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Sample records for amphetamine methamphetamine mda

  1. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    Science.gov (United States)

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA. PMID:27182976

  2. Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC-EI-MS after derivatization with perfluorooctanoyl chloride

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe; Jornil, Jakob

    2009-01-01

    ), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA or ecstasy). An intra-day precision of 3-6% RSD and an inter-day precision of 3-17% RSD were observed. Trueness was between 96 % and 106% for the target compounds. The limit of detection ranged from 0.07 to 0.14 ng...... cases and to 5.9 ng/mg of MDMA in 13 cases. MA was only detected once at trace level. The method, including the derivatization procedure, is simple and robust with a sensitivity that is satisfactory for measurement of amphetamines and ecstasy in hair from abusers....

  3. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Smith, Douglas A; Kisor, David F; Poklis, Justin L

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  4. Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms.

    Science.gov (United States)

    Bagnall, John; Malia, Louis; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2013-10-01

    Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds. PMID:23886544

  5. Impurities in Illicit Drug Preparations: Amphetamine and Methamphetamine.

    Science.gov (United States)

    Verweij, A M

    1989-06-01

    In this review, attention is paid to chromatographic and mass spectral properties of already identified impurities found to be present in frequently abused drug preparations of illegal origin of amphetamine and methamphetamine. The most commonly employed methods of synthesis of drugs of this type are briefly described. Special emphasis is given to the Leuckart route, found to be the preferred method, in the illicit production of amphetamine. Furthermore, some isolation and preconcentration methods for the contaminants are discussed. The importance of identifying impurities present in amphetamine or methamphetamine cannot be overestimated. These impurities originate mostly from the improper purification in the end stage of the different syntheses used in the clandestine manufacture of the substances; it is possible to differentiate between the several kinds of illegal drug preparations, synthesized by various methods, by means of so-called "route specific" impurities. Finally, a survey is given of the impurities already known to be present in amphetamine and methamphetamine, together with their mass spectral and some chromatographic properties. PMID:26266521

  6. Epigenetic landscape of amphetamine and methamphetamine addiction in rodents

    OpenAIRE

    Godino, Arthur; Jayanthi, Subramaniam; Cadet, Jean Lud

    2015-01-01

    Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advanc...

  7. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    OpenAIRE

    Takeshi Kumazawa; Kenji Hara; Chika Hasegawa; Seisaku Uchigasaki; Xiao-Pen Lee; Hiroshi Seno; Osamu Suzuki; Keizo Sato

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass sp...

  8. Epigenetic landscape of amphetamine and methamphetamine addiction in rodents.

    Science.gov (United States)

    Godino, Arthur; Jayanthi, Subramaniam; Cadet, Jean Lud

    2015-01-01

    Amphetamine and methamphetamine addiction is described by specific behavioral alterations, suggesting long-lasting changes in gene and protein expression within specific brain subregions involved in the reward circuitry. Given the persistence of the addiction phenotype at both behavioral and transcriptional levels, several studies have been conducted to elucidate the epigenetic landscape associated with persistent effects of drug use on the mammalian brain. This review discusses recent advances in our comprehension of epigenetic mechanisms underlying amphetamine- or methamphetamine-induced behavioral, transcriptional, and synaptic plasticity. Accumulating evidence demonstrated that drug exposure induces major epigenetic modifications-histone acetylation and methylation, DNA methylation-in a very complex manner. In rare instances, however, the regulation of a specific target gene can be correlated to both epigenetic alterations and behavioral abnormalities. Work is now needed to clarify and validate an epigenetic model of addiction to amphetamines. Investigations that include genome-wide approaches will accelerate the speed of discovery in the field of addiction. PMID:26023847

  9. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... as prescription drugs. 250.101 Section 250.101 Food and Drugs FOOD AND DRUG ADMINISTRATION... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine... should not be freely available to the public through over-the-counter sale. From complaints by...

  10. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenyl alkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    International Nuclear Information System (INIS)

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenyl alkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy ethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to a-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxy propane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  11. ELISA Detection of 30 New Amphetamine Designer Drugs in Whole Blood, Urine and Oral Fluid using Neogen® "Amphetamine" and "Methamphetamine/MDMA" Kits.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Baralla, Elena; Pasciu, Valeria; Varoni, Maria Vittoria; Briguglio, Irene; Demontis, Maria Piera; Boatto, Gianpiero

    2016-09-01

    Amphetamine designer drugs are central nervous system stimulants that are widely disseminated in the illegal market. Generally, in forensic laboratories, immunoassay methods are the first line of screening for these types of drugs in a biological specimen (typically blood, urine or oral fluid). In this article, we describe the cross-reactivity profiles of 30 new amphetamine designer drugs, using the Neogen(®) [Amphetamine Specific and Methamphetamine/3,4-Methylenedioxymethamphetamine (MDMA) assays] drug tests. To assess the potential matrix influence on the response, each assay was tested on whole blood, urine and oral fluid. Concentrations of 10,000 ng/mL were not sufficient to produce a positive response for the majority of the analyzed amphetamines. This clearly demonstrates that, although these kits are extremely effective for the target drugs for which they are intended (amphetamine, methamphetamine and MDMA), they cannot be used to reliably identify the tested designer drugs in real cases, as these concentrations greatly exceed those expected to be found in forensic samples. PMID:27405364

  12. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine.

    Science.gov (United States)

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese

    2011-01-01

    Amphetamine ('Speed'), methamphetamine ('Ice') and its congener 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity. PMID:21194370

  13. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine

    OpenAIRE

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese

    2011-01-01

    Amphetamine (‘Speed’), methamphetamine (‘Ice’) and its congener 3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisa...

  14. Headspace liquid-phase microextraction of methamphetamine and amphetamine in urine by an aqueous drop

    International Nuclear Information System (INIS)

    This study developed a headspace liquid-phase microextraction (LPME) method by using a single aqueous drop in combination with high performance liquid chromatography (HPLC)-UV detection for the determination of methamphetamine (MAP) and amphetamine (AP) in urine samples. The analytes, volatile and basic, were released from sample matrix into the headspace first, and then protonated and dissolved in an aqueous H3PO4 drop hanging in the headspace by a HPLC syringe. After extraction, this drop was directly injected into HPLC. Parameters affecting extraction efficiency were investigated and optimized. This method showed good linearity in the investigated concentration range of 1.0-1500 μg L-1, repeatability of the extraction (R.S.D. -1 for both analytes). Enrichment factors of about 400-fold and 220-fold were achieved for MAP and AP, respectively, at optimum conditions. The feasibility of the method was demonstrated by analyzing human urine samples

  15. Determination of amphetamine, methamphetamine, MDA and MDMA in urine samples by solid-phase microextraction and gas chromatography-mass spectrometry in selected ion monitoring%尿中苯丙胺、甲基苯丙胺、MDA和MDMA的固相微萃取和GC/MS/SIM测定

    Institute of Scientific and Technical Information of China (English)

    张绍雨; 黄增萍

    2005-01-01

    目的研究固相微萃取(SPME)用于尿中苯丙胺(AMP)、甲基苯丙胺(MET)、3,4-亚甲二氧基苯丙胺(MDA)和3,4-亚甲二氧基甲基苯丙胺(MDMA)的提取.方法样品调节至碱性和用盐饱和后用顶空SPME,内标为MET-d5.萃取纤维为100μm聚二甲基硅氧烷(PDMS).用气质联用选择离子检测(GC/MS/SIM).结果0.2μg/ml加标尿样,AMP、MET、MDA和MDMA的富集倍数分别为22,60,13和47.检出限(S/N=3)为0.4~9.5 ng/ml.线性范围为0.05~1μg/ml.0.2、0.5和1.0μg/ml加标尿样,相对回收率77.9%~112.4%,变异系数2.7%~18.0%(n=5).用该方法分析5个案件样品,和常规液液萃取结果接近.结论顶空SPME法用于尿中AMP、MET、MDA和MDMA等化合物的分析,无需有机溶剂,富集效率高,提取-富集-进样一体化,简单方便实用.

  16. Methamphetamine and amphetamine concentrations in survivors of body-packer syndrome in Japan.

    Science.gov (United States)

    Uekusa, Kyoko; Hayashida, Makiko; Saito, Nobuyuki; Mashiko, Kunihiro; Hara, Kenji; Waters, Brian; Ohno, Youkichi

    2013-04-10

    There are few reports from Japan on the analysis of fluids in survivors of body-packer syndrome. We analyzed the concentrations of stimulants in the serum, plasma and urine collected from three patients suspected of being body packers at immigration that were referred to hospitals between 2010 and 2011. The drugs were extracted with solid-phase columns and analyzed by gas chromatography-mass spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign bodies were detected in the intestinal tract on plain X-ray (X-P) and computed tomography (CT), and they were eventually removed surgically. In case 1, the patient presented with convulsions and tachycardia at admission to the hospital and one of the packets was found to have ruptured. In case 2, although the subject appeared to have an intestinal obstruction caused by the packets on the third day, he exhibited no symptoms on arrival and the packets did not appear to have ruptured. In case 3, the patient exhibited restlessness on the first day and one of the removed packets had ruptured. In all cases, methamphetamine (MA) and amphetamine (AP) were detected in serum, plasma and urine. In this study, we report the variation in MA and AP concentrations in survivors of body-packer syndrome. The serum and plasma concentrations of MA were high in subjects that exhibited symptoms of MA intoxication. MA and AP were also detected in the case in which the patient exhibited no symptoms of intoxication and the packets had not ruptured. These results suggest either that the stimulants may have seeped through the wrap of the packets, or that the subject had been abusing the drugs. PMID:23116635

  17. Amphetamine

    Science.gov (United States)

    ... and children. Amphetamine (Evekeo) is used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness and sudden attacks ... or without food. For treatment of ADHD or narcolepsy, the immediate-release tablet is usually taken with ...

  18. Comparison of (+)-methamphetamine, ±}-methylenedioxymethamphetamine (MDMA), (+)-amphetamine and ±}-fenfluramine in rats on egocentric learning in the Cincinnati water maze

    OpenAIRE

    Vorhees, Charles V.; He, Elizabeth; Skelton, Matthew R.; Graham, Devon L.; Schaefer, Tori L.; Grace, Curtis E.; Braun, Amanda A.; Amos-Kroohs, Robyn; Williams, Michael T.

    2010-01-01

    (+)-Methamphetamine (MA), (±)-3,4-methylenedioxymethamphetamine (MDMA), (+)-amphetamine (AMPH), and (±)-fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on...

  19. Simultaneous determination of methamphetamine and its metabolite, amphetamine, in urine using a high performance liquid chromatography column-switching method.

    Science.gov (United States)

    Kumihashi, Mitsuru; Ameno, Kiyoshi; Shibayama, Takayuki; Suga, Keisuke; Miyauchi, Hiroshi; Jamal, Mostofa; Wang, Weihuan; Uekita, Ikuo; Ijiri, Iwao

    2007-01-01

    We describe here a simple, precise, and highly sensitive method for the simultaneous determination of methamphetamine (MA) and amphetamine (AM) in urine using a high performance liquid chromatography (HPLC) column-switching method. A PK-2A (Shodex) column was used for extraction and deproteinization, and a CAPCELL PAK SCX semi-micro, polymer-coated cation-exchange column was employed for separation. The urine sample was mixed with an equal volume of borate buffer (0.1M, pH 9.4), and then 100 microl of the mixture was injected into the HPLC column. The column was switched for 6 min, and then 10 min later detection was performed at 210 nm. Recovery yields of the MA and AM spiked in the urine were 93.0-100.4% with a coefficient of variation of less than 1%. The calibration curves of MA and AM were in the range of 0.1-10 microg/ml with good linearity (r(2)=0.999), with the limit of qualification being 0.005 microg/ml. This method of using HPLC with column-switching can be used for both qualification and quantification of MA and its metabolite, AM, in urine, especially in forensic cases. PMID:16916628

  20. Methamphetamine-, d-Amphetamine-, and p-Chloroamphetamine-Induced Neurotoxicity Differentially Effect Impulsive Responding on the Stop-Signal Task in Rats.

    Science.gov (United States)

    Furlong, Teri M; Leavitt, Lee S; Keefe, Kristen A; Son, Jong-Hyun

    2016-05-01

    Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e., a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e., a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning 1 week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e., impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID:26846719

  1. Comparison of (+)-methamphetamine, ±-methylenedioxymethamphetamine, (+)-amphetamine and ±-fenfluramine in rats on egocentric learning in the Cincinnati water maze.

    Science.gov (United States)

    Vorhees, Charles V; He, Elizabeth; Skelton, Matthew R; Graham, Devon L; Schaefer, Tori L; Grace, Curtis E; Braun, Amanda A; Amos-Kroohs, Robyn; Williams, Michael T

    2011-05-01

    (+)-Methamphetamine (MA), (±)-3,4-methylenedioxymethamphetamine (MDMA), (+)-amphetamine (AMPH), and (±)-fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine (DA) and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be induced, yet cognitive impairments have been difficult to demonstrate. We recently showed that rats treated on a single day with MA (10 mg/kg x 4 at 2 h intervals) exhibit impaired egocentric learning (Cincinnati water maze [CWM]) without affecting spatial learning (Morris water maze [MWM]) (Herring et al., [2008] Psychopharmacology (Berl) 199:637–650). Whether this effect is unique to MA or is a general characteristic of these drugs is unknown. Accordingly, this experiment compared these drugs on CWM performance. Drugs were given s.c. in four doses at 2 h intervals. MA doses were 10 or 12.5 mg/kg/dose, AMPH 25 mg/kg/dose (to match MA12.5-induced hyperthermia), MDMA 15 mg/kg/dose (previously established hyperthermia-inducing dose), and FEN 16.5 mg/kg/dose (equimolar to MA12.5). Two weeks later, rats were tested in the CWM (2 trials/day, 21 days). AMPH and MA (both doses) induced significant increases in CWM errors and latency to reach the goal with no differences in swim speed. MDMA and FEN did not significantly alter learning. Given that FEN selectively and MDMA preferentially affect serotonin whereas AMPH selectively and MA preferentially affect DA, the data suggest that egocentric learning may be predominantly dopaminergically mediated. PMID:20730798

  2. Toxicity of amphetamines: an update.

    Science.gov (United States)

    Carvalho, Márcia; Carmo, Helena; Costa, Vera Marisa; Capela, João Paulo; Pontes, Helena; Remião, Fernando; Carvalho, Félix; Bastos, Maria de Lourdes

    2012-08-01

    Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood-brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical

  3. The fast and furious: Cocaine, amphetamines and harm reduction

    OpenAIRE

    Grund, Jean-Paul; Coffin, Philip; Jauffret-Roustide, Marie; Dijkstra, Minke; Bruin, Dick; Blanken, Peter

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant effects, including amphetamine, methamphetamine, methcathinone and cathinone and referred to as ‘amphetamines’ in this review (Holman, 1994). MDMA (3,4-methylenedioxy-N-methamphetamine or ecstasy) is a ...

  4. Development of a targeted GC/MS screening method and validation of an HPLC/DAD quantification method for piperazines–amphetamines mixtures in seized material

    Directory of Open Access Journals (Sweden)

    Yacine Boumrah

    2014-09-01

    Full Text Available Piperazine-related drugs are sold as party pills in the form of tablets, capsules, liquids or powders. These party pills can contain several piperazine derivatives, or even a mixture of piperazines and amphetamine derivatives. This paper describes a screening method using a gas chromatography–mass spectrometry technique allowing the separation and the identification of active components within these mixtures by a combined silylation and acylation derivatization procedure. The studied substances–namely: 1-benzylpiperazine (BZP, 1-(3,4-methylenedioxyben-zylpiperazine (MDBP, 1-(3-trifluoromethylphenylpiperazine (TFMPP, 1-(3-chlorophenyl piperazine (mCPP, 1-(4-methoxyphenyl piperazine (MeOPP, amphetamine, methamphetamine, ephedrine, pseudoephedrine, 3,4-methylenedioxy-N-methamphetamine (MDMA, 3,4-methylenedi-oxyamphetamine (MDA, 3,4-methylenedioxy-N-ethylamphetamine (MDEA and N-methyl-1,3-benzodioxolylbutanamine (MBDB–are separated.

  5. Methamphetamine Cured my Cocaine Addiction

    Science.gov (United States)

    Haile, Colin N.; De La Garza, Richard; Newton, Thomas F.

    2011-01-01

    Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine’s reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial screen and informal conversation suggested that all participants considered methamphetamine to have helped them stop using cocaine and eliminate cocaine craving. Methamphetamine also significantly decreased their alcohol consumption but did not alter cannabis or nicotine use. PMID:23066512

  6. Methamphetamine: Glossary

    Science.gov (United States)

    ... Home » Publications » Research Reports » Methamphetamine » Glossary Methamphetamine Email Facebook Twitter Glossary Addiction: A chronic, relapsing disease characterized by compulsive drug ...

  7. Pharmacotherapy of methamphetamine addiction: an update.

    Science.gov (United States)

    Elkashef, Ahmed; Vocci, Frank; Hanson, Glen; White, Jason; Wickes, Wendy; Tiihonen, Jari

    2008-01-01

    Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies. PMID:19042205

  8. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    OpenAIRE

    Bramness Jørgen G; Gundersen Øystein; Guterstam Joar; Rognli Eline; Konstenius Maija; Løberg Else-Marie; Medhus Sigrid; Tanum Lars; Franck Johan

    2012-01-01

    Abstract Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamine...

  9. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    OpenAIRE

    Jørgen G. Bramness; Gundersen, Øystein H.; Guterstam, Joar; Rognli, Eline B.; Konstenius, Maija; Løberg, Else-Marie; Medhus, Sigrid; Tanum, Lars; Franck, Johan

    2012-01-01

    Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems t...

  10. Methamphetamine Cured my Cocaine Addiction

    OpenAIRE

    Haile, Colin N.; De La Garza, Richard; Newton, Thomas F.

    2010-01-01

    Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine’s reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial scre...

  11. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  12. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine.

    Science.gov (United States)

    McKenna, D J; Guan, X M; Shulgin, A T

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives (+/-)fenfluramine, (+/-)norfenfluramine, (+/-)MDE, (+/-)PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners. PMID:1829838

  13. Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry.

    Science.gov (United States)

    Martins, Liliane; Yegles, Michel; Chung, Heesun; Wennig, Robert

    2005-10-15

    Enantioselective quantification of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers in hair using gas chromatography-mass spectrometry (GC-MS) is described. Hair specimens were digested with 1M sodium hydroxide at 100 degrees C for 30 min and extracted by a solid phase procedure using Cleanscreen ZSDAU020. Extracted analytes were derivatised with (S)-heptafluorobutyrylprolyl chloride and the resulting diastereoisomers were quantified by GC-MS operating in the negative chemical ionization mode. Extraction yields were between 73.0 and 97.9%. Limits of detection varied in the range of 2.1-45.9 pg/mg hair, whereas the lowest limits of quantification varied between 4.3 and 91.8 pg/mg hair. Intra- and inter-assay precision and respective accuracy were acceptable. The enantiomeric ratios (R versus S) of AM, MA, MDA, MDMA and MDEA were determined in hair from suspected amphetamine abusers. Only MA and AM enantiomers were detectable in this collective and the quantification data showed in most cases higher concentrations of (R)-MA and (R)-AM than those of the corresponding (S)-enantiomers. PMID:16154523

  14. Methamphetamine (Meth)

    Science.gov (United States)

    ... Methamphetamine is a stimulant, with effects similar to cocaine, but longer-lasting. It does not cause illness directly, but because it interferes with termperature regulation of your brain, it can bring on hyperthermia closely followed by ...

  15. Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk

    Czech Academy of Sciences Publication Activity Database

    Rambousek, Lukáš; Kačer, P.; Syslová, K.; Bumba, J.; Bubeníková-Valešová, V.; Šlamberová, R.

    2014-01-01

    Roč. 139, JUN (2014), s. 138-144. ISSN 0376-8716 Institutional support: RVO:67985823 Keywords : methamphetamine * amphetamine * pharmacokinetics * sex differences * breast feeding milk * mass spectrometry Subject RIV: FH - Neurology Impact factor: 3.423, year: 2014

  16. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    Science.gov (United States)

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented. PMID:24378313

  17. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, Akihiro [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nishida, Manami [Hiroshima University Technical Center, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Saito, Takeshi [Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1143 (Japan); Kishiyama, Izumi; Miyazaki, Shota [GL Sciences Inc., Sayamagahara 237-2, Iruma, Saitama 358-0032 (Japan); Murakami, Katsunori [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nagao, Masataka [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Namura, Akira, E-mail: namera@hiroshima-u.ac.jp [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d{sub 5} was used as an internal standard. The linear ranges were 0.01-5.0 {mu}g mL{sup -1} for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 {mu}g mL{sup -1} for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation {>=}0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 {mu}g mL{sup -1} of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio {>=} 3) in urine was 5 ng mL{sup -1} for MA and MDMA and 10 ng mL{sup -1} for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  18. Amphetamines and cannabinoids testing in hair: Evaluation of results from a two-year period.

    Science.gov (United States)

    Burgueño, María José; Alonso, Amaya; Sánchez, Sergio

    2016-08-01

    This paper presents an overview of a set of amphetamines and cannabinoids tests performed on head hair samples from the Medico-Legal sector at the Madrid Department of the Spanish National Institute of Toxicology and Forensic Sciences during the years 2013 and 2014. The hair samples were tested for five stimulant phenylalkylamine derivatives -amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (MDA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)- and/or two cannabinoids-Δ(9)-tetrahydrocannabinol (THC) and cannabinol (CBN)- by gas chromatography equipped with mass spectrometry detection in selected-ion monitoring mode, applying a method accredited to ISO/IEC 17025 standards. The test results were interpreted according to the confirmation cut-offs proposed by the Society of Hair Testing (SoHT) to identify chronic drug use. The ratios of positive results were studied in relation to gender, age, hair colour, dyeing and length of the tested samples to assess the independence from these variables or the association with them. Low, medium and high ranges of concentration were also estimated for each drug. 21.94% of the 2954 hair samples tested for phenylalkylamine derivatives were positive for one or more substances. 16.38% of the samples were positive for AP, 12.09% for MDMA and only 0.44% for MA. 6.60% of the tested samples were positive for AP/MDMA combination. A total of 3178 samples were tested for cannabinoids, resulting in 53.40% positive for THC and CBN. Simultaneous tests for phenylalkylamine derivatives and cannabinoids were performed in 2931 of the samples; 14.94% of them were positive for THC, CBN, and one or more amphetamines. According to the results from the statistical analysis, the use of THC and MDMA vary with age and gender among the Medico-Legal sector in an extended area of Spain, while the use of AP appears to be independent of these variables. On the other hand, the results of THC in

  19. A Study of the Prevalence of Psychiatric Disorders in Patients with Methamphetamine-Induced Psychosis

    OpenAIRE

    Eslami-Shahrbabaki, Mahin; Fekrat, Alireza; Mazhari, Shahrzad

    2015-01-01

    Background The abuse of narcotic drugs and psychotropic substances such as amphetamines and ecstasy has had a growing trend. Tachycardia, increased blood pressure, hallucinations, panic attacks, and psychosis are the negative effects of methamphetamine abuse. The present study aimed to assess psychiatric disorders associated with methamphetamine-induced psychotic disorder. Methods This cross-sectional study was performed from October 2013 to March 2014 on 165 patients hospitalized at Shahid B...

  20. Mind Over Matter: Methamphetamine

    Science.gov (United States)

    ... Over Matter Teaching Guide and Series / Methamphetamine Print Mind Over Matter: Methamphetamine (Meth) Order Free Publication in: ... someday you'll make the next major breakthrough. Mind Over Matter is produced by the National Institute ...

  1. Test Your Knowledge: Methamphetamine

    Science.gov (United States)

    ... can cause. Correct! Methamphetamine can also cause certain types of hallucinations, loss of appetite, and even strokes. Question 4 True or False: Methamphetamine can cause long-term damage to neurons that contain the neurotransmitter dopamine. Question 4: Options * ...

  2. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    Directory of Open Access Journals (Sweden)

    Bramness Jørgen G

    2012-12-01

    Full Text Available Abstract Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease. The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis.

  3. Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines.

    Science.gov (United States)

    Dayrit, Fabian M; Dumlao, Morphy C

    2004-08-11

    Methamphetamine hydrochloride is one of the most widely used illicit drugs in the Philippines. In this study, we describe the application of cluster analysis of trace impurities in the profiling of the seized methamphetamine drug samples. Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5 buffer solution and extracted with ethyl acetate containing three internal standards. The trace impurities were identified using gas chromatography-mass spectrometry (GC-MS) and quantified by gas chromatography with a flame ionization detector (GC-FID). Following previously reported methodologies, 30 impurity peaks were selected from the GC-FID chromatograms. The peak areas and retention times were referenced to the internal standards. The peak areas of the selected peaks were then grouped for cluster analysis. In order to check for consistency of clustering, two further cluster analyses were performed using 40 and 50 impurity peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks, while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the seized drug samples used in this study, cluster analysis using at least 40 impurity peaks showed better consistency of clustering as compared to analysis using 30 peaks only. Ten of the impurity peaks were identified, of which four were identified for the first time in methamphetamine drug samples. These are p-bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl methamphetamine. The presence of phenyl-2-propanone (P2P), N,N-dimethyl amphetamine, and N-formyl amphetamine is indicative that these casework samples were synthesized using the Leuckart method. PMID:15240018

  4. Substance use -- amphetamines

    Science.gov (United States)

    ... get through daily life. Addiction can lead to tolerance. Tolerance means you need more and more of the ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Club Drugs Methamphetamine Browse ...

  5. Amphetamine margin in sports

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1981-10-01

    The amphetamines can enhance athletic performance. That much seem clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both humans and rats. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogs of such performances have also been used and similar enhancement demonstrated. The amount of change induced by the amphetamines is usually small, of the order of a few percent. Nevertheless, since a fraction of a percent improvement can make the difference between fame and oblivion, the margin conferred by these drugs can be quite important.

  6. Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions

    OpenAIRE

    Rubin Gulaboski; Natalia N D S Cordeiro; Nuno Milhazes; Jorge Garrido; Fernanda Borges; Miguel Jorge; Pereira, Carlos M.; Ivan Bogeski; Aluska Helguera Morales; Blaze Naumoski; Fernando F Silva

    2007-01-01

    For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface waterjorganic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds—heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or ‘‘ecstasy’’)...

  7. MDA ALS Caregiver's Guide

    Science.gov (United States)

    ... R.D., C.N.S.D., L.D.N. Nutritionist MDA/ALS Center at Vanderbilt University Medical Center ... neurologists, physiatrists, therapists (physical, occupa- tional, speech, respiratory), nutritionists, social work- ers, pulmonologists, gastroenterologists and medical equipment ...

  8. Trends of Amphetamine Type Stimulants DTR Mass Load in Poznan Based on Wastewater Analysis.

    Directory of Open Access Journals (Sweden)

    Piotr Nowicki

    2014-05-01

    Full Text Available The aim of this study was to determine the monthly DTR mass load of amphetamine-type compounds in Poland as well as an investigation of cyclical behaviour by using time series analysis and especially trends analysis.Amphetamine, methamphetamine and MDMA (ecstasy were detected in wastewater samples collected from the main Wastewater Treatment Plant in the city of Poznan using liquid chromatography / tandem mass spectrometry (LC-MS-MS. Back-calculations used in the sewage epidemiology approach were applied to estimate the DTR mass load level of the drugs analyzed. Trends analysis was performed by fitting the data to a simple linear regression and then by using smoothing by means of a moving average (Mat lab 2013a. Trend analysis displays a steady tendency of increase or decrease throughout time series. When we plot the observation against time, we may notice that a straight line can describe the increase or decrease in the series as time goes on. Simple linear regression and method of last squares to estimate parameters of a straight-line model were used. Additionally, a lagged plot (autocorrelation plot was used to investigate an appearance of correlation between amphetamines throughout time.Trends analysis showed the slight increase in consumption of amphetamine and decreasing trend in case of ecstasy and methamphetamine within the investigated period. There is also visible, strong correlation between ecstasy and methamphetamine consumption which cannot be stated in case of amphetamine.Trends analysis is a very useful tool to analyse the increasing or decreasing tendency in consumption of illicit drugs based on the DTR mass load data.

  9. Research Reports: Methamphetamine

    Science.gov (United States)

    ... social ills. A 2009 report from the RAND Corporation noted that methamphetamine abuse cost the Nation approximately $ ... Archives PDF documents require the free Adobe Reader . Microsoft Word documents require the free Microsoft Word viewer . ...

  10. Rapid simultaneous determination of amphetamine,methamphetamine MDA and MDMA in urine using HS/SPME and GC/MS%顶空固相微萃取与气质联用快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA

    Institute of Scientific and Technical Information of China (English)

    李宏森; 黄克建; 林翠梧; 蒙念; 潘智文

    2007-01-01

    利用顶空固相微萃取(HS/SPME)结合气/质联用(GC/MS-SIM)技术同时快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA.80℃下采用100 μm聚二甲基硅氧烷萃取头萃取10 min,3-苯基-1-丙胺作内标,探讨了影响SPME萃取效果的萃取时间、盐浓度、酸碱条件等因素,优化了实验条件.结果:苯丙胺、甲基苯丙胺、MDA和MDMA在50~2000 ng/mL质量浓度范围内线性良好,相关系数(r2)分别为0.9985,0.9971,0.9928和0.9994,检测限(信噪比=3)0.09 ng/mL,0.02 ng/mL,1.71 ng/mL和0.15 ng/mL,定量限(信噪比=10)0.31 ng/mL,0.05 ng/mL,5.68 ng/mL,0.49 ng/mL.1 mL空白尿液加标250 ng和1 000 ng,回收率在82%~108%之间,相对标准偏差(RSD)<13%(n=5).建立的方法适用于尿液中苯丙胺、甲基苯丙胺、MDA和MDMA的同时快速检测.

  11. [A case of amotivational syndrome as a residual symptom after methamphetamine abuse].

    Science.gov (United States)

    Ashizawa, T; Saito, T; Yamamoto, M; Shichinohe, S; Ishikawa, H; Maeda, H; Toki, S; Ozawa, H; Watanabe, M; Takahata, N

    1996-10-01

    We had a case of psychiatric evidence who was homeless and exhibited severe abulia and autism on detention for assault and battery. It was thought that his past history of chronic methamphetamine abuse and his familial history played some part in his showing such symptoms. His mother was alcohol dependent. He was an ACOA (adult child of alcoholics), which might have led to his chronic abuse of methamphetamine. On the other hand, it is well-known fact that the amotivational syndrome induced by marijuana abuse is typified by a diminution of ambition, productivity, and motivation. However, it has been contended that amotivational syndrome is induced not only by marijuana but also by amphetamine and its analogs, cocaine and volatile solvents. Since we positively support this view, we diagnosed the case as amotivational syndrome after long-term methamphetamine abuse. This was also a rare criminal case of amotivational state without hallucinations and delusions after methamphetamine abuse. We suggested that the crime committed in this case was closely related to crime induced by economic problems in residual states of schizophrenic offenders. This could be a case of both ACOA and methamphetamine dependence. There were unresolved alcohol- and drug-related problems in this case. Therefore, careful early intervention in a crisis, cooperation with the authorities and the institutions concerned, and comprehensive rehabilitation should be employed to resolve such alcohol- and drug-related problems. PMID:8940805

  12. Methamphetamine produces bidirectional, concentration-dependent effects on dopamine neuron excitability and dopamine-mediated synaptic currents

    OpenAIRE

    Branch, Sarah Y.; Beckstead, Michael J.

    2012-01-01

    Amphetamine-like compounds are commonly used to enhance cognition and to treat attention deficit/hyperactivity disorder, but they also function as positive reinforcers and are self-administered at doses far exceeding clinical relevance. Many of these compounds (including methamphetamine) are substrates for dopamine reuptake transporters, elevating extracellular dopamine by inhibiting uptake and promoting reverse transport. This produces an increase in extracellular dopamine that inhibits dopa...

  13. Determination of amphetamines in hair by integrating sample disruption, clean-up and solid phase derivatization.

    Science.gov (United States)

    Argente-García, A; Moliner-Martínez, Y; Campíns-Falcó, P; Verdú-Andrés, J; Herráez-Hernández, R

    2016-05-20

    The utility of matrix solid phase dispersion (MSPD) for the direct analysis of amphetamines in hair samples has been evaluated, using liquid chromatography (LC) with fluorescence detection and precolumn derivatization. The proposed approach is based on the employment of MSPD for matrix disruption and clean-up, followed by the derivatization of the analytes onto the dispersant-sample blend. The fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) has been used for derivatization. Different conditions for MSPD, analyte purification and solid phase derivatization have been tested, using amphetamine (AMP), methamphetamine (MET), ephedrine (EPE) and 3,4-methylenedioxymethamphetamine (MDMA) as model compounds. The results have been compared with those achieved by using ultrasound-assisted alkaline digestion and by MSPD combined with conventional solution derivatization. On the basis of the results obtained, a methodology is proposed for the analysis of amphetamines in hair which integrates sample disruption, clean-up and derivatization using a C18 phase. Improved sensitivity is achieved with respect to that obtained by the alkaline digestion or by the MSPD followed by solution derivatization methods. The method can be used for the quantification of the tested amphetamines within the 2.0-20.0ng/mg concentration interval, with limits of detection (LODs) of 0.25-0.75ng/mg. The methodology is very simple and rapid (the preparation of the sample takes less than 15min). PMID:27108048

  14. Neuroimmune Basis of Methamphetamine Toxicity

    OpenAIRE

    LOFTIS, JENNIFER M.; Janowsky, Aaron

    2014-01-01

    Although it is not known which antigen-specific immune responses (or if antigen-specific immune responses) are relevant or required for methamphetamine's neurotoxic effects, it is apparent that methamphetamine exposure is associated with significant effects on adaptive and innate immunity. Alterations in lymphocyte activity and number, changes in cytokine signaling, impairments in phagocytic functions, and glial activation and gliosis have all been reported. These drug-induced changes in immu...

  15. Multiresidual analysis of emerging amphetamine-like psychoactive substances in wastewater and river water.

    Science.gov (United States)

    Senta, Ivan; Krizman, Ivona; Ahel, Marijan; Terzic, Senka

    2015-12-18

    Besides the common illicit drugs, such as cocaine, heroin, and marijuana, there is a growing concern about the use of modern "designer drugs" that have emerged in large numbers over the past few years. In this work, a sensitive and selective method for simultaneous determination of 25 synthetic amphetamine-like psychoactive compounds, including amphetamine, sympathomimetic substituted amphetamines, synthetic cathinones and ketamine, in raw wastewater (RW), secondary effluent (SE) and river water was developed. Samples were enriched by solid-phase extraction (SPE) on mixed-mode reversed-phase/strong cation-exchange sorbent (Oasis MCX) and analysed by reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-MS/MS). The target compounds were separated on a Synergi Polar column and detected using multiple reaction monitoring (MRM) in positive ionisation mode. Accurate quantification was achieved by using several deuterated analogues as surrogate standards. Careful optimisation and validation of the procedure resulted in a reliable determination of all target analytes in low ng/L range for all matrices, which makes the method suitable for the application in wastewater-based epidemiology. The method was applied for assessment of selected compounds in municipal wastewater and river water from Croatia. It was shown that most of the wastewater samples contained detectable levels of the well-known synthetic illicit drugs, amphetamine and 3,4-methylenedioxy-methamphetamine (MDMA) (concentrations up to 545ng/L and 55ng/L in RW, respectively), as well as ephedrine (up to 108ng/L) and pseudoephedrine (up to 698ng/L), which are used as ingredients of popular over-the counter cough and cold medications. Other target amphetamine-like psychoactive substances, recently reported for their potential abuse, were detected only occasionally and in low concentrations (<10ng/L). PMID:26607313

  16. New Approaches to the Methamphetamine Epidemic

    OpenAIRE

    Zusman, Mara B.

    2004-01-01

    Methamphetamine abuse has become an epidemic in the United States. As methamphetamine becomes increasingly available, more and more people are trying – and becoming addicted to – this potent drug. But although methamphetamine is made using over-the-counter (OTC) drugs containing pseudoephedrine, shifting OTC drugs containing pseudoephedrine to prescription status is not the solution to the methamphetamine crisis. Rather, society must adopt a comprehensive...

  17. Methamphetamine induces the release of endothelin.

    Science.gov (United States)

    Seo, Jeong-Woo; Jones, Susan M; Hostetter, Trisha A; Iliff, Jeffrey J; West, G Alexander

    2016-02-01

    Methamphetamine is a potent psychostimulant drug of abuse that increases release and blocks reuptake of dopamine, producing intense euphoria, factors that may contribute to its widespread abuse. It also produces severe neurotoxicity resulting from oxidative stress, DNA damage, blood-brain barrier disruption, microgliosis, and mitochondrial dysfunction. Intracerebral hemorrhagic and ischemic stroke have been reported after intravenous and oral abuse of methamphetamine. Several studies have shown that methamphetamine causes vasoconstriction of vessels. This study investigates the effect of methamphetamine on endothelin-1 (ET-1) release in mouse brain endothelial cells by ELISA. ET-1 transcription as well as endothelial nitric oxide synthase (eNOS) activation and transcription were measured following methamphetamine treatment. We also examine the effect of methamphetamine on isolated cerebral arteriolar vessels from C57BL/6 mice. Penetrating middle cerebral arterioles were cannulated at both ends with a micropipette system. Methamphetamine was applied extraluminally, and the vascular response was investigated. Methamphetamine treatment of mouse brain endothelial cells resulted in ET-1 release and a transient increase in ET-1 message. The activity and transcription of eNOS were only slightly enhanced after 24 hr of treatment with methamphetamine. In addition, methamphetamine caused significant vasoconstriction of isolated mouse intracerebral arterioles. The vasoconstrictive effect of methamphetamine was attenuated by coapplication of the endothelin receptor antagonist PD145065. These findings suggest that vasoconstriction induced by methamphetamine is mediated through the endothelin receptor and may involve an endothelin-dependent pathway. PMID:26568405

  18. Irreversible brain damage caused by methamphetamine

    Directory of Open Access Journals (Sweden)

    Sebastian Moeller

    2016-03-01

    Full Text Available Methamphetamine is an addictive scene substance usage of which is increasing rapidly. While methamphetamine often causes neuropsychiatric symptoms like anxiety, psychosis and hallucinations, reports of structural ongoing cerebral alterations are rare. We here report a case of this kind of damage caused through methamphetamine use.

  19. Analysis of amphetamines illegally produced in Serbia

    OpenAIRE

    VLATKA VAJS; SLOBODAN PETROVIC; SONJA BANOVIC STEVIC; MARINA NEVESCANIN

    2008-01-01

    Forensic practice in the Republic of Serbia faced the illegal production of amphetamine for the first time in 2003. This paper presents the results of the chemical characterization of 32 batches of amphetamine samples from three separate cases, for the purpose of identification of the active components and additives. Through the profiling of impurities of all samples, using gas chromatography/mass spectrometry (GC/MS), 30 compounds associated with amphetamine were identified. The results of t...

  20. Chronic variable stress and intravenous methamphetamine self-administration - Role of individual differences in behavioral and physiological reactivity to novelty.

    Science.gov (United States)

    Taylor, S B; Watterson, L R; Kufahl, P R; Nemirovsky, N E; Tomek, S E; Conrad, C D; Olive, M F

    2016-09-01

    Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. PMID:27163191

  1. The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

    OpenAIRE

    Lewis, Candace R; Kelsey eStaudinger; Lena eScheck; M Foster eOlive

    2013-01-01

    The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH) causes great harm to both the individual user and to society; yet, no studies have examined the effects...

  2. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Directory of Open Access Journals (Sweden)

    Marcelo Carvalho Lasmar

    2007-06-01

    laboratories of toxicology of the development countries as Brazil. It was chosen for development and validation a gas chromatography method with flame ionization detection. The analytic validation results for MDMA, MDA and MDEA were linearity range of 1.0 to 500.0 µg/mL, intra and interassay coefficient of variation lower than 9.5% and quantification limit of 1.0 µg/mL. The detection limits were 0.7 µg/mL, 0.8 µg/mL and 0.6 µg/mL respectively to MDMA, MDA and MDEA. The method showed a good seletivity as the epinephrine, cocaine, amphetamine, methamphetamine, acethyl salicilic acid, diethyl barbituric acid, p-aminobenzoyl diethyl barbituric, paracetamol and caffeine presences did not interfere with the measurement of the three analytes.

  3. Maxillary sinus manifestations of methamphetamine abuse.

    Science.gov (United States)

    Faucett, Erynne A; Marsh, Katherine M; Farshad, Kayven; Erman, Audrey B; Chiu, Alexander G

    2015-01-01

    Methamphetamines are the second most commonly used illicit drug worldwide and cost the United States health-care system ∼$23.4 billion annually. Use of this drug affects multiple organ systems and causes a variety of clinical manifestations. Although there are commonly known sequelae of methamphetamine abuse such as "meth mouth," there is limited evidence regarding maxillary sinus manifestations. The following cases highlight the initial evaluation and management of two methamphetamine abusers with loculated purulent collections within the maxillary sinus as a result of methamphetamine abuse. Our aim was to delineate the otolaryngologic symptoms associated with the patients' methamphetamine abuse. Computed tomography and magnetic resonance imaging studies revealed loculated purulent collections within the maxillary sinus of probable odontogenic origin in both patients. Methamphetamine abuse leading to rampant caries and poor oral hygiene may predispose individuals for craniofacial infections and fluid collections. These cases illustrate the development of maxillary sinusitis and maxilla mucoceles that have been associated with methamphetamine use. PMID:25675268

  4. Analysis of amphetamines illegally produced in Serbia

    Directory of Open Access Journals (Sweden)

    VLATKA VAJS

    2008-07-01

    Full Text Available Forensic practice in the Republic of Serbia faced the illegal production of amphetamine for the first time in 2003. This paper presents the results of the chemical characterization of 32 batches of amphetamine samples from three separate cases, for the purpose of identification of the active components and additives. Through the profiling of impurities of all samples, using gas chromatography/mass spectrometry (GC/MS, 30 compounds associated with amphetamine were identified. The results of the analysis of powder tartrate, sulfate and phosphate salts of amphetamine, as well as variously formulated tablets are presented in this study. The analyses showed that the amphetamines were synthesized by the Leuckart method in all cases.

  5. Methamphetamine Use and Pulmonary Hypertension

    Science.gov (United States)

    ... one com- ponent of the once-popular anti-obesity drug known as Fen-Phen. Fen-Phen has since been withdrawn from the market because of a potential link between use of that drug and development of PH and heart valve problems. A high rate of stimulant use (including methamphetamine or cocaine depend- ...

  6. Amphetamines

    Science.gov (United States)

    ... unpredictably. Other long-term effects include: physical exhaustion insomnia and restlessness dizziness and blurred vision headaches reduced appetite and health problems from not eating properly higher chances of ...

  7. Amphetamine

    Science.gov (United States)

    ... along with a reduced calorie diet and an exercise plan for weight loss in obese people unable ... supplements you are taking, especially glutamic acid (L-glutamine).tell your doctor if you have hyperthyroidism (condition ...

  8. The effects of conditioning with amphetamine on the thermic effects of amphetamine and pentobarbital.

    Science.gov (United States)

    Hinson, R E; Streather, A; Cosburn, G

    1991-01-01

    1. Rats were injected with amphetamine (1.5 mg/kg) in the presence of a distinctive set of environmental stimuli (CS1) and saline in the presence of a different set of environmental stimuli (CS2) on different days for a total of 10 amphetamine and 20 saline injections. 2. The hyperthermic effect of amphetamine first increased but then declined to levels seen during the very first drug administration. 3. Following the conditioning phase, half the rats were injected with amphetamine in CS1 and half in CS2. Although there was little thermic effect of amphetamine injected in CS1, there was pronounced hyperthermia following amphetamine in CS2. 4. Next, pentobarbital (30 mg/kg) was administered to half the rats in CS1 and half in CS2. The hypothermic effect of pentobarbital was attenuated in CS2. PMID:1763195

  9. Biosynthesis of amphetamine analogs in plants.

    Science.gov (United States)

    Hagel, Jillian M; Krizevski, Raz; Marsolais, Frédéric; Lewinsohn, Efraim; Facchini, Peter J

    2012-07-01

    Amphetamine analogs are produced by plants in the genus Ephedra and by Catha edulis, and include the widely used decongestants and appetite suppressants pseudoephedrine and ephedrine. A combination of yeast (Candida utilis or Saccharomyces cerevisiae) fermentation and subsequent chemical modification is used for the commercial production of these compounds. The availability of certain plant biosynthetic genes would facilitate the engineering of yeast strains capable of de novo pseudoephedrine and ephedrine biosynthesis. Chemical synthesis has yielded amphetamine analogs with myriad functional group substitutions and diverse pharmacological properties. The isolation of enzymes with the serendipitous capacity to accept novel substrates could allow the production of substituted amphetamines in synthetic biosystems. Here, we review the biology, biochemistry and biotechnological potential of amphetamine analogs in plants. PMID:22502775

  10. Recent topics on pharmacotherapy for amphetamine-type stimulants abuse and dependence.

    Science.gov (United States)

    Chen, Hongxian; Wu, Jin; Zhang, Jichun; Hashimoto, Kenji

    2010-12-01

    Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), and 3,4-methylenedioxymethamphetamine (MDMA; ecstasy), has become a major public health problem worldwide. Use of these stimulants has significant psychiatric and medical consequences, including psychosis, dependence, overdose, and death. METH abuse in particular is an extremely serious and growing problem in many countries. The development of treatments for METH-related problems is particularly critical for users who experience persistent psychosis, pregnant women and women with children, gay and bisexual men, and users involved in the criminal justice system. However, there are currently no pharmacological treatments for the wide range of symptoms associated with METH-related problems. One of the reasons for this problem is that our knowledge of the cellular and molecular mechanisms underlying the development of METH-induced psychosis and dependence is limited. In this article, we review recent reports on potential pharmacotherapies (naltrexone, minocycline, antioxidants, immunotherapy, and dopaminergic, serotonergic, cholinergic, and GABAergic agents) for the treatment of ATS abusers. PMID:21208168

  11. 甲基苯丙胺依赖与中脑边缘多巴胺神经系统相关研究%Methamphetamine Dependence and Mesocorticolimbic Dopaminergic System

    Institute of Scientific and Technical Information of China (English)

    陈群; 周文华

    2012-01-01

    以甲基苯丙胺为代表的苯胺类中枢兴奋剂滥用问题日益突出,文章对甲基苯丙胺依赖的作用途径和机制进行了概述,包括中脑边缘系统多巴胺神经通路、多巴胺受体、多巴胺转运体及其他神经递质,最后提出了当前甲基苯丙胺成瘾治疗研究的主要方向.%As one of the amphetamine type stimulants, methamphetamine has been abused widely in China. The methamphetamine dependence is related to the mesocorticolimbic dopaminergic system. This paper describes the mechanisms underlying methamphetamine dependence on the dopamine release, dopamine receptors and dopamine transporter.

  12. Towards an MDA-based development methodology

    NARCIS (Netherlands)

    Gavras, Anastasius; Belaunde, Mariano; Ferreira Pires, Luis; Almeida, João Paolo A.; Oquendo, Flavio; Warboys, Brian C.; Morrison, Ron

    2004-01-01

    This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

  13. Chronic amphetamine treatment increases striatal calmodulin in rats

    International Nuclear Information System (INIS)

    A radioimmunoassay was developed to measure calmodulin in striatum from rats treated with one dose or repeated injections of amphetamine. Chronic, but not acute, amphetamine treatment resulted in a significant increase in total calmodulin levels in striatal homogenates. This effect may be linked to the behavioral sensitization which develops after chronic amphetamine treatments. (Auth.)

  14. Determination of amphetamine by HPLC after acetylation.

    Science.gov (United States)

    Veress, T

    2000-01-01

    An analytical procedure has been developed for the HPLC determination of amphetamine by off-line pre-column derivatization. The proposed procedure consists of sample preparation by acetylation of amphetamine with acetic anhydride and a subsequent reversed-phase HPLC separation on an octadecyl silica stationary phase with salt-free mobile phase (tetrahydrofuran, acetonitrile, 0.1% triethylamine in water, 15:15:70 v/v) applying UV-detection. The applicability of the elaborated procedure is demonstrated with results obtained by analysis of real samples seized in the Hungarian black market. PMID:10641931

  15. Ecstasy, Methamphetamine and Other Club Drugs

    Science.gov (United States)

    ... and premature birth Zika virus and pregnancy Microcephaly Medicine safety and pregnancy Birth defects prevention Learn how ... other club drugs Ecstasy, methamphetamine and other club drugs E-mail to a friend Please fill in ...

  16. Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.

    Science.gov (United States)

    Marks, Katherine R; Lile, Joshua A; Stoops, William W; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

    2016-06-01

    Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of D-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and "positive" subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone.Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6 to 7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected.Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like "positive" subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10-mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior. PMID:27043121

  17. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre

    2012-11-01

    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  18. Structural characterization of a therapeutic anti-methamphetamine antibody fragment: oligomerization and binding of active metabolites.

    Directory of Open Access Journals (Sweden)

    Eric C Peterson

    Full Text Available Vaccines and monoclonal antibodies (mAb for treatment of (+-methamphetamine (METH abuse are in late stage preclinical and early clinical trial phases, respectively. These immunotherapies work as pharmacokinetic antagonists, sequestering METH and its metabolites away from sites of action in the brain and reduce the rewarding and toxic effects of the drug. A key aspect of these immunotherapy strategies is the understanding of the subtle molecular interactions important for generating antibodies with high affinity and specificity for METH. We previously determined crystal structures of a high affinity anti-METH therapeutic single chain antibody fragment (scFv6H4, K(D = 10 nM in complex with METH and the (+ stereoisomer of 3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy". Here we report the crystal structure of scFv6H4 in homo-trimeric unbound (apo form (2.60Å, as well as monomeric forms in complex with two active metabolites; (+-amphetamine (AMP, 2.38Å and (+-4-hydroxy methamphetamine (p-OH-METH, 2.33Å. The apo structure forms a trimer in the crystal lattice and it results in the formation of an intermolecular composite beta-sheet with a three-fold symmetry. We were also able to structurally characterize the coordination of the His-tags with Ni(2+. Two of the histidine residues of each C-terminal His-tag interact with Ni(2+ in an octahedral geometry. In the apo state the CDR loops of scFv6H4 form an open conformation of the binding pocket. Upon ligand binding, the CDR loops adopt a closed formation, encasing the drug almost completely. The structural information reported here elucidates key molecular interactions important in anti-methamphetamine abuse immunotherapy.

  19. Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

    Directory of Open Access Journals (Sweden)

    R.C.S Martins

    2008-01-01

    Full Text Available Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip, methamphetamine (7 mg/kg, ip, or modafinil (100 mg/kg, ip subsequent to paradoxical sleep deprivation (PSD for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01. Regarding slow wave sleep (SWS, rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05. In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05. Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

  20. Methamphetamine

    Science.gov (United States)

    ... function. Methamphetamine’s ability to release dopamine rapidly in reward regions of the brain produces the euphoric “rush” or “flash” that many ... accompanied by chemical and molecular changes in the brain. Imaging studies ... of the dopamine system that are associated with reduced motor skills and ...

  1. Methamphetamine

    Science.gov (United States)

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... excessive tiredness slow or difficult speech seizures motor tics or verbal tics believing things that are not ...

  2. Methamphetamine

    Science.gov (United States)

    ... Read more NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home Site Map FAQs Accessibility Privacy FOIA(NIH) Working at NIDA Contact Subscribe Archives PDF documents require the free Adobe Reader . Microsoft Word documents require the free Microsoft Word ...

  3. Methamphetamine

    Science.gov (United States)

    ... Substances Act DEA Museum and Visitors Center Doing Business with DEA Drug Disposal Employee Assistance Program Extortion Scam Alert For Victims of Crime How do I...? National Clandestine Laboratory Register Registration ...

  4. Methamphetamine

    Science.gov (United States)

    ... in your family has or has ever had depression, bipolar disorder (mood that changes from depressed to abnormally excited), or mania (frenzied, abnormally excited mood), facial or motor tics (repeated uncontrollable movements), verbal tics ( ...

  5. Functional and Structural Brain Changes Associated with Methamphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Bruce R. Russell

    2012-10-01

    Full Text Available Methamphetamine (MA is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET and functional and structural magnetic resonance imaging (MRI. The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

  6. Boltushka: A Homemade Amphetamine-Type Stimulant and HIV Risk in Odessa, Ukraine

    Science.gov (United States)

    Chintalova-Dallas, Repsina; Case, Patricia; Kitsenko, Nataliya; Lazzarini, Zita

    2009-01-01

    Background Homemade amphetamine-type stimulants (ATSs) have been reported in Russia and Eastern Europe for decades. Recipes differ geographically and over time producing differing active ingredients. Vint and jeff (active ingredients methamphetamine and methcathinone, respectively) are two such homemade ATSs originally produced from over-the-counter cold medications and household chemicals. Methods During a Rapid Policy Assessment and Responses (RPAR) project in Odessa, Ukraine, researchers found use of boltushka, a novel homemade ATS. Fourteen supplemental qualitative interviews were conducted, including ten interviews with boltushka injectors and four interviews with pharmacists. We report patterns of boltushka use among local injection drug users (IDUs) as well as the role of laws, regulations, and current pharmacy practices. Results Legal restrictions on over-the-counter cold medicines in Ukraine led to products containing phenypropanolamine (PPA), which oxidized with KMnO4 (potassium permanganate), produces a weak ATS, cathinone, called boltushka. Boltushka’s ingredients are easily available in pharmacies or on the black market. IDUs reported a mean age at first use of 16 years old (range 12–21). While published data are scant, anecdotal evidence reported here include amphetamine-like effects on energy and appetite, binging patterns of use, and some reports of shaking and other neurological damage consistent with earlier reports from exposure to KMnO4. Users reported sharing syringes and other non-sterile injection practices. No users reported specific treatment or prevention programs for boltushka users. Conclusions Although Ukrainian government regulations have limited access to precursor chemicals, IDUs have continued to make and use boltushka. The actual extent and demographics of boltushka use are unknown. Besides risk of bloodborne disease, the health effects of injected homemade ATSs and their constituent chemicals are poorly documented

  7. Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry

    Science.gov (United States)

    Crevelin, Eduardo J.; Salami, Fernanda H.; Alves, Marcela N. R.; De Martinis, Bruno S.; Crotti, Antônio E. M.; Moraes, Luiz A. B.

    2016-02-01

    Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

  8. Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry

    Science.gov (United States)

    Crevelin, Eduardo J.; Salami, Fernanda H.; Alves, Marcela N. R.; De Martinis, Bruno S.; Crotti, Antônio E. M.; Moraes, Luiz A. B.

    2016-05-01

    Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

  9. Wipe sampling of amphetamine-type stimulants and recreational drugs on selected household surfaces with analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

    International Nuclear Information System (INIS)

    Highlights: • Degree of sorption of eight drugs on eleven countertop surfaces was investigated. • Surface composition, volatility and solvent composition played a role in sorption. • Solvent-dependent migration was a key factor of consideration during remediation. • SPME-assisted volatility studies provided evidence for varying degrees of recovery. • Rapid three minute UPLC-QTOF method was developed to quantify the eight compounds. -- Abstract: Sorption characteristics of eight drugs related to recreational and clandestine activity—amphetamine, cocaine, heroin, N-formyl amphetamine, N-formyl methamphetamine, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA), and pseudoephedrine—were evaluated on selected kitchen countertop surfaces. Methanol-dampened Whatman™ 40 filter paper wipes were used to collect samples from eleven surfaces including alkyd resin, ceramic tiles, glass, granite, laminate, limestone, marble, quartz compac, quartz real, soap stone, and stainless steel. The filter paper wipes were analyzed by a rapid three-minute UPLC-QTOF method, following ammonium acetate buffer (pH 5.8–6.2) extraction. The average percentage recoveries after 15 h of exposure to the surface materials tested, was found to be highest for cocaine and MDMA and lowest for amphetamine and methamphetamine. Among the eleven countertop surfaces, overall recoveries for marble were observed to be the least, whereas soapstone, quartz compac and stainless steel were among the highest. Scanning electron microscopic images of the surfaces provided a unique view of surface irregularities that potentially influenced drug recovery. Aging, migration, solvent composition, and volatility were examined. The variation in recovery of drugs was attributed to four key factors: compound volatility, surface composition, surface—compound interaction, and solvent composition

  10. Wipe sampling of amphetamine-type stimulants and recreational drugs on selected household surfaces with analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J.M.; Boles, Jeffrey O., E-mail: jboles@tntech.edu

    2013-06-15

    Highlights: • Degree of sorption of eight drugs on eleven countertop surfaces was investigated. • Surface composition, volatility and solvent composition played a role in sorption. • Solvent-dependent migration was a key factor of consideration during remediation. • SPME-assisted volatility studies provided evidence for varying degrees of recovery. • Rapid three minute UPLC-QTOF method was developed to quantify the eight compounds. -- Abstract: Sorption characteristics of eight drugs related to recreational and clandestine activity—amphetamine, cocaine, heroin, N-formyl amphetamine, N-formyl methamphetamine, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA), and pseudoephedrine—were evaluated on selected kitchen countertop surfaces. Methanol-dampened Whatman™ 40 filter paper wipes were used to collect samples from eleven surfaces including alkyd resin, ceramic tiles, glass, granite, laminate, limestone, marble, quartz compac, quartz real, soap stone, and stainless steel. The filter paper wipes were analyzed by a rapid three-minute UPLC-QTOF method, following ammonium acetate buffer (pH 5.8–6.2) extraction. The average percentage recoveries after 15 h of exposure to the surface materials tested, was found to be highest for cocaine and MDMA and lowest for amphetamine and methamphetamine. Among the eleven countertop surfaces, overall recoveries for marble were observed to be the least, whereas soapstone, quartz compac and stainless steel were among the highest. Scanning electron microscopic images of the surfaces provided a unique view of surface irregularities that potentially influenced drug recovery. Aging, migration, solvent composition, and volatility were examined. The variation in recovery of drugs was attributed to four key factors: compound volatility, surface composition, surface—compound interaction, and solvent composition.

  11. T-Mobile MDA II v Linuxu

    OpenAIRE

    Michl, Zbyněk

    2009-01-01

    Diplomová práce se zabývá mobilním digitálním asistentem T-Mobile MDA II v operačním systému Linux. První část práce je zaměřena na identifikaci zařízení a specifikaci parametrů MDA II. Druhá část popisuje výběr GNU distribuce s Linuxovým zavaděčem a porovnává současný stav podpory MDA II v různých verzích Linuxového jádra. Poslední část práce se věnuje implementaci kódu některých komponent a jeho začlenění do Linuxového jádra. MSc. thesis deals with mobile digital assistant T-Mobile MDA I...

  12. Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Daniele Z., E-mail: daniele.dzs@dpf.gov.br [Setor Tecnico-Cientifico, Superintendencia Regional do Departamento de Policia Federal no Rio Grande do Sul, 1365 Ipiranga Avenue, Azenha, Zip Code 90160-093 Porto Alegre, Rio Grande do Sul (Brazil); Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Pechansky, Flavio [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Duarte, Paulina C.A.V. [Secretaria Nacional de Politicas sobre Drogas (SENAD), Esplanada dos Ministerios, Block ' A' , 5th floor, Zip Code 70050-907 Brasilia, Distrito Federal (Brazil); De Boni, Raquel [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Froehlich, Pedro E.; Limberger, Renata P. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil)

    2011-06-24

    Graphical abstract: Highlights: > Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. > Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. > Linear range 2(4)-256 ng mL{sup -1}, detection limits 0.5-2 ng mL{sup -1}. > Accuracy 98-112%, precision <15% of RSD, recovery 77-112%. > Importance of residual evaluation in checking model goodness-of-fit. - Abstract: A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal{sup TM} device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL{sup -1} (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL{sup -1}. The detection limits were 0.5 ng mL{sup -1} (MET), 1 ng mL{sup -1} (MPH) and 2 ng mL{sup -1} (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal{sup TM} device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

  13. Does methamphetamine affect bone metabolism?

    International Nuclear Information System (INIS)

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

  14. Amphetamine-type stimulants and HIV infection among men who have sex with men: implications on HIV research and prevention from a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Nga Thi Thu Vu

    2015-02-01

    Full Text Available Introduction: HIV infections and the use of amphetamine-type stimulants (ATS among men who have sex with men (MSM have been increasing internationally, but the role of ATS use as a co-factor for HIV infection remains unclear. We aimed to summarize the association between ATS use and HIV infection among MSM. Methods: We conducted a systematic search of MEDLINE, EMBASE, GLOBAL HEALTH and PsycINFO for relevant English, peer-reviewed articles of quantitative studies published between 1980 and 25 April 2013. Pooled estimates of the association – prevalence rate ratios (PRR, cross-sectional studies, odds ratio (OR, case-control studies and hazard ratio (HR, longitudinal studies, with 95% Confidence Intervals (CI – were calculated using random-effects models stratified by study design and ATS group (meth/amphetamines vs. ecstasy. We assessed the existence of publication bias in funnel plots and checked for sources of heterogeneity using meta-regression and subgroup analysis. Results: We identified 6710 article titles, screened 1716 abstracts and reviewed 267 full text articles. A total of 35 publications were eligible for data abstraction and meta-analysis, resulting in 56 records of ATS use. Most studies (31/35 were conducted in high-income countries. Published studies used different research designs, samples and measures of ATS use. The pooled association between meth/amphetamine use and HIV infection was statistically significant in all three designs (PRR=1.86; 95% CI: 1.57–2.17; OR=2.73; 95% CI: 2.16–3.46 and HR=3.43; 95% CI: 2.98–3.95, respectively, for cross-sectional, case-control and longitudinal studies. Ecstasy use was not associated with HIV infection in cross-sectional studies (PRR=1.15; 95% CI: 0.88–1.49; OR=3.04; 95% CI: 1.29–7.18 and HR=2.48; 95% CI: 1.42–4.35, respectively, for cross-sectional, case-control and longitudinal studies. Results in cross-sectional studies were highly heterogeneous due to issues with ATS

  15. Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Elena Escubedo

    2011-06-01

    Full Text Available Amphetamine derivatives such as methamphetamine (METH and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy” are widely abused drugs in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS production seems to be one of the main causes. Recent research has demonstrated that blockade of a7 nicotinic acetylcholine receptors (nAChR inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, a7 nAChR antagonists (methyllycaconitine and memantine attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to a7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on a7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on a7 and heteromeric nAChR populations have been found.

  16. False-Positive TDxFLx urine Amphetamine/Metamphetamine II assay from Ofloxacin

    International Nuclear Information System (INIS)

    Immunoassays are widely used in testing urine for illicit drugs. Ofloaxcin and a number of other quinolones were found to induce false-positive opiates (OP) urine immunoassays. This can result in misleading conclusions in the concept of drug abuse The aim of present study was to evaluate the effects of ofloxacin in theraputic doses on the induction of false-positive urine immunoassays for common drugs of abuse in healthy male volunteers. The study was conducted on 6 healthy male volunteers, aging between 35-45 years. Two doses of 400 mg ofloxacin each, were given orally to each volunteer at 12 hours interval and urine samples were collected before ofloaxcin administration and 5-7.5 hours after the second dose. Urine samples were subjected for OP, amphetamine/methamphetamine II (AM/MA II), cocaine and cannabinoids assays on TDxFLx analyzer. Ofloxacin produced significant increase (Pcutoff) for AM/MA II assays, were found in all volunteers after ofloaxcin administration. The study recomends strongly the confirmation of positive urine immunoassay results for drugs of abuseby a more specific methodology e.g. gas chromatography/ mass spectroscopy (GC/MS). (author)

  17. Kadar Malondialdehid (MDA) Pada Kejadian Dismenore Primer

    OpenAIRE

    Prabudi, M Oky; Nasution, Syamsul A.; M. Fahdhy; Lubis, Rushakim; Edianto, Deri; Yusuf, M.

    2014-01-01

    Objective: To determine differences in MDA levels in menarche age adolescents with and without primary dysmenorrhea Methods: The study used a case control design with comparative analytical approach method and correlative analysis. The analysis carried out in the form of bivariate variables. Subjects were students at the elementary and junior high schools and the Integrated Al-Ulum Al-Washliyah MTsS in Medan. All the girls who have been menstruating for 6 -12 months since menarche and ha...

  18. On MDA - SOA based Intercloud Interoperability framework

    Directory of Open Access Journals (Sweden)

    Tahereh Nodehi

    2013-01-01

    Full Text Available Cloud computing has been one of the latest technologies which assures reliable delivery of on - demand computing services over the Internet. Cloud service providers have established geographically distributed data centers and computing resources, which are available online as service. The clouds operated by different service providers working together in collaboration can open up lots more spaces for innovative scenarios with huge amount of resources provisioning on demand. However, current cloud systems do not support intercloud interoperability. This paper is thus motivated to address Intercloud Interoperabilityby analyzing different methodologies that have been applied to resolve various scenarios of interoperability. Model Driven Architecture (MDA and Service Oriented Architecture (SOA method have been used to address interoperability in various scenarios, which also opens up spaces to address intercloud interoperability by making use of these well accepted methodologies. The focus of this document is to show Intercloud Interoperability can be supported through a Model Driven approach and Service Oriented systems. Moreover, the current state of the art in Intercloud, concept and benefits of MDA and SOA are discussed in the paper. At the same time this paper also proposes a generic architecture for MDA - SOA based framework, which can be useful for developing applications which will require intercloud interoperability. The paper justi fies the usability of the framework by a use - case scenario for dynamic workload migration among heterogeneous clouds.

  19. Death by 'ice': fatal methamphetamine intoxication of a body packer case detected by postmortem computed tomography (PMCT) and validated by autopsy.

    Science.gov (United States)

    Bin Abdul Rashid, Saiful Nizam; Rahim, Amir Saad Abdul; Thali, Michael J; Flach, Patricia M

    2013-03-01

    Fatal acute methamphetamine (MA) poisoning in cases of internal drug trafficking is rarely described in the literature. This case study reports an MA 'body packer' who died from fatal methamphetamine intoxication due to leaking drug packages in the alimentary tract. The deceased was examined by postmortem computed tomography (PMCT), and the results were correlated to subsequent autopsy and toxicological findings. The deceased was arrested by the police when he was found disoriented in the city of Kuala Lumpur. He was transferred to the emergency department on suspicion of drug abuse. The initial drug screening was reactive for amphetamines. Shortly after admission to the hospital, he died despite rigorous resuscitation attempts. The postmortem plain chest and abdominal radiographs revealed multiple suspicious opacities in the gastrointestinal tract attributable to body packages. An unenhanced whole body PMCT revealed twenty-five drug packages, twenty-four in the stomach and one in the transverse colon. At least two were disintegrating, and therefore leaking. The autopsy findings were consistent with the PMCT results. Toxicology confirmed the diagnosis of fatal methamphetamine intoxication. PMID:23404531

  20. A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis.

    Science.gov (United States)

    Brewer, Kimberly; Shults, Theodore F; Machin, Jacob; Kudrimoti, Sucheta; Eisenberg, Rodney L; Hartman, Petra; Wang, Caroline; Fenger, Clara; Beaumier, Pierre; Tobin, Thomas

    2016-08-01

    Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed. PMID:27493286

  1. The Effectiveness of Neurofeedback Therapy in Craving of Methamphetamine Use

    OpenAIRE

    Peyman Hashemian

    2015-01-01

    Introduction: Relapse in methamphetamine dependency is one of the most difficult parts to treat. Therefore treatment of craving for usage is one of the essential sections of treatment in methamphetamine dependency (addiction). This study evaluates the effect of neurofeedback therapy on craving for use. Methods: In this study 20 male patient with methamphetamine dependency who diagnosed on the basis of DSM-V were selected. None of the patients had any psychiatric and neurolog...

  2. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    OpenAIRE

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2007-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day b...

  3. The synthesis, mass spectrometric properties and identification of some N,N-di-(β-arylisopropyl)formamides related to the synthesis of ring-modified amphetamines.

    Science.gov (United States)

    Błachut, Dariusz; Danikiewicz, Witold; Wojtasiewicz, Krystyna; Olejnik, Marian; Kalinowska, Iwona; Szawkało, Joanna; Czarnocki, Zbigniew

    2011-03-20

    This study examines the electron impact (EI) induced mass spectrometric behavior of several N,N-di-(β-arylisopropyl)formamides, which are connected to the Leuckart synthesis of some amphetamine analogues. Emphasis is laid on the fragmentation paths, which are common for all compounds under investigation and may be used in construction of the prediction scheme useful for identification of similar impurities, especially in absence of desirable authentic material. On the basis of this scheme several new N,N-di-(β-arylisopropyl)formamides have been identified in selected amphetamine analogues synthesized by the Leuckart method, including 4-methylthioamphetamine (4-MTA), 4-fluoroamphetamine (4-FA), 4-methylamphetamine, 3-trifluoromethylamphetamine, 3,4-methylenedioxyamphetamine (MDA), 2,5-dimethoxyamphetamine (2,5-DMA), 2,4,5- and 3,4,5-trimethoxyamphetamines (2-TMA and 3-TMA). PMID:20846801

  4. Methamphetamine: A molecular and pathological exacerbate of HIV neurocognitive disorder

    Directory of Open Access Journals (Sweden)

    Shahid Salaria

    2005-12-01

    Full Text Available The use of the recreational drug methamphetamine is becoming more widespread, and it is accompanied by unsafe sexual behaviours that increase the transmission of the human immunodeficiency virus (HIV. This article reviews the available literature of the effect of methamphetamine on the HIV infected brain, and in particular the molecular disturbances and neuropathology associated within this cohort. Our molecular research indicates that methamphetamine and HIV have a synergistic pathological impact on neuronal cell injury and death, which may be mediated by an upregulation of interferon inducible genes observed within this group, thereby contributing to the neurocognitive deficits observed in clinical populations of HIV infected methamphetamine abusers.

  5. Comparison of periodontal manifestations in amphetamine and opioids' consumers

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi

    2016-03-01

    Full Text Available Background: Drug abuse is one of the most important etiologic and deteriorating factors in periodontal disease. Amphetamines and opioids, the most commonly used drugs worldwide, play an important role in this regard. The aim of this study was to compare the periodontal status of amphetamines and opioids consumers in Kermanshah city, Iran in 1393. Methods: Three drug rehabilitation clinics were selected randomly in Kermanshah. According to inclusion and exclusion criteria, 20 amphetamine consumers and 20 opioid consumers were selected randomly and participated in this study. A questionnaire for drug use and periodontal variables was designed. The collected data were entered into SPSS-18 software and Mann-Whitney and t-test were used for statistical analysis. Results: Pocket depth, gingival index and gingival bleeding in amphetamines users were more than those in opioids consumers (P<0.021. Plaque index and gingival recession in opioids users were more than those of amphetamines consumers (P<0.001. The number of periodontal disease cases in amphetamines group were 13 persons (65% and in opioids group 8 persons (40%. Conclusion: Our study showed that periodontal hygine in amphetamine consumers was worse than opioid consumers.

  6. Development of a harmonised method for the profiling of amphetamines V: Determination of the variability of the optimised method.

    Science.gov (United States)

    Lock, Eric; Aalberg, Laura; Andersson, Kjell; Dahlén, Johan; Cole, Michael D; Finnon, Yvonne; Huizer, Henk; Jalava, Kaisa; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki

    2007-06-14

    amphetamine were prepared. Six of them were synthesised via the Leuckart route, three via the nitrostyrene route and three via the reductive amination route [A.M.A. Verweij, Impurities in illicit drug preparations: amphetamine and methamphetamine, Forensic Sci. Rev. 1 (1989) 2-11]. Taking into account all studied target compounds and the average results from four laboratories, the within day variation was around 6% for FID and 5% for MS, the between days variation was around 10% for FID and 8% for MS. For NPD detection, within day variation was 5% and between days variation 9% (only one laboratory). Finally, the inter-laboratory variation was about 12% for FID (four laboratories) and 10% for MS (three laboratories). PMID:17178203

  7. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Shim, Irene; White, Peter Cyril; Abdali, Salim

    2012-01-01

    -molecular orbital calculations by use of the Gaussian 03W pro- gram, based on complete geometry minimizations of the conformational energy of the S-(+)-amphetamine molecule, the S-(+)-amphetamine-H+ ion, and the R-(–)-amphetamine molecule. Following this, harmonic frequency calculations have been made, providing...... am- phetamine-H+ sulfate. According to the present study the AMPH+ ion in aqueous sulfate solution seems to adopt a con- formation in which the phenyl and ammonium groups are in transpositions, similar to what has been found in the solid state....

  8. METHAMPHETAMINE: WHERE WILL THE STAMPEDE TAKE US?

    Science.gov (United States)

    Sullivan, Danny; McDonough Michael

    2015-09-01

    Methamphetamine, particularly "ice", currently preoccupies the media and there are a range of government initiatives which seem to follow media interest. We summarise the progress of government attention, briefly review health concerns associated with methamphetamine use, and summarise the evidence for treatments, including psychosocial interventions and medications. Amid concerns that governments will seek to fund any promising initiative in order to be perceived as responding to an epidemic, we caution that existing treatments should not be abandoned in favour of untested but potentially attractive treatments. Harm reduction and outpatient psychological treatments remain the mainstay of drug treatment programs and may be more cost-effective and broader-reaching than inpatient, medication-based detoxifications. PMID:26554196

  9. Duration of detection of methamphetamine in hair after abstinence.

    Science.gov (United States)

    Suwannachom, Natiprada; Thananchai, Thiwaphorn; Junkuy, Anongphan; O'Brien, Timothy E; Sribanditmongkol, Pongruk

    2015-09-01

    Researchers in the field of hair analysis have known for at least two decades that test results for many chemical compounds remain positive for a considerable period of time after subjects have reported cessation of use. These findings were generally based on small sample populations or individual case studies. Within the last decade, hair analyses of larger populations have investigated the phenomenon of residual positives in abstinent individuals in order to determine the period of time required for various compounds to present negative hair test results at internationally accepted cutoff levels. Such data has primarily been used to establish guidelines for retesting former abusers of illicit drugs in order to evaluate claims of abstinence. To date, research has focused on cocaine and opiates. The present study is the first to examine the duration of detection of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of chronic MA users who recently ceased their consumption of the drug. The study population (n=63) consisted of inpatients at a hospital drug rehabilitation program in Chiang Mai, Thailand. Drug taking behavior was collected by personal interview at the time of enrollment. Subjects provided hair samples at approximately monthly intervals for MA and AP analysis by gas chromatography-mass spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP concentrations in hair at the beginning of abstinence with corresponding duration of detection indicated great individual variability for the rate of clearance of MA and AP from hair. In regard to duration of detection, the majority of chronic MA users remained MA positive for up to about 90 days of reported abstinence, but by 120 days, the detection rate had fallen to about 16%. All subjects tested negative for MA after 153 days of abstinence. For AP, the limit of the duration of detection was reached at 106 days. With the adoption of a margin of safety to compensate for

  10. Powerful Behavioral Interactions Between Methamphetamine and Morphine

    OpenAIRE

    Trujillo, Keith A.; Smith, Monique L; Guaderrama, Melissa M.

    2011-01-01

    Use of drugs of abuse in combination is common among recreational users and addicts. The combination of a psychomotor stimulant with an opiate, known as a ‘speedball’, reportedly produces greater effects than either drug alone and has been responsible for numerous deaths. Historically, the most popular speedball combination is that of cocaine and heroin. However, with the growing popularity of methamphetamine in recent years, there has been increased use of this drug in combination with other...

  11. Intracerebral haemorrhage and vasculitis secondary to amphetamine use.

    OpenAIRE

    Salanova, V.; Taubner, R.

    1984-01-01

    We report a case of amphetamine-related intracranial haemorrhage and vasculitis, responding to immunosuppressants. Angiograms obtained before and after therapy are shown; the importance of immunosuppressive therapy is discussed.

  12. Synthesis of polystyrene, poly(styrene/4-vinylpyridine), poly(p-nitrostyrene) and poly(p-aminostyrene)-coated silica and their extraction capabilities for amphetamine

    International Nuclear Information System (INIS)

    Several novel organic-inorganic hybrid materials, including polystyrene-coated silica (SG-PS), poly(styrene/4-vinylpyridine)-coated silica (SG-PVP), poly(p-nitrostyrene)-coated silica (SG-PS-NO2) and poly(p-aminostyrene)-coated silica (SG-PS-NH2), were synthesized in order to improve the extraction methods of harmful stimulants via solid phase extraction. The materials were characterized using infrared spectra (IR), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) surface area measurement and thermogravimetric analysis (TG). The application of the new materials in solid phase extraction columns to extract methamphetamine revealed that the extraction capability of poly(styrene/4-vinylpyridine)-coated silica is the best among the four materials, which provides novel supporter materials for extracting amphetamine-derived drugs.

  13. Residual effects of intranasal methamphetamine on sleep, mood, and performance

    Science.gov (United States)

    Perez, Audrey; Kirkpatrick, Matthew G.; Gunderson, Erik W.; Marrone, Gina; Silver, Rae; Foltin, Richard W.; Hart, Carl L.

    2008-01-01

    Although intranasal methamphetamine abuse has increased, there are no published data investigating the residual effects of the drug under controlled conditions. Thus, the current study examined the residual effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Non-treatment seeking methamphetamine abusers (n = 11) completed this two-week, in-patient, within-participant, double-blind study. The study consisted of 4 two-day blocks of sessions; each block was separated by at least 24 hrs. At approximately 1000 hrs, on the first day of each block, participants received one of four intranasal methamphetamine doses (0, 12, 25, 50 mg/70 kg). Lights were turned out at 2300 hrs that evening and sleep measures were assessed. On the morning of the second day of each block, methamphetamine plasma levels, cardiovascular measures, mood, subjective reports of the previous evening's sleep, and psychomotor performance were assessed to determine residual drug effects. The larger methamphetamine doses (25 and 50 mg) markedly disrupted subjective measures of that night's sleep and some indices of next-day mood, but only the largest dose (50 mg) dose decreased objective measures of that night's sleep and increased next-day physiological measures. Methamphetamine did not produce any negative residual effects on early next-day performance. Future studies should assess methamphetamine-related residual effects following repeated doses administered over consecutive days. PMID:18078723

  14. Effects of methamphetamine dependence and HIV infection on cerebral morphology

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.; Fennema-Notestine, Christine; Mindt, Monica Rivera; Marcotte, Thomas L.; Heaton, Robert K.; Ellis, Ronald J.; Grant, Igor

    2005-01-01

    OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age- and...... education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced...... increases, and in one of these structures-the nucleus accumbens-there appeared to be a larger effect in younger methamphetamine abusers. Neurocognitive impairment was associated with decreased cortical volumes in HIV-positive participants but with increased cortical volumes in methamphetamine...

  15. Environmental enrichment does not reduce the rewarding and neurotoxic effects of methamphetamine.

    Science.gov (United States)

    Thiriet, Nathalie; Gennequin, Benjamin; Lardeux, Virginie; Chauvet, Claudia; Decressac, Mickael; Janet, Thierry; Jaber, Mohamed; Solinas, Marcello

    2011-01-01

    Abuse of amphetamine analogues, such as methamphetamine (METH), represents an important health problem because of their powerful addictive and neurotoxic effects. Abuse of METH induces dopamine neuron terminals loss and cell death in the striatum similar to what is found in other neurodegenerative processes. Exposing mice and rats to enriched environments (EE) has been shown to produce significant protective effects against drug-induced reward as well as against neurodegenerative processes. Here, we investigated whether exposure to EE could reduce the METH-induced reward and neurotoxicity. For this, we reared mice for 2 months during early stages of life in standard environments or EE and then, at adulthood, we tested the ability of METH to induce conditioned place preference and neurotoxicity. We found that, contrary to what we found with other drugs such as cocaine and heroin, EE was unable to reduce the rewarding effects of METH. In addition, contrary to what we found with other toxins such as MPTP, EE did not diminish the striatal neurotoxicity induced by METH (4 x 10 mg/kg) as measured by dopamine content, tyrosine hydroxylase protein levels and apoptosis. Our results demonstrate that the rewarding and neurotoxic effects of METH are not reduced by EE and highlight the great risks associated with the increased popularity of this drug amongst the young population. PMID:20143198

  16. Involvement of dorsal striatal α1-containing GABAA receptors in methamphetamine-associated rewarding memories.

    Science.gov (United States)

    Jiao, D-L; Liu, Y; Long, J-D; Du, J; Ju, Y-Y; Zan, G-Y; Liu, J-G; Zhao, M

    2016-04-21

    Rewarding memories induced by addictive drugs may contribute to persistent drug-seeking behaviors, which is an important contributing factor to drug addiction. However, the biological mechanisms underlying drug-associated rewarding memories have not yet been fully understood, especially the new synthetic drugs, such as amphetamine-type stimulants (ATS). In this study, using the rat-conditioned place preference (CPP) model, a classic animal model for the reward-associated effects of addictive drugs, we found that the expression level of GABAA α1 subunits was significantly decreased in the dorsal striatum (Dstr) after conditioned methamphetamine (METH) pairing, and no significant differences were observed in the other four rewarding memory-associated areas (medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala (Amy), and dorsal hippocampus (DH)). Intra-Dstr injection of either the GABAA receptor agonist muscimol or the specific α1GABAA receptor-preferring benzodiazepine (BDZ) agonist zolpidem significantly abolished METH CPP formation. Thus, this study extends previous findings by showing that GABAA receptors, particularly the α1-containing GABAA receptors, may be strongly implicated in METH-associated rewarding memories. This work provides us with a new perspective on the goal of treating ATS addiction. PMID:26868969

  17. Development of modified MDA (M-MDA), PWR fuel cladding tube for high duty operation in future

    International Nuclear Information System (INIS)

    A new cladding material of M-MDA has been developed in order to prepare for a strong growing demand for advanced fuel which can maintain its integrity even under high duties due to more efficient operation such as higher burnup, higher LHR, and longer operation cycle which will contribute the suppression of environmental burdens like CO2 emission. The main aim of M-MDA is to have excellent corrosion resistance while the other properties are inherited from MDA, which has been adopted to the step 2 fuel, instead of Zry-4, of Japanese PWR plant whose upper limit of assembly discharged burnup is 55 MWd/kgU. And we could confirm that the main aim of M-MDA was achieved by means of out-of-pile tests. In order to confirm improvement of corrosion resistance of M-MDA in the actual operation, irradiation test of M-MDA in the commercial reactor of Vandellos II is ongoing. The latest results of on-site examination after every end of cycle showed that oxide thickness of M-MDA-SR was much smaller than that of MDA at rod discharged burnup of approximately 60 MWd/kgU. The final irradiation cycle was completed on April 2007 and then we will obtain corrosion data of M-MDA over 70 MWd/kgU. M-MDA is a candidate alloy for advanced fuel under higher duty usage. (authors)

  18. Amphetamines, the pregnant woman and her children: a review.

    Science.gov (United States)

    Oei, J L; Kingsbury, A; Dhawan, A; Burns, L; Feller, J M; Clews, S; Falconer, J; Abdel-Latif, M E

    2012-10-01

    The objective of this study is to review and summarize available evidence regarding the impact of amphetamines on pregnancy, the newborn infant and the child. Amphetamines are neurostimulants and neurotoxins that are some of the most widely abused illicit drugs in the world. Users are at high risk of psychiatric co-morbidities, and evidence suggests that perinatal amphetamine exposure is associated with poor pregnancy outcomes, but data is confounded by other adverse factors associated with drug-dependency. Data sources are Government data, published articles, conference abstracts and book chapters. The global incidence of perinatal amphetamine exposure is most likely severely underestimated but acknowledged to be increasing rapidly, whereas exposure to other drugs, for example, heroin, is decreasing. Mothers known to be using amphetamines are at high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their infants may escape detection, because the signs of withdrawal are usually less pronounced than opiate-exposed infants. There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide concern, but robust research, especially for childhood outcomes, remains scarce. We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase provision of early-intervention services for affected children and their families. PMID:22652562

  19. Effects of d-amphetamine upon psychosocial stress responses.

    Science.gov (United States)

    Childs, Emma; Bershad, Anya K; de Wit, Harriet

    2016-07-01

    Psychostimulant drugs alter the salience of stimuli in both laboratory animals and humans. In animals, stimulants increase rates of responding to conditioned incentive stimuli, and in humans, amphetamine increases positive ratings of emotional images. However, the effects of stimulants on real-life emotional events have not been studied in humans. In this study, we examined the effect of d-amphetamine on responses to acute psychosocial stress using a public speaking task. Healthy volunteers (N=56) participated in two experimental sessions, one with a psychosocial stressor (the Trier Social Stress Test) and one with a non-stressful control task. They were randomly assigned to receive d-amphetamine (5 mg n=18, 10 mg n=20) or placebo (n=18) on both sessions under double blind conditions. Salivary cortisol, subjective mood, and vital signs were measured at regular intervals during the session. Subjects also provided cognitive appraisals of the tasks before and after their performances. Amphetamine produced its expected mood and physiological effects, and the Trier Social Stress Test produced its expected effects on cortisol and mood. Although neither dose of amphetamine altered cardiovascular or hormonal responses to stress, amphetamine (10 mg) increased participants' pre-task appraisals of how challenging the task would be, and it increased post-task ratings of self-efficacy. Paradoxically, it also increased ratings of how stressful the task was, and prolonged aversive emotional responses. These findings suggest that amphetamine differentially affects stress response components: it may increase participants' appraisals of self-efficacy without dampening the direct emotional or physiological responses to the stress. PMID:27235381

  20. Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport

    International Nuclear Information System (INIS)

    The accumulation of 5 nM d-[3H]amphetamine (d-[3H]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[3H]AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-[3H]AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of [3H] dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-[3H]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed

  1. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    Energy Technology Data Exchange (ETDEWEB)

    Zaczek, R.; Culp, S.; De Souza, E.B. (Addiction Research Center, Baltimore, MD (USA))

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  2. Potential Effects of Chrysin on MDA-MB-231 Cells

    OpenAIRE

    Maimunah Ahmad; Khoo Boon Yin; Thaneswary Yogarajah; Anizah Rahumatullah; Teh Ban Hong

    2010-01-01

    This study aims to elucidate the effects of chrysin on human ER-negative breast cancer cell line, MDA-MB-231. The study demonstrated that treatment of MDA-MB-231 cells with 20 µM chysin for 48 h significantly inhibited the growth of MDA-MB-231 cells and induced cytoplasmic lipid accumulation in the cells, but that the observed of cell death was not caused by apoptosis. The expression of PPARalpha mRNA in chrysin-treated MDA-MB-231 cells was significantly increased, which was likely associated...

  3. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    Directory of Open Access Journals (Sweden)

    Joshua L. Fenderson

    2013-01-01

    Full Text Available The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS. She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  4. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    Directory of Open Access Journals (Sweden)

    Vo K

    2015-01-01

    Full Text Available Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Significant differences were found between students reporting (n=79; 4.0% and not reporting (n=1,897; 96% amphetamine-stimulant use in the past month – in terms of race/ethnicity, class standing, residence, health symptoms, self-health report – in addition to alcohol, tobacco, pain-reliever, and antidepressant use. Health symptoms reported more often by stimulant users included depression, diarrhea, difficulty sleeping, fatigue, dizziness, difficulty concentrating, and nicotine craving. Health care providers of college students should query these patients about symptoms that could be related to depression and amphetamine use. In particular, they should provide education at the point of care around the risks of amphetamine use in general and the specific risks in those students who have symptoms of depression and/or are taking antidepressant medication. Prevention programs should also target the risks of concurrent use of amphetamines, antidepressants, and other drugs among college students. Keywords: stimulant use, depression, college students, self-medication

  5. Attention performance among Brazilian truck drivers and its association with amphetamine use: pilot study

    Directory of Open Access Journals (Sweden)

    Lucio Garcia de Oliveira

    2013-10-01

    Full Text Available The aim of this article was to describe the attention functioning of twenty-two truck drivers and its relationship with amphetamine use. Those drivers who reported using amphetamines in the twelve months previous to the interview had the best performance in a test evaluating sustained attention functioning. Although amphetamine use may initially seem advantageous to the drivers, it may actually impair safe driving. The findings suggest the importance of monitoring the laws regarding amphetamine use in this country.

  6. Towards an MDA-based development methodology for distributed applications

    NARCIS (Netherlands)

    Gavras, A.; Belaunde, M.; Ferreira Pires, L.; Andrade Almeida, J.P.; van Sinderen, M.J.; Ferreira Pires, L.

    2004-01-01

    This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

  7. Correlates of Trading Sex for Methamphetamine in a Sample of HIV-Negative Heterosexual Methamphetamine Users

    OpenAIRE

    Semple, Shirley J.; Steffanie A Strathdee; Zians, Jim; Patterson, Thomas L.

    2011-01-01

    While many studies have examined correlates of trading sex for money, few have examined factors associated with exclusive trading of sex for drugs. We identified sociodemographic, behavioral, and psychological correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual men and women who were enrolled in a sexual risk reduction intervention in San Diego, California. Of 342 participants, 26% overall (21% of males and 31% of females) reported trading sex for methamphet...

  8. Bupropion Attenuates Methamphetamine Self-Administration in Adult Male Rats

    OpenAIRE

    Reichel, Carmela M.; Murray, Jennifer E.; Grant, Kathleen M.; Bevins, Rick A.

    2008-01-01

    Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphe...

  9. Methamphetamine Craving Induced in an Online Virtual Reality Environment

    OpenAIRE

    Culbertson, Christopher; Nicolas, Sam; Zaharovits, Itay; London, Edythe D.; De La Garza, Richard; Brody, Arthur L.; Newton, Thomas F.

    2010-01-01

    The main aim of this study was to assess self-reported craving and physiological reactivity in a methamphetamine virtual reality (METH-VR) cue model created using Second Life, a freely available online gaming platform. Seventeen, non-treatment seeking, individuals that abuse methamphetamine (METH) completed this one-day, outpatient, within-subjects study. Participants completed four test sessions: 1) METH-VR 2) neutral-VR 3) METH-video 4) neutral-video in a counterbalanced (latin square) fash...

  10. Apparent hallucinations in monkeys during around-the-clock amphetamine for seven to fourteen days. Possible relevance to amphetamine psychosis.

    Science.gov (United States)

    Nielsen, E B; Lyon, M; Ellison, G

    1983-04-01

    Schizophrenia-like symptoms have been experimentally produced in humans by a single, large dose of amphetamine or by relatively low level, but continuous administration of the drug. In animal studies of the psychotomimetic properties of amphetamine, high doses and, in particular, repeated daily-injection drug schedules have often been used. However, amphetamine psychosis is not always a prominent effect of repeated intake drug schedules in humans and available clinical evidence suggests that psychosis develops more readily when the drug is taken in a continuous fashion over longer periods. The state produced by single large doses of amphetamine, although clearly abnormal, has been said to bear less resemblance to schizophrenia than the delayed paranoid symptoms developing after longer periods of continuous intake. In the present experiments we have studied the behavioral effects of 7 to 14 days of continuous administration of amphetamine to monkeys (Cercopithecus aethiops) using subcutaneously implanted silicone capsules releasing approximately .7 to 1.5 mg/kg/day of d-amphetamine base. Around-the-clock TV monitoring of the animals revealed a general biphasic sequence of drug effects, although considerable individual variation occurred: a) an "acute" phase dominated by stereotyped movements and/or prolonged staring, lasting for 2 to 5 days; b) a "late" phase peaking during days 5 to 10 after capsule implantation and characterized by highly individual, but striking sequences of: (1) Attack or sudden threat reactions directed at invisible objects; (2) rapid orienting and flight behavior without apparent cause; (3) sudden startle reactions; (4) prolonged vocalization; (5) visual tracking of invisible objects, sometimes involving coordinated patterns of "eating behavior" and (6) prolonged and rapid grooming directed at various parts of the body. These behaviors might be termed "hallucinatory" since no eliciting stimuli could be determined for their occurrence. Motor

  11. The Comparsion of the Efficacy of Group Psychotherapy Based on Acceptance and Commitment Therapy, and Mindfulness on Craving and Cognitive Emotion Regulation in Methamphetamine Addicts

    Directory of Open Access Journals (Sweden)

    Ahmadreza Kiani

    2013-01-01

    Full Text Available Aim: Today, third wave therapies in psychotherapy shift their attention from challenging cognitions to awareness and acceptance of feelings, emotions, cognitions and behaviors. Therefore, this research aimed to compare of efficacy of group psychotherapy based on acceptance and commitment therapy, with mindfulness on craving and cognitive emotion regulation in methamphetamine addicts. Method: Research method was semi experimental research design with pre-post test and follow up. The population of research was included all of methamphetamine addicts in baharestan, Isfahan. Drug abusers was 34 participants that refered to addiction rehabilitation centers and selected by snowball sampling and finaly divided to 2groups by radomization (acceptance and commitment therapy group and mindfulness groups. Each groups recieved treatment in 12 sessions (At First 2 sessions per week and at last 1 session per week. Two groups assessed by craving test (Ekhtiary, 1387 and cognitive emotion regulation (garnefski et al, 2002, in pretest, post test and follow up. Results: The results showed that two treatment groups had significant effect on craving intensity in post test and follow up. In addition, there was no significant difference in comparing of the efficacy of these two treatments on cognitive emotion regulation and it means that both two traetments had same effect on cognitive emotion regulatin. Conclusion: we can say that acceptance and commitmet therapy and mindfulnesshave effect on reduction psychopathology from using amphetamines due to same theraputic factors.

  12. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    Science.gov (United States)

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

    Methamphetamine (METH), an illegal psycho-stimulant, is widely known as a recreational drug. In addition to its addictive effect, METH induces neurotoxicity via multiple mechanisms. The major contributors to METH-induced neurotoxicity are reactive oxygen species, which lead to cell death through apoptotic pathway and disturbances in mitochondria, the generation of neuroinflammation, and autophagy. Melatonin, a neurohormone secreted by the pineal gland, is a potent antioxidant compound that plays a beneficial role by protecting against the oxidative stress caused by METH. Melatonin also plays a role in maintaining mitochondrial homeostasis. Nanomolar concentrations of melatonin have been shown to protect against the inflammation caused by METH and to prevent the decrease in neurogenesis caused by METH in progenitor cells obtained from adult rat hippocampal tissue. The intent of this review is to describe the underlying mechanisms involving melatonin that protect against the neurodegeneration caused by METH. PMID:25248807

  13. Brain SPECT with 123I-isopropyl amphetamine in epilepsy

    International Nuclear Information System (INIS)

    Ten patients were studied with N-isopropyl I-123 p-iodoamphetamine. Single photon emission computed tomography (SPECT) was carried out by hand of a rotating gamma camera system (Gammatome T9000/CGR, high resolution collimator). During 1 rotation (3600) 64 frames (4k matrix) were acquired within 20 min 1 hour after injection of 6.5 mCi I-123 labeled amphetamine. The content of I-124 was less than 2%. After reconstruction of transverse slices coronar and sagittal reconstructions were rapidly performed using an array processor. Nine patients suffered from epilepsy and one from severe migraine. Excellent differentiation between gray and white matter of the cerebral cortex and the basal ganglia was evident in all of the cases. In 2 out of 3 patients with epilepsy and negative CT results SPECT revealed circumscribed areas with increased amphetamine uptake in accordance with the EEG findings. In 4 out of 6 cases with positive CT findings SPECT lesions with diminished amphetamine uptake could be established. One patient with severe migraine showed focal increased amphetamine uptake in accordance with the respective clinical results. (orig.)

  14. Amphetamine alters neural response to sucrose in healthy women.

    Science.gov (United States)

    Melrose, A James; Bailer, Ursula; Wierenga, Christina E; Bischoff-Grethe, Amanda; Paulus, Martin P; Kaye, Walter H

    2016-06-30

    Amphetamine, likely via action on the brain's dopaminergic systems, induces anorectic eating behavior and blunts dopaminergic midbrain activation to rewards. Past work has hypothesized that this blunted reward responsivity is a result of increasing tonic over phasic DA activity. We sought to extend past findings to sweet taste during fMRI following single-blind administration of dextroamphetamine and placebo in 11 healthy women. We hypothesized that neural response in both limbic and cognitive sweet taste circuits would mirror past work with monetary rewards by effectively blunting sweet taste reward, and 'equalizing' it's rewarding taste with receipt of water. Behavioral results showed that amphetamine reduced self-reported hunger (supporting the existence of amphetamine anorexia) and increased self-report euphoria. In addition, region of Interest analysis revealed significant treatment by taste interactions in the middle insula and dorsal anterior cingulate confirming the 'equalizing' hypothesis in the cingulate, but unlike monetary reinforcers, the insula actually evinced enhanced separation between tastes on the amphetamine day. These results suggest a divergence from prior research using monetary reinforcers when extended to primary reinforcers, and may hint that altering dopaminergic signaling in the insula and anterior cingulate may be a target for pharmacological manipulation of appetite, and the treatment of obesity. PMID:27179312

  15. Componentes MDA para patrones de diseño

    OpenAIRE

    Martínez, Liliana Inés

    2008-01-01

    La arquitectura Model-Driven (Model-Driven Architecture o MDA) es un framework para el desarrollo de software definido por el Object Management Group (OMG) (MDA, 2007). Su propuesta es elevar el nivel de abstracción en el que se desarrollan sistemas complejos separando la especificación de la funcionalidad de un sistema de su implementación en una plataforma tecnológica específica. MDA promueve el uso de modelos y transformaciones de modelos para el desarrollo de sistemas de software. El p...

  16. Automated code generation support for BI with MDA TALISMAN

    Directory of Open Access Journals (Sweden)

    Óscar Sanjuan-Martínez

    2009-12-01

    Full Text Available Model Driven Engineering (MDE is gaining ever more strength due to the fact that with MDE the software development can be much more productive and this is the way to go closer to real software industrialization. With MDA TALISMAN, we have succeeded in creating complex software solutions for food traceability adapted to different customers, ready to be deployed. We rely on the approach to MDE most extended at present, MDA (Model-Driven Development but as we shall see, we also use the main pillars that support the Software Factories, The proposal from Microsoft to MDE. Besides, in this paper we present five cases of success with MDA TALISMAN.

  17. BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine

    OpenAIRE

    Manning, Elizabeth E.; Halberstadt, Adam L.; van den Buuse, Maarten

    2015-01-01

    Background: One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Methods: Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-am...

  18. Short Communication: Methamphetamine Treatment Increases in Vitro and in Vivo HIV Replication

    OpenAIRE

    Toussi, Sima Shelly; Joseph, Aviva; Zheng, Jian Hua; Dutta, Monica; Santambrogio, Laura; Goldstein, Harris

    2009-01-01

    To delineate the mechanistic basis for the epidemiological association between methamphetamine use and accelerated progression to AIDS, we evaluated the direct in vitro and in vivo effects of methamphetamine on HIV-1 replication. Methamphetamine administration significantly increased HIV-1 production by both HIV-infected monocytes and CD4 T lymphocytes in vitro. In addition, in vivo methamphetamine treatment increased HIV production and viremia in mice transgenic for a replication-competent H...

  19. Radiometric Testing of Magnesium Diboride Array (MDA) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective is to develop a 2-Dimensional Far Infra-Red Magnesium Diboride Array (2D FIR MDA) to use in NASA’s future planetary exploration instruments. The...

  20. A MDA Approach for Navigational and User Perspectives

    OpenAIRE

    González, Magalí; Casariego, Jorge; Bareiro, Juan José; Cernuzzi, Luca; Pastor López, Oscar

    2011-01-01

    The study presented in this paper focuses on a navigational and user perspectives analysis of Web applications, highlighting some of their critical points for modeling. To consider these critical points, we propose a notational definition focused on a general metamodel, consisting of three specific metamodels: the Navigational Tree, the Node, and Roles. The metamodels have been implemented with a specific MDA (Model Driven Architecture) tool called AndroMDA, to generate applicatio...

  1. Ceruloplasmin and serum MDA levels in hypothyroid patients

    OpenAIRE

    Bhattacharya, Aruna; Saha, Rama; Mondal, Tridbeshwar; Choudhuri, Subhadeep; Gupta, Soma

    2014-01-01

    The present study was designed to investigate the relationship between serum levels of MDA which is a marker of oxidative stress and Ceruloplasmin with thyroid hormone status in hypothyroid females pre &posttreatment.The study group comprised of 46 patients with primary hypothyroidism, The patients were reevaluated after 6 months of L-thyroxine therapy. The patients were compared with equal number of normal healthy controls. Serum MDA and Ceruloplasmin were measured according to an enzyma...

  2. BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

    Directory of Open Access Journals (Sweden)

    Elizabeth E Manning

    2013-06-01

    Full Text Available Brain-derived neurotrophic factor (BDNF has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

  3. Enantiomeric profiling of chiral drug biomarkers in wastewater with the usage of chiral liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Castrignanò, Erika; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2016-03-18

    This paper proposes a novel multi-residue enantioselective method utilising a CBH (cellobiohydrolase) column, for the analysis of 56 drug biomarkers in wastewater. These are: opioid analgesics, amphetamines, cocaine, heroin, stimulants, anaesthetics, sedatives, anxiolytics, designer drugs, phosphodiesterase-5 (PDE5) inhibitors, amphetamine and methamphetamine drug precursors. Satisfactory enantiomeric separation was obtained for 18 pairs of enantiomers including amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and its metabolites HMA (4-hydroxy-3-methoxyamphetamine) and HMMA (4-hydroxy-3-methoxy-methamphetamine), PMA (para-methoxyamphetamine), MDA ((±)- 3,4-methylenedioxyamphetamine) and mephedrone. The method was applied in a one week monitoring study of a large wastewater treatment plant in the UK. Most target drugs were found at quantifiable concentrations in analysed samples. Enantiomeric profiling revealed that amphetamine, methamphetamine and MDMA were found enriched with R-(-)-enantiomers, probably due to their stereoselective metabolism favouring S-(+)-enantiomers. MDA was either enriched with R-(-)- or S-(+)-enantiomer indicating that its presence might be due to either abuse of racemic MDA or abuse of racemic MDMA respectively. Non-racemic enantiomeric fractions were also observed in the case of HMMA and mephedrone suggesting enantioselective metabolism. To the authors' knowledge, this is the first time chiral separation and wastewater profiling of mephedrone, PMA, MDMA and its metabolites HMA and HMMA have been reported. PMID:26896918

  4. Current preclinical studies on neuroinflammation and changes in blood-brain barrier integrity by MDMA and methamphetamine.

    Science.gov (United States)

    O'Shea, Esther; Urrutia, Andrés; Green, A Richard; Colado, M Isabel

    2014-12-01

    The blood-brain barrier (BBB) is essential in the maintenance of brain homeostasis both by preserving normal brain functioning and also by protecting the brain from exposure to a range of potentially harmful substances. This review presents some of the evidence of BBB disruption following exposure to the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methamphetamine (METH), two drugs of abuse which are widely consumed recreationally by younger sectors of the population. Both MDMA and METH have been shown to produce disruption of the BBB as reflected by IgG extravasation and Evans Blue leakage. In particular, METH decreases the expression of basal lamina proteins associated with an increase in matrix metalloproteinase activity. These changes in BBB integrity appear to be related to MDMA-induced activation of the mitogen-activated protein kinase (MAPK) JNK1/2. The consequences of the disruption in the BBB by these two drugs remain to be established, but there is evidence in the literature that, at least in the case of METH, increased matrix metalloproteinase (MMP) activity may be related to increased behavioural sensitization and reward perhaps because of the modification of the passage of the drug into the CNS. In addition, the high incidence of AIDS-related neurologic disease in METH users may also be related to increased entry into the brain of virally derived neurotoxic products. This article is part of the Special Issue entitled 'CNS Stimulants'. PMID:24594477

  5. Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

    Science.gov (United States)

    Kohl, Randall Lee

    Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

  6. Association Study of Serine Racemase Gene with Methamphetamine Psychosis

    Science.gov (United States)

    Yokobayashi, E; Ujike, H; Kotaka, T; Okahisa, Y; Takaki, M; Kodama, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Kuroda, S

    2011-01-01

    Experimental studies have demonstrated that not only dopaminergic signaling but also glutamatergic/NMDA receptor signaling play indispensable roles in the development of methamphetamine psychosis. Our recent genetic studies provided evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1, and G72, which are involved in glutamate release and regulation of co-agonists for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine racemase converts l-serine to d-serine, which is an endogenous co-agonist for NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were proven to affect the transcription activity of SRR. Therefore, we examined these SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched controls. There was no significant association between methamphetamine psychosis and any SNP examined or between the disorder and haplotypes comprising the three SNPs. However, rs408067 was significantly associated with the prognosis for methamphetamine psychosis and multi-substance abuse status. The patients with C-positive genotypes (CC or CG) of rs408067 showed better prognosis of psychosis after therapy and less abuse of multiple substances than the patients with GG genotypes. Because the C allele of rs408067 reduces the expression of SRR, a lower d-serine level or reduced NMDA receptor activation may affect the prognosis of methamphetamine psychosis and multiple substance abuse. Our sample size is, however, not large enough to eliminate the possibility of a type I error, our findings must be confirmed by replicate studies with larger samples. PMID:21886585

  7. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    OpenAIRE

    Vo K; Neafsey PJ; Lin CA

    2015-01-01

    Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Signif...

  8. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    OpenAIRE

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of ...

  9. Pengaruh Timbal (Pb Terhadap Kadar MDA Serum Tikus Putih Jantan

    Directory of Open Access Journals (Sweden)

    Endrinaldi .

    2014-09-01

    Full Text Available AbstrakTimbal (Pb merupakan logam berat bersifat toksik yang konsentrasinya di lingkungan saat ini dipandang sebagai zat berbahaya. Pb dalam bentuk senyawa berasal dari pembakaran bahan bakar kendaraan bermotor, emisi industry dan dari penggunaan cat bangunan yang mengandung Pb. Toksisitas Pb menghambat enzim yang berperan sebagai antioksidan dan merusak sel hati.Tujuan studi ini adalah untuk melihat pengaruh timbal (Pb terhadap kadar malondialdehid (MDA tikus putih jantan. Desain penelitian ini adalah eksperimental menggunakan 25 ekor tikus putih jantan yang dibagi menjadi lima kelompok, yaitu kelompok kontrol, dan kelompok perlakuan dengan pemberian Pb asetat dengan dosis konsentrasi 5, 10, 20 dan 40 mg/kg BB selama 26 hari.Hasil penelitian menunjukkan terjadinya peningkatan rerata kadar MDA serum secara bermakna (p < 0,05, setelah pemberian Pb asetat selama 26 hari. Peningkatan kadar MDA secara bermakna terjadi antara kelompok kontrol dibandingkan dengan kelompok tikus yang diberi dosis 5, 10, 20 dan 40 mg/kg BB.Kesimpulan yang dapat diambil dari studi ini adalah bahwa pemberian Pb asetat meningkatkan kadar MDA serum tikus.Kata kunci: Pb asetat, MDAAbstractLead (Pb is atoxi cheavy metal concentrationsin the environment are now seenas a dangerous substance. Pb in the form of compounds derived from burningmotor vehicle fuel. Pb toxicityinhibitsan enzyme that acts as an antioxidant and liver cell damage.The purpose of this study was to observe the effect of lead (Pb on levels of malondialdehyde (MDA male whiterats. Experimental research design was used 25 white male rats were divided into five groups, namely the control group and the group treated with the administration of Pb acetate at a dose concentration of 5, 10, 20, and 40 mg / kg body weight for 26 days.The results showed an average increase in level of MDA, after administration of Pb acetate for 26 days were significantly (p <0.05. Increase in level of MDA of serum were significantly (p

  10. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  11. Treatment utilization and barriers to treatment: Results of a survey of dependent methamphetamine users

    Directory of Open Access Journals (Sweden)

    Lee Nicole K

    2011-02-01

    Full Text Available Abstract Background Australia has one of the highest rates of methamphetamine use in the world; however, treatment access for methamphetamine is comparatively low. This descriptive study aimed to identify patterns of treatment utilization and perceived barriers to accessing treatment among dependent methamphetamine users in the hope that such information will enable services to more appropriately respond to this group. Methods One hundred and twenty-six methamphetamine users who had a current or past history of methamphetamine dependence were interviewed about their experiences of, and perceived barriers to, treatment. Results Treatment utilization among methamphetamine users was reportedly low. One of the main reasons cited for not accessing treatment was that methamphetamine users did not perceive their drug use to be a problem (despite apparent levels of dependence. Self-detoxification with the use of other licit and illicit drugs was high among this group. Participants identified a lack of confidence in the ability of treatment services to address methamphetamine dependence and the 'opiate-centric' nature of treatment services as significant blocks to treatment entry. Suggestions for improvement by participants included operating specialist services for methamphetamine users, placing an emphasis on responsiveness and routinely involving case management services for this group. Discussion and Conclusions To improve service delivery, treatment services should reorient their services to better address the needs of methamphetamine users by making small changes such as specific opening times for methamphetamine users or using a dedicated space for methamphetamine treatment. Alternative options such as online treatments and specialist methamphetamine clinics should be considered for methamphetamine users.

  12. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, "dark net") as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ(9)-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated

  13. Neuropharmacology of new psychoactive substances (NPS: focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants

    Directory of Open Access Journals (Sweden)

    Cristina eMiliano

    2016-04-01

    Full Text Available New psychoactive substances (NPS are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, dark net as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments. The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%(WDR, 2014. Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues. Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of

  14. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, “dark net”) as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence

  15. [Study on the optimization methods of common-batch identification of amphetamine samples].

    Science.gov (United States)

    Zhang, Jianxin; Zhang, Daming

    2008-07-01

    The essay introduced the technology of amphetamine identification and its optimization method. Impurity profiling of amphetamine was analyzed by GC-MS. Identification of common-batch amphetamine samples could be successfully finished by the data transition and pre-treating of the peak areas. The analytical method was improved by optimizing the techniques of sample extraction, gas chromatograph, sample separation and detection. PMID:18839544

  16. Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

    OpenAIRE

    Ersche, Karen D.; Clark, Luke; London, Mervyn; Robbins, Trevor W.; Sahakian, Barbara J.

    2006-01-01

    Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants ...

  17. Development of a harmonised method for the profiling of amphetamines VI: Evaluation of methods for comparison of amphetamine.

    Science.gov (United States)

    Andersson, Kjell; Lock, Eric; Jalava, Kaisa; Huizer, Henk; Jonson, Sten; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki; Dujourdy, Laurence; Dahlén, Johan

    2007-06-14

    Amphetamine samples were analysed by gas chromatography-mass spectrometry (GC-MS), and the peak areas of 33 target compounds were transformed by applying various pretreatment techniques. The objective was to optimise the ability of a number of distance metrics to establish links between samples of amphetamine originating from the same batch (henceforth referred to as linked distances). Furthermore, partial least squares discriminant analysis (PLS-DA) was used to evaluate the effects of various pretreatment methods on separation of amphetamine batches synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The most efficient way to pretreat GC-MS data varied for the different distance metrics, although best results were obtained when data were normalised to the sum of peak areas, and either the fourth root or a logarithm was applied to the normalised data. When pretreating normalised data by fourth root transformation, Pearson correlation was the distance metric that was most successful at finding linked samples. Normalisation and the use of fourth root also represented the best method of pretreating data when employing PLS-DA to separate samples synthesised by different routes. To achieve a faster and more user-friendly procedure for evaluating chromatograms, experiments were performed in which the number of target compounds used to compare samples was reduced. The effect of each compound that was removed was studied by applying PLS-DA and by using Pearson correlation to calculate linked distances as well as unlinked distances (between samples from different batches of amphetamine). Considering both links between samples from the same batch and separation of samples synthesised by different routes, the best results were obtained with the data set comprising 26 compounds. Finally, it was found that the profiling method developed in this work was superior to an existing technique with respect to separating linked

  18. Lung counting: summing techniques to reduce the MDA.

    Science.gov (United States)

    Kramer, Gary H; Hauck, Barry M; Allen, Steve A; Dantas, Bernardo M; Dantas, Ana Letícia A; Azeredo, Adelaide M G F

    2003-08-01

    The new dose limits recently adopted in Canada (and elsewhere in the world) have made it more difficult to detect some radionuclides by in vivo counting at the average dose limit of 20 mSv. This is particularly true for natural uranium. Two techniques have been developed by the Human Monitoring Laboratory to reduce the Minimum Detectable Activity (MDA) for the lung counting of this nuclide. The first technique, developed in collaboration with Cameco, is to either sum sequential counts of an individual or to sum spectra of a group of workers similarly occupationally exposed. This technique offers a reduction in the MDA of up to a factor of three. The second technique, developed in collaboration with CNEN, involves the summing of photopeaks within an individual spectrum and offers a reduction in the MDA of up to a factor of two. PMID:12938970

  19. Automated code generation support for BI with MDA TALISMAN

    OpenAIRE

    Óscar Sanjuan-Martínez; B. Cristina Pelayo G-Bustelo; Elías Palacios-González; Héctor Fernández-Fernández; Vicente García-Díaz; Juan Manuel Cueva Lovelle

    2009-01-01

    Model Driven Engineering (MDE) is gaining ever more strength due to the fact that with MDE the software development can be much more productive and this is the way to go closer to real software industrialization. With MDA TALISMAN, we have succeeded in creating complex software solutions for food traceability adapted to different customers, ready to be deployed. We rely on the approach to MDE most extended at present, MDA (Model-Driven Development) but as we shall see, we also use the main pi...

  20. Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

    International Nuclear Information System (INIS)

    Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intact rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion

  1. Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics.

    Science.gov (United States)

    Mori, Tomohisa; Iwase, Yoshiyuki; Murata, Asami; Iwata, Noriyuki; Suzuki, Tsutomu

    2016-06-01

    While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. PMID:26992824

  2. Quantitative Silylation Speciations of Primary Phenylalkyl Amines, Including Amphetamine and 3,4-Methylenedioxyamphetamine Prior to Their Analysis by GC/MS.

    Science.gov (United States)

    Molnár, Borbála; Fodor, Blanka; Boldizsár, Imre; Molnár-Perl, Ibolya

    2015-10-20

    A novel, quantitative trimethylsilylation approach derivatizing 11 primary phenylalkyl amines (PPAAs), including amphetamine (A) and 3,4-methylenedioxyamphetamine (MDA), was noted. Triggering the fully derivatized ditrimethylsilyl (diTMS) species with the N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) reagent, a new principle was recognized followed by GC/MS. In the course of method optimization, the complementary impact of solvents (acetonitrile, ACN; ethyl acetate, ETAC; pyridine, PYR) and catalysts (trimethylchlorosilane, TMCS; trimethyliodosilane, TMIS) was studied: the role of solvent and catalyst proved to be equally crucial. Optimum, proportional, huge responses were obtained with the MSTFA/PYR = 2/1-9/1 (v/v) reagent applying catalysts; A and MDA needed the TMIS, while the rest of PPAAs provided the diTMS products also with TMCS. Similar to derivatives generated with hexamethyldisilazane and perfluorocarboxylic acid (HMDS and PFCA) ( Molnár et al. Anal. Chem. 2015 , 87 , 848 - 852 ), the fully silylated PPAAs offer several advantages. Both of our methods save time and cost by allowing for direct injection of analytes into the column; this is in stark contrast with the requirement to evaporate acid anhydrides by nitrogen prior to their injection. Efficiences of the novel catalyzed trimethylsilylation (MSTFA) and our recently introduced (now, for A and MDA extended) acylation principle were contrasted. Catalyzed trimethylsilylation led to diTMS derivatives resulting in on average a 1.7 times larger response compared to the corresponding acylated species. Catalyzed trimethylsilylation of PPAAs, A, and MDA were characterized with retention, mass fragmentation, and analytical performance properties (R(2), LOQ values). The practical utility of ditrimethylsilyation was shown by analyzing A in urine and mescaline (MSC) in cactus samples. PMID:26412806

  3. The meth brain: methamphetamines alter brain functions via NMDA receptors

    Czech Academy of Sciences Publication Activity Database

    Proft, Juliane; Weiss, Norbert

    2015-01-01

    Roč. 34, č. 1 (2015), s. 1-3. ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S Institutional support: RVO:61388963 Keywords : ion channel * methamphetamine * piriform cortex * NMDA receptor * AMPA receptor Subject RIV: CE - Biochemistry Impact factor: 1.173, year: 2014

  4. Correlation between malondialdehyde (MDA and uric acid levels in preeclampsia

    Directory of Open Access Journals (Sweden)

    T. Sharmila Krishna

    2015-06-01

    Conclusion: Serum MDA and uric acid may be included as additional markers for screening and progression of preeclampsia, thereby helpful in effectively treating the condition at an early stage. [Int J Res Med Sci 2015; 3(6.000: 1443-1445

  5. A microbial detection array (MDA for viral and bacterial detection

    Directory of Open Access Journals (Sweden)

    McLoughlin Kevin S

    2010-11-01

    Full Text Available Abstract Background Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced. Methods We designed a pan-Microbial Detection Array (MDA to detect all known viruses (including phages, bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence. Results In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR. Conclusions The MDA can be used to identify the suite of viruses and bacteria present in complex samples.

  6. Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class

    OpenAIRE

    Lewin, Anita H.; Miller, Gregory M.; Gilmour, Brian

    2011-01-01

    The demonstrated ability of amphetamine to functionally activate the rat trace amine associated receptor 1 (rTAAR1) and the subsequent reports of amphetamine activation of TAAR1 in rhesus monkey mouse, human, and human-rat chimeric TAAR1-expressing cell lines has led to speculation as to the role of this receptor in the central nervous system (CNS) responses associated with amphetamine and its analogs. The agonist potencies of ten pairs of enantiomeric amphetamines, including several with kno...

  7. Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine

    OpenAIRE

    Bredholt, Therese; Ersvær, Elisabeth; Erikstein, Bjarte Skoe; Sulen, André; Reikvam, Håkon; Aarstad, Hans Jørgen; Johannessen, Anne Christine; Vintermyr, Olav Karsten; Bruserud, Øystein; Gjertsen, Bjørn Tore

    2013-01-01

    Background: Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone d...

  8. Amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine.

    Directory of Open Access Journals (Sweden)

    Dan P Covey

    Full Text Available Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.

  9. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice 1,2,3

    OpenAIRE

    Storey, Granville P; Gonzalez-Fernandez, Gabriel; Bamford, Ian J.; Hur, Matthew; McKinley, Jonathan W.; Heimbigner, Lauren; Minasyan, Ani; Walwyn, Wendy M.; Bamford, Nigel S.

    2016-01-01

    Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promo...

  10. The relationship of quality and price of the psychostimulants cocaine and amphetamine with health care outcomes

    NARCIS (Netherlands)

    T.M. Brunt; M. van Laar; R.J.M. Niesink; W. van den Brink

    2010-01-01

    A major component of the illicit drug market can be subcategorized as the psychostimulant drug market, with cocaine and amphetamine as popular constituents. In The Netherlands, an increase in both health care outcomes addiction treatment and hospital admissions was noted for both amphetamine and coc

  11. Functional magnetic resonance imaging investigation of the amphetamine sensitization model of schizophrenia in healthy male volunteers

    OpenAIRE

    O'Daly, Owen G; Joyce, Daniel; Stephan, Klaas E.; Murray, Robin M G; Shergill, Sukhwinder S.

    2011-01-01

    These transient load-dependent abnormalities of frontal and temporal activity induced by amphetamine sensitization support neuroimaging findings in schizophrenic patients, implying that amphetamine sensitization may help to bridge pathophysiological theories of schizophrenia that focus on pharmacological (dopaminergic) and cognitive mechanisms, respectively.

  12. Acute Demyelination in a Person with Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Serge Weis

    2011-01-01

    Full Text Available We report the case of a 31-year-old woman, admitted to the hospital for chest pain, dying a few days later from septic multiorgan failure, and showing at autopsy foci of acute demyelination in the occipital lobe. Gas chromatography/mass spectrometry analysis revealed the presence of amphetamine in the demyelinated area, which might be considered as the pathogenic agent, since other causes for demyelination could be excluded. This case represents the first report showing a demyelinating process due to a street drug.

  13. Risk factors of schizophrenia development in patients with amphetamines dependence and psychosis (amphetamine-induced psychosis and schizophrenia, and without psychosis [Czynniki ryzyka rozwoju schizofrenii u pacjentów uzależnionych od amfetaminy i jej pochodnych z psychozą (pointoksykacyjną lub schizofrenią oraz bez psychozy

    Directory of Open Access Journals (Sweden)

    Rabe-Jabłońska, Jolanta

    2012-08-01

    Full Text Available Aim. Amphetamine and its derivates can induce, usually after many intoxications, schizophrenia-like psychosis. These disorders appeared only in part patients with amphetamine dependence. Aim of the study was to establish prevalence of selective risk factors of schizophrenia development in amphetamine users: 1 with amphetamine – induced schizophrenia – like psychosis, 2 with schizophrenia, and 2 without psychotic symptoms. Material. In the study 3 groups of subjects were included: 30 amphetamine users with amphetamine induced schizophrenia – like psychosis, 30 amphetamine users with schizophrenia and 30 amphetamine users without psychotic symptoms (37 female and 53 male in mean age=17.78 years . Methods. Amphetamine dependence, schizophrenia and schizophrenia-like psychosis induced amphetamine were diagnosed according to ICD-10 criteria after at least 1 year of amphetamine abstinence. The next procedure was used: 1 Structured interview with subjects and their mothers/caregivers regarding: a amphetamines use (duration of abuse, doses of psychoactive substance b family history of psychosis (especially schizophrenia 2 The Questionnaire of Child Development for assessment of prevalence of selected risk factors of schizophrenia development 3 The Premorbid Adjustment Scale (Cannon – Spoor for assessment of premorbid psychosocial functioning in thelast year before psychosis. Conclusions. Amphetamines users with amphetamine-induced psychosis were more similar in prevalence of selective risk factors of schizophrenia development to subjects with schizophrenia and amphetamine dependence than to amphetamine users without psychosis. Amphetamine-induced psychosis developed more frequently in amphetamine users who used higher amphetamine doses and with familial history of psychosis.

  14. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Science.gov (United States)

    2010-10-01

    ... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... results involving marijuana, cocaine, amphetamines, or PCP? (a) As the MRO, you must verify a confirmed positive test result for marijuana, cocaine, amphetamines, and/or PCP unless the employee presents...

  15. Methamphetamine: An update on epidemiology, pharmacology, clinical phenomenology, and treatment literature

    OpenAIRE

    Courtney, KE; Ray, LA

    2014-01-01

    Background: Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods: We first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and a...

  16. A Study of the Phenomenology of Psychosis Induced by Methamphetamine: A Preliminary Research

    OpenAIRE

    Ghaffari-Nejad, Alireza; Ziaadini, Hassan; Saffari-Zadeha, Samaneh; Kheradmand, Ali; Pouya, Fatemeh

    2014-01-01

    Background Psychotic disorder due to industrial drug, such as methamphetamine addiction, is one of the important causes for referral to psychiatric hospital. Psychotic symptoms in these patients are varied. A group of researchers believe that methamphetamine-induced psychosis is completely similar to schizophrenia. Others believe that at least some cases of permanent psychotic clinical manifestation due to methamphetamine abuse are different from schizophrenia. In the present study, the exist...

  17. Methamphetamine: An update on epidemiology, pharmacology, clinical phenomenology, and treatment literature

    OpenAIRE

    Courtney, KE; Ray, LA

    2014-01-01

    © 2014 Elsevier Ireland Ltd. Background: Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods: We first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prev...

  18. Bupropion differentially impacts acquisition of methamphetamine self-administration and sucrose-maintained behavior

    OpenAIRE

    Reichel, Carmela M.; Linkugel, Jessica D.; Bevins, Rick A.

    2008-01-01

    Bupropion reduces the subjective effects and cue-induced craving for methamphetamine in humans. Given these effects of bupropion on methamphetamine in humans and its widespread clinical use, a preclinical model of drug-taking was used to determine if pretreatment with bupropion would alter the acquisition of methamphetamine self-administration. During acquisition, rats were given saline or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8 days, each response on the...

  19. At the Borders, on the Edge: Use of Injected Methamphetamine in Tijuana and Ciudad Juarez, Mexico

    OpenAIRE

    Patricia, Case; Ramos, Rebeca; Brouwer, Kimberly C.; Firestone-Cruz, Michelle; Pollini, Robin A.; Strathdee, Steffanie A; Fraga, Miguel A.; PATTERSON, THOMAS L.

    2008-01-01

    Injection drug use is of increasing concern along the US–Mexico border where Tijuana and Ciudad (Cd.) Juarez are located. Methamphetamine has long been manufactured and trafficked through Mexico, with low rates of use within Mexico. With methamphetamine use now considered epidemic in the United States, and with associated individual and community harms such as HIV, STDs, domestic violence and crime, there is concern that rates of methamphetamine in the Northwestern border regions of Mexico ma...

  20. During-treatment Outcomes among Female Methamphetamine-Using Offenders in Prison-based Treatments

    OpenAIRE

    Rowan-Szal, Grace A.; Joe, George W.; SIMPSON, D. DWAYNE; Greener, Jack M.; Vance, Jerry

    2009-01-01

    An increasingly important treatment group is the expanding population of methamphetamine-using female offenders. This study focused on women methamphetamine-using offenders (n = 359) who were treated either in a modified TC program (CLIFF-TC: n = 234) designed for non-violent offenders with significant impairment from methamphetamine use or the standard “outpatient” treatment (OTP: n = 125). All participants were assessed on motivation, psychological and social functioning, and treatment enga...

  1. Decontamination of clothing and building materials associated with the clandestine production of methamphetamine.

    Science.gov (United States)

    Serrano, Kate A; Martyny, John W; Kofford, Shalece; Contreras, John R; Van Dyke, Mike V

    2012-01-01

    This study was designed to determine how easily methamphetamine can be removed from clothing and building materials, utilizing different cleaning materials and methods. The study also addressed the penetration of methamphetamine into drywall and the ability of paints to encapsulate the methamphetamine on drywall. Clothing and building materials were contaminated in a stainless steel chamber by aerosolizing methamphetamine in a beaker heater. The amount of methamphetamine surface contamination was determined by sampling a grid pattern on the material prior to attempting to clean the materials. After cleaning, the materials were again sampled, and the degree of decontamination noted. We found that household clothing and response gear worn by first responders was easily decontaminated using a household detergent in a household washing machine. A single wash removed over 95% of the methamphetamine from these materials. The study also indicated that methamphetamine-contaminated, smooth non-porous surfaces can be easily cleaned to below detectable levels using only mild cleaners. More porous surfaces such as plywood and drywall were unlikely to be decontaminated to below regulatory levels even with three washes using a mild cleaner. This may be due to methamphetamine penetration into the paint on these surfaces. Evaluation of methamphetamine contamination on drywall indicated that approximately 40% of the methamphetamine was removed using a wipe, while another 60% remained in the paint layer. Stronger cleaners such as those with active ingredients including sodium hypochlorite or quaternary ammonia and commercial decontamination agents were more effective than mild detergent-based cleaners and may reduce methamphetamine contamination to below regulatory levels. Results from the encapsulation studies indicate that sprayed on oil-based paint will encapsulate methamphetamine on drywall and plywood surfaces up to 4.5 months, while latex paints were less effective. PMID

  2. Theories of Addiction: Methamphetamine Users’ Explanations for Continuing Drug Use and Relapse

    OpenAIRE

    Newton, Thomas F.; De La Garza, Richard; Kalechstein, Ari D.; Tziortzis, Desey; Jacobsen, Caitlin A.

    2009-01-01

    A variety of preclinical models have been constructed to emphasize unique aspects of addiction-like behavior. These include Negative Reinforcement (“Pain Avoidance”), Positive Reinforcement (“Pleasure Seeking”), Incentive Salience (“Craving”), Stimulus Response Learning (“Habits”), and Inhibitory Control Dysfunction (“Impulsivity”). We used a survey to better understand why methamphetamine-dependent research volunteers (N = 73) continue to use methamphetamine, or relapse to methamphetamine us...

  3. Depression, craving and amphetamine use: Findings from a study on the efficacy of extended release naltrexone for treating amphetamine dependence in Iceland

    OpenAIRE

    Krantz, Sofia Birgitta, 1983-

    2014-01-01

    Amphetamine dependence is a serious, growing problem around the world and Iceland is no exception. Neuropsychological theory, animal studies and a few clinical studies suggest that naltrexone might be beneficial in the treatment of amphetamine dependence. However, depression might affect outcomes in treatment of substance dependence. In the current study, 32 participants were followed six months after completing a 24 week randomized, placebo-controlled, double-blind clinical trial testing the...

  4. Ab Initio Calculations and Raman and SERS Spectral Analyses of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Nørbygaard, Thomas; White, Peter C.;

    2011-01-01

    For the first time, the differences between the spectra of amphetamine and amphetamine-H+ and between different conformers are thoroughly studied by ab initio model calculations, and Raman and surface-enhanced Raman spectroscopy (SERS) spectra are measured for different species of amphetamine....... The spectra of amphetamine and amphetamine-H+ sampleswere obtained and assigned according to a comparison of the experimental spectra and the ab initio MO calculations, performed using the Gaussian 03W program (Gaussian, Inc., Pittsburgh, PA). The analyses were based on complete geometry minimization...... with internal bonds (sulfates, hydrogen phosphates, etc.) need to be taken into account when employing these spectra for identification purposes. These results also show how Raman spectroscopy can assist the forensic community in drug profiling studies. Furthermore, because their spectra are different...

  5. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  6. Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

    International Nuclear Information System (INIS)

    We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation

  7. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia. PMID:26965573

  8. Radiohalogenated amphetamine analogs for blood flow and serotonin receptor studies

    International Nuclear Information System (INIS)

    The 4-radiohalo-2,5-dimethoxyamphetamine hallucinogens were first utilized in the 1970's for cerebral imaging studies by T. Sargent and A.T. Shulgin. Subsequently, other radioiodinated amphetamine analogs and distantly related diamines have been synthesized and used for clinical single photon studies of cerebral blood flow. A generator system for the production of the short-lived positron emitter 122I (3.5 min half-life) was developed, and several amphetamine and diamine compounds have been labeled with 122I for positron emission tomography (PET) studies of regional cerebral blood flow in animals and humans. The short half-life of 122I requires that the radiochemical syntheses be rapid and efficient. Both electrophilic deprotonation and demetallation reactions have been utilized to achieve this goal. Recently, there has been considerable evidence that some 4-halo-2,5-dimethoxyamphetamine analogs are highly specific serotonin receptor agonists. This has lead to the speculation that the binding of these agonists to a serotonin 5-HT2 receptor sub-type may be involved in hallucinogenesis. In an effort to help elucidate the role of these agents, several radioiodinated and radiobrominated 4-halo-2,5-dimethoxyamphetamine analogs have been synthesized for in vitro binding studies. Studies examining the in vivo interaction of these analogs with serotonin 5-HT2 receptors have been initiated with the synthesis of 4-(18F)fluoroalkyl-2,5-dimethoxyamphetamines

  9. The Comparison of Attentional Bias and Difficulty of Emotional States Regulation and Their Correlation with Craving Severity in Drug Abuser Methamphetamines and Crack

    Directory of Open Access Journals (Sweden)

    Raheleh Haghiaght

    2014-08-01

    Full Text Available Background: Today, within creased substance, type of substance used has changed. Therefore, drug abuse in population of crack to the stimulant drugs (amphetamine particularly crystal is expanding and increasing. Therefore, the purpose of the present study was the comparison of attentional bias and difficulty of emotional states regulation and their correlation with craving severity in drug abuser methamphetamines and crack. Materials and Methods: Type of research was descriptive analytical correlation. Population was total of users with methamphetamines and crack in summer and fall 2011 at the city of Isfahan, and 34 users with crystal with daily at least one year were selected on the basis of the snow ball sampling and 31 users with crack with daily at least one year were selected on the basis of the sample sampling. The difficulties emotion regulation scale (DERS, Stroop test and OCDUS were used as the outcome measures. For findings used of descriptive statistics and multivariate analysis of covariance (MANCOVA and regression analysis were used. Results: The results of analysis of variance showed that between drug abuser crystal and crack significantly differed of attentional bias and difficulty of emotional states regulation. The greatest differences to components of a lack of transparency, lack of emotional awareness, limit emotional states regulation strategies and of emotional responses. But, only the variable non-acceptance negative emotional of subscale of the difficulty of emotional states regulation was able to craving (as an important indicator of durable use substance in of both crack and crystal predicted. This variable is only 13% of the variance craving in drug abuser crack and crystal can be explained. Other findings showed that although there is no difference between the two groups in the intensity of craving, but attentional bias among drug abuser crack and crystal was a significant difference. Conclusion: Overall, can be said

  10. Correlation between malondialdehyde (MDA) and uric acid levels in preeclampsia

    OpenAIRE

    T. Sharmila Krishna; E.Venkata Rao; Sowjanya, B.; A. Saseekala; Naidu, J.N.

    2015-01-01

    Background: Hypertensive disorders of human pregnancy, such as preeclampsia, complicates a sizeable percentage of all pregnancies, need its early indication and warning. The aim of present study was to determine the association between lipid peroxidation product, serum malondialdehyde (MDA) and serum uric acid levels in preeclampsia and find out any association between these two parameters in preeclampsia. Methods: Thirty preeclampsia and thirty gestational age matched normotensive pregna...

  11. Designing secure data warehouses by using MDA and QVT

    OpenAIRE

    Soler, Emilio; Trujillo Mondéjar, Juan Carlos; Blanco Bueno, Carlos; Fernández-Medina Patón, Eduardo

    2009-01-01

    The Data Warehouse (DW) design is based on multidimensional (MD) modeling which structures information into facts and dimensions. Due to the confidentiality of the data that it stores, it is crucial to specify security and audit measures from the early stages of design and to enforce them throughout the lifecycle. Moreover, the standard framework for software development, Model Driven Architecture (MDA), allows us to define transformations between models by proposing Query/View/Transformation...

  12. 360 degree port MDA - a strategy to improve port security

    OpenAIRE

    Leary, Timothy P.

    2006-01-01

    CHDS State/Local Our national security and prosperity depend in part on secure and competitive ports. Effective public and private sector collaboration is needed in a world with myriad security challenges and fierce global competition. Although steps have been taken in the years since 9/11 to realize these twin goals, much more needs to be done. The current maritime domain awareness (MDA) paradigm needs to be expanded to provide comprehensive awareness of intermodal operations in our ports...

  13. UV Decontamination of MDA Reagents for Single Cell Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Janey; Tighe, Damon; Sczyrba, Alexander; Malmatrom, Rex; Clingenpeel, Scott; Malfatti, Stephanie; Rinke, Christian; Wang, Zhong; Stepanauskas, Ramunas; Cheng, Jan-Fang; Woyke, Tanja

    2011-03-18

    Single cell genomics, the amplification and sequencing of genomes from single cells, can provide a glimpse into the genetic make-up and thus life style of the vast majority of uncultured microbial cells, making it an immensely powerful and increasingly popular tool. This is accomplished by use of multiple displacement amplification (MDA), which can generate billions of copies of a single bacterial genome producing microgram-range DNA required for shotgun sequencing. Here, we address a key challenge inherent to this approach and propose a solution for the improved recovery of single cell genomes. While DNA-free reagents for the amplification of a single cell genome are a prerequisite for successful single cell sequencing and analysis, DNA contamination has been detected in various reagents, which poses a considerable challenge. Our study demonstrates the effect of UV irradiation in efficient elimination of exogenous contaminant DNA found in MDA reagents, while maintaining Phi29 activity. Consequently, we also find that increased UV exposure to Phi29 does not adversely affect genome coverage of MDA amplified single cells. While additional challenges in single cell genomics remain to be resolved, the proposed methodology is relatively quick and simple and we believe that its application will be of high value for future single cell sequencing projects.

  14. Enhanced upregulation of CRH mRNA expression in the nucleus accumbens of male rats after a second injection of methamphetamine given thirty days later.

    Directory of Open Access Journals (Sweden)

    Jean Lud Cadet

    Full Text Available Methamphetamine (METH is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg on transcriptional effects of a second METH (2.5 mg/kg injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS or METH-challenged (SM; and METH-pretreated followed by saline-challenged (MS or METH-challenged (MM. Microarray analyses revealed that METH (2.5 mg/kg produced acute changes (1.8-fold; P<0.01 in the expression of 412 (352 upregulated, 60 down-regulated transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh, oxytocin (Oxt, and vasopressin (Avp that were upregulated. Injection of METH (10 mg/kg altered the expression of 503 (338 upregulated, 165 down-regulated transcripts measured one month later (MS group. These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug.

  15. Aggregate versus day level association between methamphetamine use and HIV medication non-adherence among gay and bisexual men

    OpenAIRE

    Parsons, Jeffrey T.; Kowalczyk, William; Botsko, MICHAEL; Tomassilli, Julia; Golub, Sarit A.

    2013-01-01

    Methamphetamine use is associated with HIV infection, especially among gay and bisexual men. Methamphetamine use contributes to disease progression both directly, by increasing viral load and damaging the immune system, and indirectly, by decreasing medication adherence. Research examining the association of methamphetamine use and non-adherence has traditionally compared groups of users and nonusers on adherence, compared methamphetamine use between participants above or below some threshold...

  16. Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

    Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

  17. Methamphetamine Inhibits HIV-1 Replication in CD4+ T Cells by Modulating Anti–HIV-1 miRNA Expression

    OpenAIRE

    Mantri, Chinmay K.; Mantri, Jyoti V.; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamph...

  18. SIMULATING BRAIN REACTION TO METHAMPHETAMINE REGARDING CONSUMER PERSONALITY

    Directory of Open Access Journals (Sweden)

    Maryam Keyvanara

    2015-07-01

    Full Text Available Addiction, as a nervous disease, can be analysed using mathematical modelling and computer simulations. In this paper, we use an existing mathematical model to predict and simulate human brain response to the consumption of a single dose of methamphetamine. The model is implemented and coded in Matlab. Three types of personalities including introverts, ambiverts and extroverts are studied. The parameters of the mathematical model are calibrated and optimized, according to psychological theories, using a real coded genetic algorithm. The simulations show significant correlation between people response to methamphetamine abuse and their personality. They also show that one of the causes of tendency to stimulants roots in consumers personality traits. The results can be used as a tool for reducing attitude towards addiction

  19. Physical Victimization of Rural Methamphetamine and Cocaine Users

    Science.gov (United States)

    Kramer, Teresa L.; Borders, Tyrone F.; Tripathi, Shanti; Lynch, Christian; Leukefeld, Carl; Falck, Russel S.; Carlson, Robert G.; Booth, Brenda M.

    2012-01-01

    Substance use and physical violence often co-occur, but little has been published on the correlates associated with receipt of partner versus non-partner physical violence for rural users of methamphetamine and/or cocaine. In this study, participants’ substance use, depression and past-year physical victimization were assessed. In separate logistic regression models, received partner violence in females was associated with age; alcohol, cocaine and methamphetamine abuse/dependence; and number of drugs used in the past six months. In males, received non-partner violence was associated with age, cocaine abuse/dependence and being Caucasian. Findings suggest a relationship between stimulant use and received violence among rural substance users and a need for victimization screenings in settings where such individuals seek health care. PMID:22455188

  20. Swimming exercise attenuates psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats

    Science.gov (United States)

    Damghani, Fatemeh; Bigdeli, Imanollah; Miladi-Gorji, Hossein; Fadaei, Atefeh

    2016-01-01

    Objective(s): This study evaluated the effect of swimming exercise during spontaneous methamphetamine (METH) withdrawal on the anxiety, depression, obsessive-compulsive disorder (OCD) and voluntary METH consumption in METH-dependent rats. Materials and Methods: Male Wistar rats were repeatedly administered with bi-daily doses of METH (2 mg/kg, subcutaneous) over a period of 14 days. Exercised rats were submitted to swimming sessions (45 min/day, five days per week, for 14 days) during spontaneous METH-withdrawal. Then, all animals were tested for the assessment of anxiety by using the elevated plus-maze (EPM), the grooming behaviors (OCD), and depression using forced swimming test (FST) and voluntary METH consumption using a two-bottle choice (TBC) paradigm for the assessment of craving. Results: The results showed that the swimmer METH-withdrawn rats exhibited an increase in EPM open arm time and entries and a reduction of immobility and grooming behaviors compared with the sedentary METH groups. Also, voluntary METH consumption was less in the swimmer METH-withdrawn rats than the sedentary METH groups throughout 5–8 days. Conclusion: This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH. PMID:27482339

  1. Methamphetamine and the hypothalamic-pituitary-adrenal axis

    OpenAIRE

    Zuloaga, Damian G.; Jacosbskind, Jason S.; Raber, Jacob

    2015-01-01

    Psychostimulants such as methamphetamine (MA) induce significant alterations in the function of the hypothalamic-pituitary-adrenal (HPA) axis. These changes in HPA axis function are associated with altered stress-related behaviors and might contribute to addictive processes such as relapse. In this mini-review we discuss acute and chronic effects of MA (adult and developmental exposure) on the HPA axis, including effects on HPA axis associated genes/proteins, brain regions, and behaviors such...

  2. Methamphetamine Self-Administration Acutely Decreases Monoaminergic Transporter Function

    OpenAIRE

    McFadden, Lisa M.; Stout, Kristen A.; Vieira-Brock, Paula L.; Allen, Scott C.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.; Fleckenstein, Annette E.

    2011-01-01

    Numerous pre-clinical studies have demonstrated that non-contingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of non-contingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute i...

  3. Sex differences in social interaction of methamphetamine-treated rats

    Czech Academy of Sciences Publication Activity Database

    Šlamberová, R.; Mikulecká, Anna; Pometlová, M.; Schutová, B.; Hrubá, L.; Deykun, K.

    2011-01-01

    Roč. 22, č. 7 (2011), s. 617-623. ISSN 0955-8810 R&D Projects: GA MŠk(CZ) 1M0517 Grant ostatní: GA ČR(CZ) GAP303/10/0580 Institutional research plan: CEZ:AV0Z50110509 Keywords : estrogen * methamphetamine * rat * sex difference * social behavior * testosterone Subject RIV: FH - Neurology Impact factor: 2.720, year: 2011

  4. Mechanisms Underlying Methamphetamine-Induced Dopamine Transporter Complex Formation

    OpenAIRE

    Hadlock, Gregory C.; Baucum, Anthony J.; King, Jill L.; Horner, Kristen A.; Cook, Glen A.; Gibb, James W.; Wilkins, Diana G; Hanson, Glen R.; Fleckenstein, Annette E.

    2009-01-01

    Repeated, high-dose methamphetamine (METH) administrations cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. In rats, this treatment also causes the formation of high-molecular mass (greater than approximately 120 kDa) dopamine transporter (DAT)-associated complexes, the loss of DAT monomer immunoreactivity, and a decrease in DAT function, as assessed in striatal synaptosomes prepared 24 h after METH treatment. The present study extends ...

  5. Methamphetamine residue dermal transfer efficiencies from household surfaces.

    Science.gov (United States)

    Van Dyke, Mike; Martyny, John W; Serrano, Kate A

    2014-01-01

    Methamphetamine contamination from illegal production operations poses a potential health concern for emergency responders, child protective services, law enforcement, and children living in contaminated structures. The objective of this study was to evaluate dermal transfer efficiencies of methamphetamine from contaminated household surfaces. These transfer efficiencies are lacking for methamphetamine, and would be beneficial for use in exposure models. Surfaces were contaminated using a simulated smoking method in a stainless steel chamber. Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer efficiencies were obtained using cotton gloves for two hand conditions, dry or saliva moistened (wet). In addition, three contact scenarios were evaluated for both hand conditions: one, two, or three contacts with contaminated surfaces. Dermal transfer efficiencies were calculated for both hand conditions and used as inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS-Multimedia, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, N.C.). Results of this study showed that average dermal transfer efficiencies of methamphetamine ranged from 11% for dry hands to 26% for wet hands. There was a significantly higher wet transfer as compared to dry transfer for all surfaces. For wet hands, dermal transfer depended on surface type with higher transfer from carpet and linoleum as compared to drywall. Based on our estimates of dermal transfer efficiency, a surface contamination clearance level of 1.5 μg/100 cm(2) may not ensure absorbed doses remain below the level associated with adverse health effects in all cases. Additional dermal transfer studies should be performed using skin surrogates that may better predict actual skin transfer. PMID:24579754

  6. Risk factors for methamphetamine use in youth: a systematic review

    OpenAIRE

    Russell, Kelly; Dryden, Donna M.; Liang, Yuanyuan; Friesen, Carol; O'Gorman, Kathleen; Durec, Tamara; Wild, T. Cameron; Klassen, Terry P

    2008-01-01

    Background Methamphetamine (MA) is a potent stimulant that is readily available. Its effects are similar to cocaine, but the drug has a profile associated with increased acute and chronic toxicities. The objective of this systematic review was to identify and synthesize literature on risk factors that are associated with MA use among youth. More than 40 electronic databases, websites, and key journals/meeting abstracts were searched. We included studies that compared children and adolescents ...

  7. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

    Directory of Open Access Journals (Sweden)

    Neema Yazdani

    2015-12-01

    Full Text Available Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1 and RUN and FYVE domain-containing 1 (Rufy1. Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2, a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15. Transcription activator-like effector nucleases (TALENs-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for

  8. SIMULATING BRAIN REACTION TO METHAMPHETAMINE REGARDING CONSUMER PERSONALITY

    OpenAIRE

    Maryam Keyvanara; Seyed Amirhassan Monadjemi

    2015-01-01

    Addiction, as a nervous disease, can be analysed using mathematical modelling and computer simulations. In this paper, we use an existing mathematical model to predict and simulate human brain response to the consumption of a single dose of methamphetamine. The model is implemented and coded in Matlab. Three types of personalities including introverts, ambiverts and extroverts are studied. The parameters of the mathematical model are calibrated and optimized, according to psychological theori...

  9. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-12-01

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), liver (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  10. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    International Nuclear Information System (INIS)

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with (11C)d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of (11C)d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  11. Partial MHC/neuroantigen peptide constructs: a potential neuroimmune-based treatment for methamphetamine addiction.

    Directory of Open Access Journals (Sweden)

    Jennifer M Loftis

    Full Text Available Relapse rates following current methamphetamine abuse treatments are very high (∼40-60%, and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-A(b/mMOG-35-55, in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.. Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2 levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments.

  12. The Effects of Methamphetamine Self-Administration on Cortical Monoaminergic Deficits Induced by Subsequent High-Dose Methamphetamine Administrations

    OpenAIRE

    McFadden, Lisa M.; Hanson, Glen R.; Fleckenstein, Annette E.

    2013-01-01

    Preclinical models suggest that repeated high-dose methamphetamine (METH) exposures, administered in a “binge-like” pattern, acutely decrease norepinephrine (NE), and acutely and persistently decrease serotonin (5-hydroxytryptamine; 5HT) content in the frontal cortex. However, the impact of METH self-administration on this region is unknown. Because of the importance of the monoaminergic neurons in the frontal cortex to a variety of cognitive and addictive processes, effects of METH self-admi...

  13. Methamphetamine Self-Administration Causes Persistent Striatal Dopaminergic Alterations and Mitigates the Deficits Caused by a Subsequent Methamphetamine Exposure

    OpenAIRE

    McFadden, Lisa M.; Hadlock, Greg C.; Allen, Scott C.; Vieira-Brock, Paula L.; Kristen A Stout; Ellis, Jonathan D; Hoonakker, Amanda J.; Andrenyak, David M.; Nielsen, Shannon M.; Wilkins, Diana G; Hanson, Glen R.; Fleckenstein, Annette E.

    2012-01-01

    Preclinical studies have demonstrated that repeated methamphetamine (METH) injections (referred to herein as a “binge” treatment) cause persistent dopaminergic deficits. A few studies have also examined the persistent neurochemical impact of METH self-administration in rats, but with variable results. These latter studies are important because: 1) they have relevance to the study of METH abuse; and 2) the effects of noncontingent METH treatment do not necessarily predict effects of contingent...

  14. Amphetamine poisoning in a dog: case report, literature review and veterinary medical perspectives.

    Science.gov (United States)

    Diniz, Pedro Paulo V P; Sousa, Marlos G; Gerardi, Daniel G; Tinucci-Costa, Mirela

    2003-12-01

    Amphetamine abuse in human beings has increased, resulting in many reports of toxicity and death. In the US over 4 million people have abused amphetamines at least once, thus small animals are exposed to increased accidental poisoning risk. This report describes an acute amphetamine poisoning in a dog due to ingestion of 15 mg/kg fenproporex, leading to typical signs of catecholamines release and effects in different organ systems. Similar clinical and laboratory findings observed in human beings are reviewed and physiopathogenic mechanisms discussed, as well as the therapeutic approaches available in veterinary medicine. PMID:14640484

  15. DMPD: MDA5/RIG-I and virus recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18272355 MDA5/RIG-I and virus recognition. Takeuchi O, Akira S. Curr Opin Immunol. ...2008 Feb;20(1):17-22. Epub 2008 Feb 12. (.png) (.svg) (.html) (.csml) Show MDA5/RIG-I and virus recognition.... PubmedID 18272355 Title MDA5/RIG-I and virus recognition. Authors Takeuchi O, Akira S. Publication Curr Opi

  16. Demand for Substance Abuse Treatment Related to Use of Crystal Methamphetamine in Ontario: An Observational Study

    Science.gov (United States)

    Brands, Bruna; Corea, Larry; Strike, Carol; Singh, Veeran-Anne S.; Behrooz, Renee C.; Rush, Brian

    2012-01-01

    Concerns about methamphetamine/crystal methamphetamine (MA) have featured prominently in the Canadian media and on addiction treatment agency agendas. We examined MA admissions at addiction treatment agencies to determine if a service gap existed. In 2006, all addiction treatment agencies (n = 124) in Ontario, Canada were invited to complete an…

  17. Methamphetamine Use among Rural White and Native American Adolescents: An Application of the Stress Process Model

    Science.gov (United States)

    Eitle, David J.; Eitle, Tamela McNulty

    2013-01-01

    Methamphetamine use has been identified as having significant adverse health consequences, yet we know little about the correlates of its use. Additionally, research has found that Native Americans are at the highest risk for methamphetamine use. Our exploratory study, informed by the stress process model, examines stress and stress buffering…

  18. The Impact of the Media in Influencing Extension's Perceptions of Methamphetamine

    Science.gov (United States)

    Beaudreault, Amy R.

    2013-01-01

    The study reported here explored media dependency and moral panic involving methamphetamine perceptions among a national sample of Extension Directors through survey methodology. With a 70.0% response rate, the questionnaire concentrated on demographics; methamphetamine knowledge, information sources, and dependency; and perceptions of the media.…

  19. Methamphetamine Use, Self-Reported Violent Crime, and Recidivism Among Offenders in California Who Abuse Substances

    Science.gov (United States)

    Cartier, Jerome; Farabee, David; Prendergast, Michael L.

    2006-01-01

    This study uses data from 641 state prison parolees in California to examine the associations between methamphetamine use and three measures of criminal behavior: (a) self-reported violent criminal behavior, (b) return to prison for a violent offense, and (c) return to prison for any reason during the first 12 months of parole. Methamphetamine use…

  20. Methamphetamine and 3,4-methylenedioxymethamphetamine interact with central nicotinic receptors and induce their up-regulation

    International Nuclear Information System (INIS)

    Previous work from our group indicated that α7 nicotinic acetylcholine receptors (α7 nAChR) potentially play a role in methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity. The aims of the present study were two-fold: (1) to demonstrate the interaction of METH and MDMA with homomeric α7 nAChR ([3H]methyllycaconitine binding) and other heteromeric subtypes ([3H]epibatidine binding); and (2) to show the effects of amphetamine derivative pretreatment on the density of binding sites. METH and MDMA displaced [3H]methyllycaconitine and [3H]epibatidine binding in membranes from NGF-differentiated PC 12 cells and mouse brain, with Ki values in the micromolar range, MDMA revealing a greater affinity than METH. In addition, METH and MDMA induced a time- and concentration-dependent increase in [3H]methyllycaconitine and [3H]epibatidine binding; which had already been apparent after 6 h of pretreatment, and which peaked in differentiated PC 12 cells after 48 h. The highest increases were found in [3H]epibatidine binding, with MDMA inducing higher increases than METH. Treatment with METH and MDMA increased Bmax of high-affinity sites for both radioligands without affecting Kd. The heightened binding was inhibited by pretreatment with cycloheximide, suggesting the participation of newly synthesised proteins while inhibition of protein trafficking to plasma membrane did not block up-regulation. The effects of protein kinase and cyclophilin inhibitors on such up-regulation were explored, revealing a rapid, differential and complex regulation, similar to that described for nicotinic ligands. All of these results demonstrate that METH and MDMA have affinity for, and can interact with, nAChR, inducing their up-regulation, specially when higher doses are used. Such effects may have a role in METH- and MDMA-induced neurotoxicity, cholinergic neurotransmission, and in processes related to addiction and dependence

  1. Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.

    Directory of Open Access Journals (Sweden)

    Jean Lud Cadet

    Full Text Available Methamphetamine (METH is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2, thyrotropin-releasing hormone (TRH, brain derived neurotrophic factor (BDNF, c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD, glutathione peroxidase (GPx-1, and heme oxygenase-1 (Hmox-1. These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to

  2. Applying UML and MDA to Real Systems Design

    CERN Document Server

    Oliver, Ian

    2011-01-01

    Traditionally system design has been made from a black box/functionality only perspective which forces the developer to concentrate on how the functionality can be decomposed and recomposed into so called components. While this technique is well established and well known it does suffer fromsome drawbacks; namely that the systems produced can often be forced into certain, incompatible architectures, difficult to maintain or reuse and the code itself difficult to debug. Now that ideas such as the OMG's Model Based Architecture (MDA) or Model Based Engineering (MBE) and the ubiquitous modelling language UML are being used (allegedly) and desired we face a number of challenges to existing techniques.

  3. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit; Constantinescu, Andreea; Leo, Damiana; Konrad, Lisa; Rickhag, Karl Mattias; Sørensen, Gunnar; Efimova, Evgenia V; Kong, Eryan; Willeit, Matthäus; Sotnikova, Tatyana D; Kudlacek, Oliver; Gether, Ulrik; Freissmuth, Michael; Pollak, Daniela D; Gainetdinov, Raul R; Sitte, Harald H

    2014-01-01

    Addiction to psychostimulants (ie, amphetamines and cocaine) imposes a major socioeconomic burden. Prevention and treatment represent unmet medical needs, which may be addressed, if the mechanisms underlying psychostimulant action are understood. Cocaine acts as a blocker at the transporters for...

  4. Comparative Cardiac Risks of Methylphenidate and Amphetamines in Treatment of ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available The risk for adverse cardiac events in subjects between 3 and 20 years of age treated with methylphenidate or amphetamine salts for ADHD was determined in a retrospective study at University of Florida, Gainesville, FL.

  5. Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

    OpenAIRE

    Hossein Kaviani

    2006-01-01

    "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine) were tested using electromyography (EMG) to measure eye-blink muscle (orbicular oculi) while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two dr...

  6. Behavioural and molecular responses to amphetamine in the neurokinin-1 receptor knock-out mouse

    OpenAIRE

    Slone-Murphy, J.

    2011-01-01

    The neurokinin-1 receptor knock-out (NK1R-/-) mouse is hyperactive and shows deficits in attentional processing, and has recently been put forward as a model of attention deficit hyperactivity disorder (ADHD). Acute amphetamine, a first-line treatment for ADHD and a drug of abuse, paradoxically reduces the hyperactivity of NK1R-/- mice, and the characteristic amphetamine-stimulated increase in striatal dopamine efflux seen in wild-type animals is attenuated in NK1R-/- mice. The...

  7. Serotonergic neurotransmission in the ventral hippocampus is enhanced by corticosterone and altered by chronic amphetamine treatment

    OpenAIRE

    Barr, Jeffrey L.; Forster, Gina L.

    2011-01-01

    The ventral hippocampus modulates anxiety-like behavior in rats, and serotonergic transmission within the hippocampus facilitates adaptation to stress. Chronic amphetamine treatment results in anxiety-like behavior in rats and reduced monoamine concentrations in the ventral hippocampus. Since reduced hippocampal serotonergic transmission in response to stress is observed in rats that display high anxiety-like behavior, anxiety states in amphetamine-treated rats may be associated with reduced ...

  8. Dopaminergic Actions of D-Amphetamine on Schedule-Induced Polydipsia in Rats

    Science.gov (United States)

    Pellon, Ricardo; Ruiz, Ana; Rodriguez, Cilia; Flores, Pilar

    2007-01-01

    Schedule-induced polydipsia in rats was developed by means of a fixed-time 60-s schedule of food presentation. The acute administration of d-amphetamine sulfate (0.1-3.0 mg/kg) produced a dose-dependent decrease in the rate of licking. D-Amphetamine shifted to the left the temporal distribution of adjunctive drinking within interfood intervals.…

  9. Effect of dexamethasone on protein extravasation in the brain in acute hypertension induced by amphetamine

    International Nuclear Information System (INIS)

    Amphetamine produces protein leakage in the brain when given to rats under nitrous oxide anesthesia. The blood-brain barrier dysfunction is caused by the combined effect of blood pressure increase and vasodilatation. In the present experiments pretreatment with dexamethasone, 2 mg. kg-1, diminished the amphetamine-induced extravasation of Evans blue albumin and 125IHSA in the rats' brain. Possible explanations to the effect of dexamethasone on cerebrovascular permeability are discussed. (author)

  10. Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats

    OpenAIRE

    Burke, Andrew R.; Renner, Kenneth J.; Forster, Gina L.; Watt, Michael J.

    2010-01-01

    The mesocorticolimbic dopamine system, which governs components of reward and goal-directed behaviors, undergoes final maturation during adolescence. Adolescent social stress contributes to adult behavioral dysfunction, and is linked to adult psychiatric and addiction disorders. Here, behavioral, corticosterone, and limbic dopamine responses to amphetamine were examined in adult male rats previously exposed to repeated social defeat stress during mid-adolescence. Amphetamine (2.5 mg/kg, ip) w...

  11. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo

    OpenAIRE

    Liu, Christina H.; Yang, Jinsheng; Ren, Jia Q.; Liu, Charng-Ming; You, Zerong; LIU, PHILIP K.

    2013-01-01

    How amphetamine affects the neuroglia in living brains is not well understood. In an effort to elucidate this effect, we investigated neuroglia in response to amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is a random-sequence sODN (Ran). Using cyanine 5.5-superparamagnetic iron oxide nanoparticle (Cy5....

  12. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  13. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Interaction energy between several armchair CNTs and amphetamine is investigated. • The adsorption of amphetamine molecule is observed to be exothermic and physical in nature. • HOMO–LUMO for pure CNTs, amphetamine and their corresponded complexes are studied. • Density of states (DOS) near the Fermi level is calculated and presented. - Abstract: The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of −1.13 to −1.88 and −1.27 to −2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule

  14. Amphetamine administration into the ventral striatum facilitates behavioral interaction with unconditioned visual signals in rats.

    Directory of Open Access Journals (Sweden)

    Rick Shin

    Full Text Available BACKGROUND: Administration of psychomotor stimulants like amphetamine facilitates behavior in the presence of incentive distal stimuli, which have acquired the motivational properties of primary rewards through associative learning. This facilitation appears to be mediated by the mesolimbic dopamine system, which may also be involved in facilitating behavior in the presence of distal stimuli that have not been previously paired with primary rewards. However, it is unclear whether psychomotor stimulants facilitate behavioral interaction with unconditioned distal stimuli. PRINCIPAL FINDINGS: We found that noncontingent administration of amphetamine into subregions of the rat ventral striatum, particularly in the vicinity of the medial olfactory tubercle, facilitates lever pressing followed by visual signals that had not been paired with primary rewards. Noncontingent administration of amphetamine failed to facilitate lever pressing when it was followed by either tones or delayed presentation or absence of visual signals, suggesting that visual signals are key for enhanced behavioral interaction. Systemic administration of amphetamine markedly increased locomotor activity, but did not necessarily increase lever pressing rewarded by visual signals, suggesting that lever pressing is not a byproduct of heightened locomotor activity. Lever pressing facilitated by amphetamine was reduced by co-administration of the dopamine receptor antagonists SCH 23390 (D1 selective or sulpiride (D2 selective. CONCLUSIONS: Our results suggest that amphetamine administration into the ventral striatum, particularly in the vicinity of the medial olfactory tubercle, activates dopaminergic mechanisms that strongly enhance behavioral interaction with unconditioned visual stimuli.

  15. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Hafizi, Hamid [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Najafi Chermahini, Alireza, E-mail: anajafi@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mohammadnezhad, Gholamhossein [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Teimouri, Abbas [Chemistry Department, Payame Noor University (PNU), Tehran 19395-4697 (Iran, Islamic Republic of)

    2015-02-28

    Graphical abstract: - Highlights: • Interaction energy between several armchair CNTs and amphetamine is investigated. • The adsorption of amphetamine molecule is observed to be exothermic and physical in nature. • HOMO–LUMO for pure CNTs, amphetamine and their corresponded complexes are studied. • Density of states (DOS) near the Fermi level is calculated and presented. - Abstract: The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of −1.13 to −1.88 and −1.27 to −2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule.

  16. Combination of modafinil and d-Amphetamine for the treatment of cocaine dependence: A preliminary investigation

    Directory of Open Access Journals (Sweden)

    Joy M Schmitz

    2012-08-01

    Full Text Available Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%. Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤ 80%. Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

  17. Learning and cross drug effects: thermic effects of pentobarbital and amphetamine.

    Science.gov (United States)

    Hinson, R E; Rhijnsburger, M

    1984-06-25

    The effects of environmental cues explicitly paired or unpaired with pentobarbital on the thermic effects of pentobarbital and amphetamine were investigated. Rats received 19 injections of pentobarbital in a distinctive environment and were subsequently tested for the thermic effects of pentobarbital and amphetamine in the distinctive environment, another environment previously associated only with saline, or in the colony room not previously associated with injections. Rats tested in the context of the environmental cues previously associated with pentobarbital were tolerant to the hypothermic effect of pentobarbital, but rats tested in the environment previously associated only with saline or in the colony room were not tolerant. Pentobarbital-experienced rats administered amphetamine in the context of the usual pentobarbital cues exhibited an exaggerated hyperthermic reaction compared to previously drug-naive rats administered amphetamine. Pentobarbital-experienced rats injected with amphetamine in the homeroom exhibited a smaller hyperthermic response than previously drug-naive rats administered amphetamine in the home room. These results demonstrate that an animal's response to a drug can be affected by cues paired and unpaired with drug administration. PMID:6738300

  18. Differential effects of the ascorbyl and tocopheryl derivative on the methamphetamine-induced toxic behavior and toxicity

    International Nuclear Information System (INIS)

    A previous study showed that high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. Furthermore, the combination of methamphetamine and morphine increased lethality in mice. We recently surmised that the rise in SIB and mortality induced by methamphetamine and/or morphine may be related to oxidative stress. The present study was designed to determine whether an antioxidant could inhibit SIB or mortality directly induced by methamphetamine and/or morphine. The SIB induced by 20 mg/kg of methamphetamine was abolished by the administration of Na L-ascorbyl-2-phosphate (APS: 300 mg/kg), but not Na DL-α-tocopheryl phosphate (TPNa: 200 mg/kg). In contrast, APS (300 mg/kg) and TPNa (200 mg/kg) each significantly attenuated the lethality induced by methamphetamine and morphine. The present study showed that the signal intensity of superoxide adduct was increased by 20 mg/kg of methamphetamine in the heart and lungs, and methamphetamine plus morphine tended to increase superoxide adduct in all of the tissues measured by ESR spin trap methods. Adduct signal induced in brain by methamphetamine administration increased in significance, but in mouse administrated methamphetamine plus morphine. There are differential effects of administration of methamphetamine and coadministration of methamphetamine plus morphine on adduct signal. These results suggest that APS and TPNa are effective for reducing methamphetamine-induced toxicity and/or toxicological behavior. While APS and TPNa each affected methamphetamine- and/or morphine-induced toxicology and/or toxicological behavior, indicating that both drugs have antioxidative effects, their effects differed

  19. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

    Science.gov (United States)

    Yazdani, Neema; Parker, Clarissa C; Shen, Ying; Reed, Eric R; Guido, Michael A; Kole, Loren A; Kirkpatrick, Stacey L; Lim, Jackie E; Sokoloff, Greta; Cheng, Riyan; Johnson, W Evan; Palmer, Abraham A; Bryant, Camron D

    2015-12-01

    Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention and treatment of substance abuse and possibly other psychiatric disorders. PMID:26658939

  20. Correlates of transient versus persistent psychotic symptoms among dependent methamphetamine users.

    Science.gov (United States)

    McKetin, Rebecca; Gardner, Jonathon; Baker, Amanda L; Dawe, Sharon; Ali, Robert; Voce, Alexandra; Leach, Liana S; Lubman, Dan I

    2016-04-30

    This study examined correlates of transient versus persistent psychotic symptoms among people dependent on methamphetamine. A longitudinal prospective cohort study of dependent methamphetamine users who did not meet DSM-IV criteria for lifetime schizophrenia or mania. Four non-contiguous one-month observation periods were used to identify participants who had a) no psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient psychotic symptoms, n=85); and, (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent psychotic symptoms, n=37). Psychotic symptoms were defined as a score of 4 or greater on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content. Relative no psychotic symptoms, both transient and persistent psychotic symptoms were associated with childhood conduct disorder and comorbid anxiety disorders. Earlier onset methamphetamine use and being male were more specifically related to transient psychotic symptoms, while a family history of a primary psychotic disorder and comorbid major depression were specifically related to persistent psychotic symptoms. We conclude that there are overlapping but also distinct clinical correlates of transient versus persistent psychotic symptoms, suggesting potentially heterogeneous etiological pathways underpinning the psychotic phenomena seen amongst people who use methamphetamine. PMID:27086229

  1. An agent oriented information system: an MDA based development

    Directory of Open Access Journals (Sweden)

    Mohamed Sadgal

    2012-09-01

    Full Text Available Information systems (IS development should not only accomplish functional models but also conceptual models to represent the organizational environment in which it will have to evolve and must be aligned with strategic objectives. Generally, a significant innovations in the enterprise, is to organize its IS around its business processes. Otherwise, business models must be enriched by the agent paradigm to reduce the complexity involved in solving a problem by the structuring of knowledge on a set of intelligent agents, the association between agents and activities and collaboration among agents. To do this, we propose an agent oriented approach based on the model-driven-architecture (MDA for the information system development. This approach uses in its different phases, the BPMN language for the business processes modeling, AML language for the agent modeling, and JADEX platform for the implementation. The IS development is realized by different automated mappings from source models to target models.

  2. 美沙酮维持治疗门诊病人滥用"冰毒"行为调查%INVESTIGATION ON METHAMPHETAMINE ABUSE AMONG OPIATE ADDICTS UNDER METHADONE MAINTENANCE TREATMENT

    Institute of Scientific and Technical Information of China (English)

    伏新艳; 高菁; 潘蕾; 方欣; 车驰

    2012-01-01

    Objective: To understand the situation of methamphetamine abuse among opiate addicts during methadone maintenance treatmen( MMT) , found possible risk of drug abuse among them and provide scientific data for the improvement of MMT. Methods: A survey was conducted on 462 patients in 4 MMT clinics with a self - designed questionnaire, the main contents of which were general conditions, drug abuse and physical status of the patients. Urine tests were also made for amphetamine use ( colloidal gold rapid detection ) . Results: Among 462 cases, 86 cases were amphetamine urine test positive, the positive rate was 18. 61% , with male s positive rate 18.52% and female s positive rate 19.05%. The chi -square test showed that there was no significant difference at variables of gender, age, marital status, occupation classification, level of education, between subjects with amphetamine urine test positive and those with negative urine test. Conclusion: There exists amphetamine abuse phenomenon among opiate addicts on MMT.%目的:了解接受美沙酮维持治疗(methadone maintenance treatment.MMT)的阿片类药物成瘾者接受MMT期间是否存在滥用"冰毒"的行为及发生率,为有关部门及时掌握可能存在的隐匿药物滥用风险,为进一步完善MMT措施提供客观数据与科学建议.方法:采用自编的对某地4所美沙酮维持治疗门诊收治的462名患者进行问卷调查,并对调查对象进行苯丙胺类尿检(胶体金法快速检测).结果:462例被调查对象中苯丙胺类尿检阳性86例,阳性检出率达18.61%,其中,男性阳性率占18.52%,女性阳性率占19.05%.X2检验结果显示,男女性别、年龄、婚姻状况、职业、受教育程度尿检阳性率的差异均无统计学意义(P>0.05).结论:接受美沙酮维持治疗的阿片类药物成瘾者有滥用冰毒的现象.

  3. Behavioral and growth effects induced by low dose methamphetamine administration during the neonatal period in rats

    OpenAIRE

    Williams, Michael T.; Moran, Mary S.; Vorhees, Charles V.

    2004-01-01

    The investigation of methamphetamine exposure during neonatal development in rats has demonstrated that long-term spatial learning deficits are induced. A previous dose–response study showed that administration of 5 mg/kg methamphetamine, four times daily from postnatal days 11 to 20 produced these deficits, although the effects were not as severe as at higher doses of 10 or 15 mg/kg. This study examined concentrations of methamphetamine at or below 5 mg/kg given over the same period of time....

  4. A comparative study of the effects of methamphetamine on memory in existing and recovering addicts from a South African population

    Directory of Open Access Journals (Sweden)

    Cindy van Wyk

    2012-07-01

    Full Text Available Memory is a complex of systems by which an organism registers, stores and retrieves exposure toan event or experience. Literature purports that methamphetamine users and dependents havebeen found to exhibits signs of memory impairment. The aim of the research was to establishthe possible existence of significant differences in memory in current methamphetamine users,recovering methamphetamine users, and a matched drug naïve control group. Cognitivefunctioning was assessed via a neurocognitive test battery that examined the memory of14 current methamphetamine users, 17 recovering methamphetamine addicts, and 18 drugnaïve control participants who were matched according to the demographic variables of age,gender and educational status. The results indicated that recovering methamphetamine usersexperienced the greatest impairment in memory in comparison to both the control group andcurrent users of methamphetamine. The current users of methamphetamine also experiencedsome impairment in memory functioning in visual acquisition and retention. The poorperformance of the recovering addicts is explained by the juxtaposition of the stimulatingand supplemental effect of methamphetamine as experienced by the current users versus theneurotransmitter depletion and structural changes in the brain experienced by the recoveringaddicts. The control group showed a superior performance since they did not suffer from theneurotoxic effects of methamphetamine.

  5. Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

    Directory of Open Access Journals (Sweden)

    Petra Suchankova

    Full Text Available The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL as well as GHS-R1A (GHSR genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104 and controls from the general population (n = 310. A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc  = 0.02. A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc  = 0.03. The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.

  6. Integrating Software Architecture Concepts into the MDA Platform with UML Profile

    Directory of Open Access Journals (Sweden)

    Adel Alti

    2007-01-01

    Full Text Available Architecture Description Languages (ADLs provide an abstract representation of software systems. Achieving a concrete mapping of such representation into the implementation is one of the principal aspects of MDA (Model Driven Architecture. Integration of ADLs within MDA confers to the MDA platform a higher level of abstraction and a degree of reuse of ADLs. Indeed they have significantly different platform metamodels which make the definition of mapping rules complex. This complexity is clearly noticeable when some software architecture concepts cannot be easily mapped to MDA platform. In this research, we propose to integrate software architecture within MDA. We define also strategy for direct transformation using a UML profile. It represents both software architecture model (PIM and MDA platform model (PSM in UML meta-model then elaborates transformation rules between results UML meta-models. The goal is to automate the process of deriving implementation platform from software concepts.

  7. Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

    OpenAIRE

    You, Mi-Kyoung; Kim, Min-Sook; Jeong, Kyu-Shik; Kim, Eun; Kim, Yong-Jae; Kim, Hyeon-A

    2016-01-01

    BACKGROUND/OBJECTIVES The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various conc...

  8. Digital Droplet Multiple Displacement Amplification (ddMDA) for Whole Genome Sequencing of Limited DNA Samples

    OpenAIRE

    Minsoung Rhee; Yooli K Light; Meagher, Robert J.; Anup K. Singh

    2016-01-01

    Multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template D...

  9. Adenovirus vector expressing mda-7 selectively kills hepatocellular carcinoma cell line Hep3B

    Institute of Scientific and Technical Information of China (English)

    Xin-Bo Xue; Kun Chen; Cong-Jun Wang; Jian-Wei Zheng; Yuan Yu; Zhi-Hai Peng; Zai-De Wu

    2008-01-01

    BACKGROUND: Melanoma differentiation associated gene-7 (mda-7) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells both in vitro and in vivo through activation of various intracellular signaling pathways. In this study, we investigated the potential effect of mda-7 on human hepatocellular carcinoma (HCC) in vitro. METHODS: Cells from the human HCC cell line Hep3B and the human liver cell line L-02 were assigned to three groups. One was cultured in Dulbecco's modiifed Eagle's medium without serum (control). The others were transfected with adenovirus expressing the mda-7 gene (Ad.mda-7) or adenovirus vector serving as negative control (Ad.vec). The expression of MDA-7 and Bcl-2 proteins in Hep3B and L-02 cells was conifrmed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. The methyl thiazolyl tetrazolium colorimetric assay and lfow cytometry were used to assess tumor cell proliferation and the cell cycle. Hoechst and Annexin-V/propidium iodide staining were used to study mda-7 gene expression in Hep3B and L-02 cells. The expression of MDA-7, Bcl-2 and Bax proteins were detected by Western blotting. RESULTS: The mda-7 gene was expressed in Hep3B and L-02 cells. The protein concentrations of MDA-7 in supernatants were 790 and 810 pg/ml, respectively. mda-7 induced Hep3B growth suppression and apoptosis, compared with Ad.mda-7 and control (P CONCLUSIONS: mda-7 selectively induces growth inhibi-tion and apoptosis in the HCC cell line Hep3B but not in the normal liver cell line L-02 via downregulating the anti-apoptosis protein Bcl-2. It could be an ideal gene for gene therapy in HCC.

  10. MD&A – Counterpart to or Distraction from Financial Reporting

    OpenAIRE

    Kevin Girdharry; Elena Simonova; Rock Lefebvre

    2011-01-01

    MD&A content has been an ongoing topic of recent debate with the views divided on the impact that regulated content has on the quality of the MD&A. Complexity has amplified as a result of emerging issues of particular importance to investors such as transition to IFRS, the environment and executive compensation. This paper examines companies’ compliance with requirements of the Canadian Securities Administrators for MD&A disclosures, and aims to advance understand on whether following CSA req...

  11. High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

    Science.gov (United States)

    Madularu, Dan; Kulkarni, Praveen; Yee, Jason R; Kenkel, William M; Shams, Waqqas M; Ferris, Craig F; Brake, Wayne G

    2016-06-01

    The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders. PMID:27154458

  12. Cure Kinetics of DGEBA/MDA System with Various Contents of NPG

    Energy Technology Data Exchange (ETDEWEB)

    Lee, H.K. [Woosuk Univerisity, Wanju (Korea, Republic of); Kim, Y.L.; Lee, J.Y.; Kim, S.W. [The University of Seoul, Seoul (Korea, Republic of)

    1999-05-01

    The isothermal cure behavior of diglycidyl ether of bisphenol A(DGEBA)/4,4`- methylene dianiline(MDA) system with various contents of neopentyl glycol(NPG) has been analyzed by differential scanning calorimetry(DSC). To increase the cure rate of DGEBA/MDA system, NPG was introduced as an accelerator. Regardless of the NPG content, the shape of the conversion curves showed sigmoid indicating that DGEBA/MDA/NPG system followed autocatalytic cure reaction. The cure reaction of DGEBA/MDA system increased with the increment of NPG content and it was due to the catalytic role of hydroxyl groups of NPG. (author). 21 refs., 6 figs., 2 tabs.

  13. Personality and the subjective effects of acute amphetamine in healthy volunteers.

    Science.gov (United States)

    White, Tara L; Lott, David C; de Wit, Harriet

    2006-05-01

    Individual differences in the positive mood and other subjective effects of d-amphetamine have been linked to personality traits related to sensation seeking. The current study extends these associations to separate personality traits of reward sensitivity, physical fearlessness, and impulsivity. A total of 128 healthy volunteers received oral doses of d-amphetamine (10 and 20 mg) or placebo in counterbalanced order. Their responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Participants completed the Multidimensional Personality Questionnaire Brief Form to assess personality traits related to reward sensitivity (Agentic Positive Emotionality and Social Potency (SP)), physical fear (Harm Avoidance (HA)), and impulsivity (Control (CL)). Participants were rank ordered on each trait, and individuals with scores in the top and bottom thirds of scores on each trait were compared using ANCOVA. High trait physical fearlessness (low HA) was associated with greater positive activational effects of 10 mg d-amphetamine. High trait reward sensitivity (high SP) was marginally associated with greater positive activational effects of 20 mg d-amphetamine. High trait impulsivity (low CL) was unrelated to positive drug effects in response either dose. The two separate personality traits of physical fearlessness and reward sensitivity are associated with d-amphetamine effects on mood in healthy volunteers. Implications for the vulnerability to psychostimulant addiction in healthy nonaddicts are discussed. PMID:16237380

  14. The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia

    International Nuclear Information System (INIS)

    To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity

  15. Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment

    DEFF Research Database (Denmark)

    Gonçalves, J; Baptista, S; Olesen, MV; Malva, JO; Woldbye, David Paul Drucker; Silva, AP

    2012-01-01

    Methamphetamine (METH) is a psychostimulant drug that causes irreversible brain damage leading to several neurological and psychiatric abnormalities, including cognitive deficits. Neuropeptide Y (NPY) is abundant in the mammalian central nervous system (CNS) and has several important functions, b...

  16. Acute respiratory distress syndrome in a woman with heroin and methamphetamine misuse.

    Science.gov (United States)

    Yeh, P S; Yuan, A; Yu, C J; Kuo, S H; Luh, K T; Yang, P C

    2001-08-01

    Methamphetamine, heroin, and cannabis are three of the most commonly misused drugs in Asia. In Taiwan, cases of misuse of methamphetamine have been increasing. In this paper, we report the case of a 23-year-old woman who had a 10-year history of smoking methamphetamine and intermittent use of heroin for 3 to 4 years. She developed pulmonary toxic effects associated with misuse of heroin and methamphetamine. She was brought to the emergency room because of consciousness disturbance and acute respiratory failure. Her symptoms of rapid progression of refractory hypoxemia, ill-defined densities over both lung fields, and normal pulmonary artery wedge pressure were consistent with acute respiratory distress syndrome. Rapid resolution of infiltrations and improvement of oxygenation were observed after mechanical ventilation with positive end-expiratory pressure support and oxygen therapy. She was discharged on the fifteenth hospital day without any sequela except for mild exertional dyspnea. PMID:11678007

  17. Treatment of Methamphetamine Dependence with Electroconvulsive Therapy (ECT in Iran: A Critical Note.

    Directory of Open Access Journals (Sweden)

    Babak Roshanaei-Moghaddam

    2014-09-01

    Full Text Available This comment article reviews the literature to explore whether the use of ECT for the treatment of methamphetamine dependence can be justified by scientific rationale and/or evidence.This article reviews the literature on the use of ECT in addictive disorders. It describes a patient with methamphetamine dependence treated with ECT. It then offers a historical review of the moral and ethical difficulties encountered in the treatment of addictive disorders. It proposes a dynamic understanding as to why clinicians might deploy such brutal actions in the face of hopeless and emotionally intense encounters.We found no scientific evidence or justification for ECT as a treatment of methamphetamine dependence or as the first line treatment for methamphetamine-induced psychiatric comorbidities.the current available evidence does not support using ECT for the treatment of addictive disorders, and hence is unethical, unacceptable and inhumane and warrants immediate social and political attention.

  18. The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury.

    Science.gov (United States)

    Rau, Thomas; Ziemniak, John; Poulsen, David

    2016-01-01

    Methamphetamine is a psychostimulant that was initially synthesized in 1920. Since then it has been used to treat attention deficit hyperactive disorder (ADHD), obesity and narcolepsy. However, methamphetamine has also become a major drug of abuse worldwide. Under conditions of abuse, which involve the administration of high repetitive doses, methamphetamine can produce considerable neurotoxic effects. However, recent evidence from our laboratory indicates that low doses of methamphetamine can produce robust neuroprotection when administered within 12h after severe traumatic brain injury (TBI) in rodents. Thus, it appears that methamphetamine under certain circumstances and correct dosing can produce a neuroprotective effect. This review addresses the neuroprotective potential of methamphetamine and focuses on the potential beneficial application for TBI. PMID:25724762

  19. Unique aspects of mda-7/IL-24 antitumor bystander activity: establishing a role for secretion of MDA-7/IL-24 protein by normal cells.

    Science.gov (United States)

    Su, Zhaozhong; Emdad, Luni; Sauane, Moira; Lebedeva, Irina V; Sarkar, Devanand; Gupta, Pankaj; James, C David; Randolph, Aaron; Valerie, Kirstoffer; Walter, Mark R; Dent, Paul; Fisher, Paul B

    2005-11-17

    Melanoma differentiation associated gene-7 (mda-7) was cloned using subtraction hybridization from terminally differentiated human melanoma cells. Based on structural and functional properties, mda-7 is now recognized as interleukin-24 (IL-24), a new member of the expanding IL-10 gene family. Unique properties of mda-7/IL-24 include its ability to selectively induce growth suppression, apoptosis and radiosensitization in diverse human cancer cells, without causing similar effects in normal cells. The utility of mda-7/IL-24, administered by means of a replication-incompetent adenovirus, as a gene therapy for cancer has recently received validation in patients, highlighting an important phenomenon initially observed in pancreatic tumor cells, namely a 'potent bystander apoptosis-inducing effect' in adjacent tumor cells not initially receiving this gene product. We presently investigated the contribution of mda-7/IL-24 secreted by normal cells in mediating this 'bystander effect', and document that normal cells induced to produce mda-7/IL-24 following infection with recombinant adenoviruses expressing this cytokine secrete mda-7/IL-24, which modifies the anchorage-independent growth, invasiveness, survival and sensitivity to radiation of cancer cells that contain functional IL-20/IL-22 receptors, but not in cancer cells that lack a complete set of receptors. Moreover, the combination of secreted mda-7/IL-24 and radiation engenders a 'bystander antitumor effect' not only in inherently mda-7/IL-24 or radiation-sensitive cancer cells, but also in tumor cells overexpressing the antiapoptotic proteins bcl-2 or bcl-x(L) and displaying resistance to either treatment alone. The present studies provide definitive evidence that secreted mda-7/IL-24 from normal cells can induce direct antitumor and radiation-enhancing effects that are dependent on the presence of canonical receptors for this cytokine on tumor cells. Moreover, we now describe a novel means of enhancing mda-7/IL

  20. Trends in Production, Trafficking and Consumption of Methamphetamine and Cocaine in Mexico

    OpenAIRE

    Brouwer, Kimberly C.; Case, Patricia; Ramos, Rebeca; Magis-Rodríguez, Carlos; Bucardo, Jesus; PATTERSON, THOMAS L.; Strathdee, Steffanie A

    2006-01-01

    Over the past decade, Mexico has experienced a significant increase in trafficking of cocaine and trafficking and production of methamphetamine. An estimated 70% of U.S. cocaine originating in South America passes through the Central America-Mexico corridor. Mexico-based groups are now believed to control 70%–90% of methamphetamine production and distribution in the U.S. Increased availability of these drugs at reduced prices has led to a parallel rise in local drug consumption. Methamphetami...

  1. Family conflict and depression in HIV-negative heterosexuals: The role of methamphetamine use

    OpenAIRE

    Semple, Shirley J.; Strathdee, Steffanie A.; Zians, Jim; Thomas L Patterson

    2009-01-01

    Previous research has reported elevated levels of depressive symptoms among methamphetamine users, but little attention has been paid to possible links between family environment and psychological distress. This study examined relationships between family conflict, substance use, and depressive symptoms in a sample of 104 heterosexual methamphetamine users in San Diego, CA. Eighty-nine percent of the sample reported conflict with a family member in the past year. Conflict was reported most of...

  2. Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

    OpenAIRE

    Buonocore Michael; Caputo Gary; Yeo Khung; Lopez Javier E; Schaefer Saul

    2009-01-01

    Abstract Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enh...

  3. Fast Uptake and Long-Lasting Binding of Methamphetamine in the Human Brain: Comparison with Cocaine

    OpenAIRE

    Fowler, Joanna S.; Volkow, Nora D.; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald

    2008-01-01

    Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokineti...

  4. Frequency of Psychiatric Disorders in Children of Opioid or Methamphetamine-Dependent Patients

    OpenAIRE

    Parvaresh, Noushin; Mazhari, Shahrzad; Nazari-Noghabi, Maryam

    2015-01-01

    Background Addiction is one of the main problems of human societies, which is more common in developing countries. In addition, it causes to personal and social problems and family problem. The aim of this study was to examine the prevalence of psychiatric disorders in children 5-15 years old of opioid or methamphetamine dependence patients. Methods For this study, three groups including: (1) children of parents addicted to opium, (2) children of parents addicted to methamphetamine, and (3) c...

  5. Longitudinal investigation of methamphetamine use among gay and bisexual men in New York City: Findings from project BUMPS

    OpenAIRE

    Halkitis, Perry N.; Green, Kelly A.; Mourgues, Paris

    2005-01-01

    In recent years, methamphetamine has become a drug more commonly used among gay and bisexual men in New York City. Part of a longitudinal investigation of drug abuse in this population involved assessing the patterns and context of methamphetamine use during the course of 1 year. Findings indicate that among self-identified club-drug-using men, methamphetamine is widely used by men across age groups, educational level, racelethnicity, and HIV status. Participants reported use of methamphetami...

  6. Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

    OpenAIRE

    Baladi, Michelle G.; Newman, Amy H.; Nielsen, Shannon M.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 rece...

  7. Individual, Social, and Environmental Factors Associated with Initiating Methamphetamine Injection: Implications for Drug Use and HIV Prevention Strategies

    OpenAIRE

    Marshall, Brandon DL; Wood, Evan; Shoveller, Jean A.; Buxton, Jane A.; Montaner, Julio SG; Kerr, Thomas

    2011-01-01

    The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June 2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study's commencement were eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. T...

  8. Effects of Family-Centered Empowerment Model Based Education Program on Quality of Life in Methamphetamine Users and Their Families

    OpenAIRE

    Ghasemi, Afsaneh; Rahimi Foroshani, Abbass; Kheibar, Nasrin; Latifi, Marziye; Narges KHANJANI; Eshagh Afkari, Mohammad; Taghdisi, Mohammad Hossein; Ghasemi, Faranak; Shojaeizadeh, Davoud; Dastoorpour, Maryam

    2014-01-01

    Background: Nowadays there are more concerns about drug treatment of methamphetamine abusers whereas quality of life (QOL) related supportive psychotherapy is less credited. Objectives: This study aimed to evaluate the effects of family-centered empowerment model on social support and QOL of methamphetamine users and their families. Patients and Methods: This study was a randomized clinical trial; individuals were randomly allocated to three groups: a group for educating methamphetamine users...

  9. A comparative study of the effects of methamphetamine on memory in existing and recovering addicts from a South African population

    OpenAIRE

    Cindy van Wyk; Anita D. Stuart

    2012-01-01

    Memory is a complex of systems by which an organism registers, stores and retrieves exposure toan event or experience. Literature purports that methamphetamine users and dependents havebeen found to exhibits signs of memory impairment. The aim of the research was to establishthe possible existence of significant differences in memory in current methamphetamine users,recovering methamphetamine users, and a matched drug naïve control group. Cognitivefunctioning was assessed via a neurocognitive...

  10. Striatal Dopamine D2/D3 Receptor Availability is Reduced in Methamphetamine Dependence and is Linked to Impulsivity

    OpenAIRE

    Lee, Buyean; London, Edythe D.; Poldrack, Russell A.; Farahi, Judah; Nacca, Angelo; Monterosso, John R.; Mumford, Jeanette A.; Bokarius, Andrew V.; Dahlbom, Magnus; Mukherjee, Jogeshwar; Robert M Bilder; Brody, Arthur L.; Mandelkern, Mark A.

    2009-01-01

    While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D2/D3 receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [18F]fallypride to measure striatal dopamine D2/D3 receptor availability. The methamphetamine-dependent subjects reported recent use of th...

  11. [The role of CC-chemokine ligand 2 in the development of psychic dependence on methamphetamine].

    Science.gov (United States)

    Saika, Fumihiro; Kiguchi, Norikazu; Kishioka, Shiroh

    2015-10-01

    Addiction is described as a chronic neurological disorder associated with plasticity in the mesolimbic system. Recently, it has been suggested that neuroinflammation plays an important role in the induction of neuronal plasticity and the formation of pathogenesis in chronic neurological disorders. Therefore, we examined the role of CC-chemokine ligand 2 (CCL2), a proinflammatory chemokine, in the development of psychic dependence on methamphetamine. In mice treated with methamphetamine, CCL2 mRNA was significantly increased in prefrontal cortex and nucleus accumbens. Moreover, phosphorylated tyrosine hydroxylase serine40 (pTH Ser40) levels in the ventral tegmental area (VTA) were increased by methamphetamine. Similarly, pTH Ser40 levels in the VTA were also increased by the intracerebroventricular administration of recombinant CCL2. The increment of pTH Ser40 levels in the VTA by methamphetamine was attenuated by RS504393, a selective CC-chemokine receptor 2 (CCR2) antagonist, indicating that the increased CCL2 activates the brain reward system via CCR2 activation. In the conditioned place preference test, methamphetamine produced place preference in a dose-dependent manner, which was attenuated by RS504393. These results suggest that the activation of the brain reward system via CCL2-CCR2 pathway plays an important role in the development of psychic dependence on methamphetamine. PMID:26946780

  12. Association Study of Two Cannabinoid Receptor Genes, CNR1 and CNR2, with Methamphetamine Dependence

    Science.gov (United States)

    Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H

    2011-01-01

    Several studies have suggested that the endocannabinoid system plays significant roles in the vulnerability to psychiatric disorders including drug abuse. To examine the possible association of the CNR1 and CNR2 genes, which encode cannabinoid receptors CB1 and CB2, with methamphetamine dependence, we investigated three single nucleotide polymorphisms (SNPs) (rs806379, rs1535255, rs2023239) in intron 2 of the CNR1 gene and a nonsynonymous SNP, Q63R, in the CNR2 gene. The study samples consisted of 223 patients with methamphetamine dependence and 292 age- and sex- matched controls. There were no significant differences between the patients and controls in genotypic or allelic distribution of any SNP of the CNR1 and CNR2 genes. We also analyzed the clinical features of methamphetamine dependence. Rs806379 of the CNR1 gene showed a significant association with the phenotype of latency of psychosis after the first consumption of methamphetamine. Patients with the T allele or T-positive genotypes (T/T or A/T) may develop a rapid onset of psychosis after methamphetamine abuse. The present study suggests a possibility that genetic variants of the CNR1 gene may produce a liability to the complication of psychotic state after abuse of methamphetamine; however, our findings need to be confirmed by future replications. PMID:21886587

  13. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

    Science.gov (United States)

    Volkow, N D; Chang, L; Wang, G J; Fowler, J S; Franceschi, D; Sedler, M; Gatley, S J; Miller, E; Hitzemann, R; Ding, Y S; Logan, J

    2001-12-01

    Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals. PMID:11717374

  14. Rapid Recovery of Vesicular Dopamine Levels in Methamphetamine Users in Early Abstinence.

    Science.gov (United States)

    Boileau, Isabelle; McCluskey, Tina; Tong, Junchao; Furukawa, Yoshiaki; Houle, Sylvain; Kish, Stephen J

    2016-03-01

    We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2.6 days) and later (~10 days) abstinence. Striatal [(11)C]-(+)-dihydrotetrabenazine binding was elevated (suggesting low stored dopamine) in methamphetamine users (n=28; 2.6 days after last use) relative to controls (n=22) (+28%, pimaging data support post-mortem findings and suggest that chronic methamphetamine users have low brain levels of stored dopamine during very early abstinence from MA, which could contribute to behavioral and cognitive deficits. Findings also suggest a rapid recovery of stored dopamine in some methamphetamine users who become abstinent and who therefore might not benefit from dopamine replacement medication (eg, levodopa). Further study is necessary to establish whether those users who could not maintain abstinence for the second scan might have a more severe and persistent dopamine deficiency and who could benefit from this medication. PMID:26321315

  15. Effects of adolescent social defeat on adult amphetamine-induced locomotion and corticoaccumbal dopamine release in male rats

    OpenAIRE

    Burke, Andrew R.; Forster, Gina L.; Novick, Andrew M.; Roberts, Christina L.; Watt, Michael J.

    2012-01-01

    Maturation of mesocorticolimbic dopamine systems occurs during adolescence, and exposure to social stress during this period results in behavioral dysfunction including substance abuse disorders. Adult male rats exposed to repeated social defeat in adolescence exhibit reduced basal dopamine tissue content in the medial prefrontal cortex, altered dopamine tissue content in corticoaccumbal dopamine regions following acute amphetamine, and increased amphetamine conditioned place preference follo...

  16. Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

    Directory of Open Access Journals (Sweden)

    Hossein Kaviani

    2006-04-01

    Full Text Available "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine were tested using electromyography (EMG to measure eye-blink muscle (orbicular oculi while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. Conclusion: The methodological and theoretical aspects of the study and findings will be discussed.

  17. Increased BOLD activation to predator stressor in subiculum and midbrain of amphetamine-sensitized maternal rats.

    Science.gov (United States)

    Febo, Marcelo; Pira, Ashley S

    2011-03-25

    Amphetamine, which is known to cause sensitization, potentiates the hormonal and neurobiological signatures of stress and may also increase sensitivity to stress-inducing stimuli in limbic areas. Trimethylthiazoline (5μL TMT) is a chemical constituent of fox feces that evokes innate fear and activates the neuronal and hormonal signatures of stress in rats. We used blood oxygen level dependent (BOLD) MRI to test whether amphetamine sensitization (1mg/kg, i.p. ×3days) in female rats has a lasting effect on the neural response to a stress-evoking stimulus, the scent of a predator, during the postpartum period. The subiculum and dopamine-enriched midbrain VTA/SN of amphetamine-sensitized but not control mothers showed a greater BOLD signal response to predator odor than a control putrid scent. The greater responsiveness of these two brain regions following stimulant sensitization might impact neural processing in response to stressors in the maternal brain. PMID:21134359

  18. Development of a harmonised method for the profiling of amphetamines: IV. Optimisation of sample preparation.

    Science.gov (United States)

    Andersson, Kjell; Jalava, Kaisa; Lock, Eric; Huizer, Henk; Kaa, Elisabet; Lopes, Alvaro; Poortman-van der Meer, Anneke; Cole, Michael D; Dahlén, Johan; Sippola, Erkki

    2007-06-14

    The suitability of liquid-liquid extraction (LLE) and solid-phase extraction (SPE) for the preparation of impurity extracts intended for gas chromatographic profiling analyses of amphetamine were evaluated. Both techniques were optimised with respect to the extraction of selected target compounds by use of full factorial designs in which the variables affecting the performance were evaluated. Test samples consisted of amphetamine synthesised by the Leuckart reaction, by reductive amination of benzyl methyl ketone and by the nitrostyrene route. The performance of LLE and SPE were comparable in terms of repeatability and recovery of the target compounds. LLE was considered the better choice for the present harmonised amphetamine profiling method due to the lack of information on the long-term stability of SPE columns. PMID:17134863

  19. Relationship between methamphetamine use history and segmental hair analysis findings of MA users.

    Science.gov (United States)

    Han, Eunyoung; Lee, Sangeun; In, Sanghwan; Park, Meejung; Park, Yonghoon; Cho, Sungnam; Shin, Junguk; Lee, Hunjoo

    2015-09-01

    The aim of this study was to investigate the relationship between methamphetamine (MA) use history and segmental hair analysis (1 and 3cm sections) and whole hair analysis results in Korean MA users in rehabilitation programs. Hair samples were collected from 26 Korean MA users. Eleven of the 26 subjects used cannabis with MA and two used cocaine, opiates, and MDMA with MA. Self-reported single dose of MA from the 26 subjects ranged from 0.03 to 0.5g/one time. Concentrations of MA and its metabolite amphetamine (AP) in hair were determined by gas chromatography mass spectrometry (GC/MS) after derivatization. The method used was well validated. Qualitative analysis from all 1cm sections (n=154) revealed a good correlation between positive or negative results for MA in hair and self-reported MA use (69.48%, n=107). In detail, MA results were positive in 66 hair specimens of MA users who reported administering MA, and MA results were negative in 41 hair specimens of MA users who denied MA administration in the corresponding month. Test results were false-negative in 10.39% (n=16) of hair specimens and false-positive in 20.13% (n=31) of hair specimens. In false positive cases, it is considered that after MA cessation it continued to be accumulated in hair still, while in false negative cases, self-reported histories showed a small amount of MA use or MA use 5-7 months previously. In terms of quantitative analysis, the concentrations of MA in 1 and 3cm long hair segments and in whole hair samples ranged from 1.03 to 184.98 (mean 22.01), 2.26 to 89.33 (mean 18.71), and 0.91 to 124.49 (mean 15.24)ng/mg, respectively. Ten subjects showed a good correlation between MA use and MA concentration in hair. Correlation coefficient (r) of 7 among 10 subjects ranged from 0.71 to 0.98 (mean 0.85). Four subjects showed a low correlation between MA use and MA concentration in hair. Correlation coefficient (r) of 4 subjects ranged from 0.36 to 0.55. Eleven subjects showed a poor

  20. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Science.gov (United States)

    de Oliveira, Lúcio Garcia; de Souza, Letícia Maria de Araújo; Barroso, Lúcia Pereira; Gouvêa, Marcela Júlio César; de Almeida, Carlos Vinícius Dias; Muñoz, Daniel Romero; Leyton, Vilma

    2015-01-01

    OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for. METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders). A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI) was defined as the measure for association. The significance level was established as p < 0.05. RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8) years, as well as low education (8.6 [SD = 2.3] years); 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69), having spent less than nine years at school (OR = 1.76), being autonomous (OR = 1.65), working night shifts or irregular schedules (OR = 2.05), working over 12 hours daily (OR = 2.14), and drinking alcohol (OR = 1.74). CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”); Law 12,619/2012) which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil. PMID:26398875

  1. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Directory of Open Access Journals (Sweden)

    Lúcio Garcia de Oliveira

    2015-01-01

    Full Text Available OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for.METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders. A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI was defined as the measure for association. The significance level was established as p < 0.05.RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8 years, as well as low education (8.6 [SD = 2.3] years; 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69, having spent less than nine years at school (OR = 1.76, being autonomous (OR = 1.65, working night shifts or irregular schedules (OR = 2.05, working over 12 hours daily (OR = 2.14, and drinking alcohol (OR = 1.74.CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”; Law 12,619/2012 which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil.

  2. Digital Droplet Multiple Displacement Amplification (ddMDA for Whole Genome Sequencing of Limited DNA Samples.

    Directory of Open Access Journals (Sweden)

    Minsoung Rhee

    Full Text Available Multiple displacement amplification (MDA is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently, the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet, ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.

  3. Digital Droplet Multiple Displacement Amplification (ddMDA) for Whole Genome Sequencing of Limited DNA Samples

    Science.gov (United States)

    Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.; Singh, Anup K.

    2016-01-01

    Multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently, the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology. PMID:27144304

  4. Amphetamine margin in sports. [Effects on performance of highly trained athletes

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1980-01-01

    The amphetamines can enhance athletic performance. That much seems clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both man and rat. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogues of such performance have also been used and similar enhancement demonstrated. The amount of change induced by the amphetamines is usually small, of the order of a few percent. Nevertheless, since a fraction of a percent improvement can make the difference between fame and oblivion, the margin conferred by these drugs can be quite important.

  5. Expression of Monstera deliciosa agglutinin gene (mda) in tobacco confers resistance to peach-potato aphids.

    Science.gov (United States)

    Kai, Guoyin; Ji, Qian; Lu, Yang; Qian, Zhongying; Cui, Lijie

    2012-08-01

    The aphid is one of the most serious pests that causes damage to crops worldwide. Lectins from Araceae plant had been proved useful to control the aphid. Herein, the full-length cDNA of Monstera deliciosa agglutinin (mda) gene was cloned and then introduced into tobacco and the influence of the expression of mda in transgenic tobacco against peach-potato aphids (Myzus persicae) was investigated. Among 92 regenerated plants, 59 positive tobacco lines were obtained. Real-time PCR assays and aphid bioassay test revealed that there is a positive correlation between the expression level of mda and the inhibitory effect on peach-potato aphids. The average anti-pests ability of mda transgenic tobacco was 74%, which was higher than that of other reported lectins from Araceae plant. These results indicated that MDA is one of promising insect resistance proteins selected for the control of peach-potato aphids. PMID:22660606

  6. l-Amphetamine improves poor sustained attention while d-amphetamine reduces overactivity and impulsiveness as well as improves sustained attention in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Xu Tong

    2008-01-01

    Full Text Available Abstract Background ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR, shows pronounced overactivity, impulsiveness, and deficient sustained attention. While dopamine release is decreased in SHR, norepinephrine concentrations are elevated. The primary objective of the present research was to test effects of a range of doses of the catecholamine agonists d- and l-amphetamine on ADHD-like symptoms in SHR. Methods The present study tested behavioral effects of 0.64 to 1.91 mg/kg d-amphetamine; and 1.27 to 3.81 mg/kg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY. ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Results The striking impulsiveness, overactivity, and poorer sustained attention during baseline conditions in the SHR were improved by treatment with the amphetamine isomers. The dose-response curves were, however, different for the different behaviors. Most significantly, d-amphetamine reduced overactivity and impulsiveness more efficiently than comparable doses of l-amphetamine. The lowest dose of d-amphetamine and low-to-medium doses of l-amphetamine improved sustained attention. The highest dose of d-amphetamine used interfered with SHR behavior. A second study showed that the impaired sustained attention (percent correct lever choice in the SHR was not due to impaired visual functions or poorer working memory. Discussion The present results indicate that

  7. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis.

    Science.gov (United States)

    Asdonk, Tobias; Steinmetz, Martin; Krogmann, Alexander; Ströcker, Christine; Lahrmann, Catharina; Motz, Inga; Paul-Krahe, Kathrin; Flender, Anna; Schmitz, Theresa; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2016-09-01

    Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA-5) belongs to the intracellular retinoic acid inducible gene-I like receptors and its activation promotes pro-inflammatory mechanisms. Here, we studied the effect of MDA-5 stimulation in vascular biology. To gain insights into MDA-5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA-5 agonist polyIC (long double-stranded RNA). Human coronary endothelial cell expressed MDA-5 and reacted with receptor up-regulation upon stimulation. Reactive oxygen species formation, apoptosis and the release of pro-inflammatory cytokines was enhanced, whereas migration was significantly reduced in response to MDA-5 stimulation. To test these effects in vivo, wild-type mice were transfected with 32.5 μg polyIC/JetPEI or polyA/JetPEI as control every other day for 7 days. In polyIC-treated wild-type mice, endothelium-dependent vasodilation and re-endothelialization was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticles and circulating endothelial progenitor cells significantly elevated compared to controls. Importantly, these effects could be abrogated by MDA-5 deficiency in vivo. Finally, chronic MDA-5 stimulation in Apolipoprotein E/toll-like receptor 3 (TLR3) double(-) deficient (ApoE(-/-) /TLR3(-/-) ) mice-enhanced atherosclerotic plaque formation. This study demonstrates that MDA-5 stimulation leads to endothelial dysfunction, and has the potential to aggravate atherosclerotic plaque burden in murine atherosclerosis. Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA-5. PMID:27130701

  8. The Persian methamphetamine use in methadone treatment in Iran: implication for prevention and treatment in an upper-middle income country

    OpenAIRE

    Alam-mehrjerdi, Zahra; Abdollahi, Mohammad

    2015-01-01

    As the most populated Persian Gulf country in West Asia, methamphetamine use in methadone maintenance treatment (MMT) is a new health concern in Iran. Methamphetamine use in MMT can originate in methadone misconceptions or the stimulant effects of methamphetamine use. Several research studies have highlighted the prevalence of methamphetamine use in Iran and conducting further studies on this issue is being developed. Opiate use is treated with MMT. But, there is no effective pharmacological ...

  9. Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

    International Nuclear Information System (INIS)

    I investigated the differences in brain pharmacokinetics of [11C]methamphetamine ([11C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [11C]MAP was synthesized by an automated on-line [11C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [11C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

  10. How various drugs affect anxiety-related behavior in male and female rats prenatally exposed to methamphetamine.

    Science.gov (United States)

    Macúchová, E; Ševčíková, M; Hrebíčková, I; Nohejlová, K; Šlamberová, R

    2016-06-01

    Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the

  11. Assessing Correlates of the Growth and Extent of Methamphetamine Abuse and Dependence in California

    OpenAIRE

    Gruenewald, Paul J.; Johnson, Fred W.; Ponicki, William R.; Remer, Lillian G.; LaScala, Elizabeth A.

    2010-01-01

    Using aggregate-level data, this study performed cross-sectional analyses on all 1,628 populated California zip code areas and longitudinal analyses on 581 consistently defined zip codes over six years (1995– 2000), relating place and population characteristics of these areas to rates of hospital discharges for amphetamine dependence/abuse using linear spatial models. Analyzing the data in two ways, spatial time series cross-sections and spatial difference models, amphetamin...

  12. "Nothing Is Free": A Qualitative Study of Sex Trading Among Methamphetamine Users in Cape Town, South Africa.

    Science.gov (United States)

    Watt, Melissa H; Kimani, Stephen M; Skinner, Donald; Meade, Christina S

    2016-05-01

    South Africa is facing an established epidemic of methamphetamine, known locally as "tik." Globally, methamphetamine has been linked to high rates of sexual risk behaviors, including sex trading. The goal of this study was to qualitatively examine the experiences of sex trading among methamphetamine users in Cape Town, South Africa. Individual in-depth interviews were conducted with 30 active methamphetamine users (17 men and 13 women) recruited from the community. Interviews were conducted in local languages using a semi-structured guide that included questions on sex trading experiences and perceptions of sex trading among methamphetamine users. Interviews were audio-recorded, transcribed, and analyzed using analytic memos and coding with constant comparison techniques. The data revealed that in a setting of high levels of addiction and poverty, sex was an important commodity for acquiring methamphetamine. Women were more likely to use sex to acquire methamphetamine, but men reported opportunistic cases of trading sex for methamphetamine. Four models of sex trading emerged: negotiated exchange, implicit exchange, relationships based on resources, and facilitating sex exchange for others. The expectation of sex trading created a context in which sexual violence against female methamphetamine users was common. Multiple sexual partners and inconsistent condom use in acts of sex trading put methamphetamine users at high risk of HIV. Interventions in this setting should address addiction, which is the primary driver of sex trading among methamphetamine users. Harm reduction interventions may include education about HIV and other sexually transmitted infections, availability of condoms and HIV testing, and sexual violence prevention. PMID:25567071

  13. Association Between 5HT1b Receptor Gene and Methamphetamine Dependence

    Science.gov (United States)

    Ujike, H; Kishimoto, M; Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N

    2011-01-01

    Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis. PMID:21886584

  14. The identification of an impurity product, 4,6-dimethyl-3,5-diphenylpyridin-2-one in an amphetamine importation seizure, a potential route specific by-product for amphetamine synthesized by the APAAN to P2P, Leuckart route.

    Science.gov (United States)

    Power, John D; O'Brien, John; Talbot, Brian; Barry, Michael; Kavanagh, Pierce

    2014-08-01

    During the analysis of a Customs' importation case for the suspected presence of controlled drugs, amphetamine was found to be present. The samples were also found to contain by-products from the amphetamine synthesis and these included benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, a pair of naphthalene derivatives and amphetamine dimers. During the experimental investigation of the naphthalenes formation, a series of syntheses involved the acid hydrolysis of α-phenylacetoacetonitrile (APAAN). In one such experiment with sulfuric acid, a white substance was visibly deposited on the glassware and this was identified as the pyridone derivative, 4,6-dimethyl-3,5-diphenylpyridin-2-one. This compound was subsequently found to be present in the amphetamine product seized by the Customs and also in the final product of our own laboratory synthesized amphetamine (APAAN hydrolyzed to P2P/Leuckart reaction). Interestingly, the, 4,6-dimethyl-3,5-diphenylpyridin-2-one was not found when commercially supplied P2P underwent the Leuckart reaction to yield amphetamine. This suggests that 4,6-dimethyl-3,5-diphenylpyridin-2-one may be a route specific marker to the use of APAAN as a starting material in the synthesis of P2P and subsequent Leuckart reaction to yield amphetamine. PMID:24933633

  15. Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water

    International Nuclear Information System (INIS)

    In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine-(H2O)1,2 complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S0→ S1 transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine-(H2O)1,2 are tentatively assigned

  16. The N terminus of monoamine transporters is a lever required for the action of amphetamines

    DEFF Research Database (Denmark)

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara;

    2010-01-01

    The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N t...

  17. Simultaneous Determination of Heroin, Amphetamine and their Basic Impurities and Adulterants Using Microemulsion Electrokinetic Chromatography

    Institute of Scientific and Technical Information of China (English)

    Tao WEN; Xia ZHAO; Guo An LUO; Jian WANG; Yi Ming WANG; Pan LI; Jun ZHU; Zhong Shang YU

    2005-01-01

    Simultaneous separation of 17 species of heroin, amphetamine and their basic impurities and adulterants was conducted within 10 minutes by using capillary microemulsion electrokinetic chromatography. The influences of pH and 1-butanol cosurfactant on the separation were investigated, and 1-butanol was found to be a principal factor to improve separation efficiency.

  18. Genetic NMDA receptor deficiency disrupts acute and chronic effects of cocaine but not amphetamine.

    Science.gov (United States)

    Ramsey, Amy J; Laakso, Aki; Cyr, Michel; Sotnikova, Tatyana D; Salahpour, Ali; Medvedev, Ivan O; Dykstra, Linda A; Gainetdinov, Raul R; Caron, Marc G

    2008-10-01

    NMDA receptor-mediated glutamate transmission is required for several forms of neuronal plasticity. Its role in the neuronal responses to addictive drugs is an ongoing subject of investigation. We report here that the acute locomotor-stimulating effect of cocaine is absent in NMDA receptor-deficient mice (NR1-KD). In contrast, their acute responses to amphetamine and to direct dopamine receptor agonists are not significantly altered. The striking attenuation of cocaine's acute effects is not likely explained by alterations in the dopaminergic system of NR1-KD mice, since most parameters of pre- and postsynaptic dopamine function are unchanged. Consistent with the behavioral findings, cocaine induces less c-Fos expression in the striatum of these mice, while amphetamine-induced c-Fos expression is intact. Furthermore, chronic cocaine-induced sensitization and conditioned place preference are attenuated and develop more slowly in mutant animals, but amphetamine's effects are not altered significantly. Our results highlight the importance of NMDA receptor-mediated glutamatergic transmission specifically in cocaine actions, and support a hypothesis that cocaine and amphetamine elicit their effects through differential actions on signaling pathways. PMID:18185498

  19. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.

    1991-01-01

    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  20. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    Science.gov (United States)

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  1. Effects of haloperidol and d-amphetamine on perceived quantity of food and tones.

    Science.gov (United States)

    Martin-Iverson, M T; Wilkie, D; Fibiger, H C

    1987-01-01

    The hypothesis that dopamine (DA) receptor agonists and antagonists affect "hedonia" associated with natural rewards was tested, using a psychophysical procedure previously shown to be sensitive to both the sweetness of food and the motivational state of rats. Rats were first trained to discriminate between two different quantities of a rewarding stimulus by pressing one of two levers. Perceived quantity was subsequently derived from generalization trials of intermediate quantities. Haloperidol (0.03-0.083 mg/kg), a DA receptor antagonist, did not influence perceived food quantity, an indirect marker of hedonic value. On the other hand, d-amphetamine (0.25-1.0 mg/kg) affected perceived food quantity in a dose-dependent fashion, and in the same direction as occurs after increasing hunger or food sweetness. Both haloperidol and amphetamine influenced the perceived quantity of a stimulus without natural reinforcing properties (a tone), but the effect of amphetamine on the perceived quantity of this initially neutral stimulus was opposite in direction to that observed with food. These results suggest that whereas amphetamine affects hedonic processes, haloperidol does not. In addition, it seems that haloperidol probably produces its actions through effects on motor mechanisms or by interfering with the response-facilitating properties of rewards. PMID:3124167

  2. Personality and gender differences in effects of d-amphetamine on risk taking.

    Science.gov (United States)

    White, Tara L; Lejuez, C W; de Wit, Harriet

    2007-12-01

    The effects of stimulant drugs on risk-taking behavior vary across individuals, even in healthy samples. These differences could relate to personality, which may share common mechanisms with drug effects or impulsive, risk-taking behavior. The current study investigated the role of temperament and gender in the effects of amphetamine on risk taking. Forty healthy men and women, aged 18 to 35, completed the Balloon Analogue Risk Task (BART; Lejuez et al., 2002) with three reward values after ingesting placebo or d-amphetamine (10, 20 mg). They completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF; Patrick et al., 2002), with three main scales: Trait reward sensitivity (Agentic Positive Emotionality; AgPEM), impulsivity (Constraint; CON), and negative affect (Negative Emotionality; NEM). d-Amphetamine (20 mg) decreased risk behavior in low AgPEM males, but increased risk behavior in high AgPEM males, producing positive correlations with AgPEM in men (r >or= +.55, pdrug did not affect risk-taking in women. There was evidence of discriminant validity between the AgPEM, NEM, and CON dimensions and behavioral responses to amphetamine. Implications for treatment and addiction are discussed. (c) 2008 APA, all rights reserved. PMID:18179313

  3. Effectiveness of Hope Therapy Protocol on Depression and Hope in Amphetamine Users

    Directory of Open Access Journals (Sweden)

    Sadeghi

    2015-12-01

    Full Text Available Background Addiction has surpassed the boundaries of health and treatment and turned into a social crisis and a debilitating and major concern in today’s world. Amphetamine, one of the addictive drugs, is classified as psycho-stimulants drugs, which increase arousal, alertness, and motor activity. Humans report that this drug produces a significant euphoria and is highly addictive. Objectives The present study aimed to evaluate the effectiveness of hope therapy protocol (HTP on depression reduction and hope increase in amphetamine users. Patients and Methods This study has a quasi-experimental design with experimental and control groups. The sample included all amphetamine consumers referring to day drug addiction treatment center in Ray City, Iran, selected with convenience method. In order to analyze the data, multivariate analysis of covariance (MANCOVA was applied using SPSS software. Results The results showed that F value of mean scores in depression and hope post-tests of the experimental and control groups are 24.94 and 25.73, respectively, which are significant (P < 0.01. Therefore, hope therapy training could reduce depressive symptoms in amphetamine consumers and improve their hope. Conclusions Performing HTP can improve hopefulness and symptoms of patients, specially addicted ones. In addition, it can prevent substance abusers from returning to drugs and leaving the treatment period unfinished.

  4. Medial prefrontal cortex infusions of bupivacaine or AP-5 block extinction of amphetamine conditioned place preference.

    Science.gov (United States)

    Hsu, Emily; Packard, Mark G

    2008-05-01

    The present experiments used reversible lesion techniques and intra-mPFC infusions of the n-methyl D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP-5) to examine the role of the mPFC in extinction of an amphetamine conditioned place preference (CPP). Following initial training and testing for an amphetamine (2 mg/kg) CPP, adult male Long-Evans rats were given extinction trials that were identical to training, except in the absence of peripheral amphetamine injections. Immediately prior to each extinction trial, rats received intra-mPFC infusions of the anesthetic drug bupivacaine (0.75% solution/0.5 microl), AP-5 (1.25, 2.5, 5.0 microg/0.5 microl), or saline. Following extinction training, rats were given a second CPP test session. Rats receiving intra-mPFC infusions of saline displayed extinction of CPP behavior. In contrast, intra-mPFC infusions of bupivacaine or AP-5 (2.5, 5.0 microg) blocked CPP extinction. The findings indicate (1) the mPFC mediates extinction of approach behavior to drug-associated environmental contexts, and (2) NMDA receptor blockade within the mPFC is sufficient to block extinction of amphetamine CPP behavior. PMID:17905604

  5. Acute but not delayed amphetamine treatment improves behavioral outcome in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, Karsten; Kristiansen, Uffe;

    2011-01-01

    OBJECTIVES: The objective of this study was to examine the effects of d-amphetamine (amph) upon recovery after embolic stroke in rats. METHODS: Ninety-three rats were embolized in the right middle cerebral artery and assigned to: (1) controls; (2) combination (acute amph and later amph-facilitate...

  6. Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+, K+-ATPase activity

    International Nuclear Information System (INIS)

    Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (370C) resulted in a time-dependent decrease in specific (+)-[3H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[3H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[3H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[3H]amphetamine binding, suggesting the involvement of Na+, K+-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na+,K+-ATPase activity and the number of specific high-affinity binding sites for [3H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[3H]amphetamine and [3H]ouabain binding. These data suggest that the (+)-[3H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na+,K+-ATPase activity, and the latter may be involved in the glucostatic regulation of appetite

  7. Initial Feasibility and Acceptability of a Comprehensive Intervention for Methamphetamine-Using Pregnant Women in South Africa

    Directory of Open Access Journals (Sweden)

    Hendrée E. Jones

    2014-01-01

    Full Text Available The purpose of the present study was to determine the feasibility, acceptability, and initial efficacy of a women-focused intervention addressing methamphetamine use and HIV sexual risk among pregnant women in Cape Town, South Africa. A two-group randomized pilot study was conducted, comparing a women-focused intervention for methamphetamine use and related sexual risk behaviors to a psychoeducational condition. Participants were pregnant women who used methamphetamine regularly, had unprotected sex in the prior month, and were HIV-negative. Primary maternal outcomes were methamphetamine use in the past 30 days, frequency of unprotected sexual acts in the past 30 days, and number of antenatal obstetrical appointments attended. Primary neonatal outcomes were length of hospital stay, birth weight, and gestational age at delivery. Of the 57 women initially potentially eligible, only 4 declined to participate. Of the 36 women who were eligible and enrolled, 92% completed all four intervention sessions. Women in both conditions significantly reduced their methamphetamine use and number of unprotected sex acts. Therefore, delivering comprehensive interventions to address methamphetamine use and HIV risk behaviors among methamphetamine-using pregnant women is feasible in South Africa. Further testing of these interventions is needed to address methamphetamine use in this vulnerable population.

  8. Rapid quantification of methamphetamine: using attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR and chemometrics.

    Directory of Open Access Journals (Sweden)

    Juanita Hughes

    Full Text Available In Australia and increasingly worldwide, methamphetamine is one of the most commonly seized drugs analysed by forensic chemists. The current well-established GC/MS methods used to identify and quantify methamphetamine are lengthy, expensive processes, but often rapid analysis is requested by undercover police leading to an interest in developing this new analytical technique. Ninety six illicit drug seizures containing methamphetamine (0.1%-78.6% were analysed using Fourier Transform Infrared Spectroscopy with an Attenuated Total Reflectance attachment and Chemometrics. Two Partial Least Squares models were developed, one using the principal Infrared Spectroscopy peaks of methamphetamine and the other a Hierarchical Partial Least Squares model. Both of these models were refined to choose the variables that were most closely associated with the methamphetamine % vector. Both of the models were excellent, with the principal peaks in the Partial Least Squares model having Root Mean Square Error of Prediction 3.8, R(2 0.9779 and lower limit of quantification 7% methamphetamine. The Hierarchical Partial Least Squares model had lower limit of quantification 0.3% methamphetamine, Root Mean Square Error of Prediction 5.2 and R(2 0.9637. Such models offer rapid and effective methods for screening illicit drug samples to determine the percentage of methamphetamine they contain.

  9. Effect of Abstinence on Depression, Anxiety, and Quality of Life in Chronic Methamphetamine Users in a Therapeutic Community

    OpenAIRE

    Bagheri; Mokri,; Khosravi; Kabir

    2015-01-01

    Background During withdrawal, patients experience different symptoms. These symptoms are associated with relapse. Understanding different outcomes of methamphetamine abstinence is useful for finding better treatments for dependence. Objectives This study aimed to show the effects of abstinence on depression, anxiety, and quality of life in methamphetamine users. Patients and Methods ...

  10. The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Candace R. Lewis

    2013-06-01

    Full Text Available The maternal separation (MS paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH causes great harm to both the individual user and to society; yet, no studies have examined the effects of MS on METH SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2 in the nucleus accumbens (NAc core were also investigated. Long-Evans pups and dams were separated on postnatal days (PND 2-14 for either 180 (MS180 or 15 min (MS15. Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion in 15 2-hr daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

  11. Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression.

    Science.gov (United States)

    Jiang, Mingjin; Chen, Yifei; Li, Chan; Peng, Qiuxian; Fang, Miao; Liu, Wei; Kang, Qunzhao; Lin, Yingbo; Yung, Ken Kin Lam; Mo, Zhixian

    2016-07-01

    Others and we have reported that rhynchophylline reverses amphetamine-induced conditioned place preference (CPP) effect which may be partly mediated by amelioration of central neurotransmitters and N-methyl-d-aspartate receptor 2B (NR2B) levels in the rat brains. The current study investigated the inhibiting effects of rhynchophylline on methamphetamine-induced (METH-induced) CPP in adult zebrafish and METH-induced locomotor activity in tyrosine hydroxylase-green fluorescent protein (TH-GFP) transgenic zebrafish larvae and attempted to confirm the hypothesis that these effects were mediated via regulation of neurotransmitters and dopaminergic and glutamatergic systems. After baseline preference test (on days 1-3), zebrafish were injected intraperitoneally METH (on days 4, 6 and 8) or the same volume of fish physiological saline (on days 5 and 7) and were immediately conditioned. Rhynchophylline was administered at 12h after injection of METH. On day 9, zebrafish were tested for METH-induced CPP. Results revealed that rhynchophylline (100mg/kg) significantly inhibited the acquisition of METH-induced CPP, reduced the content of dopamine and glutamate and down-regulated the expression of TH and NR2B in the CPP zebrafish brains. Furthermore, the influence of rhynchophylline on METH-induced locomotor activity was also observed in TH-GFP transgenic zebrafish larvae. Results showed that rhynchophylline (50mg/L) treatment led to a significant reduction on the locomotor activity and TH expression in TH-GFP transgenic zebrafish larvae. Taken together, these data indicate that the inhibition of the formation of METH dependence by rhynchophylline in zebrafish is associated with amelioration of the neurotransmitters dopamine and glutamate content and down-regulation of TH and NR2B expression. PMID:27009763

  12. Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

    OpenAIRE

    Kim, Jin Joo; Ha, Ae Wha; Kim, Hee Sun; Kim, Woo Kyoung

    2011-01-01

    This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly d...

  13. Acute methoxetamine and amphetamine poisoning with fatal outcome: A case report

    Directory of Open Access Journals (Sweden)

    Marek Wiergowski

    2014-08-01

    Full Text Available Methoxetamine (MXE is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdańsk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 μg/ml was within the non-toxic range, while MXE (0.32 μg/ml was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them.

  14. Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers.

    Science.gov (United States)

    Mick, Inge; Myers, Jim; Ramos, Anna C; Stokes, Paul R A; Erritzoe, David; Colasanti, Alessandro; Gunn, Roger N; Rabiner, Eugenii A; Searle, Graham E; Waldman, Adam D; Parkin, Mark C; Brailsford, Alan D; Galduróz, José C F; Bowden-Jones, Henrietta; Clark, Luke; Nutt, David J; Lingford-Hughes, Anne R

    2016-06-01

    Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions. PMID:26552847

  15. Amphetamine-related myocardial infarction in a 42-year old man.

    Science.gov (United States)

    Smędra, A; Szustowski, S; Berent, J

    2015-01-01

    Myocardial infarction is an infrequent condition in young adults. In most cases, it occurs due to causes other than atherosclerosis of the coronary arteries, including blood hypercoagulability, congenital anomalies of the coronary arteries, their inflammation or spasm induced by amphetamine or cocaine use. Amphetamine and its derivatives, via increasing the levels of epinephrine, serotonin and dopamine in the central nervous system, exert their effect also on the cardiovascular system, causing coronary spasm, enhancing platelet aggregation and inducing tachyarrhythmias. The paper presents a case of a 42-year-old man admitted to the emergency department because of emaciation and dehydration. The man was conscious, without contact, with a significant elevation of body temperature and tachycardia. On the basis of examinations, a fresh infarction of the anterolateral wall of the heart was diagnosed and the patient was transferred to a cardiac intensive care unit. There, laboratory tests revealed significantly elevated markers of myocardial necrosis and the presence of amphetamine in blood and urine. In spite of the institution of treatment the patient developed cardiorespiratory arrest. Advanced resuscitation procedures were undertaken, however, they proved unsuccessful. The presence of an infarction focus was confirmed in autopsy. Toxicological analysis of the blood for the presence of alcohol-like substances detected amphetamine at a concentration of 269.5 ng/ml. After examining the complete body of evidence it was established that the patient had died of acute cardiorespiratory failure secondary to an extensive fresh myocardial infarction. As indicated by the accumulated data, the most probable cause of myocardial infarction was amphetamine poisoning. PMID:27003867

  16. Optimization of a methamphetamine conjugate vaccine for antibody production in mice.

    Science.gov (United States)

    Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

    2016-06-01

    There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. PMID:27039212

  17. Text Messaging Reduces HIV Risk Behaviors among Methamphetamine-using Men Who Have Sex with Men

    Science.gov (United States)

    Reback, Cathy J.; Grant, Deborah Ling; Fletcher, Jesse B.; Branson, Catherine M.; Shoptaw, Steven; Bowers, Jane Rohde; Charania, Mahnaz; Mansergh, Gordon

    2016-01-01

    Text-messaging interventions present a novel approach for targeting high-risk men who have sex with men (MSM) who may not respond to or may be difficult to reach for face-to-face or site-based interventions. Project Tech Support (N = 52) was an open label pilot study testing the feasibility and utility of a text-messaging intervention to reduce methamphetamine use and high-risk sexual behaviors among out-of-treatment MSM. Participants in the two-week intervention received social support and health education text messages transmitted in real-time. At follow-up, there were significant decreases in frequency of methamphetamine use and unprotected sex while on methamphetamine (both p < .01), and a significant increase in self-reported abstinence from methamphetamine use (13.3% vs. 48.9%; p<.001). Additionally, participants reported reductions of unprotected anal intercourse with HIV-positive partners (p < .01); with HIV-negative partners, participants reported fewer insertive and receptive episodes (both p < .05). Findings demonstrate that text messaging is a promising intervention for reaching and potentially changing HIV high-risk behaviors among out-of-treatment, methamphetamine-using MSM. PMID:22610370

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  6. Current Bancroftian Filariasis Elimination on Thailand-Myanmar Border: Public Health Challenges toward Postgenomic MDA Evaluation

    OpenAIRE

    Bhumiratana, Adisak; Intarapuk, Apiradee; Koyadun, Surachart; Maneekan, Pannamas; Sorosjinda-Nunthawarasilp, Prapa

    2013-01-01

    From regional and global perspectives, Thailand has progressed toward lymphatic filariasis transmission-free zone in almost entire endemic provinces, being verified by WHO by the end of 2012 after the 5-year implementation of mass drug administration (MDA) with diethylcarbamazine and albendazole as part of the National Program to Eliminate Lymphatic Filariasis (PELF) (2002–2006) and a 4-year expansion of post-MDA surveillance (2007–2010). However, Thai PELF has been challenging sensitive situ...

  7. Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Yao; Jianxin Yao; Xia He; Zhanfeng Li; Yongbiao Liu

    2013-01-01

    Objective: The aim of the study was to investigate the apoptosis induced by piperlongumine on human breast adenoma MDA-MB-231 cells and the mechanism involved. Methods: Human breast adenoma MDA-MB-231 cells line was cultured in vitro. The inhibitory effect of piperlongumine on the proliferation of human breast adenoma MDA-MB-231 cells was measured by CCK-8 assay. Distribution of cell cycle was analyzed by flow cytometry. The apoptosis rates of MDA-MB- 231 cells were measured using Annexin V/PI staining. The flow cytometry with the probe of DCFH-DA was used to detect the intracellular reactive oxygen species levels. Western blot was used to explore the protein expression of Bcl-2 and Bax. Results: The CCK-8 assay showed that piperlongumine had an inhibiting effect on the proliferation of MDA-MB-231 cells in a concentration- and time-dependent manner. MDA-MB-231 cells were markedly arrested at G0/G1 phase after treatment of piperlongumine. Piperlongumine induced apoptosis of MDA-MB-231 cells obviously. The level of intracellular reactive oxygen species was increased in a dose-dependent manner. The antioxidant N-acetyl-L-cystein inhibited the apoptosis of cells and the level of intracellular reactive oxygen species was also decreased. By Western blot analysis, we found the expression of Bax was up-regulated whereas that of Bcl-2 was down-regulated in a concentration-dependent manner. Conclusion: Piperlongumine possesses a significant function for inhibiting proliferation, arresting cells at G0/G1 phase and inducing apoptosis of MDA-MB-231 cells, which seems to be associated with the increased generation of intracellular reactive oxygen species as well as the down-regulation of Bcl-2 and up-regulation of Bax.

  8. Free radical production induced by methamphetamine in rat striatal synaptosomes

    International Nuclear Information System (INIS)

    The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 μM) prevented METH-induced ROS production, thus implicating calcium and α7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 μM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 μM) for 30 min reduced [3H]DA uptake by 60%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of α7 nicotinic receptors and Ca2+ entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates α7 nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca2+. This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA

  9. HIV-1, Methamphetamine and Astrocytes at Neuroinflammatory crossroads

    Directory of Open Access Journals (Sweden)

    Kathleen eBorgmann

    2015-10-01

    Full Text Available As a popular psychostimulant, methamphetamine (METH use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10-15% of human immunodeficiency virus-1 (HIV-1 patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND through direct and indirect mechanisms. Repetitive METH use decreases adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression towards AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte number and activity, cytokine signaling, phagocytic function, and CNS infiltration through the blood brain barrier. Further, METH triggers the neuronal dopamine reward pathway and leads to altered neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation. Neuroinflammation modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress and excitotoxicity. Pathologically, glial activation is a hallmark of both HIV-1 and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, neuroinflammation and HAND are carefully reviewed. Interventions targeting astrocytes in HAND and METH are presented as potential novel therapeutic approaches.

  10. Modification of Monoaminergic Activity by MAO Inhibitors Influences Methamphetamine Actions

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2006-01-01

    Full Text Available Methamphetamine (METH abuse is a serious health and social problem worldwide. At present, however, there are no effective medications for the treatment of METH abuse. Of the intracellular METH target proteins, monoamine oxidase (MAO is involved in the regulation of monoaminergic tone in the brain, resulting in the modulation of METHinduced behavioral abnormalities in mammals. The METH-induced expression of increased motor activity, stereotypy, and sensitization is closely associated with monoaminergic transmission in the brain. Modifi cation of MAO activity by MAO inhibitors can influence METH action. Of the MAO inhibitors, the propargylamine derivative clorgyline, an irreversible MAO-A inhibitor, effectively blocks METH-induced hyperlocomotion and behavioral sensitization in rodents. Analysis of the associated monoaminergic activity indicates an involvement of altered striatal serotonergic transmission as well as an increased dopaminergic tone. Some effects of MAO inhibitors on METH action appear to be independent of MAO, suggesting complex mechanisms of action of MAO inhibitors in METH abuse. This review describes current research to find effective treatment for METH abuse, using MAO inhibitors.

  11. Rhynchophylline Protects Cultured Rat Neurons against Methamphetamine Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Dan Dan Xu

    2012-01-01

    Full Text Available Rhynchophylline (Rhy is an active component isolated from species of the genus Uncaria which has been used for the treatment of ailments to the central nervous system in traditional Chinese medicine. Besides acting as a calcium channel blocker, Rhy was also reported to be able to protect against glutamate-induced neuronal death. We thus hypothesize that Rhy may have neuroprotective activity against methamphetamine (MA. The primary neurons were cultured directly from the cerebral cortex of neonatal rats, acting as in vitro model in the present study. The neurotoxicity of MA and the protective effect of Rhy were evaluated by MTT assay. The effects of MA, Rhy or their combination on intracellular free calcium concentration ([Ca2+]i were determined in individual neocortical neurons by the Fluo-3/AM tracing method. The MTT assay demonstrated that MA has a dose-dependent neurotoxicity in neuronal cultures. The addition of Rhy prior to the exposure to MA prevented neuronal death. Time course studies with the Fluo-3/AM probe showed that Rhy significantly decreased neuronal [Ca2+]i which was elevated by the exposure to MA. Our results suggested that Rhy can protect the neuronal cultures against MA exposure and promptly attenuate intracellular calcium overload triggered by MA challenge. This is the first report demonstrating an inhibitory effect of Rhy against MA impairment in cultured neurons in vitro.

  12. The effects of vasopressin and oxytocin on methamphetamine-induced place preference behaviour in rats.

    Science.gov (United States)

    Subiah, Cassandra O; Mabandla, Musa V; Phulukdaree, Alisa; Chuturgoon, Anil A; Daniels, Willie M U

    2012-09-01

    Methamphetamine is a highly addictive stimulant drug whose illicit use and resultant addiction has become an alarming global phenomenon. The mesolimbic dopaminergic pathway has been shown to be fundamental to the establishment of addictive behaviour. This pathway, as part of the reward system of the brain, has also been shown to be important in classical conditioning, which is a learnt response. Within the modulation of learning and memory, the neurohypophyseal hormones vasopressin and oxytocin have been reported to play a vital role, with vasopressin exerting a long- term facilitatory effect and oxytocin exerting an inhibitory effect. Therefore we adopted a conditioned place preference model to investigate whether vasopressin V1b receptor antagonist SSR 149415 or oxytocin treatment would cause a decrease in the seeking behaviour in a reinstatement paradigm. Behavioural findings indicated that methamphetamine induced a change in the place preference in the majority of our animals. This change in place preference was not seen when vasopressin was administered during the extinction phase. On the other hand the methamphetamine-induced change in place preference was enhanced during the reinstatement phase in the animals that were treated with oxytocin. Striatal dopamine levels were determined, as methamphetamine is known to increase dopamine transmission in this area. Significant changes in dopamine levels were observed in some of our animals. Rats that received both methamphetamine and oxytocin had significantly higher striatal dopamine than those that received oxytocin alone. Western blot analysis for hippocampal cyclic AMP response element binding protein (CREB) was also conducted as a possible indicator of glutamatergic NMDA receptor activity, a pathway that is important for learning and memory. The Western blot analysis showed no changes in hippocampal pCREB expression. Overall our data led us to conclude that methamphetamine treatment can change place preference

  13. Theories of addiction: methamphetamine users' explanations for continuing drug use and relapse.

    Science.gov (United States)

    Newton, Thomas F; De La Garza, Richard; Kalechstein, Ari D; Tziortzis, Desey; Jacobsen, Caitlin A

    2009-01-01

    A variety of preclinical models have been constructed to emphasize unique aspects of addiction-like behavior. These include Negative Reinforcement ("Pain Avoidance"), Positive Reinforcement ("Pleasure Seeking"), Incentive Salience ("Craving"), Stimulus Response Learning ("Habits"), and Inhibitory Control Dysfunction ("Impulsivity"). We used a survey to better understand why methamphetamine-dependent research volunteers (N = 73) continue to use methamphetamine, or relapse to methamphetamine use after a period of cessation of use. All participants met DSM-IV criteria for methamphetamine abuse or dependence, and did not meet criteria for other current Axis I psychiatric disorders or dependence on other drugs of abuse, other than nicotine. The questionnaire consisted of a series of face-valid questions regarding drug use, which in this case referred to methamphetamine use. Examples of questions include: "Do you use drugs mostly to make bad feelings like boredom, loneliness, or apathy go away?", "Do you use drugs mostly because you want to get high?", "Do you use drugs mostly because of cravings?", "Do you find yourself getting ready to take drugs without thinking about it?", and "Do you impulsively take drugs?". The scale was anchored at 1 (not at all) and 7 (very much). For each question, the numbers of participants rating each question negatively (1 or 2), neither negatively or affirmatively (3-5), and affirmatively (6 or 7) were tabulated. The greatest number of respondents (56%) affirmed that they used drugs due to "pleasure seeking." The next highest categories selected were "impulsivity" (27%) and "habits"(25%). Surprisingly, many participants reported that "pain avoidance" (30%) and "craving" (30%) were not important for their drug use. Results from this study support the contention that methamphetamine users (and probably other drug users as well) are more heterogeneous than is often appreciated, and imply that treatment development might be more successful if

  14. The pharmacokinetics and liver metabolism of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) in rats.

    Science.gov (United States)

    Ravis, W R; Valaer, A K; Brzozowski, D; Clark, C R

    1994-01-01

    The metabolism and disposition of N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA) was studied by utilizing rat liver slices as well as by intravenous pharmacokinetic studies in rats. In the liver slice experiments, N-OH MDA (16 micrograms/ml) was incubated with rat liver slices and the disappearance of N-OH MDA and the appearance of MDA were observed over 2 hours. Drug and metabolites were assayed by a reverse phase high performance liquid chromatographic procedure including a C8 column and UV detection. N-OH MDA disappeared from the plasma at an apparent first-order rate with a t1/2 of 36.3 +/- 8.4 min. By the end of 2 hours, approximately 85% of the N-OH MDA was biotransformed to MDA. Following placement of jugular cannulas in rats, a dose of 15 mg/kg of N-OH MDA was administered intravenously. With rapid blood sampling, a t1/2 of 0.86 +/- 0.12 min was observed for N-OH MDA. A total body clearance of 9.09 +/- 2.06 L/hr/kg and a volume of distribution of 0.184 +/- 0.022 L/kg were noted. Plasma concentrations of MDA were observed after the N-OH MDA dose to rats. The MDA t1/2 after N-OH MDA dosing was 1.68 +/- 0.29 hours with peak plasma concentrations at 8 min. No other major metabolites could be detected in liver slice, plasma, or urine samples. Both sets of studies demonstrate the rapid conversion of N-OH MDA to MDA in rats. PMID:8208060

  15. How Long Does Craving Predict Use of Methamphetamine? Assessment of Use One to Seven Weeks After the Assessment of Craving

    Directory of Open Access Journals (Sweden)

    Gantt P. Galloway

    2008-01-01

    Full Text Available Aims: This study lays the foundation for a clinical prediction model based on methamphetamine craving intensity and its ability to predict the presence or absence of within-treatment methamphetamine use.Design: We used a random effects logistic approach for estimating repeated-measures, generalized linear mixed models (GLMM using craving as the sole predictor of methamphetamine. A multivariate GLMM included craving, length of treatment, treatment assignment, and methamphetamine use the previous week as covariates to control for potential confounds. We performed receiver operating characteristic (ROC analyses to evaluate predictive accuracy. We investigated further whether methamphetamine craving predicted subsequent use more accurately at intervals more proximal to versus those more distal to assessment, examining one-week periods ending one to seven weeks after assessment of craving.Setting: The study was part of the Center for Substance Abuse Treatment (CSAT Methamphetamine Treatment Project (MTP.Subjects: Analyses were based on data from 691 methamphetamine dependent outpatients enrolled in the MTP.Measurements: Craving was assessed by self-report on a 0–100 scale. Self-reported methamphetamine use was toxicologically verified. Craving and drug use were assessed weekly for 8 weeks.Findings: In the univariate analysis craving predicted methamphetamine use in the week immediately following the craving report (p <0.0001, with subject-specific use increasing 0.38% for each one-point increase in craving on a 0–100 scale. In the multivariate analysis the probability of use decreased by 2.45% for each week in treatment, increased by 33.11% for previous methamphetamine use, and the probability of methamphetamine use still increased with craving, rising 0.28% for each one-point increase in craving score (all p <0.0001. Predictive accuracy was strongest at the one-week time-lag and declined in magnitude the more distal the assessment period

  16. Development of an automated data processing method for sample to sample comparison of seized methamphetamines.

    Science.gov (United States)

    Choe, Sanggil; Lee, Jaesin; Choi, Hyeyoung; Park, Yujin; Lee, Heesang; Pyo, Jaesung; Jo, Jiyeong; Park, Yonghoon; Choi, Hwakyung; Kim, Suncheun

    2012-11-30

    The information about the sources of supply, trafficking routes, distribution patterns and conspiracy links can be obtained from methamphetamine profiling. The precursor and synthetic method for the clandestine manufacture can be estimated from the analysis of minor impurities contained in methamphetamine. Also, the similarity between samples can be evaluated using the peaks that appear in chromatograms. In South Korea, methamphetamine was the most popular drug but the total seized amount of methamphetamine whole through the country was very small. Therefore, it would be more important to find the links between samples than the other uses of methamphetamine profiling. Many Asian countries including Japan and South Korea have been using the method developed by National Research Institute of Police Science of Japan. The method used gas chromatography-flame ionization detector (GC-FID), DB-5 column and four internal standards. It was developed to increase the amount of impurities and minimize the amount of methamphetamine. After GC-FID analysis, the raw data have to be processed. The data processing steps are very complex and require a lot of time and effort. In this study, Microsoft Visual Basic Application (VBA) modules were developed to handle these data processing steps. This module collected the results from the data into an Excel file and then corrected the retention time shift and response deviation generated from the sample preparation and instruments analysis. The developed modules were tested for their performance using 10 samples from 5 different cases. The processed results were analyzed with Pearson correlation coefficient for similarity assessment and the correlation coefficient of the two samples from the same case was more than 0.99. When the modules were applied to 131 seized methamphetamine samples, four samples from two different cases were found to have the common origin and the chromatograms of the four samples were appeared visually identical

  17. “Tweaking and Geeking, Just Having Some Fun”: An Analysis of Methamphetamine Poems

    Science.gov (United States)

    Sexton, Rocky L.; Carlson, Robert G.; Leukefeld, Carl G.; Booth, Brenda M.

    2013-01-01

    There is a body of methamphetamine-themed poetry that speaks regretfully of the highly negative experiences of those in recovery from methamphetamine (MA) addiction or who feel trapped in an MA-using lifestyle. During ethnographic research in western Kentucky, the author collected two MA-themed poems from active MA users that differ from other MA poetry. They describe misadventures that occur during MA “binges.” However, the text and tone of the poems are comically ironic and represent optimism rather than regret toward MA use. Analyzing these poems provide valuable insights into local patterns of MA use, related terminology, and attitudes toward MA use. PMID:21053760

  18. Analysis of forensic samples of "Ecstasy" tablets seized in Novi Sad during the 2004 year

    Directory of Open Access Journals (Sweden)

    Zgonjanin Dragana M.

    2005-01-01

    Full Text Available The paper presents results of the analysis of illicit synthetic drugs in the form of tablets distributed under the name "Ecstasy", seized by the police in the broader area of Novi Sad 2004. A huge number of tablets has been analyzed (n=121, of various colours and with impressed symbols from the total amount of 93 seizures, which totally amounted to 1458 tablets. Regarding the number of seizures ecstasy (3,4-methylendioxy-N-meth-yl-amphetamine - MDMA is dominant among all, and according to the quantity of seized tablets it is amphetamine (AP, while other amphetamine-type drugs (methamphetamine MA 3,4-methylendioxiamphetamine - MDA, 3,4-methylendioxi-N-ethyl-amphetamine MDEA have been found in rather small quantities and very rarely. Tablets mostly contain caffeine as an additive. In the analytical procedure, the samples of tablets were subjected to liquid-liquid extraction and afterwards analyzed on the GCD (GC-EI Hewlett-Packard instrument. The method is fast reliable and reproducible for the analysis of amphetamine, methamphetamine MDA, MDMA, MDEA, as well as various additives in the samples of seized tablets.

  19. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal

    OpenAIRE

    Li, Hao; Scholl, Jamie L.; Tu, Wenyu; Hassell, James; Watt, Michael J.; Forster, Gina L.; Renner, Kenneth J.

    2014-01-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, increases in stress-induced ventral hippocampal serotonin have been linked to coping mechanisms. The goal of this study is to understand neurobiological changes induced by amphetamine that contribute to stress-sen...

  20. Surveillance of Diversion and Nonmedical Use of Extended-Release Prescription Amphetamine and Oral Methylphenidate in the United States

    OpenAIRE

    Sembower, Mark A.; Ertischek, Michelle D.; Buchholtz, Chloe; Dasgupta, Nabarun; Schnoll, Sidney H.

    2013-01-01

    This article examines rates of nonmedical use and diversion of extended-release amphetamine and extended-release oral methylphenidate in the United States. Prescription dispensing data were sourced from retail pharmacies. Nonmedical use data were collected from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Drug Diversion Program and Poison Center Program. Drug diversion trends nearly overlapped for extended-release amphetamine and extended-release oral met...

  1. Behavioral effects of prenatal d-amphetamine in rats: a parallel trial to the Collaborative Behavioral Teratology Study.

    Science.gov (United States)

    Vorhees, C V

    1985-01-01

    Pregnant Sprague-Dawley rats treated with 0, 0.5 or 2.0 mg/kg of d-amphetamine sulphate on days 12-15 of gestation or left untreated as part of the NCTR Collaborative Behavioral Teratology Study were assigned to either the Collaborative Study or Cincinnati Test protocol after birth. Offspring assigned to the Cincinnati test system were evaluated for growth, mortality, incisor eruption, eye opening, vaginal patency, surface righting, negative geotaxis, pivoting, auditory startle, olfactory orientation, swimming ontogeny, figure-8 activity, and complex water maze (Biel) problem solving. Amphetamine at both doses caused fewer offspring to be born per litter and reduced the proportion of males born in the 0.5 mg/kg group. Amphetamine produced no reliable effects on offspring growth as reflected by weight or survival. The 0.5 mg/kg amphetamine group showed delayed eye opening, but the 2.0 mg/kg group did not. Amphetamine produced no significant effects on other physical landmarks of development or on measures of behavioral performance except swimming ontogeny. Early swimming direction scores were significantly lower in the amphetamine groups compared to controls, but the effect was isolated; no other aspect of swimming was affected. It was concluded that at the doses and exposure period used here, d-amphetamine appears to be at best weakly behaviorally teratogenic using the Cincinnati test system. This finding is in general agreement with the results obtained with the same treatment regiment in the NCTR Collaborative Study. Both test systems appear comparable at correctly identifying the low level of behavioral teratogenicity of moderate doses of prenatal d-amphetamine. PMID:3835471

  2. Effect of MK-801 on methamphetamine-induced dopaminergic neurotoxicity: long-term attenuation of methamphetamine-induced dopamine release

    International Nuclear Information System (INIS)

    Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum using [3H] WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 g/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli

  3. Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs.

    Science.gov (United States)

    Ma, Ming; Zhao, Lianmei; Sun, Guogui; Zhang, Chao; Liu, Lihua; Du, Yanyan; Yang, Xingxiao; Shan, Baoen

    2016-05-01

    Interleukin-24 (IL-24) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells

  4. Reinforcing effects of methamphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder-the Spontaneously Hypertensive Rat

    Directory of Open Access Journals (Sweden)

    Ryu Jong

    2010-12-01

    Full Text Available Abstract Substrains of the Spontaneously Hypertensive rat (SHR, a putative animal model of Attention-Deficit/Hyperactivity Disorder (ADHD, have demonstrated increased sensitivity to many drugs of abuse, including psychostimulants. Therefore, it was suggested that studies in SHR may help elucidate ADHD and comorbidity with substance use disorder (SUD. However, the drug intake profile of the SHR in the most relevant animal model of drug addiction, the self-administration (SA test, and its response on the conditioned place preference (CPP paradigm are not yet determined. In the present study, we employed SA and CPP tests to investigate the reinforcing effects of the psychostimulant methamphetamine in an SHR substrain obtained from Charles River, Japan (SHR/NCrlCrlj. Concurrent tests were also performed in Wistar rats, the strain representing "normal" heterogeneous population. To address if the presence of ADHD behaviors further increases sensitivity to the rewarding effect of methamphetamine during adolescence, a critical period for the onset of drug abuse, CPP tests were especially conducted in adolescent Wistar and SHR/NCrlCrlj. We found that the SHR/NCrlCrlj also acquired methamphetamine SA and CPP, indicating reinforcing effects of methamphetamine in this ADHD animal model. However, we did not observe increased responsiveness of the SHR/NCrlCrlj to methamphetamine in both SA and CPP assays. This indicates that the reinforcing effects of methamphetamine may be similar in strains and that the SHR/NCrlCrlj may not adequately model ADHD and increased sensitivity to methamphetamine.

  5. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines

    Directory of Open Access Journals (Sweden)

    Mohammed A. Al Shehri

    2016-07-01

    Full Text Available A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient’s original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries.

  6. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines.

    Science.gov (United States)

    Al Shehri, Mohammed A; Youssef, Ali A

    2016-07-01

    A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient's original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries. PMID:27358538

  7. Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration.

    Science.gov (United States)

    Caprioli, Daniele; Zeric, Tamara; Thorndike, Eric B; Venniro, Marco

    2015-09-01

    Recent studies have shown that when given a mutually exclusive choice between cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine. Here, we used a discrete choice procedure to assess whether palatable food preference generalizes to rats with a history of limited (3 hours/day) or extended (6 or 9 hours/day) access to methamphetamine self-administration. On different daily sessions, we trained rats to lever-press for either methamphetamine (0.1-0.2 mg/kg/infusion) or palatable food (five pellets per reward delivery) for several weeks; regular food was freely available. We then assessed food-methamphetamine preference either during training, after priming methamphetamine injections (0.5-1.0 mg/kg), following a satiety manipulation (palatable food exposure in the home cage) or after 21 days of withdrawal from methamphetamine. We also assessed progressive ratio responding for palatable food and methamphetamine. We found that independent of the daily drug access conditions and the withdrawal period, the rats strongly preferred the palatable food over methamphetamine, even when they were given free access to the palatable food in the home cage. Intake of methamphetamine and progressive ratio responding for the drug, both of which increased or escalated over time, did not predict preference in the discrete choice test. Results demonstrate that most rats strongly prefer palatable food pellets over intravenous methamphetamine, confirming previous studies using discrete choice procedures with intravenous cocaine. Results also demonstrate that escalation of drug self-administration, a popular model of compulsive drug use, is not associated with a cardinal feature of human addiction of reduced behavioral responding for non-drug rewards. PMID:25582886

  8. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

    2016-04-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

  9. Differential Influence of Dopamine Transport Rate on the Potencies of Cocaine, Amphetamine, and Methylphenidate

    OpenAIRE

    Calipari, Erin S.; Ferris, Mark J.; Siciliano, Cody A.; JONES, SARA R.

    2014-01-01

    Dopamine transporter (DAT) levels vary across brain regions and individuals, and are altered by drug history and disease states; however, the impact of altered DAT expression on psychostimulant effects in brain has not been systematically explored. Using fast scan cyclic voltammetry, we measured the effects of elevated DAT levels on presynaptic dopamine parameters as well as the uptake inhibition potency of the blockers cocaine and methylphenidate (MPH) and the releaser amphetamine (AMPH) in ...

  10. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  11. Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

    OpenAIRE

    Cherkasova, Mariya V.; Faridi, Nazlie; Casey, Kevin F; O'Driscoll, Gillian A; Hechtman, Lily; Joober, Ridha; Baker, Glen B.; Palmer, Jennifer; Dagher, Alain; Leyton, Marco; Benkelfat, Chawki

    2014-01-01

    Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [11C]raclopride PET with a d-amphetamine chal...

  12. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users. PMID:22005052

  13. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Abhilasha Shete; Vibhor Kumar Jain; Bindu nee Giri Jain

    2010-01-01

    Tinospora cordifolia is reported to have CNS active principle and is used for thetreatment of various neurological disorders. Hence, the effect of aqueous ethanolicextract of Tinospora cordifolia was investigated for its putative antipsychotic activityusing amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administeredacutely to mice as standard drug. Control animals received vehicle (10% DMSO). The invivo receptor binding studies were carried out to correlate the antipsychoti...

  14. ANTIPSYCHOTIC ACTIVITY OF AQUEOUS ETHANOLIC EXTRACT OF TINOSPORA CORDIFOLIA IN AMPHETAMINE CHALLENGED MICE MODEL

    OpenAIRE

    Bindu nee Giri Jain; Vibhor Kumar Jain; Abhilasha Shete

    2010-01-01

    Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p.) was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO). The in vivo receptor binding studies were carried out to correlate the antipsy...

  15. Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus.

    OpenAIRE

    Dougan, D. F.; Duffield, A. M.; Duffield, P. H.; Wade, D. N.

    1986-01-01

    The stereoselective accumulation of alpha-methyl-p-tyramine (AMPT) and alpha-methyl-p-octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)- and (-)-isomers of amphetamine (Amphet) and the acute administration of (+)- and (-)-AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Two h after the administration of (+)- or (-)-AMPT (5 mg kg-1 i.p.), the concentrations of the isomers in striatal tissue...

  16. Performance and subjective effects of diazepam and d-amphetamine in high and low sensation seekers

    OpenAIRE

    Kelly, Thomas H.; Delzer, Timothy A.; Martin, Catherine A.; Harrington, Nancy G.; Hays, Lon R.; Bardo, Michael T.

    2009-01-01

    Although sensation-seeking status is associated with age of initiation and amount of drug use among adolescents, and sensitivity to the behavioral and reinforcing effects of drugs among young adults, it is unclear whether sensation-seeking status among adolescents is predictive of sensitivity to the pharmacological effects of drugs (i.e. abuse potential) as adults. This study examined the acute behavioral effects of oral diazepam and d-amphetamine in young adults, ages 18–21 years, who had co...

  17. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  18. A single social defeat induces short-lasting behavioral sensitization to amphetamine

    OpenAIRE

    de Jong, JG; Wasilewski, M.; Van Der Vegt, BJ; Buwalda, B.; Koolhaas, Jacob

    2005-01-01

    Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from respon...

  19. Genetic variants in the cocaine- and amphetamine-regulated transcript gene (CARTPT) and cocaine dependence

    OpenAIRE

    Lohoff, Falk W.; Bloch, Paul J.; Weller, Andrew E.; Nall, Aleksandra H.; Doyle, Glenn A.; Buono, Russell J.; Ferraro, Thomas N.; Kampman, Kyle M.; Pettinati, Helen M.; Dackis, Charles A.; Oslin, David W.; O'Brien, Charles P.; BERRETTINI, WADE H.

    2008-01-01

    Dopaminergic brain systems have been implicated to play a major role in drug reward, thus making genes involved in these circuits plausible candidates for susceptibility to substance use disorders. The cocaine- and amphetamine-regulated transcript peptide (CARTPT) is involved in reward and feeding behavior and has functional characteristics of an endogenous psychostimulant. In this study we tested the hypothesis that variation in the CARTPT gene increases susceptibility to cocaine dependence ...

  20. The Development of Context-specific Operant Sensitization to d-Amphetamine

    OpenAIRE

    Thomas, Wesley Paul

    2009-01-01

    Animal models have previously been used to study tolerance and sensitization using two different procedures that are difficult to compare. Tolerance has been studied by administering a drug to a subject that is engaged in an operant behavior, and sensitization by administering a drug to a subject that is not engaged in an operant behavior. Previous research has shown that sensitization can occur when d-amphetamine is administered to rats emitting an operant behavior for a food presentation. T...

  1. The Effects of Progesterone Pretreatment on the Response to Oral d-Amphetamine in Women

    OpenAIRE

    Reed, Stephanie C.; Levin, Frances R.; Evans, Suzette M.

    2010-01-01

    Stimulant abuse continues to be a problem, particularly for women. There is increasing preclinical and clinical evidence showing that the hormone progesterone attenuates the behavioral effects of cocaine, and this effect is primarily observed in females. The purpose of the present study was to determine if progesterone would also alter the behavioral effects of another stimulant, oral d-amphetamine (AMPH) in women. Eighteen normal non-drug abusing women completed eight outpatient sessions ove...

  2. Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

    OpenAIRE

    Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

    2011-01-01

    Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In co...

  3. Associations Between Cocaine, Amphetamine or Psychedelic Use and Psychotic Symptoms in a Community Sample

    OpenAIRE

    Kuzenko, Nina; Sareen, Jitender; Beesdo-Baum, Katja; Perkonigg, Axel; Höfler, Michael; Simm, James; Lieb, Roselind; Wittchen, Hans-Ulrich

    2013-01-01

    Objective: To investigate whether there is an association between use of cocaine, amphetamines, or psychedelics and psychotic symptoms. Method: Cumulated data from a prospective, longitudinal community study of 2588 adolescents and young adults in Munich, Germany were used. Substance use was assessed at baseline, 4-year and 10-year follow-up using the Munich Composite International Diagnostic Interview; psychotic symptoms were assessed at 4-year and 10-year follow-up. Multinomial logist...

  4. Influence of Betaxolol on the Methamphetamine Dependence in Mice

    Science.gov (United States)

    Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong

    2016-01-01

    Objective The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. Methods The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. Results The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. Conclusion These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP. PMID:27247598

  5. Chronic Nicotine Exposure Attenuates Methamphetamine-Induced Dopaminergic Deficits.

    Science.gov (United States)

    Vieira-Brock, Paula L; McFadden, Lisa M; Nielsen, Shannon M; Ellis, Jonathan D; Walters, Elliot T; Stout, Kristen A; McIntosh, J Michael; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2015-12-01

    Repeated methamphetamine (METH) administrations cause persistent dopaminergic deficits resembling aspects of Parkinson's disease. Many METH abusers smoke cigarettes and thus self-administer nicotine; yet few studies have investigated the effects of nicotine on METH-induced dopaminergic deficits. This interaction is of interest because preclinical studies demonstrate that nicotine can be neuroprotective, perhaps owing to effects involving α4β2 and α6β2 nicotinic acetylcholine receptors (nAChRs). This study revealed that oral nicotine exposure beginning in adolescence [postnatal day (PND) 40] through adulthood [PND 96] attenuated METH-induced striatal dopaminergic deficits when METH was administered at PND 89. This protection did not appear to be due to nicotine-induced alterations in METH pharmacokinetics. Short-term (i.e., 21-day) high-dose nicotine exposure also protected when administered from PND 40 to PND 61 (with METH at PND 54), but this protective effect did not persist. Short-term (i.e., 21-day) high-dose nicotine exposure did not protect when administered postadolescence (i.e., beginning at PND 61, with METH at PND 75). However, protection was engendered if the duration of nicotine exposure was extended to 39 days (with METH at PND 93). Autoradiographic analysis revealed that nicotine increased striatal α4β2 expression, as assessed using [(125)I]epibatidine. Both METH and nicotine decreased striatal α6β2 expression, as assessed using [(125)I]α-conotoxin MII. These findings indicate that nicotine protects against METH-induced striatal dopaminergic deficits, perhaps by affecting α4β2 and/or α6β2 expression, and that both age of onset and duration of nicotine exposure affect this protection. PMID:26391161

  6. Decreased dopamine activity predicts relapse in methamphetamine abusers

    International Nuclear Information System (INIS)

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and (11C)raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  7. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  8. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

    Directory of Open Access Journals (Sweden)

    Michael Pennick

    2010-06-01

    Full Text Available Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX, a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO cells expressing human peptide transporter-1 (PEPT1. LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human, only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high-capacity system in blood (ie, red blood cells may contribute to the consistent, reproducible pharmacokinetic profile of LDX.Keywords: lisdexamfetamine dimesylate, LDX, prodrug, ADHD, absorption, Vyvanse

  9. Performance enhancing, non-prescription use of Ritalin: a comparison with amphetamines and cocaine.

    Science.gov (United States)

    Svetlov, Stanislay I; Kobeissy, Firas H; Gold, Mark S

    2007-01-01

    Ritalin, known under chemical name methylphenidate (MPH), is a psychostimulant prescribed to treat attention-deficit/hyperactivity disorder (ADHD) and other conditions. Psychotropic effects and pharmacological pathways evoked by MPH are similar, but not identical to those produced by amphetamines and cocaine. Although not completely understood in detail, MPH psychostimulation is mediated by the increase of central dopamine (DA) and possibly norepinephrine (NE) and serotonin (ST) due to decrease of their re-uptake via binding to and inhibition of DA, NE, and ST transporters. Despite similarity in psychopharmacological effects, the rewarding/ reinforcing ability of MPH appears to be significantly lower than amphetamines and especially cocaine. MPH and similar medications have been widely used on College campuses and by students preparing for exams. Nicknamed 'steroids for SATs,' MPH and related medications are purchased without prescription and their use may even be encouraged by parents and tutors. However, while widely and safely used and administered for over forty years, Ritalin generated significant controversy including MPH abuse and addiction, and adverse reactions. It is now clear that treatment of ADD/ADHD with psychostimulants prevents drug abuse and addictions. Use by those without any medical or psychiatric diagnosis is increasing. In this mini-review, we discuss psychopharmacological and behavioral aspects, and outline neurochemical mechanisms that may provoke Ritalin abuse, addiction and adverse effects compared to amphetamines and cocaine. PMID:18032226

  10. A Vodcasted, Cross-Disciplinary, Behavioral Neuroscience Laboratory Exercise Investigating the Effects of Methamphetamine on Aggression

    Science.gov (United States)

    Shanks, Ryan A.; Southard, E. Megan; Tarnowski, Laura; Bruster, Matthew; Wingate, Stacia W.; Dalman, Nancy; Lloyd, Steven A.

    2011-01-01

    This article describes a laboratory experience utilizing videos to engage students in hypothesis-driven experimentation in behavioral neuroscience. It provides students with an opportunity to investigate the effects of chronic methamphetamine exposure on aggression in adult mice using a resident-intruder paradigm. Instructors and students only…

  11. Distributed Attentional Deficits in Chronic Methamphetamine Abusers: Evidence from the Attentional Network Task (ANT)

    Science.gov (United States)

    Salo, Ruth; Gabay, Shai; Fassbender, Catherine; Henik, Avishai

    2011-01-01

    Objective: The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Methods: Thirty currently abstinent MA abusers (1 month-5 years) and 22 healthy non-substance using adults…

  12. Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals.

    Science.gov (United States)

    Salo, Ruth; Nordahl, Thomas E; Possin, Kate; Leamon, Martin; Gibson, David R; Galloway, Gantt P; Flynn, Neil M; Henik, Avishai; Pfefferbaum, Adolf; Sullivan, Edith V

    2002-08-01

    Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others. PMID:12140121

  13. Perceived Child Behavior Problems, Parenting Stress, and Maternal Depressive Symptoms among Prenatal Methamphetamine Users

    Science.gov (United States)

    Liles, Brandi D.; Newman, Elana; LaGasse, Linda L.; Derauf, Chris; Shah, Rizwan; Smith, Lynne M.; Arria, Amelia M.; Huestis, Marilyn A.; Haning, William; Strauss, Arthur; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2012-01-01

    The present study was designed to examine parenting stress, maternal depressive symptoms, and perceived child behavior problems among mothers who used methamphetamine (MA) during pregnancy. Participants were a subsample (n = 212; 75 exposed, 137 comparison) of biological mothers who had continuous custody of their child from birth to 36 months.…

  14. Family conflict and depression in HIV-negative heterosexuals: the role of methamphetamine use.

    Science.gov (United States)

    Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; Patterson, Thomas L

    2009-06-01

    Previous research has reported elevated levels of depressive symptoms among methamphetamine users, but little attention has been paid to possible links between family environment and psychological distress. This study examined relationships between family conflict, substance use, and depressive symptoms in a sample of 104 heterosexual methamphetamine users in San Diego, California. Eighty-nine percent of the sample reported conflict with a family member in the past year. Conflict was reported most often with parents and siblings. Sources of conflict included drug use, lifestyle issues, interpersonal and communication issues, and concern for other family members. In regression analyses, being female, being a polydrug user, and facing social and legal stressors were associated with higher levels of family conflict. Multiple regression analyses also revealed a positive association between family conflict and depressive symptoms. Contrary to expectation, methamphetamine dose did not moderate the relationship between family conflict and depressive symptoms. Reducing family conflict may be an important first step toward ameliorating depressive symptoms and creating more supportive environments for methamphetamine users who are in urgent need of effective interventions. PMID:19586151

  15. Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods.

    Science.gov (United States)

    Kunalan, Vanitha; Nic Daéid, Niamh; Kerr, William J; Buchanan, Hilary A S; McPherson, Allan R

    2009-09-01

    Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of "route specific" impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the "target impurities" recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes. PMID:19637924

  16. Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement.

    Science.gov (United States)

    Gong, Xiaokang; Yue, Kai; Ma, Baomiao; Xing, Junqiao; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying

    2016-05-01

    Despite the high prevalence of methamphetamine (METH) use, no FDA-approved pharmacological treatment is currently available for individuals with a METH addiction. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance derived from corydalis and stephania that has been used in traditional Asian medicine for its analgesic, sedative and hypnotic properties. Previous pharmacological studies of l-THP indicated that it not only binds to D1 and D2 receptors but also has a low affinity for D3 receptors and may function as an antagonist. The unique pharmacological profile of l-THP suggests that it may have potential therapeutic effects on drug addiction; however, the effects of l-THP in individuals with METH addictions are largely unknown. In this study, we investigated the effects of l-THP on METH self-administration and METH-induced reinstatement. In our experiments, l-THP (1.25, 2.50 and 5.00 mg/kg, i.p.) decreased METH self-administration under the fixed-ratio 1 schedule. l-THP (2.50 and 5.00 mg/kg, i.p) also prevented the METH-induced reinstatement of METH-seeking behaviors. Interestingly, l-THP (1.25 and 2.50mg/kg, i.p) did not affect locomotor activity following METH injection (1mg/kg) suggesting that the observed effects of l-THP (2.50mg/kg) on METH-induced reinstatement were not due to motor impairments. Thus, l-THP (a natural, mixed dopamine (DA) receptor antagonist) attenuates METH self-administration and METH-induced reinstatement. PMID:26806555

  17. Effect of amlodipine on apoptosis of human breast carcinoma MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods: Light microscopy was used to determine the effects of amiodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen (PCNA) and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results: Amlodipine concentration of 8.25 Ixmol/L (1/2 of IC50) affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion: The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.

  18. Effect of neurotrophin-3 on SOD and MDA in rats after acute spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    GUO Shu-zhang; REN Xian-jun; JIANG Tao; OUYANG Zhong

    2007-01-01

    Objective: To investigate the effect of neurotrophin-3 on the expressions of SOD and MDA in the injured spinal cord of rats. Methods:Totally 105 SD rats were randomly divided into 3 groups (n=35): sham group, control group and experimental group. Animal model of acute spinal cord was inflicted with Allen's method by a thin plastic tube situated in subarachnoid space below the injury level for perfusion. Rats in experimental group received 20 μl NT-3 (200 ng) from the tube at 0,4,8,12,24 h and 3,7 d after injury, and those in control group got the equal volume of normal saline at the same time points.The animals in sham group only received opening vertebral plate and putting tube in subarachnoid space.The rats were sacrificed at 4,8,12,24 h, and 3,7,14 d postinjury (n=5). And the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in blood were observed with colorimetric method. Results: The serum level of SOD reduced obviously and the level of MDA raised obviously in rats after the injury,and the activity of SOD reached the lowest on day 3 and the concentratioh of MDA reached peak at the 7 d.In the experimental group, the SOD level was obviously higher (P<0.01), and MDA level was lower than the control (P<0.01). Conclusion: NT-3 can mitigate secondary injury of spinal cord in vivo. One of mechanisms is that inhibits abnormal expression of MDA and elevates the activity of SOD, thus the injury of free radical and lipid peroxidation is attenuated.

  19. The vaporization enthalpy and vapor pressure of S (+)-methamphetamine at T = 298.15 K by correlation gas chromatography

    International Nuclear Information System (INIS)

    Highlights: • The vaporization enthalpy of (d)-methamphetamine was measured. • The vapor pressure of (d)-methamphetamine as a function of temperature was evaluated. • The vapor pressure of 4-benzylpiperidine as a function of temperature was evaluated. - Abstract: The vaporization enthalpy and vapor pressure of S (+)-methamphetamine is evaluated by correlation-gas chromatography. A vaporization enthalpy of (58.7 ± 4.3) kJ · mol−1 and a vapor pressure, p = (38 ± 9) Pa has been obtained using a variety of secondary aliphatic amines as standards. In addition, equations describing the vapor pressure temperature dependence are provided for standards and S (+)-methamphetamine covering the temperature range from T = 298.15 K to the boiling temperature. Boiling temperatures are reproduced within an interval of 8 K or less

  20. Desarrollo de un modelo basado en MDA para Gobierno Electrónico

    OpenAIRE

    Sánchez Rivero, David; Castro, Marcelo; Vargas, Alejandro; Reinoso, Elizabeth; Aparicio, María; Farfán, José; Cándido, Andrea; Castro, Dante Daniel; Cazón, Liliana; Zapana, José

    2015-01-01

    Una aplicación desarrollada, de acuerdo a las especificaciones de MDA (Model Driven Architecture), tiene como principales características: gran flexibilidad en la implementación, mejoras sustanciales en la integración de componentes, facilidad en el proceso de mantenimiento, prueba y simulación de sistemas. MDA es una arquitectura que se basa en la separación de las especificaciones de un sistema de los aspectos básicos de su implementación, tomando en cuenta una plataforma común. Y tenien...

  1. Cadmium accumulation, activities of antioxidant enzymes, and malondialdehyde (MDA) content in Pistia stratiotes L.

    Science.gov (United States)

    Li, Yong; Zhang, Shanshan; Jiang, Wusheng; Liu, Donghua

    2013-02-01

    The aquatic plant Pistia stratiotes L. (water lettuce) was studied due to its capability of absorption of contaminants in water and its subsequent use in wetlands constructed for wastewater treatment. The effects of Cd on root growth, accumulation of Cd, antioxidant enzymes, and malondialdehyde (MDA) content in P. stratiotes were investigated. The results indicated that P. stratiotes has considerable ability to accumulate Cd. Cadmium induced higher superoxide dismutase (SOD) and peroxidase (POD) activities than catalase activity, suggesting that SOD and POD provided a better defense mechanism against Cd-induced oxidative damage. The accumulation of Cd promoted MDA production. PMID:22791349

  2. Risk factors for methamphetamine use in youth: a systematic review

    Directory of Open Access Journals (Sweden)

    Durec Tamara

    2008-10-01

    Full Text Available Abstract Background Methamphetamine (MA is a potent stimulant that is readily available. Its effects are similar to cocaine, but the drug has a profile associated with increased acute and chronic toxicities. The objective of this systematic review was to identify and synthesize literature on risk factors that are associated with MA use among youth. More than 40 electronic databases, websites, and key journals/meeting abstracts were searched. We included studies that compared children and adolescents (≤ 18 years who used MA to those who did not. One reviewer extracted the data and a second checked for completeness and accuracy. For discrete risk factors, odds ratios (OR were calculated and when appropriate, a pooled OR with 95% confidence intervals (95% CI was calculated. For continuous risk factors, mean difference and 95% CI were calculated and when appropriate, a weighted mean difference (WMD and 95% CI was calculated. Results were presented separately by comparison group: low-risk (no previous drug abuse and high-risk children (reported previous drug abuse or were recruited from a juvenile detention center. Results Twelve studies were included. Among low-risk youth, factors associated with MA use were: history of heroin/opiate use (OR = 29.3; 95% CI: 9.8–87.8, family history of drug use (OR = 4.7; 95% CI: 2.8–7.9, risky sexual behavior (OR = 2.79; 95% CI: 2.25, 3.46 and some psychiatric disorders. History of alcohol use and smoking were also significantly associated with MA use. Among high-risk youth, factors associated with MA use were: family history of crime (OR = 2.0; 95% CI: 1.2–3.3, family history of drug use (OR = 4.7; 95% CI: 2.8–7.9, family history of alcohol abuse (OR = 3.2; 95% CI: 1.8–5.6, and psychiatric treatment (OR = 6.8; 95% CI: 3.6–12.9. Female sex was also significantly associated with MA use. Conclusion Among low-risk youth, a history of engaging in a variety of risky behaviors was significantly associated

  3. An animal model of differential genetic risk for methamphetamine intake

    Directory of Open Access Journals (Sweden)

    Tamara ePhillips

    2015-09-01

    Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1 agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the

  4. Methamphetamine Users Have Increased Dental Disease: A Propensity Score Analysis.

    Science.gov (United States)

    Shetty, V; Harrell, L; Clague, J; Murphy, D A; Dye, B A; Belin, T R

    2016-07-01

    Methamphetamine (MA) users are assumed to have a high burden of tooth decay. Less clear is how the distribution and severity of dental caries in MA users differ from the general population. Using a covariate-balancing propensity score strategy, we investigated the differential effects of MA use on dental caries by comparing the patterns of decayed, missing, and filled teeth in a community sample of 571 MA users with a subset of 2,755 demographically similar control individuals selected from a National Health and Nutrition Examination Survey (NHANES) cohort. Recruited over a 2-y period with a stratified sampling protocol, the MA users underwent comprehensive dental examinations by 3 trained and calibrated dentists using NHANES protocols. Propensity scores were estimated with logistic regression based on background characteristics, and a subset of closely matched subjects was stratified into quintiles for comparisons. MA users were twice as likely to have untreated caries (odds ratio [OR] = 2.08; 95% confidence interval [95% CI]: 1.55 to 2.78) and 4 times more likely to have caries experience (OR = 4.06; 95% CI: 2.24 to 7.34) than the control group of NHANES participants. Additionally, MA users were twice as likely to have 2 more decayed, missing, or filled teeth (OR = 2.08; 95% CI: 1.29 to 2.79) than the NHANES participants. The differential involvement of the teeth surfaces in MA users was quite distinctive, with carious surface involvement being highest for the maxillary central incisors, followed by maxillary posterior premolars and molars. Users injecting MA had significantly higher rates of tooth decay compared with noninjectors (P = 0.04). Although MA users experienced decayed and missing dental surfaces more frequently than NHANES participants, NHANES participants had more restored surfaces, especially on molars. The high rates and distinctive patterns of dental caries observed could be used 1) to alert dentists to covert MA use in their patients and 2) as

  5. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    Science.gov (United States)

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  6. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    Directory of Open Access Journals (Sweden)

    Panayotis K Thanos

    Full Text Available Methamphetamine (MA addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET studies have shown decreased brain glucose metabolism (BGluM in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls, or low dose (LD MA (4 mg/kg, or high dose (HD MA (8 mg/kg. Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG, and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  7. Interstitial lung disease in clinically amyopathic dermatomyositis with and without anti-MDA-5 antibody: to lump or split?

    OpenAIRE

    Ikeda, Satoshi; Arita, Machiko; Morita, Mitsunori; Ikeo, Satoshi; Ito, Akihiro; Tokioka, Fumiaki; Noyama, Maki; Misaki, Kenta; Notohara, Kenji; Ishida, Tadashi

    2015-01-01

    Background Interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM-ILD) is often refractory and rapidly progressive. Although the anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody is associated with rapidly progressive ILD (RP-ILD), differences in clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD remain unclear. Methods To clarify the differences in the clinical features and prognosis between anti-MDA...

  8. Polydrug use among IDUs in Tijuana, Mexico: correlates of methamphetamine use and route of administration by gender.

    Science.gov (United States)

    Rusch, Melanie L; Lozada, Remedios; Pollini, Robin A; Vera, Alicia; Patterson, Thomas L; Case, Patricia; Strathdee, Stefanie A

    2009-09-01

    Tijuana is situated on the Mexico-USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006-2007, IDUs > or =18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p 35 years (AOR, 0.2; 95% CI, 0.1-0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3-0.6), homeless (AOR, 1.4 (0.9-2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4-2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment. PMID:19521780

  9. Polydrug Use among IDUs in Tijuana, Mexico: Correlates of Methamphetamine Use and Route of Administration by Gender

    OpenAIRE

    Rusch, Melanie L.; Lozada, Remedios; Pollini, Robin A.; Vera, Alicia; PATTERSON, THOMAS L.; Case, Patricia; Strathdee, Stefanie A.

    2009-01-01

    Tijuana is situated on the Mexico–USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006–2007, IDUs ≥18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression ...

  10. Family Dysfunction Differentially Affects Alcohol and Methamphetamine Dependence: A View from the Addiction Severity Index in Japan

    OpenAIRE

    Kazutaka Ikeda; Yuzo Aikawa; Mitsuru Umeno; Susumu Higuchi; Eiichi Senoo; Ayako Haraguchi; Yasukazu Ogai; Nagisa Sugaya

    2011-01-01

    We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in...

  11. Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats

    OpenAIRE

    Jing, Li; Zhang, Yanan; Li, Jun-Xu

    2015-01-01

    Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown. Methods: This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamine-induced behavioral sensitiz...

  12. Transcriptional and Epigenetic Substrates of Methamphetamine Addiction and Withdrawal: Evidence from a Long-Access Self-Administration Model in the Rat

    OpenAIRE

    Cadet, Jean Lud; Brannock, Christie; Jayanthi, Subramaniam; Krasnova, Irina N.

    2014-01-01

    Methamphetamine use disorder is a chronic neuropsychiatric disorder characterized by recurrent binge episodes, intervals of abstinence, and relapses to drug use. Humans addicted to methamphetamine experience various degrees of cognitive deficits and other neurological abnormalities that complicate their activities of daily living and their participation in treatment programs. Importantly, models of methamphetamine addiction in rodents have shown that animals will readily learn to give themsel...

  13. A Pilot Trial of Integrated Behavioral Activation and Sexual Risk Reduction Counseling for HIV-Uninfected Men Who Have Sex with Men Abusing Crystal Methamphetamine

    OpenAIRE

    Mimiaga, Matthew J.; Reisner, Sari L.; Pantalone, David W.; O'Cleirigh, Conall; Mayer, Kenneth H.; Safren, Steven A.

    2012-01-01

    Crystal methamphetamine use is a major driver behind high-risk sexual behavior among men who have sex with men (MSM). Prior work suggests a cycle of continued crystal methamphetamine use and high-risk sex due to loss of the ability to enjoy other activities, which appears to be a side effect of this drug. Behavioral activation (BA) is a treatment for depression that involves learning to reengage in life's activities. We evaluated a novel intervention for crystal methamphetamine abuse and high...

  14. Improvement in measures of psychological distress amongst amphetamine misusers treated with brief cognitive-behavioural therapy (CBT).

    Science.gov (United States)

    Feeney, G F X; Connor, J P; Young, R McD; Tucker, J; McPherson, A

    2006-10-01

    This trial of cognitive-behavioural therapy (CBT) based amphetamine abstinence program (n=507) focused on refusal self-efficacy, improved coping, improved problem solving and planning for relapse prevention. Measures included the Severity of Dependence Scale (SDS), the General Health Questionnaire-28 (GHQ-28) and Amphetamine Refusal Self-Efficacy. Psychiatric case identification (caseness) across the four GHQ-28 sub-scales was compared with Australian normative data. Almost 90% were amphetamine-dependent (SDS 8.15+/-3.17). Pre-treatment, all GHQ-28 sub-scale measures were below reported Australian population values. Caseness was substantially higher than Australian normative values {Somatic Symptoms (52.3%), Anxiety (68%), Social Dysfunction (46.5%) and Depression (33.7%)}. One hundred and sixty-eight subjects (33%) completed and reported program abstinence. Program completers reported improvement across all GHQ-28 sub-scales {Somatic Symptoms (p<0.001), Anxiety (p<0.001), Social Dysfunction (p<0.001) and Depression (p<0.001)}. They also reported improvement in amphetamine refusal self-efficacy (p<0.001). Improvement remained significant following intention-to-treat analyses, imputing baseline data for subjects that withdrew from the program. The GHQ-28 sub-scales, Amphetamine Refusal Self-Efficacy Questionnaire and the SDS successfully predicted treatment compliance through a discriminant analysis function (p<.001). PMID:16431030

  15. The time-dependent and persistent effects of amphetamine treatment upon recovery from hemispatial neglect in rats.

    Science.gov (United States)

    Brenneman, Miranda M; Hylin, Michael J; Corwin, James V

    2015-10-15

    Neglect is a neuropsychological disorder characterized by the failure to report or respond to stimuli presented to the side of the body opposite a brain lesion and occurs in approximately 40% of right hemisphere strokes. The need for effective therapies to treat neglect in humans has led to the development of a rodent model. Unilateral destruction of medial agranular cortex (AGm), which is part of a cortical network for directed attention, produces severe multimodal neglect with deficits similar to those seen in humans. Amphetamines have previously been investigated for inducing plasticity and recovery of function following brain damage. Amphetamine treatment has been shown to produce recovery from visual, frontal, and sensorimotor cortex damage in animals and this recovery may be the result of axonal growth originating from the opposite, unlesioned hemisphere. The purpose of this study was to investigate whether amphetamine treatment would induce recovery from neglect produced by unilateral AGm destruction, the time frame in which amphetamine must be administered in order to be effective, and the permanence of recovery following treatment. The results indicated that subjects injected with 2mg/kg of d-amphetamine on days 0, 2, and 5 recovered in significantly fewer days than saline-treated controls, even when administration was delayed by 2 and 7 days. Additionally, these studies indicated that recovery persisted for at least 60 days suggesting that recovery is likely to be long term. PMID:26209293

  16. Association between the Regulator of G-protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia

    Science.gov (United States)

    Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H

    2011-01-01

    The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p=0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population. PMID:21886588

  17. CYP1-mediated antiproliferative activity of dietary flavonoids in MDA-MB-468 breast cancer cells

    International Nuclear Information System (INIS)

    Among the different mechanisms proposed to explain the cancer-protecting effect of dietary flavonoids, substrate-like interactions with cytochrome P450 CYP1 enzymes have recently been explored. In the present study, the metabolism of the flavonoids chrysin, baicalein, scutellarein, sinensetin and genkwanin by recombinant CYP1A1, CYP1B1 and CYP1A2 enzymes, as well as their antiproliferative activity in MDA-MB-468 human breast adenocarcinoma and MCF-10A normal breast cell lines, were investigated. Baicalein and 6-hydroxyluteolin were the only conversion products of chrysin and scutellarein metabolism by CYP1 family enzymes, respectively, while baicalein itself was not metabolized further. Sinensetin and genkwanin produced a greater number of metabolites and were shown to inhibit strongly in vitro proliferation of MDA-MB-468 cells at submicromolar and micromolar concentrations, respectively, without essentially affecting the viability of MCF-10A cells. Cotreatment of the CYP1 family inhibitor acacetin reversed the antiproliferative activity noticed for the two flavones in MDA-MB-468 cells to 13 and 14 μM respectively. In contrast chrysin, baicalein and scutellarein inhibited proliferation of MDA-MB-468 cells to a lesser extent than sinensetin and genkwanin. The metabolism of genkwanin to apigenin and of chrysin to baicalein was favored by CYP1B1 and CYP1A1, respectively. Taken together the data suggests that CYP1 family enzymes enhance the antiproliferative activity of dietary flavonoids in breast cancer cells, through bioconversion to more active products.

  18. MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

    Directory of Open Access Journals (Sweden)

    Qian Feng

    2012-11-01

    Full Text Available RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C, a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.

  19. MDA trend research on radioactive xenon measurement by HPGe γ spectrometer

    International Nuclear Information System (INIS)

    Monitoring radioactive Xenon concentration in air is effective way to screen nuclear event in CTBT verification regime. This article introduces the theory and process of radioactive Xenon measurement by HPGe gamma spectrometer and researches MDA trend of Xenon isotope base on background data. (authors)

  20. Expression pattern of mda-7/IL-24 receptors in liver cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Hong Zhu; Zhi-Bin Yang

    2009-01-01

    BACKGROUND: The mda-7/IL-24 receptor belongs to the typeⅡ cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy. METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were ampliifed by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed. RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1;BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL-20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor. CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.

  1. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M

    2014-01-01

    UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppr

  2. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

    2014-01-01

    RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interfer

  3. Collection and measurement of atmospheric contaminants during Skylab AM/MDA unmanned altitude chamber test

    Science.gov (United States)

    1972-01-01

    The analytical data obtained from both cryogenic and grab sampling of the atmosphere of the Skylab AM/MDA during an 84 hour unmanned chamber run are reported. The level of contaminants found at different points of the test chamber are tabulated. The results indicate that there was no clear trend of increasing or decreasing contaminant levels during the test run.

  4. Comparative Study of the Activity of Brain Behavioral Systems in Methamphetamine and Opiate Dependents

    Science.gov (United States)

    Alemikhah, Marjan; Faridhosseini, Farhad; Kordi, Hassan; Rasouli-Azad, Morad; Shahini, Najmeh

    2016-01-01

    Background: Substance dependency is a major problem for the general health of a society. Different approaches have investigated the substance dependency in order to explain it. Gray’s reinforcement sensitivity theory (RST) is an advanced and important neuropsychological theory in this area. Objectives: The aim of this study was to compare three systems of the revised reinforcement sensitivity theory the behavioral activation system (r-BAS), the revised behavioral inhibition system (r-BIS), and the revised fight/flight/freezing system (r-FFFS) between patients dependent on methamphetamine and opiates, and a group of controls. Patients and Methods: This research was a causal-comparative study that was conducted in the first six months of 2012. The population of the study was males of Mashhad city, who were dependent on methamphetamine or opiates, and ruling out psychotic disorders and prominent Axis II. Twenty-five people were selected by the convenient sampling method. Also, 25 non-dependent people from the patients’ relatives were selected and matched for the variables of age, gender, and education to participate in this study. Participants were evaluated using a structured clinical interview (SCID) for DSM-IV, demographic questionnaire information, and a Jackson-5 questionnaire (2009). Data were analyzed by Chi-square, K-S, and independent t-test. Results: The methamphetamine dependent group had a higher sensitivity in the r-BAS, r-BIS, and the r-Fight and r-Freezing systems compared to the control group (P 0.05). “The scores of r-BIS were also significantly higher in the methamphetamine-dependent group than the opioid-dependent and control groups. For the r-Fight variable, the methamphetamine-dependent group was higher than the opioid-dependent group”. Conclusions: The personality patterns of patients dependent on methamphetamines were different from the controls. These people have a high sensitivity to punishment cues, such as being compared in social

  5. The dopamine D1-D2 receptor heteromer exerts tonic inhibitory effect on the expression of amphetamine-induced locomotor sensitization

    Science.gov (United States)

    Shen, Maurice Y.F.; Perreault, Melissa L.; Fan, Theresa; George, Susan R.

    2014-01-01

    A role for the dopamine D1-D2 receptor heteromer in the regulation of reward and addiction-related processes has been previously implicated. In the present study, we examined the effects of D1-D2 heteromer stimulation by the agonist SKF 83959 and its disruption by a selective TAT-D1 peptide on amphetamine-induced locomotor sensitization, a behavioural model widely used to study the neuroadaptations associated with psychostimulant addiction. D1-D2 heteromer activation by SKF 83959 did not alter the acute locomotor effects of amphetamine but significantly inhibited amphetamine-induced locomotor responding across the 5 day treatment regimen. In addition, a single injection of SKF 83959 was sufficient to abolish the expression of locomotor sensitization induced by a priming injection of amphetamine after a 72-hour withdrawal. Conversely, inhibition of D1-D2 heteromer activity by the TAT-D1 peptide enhanced subchronic amphetamine-induced locomotion and the expression of amphetamine locomotor sensitization. Treatment solely with the TAT-D1 disrupting peptide during the initial 5 day treatment phase was sufficient to induce a sensitized locomotor phenotype in response to the priming injection of amphetamine. Together these findings demonstrate that the dopamine D1-D2 receptor heteromer exerts tonic inhibitory control on neurobiological processes involved in sensitization to amphetamine, indicating that the dopamine D1-D2 receptor heteromer may be a novel molecular substrate in addiction processes involving psychostimulants. PMID:25444866

  6. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina;

    2015-01-01

    and anxiety disorders. In addition, SERT is a major molecular target for psychostimulants such as cocaine and amphetamines. Amphetamine-induced transport reversal at the closely related dopamine transporter (DAT) has been shown previously to be contingent upon modulation by calmodulin kinase IIα (α......CaMKII was verified using biochemical assays and FRET analysis and colocalization of the two molecules was confirmed in primary serotonergic neurons in culture. Moreover, we found that genetic deletion of αCaMKII impaired the locomotor response of mice to 3,4-methylenedioxymethamphetamine (also known as "ecstasy......") and blunted d-fenfluramine-induced prolactin release, substantiating the importance of αCaMKII modulation for amphetamine action at SERT in vivo as well. SERT-mediated substrate uptake was neither affected by inhibition of nor genetic deficiency in αCaMKII. This finding supports the concept that uptake...

  7. Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Arnfred, Sidse M; Hemmingsen, Ralf P;

    2004-01-01

    Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for...... validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg...... valuable additional tool in assessing pig models of neuropsychiatric disorders....

  8. Cerebral radionuclide tomography using 123I-isopropyl-amphetamine in cerebral ischaemic pathology

    International Nuclear Information System (INIS)

    Thirty patients with previous cerebral ischaemic accident were explored by both computerized tomography (CT) and radionuclide tomography after injection of 123I-labeled N-isopropyl-iodo-amphetamine. All lesions that were visible at CT were also visible at radionuclide tomography. However, in 7 patients with normal CT results the latter method showed areas of cerebral activity anatomically correlated with neurological signs or vascular lesions. Cerebellar diaschisis was observed in 50% of established lesions in the carotid territory. Radionuclide tomography therefore appears as a very sensitive method to be used in ischaemic pathology with transient or regressive accidents

  9. The quantitation of N-isopropyl-p-I-123 amphetamine cerebral perfusion and function studies

    International Nuclear Information System (INIS)

    A method of quantitatively analyzing ECT sections obtained from cerebral perfusion/function studies with N-isopropyl-p-I-123 Amphetamine (IMP) is presented and illustrated by a concrete case. This analysis makes use of six pairs of regions delineating the perfusion territories of the major cerebral arteries, and produces six right-left ratios which provide objective criteria to assess pathology and, in our opinion, is an important adjunct to visual interpretation of IMP studies. Even though quantitation of rCBF with IMP is highly desirable, no satisfactory method short of arterial input sampling seems to have been used so far to obtain absolute blood flow values. (orig.)

  10. Serotonergic responses to stress are enhanced in the central amygdala and inhibited in the ventral hippocampus during amphetamine withdrawal.

    Science.gov (United States)

    Li, Hao; Scholl, Jamie L; Tu, Wenyu; Hassell, James E; Watt, Michael J; Forster, Gina L; Renner, Kenneth J

    2014-12-01

    Withdrawal from amphetamine increases anxiety and reduces the ability to cope with stress, which are factors that are believed to contribute to drug relapse. Stress-induced serotonergic transmission in the central nucleus of the amygdala is associated with anxiety states and fear. Conversely, stress-induced increases in ventral hippocampal serotonin (5-HT) levels have been linked to coping mechanisms. The goal of this study was to investigate the neurobiological changes induced by amphetamine that contribute to stress sensitivity during withdrawal. We tested the hypothesis that limbic serotonergic responses to restraint stress would be altered in male Sprague-Dawley rats chronically pretreated with amphetamine (2.5 mg/kg, intraperitoneal) and then subjected to 2 weeks of withdrawal. Amphetamine withdrawal resulted in increased stress-induced behavioral arousal relative to control treatment, suggesting that drug withdrawal induced greater sensitivity to the stressor. When microdialysis was used to determine the effects of restraint on extracellular 5-HT, stress-induced increases in 5-HT levels were abolished in the ventral hippocampus and augmented in the central amygdala during amphetamine withdrawal. Reverse dialysis of the glucocorticoid receptor antagonist mifepristone into the ventral hippocampus blocked the stress-induced increase in 5-HT levels in saline-pretreated rats, suggesting that glucocorticoid receptors mediate stress-induced increases in 5-HT levels in the ventral hippocampus. However, mifepristone had no effect on stress-induced increases in 5-HT levels in the central amygdala, indicating that stress increases 5-HT levels in this region independently of glucocorticoid receptors. During amphetamine withdrawal, the absence of stress-induced increases in ventral hippocampal 5-HT levels combined with enhanced stress-induced serotonergic responses in the central amygdala may contribute to drug relapse by decreasing stress-coping ability and heightening

  11. Adulterants and diluents in heroin, amphetamine, and cocaine found on the illicit drug market in Aarhus, Denmark

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Lindholst, Christian; Kaa, Elisabet

    2009-01-01

    The aim of the present study was to investigate the composition of heroin, amphetamine, and cocaine seized in the police district of Aarhus, the second largest city in Denmark, during a 2-year period. The purity of the active substance was measured together with the frequency and purity of...... adulterants and diluents present in the drugs. Results are compared with a similar study conducted ten years earlier. The concentrations of the active substances in illicit heroin, amphetamine, and cocaine samples have decreased significantly over a 10-year period. This finding shows that the "cutting" of...

  12. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion;

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  13. Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion;

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  14. Alterations in subcellular expression of acid-sensing ion channels in the rat forebrain following chronic amphetamine administration

    OpenAIRE

    Suman, Ajay; Mehta, Bhavi; Guo, Ming-Lei; Chu, Xiang-Ping; Fibuch, Eugene E.; Mao, Li-Min; WANG, John Q.

    2010-01-01

    Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. To explore whether ASICs are linked to addictive properties of drugs of abuse, we investigated the effect of the psychostimulant amphetamine on subcellular ASIC expression in the rat forebrain in vivo. Repeated administration of amphetamine (once daily for 7 days, 1.25 mg/kg for days 1/7, 4 mg/kg for days 2–6) induced typi...

  15. Development of a harmonized method for the profiling of amphetamines. I. Synthesis of standards and compilation of analytical data.

    Science.gov (United States)

    Aalberg, Laura; Andersson, Kjell; Bertler, Christina; Borén, Hans; Cole, Michael D; Dahlén, Johan; Finnon, Yvonne; Huizer, Henk; Jalava, Kaisa; Kaa, Elisabet; Lock, Eric; Lopes, Alvaro; Poortman-van der Meer, Anneke; Sippola, Erkki

    2005-05-10

    Reference material was synthesised for 21 substances that are frequently present as synthetic impurities, i.e. by-products, in illicitly produced amphetamine. Each of these substances is a typical by-product for at least one of the three approaches most often used to synthesise amphetamine, namely, the Leuckart, the reductive amination of benzyl methyl ketone, and the nitrostyrene routes. A large body of data on the substances was recorded, including the following: mass spectra, ultraviolet spectra, Fourier transform infrared spectra, infrared spectra in gas phase, and 1H NMR and 13C NMR spectra. PMID:15749364

  16. Correlates of Heroin and Methamphetamine Use among Homeless Male Ex-Jail and Prison Offenders

    OpenAIRE

    Nyamathi, Adeline; Salem, Benissa E.; Farabee, David; Hall, Elizabeth; Zhang, Sheldon; Marfisee, Mary; Khalilifard, Farinaz; Musto, Stefanie; Leake, Barbara

    2014-01-01

    Homeless men exiting California State jails and prisons are a heterogeneous community with varied childhood, incarceration and drug use histories. This cross-sectional study assessed whether homeless men who were discharged from either jail or prison into a residential substance abuse treatment program, differed in terms of methamphetamine and heroin use. This study utilized baseline data collected on 540 recently paroled men randomized to one of three programs that assessed the impact of a p...

  17. Methamphetamine Administration Targets Multiple Immune Subsets and Induces Phenotypic Alterations Suggestive of Immunosuppression

    OpenAIRE

    Robert Harms; Brenda Morsey; Craig W Boyer; Fox, Howard S.; Nora Sarvetnick

    2012-01-01

    Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells p...

  18. Olfactory bulbectomy increases reinstatement of methamphetamine seeking after a forced abstinence in rats.

    Science.gov (United States)

    Babinska, Zuzana; Ruda-Kucerova, Jana; Amchova, Petra; Merhautova, Jana; Dusek, Ladislav; Sulcova, Alexandra

    2016-01-15

    Drug addiction is commonly associated with depression and comorbid patients also suffer from higher cravings and increased relapse rate. To address this issue preclinically we combined the olfactory bulbectomy (OBX) model of depression and intravenous methamphetamine self-administration procedure in rats to assess differences in relapse-like behavior. Male Sprague-Dawley rats were divided randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX) was performed while the other group was sham operated. After recovery, intracardiac catheter was implanted. Intravenous self-administration procedure was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments, Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was maintained, a period of forced abstinence was initiated and rats were kept in their home-cages for 14 days. Finally, one reinstatement session was conducted in operant boxes with no drug delivery. In the reinstatement session the mean of 138.4 active nose-pokes was performed by the OBX group, while the sham group displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during maintenance phase in OBX and sham operated group respectively. OBX group also showed significantly more passive nose-pokes indicating hyperactive behavioral traits in bulbectomized rats. However, the % of active operandum preference was equal in both groups. Olfactory bulbectomy model significantly increased reinstatement of methamphetamine seeking behavior. This paradigm can be used to evaluate potential drugs that are able to suppress the drug-seeking behavior. PMID:26431766

  19. Role of the Serotonergic System in Reduced Pulmonary Function after Exposure to Methamphetamine

    OpenAIRE

    Wells, Sandra M.; Buford, Mary C.; Porter, Virginia M.; Brunell, Heather L.; Bunderson-Schelvan, Melisa; Nevin, Andrew B.; Cardozo-Pelaez, Fernando; Holian, Andrij

    2009-01-01

    Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function, as measured by transpulmonary resistance, dynamic compliance, and whole-body plethysmography compared with unexposed con...

  20. “Frontal systems” behaviors in comorbid human immunodeficiency virus infection and methamphetamine dependency

    OpenAIRE

    MARQUINE, María J.; Iudicello, Jennifer E.; Morgan, Erin E.; Brown, Gregory G.; Letendre, Scott L.; Ellis, Ronald J.; Deutsch, Reena; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2013-01-01

    Human immunodeficiency virus (HIV) infection and methamphetamine (MA) dependence are associated with neural injury preferentially involving frontostriatal circuits. Little is known, however, about how these commonly comorbid conditions impact behavioral presentations typically associated with frontal systems dysfunction. Our sample comprised 47 HIV-uninfected/MA-nondependent; 25 HIV-uninfected/MA-dependent; 36 HIV-infected/MA-nondependent; and 28 HIV-infected/MA-dependent subjects. Participan...

  1. Massive Hematochezia: A Complication of Methamphetamine-Induced Vasculitis Treated by Transcatheter Hemostasis

    Directory of Open Access Journals (Sweden)

    Daniel P. Link

    2011-01-01

    Full Text Available A long-term, heavy methamphetamine user with life-threatening rectal hemorrhage was treated with transcatheter occlusion of the bleeding arteries. The bleeding blood vessels were vulnerable submucosal arteries, part of the collateral supply to the distal colon. Visceral arteriography demonstrates severe arterial stenotic lesions of the celiac axis, superior mesenteric artery and the inferior mesenteric artery. Collateral vessels were seen with corkscrew morphology similar to that seen with thromboangiitis obliterans.

  2. Massive Hematochezia: A Complication of Methamphetamine-Induced Vasculitis Treated by Transcatheter Hemostasis

    OpenAIRE

    Link, Daniel P.; Yung-Wei Chi

    2011-01-01

    A long-term, heavy methamphetamine user with life-threatening rectal hemorrhage was treated with transcatheter occlusion of the bleeding arteries. The bleeding blood vessels were vulnerable submucosal arteries, part of the collateral supply to the distal colon. Visceral arteriography demonstrates severe arterial stenotic lesions of the celiac axis, superior mesenteric artery and the inferior mesenteric artery. Collateral vessels were seen with corkscrew morphology similar to that seen with...

  3. Dopamine transporter density of the basal ganglia assessed with I-123 IPT SPECT in methamphetamine abusers

    International Nuclear Information System (INIS)

    Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, ρ =0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT. Abuser group had lower basal ganglia DAT SBR than that of control (2.38 ± 0.20 vs 3.04 ± 0.27, ρ =0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, ρ =0.012, r=-0.924, ρ =0.009) This results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers

  4. Glial cell modulators attenuate methamphetamine self-administration in the rat

    OpenAIRE

    SNIDER, Sarah E.; Hendrick, Elizabeth S; BEARDSLEY, PATRICK M.

    2013-01-01

    Neuroinflammation induced by activated microglia and astrocytes can be elicited by drugs of abuse. Methamphetamine administration activates glial cells and increases proinflammatory cytokine production, and there is recent evidence of a linkage between glial cell activation and drug abuse-related behavior. We have previously reported that ibudilast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine), which inhibits phosphodiesterase (PDE) and pro-inflammatory activity, blocks reinstatem...

  5. Offspring of Prenatal IV Nicotine Exposure Exhibit Increased Sensitivity to the Reinforcing Effects of Methamphetamine

    OpenAIRE

    Harrod, Steven B.; Lacy, Ryan T.; Morgan, Amanda J.

    2012-01-01

    Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intravenou...

  6. Impact of COMT Val158Met on executive functioning in the context of HIV and methamphetamine

    OpenAIRE

    Bousman, Chad A.; Cherner, Mariana; Glatt, Stephen J.; Atkinson, J. Hampton; Grant, Igor; Tsuang, Ming T.; Everall, Ian P.

    2010-01-01

    The catechol-O-methyltransferease (COMT) Val allele has been linked to executive dysfunction among healthy individuals. The nature of this relationship is unknown in the context of HIV infection and/or methamphetamine (METH) dependence, two conditions that can alter dopaminergic system functioning. We sought to determine if the putative relationship between COMT and executive dysfunction could be observed among individuals with and without HIV-infection and/or METH dependence, and to explore ...

  7. Dopamine transporter density of the basal ganglia assessed with I-123 IPT SPECT in methamphetamine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Ryung; Ahn, Byeong Cheol [Kyungpook National University Medical School, Daegu (Korea, Republic of); Kewm, Do Hun [National Bugok Mental Hospital, Changryung (Korea, Republic of)] (and others)

    2005-10-15

    Functional imaging of dopamine transporter (DAT) defines integrity of the dopaminergic system, and DAT is the target site of drugs of abuse such as cocaine and methamphetamine. Functional imaging the DAT may be a sensitive and selective indicator of neurotoxic change by the drug. The aim of the present study is to evaluate the clinical implications of qualitative/quantitative analyses of dopamine transporter imaging in methamphetamine abusers. Six detoxified methamphetamine abusers (abuser group) and 4 volunteers (control group) were enrolled in this study. Brain MRI was performed in all of abuser group. Abuser group underwent psychiatric and depression assessment using brief psychiatric rating scale (BPRS) and Hamilton depression rating scale (HAMD), respectively. All of the subjects underwent I-123 IPT SPECT (IPT SPECT). IPT SPECT image was analysed with visual qualitative method and quantitative method using basal ganglia dopamine transporter (DAT) specific/non-specific binding ratio (SBR). Comparison of DAT SBR between abuser and control groups was performed. We also performed correlation tests between psychiatric and depression assessment results and DAT SBR in abuser group. All of abuser group showed normal MRI finding, but had residual psychiatric and depressive symptoms, and psychiatric and depressive symptom scores were exactly correlated (r=1.0, {rho} =0.005) each other. Five of them showed abnormal finding on qualitative visual I-123 IPT SPECT. Abuser group had lower basal ganglia DAT SBR than that of control (2.38 {+-} 0.20 vs 3.04 {+-} 0.27, {rho} =0.000). Psychiatric and depressive symptoms were negatively well correlated with basal ganglia DAT SBR (r=-0.908, {rho} =0.012, r=-0.924, {rho} =0.009) This results suggest that dopamine transporter imaging using I-123 IPT SPECT may be used to evaluate dopaminergic system of the basal ganglia and the clinical status in methamphetamine abusers.

  8. Offspring of prenatal IV nicotine exposure exhibit increased sensitivity to the reinforcing effects of methamphetamine

    OpenAIRE

    StevenBrownHarrod

    2012-01-01

    Maternal smoking during pregnancy is associated with increased substance abuse in offspring. Preclinical research shows that in utero exposure to nicotine, the primary psychoactive compound in tobacco smoke, influences the neurodevelopment of reward systems and alters motivated behavior in offspring. The present study determined if prenatal nicotine (PN) exposure altered the sensitivity to the reinforcing and aversive effects of methamphetamine (METH) in offspring using a low dose, intraven...

  9. Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

    OpenAIRE

    Itoh, Kanako; Hashimoto, Kenji; Shimizu, Eiji; Sekine, Yoshimoto; Ozaki, Norio; Inada, Toshiya; Harano, Mutsuo; Iwata, Nakao; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sora,Ichiro; Nakata, Kenji; Ujike, Hiroshi; Iyo, Masaomi

    2005-01-01

    Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP)...

  10. An Ethnographic Exploration of Self-Reported Violence Among Rural Methamphetamine Users

    OpenAIRE

    Sexton, Rocky L.; Carlson, Robert G.; Leukefeld, Carl G.; Brenda M. Booth

    2009-01-01

    Baseline and follow-up qualitative interviews with methamphetamine (MA) users in rural Kentucky and Arkansas examined their involvement in drug-related violence. Twelve baseline participants reported MA-related violence, while 20 reported violence linked to other substances. In follow-up interviews conducted 12 to 24 months later, four participants reported MA-related violence and 3 reported violence associated with other substances. Violence was rarely connected to MA’s psychoactive effects....

  11. Cognitive functions in methamphetamine induced psychosis compared to schizophrenia and normal subjects

    OpenAIRE

    Zahra Ezzatpanah; Seyed Vahid Shariat; Mehdi Tehrani-Doost

    2014-01-01

    Objective The purpose of this research was to study the cognitive functions in patients with methamphetamine-induced psychosis (MIP) in comparison with schizophrenia patients and normal subjects. Method This was a cross-sectional study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal individuals were selected via convenient sampling and were matched on age, sex and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and Wechsler Memory Tests were used to...

  12. Cortical ionotropic glutamate receptor antagonism protects against methamphetamine-induced striatal neurotoxicity

    OpenAIRE

    Gross, Noah B.; Duncker, Patrick C.; Marshall, John F.

    2011-01-01

    Binge administration of the psychostimulant drug, methamphetamine (mAMPH), produces long-lasting structural and functional abnormalities in the striatum. mAMPH binges produce non-exocytotic release of dopamine (DA), and mAMPH-induced activation of excitatory afferent inputs to cortex and striatum is evidenced by elevated extracellular glutamate (GLU) in both regions. The mAMPH-induced increases in DA and GLU neurotransmission are thought to combine to injure striatal DA nerve terminals of mAM...

  13. (+)-Methamphetamine-induced monoamine reductions and impaired egocentric learning in adrenalectomized rats is independent of hyperthermia

    OpenAIRE

    Herring, Nicole R.; Gudelsky, Gary A.; Vorhees, Charles V.; Williams, Michael T.

    2010-01-01

    Methamphetamine (MA) is widely abused and implicated in residual cognitive deficits. In rats, increases in plasma corticosterone and egocentric learning deficits are observed after a one-day binge regimen of MA (10 mg/kg × 4 at 2 h intervals). The purpose of this experiment was to determine if adrenal inactivation during and following MA exposure would attenuate the egocentric learning deficits in the Cincinnati water maze (CWM). In the first experiment, the effects of adrenalectomy (ADX) or ...

  14. Characterization of Route Specific Impurities Found in Methamphetamine Synthesized by the Leuckart and Reductive Amination Methods

    OpenAIRE

    Kunalan, Vanitha; Nic Daéid, Niamh; Kerr, William J.; Buchanan, Hilary A. S.; McPherson, Allan R.

    2009-01-01

    Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of “route specific” impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) ...

  15. Measurement of Cue-Induced Craving in Human Methamphetamine- Dependent Subjects;New Methodological Hopes for Reliable Assessment of Treatment Efficacy

    Directory of Open Access Journals (Sweden)

    Zahra Alam Mehrjerdi

    2011-09-01

    Full Text Available  Methamphetamine (MA is a highly addictive psychostimulant drug with crucial impacts on individuals on various levels. Exposure to methamphetamine-associated cues in laboratory can elicit measureable craving and autonomic reactivity in most individuals with methamphetamine dependence and the cue reactivity can model how craving would result in continued drug seeking behaviors and relapse in real environments but study on this notion is still limited. In this brief article, the authors review studies on cue-induced craving in human methamphetamine- dependent subjects in a laboratory-based approach. Craving for methamphetamine is elicited by a variety of methods in laboratory such as paraphernalia, verbal and visual cues and imaginary scripts. In this article, we review the studies applying different cues as main methods of craving incubation in laboratory settings. The brief reviewed literature provides strong evidence that craving for methamphetamine in laboratory conditions is significantly evoked by different cues. Cue-induced craving has important treatment and clinical implications for psychotherapists and clinicians when we consider the role of induced craving in evoking intense desire or urge to use methamphetamine after or during a period of successful craving prevention program. Elicited craving for methamphetamine in laboratory conditions is significantly influenced by methamphetamine-associated cues and results in rapid craving response toward methamphetamine use. This notion can be used as a main core for laboratory-based assessment of treatment efficacy for methamphetamine-dependent patients. In addition, the laboratory settings for studying craving can bridge the gap between somehow-non-reliable preclinical animal model studies and budget demanding randomized clinical trials.

  16. Frequency of Methamphetamine Use as a Major Contributor Toward the Severity of Cardiomyopathy in Adults ≤50 Years.

    Science.gov (United States)

    Neeki, Michael M; Kulczycki, Michael; Toy, Jake; Dong, Fanglong; Lee, Carol; Borger, Rodney; Adigopula, Sasikanth

    2016-08-15

    Methamphetamine is one of the most commonly abused illegal drugs in the United States. Health care providers are commonly faced with medical illness caused by methamphetamine. This study investigates the impact of methamphetamine use on the severity of cardiomyopathy and heart failure in young adults. This retrospective study analyzed patients seen at Arrowhead Regional Medical Center from 2008 to 2012. Patients were between 18 and 50 years old. All patients had a discharge diagnosis of cardiomyopathy or heart failure. The severity of disease was quantified by left ventricular systolic dysfunction: heart failure with preserved ejection fraction to mildly reduced if ejection fraction was >40% and moderate to severely depressed if ejection fraction was ≤40%. Methamphetamine abuse was determined by a positive urine drug screen or per documented history. Of the 590 patients, 223 (37.8%) had a history of methamphetamine use. More than half the population was men (n = 389, 62.3%); 41% was Hispanic (n = 243), 25.8% was Caucasian (n = 152), and 27.8% was African-American (n = 164); 60.9% were in the age range of 41 to 50 years (n = 359). Patients with a history of methamphetamine use had increased odds (odds ratio = 1.80, 95% confidence interval 1.27 to 2.57) of having a moderately or severely reduced ejection fraction. Additionally, men were more likely (odds ratio 3.13, 95% confidence interval 2.14 to 4.56) to have worse left ventricular systolic dysfunction. In conclusion, methamphetamine use was associated with an increased severity of cardiomyopathy in young adults. PMID:27374605

  17. Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.

    Directory of Open Access Journals (Sweden)

    Tomoyasu Wakuda

    Full Text Available BACKGROUND: Obstetric complications have been regarded as a risk factor for schizophrenia later in life. One of the mechanisms underlying the association is postulated to be a hypoxic process in the brain in the offspring around the time of birth. Hippocampus is one of the brain regions implicated in the late-onset dopaminergic dysfunction associated with hypoxic obstetric complications. METHODOLOGY/PRINCIPAL FINDINGS: We used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth. At 6 and 12 weeks after birth, the behavior of the pups was assessed using a methamphetamine-induced locomotion test. In addition, the histopathology of the hippocampus was examined by means of stereology. At 6 weeks, there was no change in the methamphetamine-induced locomotion. However, at 12 weeks of age, we found an elevation in methamphetamine-induced locomotor activity, which was associated with an increase of dopamine release in the nucleus accumbens. At the same age, we also found a reduction of the dentate granule cells of the hippocampus. CONCLUSIONS/SIGNIFICANCE: These results suggest that the dopaminergic dysregulation after perinatal asphyxia is associated with a reduction in hippocampal dentate granule cells, and this may partly contribute to the pathogenesis of schizophrenia.

  18. The role of the GABA system in amphetamine-type stimulant use disorders

    Directory of Open Access Journals (Sweden)

    Dongliang eJiao

    2015-05-01

    Full Text Available Abuse of amphetamine-type stimulants (ATS has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems. Findings from recent studies indicate that in addition to the traditional dopamine-ergic system, the GABA (gamma-aminobutyric acid-ergic system plays an important role in ATS abuse. However the exact mechanisms of the GABA-ergic system in amphetamine-type stimulant use disorders are not fully understood. This review discusses the role of the GABA-ergic system in ATS use disorders, including ATS induced psychotic disorders and cognitive dysfunctions. We conclude that the GABA-ergic system are importantly involved in the development of ATS use disorders through multiple pathways, and that therapies or medicines that target specific members of the GABA-ergic system may be novel effective interventions for the treatment of ATS use disorders.

  19. Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

    Directory of Open Access Journals (Sweden)

    Bindu nee Giri Jain

    2010-01-01

    Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

  20. Brain SPECT with /sup 123/I-labelled amphetamine derivatives in epilepsy and migraine

    International Nuclear Information System (INIS)

    On the basis of positron tomography (PET) results it has been well established that seizures are connected with increases in regional cerebral blood flow and metabolism. In the interictal stage, however, regionally diminished perfusion can be observed in the affected cortical areas. As changes in cerebral function due to seizures are seldom accompanied by structural changes they often cannot be detected by radiographic techniques. Here the EEG is useful, but has significant limitations: It is often difficult to lateralize or localize the origin of the seizure or to assess the severity and extent of underlying cerebral involvement. Since 1982 SPECT with /sup 123/I-labelled N-isopropyl amphetamines (IMP) has been used for the evaluation of epilepsy. By means of this technique, identical findings - ictally increased, interictally decreased tracer accumulation - as with PET were established. In addition, amphetamine SPECT can reveal increased perfusion in epileptic foci at a time when there is focal electrical discharge, even in the absence of clinically recognizable seizures. The present paper presents an overview of the authors' results in a relatively large series of patients with epilepsy. Data are also included of patients with migraine accompagnee - a disease in which EEG pathology may also be observed

  1. Heroin and amphetamine users display opposite relationships between trait and neurobehavioral dimensions of impulsivity.

    Science.gov (United States)

    Vassileva, Jasmin; Paxton, Jessica; Moeller, F Gerard; Wilson, Michael J; Bozgunov, Kiril; Martin, Eileen M; Gonzalez, Raul; Vasilev, Georgi

    2014-03-01

    The multidimensional construct of impulsivity is implicated in all phases of the addiction cycle. Substance dependent individuals (SDIs) demonstrate elevated impulsivity on both trait and laboratory tests of neurobehavioral impulsivity; however our understanding of the relationship between these different aspects of impulsivity in users of different classes of drugs remains rudimentary. The goal of this study was to assess for commonalities and differences in the relationships between trait and neurobehavioral impulsivity in heroin and amphetamine addicts. Participants included 58 amphetamine dependent (ADIs) and 74 heroin dependent individuals (HDIs) in protracted abstinence. We conducted Principal Component Analyses (PCA) on two self-report trait and six neurobehavioral measures of impulsivity, which resulted in two trait impulsivity (action, planning) and four neurobehavioral impulsivity composites (discriminability, response inhibition efficiency, decision-making efficiency, quality of decision-making). Multiple regression analyses were used to determine whether neurobehavioral impulsivity is predicted by trait impulsivity and drug type. The analyses revealed a significant interaction between drug type and trait action impulsivity on response inhibition efficiency, which showed opposite relationships for ADIs and HDIs. Specifically, increased trait action impulsivity was associated with worse response inhibition efficiency in ADIs, but with better efficiency in HDIs. These results challenge the unitary account of drug addiction and contribute to a growing body of literature that reveals important behavioral, cognitive, and neurobiological differences between users of different classes of drugs. PMID:24342174

  2. Personality and the acute subjective effects of d-amphetamine in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-03-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions. Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Drug responses were reduced via principal components analysis to three higher-order factors ('Euphoria', 'Arousal', 'Dysphoria'). Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors. High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria. In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria. These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems. PMID:23343596

  3. Effects of methylphenidate during emotional processing in amphetamine users: preliminary findings.

    Science.gov (United States)

    Bottelier, M A; Schouw, M L J; de Ruiter, M B; Ruhe, H G; Lindauer, R J L; Reneman, L

    2015-12-01

    D-amphetamine (dAMPH) and methylphenidate (MPH) are stimulants used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Preclinical studies have shown that in healthy animals, dAMPH induces dopamine (DA) dysfunction, as evidenced for instance by loss of DA levels and its transporters. It has also been suggested that DA plays an important role in emotional processing, and that altered DA-ergic intervention may modulate amygdala function. To explore the role of the DA system in emotional processing we examined emotional processing using functional magnetic resonance imaging (fMRI) in eight male recreational users of dAMPH and eight male healthy controls. We compared brain activation between both groups during an emotional face-processing task with and without an oral MPH challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1½ hours after receiving an oral dose of 35 mg MPH. A significant Valence*Group interaction (p = .037) indicated amygdala hyperreactivity to fearful facial expressions in dAMPH users that was robust against adjustment for age (p = .015). Furthermore, duration of amphetamine use in years was positively correlated with amygdala reactivity in dAMPH users (r = .76; p = .029). These exploratory findings are in line with previous findings suggesting that DA plays a role in emotional processing. PMID:25563230

  4. Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans.

    Science.gov (United States)

    Katner, Simon N; Neal-Beliveau, Bethany S; Engleman, Eric A

    2016-01-01

    Methamphetamine (MAP) addiction is substantially prevalent in today's society, resulting in thousands of deaths and costing billions of dollars annually. Despite the potential deleterious consequences, few studies have examined the long-term effects of embryonic MAP exposure. Using the invertebrate nematode Caenorhabditis elegans allows for a controlled analysis of behavioral and neurochemical changes due to early developmental drug exposure. The objective of the current study was to determine the long-term behavioral and neurochemical effects of embryonic exposure to MAP in C. elegans. In addition, we sought to improve our conditioning and testing procedures by utilizing liquid filtration, as opposed to agar, and smaller, 6-well testing plates to increase throughput. Wild-type N2 C. elegans were embryonically exposed to 50 μM MAP. Using classical conditioning, adult-stage C. elegans were conditioned to MAP (17 and 500 μM) in the presence of either sodium ions (Na+) or chloride ions (Cl-) as conditioned stimuli (CS+/CS-). Following conditioning, a preference test was performed by placing worms in 6-well test plates spotted with the CS+ and CS- at opposite ends of each well. A preference index was determined by counting the number of worms in the CS+ target zone divided by the total number of worms in the CS+ and CS- target zones. A food conditioning experiment was also performed in order to determine whether embryonic MAP exposure affected food conditioning behavior. For the neurochemical experiments, adult worms that were embryonically exposed to MAP were analyzed for dopamine (DA) content using high-performance liquid chromatography. The liquid filtration conditioning procedure employed here in combination with the use of 6-well test plates significantly decreased the time required to perform these experiments and ultimately increased throughput. The MAP conditioning data found that pairing an ion with MAP at 17 or 500 μM significantly increased the preference

  5. Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

    Science.gov (United States)

    Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

    2010-04-01

    This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

  6. OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

    Directory of Open Access Journals (Sweden)

    Muñiz P

    2014-05-01

    Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

  7. Ultra-rapid targeted analysis of 40 drugs of abuse in oral fluid by LC-MS/MS using carbon-13 isotopes of methamphetamine and MDMA to reduce detector saturation.

    Science.gov (United States)

    Di Rago, Matthew; Chu, Mark; Rodda, Luke N; Jenkins, Elizabeth; Kotsos, Alex; Gerostamoulos, Dimitri

    2016-05-01

    The number of oral fluid samples collected by the road policing authority in Victoria, Australia, requiring confirmatory laboratory analysis for drugs proscribed under Victorian legislation (methamphetamine, MDMA and Δ9-tetrahydrocannabinol) has greatly increased in recent years, driving the need for improved analysis techniques to enable expedient results. The aim of this study was to develop an LC-MS/MS-based targeted oral fluid screening technique that covers a broad range of basic and neutral drugs of abuse that can satisfy increased caseload while monitoring other compounds of interest for epidemiological purposes. By combining small sample volume, simple extraction procedure, rapid LC-MS/MS analysis and automated data processing, 40 drugs of abuse including amphetamines, benzodiazepines, cocaine and major metabolites, opioids, cannabinoids and some designer stimulants were separated over 5 min (with an additional 0.5 min re-equilibration time). The analytes were detected using a Sciex® API 4500 Q-Trap LC-MS/MS system with positive ESI in MRM mode monitoring three transitions per analyte. The method was fully validated in accordance with international guidelines and also monitored carbon-13 isotopes of MDMA and MA to reduce detector saturation effects, allowing for confirmation of large concentrations of these compounds without the need for dilution or re-analysis. The described assay has been successfully used for analysis of oral fluid collected as part of law enforcement procedures at the roadside in Victoria, providing forensic results as well as epidemiological prevalence in the population tested. The fast and reliable detection of a broad range of drugs and subsequent automated data processing gives the opportunity for high throughput and fast turnaround times for forensic toxicology. PMID:26993306

  8. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells

    OpenAIRE

    Radestock, Yvonne; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine

    2008-01-01

    Introduction Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast c...

  9. Polymorphisms in MDA-5 link protein function to clearance of hepatitis C virus

    OpenAIRE

    Hoffmann, Franziska; Schmidt, Andreas; Chevillotte, Meike Dittmann; Wisskirchen, Christian; Hellmuth, Johannes C.; Willms, Simone; Gilmore, Rachel H.; Glas, Jürgen; Folwaczny, Matthias; Müller, Tobias; Berg, Thomas; Spengler, Ulrich; Fitzmaurice, Karen; Kelleher, Dermot; Reisch, Nicole

    2015-01-01

    Among patients newly infected with hepatitis C virus (HCV), only 20–30 % clear the infection spontaneously. In the remaining 70 %, the infection persists causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. RIG-I-like helicases such as MDA-5 are cytoplasmic sensors of viral RNA that are critical for triggering innate immune resp...

  10. Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and radiosensitivity, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells. MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis. Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at 2 Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak radiosensitization with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF10) of 1.1. Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy

  11. Analysis of oxidative stress status through MN test and serum MDA levels in PCOS women.

    Science.gov (United States)

    Deepika, M L N; Nalini, S; Maruthi, G; Ramchander, Vinish; Ranjith, K; Latha, K Prasanna; Rani, V Usha; Jahan, P

    2014-04-01

    Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive healthcare problem affecting 4-12% of women and a leading cause of female infertility worldwide. The potential genetic contributors of PCOS are unclear. However, over the past decade emerging evidence has shown that increased Oxidative Stress (OS) and decreased antioxidant status were often linked with PCOS. The present case-control study was aimed to assess the reactive oxygen species induced OS in women from South India. A total of 164 individuals comprising of 89 patients and 75 controls were enrolled in the present study. For all the subjects, the frequency of micronucleated cells (MNC) in epithelial samples and serum Malondialdehyde (MDA) levels were estimated to assess genomic instability and cytotoxicity respectively. A statistically significant difference between the groups were identified with respect to Body Mass Index, Waist to Hip Ratio, luteinizing hormone and prolactin levels (< 0.05), however the mean follicle stimulating hormone was not different between the groups (p = 0.055). The frequency of MN cells (5.89 ± 4.86 vs. 2.24 ± 2.01) and mean serum MDA (360.84 ± 87.08 vs. 301.70 ± 82.82) levels were considerably higher in patients than controls (p = < 0.0001), furthermore, a positive correlation was observed between MNC and MDA levels in patients (r = 0.349, p = 0.0008) and not in controls (r = 0.104, p = 0.37), suggest high OS in PCOS women. Therefore, MN assay and serum MDA levels may serve together or individually as biomarkers of OS in PCOS women. PMID:25911850

  12. Automatisk detektering av förutbestämda former i olika miljöer

    OpenAIRE

    Forslund, Joakim

    2014-01-01

    Den här rapporten mäter i vilka miljöer det går att hitta förutbestämda former med OpenCV och en "off-the-shelf" webbkamera.   This project measures in which environments a predetermined shape can be found with OpenCV and "off-the-shelf" webcameras.  

  13. Alkaloids of Cynanchum vincetoxicum: Efficacy against MDA-MB-231 Mammary Carcinoma Cells

    OpenAIRE

    Tanner, U.; Wiegrebe, Wolfgang

    1993-01-01

    Alkaloids 1-4 from Cynanchum vincetoxicum (asclepiadaceae) (Scheme 1) do not have affinity to the oestrogen receptor but they inhibit the growth of the hormone-independent mammary carcinoma cells MDA-MB-231 (Fig. 1) and bind to nucleosides and nucleotides (Table 1). Intercalation was not observed. Die Alkaloide 1-4 aus Cynanchum vincetoxicum (Asclepiadaceae) (Scheme 1) zeigen keine Affinität zum Oestrogen-Rezeptor, hemmen aber das Wachstum der hormonunabhängigen Mammakar...

  14. Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

    OpenAIRE

    Sangiliyandi Gurunathan; Jae Woong Han; Vasuki Eppakayala; Muniyandi Jeyaraj; Jin-Hoi Kim

    2013-01-01

    Silver nanoparticles (AgNPs) have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant of Bacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spe...

  15. Phenotypic Switch Induced by Simulated Microgravity on MDA-MB-231 Breast Cancer Cells

    OpenAIRE

    Maria Grazia Masiello; Alessandra Cucina; Sara Proietti; Alessandro Palombo; Pierpaolo Coluccia; Fabrizio D’Anselmi; Simona Dinicola; Alessia Pasqualato; Veronica Morini; Mariano Bizzarri

    2014-01-01

    Microgravity exerts dramatic effects on cell morphology and functions, by disrupting cytoskeleton and adhesion structures, as well as by interfering with biochemical pathways and gene expression. Impairment of cells behavior has both practical and theoretical significance, given that investigations of mechanisms involved in microgravity-mediated effects may shed light on how biophysical constraints cooperate in shaping complex living systems. By exposing breast cancer MDA-MB-231 cells to simu...

  16. Ionizing radiation enhances therapeutic activity of mda-7/IL-24: overcoming radiation- and mda-7/IL-24-resistance in prostate cancer cells overexpressing the antiapoptotic proteins bcl-xL or bcl-2.

    Science.gov (United States)

    Su, Z-Z; Lebedeva, I V; Sarkar, D; Emdad, L; Gupta, P; Kitada, S; Dent, P; Reed, J C; Fisher, P B

    2006-04-13

    Subtraction hybridization applied to terminally differentiating human melanoma cells identified mda-7/IL-24, a cytokine belonging to the IL-10 gene superfamily. Adenoviral-mediated delivery of mda-7/IL-24 (Ad.mda-7) provokes apoptosis selectively in a wide spectrum of cancers in vitro in cell culture, in vivo in human tumor xenograft animal models and in patients with advanced carcinomas and melanomas. In human prostate cancer cells, a role for mitochondrial dysfunction and induction of reactive oxygen species in the apoptotic process has been established. Ectopic overexpression of bcl-xL and bcl-2 prevents these changes including apoptosis induction in prostate tumor cells by Ad.mda-7. We now document that this resistance to apoptosis can be reversed by treating bcl-2 family overexpressing prostate tumor cells with ionizing radiation in combination with Ad.mda-7 or purified GST-MDA-7 protein. Additionally, radiation augments apoptosis induction by mda-7/IL-24 in parental and neomycin-resistant prostate tumor cells. Radiosensitization to mda-7/IL-24 is dependent on JNK signaling, as treatment with the JNK 1/2/3 inhibitor SP600125 abolishes this effect. Considering that elevated expression of bcl-xL and bcl-2 are frequent events in prostate cancer development and progression, the present studies support the use of ionizing radiation in combination with mda-7/IL-24 as a means of augmenting the therapeutic benefit of this gene in prostate cancer, particularly in the context of tumors displaying resistance to radiation therapy owing to bcl-2 family member overexpression. PMID:16331261

  17. Solid film lubricants and thermal control coatings flown aboard the EOIM-3 MDA sub-experiment

    Science.gov (United States)

    Murphy, Taylor J.; David, Kaia E.; Babel, Hank W.

    1995-01-01

    Additional experimental data were desired to support the selection of candidate thermal control coatings and solid film lubricants for the McDonnell Douglas Aerospace (MDA) Space Station hardware. The third Evaluation of Oxygen Interactions With Materials Mission (EOIM-3) flight experiment presented an opportunity to study the effects of the low Earth orbit environment on thermal control coatings and solid film lubricants. MDA provided five solid film lubricants and two anodic thermal control coatings for EOIM-3. The lubricant sample set consisted of three solid film lubricants with organic binders one solid film lubricant with an inorganic binder, and one solid film lubricant with no binder. The anodize coating sample set consisted of undyed sulfuric acid anodize and cobalt sulfide dyed sulfuric acid anodize, each on two different substrate aluminum alloys. The organic and inorganic binders in the solid film lubricants experienced erosion, and the lubricating pigments experienced oxidation. MDA is continuing to assess the effect of exposure to the low Earth orbit environment on the life and friction properties of the lubricants. Results to date support the design practice of shielding solid film lubricants from the low Earth orbit environment. Post-flight optical property analysis of the anodized specimens indicated that there were limited contamination effects and some atomic oxygen and ultraviolet radiation effects. These effects appeared to be within the values predicted by simulated ground testing and analysis of these materials, and they were different for each coating and substrate.

  18. Optimal Electroporation Condition for Small Interfering RNA Transfection into MDA-MB-468 Cell Line

    Directory of Open Access Journals (Sweden)

    Rita Arabsolghar

    2012-09-01

    Full Text Available Background: Electroporation is a valuable tool for small interfering RNA (siRNA delivery into cells because it efficiently transforms a wide variety of cell types. Since electroporation condition for each cell type must be determined experimentally, this study presents an optimal electroporation strategy to reproducibly and efficiently transfect MDA-MB 468 human breast cancer cell with siRNA. Methods: To identify the best condition, the cells were firstly electroporated without siRNA and cell viability was determined by trypan blue and MTT assays. Then siRNA transfection in the best condition was performed. Western blot analysis was used for monitoring successful siRNA transfection. Results: The best condition for electroporation of this cell line was 220 volt and 975 µF in exponential decay using the Gene Pulser X cell electroporation system. Our data demonstrated that by using proper electroporation condition, DNA methyl transferase mRNA was silenced by 10 nmol DNMT1 siRNA in MDA-MB 468 cells when compared with negative control siRNA electroporation. Analysis of cell viability demonstrated that optimal electroporation condition resulted in 74% and 78% cell viability by trypan blue staining and MTT assay, respectively. Conclusion: Transfection of the MDA-MB-468 breast cancer cell line with siRNA in the obtained electroporation condition was successful and resulted in effective gene silencing and high cellular viability.

  19. Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors.

    Science.gov (United States)

    Zhou, Zhu; Wang, Ying; Tan, Hua; Bharti, Veni; Che, Yi; Wang, Jun-Feng

    2015-08-31

    A lack of behavioral tests and animal models for manic-depressive bipolar disorder is recognized as an important factor limiting development of novel pharmaceutical treatments for the disorder. Repeated amphetamine-induced hyperactivity is a commonly used animal model for mania. However, hyperactivity represents only one facet of mania and is also seen in other disorders. Increased engagement in risk taking behavior is frequently observed in the manic phase of bipolar disorder. In the present study, we analyzed the effect of the most commonly used mood stabilizer lithium on repeated amphetamine treatment-induced risk-taking behaviors in rats using elevated plus maze and wire-beam bridge tests. We found that repeated amphetamine treatment not only increased locomotor activity, but also increased risk taking behaviors in rats, and further that chronic lithium treatment inhibited the amphetamine-increased risk taking behavior. Our studies suggest that these tests may be useful tools to analyze the pharmacological validity of new and improved anti-manic drugs in animals. PMID:26219985

  20. On-fiber derivatization for direct immersion solid-phase microextraction Part I : Acylation of amphetamine with pentafluorobenzoyl chloride

    NARCIS (Netherlands)

    Koster, EHM; Bruins, CHP; Wemes, C; de Jong, GJ

    2001-01-01

    On-fiber derivatization has been used for solid-phase microextraction (SPME) with gas chromatography in order to increase the extractability and detectability. Amphetamine, which has been used as a model compound, was derivatized with pentafluorobenzoyl chloride that was loaded on the fiber prior to

  1. The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics

    NARCIS (Netherlands)

    Staay, van der F.J.; Pouzet, B.; Mahieu, M.; Nordquist, R.E.; Schuurman, T.

    2009-01-01

    Rationale Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to h

  2. Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

    OpenAIRE

    Ukairo, Okechukwu T.; Ramanujapuram, Suneetha; Surratt, Christopher K.

    2006-01-01

    Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transporter (DAT) function. The resultant potentiation of dopaminergic neurotransmission is associated with psychostimulant addiction. Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphenidate (Ritalin™) and benztropine in CHO cells expressing wildtype DAT; cocaine potency also decreased in DAT-expr...

  3. Association of Cocaine- and Amphetamine-Regulated Transcript (CART) Messenger RNA Level, Food Intake, and Growth in Channel Catfish

    Science.gov (United States)

    Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine ...

  4. Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide in the central nervous system of the frog Rana esculenta

    NARCIS (Netherlands)

    Lazar, G.; Calle, M.; Roubos, E.W.; Kozicz, L.T.

    2004-01-01

    ddThe distribution of cocaine- and amphetamine-regulated transcript peptide (CARTp)-like immunoreactivity was studied only in the rat central nervous system (CNS). In mammals, CART peptides occur among others in brain areas that control feeding behavior. We mapped CARTp-immunoreactive structures in

  5. Effectiveness and safety of amphetamine for ADHD in population between 6 and 19 years: a systematic review

    Directory of Open Access Journals (Sweden)

    José Calleja

    2012-09-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD drug treatment is based on psychostimulants, and methylphenidate is still the most widely used one. Other psychostimulants used include amphetamines, hence the importance of knowing both its effectiveness and safety. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of amphetamine in ADHD in the 6-19 year-old population. Methods: A systematic review of studies that evaluated the effectiveness of interventions comparing amphetamine to methylphenidate was conducted. The outcomes measured were educational performance, psychosocial functioning, quality of life and adverse effects. The following databases were searched up to February 2012 in English and Spanish: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles that met inclusion criteria were assessed by two researchers independently. Results: Of the 114 studies found initially, four were included, among which a systematic review, a primary article and two clinical guidelines. Conclusions: The evidence on amphetamine for ADHD treatment recommends its use as an alternative to MPH. Further good-quality studies are needed.

  6. Effects of "D"-Amphetamine and Ethanol on Variable and Repetitive Key-Peck Sequences in Pigeons

    Science.gov (United States)

    Ward, Ryan D.; Bailey, Ericka M.; Odum, Amy L.

    2006-01-01

    This experiment assessed the effects of "d"-Amphetamine and ethanol on reinforced variable and repetitive key-peck sequences in pigeons. Pigeons responded on two keys under a multiple schedule of Repeat and Vary components. In the Repeat component, completion of a target sequence of right, right, left, left resulted in food. In the Vary component,…

  7. Methamphetamine Increases Locomotion and Dopamine Transporter Activity in Dopamine D5 Receptor-Deficient Mice

    OpenAIRE

    Hayashizaki, Seiji; Hirai, Shinobu; Ito, Yumi; Honda, Yoshiko; Arime, Yosefu; Sora, Ichiro; Okado, Haruo; Kodama, Tohru; Takada, Masahiko

    2013-01-01

    Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behaviora...

  8. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): Novel gene therapeutic for metastatic melanoma

    International Nuclear Information System (INIS)

    A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed 'differentiation therapy of cancer' with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display elevated expression in normal melanocytes and nevi with progressive loss of expression as a consequence of melanoma development and progression to metastasis. Based on structure, biochemical properties and chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a member of the expanding IL-10 family of cytokines. In vitro cell culture and in vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell death (apoptosis) in multiple human cancers (including melanomas), without harming normal cells, and promotes profound anti-tumor activity in nude mice containing human tumor xenografts. Based on these remarkable properties, a Phase I clinical trial was conducted to test the safety of administration of mda-7/IL-24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and to promote significant clinical activity, particularly in the context of patients with metastatic melanoma. These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the 'bench to the bedside.'

  9. Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5.

    Science.gov (United States)

    Uchikawa, Emiko; Lethier, Mathilde; Malet, Hélène; Brunel, Joanna; Gerlier, Denis; Cusack, Stephen

    2016-05-19

    RIG-I and MDA5 sense virus-derived short 5'ppp blunt-ended or long dsRNA, respectively, causing interferon production. Non-signaling LGP2 appears to positively and negatively regulate MDA5 and RIG-I signaling, respectively. Co-crystal structures of chicken (ch) LGP2 with dsRNA display a fully or semi-closed conformation depending on the presence or absence of nucleotide. LGP2 caps blunt, 3' or 5' overhang dsRNA ends with 1 bp longer overall footprint than RIG-I. Structures of 1:1 and 2:1 complexes of chMDA5 with short dsRNA reveal head-to-head packing rather than the polar head-to-tail orientation described for long filaments. chLGP2 and chMDA5 make filaments with a similar axial repeat, although less co-operatively for chLGP2. Overall, LGP2 resembles a chimera combining a MDA5-like helicase domain and RIG-I like CTD supporting both stem and end binding. Functionally, RNA binding is required for LGP2-mediated enhancement of MDA5 activation. We propose that LGP2 end-binding may promote nucleation of MDA5 oligomerization on dsRNA. PMID:27203181

  10. REGIONALIZATION OF AGRICULTURAL MANAGEMENT BY USING THE MULTI-DATA APPROACH (MDA

    Directory of Open Access Journals (Sweden)

    G. Bareth

    2012-07-01

    Full Text Available Regional process-based (agro-ecosystem modelling depends mainly on data availability of land use, weather, soil, and agricultural management. While land use, weather, and soil data are available from official sources or can be captured with monitoring systems, management data are usually derived from official statistics for administrative units. For numerous spatial modeling approaches, these data are not satisfying. Especially for process-based agro-ecosystem modeling on regional scales, spatially disaggregated and land use dependent information on agricultural management is a must. Information about date of sowing, dates of fertilization, dates of weeding etc. are required as input parameters by such models. These models consider nitrogen (N- and carbon (C-matter fluxes but essential amounts of N-/C-input and N-/C-output are determined by crop management. Therefore, in this contribution a RS- and GIS-based approach for regional generation of management data is introduced. The approach is based on the Multi-data Approach (MDA for enhanced land use/land cover mapping. The MDA is a combined RS and GIS approach. The retrieved information from multitemporal and multisensoral remote sensing analysis is integrated into official land use data to enhance both the information level of existing land use data and the quality of the land use classification. The workflow of the MDA to generate enhanced land use and land cover data consists basically of two components: (a the methods and data of the remote sensing analysis and (b the methods and data of the GIS analysis. The MDA results in disaggregated land use data which can be used to link crop management information about the major crops and especially crop rotations like date of sowing, fertilization, irrigation, harvest etc. to the derived land use classes. Consequently, depending on the land use, a distinct management is given in a spatial context on regional scale. In this contribution, three case

  11. Glycogen synthase kinase-3β inhibition in the medial prefrontal cortex mediates paradoxical amphetamine action in a mouse model of ADHD

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2015-03-01

    Full Text Available Psychostimulants show therapeutic efficacy in the treatment of attention-deficit hyperactivity disorder (ADHD. It is generally assumed that they ameliorate ADHD symptoms via interfering with monoaminergic signaling. We combined behavioral pharmacology, neurochemistry and molecular analyses to identify mechanisms underlying the paradoxical calming effect of amphetamine in low trait anxiety behavior (LAB mice, a novel multigenetic animal model of ADHD. Amphetamine (1 mg/kg and methylphenidate (10 mg/kg elicited similar dopamine and norepinephrine release in the medial prefrontal cortex (mPFC and in the striatum of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased locomotor activity. This argues against changes in dopamine and/or norepinephrine release as mediators of amphetamine paradoxical effects. Instead, the calming activity of amphetamine corresponded to the inhibition of glycogen synthase kinase3β (GSK3β activity, specifically in the mPFC. Accordingly, not only systemic administration of the GSK3β inhibitor TDZD-8 (20 mg/kg, but also local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3 mg/kg abolished the effects of amphetamine (1 mg/kg on the locomotion and on the phosphorylation of GSK3β at the level of the mPFC. Taken together, the paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a decreased GSK3β activity in the mPFC. This effect appears to be independent of dopamine or norepinephrine release, but contingent on NMDA receptor signaling.

  12. The role of dopamine receptor subtypes in the discriminative stimulus effects of amphetamine and cocaine in rats.

    Science.gov (United States)

    Filip, M; Przegaliński, E

    1997-01-01

    The role of dopamine (DA) receptor subtypes in the discriminative stimuli of the psychostimulant drugs of abuse amphetamine and cocaine was evaluated by the ability of DA D1, D2 and D3 receptor subtype ligands to either substitute for or antagonize these effects. Separate groups of rats were trained to discriminate between amphetamine (0.5 mg/kg) and saline, and between cocaine (5 mg/kg) and saline. Both the training drugs evoked cross-substitution. In further substitution experiments, (+)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H -3-benzazepine (SKF 38393; 5-20 mg/kg), a selective D1 agonist, moderately substituted for cocaine, but not for amphetamine. The D2 agonist bromocriptine (2.5-20 mg/kg) mimicked both training drugs' cues. Pramipexole, a D3-preferring agonist, in a dose of 0.5 mg/kg induced over 80% substitution for cocaine, and a weaker one (ca. 62%) for amphetamine. Combination tests with DA antagonists showed that the D1 antagonist (+)-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H -3-benzazepine (SCH 23390; 0.01-2 mg/kg), and the D2 blocker raclopride (0.13-1 mg/kg) significantly (78-100%) attenuated the effects of psychostimulants, while the D3-preferring antagonist cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232; 5-20 mg/kg) did not affect them. The present results indicate a critical role of D2 receptor subtypes in the discriminative stimuli of amphetamine and cocaine in rats, as well as a less pronounced involvement of D1 and D3 subtypes in the effects under study. PMID:9431548

  13. Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Raab, Marc S.; Anderhub, Simon;

    2012-01-01

    Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The...... analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in...

  14. Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model.

    Science.gov (United States)

    Li, Jipeng; Fu, Jia; Huang, Xing; Lu, Diannan; Wu, Jianzhong

    2016-09-01

    Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications. PMID:27367616

  15. Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model

    Science.gov (United States)

    Li, Jipeng; Fu, Jia; Huang, Xing; Lu, Diannan; Wu, Jianzhong

    2016-09-01

    Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications.

  16. Computer aided retrieval of common-batch members in Leuckart amphetamine profiling.

    Science.gov (United States)

    Jonson, C S; Strömberg, L

    1993-11-01

    Comparison of profiles is a well established way to find links between confiscated drugs. It is a laborious and time consuming task to manually compare large numbers of profiles to find common-batch links. To facilitate the comparison a computerized method has been developed. It is described and applied to a set of amphetamine impurity profiles. From each profile, areas of selected peaks are fed to the computer. By using quotients of corresponding peaks, the computer finds pairs of closely related profiles. With a sufficient numbers of peaks, the method is tolerant to variations in intensity between profiles, random peak area variations and a few strongly deviating peak areas. The program was written in Q-basic from Microsoft and may be run on any IBM-compatible personal computer. The method may also be used for analyzing data from other forensic objects, when the descriptors chosen are affected by errors like those described in the text. PMID:8263489

  17. Distinct effects of methamphetamine on autophagy–lysosome and ubiquitin–proteasome systems in HL-1 cultured mouse atrial cardiomyocytes

    International Nuclear Information System (INIS)

    Highlights: • The psychostimulant drug methamphetamine is also known to cause cardiovascular injuries. • Methamphetamine cardiotoxicity was examined using HL-1 mouse atrial cardiomyocytes. • Methamphetamine impairs the autophagy–lysosome protein degradation system. • Methamphetamine causes myosin heavy chain degradation by the ubiquitin–proteasome system. - Abstract: The aim of this study is to investigate the molecular mechanism underling the cardiotoxicity of methamphetamine, a psychostimulant drug that is currently abused in the world. A mouse atrial cardiac cell line, HL-1, which retains phenotypes of cardiac cells and serves as a useful model for examining cardiac pathophysiology, was used for this purpose. During treatment with 1 mM methamphetamine (MAP) for 3–48 h, massive but transient cytoplasmic vacuolization (3–12 h) followed by an intracellular accumulation of granules (24–48 h) was observed under light microscopy. The vacuoles were surrounded by the lysosome membrane marker LAMP1, while the granules colocalized with the autophagy markers LC3 and p62 as well as ubiquitinated proteins. Western blot analysis showed that LC3 was activated during MAP administration, although p62 was not degraded but rather accumulated. Concordant with p62 accumulation, the nuclear translocation of an anti-oxidative transcription factor, Nrf2, and the subsequent induction of its target gene, HO-1, was observed, suggesting an impairment of autophagic protein degradation and the subsequent activation of the p62/Nrf2/HO-1 pathway. In addition, proteomic analysis revealed a reduction in myosin heavy chain (MHC) protein levels during MAP administration. The ubiquitination of MHC and the induction of the muscle sarcomere protein-specific E3 ubiquitin ligases MuRF1 and atrogin-1 were proved by immunoprecipitation and quantitative real-time PCR, respectively. Taken together, the vacuolization of lysosomes and the subsequent accumulation of autophagosomes indicate

  18. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): novel gene therapeutic for metastatic melanoma

    OpenAIRE

    Fisher, Paul B.; Sarkar, Devanand; LEBEDEVA, IRINA V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su, Zao-Zhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

    2006-01-01

    A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed ‘differentiation therapy of cancer’ with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display e...

  19. MDA Program against lymphatic filariasis: Are we on the path to success? Experience from Uttara Kannada District, Karnataka

    OpenAIRE

    Praveen Kulkarni; Ravi Kumar; Ravi Marinayakanakoppalu Rajegowda; Harshith Gowdra Channabasappa; NC Ashok

    2014-01-01

    Context: Lymphatic filariasis or elephantiasis a serious public health problem in India. Millennium Development Goals and National Health Policies purport to eliminate filariasis by 2015. The concept of mass drug administration (MDA) is to approach every individual in the target community and administer annual single dose of anti-filarial drugs (DEC or DEC+Albendazole). Aims: 1. Assess the coverage and compliance to MDA in the district. 2. Assess the awareness of elephantiasis among beneficia...

  20. Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell MDA-MB-231 In Vitro

    OpenAIRE

    Xiu-fei Gao; Qing-lin Li; Hai-long Li; Hong-yan Zhang; Jian-ying Su; Bei Wang; Pei Liu; Ai-qin Zhang

    2014-01-01

    Objective. To evaluate the effect of petroleum ether extracts of Curcuma zedoaria on the proliferation of human triple negative breast cancer cell line MDA-MB-231. Methods. The reagents were isolated from Curcuma zedoaria by petroleum ether fraction. It was assayed by CCK8 for MDA-MB-231 cellular viability with various concentrations and days, cell cycle analyses, Western Blot analysis, and Realtime Reverse Transcriptase PCR analyses for chemokines molecules including E-cadherin, and E-select...

  1. Critical review for the determination of the minimum detectable activity (MDA) of alpha-emitter radionuclides in environmental samples

    International Nuclear Information System (INIS)

    Different criteria for the calculation of the Minimum Detectable Activity (MDA) of an alpha emitter in environmental levels are reviewed in this report. Practical examples of its application to previously analyzed samples are shown. The authors propose a criteria based on prior calculations that applies to the radiochemical activities performed in the laboratory. The calculation procedure has been discussed with scientist from other laboratories in order to establish a general criteria to calculate the MDA

  2. Sustained-Release Methylphenidate in a Randomized Trial of Treatment of Methamphetamine Use Disorder

    Science.gov (United States)

    Ling, Walter; Chang, Linda; Hillhouse, Maureen; Ang, Alfonso; Striebel, Joan; Jenkins, Jessica; Hernandez, Jasmin; Olaer, Mary; Mooney, Larissa; Reed, Susan; Fukaya, Erin; Kogachi, Shannon; Alicata, Daniel; Holmes, Nataliya; Esagoff, Asher

    2014-01-01

    Background and aims No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioural support and motivational incentives. Design This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT), and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. Setting Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. Participants 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). Measurements The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events, and treatment satisfaction. Findings No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (p=0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (p=0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction. Conclusions Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioural support for moderate to severe methamphetamine use disorder but this requires confirmation. PMID:24825486

  3. Protective effect of pentoxifylline on male Wistar rat testicular germ cell apoptosis induced by 3,4-methylenedioxymeth amphetamine

    OpenAIRE

    Mahnaz Nouri; Shabnam Movassaghi; Alireza foroumadi; Mansooreh Soleimani; Zahra Nadia Sharifi

    2016-01-01

    Objective(s): 3, 4-methylenedioxymethamphetamine (MDMA) one of the methamphetamine derivatives that affect the reproductive system, has not been well understood. Many young people are consumers of drugs such as MDMA that can affect their reproductive capability. Apoptosis is the main mechanism for male infertility. Pentoxifylline (PTX) increases cAMP intracellularly and reduces tumor necrosis factor-α. This study aimed to investigate the protective effect of PTX administration in MDMA-indu...

  4. The use of amphetamine type stimulants and the normalization of recreational drug use among people who attend electronic music events

    OpenAIRE

    Sande, Matej

    2008-01-01

    The article presents the results and findings of a quantitative and qualitative research into the use of ATS and the characteristics of attending electronic music events in Slovenia. The main conclusions of the study that concern the prevalence of drug use at electronic music events point to a decrease in the prevalence of ecstasy use and an increase in the use of cocaine and methamphetamine. The analysis of the interviews in the qualitative part reflects the influence...

  5. Baseline geochemistry of soil and bedrock Tshirege Member of the Bandelier Tuff at MDA-P

    Energy Technology Data Exchange (ETDEWEB)

    Warren, R.G.; McDonald, E.V.; Ryti, R.T.

    1997-08-01

    This report provides baseline geochemistry for soils (including fill), and for bedrock within three specific areas that are planned for use in the remediation of Material Disposal Area P (MDA-P) at Technical Area 16 (TA-16). The baseline chemistry includes leachable element concentrations for both soils and bedrock and total element concentrations for all soil samples and for two selected bedrock samples. MDA-P operated from the early 1950s to 1984 as a landfill for rubble and debris generated by the burning of high explosives (HE) at the TA-16 Burning Ground, HE-contaminated equipment and material, barium nitrate sand, building materials, and trash. The aim of this report is to establish causes for recognizable chemical differences between the background and baseline data sets. In many cases, the authors conclude that recognizable differences represent natural enrichments. In other cases, differences are best attributed to analytical problems. But most importantly, the comparison of background and baseline geochemistry demonstrates significant contamination for several elements not only at the two remedial sites near the TA-16 Burning Ground, but also within the entire region of the background study. This contamination is highly localized very near to the surface in soil and fill, and probably also in bedrock; consequently, upper tolerance limits (UTLs) calculated as upper 95% confidence limits of the 95th percentile are of little value and thus are not provided. This report instead provides basic statistical summaries and graphical comparisons for background and baseline samples to guide strategies for remediation of the three sites to be used in the restoration of MDA-P.

  6. In vitro effects of phenytoin and DAPT on MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Aktas, Canan Cakir; Zeybek, N Dilara; Piskin, A Kevser

    2015-09-01

    Voltage-gated sodium channel (VGSC) activity enhances cell behaviors related to metastasis, such as motility, invasion, and oncogene expression. Neonatal alternative splice form of Nav1.5 isoform is expressed in metastatic breast cancers. Furthermore, aberrant Notch signaling pathway can induce oncogenesis and may promote the progression of breast cancers. In this study, we aimed to analyze the effect of the nNav1.5 inhibitor phenytoin and Notch signal inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl ester (DAPT) on triple negative breast cancer cell line (MDA-MB-231) via inhibition of nNav1.5 VGSC activity and Notch signaling, respectively. In order to determine the individual and combined effects of these inhibitors, the 4-[3-(4-iyodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) test, wound healing assay, and zymography were performed to detect the proliferation, lateral motility, and matrix metalloproteinase-9 (MMP9) activity, respectively. The expressions of nNav1.5, Notch4, MMP9, and tissue inhibitor of metalloproteinases-1 (TIMP1) were also detected by quantitative real-time reverse transcriptase-polymerase chain reaction. DAPT caused an antiproliferative effect when the doses were higher than 10 µM, whereas phenytoin showed no inhibitory action either alone or in combination with DAPT on the MDA-MB-231 cells. Furthermore, it was found that the lateral motility was inhibited by both inhibitors; however, this inhibitory effect was partially rescued when they were used in combination. Meanwhile, the results showed that the MMP9 activity and the ratio of MMP9 mRNA to TIMP1 mRNA were only decreased by DAPT. Thus, we conclude that the combined effect of DAPT and phenytoin is not as beneficial as using DAPT alone on MDA-MB-231 breast cancer cells. PMID:26206582

  7. Baseline geochemistry of soil and bedrock Tshirege Member of the Bandelier Tuff at MDA-P

    International Nuclear Information System (INIS)

    This report provides baseline geochemistry for soils (including fill), and for bedrock within three specific areas that are planned for use in the remediation of Material Disposal Area P (MDA-P) at Technical Area 16 (TA-16). The baseline chemistry includes leachable element concentrations for both soils and bedrock and total element concentrations for all soil samples and for two selected bedrock samples. MDA-P operated from the early 1950s to 1984 as a landfill for rubble and debris generated by the burning of high explosives (HE) at the TA-16 Burning Ground, HE-contaminated equipment and material, barium nitrate sand, building materials, and trash. The aim of this report is to establish causes for recognizable chemical differences between the background and baseline data sets. In many cases, the authors conclude that recognizable differences represent natural enrichments. In other cases, differences are best attributed to analytical problems. But most importantly, the comparison of background and baseline geochemistry demonstrates significant contamination for several elements not only at the two remedial sites near the TA-16 Burning Ground, but also within the entire region of the background study. This contamination is highly localized very near to the surface in soil and fill, and probably also in bedrock; consequently, upper tolerance limits (UTLs) calculated as upper 95% confidence limits of the 95th percentile are of little value and thus are not provided. This report instead provides basic statistical summaries and graphical comparisons for background and baseline samples to guide strategies for remediation of the three sites to be used in the restoration of MDA-P

  8. BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer-specific apoptosis.

    Science.gov (United States)

    Gupta, Pankaj; Walter, Mark R; Su, Zao-zhong; Lebedeva, Irina V; Emdad, Luni; Randolph, Aaron; Valerie, Kristoffer; Sarkar, Devanand; Fisher, Paul B

    2006-08-15

    Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that induces cancer-selective growth suppression and apoptosis in a wide spectrum of human cancers in cell culture and animal models. Additionally, recent clinical trials confirm safety and document significant clinical activity of mda-7/IL-24 in patients with diverse solid cancers and melanomas. Despite intensive study the molecular basis of tumor-cell selectivity of mda-7/IL-24 is not well characterized. Using deletion analysis, a specific mutant of MDA-7/IL-24, M4, consisting of amino acids 104 to 206, is described that retains the cancer-specific growth-suppressive and apoptosis-inducing properties of the full-length protein. Employing rationally designed mutational analysis, we show that MDA-7/IL-24 and M4 physically interact with BiP/GRP78 through their C and F helices, localize in the endoplasmic reticulum, and activate p38 MAPK and GADD gene expression, culminating in cancer-selective apoptosis. These studies provide novel mechanistic insights into the discriminating antitumor activity of MDA-7/IL-24 by elucidating BiP/GRP78 as a defined intracellular target of action and present an unparalleled opportunity to develop improved therapeutic versions of this cancer-specific apoptosis-inducing cytokine. PMID:16912197

  9. Mulige interaksjoner mellom tyrosin kinase reseptoren Axl, metabolisme og proliferasjon i brystkreftceller (MDA-MB-231)

    OpenAIRE

    Bergslien, Ingunn

    2009-01-01

    Metabolismen i kreftceller er assosiert med økt aerob glykolyse, et fenomen omtalt som Warburg effekten. Den forhøyede glykolytiske raten utgjør en av de større forskjellene, som skiller normale celler fra kreftceller, og forståelse av de underliggende mekanismene er viktig for å kunne utvikle målrettet kreftterapi. Brystkreft cellelinjen MDA-MB-231 er karakterisert som aggressiv og invasiv, og viser høye rater av aerob glykolyse, sammenlignet med brystkreft cellelinjer med lavere invasivi...

  10. Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells

    OpenAIRE

    Park, Soo-Jin; Lee, Kyoung-Pil; Im, Dong-Soon

    2014-01-01

    Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca2+ ([Ca2+]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca2+ increase in these cells. In the present study, we further investigated actions of LPE not onl...

  11. X-ray structure analysis of a 10 MDa biological macromolecule

    International Nuclear Information System (INIS)

    Vault, which has a molecular mass of 10 MDa, is the largest cytoplasmic ribonucleoprotein particle. Although vaults are found in numerous eukaryotic species, the cellular function remains nuclear. We have determined the x-ray structure of rat liver vault at 3.5 A resolution. The structure consists of 78 identical MVP (Major vault protein) chains with 39-fold dihedral symmetry. Each MVP monomer folds into 12 domains; nine structural repeat domains, a shoulder domain, a cap-helix domain, and a cap-ring domain. The shoulder domain is structurally similar to a core domain of stomatin, which is a lipid-raft component in erythrocytes and epithelial cells. (author)

  12. Mouse Strain- and Age-dependent Effects of Binge Methamphetamine on Dopaminergic Signaling

    OpenAIRE

    Good, Renee L.; Liang, Li-Ping; Patel, Manisha; Radcliffe, Richard A.

    2011-01-01

    We have shown that a single “binge” dose of methamphetamine (Meth) in mice has long-lasting effects on open-field behavior dependent on mouse strain and age. Here we further investigated the impact of genotype and age on tyrosine hydroxylase (TH) loss and dopamine (DA) metabolism due to a high binge dose of Meth (4 × 5 mg/kg × 2 hours × 2 days). Administration of high dose Meth or saline (Sal) to adolescent (PND 40) and adult (PND 80) C57BL/6 (B6), DBA/2 (DBA), and 129S6SvEv/Tac (129) mice wa...

  13. Effect of Methamphetamine on expression of HIV coreceptors and CC-chemokines by dendritic cells

    OpenAIRE

    Nair, Madhavan P.N.; Zainulabedin M Saiyed

    2010-01-01

    The United States is currently experiencing an entangled epidemic of HIV infection and use of different drugs of abuse, especially of methamphetamine (Meth). Blood monocyte-derived dendritic cells (DC) are the first line of defense against HIV-1 infection, and are the initial target of HIV-1 infection in injection drug users. DC-SIGN present on dendritic cells is the first molecule that facilitates HIV-1 infection independent of CD4 or HIV coreceptors. Chemokines are known to be HIV-1 suppres...

  14. Age-Related Differences in NMDA Receptor Subunits of Prenatally Methamphetamine-Exposed Male Rats

    Czech Academy of Sciences Publication Activity Database

    Vrajová, M.; Schutová, B.; Klaschka, Jan; Štěpánková, H.; Řípová, D.; Šlamberová, R.

    2014-01-01

    Roč. 39, č. 11 (2014), s. 2040-2046. ISSN 0364-3190 Grant ostatní: GA ČR(CZ) GAP303/10/0580; Ministerstvo školství(CZ) CSM 7/CRP/2014; Univerzita Karlova(CZ) Prvouk P34; Univerzita Karlova(CZ) 260045/SVV/2014; Prague Psychiatric Center(CZ) MH CZ–DRO: 00023752 Institutional support: RVO:67985807 Keywords : methamphetamine * in-utero * NMDA receptor subunits * hippocampus Subject RIV: FH - Neurology Impact factor: 2.593, year: 2014

  15. Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

    OpenAIRE

    Sofia Baptista; Charlène Lasgi; Caroline Benstaali; Nuno Milhazes; Fernanda Borges; Carlos Fontes-Ribeiro; Fabienne Agasse; Ana Paula Silva

    2014-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10 nM) decreased DG stem cell self-renewal, while 1 nM...

  16. Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized Texting for Adherence Building for Antiretroviral Adherence and Substance Use Assessment among HIV-Infected Methamphetamine Users

    Directory of Open Access Journals (Sweden)

    David J. Moore

    2013-01-01

    Full Text Available The feasibility, use, and acceptability of text messages to track methamphetamine use and promote antiretroviral treatment (ART adherence among HIV-infected methamphetamine users was examined. From an ongoing randomized controlled trial, 30-day text response rates of participants assigned to the intervention (individualized texting for adherence building (iTAB, n = 20 were compared to those in the active comparison condition (n = 9. Both groups received daily texts assessing methamphetamine use, and the iTAB group additionally received personalized daily ART adherence reminder texts. Response rate for methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of the time. Text-derived methamphetamine use data was correlated with data from a structured substance use interview covering the same time period (P<0.05. The iTAB group responded to 69.0% of adherence reminder texts; among those responses, 81.8% endorsed taking ART medication. Standardized feedback questionnaire responses indicated little difficulty with the texts, satisfaction with the study, and beliefs that future text-based interventions would be helpful. Moreover, most participants believed the intervention reduced methamphetamine use and improved adherence. Qualitative feedback regarding the intervention was positive. Future studies will refine and improve iTAB for optimal acceptability and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277.

  17. A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration

    OpenAIRE

    Ferris, Mark J.; Calipari, Erin S.; Rose, Jamie H.; Siciliano, Cody A.; Sun, Haiguo; Chen, Rong; JONES, SARA R.

    2015-01-01

    There are ∼1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans. It is hypothesized that amphetamine acts as a replacement therapy for cocaine through elevation of extracellular dopamine levels. Using voltammetry in brain slices, we tested the abi...

  18. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    Science.gov (United States)

    Vallöf, Daniel; Vestlund, Jesper; Engel, Jörgen A; Jerlhag, Elisabet

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU). We therefore investigated the effects of intracerebroventricular (icv) administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP) was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv) reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence. PMID:27139195

  19. The Anorexigenic Peptide Neuromedin U (NMU Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    Directory of Open Access Journals (Sweden)

    Daniel Vallöf

    Full Text Available Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU. We therefore investigated the effects of intracerebroventricular (icv administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence.

  20. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice

    OpenAIRE

    Daniel Vallöf; Jesper Vestlund; Engel, Jörgen A; Elisabet Jerlhag

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for re...