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1.
Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro.
Hörauf, JA, Kany, S, Janicova, A, Xu, B, Vrdoljak, T, Sturm, R, Dunay, IR, Martin, L, Relja, B
International journal of molecular sciences. 2020;(9)
Abstract
This paper discusses how the assembly of pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) in macromolecular protein complexes, inflammasomes, activates caspase-1. The present study investigates the molecular mechanisms of inflammasome activation in HepG2 cells and examines how short exposures to ethanol (EtOH) affect inflammasome activation. HepG2 cells were treated with lipopolysaccharide (LPS), ATP or nigericin (NIG) in a two-step model. After LPS priming, ATP or NIG were added. As inhibitors, sodium orthovanadate (general inhibitor of tyrosine phosphatases), AC-YVAD-CMK (caspase-1 inhibitor) or AZ10606120 (purinergic receptor P2X7R inhibitor) were applied after LPS priming. To monitor the inflammasome activation, the caspase-1 activity, ASC speck formation, reactive oxygen species (ROS) production and cell death were analyzed. To elucidate the mechanistical approach of EtOH to the inflammasome assembly, the cells were treated with EtOH either under simultaneous LPS administration or concurrently with ATP or NIG application. The co-stimulation with LPS and ATP induced a significant ASC speck formation, caspase-1 activation, cell death and ROS generation. The inhibition of the ATP-dependent purinoreceptor P2X7 decreased the caspase-1 activation, whereas sodium orthovanadate significantly induced caspase-1. Additional treatment with EtOH reversed the LPS and ATP-induced caspase-1 activation, ASC speck formation and ROS production. The ASC speck formation and caspase-1 induction require a two-step signaling with LPS and ATP in HepG2 cells. Inflammasome activation may depend on P2X7. The molecular pathway of an acute effect of EtOH on inflammasomes may involve a reduction in ROS generation, which in turn may increase the activity of tyrosine phosphatases.
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2.
Consumer perception and behaviour related to low-alcohol wine: do people overcompensate?
Bucher, T, Frey, E, Wilczynska, M, Deroover, K, Dohle, S
Public health nutrition. 2020;(11):1939-1947
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Abstract
OBJECTIVE Compared with standard wines, low-alcohol wines may have several social and health benefits. Innovative production processes have led to high-quality light wines. It is, however, unclear how consumers perceive and consume these alcohol-reduced wines. The current study aimed to investigate how people evaluate low-alcohol wine (Sauvignon Blanc) and if the reduction in alcohol and the information that a wine is low in alcohol influences consumption. DESIGN Randomised controlled trial (RCT). SETTING Participants were invited to a wine tasting and randomised into one of the three conditions: they either tasted a 'new white wine' (12·5 % alcohol content), a 'new low-alcohol white wine' (8·0 % alcohol content) or they tasted the low-alcohol wine but were not aware that the wine was reduced in alcohol (low-alcohol, blinded). PARTICIPANTS Ninety participants (42 % male, mean age = 41 (sd 14) years). RESULTS Mean comparisons showed similar ratings for the low-alcohol conditions and the standard alcohol condition (mean > 5·6/7). The mean consumed amount across all conditions did not differ (162 (sd 71) ml, (F2,86 = 0·43, P > 0·05)), hence people who tasted the low-alcohol wine consumed approximately 30 % less alcohol. However, participants were willing to pay more for the normal wine compared with the low-alcohol wine, (F2,87 = 3·14, P < 0·05). CONCLUSIONS Participants did not alter their drinking behaviour in response to the reduced alcohol content, and the low-alcohol wine was perceived positively. There might be an emerging market potential for wine of reduced alcohol content, but consumers may not be willing to pay the same price as for the standard wine.
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Designing Efficient Processes for Sustainable Bioethanol and Bio-Hydrogen Production from Grass Lawn Waste.
Antonopoulou, G
Molecules (Basel, Switzerland). 2020;(12)
Abstract
The effect of thermal, acid and alkali pretreatment methods on biological hydrogen (BHP) and bioethanol production (BP) from grass lawn (GL) waste was investigated, under different process schemes. BHP from the whole pretreatment slurry of GL was performed through mixed microbial cultures in simultaneous saccharification and fermentation (SSF) mode, while BP was carried out through the C5yeast Pichia stipitis, in SSF mode. From these experiments, the best pretreatment conditions were determined and the efficiencies for each process were assessed and compared, when using either the whole pretreatment slurry or the separated fractions (solid and liquid), the separate hydrolysis and fermentation (SHF) or SSF mode, and especially for BP, the use of other yeasts such as Pachysolen tannophilus or Saccharomyces cerevisiae. The experimental results showed that pretreatment with 10 gH2SO4/100 g total solids (TS) was the optimum for both BHP and BP. Separation of solid and liquid pretreated fractions led to the highest BHP (270.1 mL H2/g TS, corresponding to 3.4 MJ/kg TS) and also BP (108.8 mg ethanol/g TS, corresponding to 2.9 MJ/kg TS) yields. The latter was achieved by using P. stipitis for the fermentation of the hydrolysate and S. serevisiae for the solid fraction fermentation, at SSF.
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Bactericidal and virucidal activity of ethanol and povidone-iodine.
Sauerbrei, A
MicrobiologyOpen. 2020;(9):e1097
Abstract
Ethanol and povidone-iodine (PVP-I) are important microbicides that inactivate bacteria and viruses. The present study provides a review of literature data on the concentration-dependent bactericidal and virucidal activity of ethanol and PVP-I in vitro. A systematic search was performed using the meta-database for biomedicine PubMed. Eventually, 74 studies with original data on the reduction of bacterial and viral infectivity using in vitro tests were analyzed. A safe bactericidal effect of ethanol can be expected at concentrations between 60% and 85%, and the exposure times vary between ≤0.5 and ≥5 min. Within an exposure of up to 5 min, 80%-90% ethanol also exerts virucidal/low-level activity, which includes its action against enveloped viruses plus adeno-, noro-, and rotaviruses. For PVP-I, the best bactericidal and virucidal/high-level effect is present at a concentration range of approx. 0.08%-0.9% depending on the free iodine concentration. The maximum exposure times are 5 min for bacteria and 60 min for viruses. The available data may help optimize the significant inactivation of bacteria and viruses in various areas. However, as the conditions in application practice can vary, concrete recommendations for the application can only be derived to a limited extent.
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5.
Effect of desalted Salicornia europaea L. ethanol extract (PM-EE) on the subjects complaining memory dysfunction without dementia: a 12 week, randomized, double-blind, placebo-controlled clinical trial.
Lee, WJ, Shin, YW, Kim, DE, Kweon, MH, Kim, M
Scientific reports. 2020;(1):19914
Abstract
Desalted Salicornia europaea L. (SE) inhibits acetylcholine esterase, attenuates oxidative stress and inflammatory cytokines, and activates neurotrophic pathway. We performed 12-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy of PhytoMeal(a desalted SE)-ethanol extract (PM-EE), in improving the cognitive performance in patients with subjective memory impairment. 63 participants complaining memory dysfunction without dementia (Korean Mini-Mental State Examination [K-MMSE] score ≥ 23) were assigned to PM-EE 600 mg/day or placebo. The cognitive domain of the Alzheimer's disease assessment scale-Korean version (ADAS-K) was set as the primary outcome. After 12 weeks, there was no differences in the changes in the primary outcome or the frequency of adverse events between the groups. In the subgroup analysis for the 30 subjects with mild cognitive impairment (MCI, baseline K-MMSE scores ≤ 28), PM-EE significantly improved the color-reading score of the Korean color-word stroop test (8.2 ± 25.0 vs. - 4.7 ± 13.2, P = 0.018). Our findings suggest that PM-EE is safe but might not be effective in this setting of this study. However, PM-EE may improve the frontal executive function in the patients with MCI. Further large-sized studies with longer follow-up period is warranted (trial registration number KCT0003418).
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Evaluation and review of ways to differentiate sources of ethanol in postmortem blood.
Lin, Z, Wang, H, Jones, AW, Wang, F, Zhang, Y, Rao, Y
International journal of legal medicine. 2020;(6):2081-2093
Abstract
Accurate determination of a person's blood alcohol concentration (BAC) is an important task in forensic toxicology laboratories because of the existence of statutory limits for driving a motor vehicle and workplace alcohol testing regulations. However, making a correct interpretation of the BAC determined in postmortem (PM) specimens is complicated, owing to the possibility that ethanol was produced in the body after death by the action of various micro-organisms (e.g., Candida species) and fermentation processes. This article reviews various ways to establish the source of ethanol in PM blood, including collection and analysis of alternative specimens (e.g., bile, vitreous humor (VH), and bladder urine), the identification of non-oxidative metabolites of ethanol, ethyl glucuronide (EtG) and ethyl sulfate (EtS), the urinary metabolites of serotonin (5-HTOL/5-HIAA), and identification of n-propanol and n-butanol in blood, which are known putrefaction products. Practical utility of the various biomarkers including specificity and stability is discussed.
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The effect of acute intragastric vs. intravenous alcohol administration on inflammation markers, blood lipids and gallbladder motility in healthy men.
Lanng, AR, Gasbjerg, LS, Bergmann, NC, Gillum, MP, Rehfeld, JF, Helsted, MM, Møller, HJ, Grønbæk, H, Vilsbøll, T, Knop, FK
Alcohol (Fayetteville, N.Y.). 2020;:29-37
Abstract
Ethanol intake increases plasma concentrations of triglycerides and chronic ethanol use impairs lipid metabolism and causes chronic inflammation. The gut plays an important role in metabolic handling of nutrients, including lipids, and a leaky gut associated with alcohol intake, allowing inflammatory signals to the portal vein, has been proposed to constitute a mechanism by which ethanol induces hepatic inflammation. We compared the effects of enteral and parenteral administration of ethanol on a range of circulating inflammation markers (including soluble CD163, a marker of liver macrophage activation), lipids, cholecystokinin (CCK) and fibroblast growth factor 19 (FGF19) as well as gallbladder volume. On two separate and randomized study days, we subjected healthy men (n = 12) to double-blinded intragastric ethanol infusion (IGEI) and isoethanolemic intravenous ethanol infusion (IVEI). Blood was sampled and ultrasonographic evaluation of gallbladder volume was performed at frequent intervals for 4 h after initiation of ethanol administration on both days. Little or no effects were observed on plasma levels of inflammation markers during IGEI and IVEI, respectively. Circulating levels of total, low-density lipoprotein and high-density lipoprotein cholesterol decreased after ethanol administration independently of the administration form. Triglyceride and very low-density lipoprotein (VLDL) cholesterol concentrations increased more after IGEI compared to IVEI. IVEI had no effect on plasma CCK and caused an increased gallbladder volume whereas IGEI elicited a CCK response (P < 0.0001) without affecting gallbladder volume. Circulating FGF19 concentrations decreased equally in response to both ethanol administration forms. In conclusion, by evaluating a range of circulating inflammation markers during IGEI and IVEI we were not able to detect signs of systemic low-grade inflammation originating from the presence of ethanol in the gut. IVEI increased gallbladder volume whereas IGEI increased plasma CCK (with neutral effect on gallbladder volume), increased plasma VLDL cholesterol and triglyceride concentrations; indicating that the enteral route of administration may influence ethanol's effects on lipid metabolism.
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Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration.
Teixeira-Coelho, F, Santos, DFC, Santos, GA, Sousa, TF, Moreira, SR, Souza, MVC, Wanner, SP
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2020;(4):e9200
Abstract
The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observed before exercise and was sustained thereafter.
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Interaction of Ethanol and Oral ANS-6637, a Selective ALDH2 Inhibitor in Males: A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Cohort Study.
O'Malley, SS, Shram, MJ, Levy-Cooperman, N, Vince, B, Strumph, PM, Diamond, I, Blackburn, BK
Alcoholism, clinical and experimental research. 2020;(9):1885-1895
Abstract
BACKGROUND ANS-6637, an orally bioavailable selective and reversible aldehyde dehydrogenase-2 (ALDH2) inhibitor, is under development for drug and alcohol use disorders. During the elimination of alcohol, ALDH2 metabolizes acetaldehyde to acetate; inhibiting this enzyme can lead to aversive reactions due to the accumulation of acetaldehyde. Thus, understanding the safety and tolerability of ANS-6637 in combination with alcohol is essential. TRIAL DESIGN AND METHODS Forty eight healthy males participated in a randomized, double-blind, placebo-controlled, single-ascending dose cohort study of oral ANS-6637. Eligible participants were randomized to ANS-6637 (n = 36) or placebo (n = 12) in a 3:1 fashion in each of 6 dose cohorts (8 per cohort; ANS-6637 dose levels were 25, 50, 100, 200, 400, and 600 mg). Two hours after receiving study drug, participants drank up to 5 standard drinks, 1 every 30 minutes. Safety assessments, pharmacodynamic measures, and pharmacokinetic blood samples were obtained. RESULTS Flushing was the most common adverse event (AE) associated with ANS-6637 (24 of 36 participants) compared with placebo (3 of 12). Statistically significant, but modest, increases in heart rate (HR) occurred (+10.5 bpm after 2 drinks; +16.9 to + 20.5 bpm after 3rd through 5th drink). No participant met HR or systolic blood pressure criteria for stopping ethanol administration. There were no clinically significant QTc interval prolongations. Individuals receiving ANS-6637 reported lower ratings of liking, alcohol effects, and feeling drunk. CONCLUSIONS A single oral dose of ANS-6637 with up to 5 standards drinks over 2.5 hours was generally well tolerated in healthy males. The most common pharmacological response was flushing and an increase in HR, which are known effects of acetaldehyde accumulation and consistent with inhibition of ALDH2 with oral ANS-6637 in combination with alcohol. The results of this alcohol interaction study support further testing of ANS-6637 in individuals who consume alcohol heavily.
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Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.
McNabb, S, Harrison, TA, Albanes, D, Berndt, SI, Brenner, H, Caan, BJ, Campbell, PT, Cao, Y, Chang-Claude, J, Chan, A, et al
International journal of cancer. 2020;(3):861-873
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Abstract
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.