Evaluation of two compounds as possible radioprotectors

Radioprotecting effectiveness of S-[2-(diethylamino)ethyl] 4-methylbenzothiohydroximate hydrochloride (Dev-B-9) and S-[2-(diethylamino)ethyl]alpha-keto 4-methyl benzothiohydroximate hydrochloride (Dev-B 43) were evaluated by both survival studies in mice exposed to 10.5 Gy whole body gamma-irradiation and 24 hours deoxycytidine (CdR) excretion in urine of rats following 5 Gy irradiation. The drugs were tested after intraperitoneal (i.p.) administration. The drugs rendered significant protection in sublethal (5 Gy) irradiation but could not protect against 10.5 Gy exposure.     

Evaluation of 18F-FA-4 and 11C-pipzA-4 as radioligands for the in vivo evaluation of the high-affinity choline uptake system.

4,4'-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system. We have evaluated 4-[1-hydroxy-2-(4-(18)F-fluoromethylpiperidin-1-yl)ethyl]-4'-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl ((18)F-FA-4) and 4-[1-hydroxy-2-(4-(11)C-methylpiperazin-1-yl)ethyl]-4'-[1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl]biphenyl ((11)C-pipzA-4), an (18)F- and a (11)C-labeled derivative of A-4 as potential in vivo tracers for the HACU system. METHODS: The biodistribution of both compounds was determined in mice, and the intracerebral distribution was visualized by ex vivo and in vitro autoradiography. The in vitro affinity of the compounds was determined by a displacement study with (3)H-HC-3 on mice brain slices. RESULTS: In mice, both tracers show a high and persistent brain uptake. In vitro autoradiography shows binding to the striatum, whereas ex vivo autoradiography shows homogeneous binding throughout the brain. FA-4 and pipzA-4 inhibited the (3)H-HC-3 binding with a 50% inhibitory concentration of 57 nmol/L and 320 nmol/L, respectively. CONCLUSION: The evaluated compounds have affinity for HACU and show high uptake in the brain. In vitro binding of the compounds to the striatum cannot be inhibited by the presence of HC-3, whereas binding of HC-3 was inhibited by the presence of both FA-4 and pipzA-4, suggesting allosteric binding.     

A new precursor for the preparation of 6-[F]Fluoro- -m-tyrosine ([F]FMT): efficient synthesis and comparison of radiolabeling

For the electrophilic preparation of 6-[18F]fluoro-L-m-tyrosine ([18F]FMT), a PET tracer for measuring changes in dopaminergic function in movement disorders, a novel precursor, N-(tert-butoxycarbonyl)-3-(tert-butoxycarbonyloxy)-6-trimethylstannnyl-L-phenylalanine ethyl ester, was synthesized in four steps and 26% yield starting from L-m-tyrosine. [18F]FMT produced by two methods at two institutions was comparable in both radiochemical yield, 25-26%, and quality (chemical, enantiomeric, and radiochemical purity and specific activity) as that obtained with the original N-trifluoroacetyl-3-acetyl-6-trimethylstannyl-L-m-tyrosine ethyl ester [18F]FMT precursor.     

A novel and an effective analytical approach for the LC-MS determination of ethyl glucuronide and ethyl sulfate in urine

An alternative liquid chromatography–mass spectrometry (LC-MS) method based on no discharge (ND) atmospheric pressure chemical ionization (APCI) was developed for the simultaneous determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine in negative ion conditions. Abundant [M-H]^? species of EtG and EtS were obtained, allowing to reach limits of quantification (0.1 µg/ml for both analytes), accuracy, and precision comparable to those proposed in the literature. Additionally, the LC-ND–APCI-MS method proved to be reliable, requiring little maintenance even when high throughput analyses (i.e., 6,000 samples per year) were required.     

The acceleration of gallstone destruction with synchronous biliary lithotripsy and contact dissolution in vitro using three cholesterol-solubilizing solvent.

In the first-known application of its kind, shockwave lithotripsy and contact-solvent dissolution of large, calcified gallstone burdens were performed simultaneously with three chemical solvents, each tested separately in an in vitro model, with the combined effects on gallstone eradication examined. Two solvents, ethyl propionate and isopropyl acetate, were chosen for their solubilizing ability and potentially high level of patient safety. The third solvent, a 70%:30% mixture of methyl tert-butyl ether (MTBE) and dimethyl sulfoxide (DMSO), was chosen for its known ability to accelerate the dissolution of calcium-containing gallstones. All stones were matched for size, weight, and number. Gallstone lithotripsy performed in ethyl propionate was significantly more effective (P less than .02) in the production of fragments less than 2 mm when compared with bile; lithotripsy with isopropyl acetate and the MTBE/DMSO mixture showed no statistically significant effect. Biliary lithotripsy performed in an ethyl propionate medium may enhance gallstone dissolution and the production of small fragments (diameter less than 2 mm).     

Differentiation between decomposed remains of human origin and bigger mammals

This study is a follow-up study in the search for a human specific marker in the decomposition where the VOC-profile of decomposing human, pig, lamb and roe remains were analyzed using a thermal desorber combined with a gas chromatograph coupled to a mass spectrometer in a laboratory environment during 6 months. The combination of 8 previously identified human and pig specific compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, 3-methylthio-1-propanol, methyl(methylthio)ethyl disulfide, diethyl disulfide and pyridine) was also seen in these analyzed mammals. However, combined with 5 additional compounds (hexane, heptane, octane, N-(3-methylbutyl)- and N-(2-methylpropyl)acetamide) human remains could be separated from pig, lamb and roe remains. Based on a higher number of remains analyzed, as compared with the pilot study, it was no longer possible to rely on the 5 previously proposed esters to separate pig from human remains. From this follow-up study reported, it was found that pyridine is an interesting compound specific to human remains. Such a human specific marker can help in the training of cadaver dogs or in the development of devices to search for human remains. However, further investigations have to verify these results.     

Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

BACKGROUND/AIM: Hepatitis C virus infection (HCV) is a complex disease, most commonly chronicle (80-85%). The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. METHODS: The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. RESULTS: The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection). Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients). There was a signficant difference between the two subgroups (p < 0.001) regarding the examined values gamma-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. CONCLUSION: Based on the number of the examined patients (n = 15), we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.     

Preparation of 11C-labelled Raclopride, a new potent dopamine receptor antagonist: preliminary PET studies of cerebral dopamine receptors in the monkey

A new dopamine receptor antagonist, Raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy- 6-methoxybenzamide, FLA 870) (1), has been labelled using [11C]ethyl iodide for alkylation of the nitrogen of the pyrrolidine ring in the corresponding secondary amine (5). The synthesis of 5 and an efficient method for the preparation of [11C]ethyl iodide are described. The 11C-labelled FLA 870 (1) was purified by HPLC and then used in positron emission tomography to visualize the dopamine receptor-rich areas of the monkey brain. The images obtained show selective accumulation of FLA 870 in striatum and a 10-fold separation between the binding to caudate vs cerebellum.     

Development and validation of hydroxy ethyl starch kits for instant use in gastroesophageal reflux and gastric motility studies

A reduction method based on stannous chloride is described to prepare hydroxy ethyl starch kits for gastrointestinal reflux and gastric motility studies. Following verification of the consistency of radiolabelling, in vitro experiments were carried out to validate 99mTc hydroxy ethyl starch as a liquid phase and solid phase gastric motility imaging radiotracer. Gastroesophageal reflux, liquid phase and solid phase studies were then conducted in 13 adult volunteers to examine the in vivo stability of the radiotracer. High labelling efficiency (>95% when prepared at neutral pH) was consistently achieved, which remained stable in conditions simulating gastric environment. Twelve of the 13 volunteers did not show absorption of any radioactivity from the gastro-intestinal tract. 99mTc hydroxy ethyl starch is a new agent suitable for gastroesophageal reflux and gastric motility studies. It is available in kit form and is a more 'physiological' agent than 99mTc sulphur colloid for preparing a solid radioactive meal. 99mTc hydroxy ethyl starch represents a true carbohydrate meal, and unlike 99mTc sulphur colloid, is easy to prepare and can easily be standardized to produce a standard vegetarian meal.     

Synthesis of [131I/123I]-2-{5-(4-iodophenyl)pentyl}oxirane-2-carboxylic acid ethyl ester

A method is described for the synthesis, purification and radiolabelling of [¹²³I/¹³¹I]2-{5-(4-iodophenyl)-pentyl}oxirane-2-carboxylic acid ethyl ester. For the synthesis of this new agent, 5-phenylpentyl bromide (1), synthesized by reacting 5-phenyl-I-pentanol with sodium bromide under acidic conditions, was converted to diethyl 5-phenylpentylmalonate (2), which, on alkaline hydrolysis, yielded ethyl 5-phenyl-pentylmalonate (3). Ethyl 7-phenyl-2-methyleneheptanoate (4), prepared from the monoester (3), was oxidized with m-chloroperbenzoic acid to yield ethyl 2-(5-phenylpentyl)oxirane-2-carboxylate 5. The method of radiolabelling, based on the thallation of compound (5) and the subsequent treatment with radioiodide, resulted in a regioselective radioiodination with a 54% radiochemical yield.     

Competition for polyamine uptake into rat lung slices by WR2721 and analogues

The objective of these studies was to determine whether a series of structurally related radioprotective agents could act as substrates for the recently identified polyamine system in the lung. We have shown that WR2721 (S-2(3-aminopropylamino)ethyl phosphorothioate), S-2(4-aminobutylamino)ethyl phosphorothioate (S-ABEP or WR2822) and S-2(7-aminoheptylamino)ethyl phosphorothioate (S-AHEP) competitively inhibit the uptake of putrescine into rat lung slices. The ability of the radioprotectors to act as substrates for the polyamine uptake system was expressed as the Ki for each compound. The Ki values for WR2721, S-ABEP and S-AHEP in the absence of dithiothreitol were 48, 57 and 7 mumol dm-3 compared to 155, 88 and 15 mumol dm-3 in the presence of dithiothreitol, indicating that the disulphide form may have a higher affinity for the transport system. By analogy with other substrates for the polyamine uptake system we have concluded that it should be possible to target radioprotectors to the alveolar epithelial type I and II cells and the Clara cells in the lung, as they prossess this uptake system, and thus protect these cells from oxidative stress.     

Improved extraction of thinner components from human body fluids by headspace solid-phase microextraction with a Carboxen/polydimethylsiloxane-coated fiber

An improved method for extraction of thinner components in human whole blood and urine samples by headspace solid-phase microextraction (SPME) with a Carboxen/polydimethylsiloxane-coated fiber is presented. The body fluid samples, containing ethyl acetate, benzene, 1-butanol, toluene, butyl acetate, isoamyl acetate and ethylbenzene as internal standard (IS), were heated at 70 degrees C in a silicone-rubber septum-capped vial in the presence of distilled water plus NaCl; a Carboxen/polydimethylsiloxane-coated SPME fiber was then exposed to the headspace of the vial to allow adsorption of the compounds before capillary gas chromatography (GC) with flame-ionization detection. For whole blood, extraction efficiencies of 1-butanol, ethyl acetate and isoamyl acetate were 8.72-31.1%, and those of IS, butyl acetate, toluene and benzene were 42.9-74.1%. For urine, those of all compounds were 10.7-75.4%. The regression equations for six thinner components extracted from whole blood and urine were linear in the range of 3-500 ng/0.5 ml for ethyl acetate and 1-butanol, and 0.5-500 ng/0.5 ml for benzene, toluene, butyl acetate and isoamyl acetate. The detection limits for each of the components were 0.25-1.5 ng/0.5 ml for both samples. The coefficients of within-day and day-to-day variation for all components were satisfactory and not greater than 11 and 13%, respectively. The data obtained from actual determination of ethyl acetate, benzene and toluene in rat whole blood and urine after inhalation of the compounds were also presented.     

Interpretation of a highly positive ethyl glucuronide result together with negative fatty acid ethyl esters result in hair and negative blood results

Considering the widespread nature of alcohol-related problems, the diagnosis of excessive alcohol consumption is an important task from medical and legal viewpoints. Alcohol abuse can be documented by usual blood [e.g., carbohydrate deficient transferrin (CDT)] and liver function [e.g., γ-GT or mean corpuscular volume (MCV)] tests, and, over a long-term basis, by hair analysis. Major markers of ethanol consumption in hair are ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). Detection of EtG in hair is said to be associated with excessive alcohol consumption, whereas a negative result does not unambiguously exclude alcohol abuse. Investigations on FAEEs can also be used to monitor excessive alcohol consumption. Four FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate) are the most suitable markers for the detection of heavy alcohol consumption and show different concentrations in hair of children, adult teetotalers, and social drinkers in comparison with FAEEs concentrations found in the hair of alcoholics. The Society of Hair Testing has provided guidelines for hair testing for chronic excessive alcohol consumption, and states positive cutoffs for a 0–3 cm hair segment as 30 pg/mg and 0.5 ng/mg for EtG and FAEEs, respectively. This study reviews the difficulties in interpreting blood and hair results of a 41-year-old woman involved in a child custody legal dispute. Her EtG and FAEEs concentrations in a 0–3 cm segment were 203 pg/mg and 0.29 ng/mg, respectively, and blood parameters were in the normal range (0.6 %, 93 fl, 14 IU/l for CDT, MCV, and γ-GT, respectively). Although the high EtG concentration suggested excessive drinking behavior, the second hair marker, FAEEs, and the three bloods tests were inconspicuous and in accordance with the claim of abstinence from alcohol by the subject. The woman declared having dyed her hair more than 6 months prior to sampling, use of weight-loss medication, and consumption of about four energy drinks per day. A hair lotion based on ethanolic plant extracts was regularly used by the subject, and could have been a source of contamination. Therefore, we recommend that possible external sources of hair contamination always be taken into consideration, especially if contradictory biological results are obtained and if the subject denies any alcohol intake.     

Design,synthesis and 64Cu labeling of fatty acid analogs containing dithiosemicarbazone chelate

For the development of ⁶²Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the ⁶²Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an ω-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di(N-methylthiosemicarbazone) (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromoundecanate by successive decarboxylation and hydrolysis, and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Crafts acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [⁶⁴Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of ⁶²Cu labeled fatty acid analogs.     

丙酮酸乙酯对脓毒症休克犬血流动力学的影响

目的 探讨丙酮酸乙酯(EP)对脓毒症休克犬血流动力学的影响.方法 健康雄性杂种狗20只,用内毒素(LPS)静脉注射复制犬脓毒症休克模型,随机分为对照组(n=8)和EP实验组(n=12).对照组只接受林格氏液复苏.EP实验组另外给予丙酮酸乙酯首剂0.05g/kg,然后0.05g/(kg·h)持续泵入.脓毒症休克模型稳定后记为0小时,此后每小时收集血流动力学指标,共观察12小时.结果 EP组血压在8小时有明显回升(P＜0.05),对照组血压无此趋势,两组比较有明显差异(P＜0.05).复苏后两组的心指数(CI)均有上升(P＜0.05), EP组表现尤为明显,但两组未能有显著差异(P＞0.05).休克后中心静脉压(CVP)明显上升(P＜0.05), EP组逐渐回落,6小时后两组比较有明显差异(P＜0.05).休克后平均肺动脉压(MPAP)明显上升(P＜0.05),EP组逐渐降至基线水平,对照组无此趋势(P＜0.05).心搏指数(SVI)、左室每搏功指数(LVSWI)休克后明显下降,但两组均迅速回复到基线水平,两组差异不明显(P＞0.05).休克后右室每搏功指数(RVSWI)升高, EP组逐渐降至基线水平,对照组无此趋势,8小时后两组比较有明显差异(P＜0.05).休克后体循环血管阻力指数(SVRI)明显下降(P＜0.05),EP组逐渐上升,8小时后两组比较有明显差异(P＜0.05).休克后肺循环血管阻力指数(PVRI)明显上升(P＜0.05), EP组逐渐回落,8小时后两组比较有明显差异(P＜0.05).结论 丙酮酸乙酯可以改善脓毒症休克犬血流动力学.     

Stimulation of 125I-3-iodo-α-methyl-l-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters

IntroductionTransport of the amino acid analog ¹²³I-3-iodo-α-methyl-l-tyrosine, which is used in clinical SPECT imaging, occurs mainly via l-type amino acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly expressed in actively proliferating tumors, we made a preliminary investigation of the effects of amino acid esters on enhancement of ¹²⁵I-3-iodo-α-methyl-l-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells.MethodsBecause the sequence of the CHO-K1 LAT1 gene is not available, we confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific inhibitors. l-Gly, l-Ser, l-Leu, l-Phe, l-Met, l-Tyr, d-Tyr, l-Val and l-Lys ethyl/methyl esters were tested in combination with IMT. Time-course studies over a 3-h period were conducted, and the concentration dependence of l-Tyr ethyl and methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a proof of de-esterification of l- and D-Tyr ethyl and methyl esters in the cells (by enzymatic attack or other cause), the concentration of l- and d-Tyr was analyzed by high-performance liquid chromatography of the esters in phosphate buffer (pH 7.4) and cell homogenates at 37°C or under ice-cold conditions.ResultsInhibition tests suggested that LAT1 is involved in IMT uptake by CHO-K1 cells. Co-administration of 1 mM of l-Tyr ethyl or methyl ester with IMT produced the greatest enhancement. The de-esterification reaction was stereo selective and temperature dependent in the homogenate. De-esterification kinetics were very fast in the homogenate and very slow in the phosphate buffer.ConclusionsThe l-Tyr ethyl or methyl esters were the most effective enhancers of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid exchange function of LAT1. This result suggests that de-esterification in the cells may be caused by enzymatic attack. We will use IMT and l-Tyr ethyl or methyl esters to examine LAT1 function in tumor cells or tissues in vivo.     

Synthesis and evaluation of 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2- benzisoxazole as an in vivo radioligand for acetylcholinesterase

6-Methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole is a high affinity (K(i) = 8.2 nM) reversible inhibitor of acetylcholinesterase (AChE). The carbon-11 labeled form was prepared in high (>97%) radiochemical purity and with specific activities of 37+/-20 GBq/micromol at end of synthesis, by the alkylation of the desmethyl precursor with [11C]methyl trifluoromethanesulfonate in N,N-dimethyl-formamide at room temperature. In vivo studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distribution. Thus, despite in vitro and in vivo activity as an AChE inhibitor, 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzis oxa zole does not appear to be a good candidate for in vivo imaging studies of AChE in the mammalian brain.     

Nachweis von chronischem Alkoholmissbrauch

Background

In this study the suitability of fatty acid ethyl esters levels in sebum for detection of chronic alcohol abuse or recent heavy drinking was evaluated.

Probands and methods

Sebum samples were collected by the use of Sebutapes (CuDerm) from the forehead of 51 alcoholics undergoing withdrawal treatment, 18 social drinkers and 10 non-drinkers and analyzed for ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate by headspace solid phase microextraction and gas chromatography mass spectrometry. Multiple investigations were carried out on several of the volunteers in order to investigate the time course.

Results

The cumulative concentration of the four esters was between 1.7 and 857 ng/Sebutape. Clearly elevated values above 60 ng/Sebutape were found in cases of alcohol abuse only within 2-3 days after beginning abstinence and then declined to a strongly varying base level of 20–30 ng/Sebutape which is not substantially different to that of normal drinkers and withdrawal patients.

Conclusions

Due to the short time window and the base level which was also found in strict teetotalers, the Sebutape test proved to be unsuitable for detection of chronic alcohol abuse and also excessive drinking events occurring only several days previously. In contrast hair analysis for fatty acid ethyl esters was found to be suitable because the esters are steadily and permanently accumulated in hair from sebum dependent on drinking phases.     

α-Alkylation of amino acid derivatives: Synthesis and chiral resolution of [C]β-aminoisobutyric acid

A synthesis of ¹¹C-labeled β-aminoisobutyric acid ([¹¹C]β-AIB) and its enantiomeric resolution by high performance liquid chromatography (HPLC) are reported. β-Alanine ethyl ester 2 was converted to benzaldimine-β-alanine ethyl ester 3 in 87% yield. Treatment of the imine derivative 3 with lithium diisopropylamide (1.1 eq) in tetrahydrofuran at −78 °C, followed by addition of cold iodomethane (1.1 eq) produced the -methylated benzaldimine-β-alanine ethyl ester 4 in 73% chemical yield. Deprotection of the amino group by acidic hydrolysis followed by basic hydrolysis of the ester group produced the desired product 1 in 37% chemical yield. Labeling was accomplished using [¹¹C]methyl iodide. The radiola-beled product was purified by HPLC using a semipreparative reversed-phase C-18 column and 2 mM phosphate buffer (pH 5.9) as the mobile phase. The synthesis time was 35–40 min including HPLC purification, with 20–60% radiochemical yield (decay corrected). Radiochemical purity was >99%, with average specific activity being 450 mCi/μmol. Enantiomers of β-AIB were well separated by analytical HPLC using a chiral column and aqueous perchloric acid as the mobile phase. (S)-β-AIB was eluted at 17.4 min and the (R)-enantiomer was eluted at 20.0 min when the jacketed column was maintained at low temperature by circulation of ice-cold water, and the pH of the mobile phase was 1.05.     

Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication

The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol.