaline release in the hypothalamus. Further, psychological stress, wherein the rats were given no electrical shock, but exposed to the emotional responses such as struggling, vocalization, jumping and defecation shown by the other electrically-shocked rats, increased noradrenaline release preferentially in the hypothalamus, amygdala and locus coeruleus. Among the former two regions, stress-induced increases in noradrenaline release were significantly attenuated by ethanol in the amygdala, but not in the hypothalamus. Together with the finding that increases, in noradrenaline release are closely related to the provocation of anxiety and/or fear, ethanol, in part, reduced tension, as mentioned in the tension reduction hypothesis, by attenuating stress-induced increases in noradrenaline release in the amygdala and locus coeruleus. Moreover, ethanol, administered i.p. and directly through the microdialysis probe, increased dopamine release in the nucleus accumbens assessed by in vivo microdialysis, similarly as addictive drugs such as amphetamine did. This might be, in part, neurochemical basis for motivation of repeated drinking of ethanol.

Ethanol has been reported to cause mycelial growth in Candida tropicalis Pk233. Cultivation with ethanol in synthetic media containing glucose gave biphasic growth curves. During the first growth phase, there was an accumulation of swollen spherical yeast cells, instead of the oblong ones observed in the control culture, followed by the appearance of spherical daughter cells in chains. During the second growth phase, pseudohyphal cells appeared, projecting from the swollen yeast cells.Subtractive cloning was performed on cDNAs from both cultures to isolate genes expressed during the first phase, correlating to the process of ethanol induced hyphal growth. Subtracted cDNAs identified by homology search included a homologue of URP2 coding ribosomal protein S20, a homologue of nmt1 coding a regulator gene working on thiamine metabolism, and a homologue of MSG5 coding tyrosine phosphatase. Roles of these cloned homologues were discussed on the process of mycelial growth in this organism.

Using aortic strips isolated from guinea pigs, effects of ethanol on vascular smooth muscle tonus were studied. 50mM of ethanol significantly potentiated the contractions induced by norepinephrine and phenylephrine, but did not influence those induced by KCl and clonidine. Furthermore, ethanol significantly augmented the contraction induced by phenylephrine in the presence of verapamil, and did not have any effects on the contractions induced by A23187, Ba2+, PDBu and BAY K 8644. These results indicate that ethanol potentiates the alpha 1 adrenergic receptor-mediated contraction, depending on the extracellular calcium influx via the receptor-operated calcium channel.

The effect of the number of carbon atoms of alcohols (1 mM) on intramuscular Ca(2+)-related functions was studied using the skinned fiber technique in guinea pig skeletal muscles. The rate of calcium induced calcium release (CICR) increased steadily with increasing number of carbon atoms until 6 and then fell. Ca2+ uptake by the sarcoplasmic reticulum (SR) was not affected with the number of carbon atoms of alcohols. Ca2+ sensitivity of the contractile system was affected with the number of carbon atoms of alcohols. The pCa-tension curves were shifted to the left at low concentrations of Ca2+, and decreased at high concentrations of Ca2+ (beyond carbon atoms 6). Alcohols enhanced CICR from the SR significantly, but the cut-off in potency was observed in higher numbers of carbon atoms as observed with volatile anesthetics. These results suggested that it is possible to use alcohols instead of halothane in caffeine-halothane-contracture test (CHCT).