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Biomedical subjects

A Helander

Publications and source records attributed to A Helander.

At least 55 records · Page 3Linked to original sources
PubMed1997

Urinary 5-hydroxytryptophol following acute ethanol consumption: clinical evaluation and potential aviation applications.

HYPOTHESIS: The unknown prevalence of alcohol use and misuse among aviation pilots, crewmembers and associated support personnel call for continuous improvement of methods for detecting recent alcohol use. Early detection is essential to proper treatment and prevention of potentially catastrophic mishaps. Urinary 5-hydroxytryptophol (5HTOL), a serotonin (5HT) metabolite, has shown promise in the clinical setting as a noninvasive marker of recent alcohol consumption. METHODS: The urinary 5HTOL concentrations of 11 male and female subjects were followed for approximately 24 h following dosing with ethanol 0.6 g.kg-1. Concentrations were reported as a ratio of 5HTOL to 5-hydroxy-indoleacetic acid (5HIAA), 5HTOL/5HIAA (pmol/nmol), to compensate for urinary dilution and elevated 5HTOL levels due to dietary intake. Data from one male subject was excluded after he admitted to continued alcohol consumption subsequent to dosing and missing several urine samples. RESULTS: 5HTOL/5HIAA ratios remained above the 15 pmol/nmol cutoff for recent alcohol use for approximately 11-16 h in all except one subject. Calculations based on body weight and administered alcohol dose suggest that measurable blood alcohol levels would exist for only 5-7 h post ingestion. CONCLUSION: This study confirmed the extended elevation of 5HTOL/5HIAA ratios observed in earlier studies, even at the relatively low alcohol dose used herein. 5HTOL appears to be a marker for acute alcohol consumption worthy of further investigation by military and civilian authorities. Potential aviation applications of 5HTOL include validation of measurable blood alcohol concentrations, investigation of poor performance due to hangover effects, and as a forensic toxicology tool in aircraft accident investigations to distinguish between actual alcohol ingestion and post-mortem alcohol synthesis.

Acute Disease↗
PubMed1996

Structural studies of the O-specific chain of Hafnia alvei strain 32 lipopolysaccharide.

The structure of the O-specific side chain of the Hafnia alvei strain 32 lipopolysaccharide has been investigated. Methylation analysis, partial acid hydrolysis, Smith degradations, NMR spectroscopy, MALDI-TOF and FAB mass spectrometry in combination with collision-induced decomposition MS/MS were the principal methods used. It is concluded that the polysaccharide is composed of pentasaccharide repeating units having the following structure which is partially O-acetylated in the 2- (20%) and 3- (50%) position of the-->4)-alpha-D-GalpA-(1-->residue. [sequence :see text] A MALDI-TOF mass spectrum of the O-specific chains indicated that they consisted of up to 16 repeating units.

Carbohydrate Conformation↗
PubMed1996

Structural studies of the O-specific polysaccharide of Hafnia alvei strain 1209 lipopolysaccharide.

The structure of the O-specific side chains of the Hafnia alvei strain 1209 lipopolysaccharide has been investigated. Methylation analysis and 1H-NMR and 13C-NMR spectroscopy were the principal methods used. It is concluded that the polysaccharide is composed of pentasaccharide repeating units that have the following structure: -->3)-beta-D-Galp-(1-->4)-alpha-D-Glcp-(1-->4)-beta-D-GlepA-(1--> 3)-beta-D-GalpNAc-(1 --> 4 increases 1 alpha-L-Rhap The relative intensity of the signals from the terminal repeating unit in the 1H-NMR spectrum, the amount of 2,3,6-tri-O-methylgalactose in the methylation analysis, and the matrix-assisted laser-desorption ionisation time-of-flight (MALDI-TOF) mass spectrum of the O-polysaccharide indicated that the structure is also the biological repeating unit and that the O-chains mainly consisted of 8-11 repeating units and, on average, ten repeating units.

Carbohydrate Conformation↗
PubMed1996

Binding of enterotoxigenic Escherichia coli expressing different colonization factors to tissue-cultured Caco-2 cells and to isolated human enterocytes.

The binding of ETEC strains expressing different colonization factors to the human enterocyte-like cell line Caco-2 and to isolated human enterocytes were determined. Strains expressing CFA/I, CS2, CS4+CS6, CS5+CS6, CS7, CFA/III+CS6 and PCFO166 adhered well to both types of cells whereas bacteria producing CS1, CS6 only, or CS17 did not adhere to either Caco-2 cells or to jejunal human enterocytes, suggesting that similar binding structures are present in both cell types. However, in some instances, binding of bacteria to the two types of cells differed, e.g. bacteria expressing CS3 or PCFO9 bound well to human enterocytes but not to Caco-2 cells. Conversely, bacteria producing PCFO20 or PCFO159 only adhered to Caco-2 cells and not to jejunal enterocytes. With few exceptions, this inability to bind to human enterocytes was the same for cells from all parts of the small intestine. This study contradicts previous reports suggesting that the binding structures of Caco-2 cells are identical to those of human enterocytes.

Bacterial Adhesion↗
PubMed1996

Longitudinal comparison of carbohydrate-deficient transferrin and gamma-glutamyl transferase: complementary markers of excessive alcohol consumption.

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 during long-term monitoring of out-patients.

Adult↗
PubMed1996

Carbohydrate-deficient transferrin and gamma-glutamyl transferase levels during disulfiram therapy.

Serum samples for quantification of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) were collected from alcohol-dependent men and women upon admission to the hospital for detoxification, and repeatedly over a 3- to 5-week period of supervised disulfiram administration as outpatients. On admission, 10 of 12 patients showed CDT concentrations above the conventional cutoff limits, whereas 6 had elevated GGT values. Normalization usually occurred within 1 to 3 weeks of disulfiram treatment, after which CDT and GGT leveled out at a relatively stable individual baseline level. However, in those patients with the highest values on admission, the decline continued during the entire observation period. The time for normalization of GGT was typically longer than for CDT. In four male patients who had taken disulfiram regularly (400-800 mg every second or third day) for at least 3 months before entering the study, the CDT and GGT concentrations were stable over time and all fell within normal limits. The present results indicate that disulfiram treatment does not influence the serum level of CDT. It is also suggested that consecutive CDT and GGT measurements during outpatient treatment with disulfiram after detoxification can be used to identify the individual baseline (i.e., abstinence) values for CDT and GGT, and, furthermore, for monitoring treatment outcome.

Adult↗
PubMed1996

Laboratory testing for recent alcohol consumption: comparison of ethanol, methanol, and 5-hydroxytryptophol.

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.

Adult↗
PubMed1995

Structural studies of the O-specific chain and a core hexasaccharide of Hafnia alvei strain 1192 lipopolysaccharide.

The structure of the O-specific side-chain and a core hexasaccharide of the Hafnia alvei strain 1192 lipopolysaccharide has been investigated. Methylation analysis, NMR spectroscopy, MALDI-TOF spectrometry, and various specific chemical degradations were the principal methods used. It is concluded that the polysaccharide is composed of hexasaccharide repeating-units having the following structure which is partially O-acetylated in the 2-position of the --> 4)-alpha-D-Glc pA-(1-->(70%) and on different positions of the L-Rha residues (50%). [Formula: see text] The core hexasaccharide was found to have the following structure: [Formula: see text]

Acetylglucosamine↗
PubMed1995

5-Hydroxytryptophol conjugation in man: influence of alcohol consumption and altered serotonin turnover.

The distribution of free and conjugated forms of the serotonin (5-hydroxytryptamine) metabolite 5-hydroxytryptophol (5HTOL) in human urine was determined. 5HTOL was analyzed using a sensitive and specific gas chromatographic-mass spectrometric method. The sulfate and glucuronide conjugated forms were measured indirectly following enzymatic hydrolysis. Total 5HTOL levels in control samples ranged between 98-301 nM, in samples collected following ingestion of bananas, a food rich in serotonin, between 450-3292 nM, following alcohol consumption between 863-13326 nM, and in samples obtained from patients with serotonin producing carcinoid tumors between 1695-3793 nM. Free 5HTOL accounted for less than 4% of total 5HTOL in all samples. Sulfate conjugated 5HTOL was calculated to comprise about 17% of total 5HTOL in the control samples and 15% in the alcohol samples, whereas the mean proportion was significantly increased to 33% and 27% in the samples collected after ingestion of bananas and from patients with carcinoid tumors, respectively. The results show that conjugation with glucuronic acid followed by urinary excretion is normally the predominant route for elimination of 5HTOL in man. However, in situations of elevated levels of total 5-hydroxyindoles originating from dietary sources or serotonin producing tumors in the gut, sulfate conjugation becomes more important.

Adult↗
PubMed1995

Determination of 5-hydroxytryptophol in urine by high-performance liquid chromatography: application of a new post-column derivatization method with fluorometric detection.

The aim of the present study was to develop a high-performance liquid chromatographic (HPLC) method for determination of the serotonin metabolite 5-hydroxytryptophol (5HTOL) in human urine. 5HTOL was liberated from its conjugated form by enzymatic hydrolysis and isolated by a sample clean-up procedure on a small Sephadex G-10 column. The eluate was injected onto an isocratically eluted C18 reversed-phase column and 5HTOL was converted into a fluorescent oxazole derivative by on-line post-column reaction with benzylamine in the presence of potassium hexacyanoferrate(III). The limit of detection was about 10 nM and the intra-assay coefficients of variation were below 4% with urine samples and standard solutions. The results indicate that the method can be used as a screening method to discriminate between normal and elevated levels of total (free + conjugated) 5HTOL in urine.

Chromatography, High Pressure Liquid↗
PubMed1995

Detection of relapses in alcohol-dependent patients using carbohydrate-deficient transferrin: improvement with individualized reference levels during long-term monitoring.

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.

Adult↗
PubMed1995

Changes in serotonin metabolism during treatment with the aldehyde dehydrogenase inhibitors disulfiram and cyanamide.

The effect of the aldehyde dehydrogenase inhibitors disulfiram (Antabuse) and cyanamide (calcium carbimide, Dipsan) on the metabolism of serotonin measured as relative amounts of the metabolites 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol in urine were studied in alcoholic patients. Sixteen out of 23 patients receiving drug therapy showed elevated excretion of 5-hydroxytryptophol. However, there was a marked, 15-fold, variability in 5-hydroxytryptophol excretion rate between patients. A high degree of variability was also seen in another group of patients studied before and after introduction of drug therapy. When patients were followed during the dose interval, a time-dependent response after each single dose could be observed. The disulfiram response lasted over the course of several days whereas the response to cyanamide lasted for less than 12 hr. It is concluded that treatment with disulfiram and cyanamide affects serotonin metabolism leading to increased production of 5-hydroxytryptophol, but there is a marked inter-individual variability in degree of response.

Adult↗
PubMed1995

Distinguishing ingested ethanol from microbial formation by analysis of urinary 5-hydroxytryptophol and 5-hydroxyindoleacetic acid.

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.

Adult↗
PubMed1994

Influence of genetic variation in alcohol and aldehyde dehydrogenase on serotonin metabolism.

The influence of genetic variation in alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) on the metabolic pattern of serotonin (5-hydroxytryptamine, 5-HT) in humans was examined from the relative urinary concentrations of the end products 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL). Healthy Caucasian (Swedish) and Oriental (Chinese) subjects were genotyped for ADH2, ADH3 and ALDH2 by a PCR/SSCP technique. The 5-HTOL/5-HIAA ratios ranged between 0.9-9.4 pmol/nmol (4.4 +/- 1.8, mean +/- SD, n = 143). No significant difference in the 5-HT metabolic pattern was observed between Caucasians and Orientals (4.3 +/- 1.8 and 4.4 +/- 1.8 pmol/nmol, respectively), nor between any of the ADH2, ADH3 and ALDH2 genotypes. Despite the modulatory effects of genetic variation of these enzymes on ethanol metabolism, the present results indicate that the individual isozyme composition of ADH2, ADH3 and ALDH2 is not important for the metabolic pattern of 5-HT.

Alcohol Dehydrogenase↗
PubMed1994

Genotypic and phenotypic identification of coli surface antigen 6-positive enterotoxigenic Escherichia coli.

A polynucleotide probe comprising the gene encoding a major structural subunit protein of coli surface antigen 6 (CS6) of enterotoxigenic Escherichia coli (ETEC) was developed. Eighty-nine ETEC isolates were examined in parallel with the probe in a colony hybridization assay and in a recently developed polyclonal-antibody-based inhibition enzyme-linked immunosorbent assay (ELISA). The two assays showed a high level of concordance in the detection of CS6-positive ETEC (kappa = 0.84, P < 0.00001). Thus, 36 of the 89 ETEC isolates were identified as CS6-positive by both assays. Six strains that were negative for other colonization factor antigens were positive with the CS6 probe but negative in the ELISA, suggesting lack of surface CS6 expression in these strains. One strain was probe negative but positive in the ELISA, while the remaining 46 strains were negative in both assays. The phenotypic and genotypic assays will prove useful in vaccine-oriented studies of ETEC disease.

Antigens, Bacterial↗
PubMed1994

Detection of relapses in alcohol dependent patients using serum carbohydrate deficient transferrin: improvement with individualized reference levels.

Alcohol dependent male outpatients were monitored for a period of six months. Indicators of alcohol consumption were compared using clinical information three times per week, serum levels of carbohydrate deficient transferrin (CDT) weekly and urine samples of 5-hydroxytryptophol daily. Individualized reference values of CDT were calculated by using an increase of three times the lowest coefficient of variation in the group, which meant that an increase of < or = 30% from the lowest value of each individual was considered a significant increase, and therefore an indication of alcohol consumption. By this approach, it was possible to improve the ability to detect relapses in alcohol dependent patients using serum CDT once a week compared to CDT using reference values recommended by the manufacturer.

Alcohol Drinking↗
PubMed1994

The use of 5-hydroxytryptophol as an alcohol intake marker.

5-Hydroxytryptophol (5HTOL) occurs naturally in animals as a metabolite of serotonin. Ethanol interacts with serotonin metabolism to increase the production of 5HTOL at the expense of 5-hydroxyindoleacetic acid (5HIAA). This can be used clinically in the treatment of alcohol dependence to improve the detection of relapse in alcohol drinking, by monitoring daily the urinary 5HTOL/5HIAA ratio. In one experiment the sensitivity of this marker in detecting alcohol drinking the previous day was more than 10-fold greater than measuring urinary ethanol. Genetic polymorphism in alcohol and aldehyde dehydrogenases, which is known to influence the ethanol metabolism, does not confound the clinical use of 5HTOL as a marker. Disulfiram and cyanamide, however, will elevate urinary 5HTOL/5HIAA ratio.

Alcohol Drinking↗