Hair analysis for drugs of abuse. XVIII. 3,4-Methylenedioxymethamphetamine (MDMA) disposition in hair roots and use in identification of acute MDMA poisoning

Disposition of 3,4-methylenedioxymethamphetamine (MDMA) in hair roots was studied using rats and the hair root samples were evaluated to prove acute MDMA poisoning. The back hair of male pigmented hairy rats (n = 6) was shaved and 5 d later the animals were intraperitoneally administered with acute poisonous doses (20, 40, 60, 80 and 100 mg/kg) of MDMA. Roots of the hairs were then plucked out with a hair nipper 5 min and, 0.5, 1, 2, 6 and 24 h after injection. The hair root samples were, directly or after being washed with detergent, extracted with methanol-5 N HCl (20:1) under ultrasonication in ice-cold water for 4 h. After filtration and evaporation, the residue was derivatized with pentafluoropropionic anhydride and analyzed by GC/MS. From all samples including the 5 min sample, MDMA was detected at high concentrations (up to 156 ng/mg) accompanied by 3,4-methylenedioxyamphetamine (MDA). Some of the animals died within 2 h after administration, but in the surviving rats the MDMA concentrations in the hair roots increased up to 6 h and then slowly decreased until 24 h. The remaining MDMA after washing apparently increased from 13-31% at 0.5 h to 51-83% at 24 h in the surviving rats. These facts show that most of drugs in the hair roots are not yet immobilized in the early stage and are thereafter gradually incorporated into the hair shaft. Increase of the MDMA concentration stopped soon after death of the animal, probably due to the cessation of hair growth. Although the ratios of MDA/MDMA steadily increased over time, those after death plateaued, probably due to the cessation of metabolism after death. It was clearly shown that MDMA is more quickly incorporated into and more firmly retained in hair than methamphetamine (MA) by comparing their disposition in hair roots.     

The routine analysis of breast milk for drugs of abuse in a clinical toxicology laboratory

BACKGROUND/AIMS: Contrast-enhanced computed tomography (CECT) is used to show areas of decreased pancreatic perfusion in severe acute pancreatitis (AP). To evaluate possible adverse effects of the contrast medium (CM) on the course of AP, the impact of intravenous CM in AP of graded severity in the rat was studied. METHODS: Pancreatitis of three levels of severity was induced in Sprague-Dawley rats with intravenous cerulein hyperstimulation plus time- and pressure-controlled intraductal infusion of saline or glycodeoxycholic acid. At 7 hours, control and pancreatitis animals received intravenous ionic CM, nonionic CM, or saline. The principal outcome measures were 24-hour survival, trypsinogen activation peptides (TAP) in ascites, and histological acinar necrosis score. RESULTS: There was no measurable effect of CM on the index features in control animals or animals with mild or moderate AP. In severe AP, CM caused a significant increase in mortality, ascites TAP, and necrosis score. CONCLUSIONS: Intravenous CM increases pancreatic injury when administered early in the course of severe experimental AP. Because CM may convert borderline ischemia to irreversible necrosis, CECT performed early in pancreatitis to show poor perfusion and predict areas of necrosis may depict a self-fulfilling prophecy. Early CECT should be reconsidered and perhaps avoided.     

The use and abuse of human figure drawings.

Reviews data-based studies on human figure drawings and concludes that there is little support for their validity or for their use as devices to assess personality, behavior, emotion, or intellectual functioning. Ease of administration and anecdotal reports of predictive accuracy are presented as explanations for their continued usage. Existing valid measures of behavioral and cognitive functioning render the use of human figure drawings superfluous. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Detection of methadone, methadone metabolites, and other illicit drugs of abuse in hair of methadone-treatment subjects

PURPOSE: Penetration of piperacillin into the vitreous cavity after intravenous administration was investigated in humans. METHODS: Forty-five eyes undergoing vitrectomy between November 1993 and December 1994 were included. Each patient received a single intravenous dose of piperacillin 4 g 2 hours before ocular incision. A 0.2-mL vitreous sample was aspired at the beginning of vitrectomy, a blood sample was obtained, and piperacillin level was assessed. RESULTS: There were no detectable drug concentrations in 25 eyes. Mean vitreous drug concentration in the remaining evaluable eyes (n = 14) was 2.33 microg/mL (+/-0.76). We divided samples into two groups: 23 uninflamed (Group 1) and 16 inflamed (Group 2) eyes. Mean vitreous drug concentration was 0.42 microg/mL in Group 1 and 4.95 microg/mL in Group 2 (P < 0.2). Piperacillin concentration was higher than the minimum inhibitory concentration for gram-positive bacteria in 13% of uninflamed and 69% of inflamed eyes (P < 0.001). CONCLUSION: Studies show that intravenously administered piperacillin can penetrate the vitreous cavity in rabbits. Our study suggests that a single dose of piperacillin can produce intravitreal concentrations sufficient to kill gram-positive bacteria in inflamed eyes. The poor intraocular penetration of systemically administered piperacillin in uninflamed eyes raises questions about its usefulness as a prophylactic agent in ophthalmic surgery.     

Conditioned taste aversions and drugs of abuse: A reinterpretation.

A new hypothesis (and supporting data) provides a solution to the 25-yr-old paradox whereby positively reinforcing drugs of abuse also support a conditioned taste aversion (CTA). The results show that unlike LiCl-induced CTAs, morphine- and cocaine-induced suppression of conditioned stimulus (CS) intake depends on the rewarding properties of the gustatory CS. This finding argues against the long-standing CTA interpretation in favor of a new reward comparison account. That is, rats decrease intake of a gustatory CS following taste–drug pairings because the value of the CS is outweighed by that of a highly reinforcing psychoactive drug. Suppression of CS intake, then, is a consequence of the well-documented positive reinforcing, rather than the hypothetical aversive, properties of drugs of abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use of human subjects in psychological research.

A discussion of the ethics involved in using human subjects for psychological research. Emphasis is placed on the principles of consent, confidentiality, and standard or acceptable procedures. The 10 basic principles governing medical research laid down by the Nuremburg tribunal are quoted in full. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The competition of affective responses in human subjects.

"The present study is an attempt to study competing responses in human affective behavior. The following hypothesis was tested: a reduction of the magnitude of a conditioned anxiety response can be produced by the simultaneous elicitation of certain other affects. The procedure… consisted of the simultaneous tachistoscopic presentation of two letters, one having an anxiety response conditioned to it under hypnosis, and the other a response of either sadness, contentment, or delight. In the control condition the other letter was affectively neutral. The competing affects hypothesis was confirmed for the pairing of contentment and anxiety (only)." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The intestinal phase of gastric secretion. Response to liver extract infusion into the proximal jejunum of healthy human subjects

A Levine tube was placed under radiological control in the stomach, and a thin polyethylene tube in the proximal jejunum of 6 healthy volunteers. The stomach and proximal part of jejunum were perfused for 2 hours with 1% acetylcholine, 20% meat extract (Bovril), and 15% liver extract (LE) alone and in combination with simultaneous infusion of different doses of exogenous pentagastrin intravenously. A significant increase in serum gastrin concentration was found with antral perfusion of LE only, whereas perfusion of the proximal jejunum did not change the basal level of the serum gastrin concentration. No change from control values was observed in gastric acid, and pepsin output on perfusing proximal jejunum with LE alone, or in combination with pentagastrin. Reflux to the stomach varied between 0-1.4%, as determined by addition of radioactive B12 to the perfusates. The experiments showed that gastrin was released from the antrum of the stomach by perfusion with 15 per cent LE, but not from the jejunum under the present experimental conditions. In the present experiments Bovril and acetylcholine perfusions did not cause significant responses from the antrum or from the proximal jejunum.     

Molecular and cell biological analyses for intestinal absorption and renal excretion of drugs

Intestinal absorption and renal tubular secretion are transport processes determining the availability and the disposition of drugs in the body. In this review, our studies on the molecular and cell biological analyses of intestinal absorption and renal secretion of drugs are described. We evaluated the transepithelial transport and the cellular accumulation of peptide-like drugs such as beta-lactam antibiotics and bestatin (a dipeptide-like antineoplastic agent) in the human adenocarcinoma colon cell line, Caco-2, as an in vitro model for studying absorption mechanisms of these drugs. We have found that the transcellular transport of these peptide-like drugs is mediated by both the apically- and basolaterally-localized peptide transporters. To characterize molecular aspects of absorption of the peptide-like drugs, we studied cDNA cloning of H+/peptide cotransporters, PEPT1 and PEPT2, expressed in rats. The rat PEPT1 has been shown to mediate the H- coupled uphill transport of beta-lactam antibiotics across the brush-border membranes of the intestinal and renal epithelia. The rat PEPT2 is expressed predominantly in the kidney, but not in the intestine, mediating tubular reabsorption of the peptide-like drugs. We examined the transcellular transport of organic cations across monolayers of the kidney epithelial cell line, LLC-PK1. We have found that LLC-PK1 cells possess the H+/organic cation antiporter and the membrane potential-sensitive organic cation transporter in the apical and basolateral membranes, respectively, thereby tetraethylammonium (TEA) being transported unidirectionally from the basolateral to the apical side of the monolayers. We have isolated a cDNA encoding a rat kidney-specific organic cation transporter, OCT 2, which transports TEA in a H(+)-gradient independent manner, suggesting that OCT2 is localized to the basolateral membranes of renal tubular cells. In addition, a cDNA encoding a novel rat organic anion transporter, OAT-K1, has been cloned. OAT-K1 is expressed exclusively in the renal proximal tubules, and mediates the transport of methotrexate. Analyses of the molecular and cell biological mechanisms for drug absorption and secretion will provide information for the understanding of organ specific drug transport systems and for the development of drug design and/or drug delivery system.     

Ethical and practical issues involved in behavioral pharmacology research that administers drugs of abuse to human volunteers

Researchers carrying out non-therapeutic research that involves the administration of drugs of abuse to human volunteers can be faced with many ethical and practical questions. The history of this type of research is relatively brief, with little in the way of published information relevant to carrying out behavioral pharmacological research with human participants. The aim of this article is to raise issues that occur in most studies of this type and to provide solutions that we have found acceptable and which have been approved by a variety of institutions and regulatory agencies. Clearly, there are other approaches that would work equally as well, and we are not attempting to provide 'the' answer to many of the issues raised. We believe that raising these issues and providing our perspectives is important for stimulating others to discuss them and for all of us to strive, where possible, to reach a consensus concerning ethical practices and to become aware of gaps and pitfalls. The topics discussed range from the nuts and bolts of acquiring and keeping track of drugs, to selecting research participants and designing ethical studies that protect our volunteers while still collecting scientifically useful data.     

The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA

The treatment of malaria tropica is becoming difficult because of the increasing drug resistance rates of Plasmodium falciparum against several of the currently available antimalarias. A fixed combination of rifampicin, co-trimoxazole and isoniazid (CotrifazidTM, CF) was found to be highly effective for the treatment of malaria tropica. The aim of the present study in Kenya was to scrutinize this finding in a 14-day trial. Patients with malaria tropica were given in an open, double-arm randomized study CF for 5 days, or chloroquine or pyrimethamine/sulphadoxine as the control. Because of an apparently better activity and tolerance of CF, the randomization had to be stopped after the enrollment of 50 patients. A total of 61 patients in both groups (35 of them between 2 months and 6 years of age) were available for final analysis. All 41 patients treated with CF, originally positive in their blood smears, turned negative; in 2 cases blood smear positivity reappeared on day 14. There were 7 failures in the control group, 4 of them a primary one. Four of those failures were turned negative with CF, 2 failed with CF also, and 1 disappeared. The tolerance of CF was excellent even in infants. In our experience, CF is very well suited for the treatment of malaria tropica, also in cases of apparent drug resistance of P. falciparum against other antimalarials, and even in severe cases of the disease.     

Comment on "The use and abuse of human figure drawings."

Comments on R. W. Motta et al's (see record 1994-04005-001) conclusion that the use of human figure drawings to assess intelligence is invalid. While Motta et al are generally successful in documenting the shortcomings of these tests, their literature review is not exhaustive. However, the arguments of Motta et al should be heeded because they are based on empirical data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of Triage screening for drugs of abuse in postmortem blood and urine samples

BACKGROUND: Impaired changes in gastric epithelium proliferation have been described in Helicobacter pylori infection, and a progressive increase of proliferating cells has been shown with the progression of mucosal lesions. AIMS: Purpose of this investigation was to study the effect of eradication on bacterium-induced proliferative changes, evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS: This retrospective study was performed, before and after therapy, in five different groups of patients with progressive stages of Helicobacter pylori damage (N: normality; HG: histological gastritis with normal endoscopy; EHG: histological gastritis with endoscopic chronic erosions; CIM: complete intestinal metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after eradication, a normalization of PCNA LI was observed in the areas of gastritis, but not in those of intestinal metaplasia, which showed on unchanged type. Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only associated to intestinal metaplasia. The protein was also expressed in the cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest that the development of intestinal metaplasia may be associated with an alteration in the control of gastric epithelium proliferation and could represent an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes are necessary for a complete progression to neoplastic disease. A long-term follow-up on extension, type, proliferative situation and oncoprotein expression in areas of intestinal metaplasia may be helpful to explain whether the present data provide new information on the mechanism of Helicobacter pylori induced gastric carcinogenesis.     

Determination of amphetamine, methamphetamine and amphetamine-derived designer drugs or medicaments in blood and urine

This paper reviews procedures for the determination of amphetamine, methamphetamine and amphetamine-derived designer drugs or medicaments in blood and urine. Papers published from 1991 to early 1997 were taken into consideration. Gas chromatographic and liquid chromatographic procedures with different detectors (e.g., mass spectrometer or diode array) were considered as well as the seldom used thin-layer chromatography and capillary electrophoresis. Enantioselective procedures are also discussed. A chapter deals with amphetamine-derived medicaments, e.g. anoretics, antiparkinsonians or vasodilators, which are metabolized to amphetamine or methamphetamine. Differentiation of an intake of such medicaments from amphetamine or methamphetamine intake is discussed. Basic information about the biosample assayed, internal standard, work-up, GC column or LC column and mobile phase, detection mode, reference data and validation data of each procedure is summarized in Tables. Examples of typical applications are presented.     

Ingestion of chromium(VI) in drinking water by human volunteers: absorption, distribution, and excretion of single and repeated doses

This study examines the magnitude of hexavalent chromium [Cr(VI)] absorption, distribution, and excretion following oral exposure to 5 and 10 mg Cr(VI)/L in drinking water administered as a single bolus dose (0.5 L swallowed in 2 min) or for 3 d at a dosage of 1 L/d (3 doses of 0.33 L each day, at 6-h intervals). Adult male volunteers ingested deionized water containing various concentrations of potassium chromate, and samples of urine, plasma, and red blood cells (RBCs) were collected and analyzed for total chromium throughout the studies. In the bolus dose studies, a fairly consistent pattern of urinary chromium excretion was observed, with an average half life of about 39 h. However, 4-d total urinary chromium excretion and peak concentrations in urine and blood varied considerably among the 5 volunteers. Studies of repeated exposure to smaller volumes ingested at a more gradual rate (i.e., 0.33 L over 5-15 min) showed similar urinary chromium excretion patterns but generally lower chromium uptake/excretion. Given that sustained elevations in RBC chromium levels provide a specific indication of chromium absorption in the hexavalent state, these data suggest that virtually all (> 99.7%) of the ingested Cr(VI) at 5 and 10 mg Cr(VI)/L was reduced to Cr(III) before entering the blood-stream. The interindividual differences in total chromium uptake and excretion are plausibly explained by ingestion of appreciable doses on an empty stomach, which likely results in the formation of well-absorbed Cr(III) organic complexes in gastrointestinal tissues and possibly the blood. The lack of any clinical indications of toxicity in the volunteers and the patterns of blood uptake and urinary excretion of chromium are consistent with a predominant uptake of Cr(III) organic complexes [derived from Cr(VI)] that are excreted more slowly than inorganic forms of Cr(III). Therefore, it appears that the endogenous reducing agents within the upper gastrointestinal tract and the blood provide sufficient reducing potential to prevent any substantial systemic uptake of Cr(VI) following drinking-water exposures at 5-10 mg Cr(VI)/L. Based on these data, the chemical environment in the gastrointestinal tract and the blood is effective even under relative fasting conditions in reducing Cr(VI) to one or more forms of Cr(III).     

Validation of an automated microplate enzyme immunoassay for screening of postmortem blood for drugs of abuse

The objective of this study was to compare the sensitivity and specificity of an enzyme immunoassay employing antibodies bound to a microtiter plate (MPEIA) with those of two radioimmunoassays for screening postmortem blood from selected coroner's cases for drugs of abuse. The radioimmunoassays were a coated-tube radioimmunoassay (CTRIA) and a double antibody radioimmunoassay (DARIA). Specimens consisted of 260 postmortem blood specimens from coroner's cases. Immunoassay results (positive or negative) were compared with confirmed results on those cases by gas chromatography-mass spectrometry, alone or in combination with gas-liquid chromatography using either a nitrogen-phosphorus or flame-ionization detector. Sensitivity was calculated as the true-positive rate using chromatographic confirmation as the reference standard. Specificity was calculated as the true-negative rate. Sensitivity and specificity were calculated for 5-7 potential cutoff concentrations for the drug classes opiates, amphetamines, cocaine and metabolites, and barbiturates. For opiates, the sensitivity and specificity were 99% and 93%, respectively, for the MPEIA at a cutoff of 20-ng/mL morphine, compared with 94% and 96% for the CTRIA at a cutoff of 5-ng/mL morphine and > 99% and 96% for the DARIA at 20-ng/mL morphine. For cocaine and metabolites, the sensitivity and specificity were 96% and 93%, respectively, for the MPEIA at 50-ng/mL benzoylecgonine, compared with 93% and 96% for CTRIA at 50-ng/mL benzoylecgonine and 98% and 97% for the DARIA at 50-ng/mL benzoylecgonine. For amphetamines, the sensitivity and specificity were >99% and 91%, respectively, for the MPEIA at 25-ng/mL methamphetamine, compared with 93% and 86% for the CTRIA at 25-ng/mL methamphetamine and 83% and 89% for the DARIA at 50-ng/mL methamphetamine. For barbiturates, the sensitivity and specificity were > 99% and 92%, respectively, for the MPEIA at 50-ng/mL secobarbital, compared with 91% and 87% for the CTRIA at 500-ng/mL secobarbital and 79% and 95% for the DARIA at a cutoff of 1000-ng/mL phenobarbital.