Approaches and reporting of alcohol and other drug testing for injured patients in hospital-based studies: A systematic review.

ISSUE: Hospital alcohol and/or other drug (AOD) testing is important for identifying AOD-related injuries; however, testing methods vary. This systematic review aimed to examine biological AOD testing methods from hospital-based studies of injured patients and quantify what proportion reported key information on those testing methods. APPROACH: Observational studies published in English from 2010 onwards involving biological AOD testing for injured patients presenting to hospital were included. Studies examining single injury causes were excluded. Extracted data included concentration thresholds for AOD detection (e.g., lower limits of detection, author-defined cut-offs), test type (e.g., immunoassay, breathalyser) and approach (e.g., routine, clinical discretion), timing of testing, sample type and the proportion of injured cases tested for AODs. KEY FINDINGS: Of 83 included studies, 76 measured alcohol and 37 other drugs. Forty-nine studies defined blood alcohol concentration thresholds (ranging from 0 to 0.1 g/100 mL). Seven studies defined concentration thresholds for other drugs. Testing approach was reported in 39/76 alcohol and 18/37 other drug studies. Sample type was commonly reported (alcohol: n = 69/76; other drugs: n = 28/37); alcohol was typically measured using blood (n = 60) and other drugs using urine (n = 20). Studies that reported the proportion of cases tested (alcohol: n = 53/76; other drugs: n = 28/37), reported that between 0% and 89% of cases were not tested for alcohol and 0% and 91% for other drugs. Timing of testing was often unreported (alcohol: n = 61; other drugs: n = 30). IMPLICATIONS AND CONCLUSION: Variation in AOD testing methods alongside incomplete reporting of those methods limits data comparability and interpretation. Standardised reporting of testing methods will assist AOD-related injury surveillance and prevention.

Subjective intoxication predicts alcohol-related consequences at equivalent alcohol concentrations in young adults using ecological momentary assessment and alcohol sensors.

OBJECTIVE: Subjective intoxication (SI) when drinking may serve as an internal barometer of whether to continue drinking or engage in potentially unsafe behavior. Mobile assessments offer the potential to use SI as a prospective risk indicator during drinking episodes; little evidence exists for the validity of real-time SI measures. We test the correspondence of SI with estimated blood alcohol concentration and transdermal alcohol concentration (TAC) in young adults' natural settings. We provide a novel test of whether SI features (peak and mean SI) uniquely predict consequences adjusting for alcohol concentration. METHOD: Two hundred twenty-two heavy-drinking young adults (Mage = 22.3, 64% female, 79% non-Hispanic White, 84% undergraduates) participated in a 6-day study that used ecological momentary assessment of drinking and TAC sensors. SI was assessed every 30 min during drinking episodes. Multilevel modeling was used to test hypotheses. RESULTS: Momentary SI and estimated blood alcohol concentration had moderate associations at the moment and day levels (standardized ßs = 0.5-0.6); SI was moderately associated with TAC at the day level (ßs = 0.5). Associations between SI and alcohol concentration varied widely between persons and across days. Day-level SI features predicted consequences when adjusting for alcohol concentration (incidence rate ratios, IRRs = 1.29-1.70). CONCLUSIONS: Our two-item SI measure shows evidence of validity in real-world settings with heavy-drinking young adults. SI was significantly correlated with alcohol concentration and was a unique predictor of consequences. The strength of these associations varied greatly across persons and days. Real-time SI measurement may be useful in preventive interventions, but continued research is needed into when and for whom momentary SI is most predictive of risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Modeling Postmortem Ethanol Production/Insights into the Origin of Higher Alcohols.

The forensic toxicologist is challenged to provide scientific evidence to distinguish the source of ethanol (antemortem ingestion or microbial production) determined in the postmortem blood and to properly interpret the relevant blood alcohol concentration (BAC) results, in regard to ethanol levels at death and subsequent behavioral impairment of the person at the time of death. Higher alcohols (1-propanol, 1-butanol, isobutanol, 2-methyl-1-butanol (isoamyl-alcohol), and 3-methyl-2-butanol (amyl-alcohol)) are among the volatile compounds that are often detected in postmortem specimens and have been correlated with putrefaction and microbial activity. This brief review investigates the role of the higher alcohols as biomarkers of postmortem, microbial ethanol production, notably, regarding the modeling of postmortem ethanol production. Main conclusions of this contribution are, firstly, that the higher alcohols are qualitative and quantitative indicators of microbial ethanol production, and, secondly that the respective models of microbial ethanol production are tools offering additional data to interpret properly the origin of the ethanol concentrations measured in postmortem cases. More studies are needed to clarify current uncertainties about the origin of higher alcohols in postmortem specimens.

Cannabis Legalization and Detection of Tetrahydrocannabinol in Injured Drivers.

BACKGROUND: The effect of cannabis legalization in Canada (in October 2018) on the prevalence of injured drivers testing positive for tetrahydrocannabinol (THC) is unclear. METHODS: We studied drivers treated after a motor vehicle collision in four British Columbia trauma centers, with data from January 2013 through March 2020. We included moderately injured drivers (those whose condition warranted blood tests as part of clinical assessment) for whom excess blood remained after clinical testing was complete. Blood was analyzed at the provincial toxicology center. The primary outcomes were a THC level greater than 0, a THC level of at least 2 ng per milliliter (Canadian legal limit), and a THC level of at least 5 ng per milliliter. The secondary outcomes were a THC level of at least 2.5 ng per milliliter plus a blood alcohol level of at least 0.05%; a blood alcohol level greater than 0; and a blood alcohol level of at least 0.08%. We calculated the prevalence of all outcomes before and after legalization. We obtained adjusted prevalence ratios using log-binomial regression to model the association between substance prevalence and legalization after adjustment for relevant covariates. RESULTS: During the study period, 4339 drivers (3550 before legalization and 789 after legalization) met the inclusion criteria. Before legalization, a THC level greater than 0 was detected in 9.2% of drivers, a THC level of at least 2 ng per milliliter in 3.8%, and a THC level of at least 5 ng per milliliter in 1.1%. After legalization, the values were 17.9%, 8.6%, and 3.5%, respectively. After legalization, there was an increased prevalence of drivers with a THC level greater than 0 (adjusted prevalence ratio, 1.33; 95% confidence interval [CI], 1.05 to 1.68), a THC level of at least 2 ng per milliliter (adjusted prevalence ratio, 2.29; 95% CI, 1.52 to 3.45), and a THC level of at least 5 ng per milliliter (adjusted prevalence ratio, 2.05; 95% CI, 1.00 to 4.18). The largest increases in a THC level of at least 2 ng per milliliter were among drivers 50 years of age or older (adjusted prevalence ratio, 5.18; 95% CI, 2.49 to 10.78) and among male drivers (adjusted prevalence ratio, 2.44; 95% CI, 1.60 to 3.74). There were no significant changes in the prevalence of drivers testing positive for alcohol. CONCLUSIONS: After cannabis legalization, the prevalence of moderately injured drivers with a THC level of at least 2 ng per milliliter in participating British Columbia trauma centers more than doubled. The increase was largest among older drivers and male drivers. (Funded by the Canadian Institutes of Health Research.).

Oxidative stress and biochemical indicators in blood of patients addicted to alcohol treated for acute ethylene glycol poisoning.

Ethylene glycol (EG), in addition to its neurotoxic and nephrotoxic effects, evokes oxidative stress. The aim of this study was to assess the influence of the ethylene glycol on the biochemical indicators and oxidoreductive balance of patients treated for acute poisoning. The total study group consisted of 56 persons including 26 alcoholics who took EG as a substitute for ethyl alcohol in the course of alcohol dependence syndrome and 30 controls. Severity of poisoning, results of acid-base parameters, biochemical, and toxicological tests as well as biomarkers of the oxidative stress in blood were analyzed during the patients' hospitalization. The key issue was to assess the oxidative stress and biochemical disturbances caused by EG and the type of treatment applied in the course of poisoning. Significant changes in some parameters were found both at time of diagnosis and after treatment initiation (ethanol as an antidote and hemodialysis). The most important differences included the activity of hepatic parameters (aspartate aminotransferase, AST) and oxidative stress markers like catalase (CAT); correlation of the lipid peroxidation products level (TBARS) with urea concentration has been shown. On the last day of the hospitalization, in some cases, the mutual correlation between the evaluated markers were observed, for example, between alanine transaminase (ALT) and glutathione reductase (GR), and urea concentration and glutathione level (GSH/GSSG). The concentration of ions (H+) had a major impact on the oxidoreductive balance, correlating with the elevated GR and GSH/GSSG levels.

Development and validation of an analytical method for the simultaneous determination of the alcohol biomarkers ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol in human blood.

As alcohol is the most common addictive substance worldwide, it is inevitable to advance the established research. New and more substantial analytical methods can be applied to reply to complex questions in legal or forensic contexts. Therefore, an analytical method for the simultaneous determination of four different alcohol biomarkers-ethyl glucuronide, ethyl sulfate, N-acetyltaurine, and 16:0/18:1-phosphatidylethanol-in human blood was developed, validated, and verified. Despite the different chemical properties of the analytes, a specific determination via HPLC-MS/MS was achieved using a novel type of a Phenomenex Luna® Omega Sugar column. Furthermore, all criteria for a successful validation were fulfilled according to forensic guidelines. The method proved to be linear and demonstrates selectivity and sufficient sensitivity for every biomarker. LODs obtained with this method of 2.6 ng/ml (EtG), 4.7 ng/ml (EtS), 12.5 ng/ml (NAcT), and 6.9 ng/ml (PEth) were in an acceptable range for routine applications, and the stability of all analytes over a range of 12 h is given. The verification of the new developed method was performed with authentic samples. Thus, whole blood and postmortem samples were analyzed to obtain information about the drinking behavior, which can answer complex questions regarding alcohol consumption.

Long-term alcohol drinking in High Drinking in the Dark mice is stable for many months and does not show alcohol deprivation effects.

We have modelled genetic risk for binge-like drinking by selectively breeding High Drinking in the Dark-1 and -2 (HDID-1 and HDID-2) mice for their propensity to reach intoxicating blood alcohol levels (BALs) after binge-like drinking in a single bottle, limited access paradigm. Interestingly, in standard two-bottle choice (2BC) tests for continuously available alcohol versus water, HDID mice show modest levels of preference. This indicates some degree of independence of the genetic contributions to risk for binge-like and sustained, continuous access drinking. We had few data where the drinking in the dark (DID) tests of binge-like drinking had been repeatedly performed, so we serially offered multiple DID tests to see whether binge-like drinking escalated. It did not. We also asked whether HDID mice would escalate their voluntary intake with prolonged exposure to alcohol 2BC. They did not. Lastly, we assessed whether an alcohol deprivation effect (ADE) developed. ADE is a temporary elevation in drinking typically observed after a period of abstinence from sustained access to alcohol choice. With repetition, these periods of ADE sometimes have led to more sustained elevations in drinking. We therefore asked whether repeated ADE episodes would elevate choice drinking in HDID mice. They did not. After nearly 500 days of alcohol access, the intake of HDID mice remained stable. We conclude that a genetically-enhanced high risk for binge-like drinking is not sufficient to yield alterations in long-term alcohol intake.

Profiling of extracellular vesicle-bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates.

BACKGROUND: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease. METHODS: In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking. RESULTS: We identified a list of up- and downregulated EV-miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased production of the inflammatory cytokines TNFα or IL-6 in peripheral blood mononuclear cells after stimulation. CONCLUSION: This exploratory study identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking and provide a mechanism to explain alcohol-induced peripheral inflammation.

Pyruvate and Glutamine Define the Effects of Cholecystokinin and Ethanol on Mitochondrial Oxidation, Necrosis, and Morphology of Rat Pancreatic Acini.

OBJECTIVES: The objective of this study was to test whether pyruvate and glutamine affect the ethanol and cholecystokinin (CCK) effects on the mitochondrial function, viability, and morphology of rat pancreatic acini. METHODS: Respiration was measured with Clark oxygen electrode. Mitochondrial membrane potential, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), cell morphology, and viability were studied with fluorescence microscopy. RESULTS: In vitro, CCK (0.1 nM) caused pyruvate-dependent stimulation of basal and uncoupled respiration, and the effects were abolished by ethanol (20 mM). The combination of ethanol with CCK (2 hours) caused necrosis of approximately 40% acinar cells in medium with glucose, but not with pyruvate and/or glutamine. Cholecystokinin (10 nM) or ethanol with 0.1 nM CCK caused plasma membrane blebbing not related to apoptosis only when both glutamine and pyruvate were present. Glutamine, but not pyruvate, decreased NAD(P)H level and prevented the effects of ethanol with CCK on mitochondrial membrane potential and NAD(P)H, but, in combination with CCK and ethanol, decreased the uncoupled respiration. In vivo, the combination of ethanol (4 g/kg) and CCK (20 pmol/kg) suppressed basal and uncoupled respiration and caused acinar cell blebbing, but not necrosis. CONCLUSIONS: The lack of sufficient substrate supply in vitro makes pancreatic acinar cells susceptible to necrosis caused by ethanol and CCK in clinically relevant concentrations.

High alcohol-producing Klebsiella pneumoniae causes fatty liver disease through 2,3-butanediol fermentation pathway in vivo.

High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production in vivo remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) Kpn and constructed an adh (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc Kpn W14 strain (W14Δadh) using CRISPR-Cas9 system. Subsequently, we established the mouse model via gavage administration of HiAlc Kpn W14 and W14 Δadh strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc Kpn W14-fed mice, W14Δadh-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol via the 2,3-butanediol fermentation pathway in HiAlc Kpn, which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes in vivo.

Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations.

BACKGROUND: Poisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication. METHODS: Blood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x2) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05). RESULTS: Of the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 µg/mL ± 0.45 and 0.38 µg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic. CONCLUSION: The application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.

Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele.

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2-ALDH2*1/*1 (n = 23), ADH1B*2/*2-ALDH2*1/*2 (n = 27), and ADH1B*1/*1-ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.

Isobutylene contamination of blood collected in 10-ml evacuated blood collection tubes with gray conventional rubber stoppers.

Dual-column headspace gas chromatographic analysis with two flame-ionization detectors is a commonly used analytical technique for forensic blood ethanol quantitation. This technique is also applicable to the identification and quantitation of other volatile organic compounds such as methanol in biological samples. Compound identification by retention time is limited to those compounds with known retention times programmed into the instrument method. Historically, an early-eluting peak from an unidentified compound has been observed in both chromatograms from antemortem blood samples analyzed for ethanol concentration with this technique. The unidentified compound's retention time matches that of methanol on one column but not on the second column. This previously unidentified compound has been identified as isobutylene. The proposed source of the isobutylene contamination historically observed in antemortem blood samples collected in 10-ml gray-top blood collection tubes is the conventional rubber stopper. Isobutylene was detected in deionized water stored in each of the seven lots of 10-ml blood tubes tested; the expiration dates of the tubes tested spanned the years 2002-2022. Misidentification of isobutylene as methanol is possible when using a single-column gas chromatographic system. The presence of isobutylene in blood collected in a gray-top collection tube does not represent laboratory contamination, is not an interferent with blood ethanol quantitation, and does not affect the ethanol concentration in the blood. A 0.150 g/dl aqueous ethanol standard was stored in a gray-top tube to evaluate the potential impact of isobutylene on ethanol quantitation. The solution's average ethanol concentration measured after storage was 0.150 g/dl.

Summary statistics for drugs and alcohol concentration recovered in post-mortem femoral blood in Western Switzerland.

In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework. To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs. This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC). The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.

The dosing procedure that "makes the poison": Comparing the effects of single versus cumulative alcohol administration methods on emotion recognition.

BACKGROUND: Most people often consume alcohol cumulatively and gradually. Yet almost scientific knowledge about alcohol's acute effects on cognition, behavior, and affect stems from laboratory studies that employ a single beverage administration procedure. OBJECTIVE: This study tests the hypothesis that alcohol's acute effects depend on both methods of administration and alcohol blood level. We introduce a new laboratory procedure for studying cumulative alcohol drinking and examine alcohol's effects on emotion recognition as a function of both alcohol administration method and alcohol blood level. METHODS: Participants were recruited for one of two studies. One study employed a between-subject design using a single alcoholic dose. Participants were randomly assigned to drink either placebo (0.00%), low (0.03%), moderate (0.06%), or high (0.09%) alcohol levels. The second study employed a within-subject design using a cumulative alcoholic administration method, in which each participant drank four drinks (placebo, followed by three alcoholic drinks). Both groups reached similar breath alcohol concentrations. In both studies, participants attended a single study session, in which emotion recognition was examined following alcohol administration. RESULTS: Single alcoholic beverage administration method caused greater impairment in emotion recognition ability, specifically for anger, happiness, and fear, as compared with cumulative administration method, even though breath alcohol levels were similar in both conditions. CONCLUSIONS: This paper presents questions concerning the internal validity of previous laboratory studies that use a single beverage administration procedure. Insights into the effects of alcohol on behavior, as well as regarding our knowledge about models of addiction are presented.

Large-scale reanalysis of refrigerated antemortem blood samples for ethanol content at random intervals.

Ethanol stability in antemortem blood stored under various conditions has been widely studied. Most such studies have somewhat limited sample size (<50) and limited variation in the length of time between the blood draw and the first analysis and between the first analysis and the reanalysis. In the work presented here, the antemortem blood drawn for forensic purposes and stored refrigerated (~4°C) in 371 cases was analyzed for ethanol concentration using headspace gas chromatography at various times after the blood draw based on routine case flow and then also analyzed at various times within approximately 1 year after the first analysis. This methodology is intended to provide insight into the range of differences expected when cases are analyzed in the normal flow of casework and then reanalyzed at random times afterwards as occurs when reanalysis is performed by the defense or by the laboratory if the original analyst is unavailable to testify. In 22 cases, the same blood tube from the case was reanalyzed. The previously unopened blood tube from the case was analyzed in 349 cases. The 25 cases in which the blood was ethanol-negative based on the first analysis remained ethanol-negative when reanalyzed. The average difference in ethanol concentration between tests for the ethanol-positive cases was -0.004 g/dL. This decrease was statistically significant at the 0.05 level of significance. The range of differences was -0.0197 to 0.0103 g/dL. The difference measured in 85% of the ethanol-positive cases was in in the range of -0.008 to -0.001 g/dL.

Endogenous formation of 1-propanol and methanol after consumption of alcoholic beverages.

INTRODUCTION: In cases of drunk-driving, allegations that alcohol has been consumed after the incident, are proved by analyzing congener alcohols in the blood sample. 1-Propanol, one of the main congener compounds, was tested, whether it is also endogenously formed when a person has consumed alcoholic beverages. METHODS: Eleven male and 13 female volunteers consumed congener-free vodka (37.5 vol% ethanol, individual doses: 0.15-0.32 l) within one hour. Blood samples were taken up to 10 h and analyzed for ethanol and congener alcohols by headspace gas chromatography-mass spectrometry. RESULTS: Ethanol concentrations reached in blood a maximum of 0.65-1.23 g/l and decreased by 0.18 g/l/h (median values). Of the congener alcohols analyzed, only methanol and 1-propanol were detected in the plasma samples of all subjects. The endogenous methanol concentration increased from 0.66 mg/l by 0.22 mg/l/h to 2.19 mg/l (medians). 1-Propanol was not detected prior to alcohol consumption. Maximum concentrations of 0.10-0.32 mg/L were measured after 1.0-4.5 h. A plateau of the 1-propanol concentration was observed in the plasma samples of the 18 subjects lasting for 0.5-4.0 h and this alcohol was completely eliminated at ethanol concentrations of 0.17 g/l (median, range 0.03-0.55 g/l). CONCLUSION: The results of the study confirm the formation of 1-propanol after consumption of 1-propanol-free beverages, which should be taken into account when evaluating its concentration.

Disease Differentiation and Monitoring of Anti-TNF Treatment in Rheumatoid Arthritis and Spondyloarthropathies.

Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are comprehensive immunological disorders. The treatment of these disorders is limited to ameliorating the symptoms and improving the quality of life of patients. In this study, serum samples from RA, AS, and PsA patients were analyzed with metabolomic tools employing the 1H NMR method in combination with univariate and multivariate analyses. The results obtained in this study showed that the changes in metabolites were the highest for AS > RA > PsA. The study demonstrated that the time until remission or until low disease activity is achieved is shortest (approximately three months) for AS, longer for RA and longest for PsA. The statistically common metabolite that was found to be negatively correlated with the healing processes of these disorders is ethanol, which may indicate the involvement of the gut microflora and/or the breakdown of malondialdehyde as a cell membrane lipid peroxide product.

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human.

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.