Biomedical subjects

G Skopp

Publications and source records attributed to G Skopp.

At least 37 records · Page 2Linked to original sources

PubMed1997

Biochemical approach on the conservation of drug molecules during hair fiber formation.

A biochemical concept for the endogenous incorporation of drug molecules into growing hair is presented. It is based on the principles of transport across biomembranes, on the principles of biotransformation and drug melanin affinity. The approach gives explanations for current observations in hair analysis, which up to date have not been understood sufficiently. Phenomena such as the ratio of parent drug to metabolite in hair, the dependence of incorporation on the physico-chemical properties of the drug, the independence of drug incorporation on active melanogenesis (incorporation into non-pigmented hair) as well as the dependence of drug content on hair pigmentation are elucidated.

Absorption↗

PubMed1997

On cosmetically treated hair--aspects and pitfalls of interpretation.

Popular hair cosmetic treatments like bleaching or permanent waving were found to affect the stability of incorporated drugs and to cause alterations of the fibers at an ultrastructural level. This may result in a partial or complete loss of drug substances, depending on the particular drug molecule and on its concentration prior to the cosmetic treatment. Moreover, from literature, there is some evidence that drug molecules are not only incorporated into the growing fiber by passive diffusion from blood into the matrix cells and melanocytes, but that the substances enter the hair also via perspiration such as sweat and sebum. Since permed and bleached hair shows an enhanced sorption capacity, the risk of false positives or an unusually high drug concentration in cosmetically treated hair was under investigation. Virgin, permed, mildly as well as severely bleached tresses were exposed to artificial sweat or sebum containing cocaine, benzoylecgonine, 6-acetylmorphine, morphine and codeine (500 ng/g). Except codeine, the concentrations measured by GC/MS were very small and quite close to the detection limit indicating a minor importance of drug uptake into hair fiber from the endogenous-exogenous shunt via sebum or sweat. From the results it is concluded that an increased risk of false positive results in hair analysis on bleached and permanent waved hair fibers does exist, but is not particularly severe.

Drug Interactions↗

PubMed1997

Influence of sample preparation on analytical results: drug analysis [GC/MS] on hair snippets versus hair powder using various extraction methods.

The comparison of aqueous extraction methods and hair extraction by organic solvents performed on hair powder as well as on hair snippets of the same sample revealed different qualities of the procedures. Qualitative and quantitative results by the same derivatization step and GC/MS detection demonstrated, that the risk of missing a drug substance is higher using hair snippets than after drug extraction on pulverised hair. Drug recovery for opiates, cocaine and benzoylecgonine from hair was found to be best in aqueous solvents or in methanol extracts. The results are discussed under the aspects of solid-phase extraction, the hair sample representing an inhomogenous material. The localisation of drug molecules in hair, the hair swelling and penetration behavior of the particular extraction medium as well as the partition coefficient of solvent/hair phase for a particular drug substance are considered to influence the results.

Gas Chromatography-Mass Spectrometry↗

PubMed1997

A comparison of 3H-cocaine binding on melanin granules and human hair in vitro.

The in vitro experiments on the interaction of 3H-cocaine and melanin from Sepia officinalis confirmed the existence of drug binding sites on melanin granules. The results suggested that the binding of 3H-cocaine to melanin could be analyzed by assuming that the binding to the surface of pigment granules is analogous to the adsorption of a drug on a solid and follows Langmuir adsorption isotherm type I. Scatchard analysis indicated heterogeneity of binding sites. Structural and chemical alterations caused by isolation of the melanoproteins, which are heterogeneous in nature and show different physico-chemical properties, are considered to be most crucial. The studies on hair samples confirmed that melanin-drug interaction occur on the surface of melanin granules. These seem to be of minor importance compared to the drug-melanoprotein loading during melanogenesis for the observed influence of pigmentation on the drug content of hair fibers. From the results it was concluded that in vitro studies on melanin provide limited information and even drug-soaked hair must be regarded as inappropriate for the study of melanin-drug-binding in hair.

Animals↗

PubMed1997

A case report on drug screening of nail clippings to detect prenatal drug exposure.

In a case of a sudden infant death syndrome-related death of a 3-month-old infant, nail clippings were positive for cocaine by gas chromatography-mass spectroscopy analysis that revealed a prenatal exposure to the drug substance. In utero exposure to drugs has been investigated using amniotic fluid, neonatal urine, meconium, and hair samples. Nail analysis offers some advantage over hair analysis because of its continuous growth and persistence after delivery. Nail material is easy to sample in suitable amounts. Currently, the cocaine finding cannot be related to the underlying cause of death. However, this observation indicates that nail analysis may be a new and valuable tool to screen newborns for intrauterine drug exposure. In addition, it can help collect information on the prevalence of possible embryotoxic effects and the link to postnatal manifestations of different dysfunctions in infants who are born by drug abusing mothers.

Cocaine↗

PubMed1997

An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall.

A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.

Biological Transport↗

PubMed1997

Influence of pigmentation on the codeine content of hair fibers in guinea pigs.

Tortoise shell guinea pigs (n = 7) were administered codeine (1 mg/mL codeine-base) in their drinking water for 3 weeks. Black, reddish-brown and white hair was collected separately from each animal before and after treatment. The hair samples were analyzed by GC/MS. The experiment showed positive results for all hair fibers with large individual variability of drug incorporation. Low drug intake resulted in small differences of the drug content in hair fibers different in color, whereas in cases of high drug intake a strong influence of hair pigmentation on the analytical results was observed. The highest drug content was always found in black hair samples, non-pigmented hair showed the lowest drug concentrations and the drug content in reddish-brown fibers was less than in black hair samples from the same animal. From the results it was concluded, that eumelanins rather than phenomelanins are the decisive factor for codeine-melanin binding in hair and the amount of drug intake was suggested to determine the relevance of hair pigmentation on the analytical results.

Animals↗

PubMed1997

Ethyl glucuronide concentration in serum of human volunteers, teetotalers, and suspected drinking drivers.

The kinetic profile of ethanol and ethyl glucuronide (EtG) in serum was investigated in three subject groups: 1) Healthy, moderately drinking volunteers (daily intake less than 30 g ethanol) who ingested a single dose of ethanol. In this group the maximum of serum ethyl glucuronide concentration (SEtGC) and of serum ethanol concentration (SEC) did not exceed 3.7 mg/L and 1.5 g/L respectively. EtG peaked 2 to 3.5 h later than ethanol. EtG was eliminated with a terminal half-life of 2 to 3 h. EtG decreased slower than ethanol--the metabolite could still be determined in serum up to 8 h after complete ethanol elimination. 2) In serum samples of teetotalers neither ethanol nor EtG could be found. 3) In 37 of 50 serum samples of drivers suspected of driving under the influence of ethanol, SEtGC was found between the limit of detection (0.1 mg/L) and 20 mg/L. If the SEC is less than 1 g/L and the SEtGC is significantly higher than 5 mg/L, we assume alcohol misuse.

Adult↗

PubMed1996

Stability of opiates in hair fibers after exposure to cosmetic treatment.

The stability of opiates in clipped natural human hair was investigated. Hair fibers were incubated with defined solutions of morphine, codeine and dihydrocodeine (pH 7.4) until saturated. Original opiate-positive hair samples collected from drug addicts also were examined. Commercially available bleaching as well as perming formulas (Poly Blonde Ultra, Poly Lock; Henkel, Düsseldorf, Germany) were applied in vitro to the hair strands of both groups under investigation. After these treatments, the drug concentration had decreased for both bleaching and permanent waving. In the spiked hair, only 2-18% of the starting solution could be found after bleaching. About 20-30% of the drug substances could still be detected after perming. In the authentic hair samples, the drug levels of the formerly opiate positive hair fibers had also been reduced but distinct tendencies could not be observed.

Bias↗

PubMed1996

Fatal poisoning with the antidepressive agent opipramol.

An ingestion of an unknown quantity ( < or = 3000 mg) of opipramol dihydrochloride in a suicide case is described. Quantitation of opipramol and its deshydroxyethyl metabolite was performed simultaneously after liquid-liquid extraction from alkalinized samples prior to HPLC analysis. Postmortem concentrations of opipramol and of the metabolite in body fluids and organs are given. The distribution pattern of opipramol in tissue was comparable to findings from animal studies. The results showed the high uptake of opipramol in parenchymal tissues resulting in a low blood concentration. A possibly low contribution of deshydroxyethyl opipramol to the antidepressive effect may be concluded as the concentration was considerably lower in brain compared to other organs.

Adult↗

PubMed1996

Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose.

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of the inferior vena cava, the superior vena cava, the femoral and subclavian veins, and the right and left ventricles were examined for morphine, morphine-3-glucuronide and morphine-6-glucuronide, hematocrit and water content. Drug concentrations were determined by HPLC based on the native fluorescence of the analytes. Morphine glucuronides proved to be stable for a time period of 72 h. The water content ranged from 65 to 83% and hematocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences observed for drug concentrations from different sampling sites. The differences could neither be attributed to incomplete distribution during life-time nor to a diffusion process following the different distribution volumes of morphine and its conjugates. A definite relationship between the ratio of the molar concentrations of morphine and its glucuronides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and changes over time and tissue concentrations should be analysed.

Adult↗

PubMed1996

Preliminary practical findings on drug monitoring by a transcutaneous collection device.

A noninvasive and nonocclusive skin patch (Sudormed) was investigated for the systematic collection of drugs of abuse over a period of several days. First, the applicability and user friendliness were tested by volunteers. The permeability of the polyurethane dressing from the outside to the inside for an aqueous solution was shown by incubating the outside layer with Rhodamine B. No fluorescence could be detected in the cotton pad beneath. A single dose experiment using theophylline as a model compound showed that there was a delay in time before the substance could be determined in the pad. The drug content decreased with increasing time of patch application. When eight volunteers participating in a methadone treatment were monitored, the substitute drug could always be detected in the patch associated with a minor concentration of EDDP. Besides, in some of the patches investigated, indications for an abuse of cocaine and heroin were found. The so-called sweat patch appears to be a valuable tool in clinical and forensic toxicology, as it offers a longer and prospective surveillance period compared with blood and urine testing.

Drug Monitoring↗

PubMed1996

Experimental investigations on hair fibers as diffusion bridges and opiates as solutes in solution.

Diffusion experiments were performed using clipped hair fibers as diffusion bridges and aqueous solutions of morphine, codeine and dihydrocodeine. Natural as well as predamaged hair fibers were investigated. The test series were conducted at ambient temperature and at high humidity. After 312 or 372 hours the middle segments of the strands were clipped, washed and analyzed by GC/MS. Only when virgin hair samples were used the solutes passed along the fiber at full length resulting in a positive immunological finding at the end of the diffusion bridge. Most of the washing fluids were positive for opiates. All centerpieces had a high opiate content. The opiate concentration in damaged hair was significantly higher. Radial swelling of the hair fiber with radial diffusion was the first and main process to appear when hair was exposed to water. The diffusion process in hair could not be placed in a simple mathematical treatment.

Asian People↗

PubMed1995

[Hair analysis in the diagnosis of toxic hepatitis after Ecstasy abuse].

HISTORY AND CLINICAL FINDINGS: A young man, aged 18 years, was admitted to hospital for suspected hepatitis, having developed increasing jaundice without any pain. His urine was light brown in colour and the stools often liquid and pale. Every 14 days for the last 4 months he had been taking 2 tablets of "ecstasy" (methylenedioxyamphetamine; MDMA). Physical examination was unremarkable and the patient was in good general condition. TESTS: The activities of GOT, GPT and alkaline phosphatase were raised (to 903, 744 and 270 U/l, respectively) as was the bilirubin concentration (16.8 mg/dl). Tests were negative for: leptospira and the viruses of mumps, HI, varicella zoster, picornavirus, cytomegaly, Coxsackie and hepatitis, A, B and C. Ultrasound revealed hepatomegaly, with a normal echo pattern. Hair analysis demonstrated, in two different hair segments (0-2 cm and 2-4 cm, respectively) both MDMA (6.4 and 4.3 micrograms/g hair) and its metabolite MDA (0.7 and 5.0 micrograms/g hair). TREATMENT AND COURSE: No specific treatment was required. After intake of the drug had been stopped the transferase activities and bilirubin concentration became essentially normal. CONCLUSION: Hair analysis can be valuable in confirming "ecstasy" abuse, especially when it is denied, and thus contribute to clarifying the cause of toxic hepatitis.

Adolescent↗

PubMed1995

Ultrastructural alterations and environmental exposure influence the opiate concentrations in hair of drug addicts.

Hair samples were taken at autopsy from the head of 1 male and 1 female subject both known as drug abusers. Some of the strands were bleached by in-vitro cosmetic treatment. The bleached hair as well as the original hair samples were partly exposed to water or soil prior to further investigations and drug monitoring. The exposure times were 4 weeks or 6 months for water and 6 months for soil. The hair fibers were examined by transmission electron microscope (TEM) and by scanning electron microscope (SEM) investigations. The electron microscope studies confirmed that all experimental conditions had produced morphological alterations in the hair fibers. After exposure to water or to soil for 6 months as well as after storage of the clipped bleached hair in tap water at room temperature for 4 weeks, drug monitoring of formerly positive hair samples gave negative results. After storage of natural hair in soil or in water for 4 weeks the opiate levels had dramatically decreased. The samples were screened by fluorescence polarization immunoassay after enzymatic digestion. The results were confirmed by GC/MS.

Environmental Exposure↗

PubMed1995

[Congener analysis in a drinking trial with unusually high alcohol content].

The aforementioned case proves very convincingly that a very high dose of alcohol consumed within a short time span can be absorbed completely within 2 hours. Numerical models based on low to moderate alcohol consumption were lower than expected in cases of severe alcohol intake. The claim of alcohol consumption after an event can best be verified by means of a drinking experiment under intensive medical supervision.

Accidents, Traffic↗

PubMed1994

Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).

An ingestion of an unknown quantity of U 46 D-Fluid (500 g dichlorophenoxyacetic acid/l) in a suicide is described. Although 2,4-dichlorophenoxyacetic acid (2,4 D) is widely used as a herbicide, intoxications are relatively rare. Quantitation of 2,4-D was performed by diethyl ether extraction from acidified samples (viscera) or by deproteinization (blood, plasma) with methanol before HPLC analysis. Postmortem concentrations of 2,4-D in body fluids and tissues are given. The proposed method resulted in a rapid procedure most useful in cases of deliberate poisoning with phenoxyacetic herbicides.

2,4-Dichlorophenoxyacetic Acid↗

PubMedDate not supplied

Ethyl glucuronide in human hair.

Ethyl glucuronide (EtG) is considered to be a promising candidate marker of alcohol consumption, but exhibits a short window of detection in blood or urine. Keratinized tissues are known to retain foreign substances and to provide a greater retrospective window of detection than body fluids. Therefore, post-mortem hair, skin swabs, and stratum corneum samples were collected from four subjects with a reported history of alcohol misuse and from seven subjects with a report of regular, socially accepted drinking behaviour, and were investigated for EtG. Additionally, certain specimens were collected from three children, who had not yet consumed any alcoholic beverages. EtG was detectable in most of the hair and stratum corneum samples as well as in perspiration stains from alcohol-consuming subjects. The results indicated that EtG might be formed locally in very small and highly variable amounts. The most important finding was that EtG cannot be expected to be generally detectable in keratinized tissues or perspiration stains from alcohol-drinking subjects, whereas a positive result is always associated with recent alcohol consumption.

Alcohol Drinking↗