Article

Hair analysis in the detection of long-term use of non-steroidal anti-inflammatory drugs and its relation to gastrointestinal hemorrhage: An examination of 268 hair and blood samples from autopsy cases

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics and antipyretics in Western countries. Gastrointestinal (GI) disorders are common side effects of NSAIDs and other drugs. This study investigated the correlation between chronic use of these substances and GI lesions by analyzing postmortem blood and hair samples from autopsy cases. This study included 268 hair and blood samples from autopsy cases. Deceased individuals with GI lesions were selected for the case group (n = 132) and those without any GI lesions were placed in the control group (n = 136). Collection of the samples took place from 2008 until 2010 at the Institute of Legal Medicine and Forensic Sciences, Charité-Universitätsmedizin Berlin, Germany. HPLC-DAD was used to analyze the blood samples while hair samples were analyzed using LC-quadrupole-time-of-flight-MS. The proximal 0-6 cm hair segment was analyzed. The full length of shorter hair samples was analyzed when longer segments were unavailable. Method validation was performed according to the guidelines of the German Society of Toxicological and Forensic Chemistry (GTFCh). Twenty-three per cent of the case group blood samples included one or more NSAIDs while 19 % of the control group blood samples included one or more NSAIDs. In contrast, the hair analysis results demonstrated that samples from the control and case group differed significantly; 67 % of the case group tested positive for one or more NSAIDs while 38 % of the control group tested positive for one or more NSAIDs. Hair analysis results provided a strong indication of a relationship between frequent NSAID consumption and GI lesions.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Hair minerals accumulate into the cortex of the hair (Combs, 1987). Hair analysis detects the causes of some toxic cases in animals, such as the presence of lead, molybdenum, or arsenic (Harkey, 1993;Henderson, 1993;Krumbiegel et al., 2014). ...
... Hair analysis was used to prove the mineral poisoning of famous humans, such as Bonaparte Napoleon (Kintz et al., 2007), and detect drugs, such as heroin and cannabis (Sen, 2010). It plays a role in identifying the duration of exposure to the toxicity of elements, such as arsenic, lead, and molybdenum (Harkey, 1993;Henderson, 1993;Krumbiegel et al., 2014). Furthermore, the morphology of hairs can be used to identify the human gender, age, and hair pigmentation (Ali et al., 2015). ...
Article
Full-text available
Veterinary forensics have attracted less attention compared with human forensics. Animal hair morphological examination using scanning electron microscopy (SEM) and hair mineral analysis using energy-dispersive X-ray fluorescence (ED-XRF) provide reference databases for animal hair identification used in forensic investigations. This study was performed on four different animal species: large ruminants (buffalo and cattle), small ruminants (goat and sheep), carnivores (cat and dog), and equines (donkey and horse). The hair scale pattern, scale margin type, and distance between scales were identified. The hair scale pattern was imbricate in large ruminants, goat, and horse; coronal (crown-like) in carnivores and donkey; and spinous in sheep. The morphometric measurements, including cuticle layer thickness, cuticle scale height, cortex diameter, and hair shaft width were recorded. The highest cuticle thickness was found in horse, and the highest cuticle hair scale was detected in cattle. Moreover, the largest cortex diameter was measured in buffalo, whereas the smallest one was in cat. With regard the content of hair elements, some elements were specific for the hair of certain tested animals, such as bromine in sheep and magnesium and phosphorus in buffalo. In addition, vanadium and titanium were found only in cattle and dog, and the latter element was also detected in sheep. In conclusion, this study provides two techniques for animal hair identification that can be used in forensic investigations.
... Analyses of animal remains, e.g. hair or bone, at a criminal scene may help to provide evidence for contact of a suspected assailant (Bertino and Bertino, 2015;Knecht, 2012), or to diagnose some toxic cases e.g. the presence of arsenic, lead or molybdenum in animasl (Harker, 1993;Henderson, 1993;Krumbiegel et al., 2014). In restaurants, animal remain investigation can help to identify meat adulteration, e.g. ...
... Moreover, it may help to diagnose some toxic cases, e.g. arsenic, lead and molybdenum toxicity, and identify the duration of exposure (Harkey, 1993;Henderson, 1993;Krumbiegel et al., 2014). In human, hair examination is used also to detect drug abuse e.g. ...
Article
Full-text available
Animal hair examination at a criminal scene may provide valuable information in forensic investigations. However , local reference databases for animal hair identification are rare. In the present study, we provide differential histological analysis of hair of some domestic animals in Upper Egypt. For this purpose, guard hair of large ruminants (buffalo, camel and cow), small ruminants (sheep and goat), equine (horse and donkey) and canine (dog and cat) were collected and comparative analysis was performed by light microscopy. Based on the hair cuticle scale pattern, type and diameter of the medulla, and the pigmentation, characteristic differential features of each animal species were identified. The cuticle scale pattern was imbricate in all tested animals except in donkey, in which coronal scales were identified. The cuticle scale margin type, shape and the distance in between were characteristic for each animal species. The hair medulla was continuous in most of the tested animal species with the exception of sheep, in which fragmental medulla was detected. The diameter of the hair medulla and the margins differ according to the animal species. Hair shaft pigmentation were not detected in all tested animals with the exception of camel and buffalo, in which granules and streak-like pigmentation were detected. In conclusion, the present study provides a first-step towards preparation of a complete local reference database for animal hair identification that can be used in forensic investigations.
... Working with embryos and larvae requires the setup of extremely sensitive detection methods, due to the very small sample size and the high lipid content. Solid-phase extraction (SPE) and liquid-liquid extraction (LLE) are widely used for the extraction of SSRIs from biological and tissue samples [29][30][31][32][33]. Usually, SPE has better reproducibility than LLE methods; however, they are also complex and time-consuming and require large amounts of solvents. ...
Article
Full-text available
Antidepressant drugs are widely used for the treatment of common mental or other psychiatric disorders such as depression, which affect about 121 million people worldwide. This widespread use has contributed to the input of these pharmaceuticals and their metabolites into the environment. The aim of this work was to develop an analytical method to quantify the most widely used antidepressant drugs, selective serotonin reuptake inhibitors (SSRI), and their main metabolites in the environment. For this, a new and reliable miniaturized extraction method based on dispersive SPE cleanup procedure for extraction of SSRI followed by derivatization with n-heptafluorobutyrylimidazole, and detection by GC-MS was developed. The methodology, including a first-order one-compartment model, was then applied to a bioconcentration study in zebrafish (Danio rerio) eleutheroembryos. The results showed low bioaccumulation of these compounds; however, a biotransformation evidence of the parent compounds into their metabolites was observed after 6 h of exposure. These results indicate the need to integrate metabolic transformation rates to fully model and understand the bioaccumulation patterns of SSRI and their metabolites. Graphical abstract
... There are a number of studies dedicated to detection of foreign matter in hair, including drugs (1, 10, 24), medicinal products (12,15), alcohol (2,5,10), toxic substances (13), explosives (20) and others (3,11). However, there is almost no data on the physical characteristics of hair, especially its melting point. ...
Article
Full-text available
The aim of the research was to develop a method for determining the species affinity of animal hair by determining its melting temperature. The research material was selected from hair samples of livestock and wild animals. We investigated 170 hairs of 16 animal species and humans. The hair melting point was determined by an automated system for melting temperature determination Opti Melt (MPA100). In the present study, we suggest that species affiliation can be effectively determined by examining physical properties of hair, in particular by determining its melting temperature. The hair melting temperatures for different animal species are in different ranges, but the initial melting points for hair of certain animal species are similar. For example, the initial melting point for cat, sheep, hare, rabbit, and rat hair ranged from 100 to 111°C, and the hair of the wolf, bear, and fox began to melt at 139.2 to 141.2°C. The results of this research make it possible to determine the species affinity of animals according to their hair melting temperature, which had not been done before. The proposed method yields rapid results and can be used as an auxiliary method in ambiguous cases in which data obtained by microscopic examination are insufficient. It will greatly facilitate the work of forensic specialists, enriching the arsenal of available methods.
... There are a number of studies dedicated to detection of foreign matter in hair, including drugs (1, 10, 24), medicinal products (12,15), alcohol (2,5,10), toxic substances (13), explosives (20) and others (3,11). However, there is almost no data on the physical characteristics of hair, especially its melting point. ...
Article
Full-text available
The aim of the research was to develop a method for determining the species affinity of animal hair by determining its melting temperature. The research material was selected from hair samples of livestock and wild animals. We investigated 170 hairs of 16 animal species and humans. The hair melting point was determined by an automated system for melting temperature determination Opti Melt (MPA100). In the present study, we suggest that species affiliation can be effectively determined by examining physical properties of hair, in particular by determining its melting temperature. The hair melting temperatures for different animal species are in different ranges, but the initial melting points for hair of certain animal species are similar. For example, the initial melting point for cat, sheep, hare, rabbit, and rat hair ranged from 100 to 111 ° C, and the hair of the wolf, bear, and fox began to melt at 139.2 to 141.2 ° C. The results of this research make it possible to determine the species affinity of animals according to their hair melting temperature, which had not been done before. The proposed method yields rapid results and can be used as an auxiliary method in ambiguous cases in which data obtained by microscopic examination are insufficient. It will greatly facilitate the work of forensic specialists, enriching the arsenal of available methods.
Article
Herein, a matrix-free approach is presented for comprehensive environmental and forensic analysis of dyes and nonsteroidal anti-inflammatory drugs (NSAIDs) using Au-TiO2 nanohybrids coupled with surface-assisted pulsed laser desorption ionization-mass spectrometry (SALDI-MS). The Au-TiO2 nanohybrids was prepared and characterized using inductively coupled plasma-optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), surface area measurements, ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy-energy dispersive spectrometry (SEM-EDS). Initially, the optimal Au content was assessed using the survival yield (SY) method, confirming that 7.5% Au content on the TiO2 surface offered the highest ionization efficiency. Subsequently, environmental analyses of dyes and NSAIDs in water samples were performed, with sensitive detection of all analytes achieved with limits of detection (LODs) ranging from 10.0 ng mL⁻¹ to 10.0 fg mL⁻¹ and good spot-to-spot reproducibility. Additionally, the effect of potential contaminants commonly found in environmental samples, such as salts, surfactants and pesticides was also considered. Despite signal intensity reduction at high concentrations of some salts, the target analytes were detected, while the presence of surfactants and pesticides did not cause significant signal intensity reduction. Additionally, dyed and undyed Tetoron fibers and the effect of adhesive tape were evaluated. Direct analysis of the dyed Tetoron fibers on the target plate, using the nanohybrids, enabled higher detection sensitivity of the dyes, in addition to adducts of polystyrene and cellulose, the main components of the fiber. Finally, NSAIDs in oral fluid were analyzed, with sensitive detection of the analytes was observed using the nanohybrids with LODs and LOQs in the range of 0.1-10 ng mL⁻¹ and 1-20 ng mL⁻¹, respectively. The trueness of the exact mass was in the range of 0.64–6.2 ppm while the recovery of the spiked samples was in the range of 82.90-107.54%% indicating the efficiency of the Au-TiO2 nanohybrids as SALDI substrate. Thus, the Au-TiO2 nanohybrids hold considerable promise in terms of sensitivity, reproducibility, and LOD, and may significantly contribute to environmental and forensic identification.
Article
Continuous research on metabolomics is of utmost importance in the field of anti-doping control, including updating the selection of the most appropriate markers of prohibited substances, testing specimens and analytical strategies. Among metabolomics research topics, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in equine medicine and have large diversity in their chemical structures; hence, their metabolism has been widely elucidated to construct appropriate anti-doping tests. This article provides an overview of the analytical methodologies used in anti-doping analysis and the metabolic research of NSAIDs concerning issues related to the use of alternative testing matrices, sample preparation strategies and possible analytical techniques. In addition, the metabolic pathways of chosen NSAIDs in horses, associated analytical problems and future research directions are discussed.
Article
Scat hair presents a diverse profile of hairs for morphological assessment that may find versatile applications in wildlife forensic investigations. Successful morphological assessment of scat hair microstructure, however, depends on a robust sectioning methodology. We assessed the feasibility and efficacy of a cryosectioning technique compared to that of a gold standard hand‐sectioning technique. Scat hairs were embedded in paraffin wax and hand‐sectioned, while cryopreserved scat hairs were sectioned with a cryostat. The results showed that cryosectioning preserved the pristine morphology of the scat hair and provided cross sections more amenable to high‐resolution imaging of hair internal microstructure than hand‐sectioning. The cryosectioning technique may find novel applications as a more reliable and robust technique to aid (i) scat hair internal microstructure analysis for cross‐referencing with species identification keys in wildlife forensic studies and (ii) downstream toxicological analysis in wildlife forensic studies as hair biochemistry is not altered during cryopreservation.
Article
Full-text available
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2–selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis. To confirm the superiority of celecoxib, a cyclooxygenase-2-selective NSAID, to loxoprofen in the incidence of gastroduodenal (GD) endoscopic ulcers. A randomised, multicentre, placebo-controlled, double-blind, phase IV clinical trial in healthy Japanese volunteers [mean age 57.5 (range: 40–74) years; >70% female], stratified by Helicobacter pylori status at screening (∼40% positive) and randomised 2:2:1 to receive celecoxib 100 mg b.d., loxoprofen 60 mg t.d.s. or placebo. Primary end point was incidence of any GD endoscopic ulcers after 2 weeks of treatment. Of 190 randomised subjects, 189 received at least one dose of celecoxib (n = 76), loxoprofen (n = 76), or placebo (n = 37). Incidence of GD ulcers was 1.4%, 27.6% and 2.7% in the celecoxib, loxoprofen and placebo groups respectively (P < 0.0001 in favour of the celecoxib group); incidence of adverse events (AEs) was 34.2%, 51.3% and 21.6% in the celecoxib, loxoprofen and placebo groups respectively. No serious or severe AEs were reported. Celecoxib 100 mg b.d. was superior to loxoprofen 60 mg t.d.s. regarding the incidence of gastro-duodenal endoscopic ulcers over 2 weeks. Celecoxib was well tolerated and no major safety concerns were observed. ClinicalTrials.gov NCT00994461.
Article
Full-text available
The UV spectra and relative retention times (RRT) of 2682 toxicologically relevant substances were measured by high-performance liquid chromatography with diode array detection (HPLC-DAD) in an acetonitrile phospate buffer (pH 2.3) mixture on an RP8 column and were arranged in a database. A complete survey of the molecular structures of all database entries showed the presence of 1650 different chromophores or chromophore combinations. The specificity of the UV spectrum for substance identification was determined by calculation of the similarity indices (SI) of all possible substance pairs within the database with an SI > 0.9990, which indicated spectral identity. In a similar way, the RRT was evaluated for all possible pairs: two compounds were declared indistinguishable because the RRT of at least one of them fell into the RRT error window of the other. Although the use of the RRT alone produced unsatisfactory identification results, 1619 substances (60.4%) were unambiguously identified by their UV spectrum only. This rate was increased to 84.2% by the combination of spectrum and RRT. The selectivity parameters discrimination power (DP) and mean list length (MLL) were calculated (DP = 0.9999, MLL = 1.253) and compared with literature data, which proved HPLC-DAD to be one of the most reliable methods for substance identification in toxicological analysis. The practical relevance of the results for systematic toxicological analysis is demonstrated by the example of a multidrug intoxication and in the context of sample preparation methods routinely used.
Article
Full-text available
Hair differs from other materials used for toxicological analysis because of its unique ability to serve as a long-term storage of foreign substances with respect to the temporal appearance in blood. Over the last 20 years, hair testing has gained increasing attention and recognition for the retrospective investigation of chronic drug abuse as well as intentional or unintentional poisoning. In this paper, we review the physiological basics of hair growth, mechanisms of substance incorporation, analytical methods, result interpretation and practical applications of hair analysis for drugs and other organic substances. Improved chromatographic-mass spectrometric techniques with increased selectivity and sensitivity and new methods of sample preparation have improved detection limits from the ng/mg range to below pg/mg. These technical advances have substantially enhanced the ability to detect numerous drugs and other poisons in hair. For example, it was possible to detect previous administration of a single very low dose in drug-facilitated crimes. In addition to its potential application in large scale workplace drug testing and driving ability examination, hair analysis is also used for detection of gestational drug exposure, cases of criminal liability of drug addicts, diagnosis of chronic intoxication and in postmortem toxicology. Hair has only limited relevance in therapy compliance control. Fatty acid ethyl esters and ethyl glucuronide in hair have proven to be suitable markers for alcohol abuse. Hair analysis for drugs is, however, not a simple routine procedure and needs substantial guidelines throughout the testing process, i.e., from sample collection to results interpretation.
Book
Der Arzneiverordnungs-Report berichtet jedes Jahr über die vertragsärztlichen Arzneiverordnungen. Im Jahre 2010 haben 140 303 Vertragsärzte 791 Millionen Verordnungen (davon 626 Mio. Arzneimittelverordnungen) rezeptiert. Die Arzneimittelausgaben betrugen 32,0 Mrd. € (+1,0%). Erstmals wurden Arzneimittel für seltene Krankheiten analysiert, die Kosten von 1,6 Mrd. € verursachten. Trotz eines moderaten Ausgabenanstiegs sind die Einsparmöglichkeiten vor allem bei Generika und teuren Analogpräparaten weiter gestiegen. Auf der Basis nationaler Preisvergleiche errechnen sich Wirtschaftlichkeitspotenziale von 4,7 Mrd. €. Noch mehr könnte eingespart werden, wenn die hohen deutschen Arzneimittelpreise auf das Niveau europäischer Nachbarländer gesenkt würden. So zeigt ein exemplarischer Preisvergleich mit britischen Arzneimitteln Wirtschaftlichkeitsreserven von insgesamt 12,1 Mrd. €. Presseecho zum Arzneiverordnungs-Report 2010 „Mit extrem hohen Preisen greift die Pharmaindustrie in die Taschen der deutschen Beitragszahler“ (Aachener Nachrichten 15.09.2010) „Ob Gesundheitsminister Philipp Rössler und seine FDP sich trauen, die Milliardengewinne der Pharmaindustrie anzutasten? Bisher hat deren Lobby immer gesiegt.“ (Hessische Allgemeine Kassel 15.09.2010) „Wie aus dem Arzneiverordnungsreport 2010 weiter hervorgeht, könnten die Krankenkassen 9,4 Milliarden Euro jährlich einsparen, wenn die Medikamente hier so billig wären wie etwa in Schweden.“ (Bayernkurier 18.09.2010) "Wir sind die Zahlmeister. Warum lässt sich das Gesundheitswesen in Deutschland melken wie kaum ein anderes?" (Die Zeit 21.10.2010)
Article
BACKGROUND & AIMS: Patients with risk factors for gastrointestinal (GI) disorders who continuously use non-steroidal anti-inflammatory drugs (NSAIDs) should also take gastroprotective agents (GPAs), such as proton-pump inhibitors (PPIs). However, it is not clear how many physicians continue to prescribe GPAs to these patients, and whether stopping the prescription increases GI complications. METHODS: We performed a retrospective, observational, longitudinal study using a validated electronic database of representative general practitioners in France. We analyzed data for 1856 patients at risk for GI events (older than 65 years, past history of GI ulcer, or receiving antiplatelet agents) who received prescriptions for a NSAID and PPI from 2007 to 2009. Kaplan-Meier curves were used to determine the probability of still being prescribed a GPA at 12 and 24 months after the first prescription. Multivariate logistic regression analysis was used to identify factor associated with non-persistence. GI complications rates were compared using the Student t test. RESULTS: The probability of still being prescribed a PPI along with a NSAID 1 year after the study began was 77.5% (95% confidence interval [CI], 75.6%-79.4%) and 68.3% after 2 years (95% CI, 66.1%-70.4%). Risk factors for no longer receiving a prescription for a PPI included switching to a COX2-selective inhibitor (hazard ratio [HR], 2.50; 95% CI, 1.91-3.28; P<.001) or to a non-selective NSAID (HR, 1.63; 95% CI, 1.33-1.99; P<.001), and female sex (HR, 1.25; 95% CI, 1.05-1.45; P<.05). In 50% of these cases, the PPI was reintroduced within 6 months, without a specific reason in 70% of the cases. The risk for upper GI injury was higher among patients with discontinued prescriptions for PPIs (odds ratio, 1.45; 95% CI, 1.06-2.09; P=.02) CONCLUSIONS: Within 2 years after prescribing a PPI, physicians do not renew this prescription for about 33% of patients receiving continuous NSAIDs. This increases the risk for GI adverse events among these patients.
Article
Aim: To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies. Methods: We performed a nested case-control study in persons aged 40-90 years old included in the period 2001-2005. Potential cases were selected through a computer search followed by an individual blinded review. Controls matched for age, sex and calendar year were randomly selected. The exposure window was defined as 0-30 days before the index date. Adjusted odds ratios were obtained through unconditional logistic regression models. Results: In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases. Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41-2.09), metamizole (1.52; 1.09-2.13), low-dose aspirin (1.74; 1.37-2.21), other antiplatelet drugs (1.73; 1.27-2.36), and oral anticoagulants (2.00; 1.44-2.77). We did not find an increased risk with current use of oral corticosteroids (1.11; 0.66-1.86), SSRIs (1.05; 0.77-1.42), or paracetamol (1.00; 0.82-1.23). Acid-suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39-0.85), particularly in users with antecedents of peptic ulcer (0.16; 0.05-0.58). We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period. Conclusions: The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological research.
Article
Backgrounds: Gastrointestinal (GI) toxicity is an undesirable effect of nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a multicenter study in Japan to clarify the GI risk grade in patients with NSAID-induced GI bleeding. Methods: Patients with emergent endoscopic hemostasis by nonvariceal bleeding were registered from 36 hospitals in Hiroshima. In cases with NSAID use, the GI risk grade (low, moderate, or high) was evaluated, and concomitant drugs were investigated. We asked 79 gastroenterologists and 234 orthopedists what concomitant drugs they would prescribe to 3 simulated patients. Results: A total of 1,350 patients were registered. NSAIDs were used in 278 cases (21%). Concerning the risk grade in each patient, the largest group was the moderate-risk group (203 patients; 73%), while the high-risk group comprised 10% of all NSAID users with bleeding. A proton pump inhibitor (PPI) or misoprostol was administrated to only 20 patients (7%). A small number of the gastroenterologists and orthopedists who responded to the questionnaire would prescribe PPI or misoprostol to simulated patients with short-term loxoprofen use. Conclusions: In NSAID users with GI bleeding, the moderate-risk group was the largest group for GI toxicity in Japan. In these cases, PPI or misoprostol was not commonly medicated in clinical practice.
Article
Low-dose aspirin use is associated with an increased risk for gastrointestinal ulceration and bleeding. At-risk low-dose aspirin users are therefore recommended to take proton-pump inhibitors. However, it is poorly understood which aspirin users are at risk to develop such complications. It is assumed that the known risk factors for NSAID-induced upper gastrointestinal events also apply to low-dose aspirin users. The conventional risk factors for upper gastrointestinal complications associated with aspirin therapy include: (1) a history of peptic ulcer disease or gastrointestinal bleeding, (2) older age, (3) concomitant use of NSAIDs, including coxibs, (4) concomitant use of anticoagulants or other platelet aggregation inhibitors, (5) the presence of severe co-morbidities, and (6) high aspirin dose. In patients with a history of peptic ulcer disease, Helicobacter pylori infection should be assessed and treated. This review focuses on the evidence for upper gastrointestinal risk factors in aspirin users.
Article
The retrospective investigation of the exposure to toxic substances by general unknown screening of hair is still a difficult task because of the large number of possible poisons, the low sample amount and the difficult sample matrix. In this study the use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was tested as a promising technique for this purpose. In the optimized procedure, 20mg hair were decontaminated with water and acetone and two times extracted by 18h incubation with 0.5ml of a mixture of methanol/acetonitrile/H(2)O/ammonium formate at 37°C. A mixture of deuterated standards from different drug groups was added for quantification and method control. The united extracts were evaporated to a residue of 0.5ml and 5μl were injected without clean-up for LC-QTOF-MS measurement (instrument Agilent 6530) with positive electrospray ionization and in data dependent acquisition mode. For peak identification the accurate mass data base and spectral library of the authors was used which contains accurate mass CID spectra of more than 2500 and theoretically calculated accurate mass data of more than 7500 toxicologically relevant substances. Validation at the example of 24 illegal drugs, their metabolites and benzodiazepines resulted in limits of detection of 0.003-0.015ng/mg, and limits of quantification of 0.006-0.021ng/mg with good accuracy and intra- and interday reproducibility. The matrix effect by ion suppression/enhancement was 72-107% for basic drugs and 42-75% for benzodiazepines. Yields of the hair extraction above 90% were determined for 59 drugs or metabolites. The method was applied to hair samples from 30 drug fatalities and from 60 death cases with known therapeutic drug intake at life time. Altogether 212 substances were identified with a frequency per drug of 1-40 (mean 4.2) and per case of 2-33 (mean 10.2), between them 35 illegal drug related substances and 154 therapeutic drugs. Comparison with the data known from case histories and from the analysis of blood, urine and gastric content showed only a low agreement, with many unexpected drugs detected and many reported drugs not detected in hair. Basic drugs and metabolites such as opioides, cocaine, amphetamines, several groups of antidepressants, neuroleptics, beta-blockers or the metamizole metabolite noramidopyrine were found with high frequency whereas acidic and several neutral drugs such as cannabinoids, salicylic acid, furosemide, barbiturates, phenprocoumone or cardiac glycosides could not be detected with sufficient sensitivity, mainly because of the low ion yield of positive ESI for these compounds. The advantage of a comprehensive acquisition of all substances is paid by a lower sensitivity in comparison to targeted screening LC-MS/MS procedures. In conclusion, the procedure of sample preparation and LC-QTOF-MS analysis proved to be a robust and sensitive routine method in which the qualitative screening for a wide variety of toxic substances in hair is combined with the quantitative determination of selected illegal drugs.
Article
Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
Article
To interpret the results of hair analysis tests accurately and to understand the appropriate role of hair analysis in drug abuse testing, a basic understanding of the biology of hair is necessary. Although hair may appear to be a simple structure, it is actually a complex part of the anatomy whose biology is only partially understood. Hair grows from small organs (follicles) located within the complex microenvironment of the skin which has multiple layers of tissue, three glands whose secretions bathe hair, and multiple vascular systems which are capable of transferring drugs to hair at many levels along the length of the hair shaft. The advantages and disadvantages of using scalp, beard, or pubic hair as specimens for hair analysis are also considered.
Article
The model generally proposed to explain the incorporation of drugs into hair is one in which drugs enter hair only by passive diffusion from the blood stream into the growing cells at the base of the hair follicle. However, this model may be over-simplified. More recent experimental findings suggest that drugs may enter hair from multiple sites, via multiple mechanisms, and at various times during the hair growth cycle. A more complex model is proposed in which drugs and metabolites are incorporated into hair during formation of the hair shaft (via diffusion from blood to the actively growing follicle), after formation (via secretions of the apocrine and sebaceous glands), and after hair has emerged from the skin (from the external environment). Further, drugs can be transferred to hair from multiple body compartments or pools located in tissues surrounding the hair follicle. These mechanisms could also be drug-specific. A more precise understanding of the mechanisms involved in the incorporation of drugs into hair is critical for forensic scientists in order to interpret the results of hair analysis properly.
Article
Proton pump inhibitors have dramatically influenced the management of acid-peptic disorders in recent years. They all have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4. There is some variation in their potential for drug interactions due to differences in enzyme inhibition. Relatively few serious adverse effects have been reported for the proton pump inhibitors. Comparative studies of acid suppression suggest that lansoprazole and pantoprazole have a potency similar to that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset of maximal acid suppression than the other proton pump inhibitors. Comparative studies using proton pump inhibitors for the treatment of reflux oesophagitis, duodenal ulcer healing and Helicobacter pylori eradication show little overall difference in outcome between the proton pump inhibitors when used in their standard doses. Lansoprazole and rabeprazole provide earlier and better symptom relief than the other proton pump inhibitors in some studies of peptic ulcer treatment. The few studies of gastric ulcer treatment suggest that there is an advantage in using the proton pump inhibitors that have a higher standard daily dose.
Article
The relationship between xenobiotic concentrations in hair and the degree of systemic xenobiotic exposure is poorly defined. The purpose of this study was to evaluate the effect of dose, time, and pigment on the hair incorporation of cocaine (COC) and its metabolites, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine (NCOC). COC was administered by the i.p. route to male Long-Evans (LE) rats at three doses (5, 10, and 20 mg/kg) once daily for 5 days. Fourteen days after the initial injection, the hair was collected and analyzed by gas chromatography/mass spectrometry for the compounds of interest. COC, EME, and NCOC were preferentially incorporated into pigmented hair in a dose-dependent manner. None of the analytes were detected in nonpigmented hair. The plasma pharmacokinetic profile of each analyte was determined at each dose. After normalizing for the plasma concentrations, the incorporation of COC into pigmented hair was 2 orders of magnitude greater than BE. The time course of COC and metabolite distribution into hair was also investigated from 1 h to 14 days after a single dose. After COC disappears from plasma, there is a 3-day delay before maximal hair concentrations are reached in pigmented hair. In nonpigmented hair, concentrations of BE and COC did not exceed 0.25 ng/mg and were undetectable after 4 h and 2 days, respectively. This study demonstrates that the pigment-mediated differences in the incorporation of COC and its metabolites noted at 14 days after dosing are also evident a few hours after drug administration.
Article
Analysis of human hair for drug residues is being used increasingly as a diagnostic tool in the investigation of drug use and abuse. Hair analysis is complementary to urine/blood testing in that it can provide an extensive historical record of drug use, is noninvasive, impersonal and can facilitate retesting. However, the technique has not been studied in horses. That the systemic administration of drugs in horses could be identified by the detection of drug residues in hair. To evaluate hair analysis as a potential retrospective diagnostic test for drug administration in horses by studying the deposition of systemically administered drugs in tail hair. Tail hairs (n = 40-50) from 4 horses with known drug histories were washed, chopped into 3-5 mm fragments and extracted overnight, in 0.1 mol/l hydrochloric acid, prior to solid-phase extraction and analysis by high-performance liquid chromatography. Horse 1, a 3-year-old Thoroughbred colt (gastric ulcer), was treated for 14 days with omeprazole; Horse 2, a 3-year-old Thoroughbred colt (anaerobic infection), was treated for 5 days with metronidazole; Horse 3, an 8-year-old Thoroughbred gelding (sinusitis), was treated for 10 days with trimethoprim/sulphadiazine; and Horse 4, a 3-year-old Thoroughbred colt (respiratory infection), was treated for 5 days with procaine benzylpenicillin. Omeprazole was not detected in tail hair. Metronidazole was detected in tail hair at a concentration of 0.57 ng/mg, trimethoprim and sulphadiazine at concentrations of 9.14 and 2.26 ng/mg, respectively, and procaine at a concentration of 1.66 ng/mg. The data presented suggest that hair analysis may become a useable technique for the retrospective detection of drug administration in horses. This technique could ultimately be used as part of a prepurchase veterinary examination to identify misuse of anti-inflammatory and sedative drugs, in an in-training testing programme to identify use of anabolic agents, or to provide evidence to support post race blood or urine test results. Clearly, more extensive research will be required to evaluate the effectiveness of the technique over a much broader range of drugs.
Article
In recent years, photodiode array detectors (DADs) have been much improved with respect to wavelength accuracy and resolution, sensitivity, linearity and software operation. UV spectra of drugs measured with up-to-date DADs from different manufacturers are in excellent agreement, have the same quality as measured by a conventional UV spectrometer and are highly reproducible. The calculation of similarity parameters by the DAD software includes the entire range of the spectra compared and allows recognition of very small differences. It was shown in a systematic study of more than 2500 toxicologically relevant substances that UV spectra have a very high specificity with respect to substance structure. Therefore, HPLC-DAD in combination with a comprehensive database of UV spectra and retention parameters is one of the most efficient techniques used in systematic toxicological analysis (STA). Furthermore, the method is advantageous for the identification of metabolites, since in many cases they have the same or very similar UV spectra compared with their respective parent substances and their retention times on reversed-phase columns are shifted in a manner typical of the particular biotransformation reaction. Beside these general aspects, practical applications of HPLC-DAD for STA are reviewed with respect to sample preparation and chromatographic conditions. The efficiency of the method is demonstrated for an example of a routine procedure using liquid-liquid extraction with CH 2 Cl 2 and protein precipitation for sample preparation, a system of three isocratic mobile phases with different acetonitrile/phosphate buffer ratios and RP8 columns for chromatography and a database of 2682 UV spectra and relative retention times for substance identification.
Upper gastrointestinal bleeding associated with
  • Fj Abajo
  • Gil
  • Bryant V Mj
  • J Timoner
  • B Oliva
  • Garcia-Rodriguez
  • La
de Abajo FJ, Gil MJ, Bryant V, Timoner J, Oliva B, Garcia-Rodriguez LA. Upper gastrointestinal bleeding associated with Forensic Sci Med Pathol (2014) 10:18–28
other drugs and interactions: a nested case-control study in a new general practice database
  • Nsaids
NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database. Eur J Clin Pharmacol. 2013;69:691-701.
  • U Schwabe
  • D Paffrath
Schwabe U, Paffrath D. Arzneiverordnungs-Report 2011: Aktuelle Daten, Kosten, Trends und Kommentare. Springer, DE; 2011.
Upper gastrointestinal bleeding associated with
  • F J De Abajo
  • M J Gil
  • V Bryant
  • J Timoner
  • B Oliva
  • L A Garcia-Rodriguez
de Abajo FJ, Gil MJ, Bryant V, Timoner J, Oliva B, Garcia-Rodriguez LA. Upper gastrointestinal bleeding associated with Forensic Sci Med Pathol (2014) 10:18-28 27