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Anders Helander - One of the best experts on this subject based on the ideXlab platform.

  • comparison between the urinary alcohol markers etg ets and gtol 5 hiaa in a controlled drinking experiment
    Alcohol and Alcoholism, 2008
    Co-Authors: Gudrun Hoiseth, Jean Paul Bernard, Nicolai Stephanson, Per T Normann, Asbjorg S Christophersen, Jorg Morland, Anders Helander
    Abstract:

    Aim: Urinary ethyl glucuronide (EtG), ethyl sulfate (EtS), and the ratio between 5-Hydroxytryptophol-glucuronide and 5-hydroxyindole-3-acetic acid (GTOL/5-HIAA) are all suggested as biomarkers for recent alcohol ingestion with longer detection times than measurement of ethanol itself. The aim of this controlled study was to compare the sensitivities and detection times of EtG, EtS, and GTOL/5-HIAA, after a single ingestion of ethanol. Methods: 0.5 g ethanol/kg body weight was ingested by 10 healthy male volunteers in a fasted state. Ethanol, EtG, EtS, and GTOL/HIAA levels were measured in urine samples collected during a 45-50 h period. The total amount of ethanol excreted as EtG and EtS was also determined. Results: Urinary EtG, EtS, and GTOL/5-HIAA showed 100% sensitivity as biomarkers for recent drinking. Compared to ethanol testing in urine, the detection times for GTOL/5-HIAA were ∼5 h longer and for EtG and EtS ∼25 h longer. The maximum EtG concentrations were higher than for EtS in all subjects, and a higher fraction of the ethanol dose was excreted as EtG (median 0.019%) compared with EtS (median 0.011%). Conclusions: This study is the first controlled experiment comparing the time-courses for ethanol, EtG, EtS, and GTOL/5-HIAA in urine. In cases where surveillance of alcohol relapse is needed, measurements of urinary EtG and EtS are sensitive and specific alternatives to ethanol testing. The GTOL/5-HIAA ratio is equally sensitive but with a much shorter window of detection.

  • biomarkers to disclose recent intake of alcohol potential of 5 Hydroxytryptophol glucuronide testing using new direct uplc tandem ms and elisa methods
    Alcohol and Alcoholism, 2007
    Co-Authors: Olof Beck, Nikolai Stephanson, Michael Bottcher, Norbert Dahmen, Christoph Fehr, Anders Helander
    Abstract:

    Aims: This study compared two new methods for direct determination of 5-Hydroxytryptophol glucuronide (GTOL) in urine, a biomarker for detection of recent alcohol consumption. Methods: Urine samples were collected from ten alcoholic patients during recovery from intoxication. A direct injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measurement of the urinary GTOL to 5-hydroxyindoleacetic acid (5-HIAA) ratio, and an ELISA assay for direct measurement of GTOL, were used. Comparison was made with the urinary ethanol and ethyl glucuronide (EtG) concentrations. Results: The breath ethanol concentration on admission ranged between 1.0-3.1 g/l. The UPLC-MS/MS method showed a median detection time of 39 h for an elevated urinary GTOL/5-HIAA ratio, while EtG was detected for a median of 65 h. Determination of GTOL by the ELISA assay showed 87% sensitivity in detecting positive samples at a 44% specificity, as compared with the UPLC-MS/MS method. Conclusions: The lower sensitivity of the urinary GTOL/5-HIAA ratio compared with EtG for recent drinking may be clinically useful, in cases where the EtG test provides an unwanted high sensitivity for intake of only small amounts of alcohol or unintentional ethanol exposure.

  • alcohol biomarker analysis simultaneous determination of 5 Hydroxytryptophol glucuronide and 5 hydroxyindoleacetic acid by direct injection of urine using ultra performance liquid chromatography tandem mass spectrometry
    Journal of Mass Spectrometry, 2007
    Co-Authors: Nikolai Stephanson, Anders Helander, Olof Beck
    Abstract:

    A direct ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) for simultaneous measurement of urinary 5-Hydroxytryptophol glucuronide (GTOL) and 5-hydroxyindoleacetic acid (5-HIAA) was developed. The GTOL/5-HIAA ratio is used as an alcohol biomarker with clinical and forensic applications. The method involved dilution of the urine sample with deuterated analogues (internal standards), reversed-phase chromatography with gradient elution, electrospray ionisation and monitoring of two product ions per analyte in selected reaction monitoring mode. The measuring ranges were 6.7-10 000 nmol/l for GTOL and 0.07-100 micromol/l for 5-HIAA. The intra- and inter-assay imprecision, expressed as the coefficient of variation, was below 7%. Influence from ion suppression was noted for both compounds but was compensated for by the use of co-eluting internal standards. The accuracy in analytical recovery of added substance to urine samples was 96 and 98%, respectively, for GTOL and 5-HIAA. Method comparison with GC-MS for GTOL in 25 authentic patient samples confirmed the accuracy of the method with a median ratio between methods (GC-MS to UPLC-MS/MS) of 1.14 (r(2) = 0.975). The difference is explained by the fact that the GC-MS method also measures unconjugated 5-Hydroxytryptophol naturally present in urine. The comparison with data for 5-HIAA obtained by an HPLC method demonstrated a median ratio of 1.05 between the methods. The UPLC-MS/MS method was capable of measuring endogenous GTOL and 5-HIAA levels in urine, which agreed with the literature data. In conclusion, a fully validated and robust direct method for the routine measurement of urinary GTOL and 5-HIAA was developed.

  • determination of urinary 5 Hydroxytryptophol glucuronide by liquid chromatography mass spectrometry
    Journal of Chromatography B, 2005
    Co-Authors: Nikolai Stephanson, Anders Helander, Helen Dahl, Olof Beck
    Abstract:

    5-Hydroxytryptophol glucuronide (GTOL) is the major excretion form of 5-Hydroxytryptophol (5-HTOL), a minor serotonin metabolite under normal conditions. Because the concentration of 5-HTOL is markedly increased following consumption of alcohol, measurement of 5-HTOL is used as a sensitive biomarker for detection of recent alcohol intake. This study describes the development and evaluation of a liquid chromatography-electrospray ionization mass spectrometry (LC-MS) procedure for direct quantification of GTOL in human urine. Deuterium labelled GTOL (GTOL-(2)H(4)) was used as internal standard. GTOL was isolated from urine by solid-phase extraction on a C(18) cartridge prior to injection onto a gradient eluted Hypurity C(18) reversed-phase HPLC column. The detection limit of the method was 2.0 nmol/L and the measuring range 6-8500 nmol/L. The intra- and inter-assay coefficients of variation were <3.5% (n=10) and <6.0% (n=9), respectively. The new LC-MS method was highly correlated with an established GC-MS method for urinary 5-HTOL (r(2)=0.99, n=70; mean 5-HTOL/GTOL ratio=1.10). This is the first direct assay for quantification of GTOL in urine. The method is suitable for routine application.

  • 5 Hydroxytryptophol as a marker for recent alcohol intake
    Addiction, 2003
    Co-Authors: Olof Beck, Anders Helander
    Abstract:

    Aims  To review the mechanism behind the alcohol-induced shift in serotonin metabolism, and the use of urinary 5-Hydroxytryptophol (5-HTOL) as a biochemical marker of acute alcohol consumption. Background  The serotonin metabolite 5-HTOL is a normal, minor constituent of urine and is excreted mainly in conjugated form with glucuronic acid. The formation of 5-HTOL increases dramatically after alcohol intake, due to a metabolic interaction, and the elevated urinary excretion remains for some time (>5–15 hours depending on dose) after ethanol has been eliminated. This biochemical effect can be used for detection of recent alcohol intake. Results  5-HTOL is determined by the gas chromatography-mass spectrometry (GC-MS) or liquid chromatography and mass spectrometry (LC-MS) techniques. A new ELISA method for 5-HTOL glucuronide provides a promising clinical assay. The most robust way to use the marker is by measuring the ratio of 5-HTOL to 5-hydroxyindoleacetic acid, because this compensates for urine dilution and dietary intake of serotonin. 5-HTOL is a very sensitive and specific indicator of recent alcohol consumption and, as such, a valuable complement to self-report. In clinical use, 5-HTOL is effective for monitoring lapses into drinking during out-patient treatment and for objective evaluation of treatment efforts. Other applications include detection of high-risk patients in elective surgery, monitoring of disulfiram treatment and a method to rule out artefactual ethanol formation in forensic toxicology. 5-HTOL can also be used as a sensitive reference method for validation of self-report data in clinical alcohol research. Conclusions  An elevated urinary 5-HTOL level can serve as a sensitive and reliable marker for recent alcohol intake with a number of clinical and forensic applications.

Olof Beck - One of the best experts on this subject based on the ideXlab platform.

  • alcohol biomarker analysis simultaneous determination of 5 Hydroxytryptophol glucuronide and 5 hydroxyindoleacetic acid by direct injection of urine using ultra performance liquid chromatography tandem mass spectrometry
    Journal of Mass Spectrometry, 2007
    Co-Authors: Nikolai Stephanson, Anders Helander, Olof Beck
    Abstract:

    A direct ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) for simultaneous measurement of urinary 5-Hydroxytryptophol glucuronide (GTOL) and 5-hydroxyindoleacetic acid (5-HIAA) was developed. The GTOL/5-HIAA ratio is used as an alcohol biomarker with clinical and forensic applications. The method involved dilution of the urine sample with deuterated analogues (internal standards), reversed-phase chromatography with gradient elution, electrospray ionisation and monitoring of two product ions per analyte in selected reaction monitoring mode. The measuring ranges were 6.7-10 000 nmol/l for GTOL and 0.07-100 micromol/l for 5-HIAA. The intra- and inter-assay imprecision, expressed as the coefficient of variation, was below 7%. Influence from ion suppression was noted for both compounds but was compensated for by the use of co-eluting internal standards. The accuracy in analytical recovery of added substance to urine samples was 96 and 98%, respectively, for GTOL and 5-HIAA. Method comparison with GC-MS for GTOL in 25 authentic patient samples confirmed the accuracy of the method with a median ratio between methods (GC-MS to UPLC-MS/MS) of 1.14 (r(2) = 0.975). The difference is explained by the fact that the GC-MS method also measures unconjugated 5-Hydroxytryptophol naturally present in urine. The comparison with data for 5-HIAA obtained by an HPLC method demonstrated a median ratio of 1.05 between the methods. The UPLC-MS/MS method was capable of measuring endogenous GTOL and 5-HIAA levels in urine, which agreed with the literature data. In conclusion, a fully validated and robust direct method for the routine measurement of urinary GTOL and 5-HIAA was developed.

  • biomarkers to disclose recent intake of alcohol potential of 5 Hydroxytryptophol glucuronide testing using new direct uplc tandem ms and elisa methods
    Alcohol and Alcoholism, 2007
    Co-Authors: Olof Beck, Nikolai Stephanson, Michael Bottcher, Norbert Dahmen, Christoph Fehr, Anders Helander
    Abstract:

    Aims: This study compared two new methods for direct determination of 5-Hydroxytryptophol glucuronide (GTOL) in urine, a biomarker for detection of recent alcohol consumption. Methods: Urine samples were collected from ten alcoholic patients during recovery from intoxication. A direct injection ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for measurement of the urinary GTOL to 5-hydroxyindoleacetic acid (5-HIAA) ratio, and an ELISA assay for direct measurement of GTOL, were used. Comparison was made with the urinary ethanol and ethyl glucuronide (EtG) concentrations. Results: The breath ethanol concentration on admission ranged between 1.0-3.1 g/l. The UPLC-MS/MS method showed a median detection time of 39 h for an elevated urinary GTOL/5-HIAA ratio, while EtG was detected for a median of 65 h. Determination of GTOL by the ELISA assay showed 87% sensitivity in detecting positive samples at a 44% specificity, as compared with the UPLC-MS/MS method. Conclusions: The lower sensitivity of the urinary GTOL/5-HIAA ratio compared with EtG for recent drinking may be clinically useful, in cases where the EtG test provides an unwanted high sensitivity for intake of only small amounts of alcohol or unintentional ethanol exposure.

  • determination of glucuronidated 5 Hydroxytryptophol gtol a marker of recent alcohol intake by elisa technique
    Clinical Biochemistry, 2007
    Co-Authors: Jutta Dierkes, Olof Beck, Stefan Borg, Manfred Wolfersdorf, Katrin Borucki, Wolfgang Weinmann, Gerhard A Wiesbeck, Friedrich M Wurst
    Abstract:

    Abstract Objectives: To compare markers of alcohol consumption. Design and methods: Measurement of urinary ethyl glucuronide, 5-Hydroxytryptophol, 5-Hydroxytryptophol glucuronide, 5-hydroxyindole acetic acid in 10 patients during alcohol withdrawal. Results: 5-Hydroxytryptophol glucuronide was measured by ELISA with good analytical precision, its diagnostic specificity and sensitivity was better than that of 5-Hydroxytryptophol and its correlation was closer to ethyl glucuronide than to 5-Hydroxytryptophol. Conclusion: Determination of 5-Hydroxytryptophol glucuronide by ELISA offers promising results in detection of previous alcohol consumption.

  • determination of urinary 5 Hydroxytryptophol glucuronide by liquid chromatography mass spectrometry
    Journal of Chromatography B, 2005
    Co-Authors: Nikolai Stephanson, Anders Helander, Helen Dahl, Olof Beck
    Abstract:

    5-Hydroxytryptophol glucuronide (GTOL) is the major excretion form of 5-Hydroxytryptophol (5-HTOL), a minor serotonin metabolite under normal conditions. Because the concentration of 5-HTOL is markedly increased following consumption of alcohol, measurement of 5-HTOL is used as a sensitive biomarker for detection of recent alcohol intake. This study describes the development and evaluation of a liquid chromatography-electrospray ionization mass spectrometry (LC-MS) procedure for direct quantification of GTOL in human urine. Deuterium labelled GTOL (GTOL-(2)H(4)) was used as internal standard. GTOL was isolated from urine by solid-phase extraction on a C(18) cartridge prior to injection onto a gradient eluted Hypurity C(18) reversed-phase HPLC column. The detection limit of the method was 2.0 nmol/L and the measuring range 6-8500 nmol/L. The intra- and inter-assay coefficients of variation were <3.5% (n=10) and <6.0% (n=9), respectively. The new LC-MS method was highly correlated with an established GC-MS method for urinary 5-HTOL (r(2)=0.99, n=70; mean 5-HTOL/GTOL ratio=1.10). This is the first direct assay for quantification of GTOL in urine. The method is suitable for routine application.

  • 5 Hydroxytryptophol as a marker for recent alcohol intake
    Addiction, 2003
    Co-Authors: Olof Beck, Anders Helander
    Abstract:

    Aims  To review the mechanism behind the alcohol-induced shift in serotonin metabolism, and the use of urinary 5-Hydroxytryptophol (5-HTOL) as a biochemical marker of acute alcohol consumption. Background  The serotonin metabolite 5-HTOL is a normal, minor constituent of urine and is excreted mainly in conjugated form with glucuronic acid. The formation of 5-HTOL increases dramatically after alcohol intake, due to a metabolic interaction, and the elevated urinary excretion remains for some time (>5–15 hours depending on dose) after ethanol has been eliminated. This biochemical effect can be used for detection of recent alcohol intake. Results  5-HTOL is determined by the gas chromatography-mass spectrometry (GC-MS) or liquid chromatography and mass spectrometry (LC-MS) techniques. A new ELISA method for 5-HTOL glucuronide provides a promising clinical assay. The most robust way to use the marker is by measuring the ratio of 5-HTOL to 5-hydroxyindoleacetic acid, because this compensates for urine dilution and dietary intake of serotonin. 5-HTOL is a very sensitive and specific indicator of recent alcohol consumption and, as such, a valuable complement to self-report. In clinical use, 5-HTOL is effective for monitoring lapses into drinking during out-patient treatment and for objective evaluation of treatment efforts. Other applications include detection of high-risk patients in elective surgery, monitoring of disulfiram treatment and a method to rule out artefactual ethanol formation in forensic toxicology. 5-HTOL can also be used as a sensitive reference method for validation of self-report data in clinical alcohol research. Conclusions  An elevated urinary 5-HTOL level can serve as a sensitive and reliable marker for recent alcohol intake with a number of clinical and forensic applications.

Stefan Borg - One of the best experts on this subject based on the ideXlab platform.

  • determination of glucuronidated 5 Hydroxytryptophol gtol a marker of recent alcohol intake by elisa technique
    Clinical Biochemistry, 2007
    Co-Authors: Jutta Dierkes, Olof Beck, Stefan Borg, Manfred Wolfersdorf, Katrin Borucki, Wolfgang Weinmann, Gerhard A Wiesbeck, Friedrich M Wurst
    Abstract:

    Abstract Objectives: To compare markers of alcohol consumption. Design and methods: Measurement of urinary ethyl glucuronide, 5-Hydroxytryptophol, 5-Hydroxytryptophol glucuronide, 5-hydroxyindole acetic acid in 10 patients during alcohol withdrawal. Results: 5-Hydroxytryptophol glucuronide was measured by ELISA with good analytical precision, its diagnostic specificity and sensitivity was better than that of 5-Hydroxytryptophol and its correlation was closer to ethyl glucuronide than to 5-Hydroxytryptophol. Conclusion: Determination of 5-Hydroxytryptophol glucuronide by ELISA offers promising results in detection of previous alcohol consumption.

  • The Urinary Ratio of 5-Hydroxytryptophol to 5-Hydroxyindole-3-Acetic Acid in Surgical Patients with Chronic Alcohol Misuse
    Alcohol (Fayetteville N.Y.), 1999
    Co-Authors: Claudia Spies, Olof Beck, Stefan Borg, Jörg Herpell, Christian Müller, Fritz Pragst, Anders Helander
    Abstract:

    Abstract The urinary ratio of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid was reported to be elevated for a period of up to 22 h following acute alcohol ingestion. Therefore, the ratio could detect continuous alcohol consumption, in what was considered to be a high-risk surgical group, on the evening prior to surgery. The aim of this study was to determine the preoperative ratio of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid in patients with continuous preoperative alcohol misuse. Forty-two patients participated in this institutionally approved study, once their written informed consent had been obtained. Chronic alcoholics were defined by meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders criteria and an ethanol consumption ⩾60 g/day. The urine samples were taken preoperatively and determined by means of gas chromatography-mass spectrometry and high performance liquid chromatography. The urinary ratio of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid was significantly increased in chronic alcoholics. The ICU stay of these patients was significantly prolonged due to an increased incidence of pneumonia and sepsis. Five chronic alcoholics died, whereas no deaths occurred in the nonalcoholic group ( p = 0.05). As the measurement of the urinary ratio of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid could detect alcohol consumption immediately prior to operation, this marker could assist the carbohydrate-deficient transferrin in screening for patients with high-level dependency; these patients were considered to be at a high risk of developing intercurrent complications.

  • comparison of breath ethanol and urinary 5 Hydroxytryptophol testing with self reports for detection of recent alcohol use during outpatient treatment a study on methadone patients
    Drug and Alcohol Dependence, 1999
    Co-Authors: Anders Helander, Joachim Von Wachenfeldt, Arto J. Hiltunen, Paula Liljeberg, Stefan Borg
    Abstract:

    Comparison of breath-ethanol and urinary 5-Hydroxytryptophol testing with self-reports for detection of recent alcohol use during outpatient treatment: a study on methadone patients

  • longitudinal comparison of carbohydrate deficient transferrin and gamma glutamyl transferase complementary markers of excessive alcohol consumption
    Alcohol and Alcoholism, 1996
    Co-Authors: Anders Helander, Annette Voltaire Carlsson, Stefan Borg
    Abstract:

    The utility of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) as biochemical markers of excessive alcohol consumption was studied in alcohol-dependent subjects. Serum samples were collected once weekly from 10 male out-patients undergoing a 6-month alcohol treatment programme. Frequency of relapse into drinking (defined as any intake of alcoholic beverage) was assessed by self-reports during patient interviews three times per week and by daily determination of the 5-Hydroxytryptophol level in urine. A marked decrease in mean CDT and GGT values was observed during the initial month. Only one patient remained totally abstinent throughout the observation period, while four had sporadic relapses (2–5 days with alcohol consumption). Both CDT and GGT remained below the respective reference limits in those patients. The other five patients drank more frequently (range 22–57 days) and increased their mean levels of CDT and GGT after the initial decrease. As determined from the values at admission and during the course of the study, CDT appeared to be the most sensitive marker in six out of the 10 patients. In one patient, both markers were affected in a parallel way, whereas two of those with frequent relapses responded to alcohol consumption with a marked increase in GGT, but with no or only a slight increase in CDT. One patient did not show any abnormal CDT or GGT values. In 54 female and 60 male serum samples collected at random from patients during admission at an alcohol detoxification unit, 35% and 58% of the CDT values exceeded the reference limits for females and males, respectively. For GGT, 59% of the female and 67% of the male values were above cut-off. Carbohydrate-deficient transferrin and GGT were not significantly correlated. Taken together, the present results indicate that measurement of both CDT and GGT will increase the possibility of identifying excessive alcohol consumption. By following changes in CDT and GGT values during a period of alcohol withdrawal, the most sensitive individual marker can be determined. This in turn allows for improved detection of relapse into heavy drinking dunng long-term monitoring of out-patients.

  • detection of relapses in alcohol dependent patients using carbohydrate deficient transferrin improvement with individualized reference levels during long term monitoring
    Alcoholism: Clinical and Experimental Research, 1995
    Co-Authors: Stefan Borg, Anders Helander, Annette Voltaire Carlsson, Annmarie Hogstrom Brandt
    Abstract:

    The present study examined whether the sensitivity of carbohydrate-deficient transferrin (CDT) in serum, a biochemical marker of recent excessive alcohol consumption, could be improved during long-term monitoring by introducing individualized cut-offs between normal and elevated CDT levels. Alcohol-dependent male outpatients (n = 22), trying to abstain from alcohol for 6 months, were monitored by comparing weekly measurements of CDT with self-reports of alcohol consumption three times/week and daily urinary levels of 5-Hydroxytryptophol (5-HTOL), a new marker of recent alcohol intake. The method used to calculate cut-offs was based on the intraindividual variation in CDT not dependent on excessive alcohol consumption or analytical variations. An increase in CDT exceeding the minimum level for each patient by 3 and 4 times the mean coefficient of variation for healthy social drinkers (i.e., by 30% and 40%) was compared as an indication of alcohol consumption, even if the value did not exceed the conventional cut-off. By using individualized CDT cut-off points, 68 and 41 episodes of drinking were detected in the patients with the cut-offs of > 30% and > 40%, respectively, as compared with 25 with the conventional limit. Most episodes could be verified clinically and/or by elevated urinary 5-HTOL levels during the 2-week period preceding each serum sampling. The results suggest that the possibility to detect relapses by CDT can be improved during long-term monitoring of alcohol-dependent outpatients by introducing individualized cut-off points between normal and elevated CDT levels.

Margareta Some - One of the best experts on this subject based on the ideXlab platform.

  • urinary excretion patterns of 5 hydroxyindole 3 acetic acid and 5 Hydroxytryptophol in various animal species implications for studies on serotonin metabolism and turnover rate
    Life Sciences, 2002
    Co-Authors: Margareta Some, Anders Helander
    Abstract:

    The concentrations of the serotonin metabolites 5-hydroxyindole-3-acetic acid (5HIAA) and 5-Hydroxytryptophol (5HTOL) were determined in spot urine samples of 12 mammalian and one fish species (cat, cow, dog, ferret, golden hamster, guinea pig, horse, monkey, mouse, rabbit, rainbow trout, rat, sheep) and compared with human data. The highest urinary concentrations of 5HTOL were found in the Sprague-Dawley rat (mean 9.5 μmol/L) and NMRI mouse (8.2 μmol/L), and the lowest in rainbow trout, cynomolgus macaque, and human urine (∼0.1 μmol/L). The highest 5HIAA concentrations were found in hamster (89.3 μmol/L) and mouse (85.2 μmol/L), and the lowest in rainbow trout, horse and sheep (range 2.0–3.7 μmol/L). Several species showed 5HIAA concentrations similar to that normally observed in human urine (∼5–40 μmol/L). This study demonstrated wide inter- and intra-species variations in the urinary concentrations of 5HIAA and 5HTOL, both separately and in the sum of concentrations. The 5HTOL/5HIAA ratio, which is used as an easily accessible index of the relative importance of the reductive and oxidative pathways for serotonin metabolism, also varied considerably between different species. This observation confirms that the much higher urinary 5HTOL/5HIAA ratio in rats (mean 0.35) compared with humans (< 0.01) is due to a higher baseline formation of 5HTOL in the rat. The monkey, ferret, hamster, and rabbit most closely resembled humans in this respect, and at least the two latter species appear to be more suitable than rats as animal models for studying serotonin metabolism and turnover rate, and the metabolic interaction with ethanol.

  • dietary serotonin and alcohol combined may provoke adverse physiological symptoms due to 5 Hydroxytryptophol
    Life Sciences, 2000
    Co-Authors: Anders Helander, Margareta Some
    Abstract:

    The urinary excretion products of serotonin (5-hydroxytryptamine, 5HT) are 5-hydroxyindole-3-acetic acid (5HIAA) and 5-Hydroxytryptophol (5HTOL), and the ratio of 5HTOL to 5HIAA is normally very low (< 0.01 ) in man. Intake of foods rich in 5HT (high amounts in banana, pineapple, and walnuts) induces a general increase in the output of 5HT metabolites, without affecting the 5HTOL/5HIAA ratio. In contrast, during metabolism of ethanol there is a shift in the catabolic pattern of 5HT, and the formation of 5HTOL increases appreciably at the expense of 5HIAA. Accordingly, the urinary 5HTOL/ 5HIAA ratio increases and does not recover to baseline levels until several hours after ethanol has been cleared from the body. When 10 healthy subjects ingested a moderate dose of ethanol (0.5 g/kg), the urinary 5HTOL/SHIAA ratio was increased approximately 70-fold on average at 4 h after intake. When the same amount of ethanol was ingested together with 3 bananas (approximately 10 mg 5HT), this ratio was increased approximately 100-fold at 4 h and still significantly higher than baseline levels at 24 h. Starting at 3-4 h after the combined intake of ethanol and banana, 7 subjects experienced one or more unpleasant symptoms (diarrhea, headache, and fatigue) which are associated with the 5HT system. The events were transient but typically lasted for several hours, and the duration correlated with the time period during which 5HTOL levels were raised. Intake of ethanol and banana separately produced much lower increases in 5HTOL output and caused no corresponding effects. This observation indicate that dietary 5HT intake together with even a moderate dose of ethanol can provoke unpleasant physiological symptoms. The symptoms may be attributed to the high concentration of 5HTOL.

  • studies on the interaction between ethanol and serotonin metabolism in rat using deuterated ethanol and 4 methylpyrazole
    Biochemical Pharmacology, 2000
    Co-Authors: Margareta Some, Stefan Svensson, Jan Olov Höög, Anders Helander
    Abstract:

    Abstract The metabolic interaction between ethanol and serotonin (5-hydroxytryptamine) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homogenates of Sprague–Dawley rats by following the transfer of deuterium from deuterated ethanol over endogenous NADH to 5-Hydroxytryptophol (5HTOL). Homogenates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum, colon, and caecum were incubated in the presence of [ 2 H 2 ]ethanol and 5-hydroxyindole-3-acetaldehyde (5HIAL), and the [ 2 H]5HTOL formed was identified and quantified using gas chromatography–mass spectrometry. ADH activity was most abundant in liver, kidney, and within the gastrointestinal tract. The highest incorporation of deuterium was obtained in homogenates of kidney, lung, and colon, whereas in brain, which contains very low ADH activity, no incorporation could be demonstrated. Addition of extra NAD + (2.4 mM) increased the formation of [ 2 H]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor of class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney, jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in the rat a metabolic interaction between ethanol and serotonin via the ADH pathway may take place in several tissues besides the liver, which is the main tissue for ethanol detoxification.

  • activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin
    FEBS Journal, 1999
    Co-Authors: Stefan Svensson, Margareta Some, Anders Helander, Anders Lundsjo, Tomas Cronholm, Jan Olov Höög
    Abstract:

    Alcohols and aldehydes in the metabolic pathways of ethanol and serotonin are substrates for alcohol dehydrogenases (ADH) of class I and II. In addition to the reversible alcohol oxidation/aldehyde reduction, these enzymes catalyse aldehyde oxidation. Class-I gg ADH catalyses the dismutation of both acetaldehyde and 5-hydroxyindole-3-acetaldehyde (5-HIAL) into their corresponding alcohols and carboxylic acids. The turnover of acetaldehyde dismutation is high (kcat = 180 min 21 ) but saturation is reached first at high concentrations (Km =3 0 m m) while dismutation of 5-HIAL is saturated at lower concentrations and is thereby more efficient (Km = 150 mm; kcat = 40 min 21 ). In a system where NAD + is regenerated, the oxidation of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid proceeds with concentration levels of the intermediary 5-HIAL expected for a two-step oxidation. Butanal and 5-HIAL oxidation is also observed for class-I ADH in the presence of NADH. The class-II enzyme is less efficient in aldehyde oxidation, and the ethanol-oxidation activity of this enzyme is competitively inhibited by acetate (Ki =1 2 m m) and 5-hydroxyindole-3-acetic acid (Ki =2m m). Reduction of 5-HIAL is efficiently catalysed by class-I gg ADH (kcat = 400 min 21 ; Km =3 3 m m) in the presence of NADH. This indicates that the increased 5-Hydroxytryptophol/5-hydroxyindole-3-acetic acid ratio observed after ethanol intake may be due to the increased NADH/NAD + ratio on the class-I ADH.

  • elevated brain 5 Hydroxytryptophol levels in experimental portal systemic encephalopathy
    Pharmacology & Toxicology, 1997
    Co-Authors: Peter B F Bergqvist, Margareta Some, Anders Helander, Gustav Apelqvist, Finn Bengtsson
    Abstract:

    : Brain tissue levels of the two serotonin metabolites 5-Hydroxytryptophol and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured in porta-caval shunted rats, an in vivo model of portal-systemic encephalopathy. An intraperitoneal challenge of L-tryptophan (280 mg/kg body weight) to sham-operated rats was also instituted to increase the brain serotonin metabolism in these rats. The results revealed significant increases in 5-Hydroxytryptophol (by 31%) and 5-HIAA (by 87%) brain levels in porta-caval shunted rats as compared to sham-operated controls. The brain 5-Hydroxytryptophol-to-5-HIAA ratio was lower in the porta-caval shunted rats. The 5-Hydroxytryptophol levels in sham rats after the L-tryptophan challenge were intermediate between the porta-caval shunted and sham rats but not statistically significant for either group. These results suggest that increased brain 5-Hydroxytryptophol levels might be associated with the pathogenesis of portal-systemic encephalopathy. Further, the elevated brain 5-Hydroxytryptophol levels in experimental portal-systemic encephalopathy are probably a result of the increased brain serotonin metabolism prevailing in this condition rather than changes in the brain redox potential.

Alan Wayne Jones - One of the best experts on this subject based on the ideXlab platform.

  • urinary excretion of methanol and 5 Hydroxytryptophol as biochemical markers of hangover
    PROCEEDINGS OF THE 14TH INTERNATIONAL CONFERENCE ON ALCOHOL DRUGS AND TRAFFIC SAFETY - T'97 HELD ANNECY FRANCE 21-26 SEPTEMBER 1997 VOL 1, 1997
    Co-Authors: Alan Wayne Jones, Preben Bendtsen, Anders Helander
    Abstract:

    Besides the acute effects of ethanol on a person's performance and behavior, the after-effects of heavy drinking, commonly referred to as the hangover state, causes impairment of mental and body functioning, such as fatigue, attention deficit, and diminished psychomotor skills. It seems likely that many accidents on the roads and in the workplace might be attributed to decreased attention and slower reaction time associated with the residual effects of an evening's heavy drinking. Although neither dose-response relationships nor the prevalence of hangover have been clearly established, experience has shown that a person's blood alcohol concentration (BAC) should exceed approximately 1.0 g/L during the acute phase of intoxication (Smith et al, 1983; Collins and Chiles 1980). The hangover starts to develop when the BAC decreases again and is approaching zero. However, the intensity and duration of hangover shows large inter- and intra-individual variations and the reduced performance in some people might persist for many hours after all ethanol has been cleared from the body (Goldberg, 1961). (A) For the covering abstract see IRRD 893732.

  • laboratory testing for recent alcohol consumption comparison of ethanol methanol and 5 Hydroxytryptophol
    Clinical Chemistry, 1996
    Co-Authors: Anders Helander, Olof Beck, Alan Wayne Jones
    Abstract:

    The ratio of 5-Hydroxytryptophol to 5-hydroxyindole-3-acetic acid (5HTOL/5HIAA) in urine was compared with concentrations of ethanol and methanol as a way to monitor recent alcohol consumption. During detoxification of alcohol-dependent subjects, ethanol persisted longer in urine than in breath or plasma. Blood and urinary methanol remained increased for 2-6 h after blood ethanol had returned to background concentrations, whereas 5HTOL/5HIAA remained increased for 6-15 h. In healthy volunteers who had ingested alcohol (range 3-98 g) the previous afternoon or evening, 87% (for men) and 59% (for women) of all drinking occasions exceeding 7 g of alcohol were identified by an increased 5HTOL/5HIAA in the first morning urine void. This compared with 32% and 12%, respectively, identified by analysis of ethanol (>200 micromol/L). No gender difference in the excretion pattern of 5HTOL/5HIAA was seen. The results demonstrate that 5HTOL/5HIAA provides a specific and more sensitive method to detect recent alcohol consumption than does ethanol or methanol.

  • distinguishing ingested ethanol from microbial formation by analysis of urinary 5 Hydroxytryptophol and 5 hydroxyindoleacetic acid
    Journal of Forensic Sciences, 1995
    Co-Authors: Anders Helander, O Beck, Alan Wayne Jones
    Abstract:

    During the metabolism of ethanol, the metabolic conversion of serotonin (5-hydroxytryptamine) is altered, and, as a consequence, the ratio of 5-Hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) excreted in urine increases appreciably. The ratio of metabolites remains elevated for several hours after ethanol is no longer detectable. In the present study, urine specimens were supplemented with glucose and Candida albicans, a common human pathogenic yeast, and the formation of ethanol and the changes in the 5HTOL/5HIAA ratio were examined during one week of storage. Despite the production of high concentrations of ethanol (peak level 171 mmol/L, or 788 mg/dL), the 5HTOL/5HIAA ratio remained constant. The urinary 5HTOL/5HIAA ratio was also compared with urinary and blood ethanol levels in specimens selected at random during forensic autopsies. Elevated 5HTOL/5HIAA ratios were found in all specimens with detectable urinary ethanol. Some specimens showed elevated ratios of serotonin metabolites even though no ethanol was detected, indicating that these subjects had consumed ethanol prior to death but that the concentration had already returned to zero or was below the detection limit. In one case, postmortem ethanol formation was suspected, because blood ethanol concentration was 16.8 mmol/L (77 mg/dL) whereas urinary ethanol was zero. The urinary 5HTOL/5HIAA ratio fell within normal limits, which confirmed the suspicion of postmortem ethanol synthesis in the blood specimen. The present results indicate that the 5HTOL/5HIAA ratio in urine provides a useful method to distinguish between ethanol that might have been synthesized postmortem, or generated in vitro, from ethanol excreted in urine as a result of drinking.