Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns.

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

Safety of Treatments for ADHD in Adults: Pairwise and Network Meta-Analyses.

OBJECTIVE: The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. METHOD: Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). RESULTS: Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). CONCLUSION: It was possible to generate evidence about the safety profile of different ADHD drugs.

Intermolecular interactions between DNA and methamphetamine, amphetamine, ecstasy and their major metabolites.

In this work, we carried out a theoretical investigation regarding amphetamine-type stimulants, which can cause central nervous system degeneration, interacting with human DNA. These include amphetamine, methamphetamine, 3,4-Methylenedioxymethamphetamine (also known as ecstasy), as well as their main metabolites. The studies were performed through molecular docking and molecular dynamics simulations, where molecular interactions of the receptor-ligand systems, along with their physical-chemical energies, were reported. Our results show that 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine (ecstasy) present considerable reactivity with the receptor (DNA), suggesting that these molecules may cause damage due to human-DNA. These results were indicated by free Gibbs change of bind (ΔGbind) values referring to intermolecular interactions between the drugs and the minor grooves of DNA, which were predominant for all simulations. In addition, it was observed that 3,4-Dihydroxymethamphetamine (ΔGbind = -13.15 kcal/mol) presented greater spontaneity in establishing interactions with DNA in comparison to 3,4-Methylenedioxymethamphetamine (ΔGbind = -8.61 kcal/mol). Thus, according with the calculations performed our results suggest that the 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine have greater probability to provide damage to human DNA fragments.

Safety and efficacy of fenproporex for obesity treatment: a systematic review.

OBJECTIVE: To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS: MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS: Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS: There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

Safety and efficacy of fenproporex for obesity treatment: a systematic review / Segurança e eficácia do fenproporex para tratamento da obesidade: revisão sistemática

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

RESUMO OBJETIVO Avaliar a evidência clínica de segurança e eficácia do Fenproporex para tratamento da obesidade. MÉTODOS Pesquisamos publicações em qualquer idioma nas bases Medline, Lilacs Cochrane Controlled Trials Register e também referências citadas por artigos e documentos relevantes. Dois autores avaliaram independentemente os estudos para inclusão e quanto ao risco de viés, dados coletados e precisão. Foram elegíveis estudos controlados com placebo que forneceram dados sobre a eficácia e segurança do Fenproporex para tratar a obesidade. RESULTADOS Apenas quatro estudos controlados preencheram critérios de inclusão. Um estudo placebo-controlado aleatorizado do Fenproporex foi encontrado nas bases eletrônicas. Três estudos controlados (em periódicos não indexados) foram identificados por buscas manuais. Pacientes com comorbidades (cardiovasculares ou outras) foram excluídos em todos os estudos. A duração dos estudos foi de 40 a 364 dias, com doses de 20 a 33,6 mg/d. Todos os estudos controlados encontraram maior perda de peso entre pacientes tratados com Fenproporex, comparados aos que receberam placebo, mas o efeito foi modesto. O Fenproporex causou reduções adicionais de peso de 4,7 kg (após um ano), 3,8 kg (após seis meses) e 1,55 kg (após dois meses), em média, em relação à dieta e exercício apenas (três ensaios). Insônia, irritabilidade e ansiedade foram os eventos colaterais mais frequentes nos quatro estudos. CONCLUSÕES Ensaios clínicos placebo-controlado aleatorizado do Fenproporex são escassos e os estudos controlados identificados apresentam importantes falhas metodológicas. Esses estudos sugerem que o Fenproporex é modestamente eficaz em promover perda de peso. Entretanto, eles não fornecem evidências de que o Fenproporex atenua a morbidade e mortalidade associada à obesidade. Esses estudos são insuficientes para avaliar o perfil risco-benefício do Fenproporex. Potencial de abuso e efeitos adversos do tipo anfetamínico são motivos de preocupação.

Withdrawal from chronic amphetamine reduces dopamine transmission in the rat lateral septum.

The lateral septum (LS) is a brain nucleus implicated in the addictive process. This study investigated whether withdrawal from chronic amphetamine (AMPH) induces alterations in dopamine (DA) transmission within the LS. Male Sprague-Dawley rats were injected with AMPH (2.5 mg/kg i.p.) or saline during 14 days and thereafter subjected to 24 hr or 14 days of withdrawal. After these withdrawal periods, we measured DA extracellular levels by in vivo microdialysis, DA tissue levels, and tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT2) expression in the LS. Our results showed a significant decrease in K(+) -induced release of DA in the LS of AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. There were no significant differences in DA tissue content and TH expression. Interestingly, there was a decrease of LS VMAT2 expression in AMPH-treated rats, 14 days after withdrawal compared with saline-treated rats. This is the first neurochemical evidence showing that withdrawal from repeated AMPH administration decreases K(+) -induced DA release in the rat LS. Our results suggest that this decrease in DA releasability could be due to a decrease in DA vesicular uptake. The possibility that these neurochemical changes are associated with AMPH abstinence syndrome should be further explored.

[Amphetamine use by truck drivers on highways of Sao Paulo State: a risk for the occurrence of traffic accidents?]. / Uso de anfetaminas por motoristas de caminhão em rodovias do Estado de São Paulo: um risco à ocorrência de acidentes de trânsito?

The use of amphetamines in Brazil is common among truck drivers, which may be an important factor in the occurrence of traffic accidents. This article seeks to estimate the prevalence of amphetamine use among truck drivers. Drivers (N = 134) were stopped on two different highways in Sao Paulo state and they were asked to answer a questionnaire and provide a urine sample for toxicological analysis. All data were analyzed on Stata 8.0. All participants were males with low levels of schooling, whose mean age was 40.8 years. The presence of amphetamines was detected in 10.8% of all urine samples collected, being commonly justified in order to make truck drivers able to maintain their state of awareness. Amphetamine use was detected among truck drivers on Sao Paulo highways. The problem is that when the stimulant effects wear off, sleepiness due to sleep deprivation reduces concentration and good driver performance, making drivers vulnerable to traffic accidents and the related effects.

Uso de anfetaminas por motoristas de caminhão em rodovias do Estado de São Paulo: um risco à ocorrência de acidentes de trânsito? / Amphetamine use by truck drivers on highways of Sao Paulo State: a risk for the occurrence of traffic accidents?

The use of amphetamines in Brazil is common among truck drivers, which may be an important factor in the occurrence of traffic accidents. This article seeks to estimate the prevalence of amphetamine use among truck drivers. Drivers (N = 134) were stopped on two different highways in Sao Paulo state and they were asked to answer a questionnaire and provide a urine sample for toxicological analysis. All data were analyzed on Stata 8.0. All participants were males with low levels of schooling, whose mean age was 40.8 years. The presence of amphetamines was detected in 10.8% of all urine samples collected, being commonly justified in order to make truck drivers able to maintain their state of awareness. Amphetamine use was detected among truck drivers on Sao Paulo highways. The problem is that when the stimulant effects wear off, sleepiness due to sleep deprivation reduces concentration and good driver performance, making drivers vulnerable to traffic accidents and the related effects.

No Brasil, é comum o uso de anfetaminas por motoristas de caminhão, o que pode culminar na ocorrência de acidentes de trânsito. O objetivo deste artigo é estimar a prevalência do uso de anfetaminas entre caminhoneiros. Motoristas (N = 134) foram abordados em duas rodovias do Estado de São Paulo e solicitados a responder um questionário, assim como a fornecer uma amostra de urina para realização de análises toxicológicas. Todos os dados foram analisados em Stata 8.0. Todos os participantes eram do sexo masculino, de idade média de 40,8 anos e de baixa escolaridade. A presença de anfetaminas foi detectada em 10,8% das amostras de urina, cujo uso foi justificado para manter a vigília durante o trabalho. O uso de anfetaminas foi detectado entre caminhoneiros em rodovias de São Paulo. Cessado o efeito estimulante, a sonolência advinda de uma possível privação de sono diminui a atenção e o bom desempenho na direção, predispondo o condutor aos acidentes de trânsito e seus custos relacionados.

Effects of single or repeated amphetamine treatment and withdrawal on lung allergic inflammation in rats.

The effects of single or repeated amphetamine (AMPH) treatment and those of AMPH withdrawals on immune-mediated lung inflammatory response were studied in rats. Two experiments were done. In the first, rats egg-albumin (OVA) sensitized were singularly or repeatedly (21 days, once daily) treated with AMPH (1.0 mg/kg) or with a similar number and volume of 0.9% NaCl. The OVA aerosol challenge was performed 12 h after the single or last repeated AMPH treatment and also 72 and 120 h after AMPH withdrawal. In the second experiment, the effects of reserpine (1.0 mg/kg/day for 5 consecutive days) on single AMPH actions on lung allergic response of rats were analyzed. Single and repeated AMPH treatment induced opposite actions on Bronchoalveolar lavage fluid (BAL) cellularity of allergic rats: single treatment decreased and repeated treatment increased the total number of cells as well as those of macrophages, neutrophils and eosinophils. Our data also showed that single but not repeated AMPH treatment decreased the number of neutrophils, monocytes and lymphocytes in the peripheral blood, and increased the total number of bone marrow cells in rats sensitized and challenged with OVA. Furthermore, it was shown that reserpine treatment precluded the effects of single AMPH treatment on cellular migration to the lung of OVA-sensitized and challenged rats. It was concluded that AMPH effects on lung inflammatory response and cell recruitment to the lung in allergic rats rely at least partially on corticosterone serum levels. The possible involvement of vesicular monoamine transporter type 2 (VMAT2) with these observed effects was discussed.

Behavioral and antiepileptic effects of acute administration of the extract of the plant Cestrum nocturnum Lin (lady of the night).

Cestrum nocturnum is a garden shrub from the family Solanaceae and is used as a remedy for different health disorders. The aim of the present work was to investigate the potential neuropharmacological action profile of decoctions obtained from dry leaves of the plant. Decoctions were tested in different neuropharmacological models-Irwin test, exploratory behavior, tests for analgesia, isoniazid- and picrotoxin-induced convulsions, and maximal electroshock seizures-in mice, as well as in amphetamine-induced stereotypies and penicillin epileptic foci in rats. Decoctions of 1 and 5% (D1 and D5) induced restlessness, and the 30% decoction (D30) induced passivity. D5 and D30 reduced significantly exploratory behavior and amphetamine-induced stereotypies within a 3-hour observation period. The latter effect was apparent during the second 60 minutes. Decoctions reduced the amount of writhes induced by acetic acid in a dose-dependent manner, but were not effective in the hot plate model. The decoctions were not effective against pharmacologically induced convulsions. However, repeated administration of five doses of D5, at 1-hour intervals, reduced the amplitude of penicillin-induced epileptic spikes in both primary and secondary foci, in curarized rats. Taken together, the results suggest that C. nocturnum possesses active substances with analgesic activity provided through a peripheral action mechanism, in parallel with some psychoactive activity that does not fit well the neuropharmacological action profile of known reference neurotropic drugs.

Consumo de alcohol y otras drogas en embarazadas / Consumption of alcohol and other drugs in pregnant women

La investigación sobre los efectos de las drogas, legales e ilegales, en el embarazo fue planificada, desde su inicio, como una forma de apoyar a quienes se desempeñan en el campo de la prevención y la asistencia a las adicciones en la sociedad uruguaya.Los instrumentos utilizados en la investigación fueron la entrevista cara a cara con la mujer en estado puerperal, dentro de las 48 horas después del nacimiento, los registros perinatales obtenidos de los archivos hospitalarios y las muestras de meconio de los recién nacidos las cuales fueron analizadas en la búsqueda de alcohol, tabaco, psicofármacos y drogas ilegales. La encuesta mostró un consumo durante la gestación de 41,7% de tabaco, 37% de alcohol, 16,5% de tranquilizantes, 68% de cafeína (mas de 400 mg/día), 1,5% de marihuana y 0,4% de pasta base.Las pruebas sobre meconio indicaron que el consumo en el embarazo fue de tabaco 51%, alcohol 40%, tranquilizantes 2,5%, marihuana 2%, anfetaminas 8,3%, cocaína/pasta base 2,5% y opiáceos 0,5%. La investigación encontró que 11% de los recién nacidos de la muestra fueron de bajo peso, y que 15% tuvieron problemas de salud. Los neonatos de madres fumadoras presentaron pesos al nacer estadísticamente más bajos que los restantes. Se halló asimismo que 8,9% de las madres carecían de control prenatal. El 34% de los médicos que controlaron el embarazo advirtió a las gestantes sobre los riesgos del hábito de fumar durante el embarazo, el 27% lo hizo en relación al consumo de alcohol y 7% sobre el uso de drogas ilegales.

The objective of the study was to estimate the prevalence of drug consumption during pregnancy through an interview and biological samples and to investigate the information given concerning risks about drug consumption during pregnancy. The 1000 interviews performed were personal within 48 hours after labor, using perinatal registries taken from hospital archives. The meconium samples were tested for alcohol, tobacco, illegal drugs and tranquilizers. Through the survey, the results about consumption during pregnancy was 41.3 % for tobacco, alcohol 36.8%, tranquilizers 16.3%, caffeine 68% (more than 400 mg/day), cannabis 1.5% and 0.4% for base paste.The consumption in the meconium samples was 51.8% for tobacco, 43.5% for alcohol, 2.5% for tranquilizers, 2% for cannabis, 8.3% for amphetamines, 2.5% for cocaine/ base paste and 0.5% for opiates. 11 % of all newborns had low birth weight and 14.8 % had health problems. Newborns from smoking mothers had lower birth weights. 8,9 % of all the mothers did not control their pregnancy. Physicians who controlled the pregnancies warned their patients about associated risks with tobacco in 34%, 27% for alcohol and 7% for illegal drugs.

Consumo de alcohol y otras drogas en embarazadas / Consumption of alcohol and other drugs in pregnant women

La investigación sobre los efectos de las drogas, legales e ilegales, en el embarazo fue planificada, desde su inicio, como una forma de apoyar a quienes se desempeñan en el campo de la prevención y la asistencia a las adicciones en la sociedad uruguaya.Los instrumentos utilizados en la investigación fueron la entrevista cara a cara con la mujer en estado puerperal, dentro de las 48 horas después del nacimiento, los registros perinatales obtenidos de los archivos hospitalarios y las muestras de meconio de los recién nacidos las cuales fueron analizadas en la búsqueda de alcohol, tabaco, psicofármacos y drogas ilegales.La encuesta mostró un consumo durante la gestación de 41,7% de tabaco, 37% de alcohol, 16,5% de tranquilizantes, 68% de cafeína (mas de 400 mg/día), 1,5% de marihuana y 0,4% de pasta base.Las pruebas sobre meconio indicaron que el consumo en el embarazo fue de tabaco 51%, alcohol 40%, tranquilizantes 2,5%, marihuana 2%, anfetaminas 8,3%, cocaína/pasta base 2,5% y opiáceos 0,5%.La investigación encontró que 11% de los recién nacidos de la muestra fueron de bajo peso, y que 15% tuvieron problemas de salud. Los neonatos de madres fumadoras presentaron pesos al nacer estadísticamente más bajos que los restantes.Se halló asimismo que 8,9% de las madres carecían de control prenatal. El 34% de los médicos que controlaron el embarazo advirtió a las gestantes sobre los riesgos del hábito de fumar durante el embarazo, el 27% lo hizo en relación al consumo de alcohol y 7% sobre el uso de drogas ilegales.

The objective of the study was to estimate the prevalence of drug consumption during pregnancy through an interview and biological samples and to investigate the information given concerning risks about drug consumption during pregnancy. The 1000 interviews performed were personal within 48 hours after labor, using perinatal registries taken from hospital archives. The meconium samples were tested for alcohol, tobacco, illegal drugs and tranquilizers. Through the survey, the results about consumption during pregnancy was 41.3 % for tobacco, alcohol 36.8%, tranquilizers 16.3%, caffeine 68% (more than 400 mg/day), cannabis 1.5% and 0.4% for base paste.The consumption in the meconium samples was 51.8% for tobacco, 43.5% for alcohol, 2.5% for tranquilizers, 2% for cannabis, 8.3% for amphetamines, 2.5% for cocaine/ base paste and 0.5% for opiates.11 % of all newborns had low birth weight and 14.8 % had health problems. Newborns from smoking mothers had lower birth weights. 8,9 % of all the mothers did not control their pregnancy.Physicians who controlled the pregnancies warned their patients about associated risks with tobacco in 34%, 27% for alcohol and 7% for illegal drugs.

Blockade of neurotensin receptors during amphetamine discontinuation indicates individual variability.

Psychostimulant-induced locomotor sensitization has been related to changes within the mesolimbic dopamine system and has been suggested to be useful to study mechanisms underlying drug craving. Neurotensin is a neuropeptide co-localized with dopamine in the mesolimbic system. The response to novelty has been suggested to be a predictor of enhanced vulnerability to behavioral sensitization. The effects of repeated treatment with the neurotensin antagonist SR48692 after amphetamine discontinuation were investigated in mice previously classified as high responders (HRs) or low responders (LRs) to novelty. Mice were repeatedly treated with 2.0mg/kg amphetamine, every other day for 11 days. During the first 7 days after amphetamine discontinuation, the animals received a daily injection of saline or 0.3mg/kg SR48692. On the eighth day after amphetamine discontinuation all subjects received a 2.0mg/kg amphetamine challenge injection. Then, mice were tested for an open field behavior and after 90min, were sacrificed for Fos expression quantification in the nucleus accumbens. Both HRs and LRs expressed amphetamine-induced sensitized locomotor activation and increased expression of Fos protein. Treatment with SR48692 prevented behavioral sensitization and Fos protein expression enhancement in LRs but not in HRs mice. These data suggest that neurotensin plays a role in individual variability to amphetamine-induced sensitization.

Effect of riluzole on MK-801 and amphetamine-induced hyperlocomotion.

N-methyl-D aspartate (NMDA) antagonists, such as MK-801, and the dopamine indirect agonist amphetamine are pharmacological models used for the evaluation of putative new treatments for schizophrenia. Since the psychotomimetic effects of NMDA antagonists have recently been linked to their ability to increase glutamate release and since the glutamate release inhibitor riluzole prevented NMDA antagonist neurotoxicity, we evaluated the effect of riluzole on hyperlocomotion induced by MK-801 (0.25 mg/kg) and amphetamine (2.5 mg/kg). Mice pretreated with riluzole (3 mg/kg) did not influence baseline or MK-801-induced behavior, but 10 mg/kg produced moderate hypolocomotion alone and somewhat prolonged MK-801-induced hyperlocomotion. Pretreatment with riluzole 10 mg/kg, but not 3 mg/kg, had a moderately depressant effect both on spontaneous and amphetamine-induced locomotion. Taken together, these results suggest that riluzole would not be particularly effective as a treatment for schizophrenia and the neurotoxic and behavioral effect of NMDA antagonists do not clearly correlate.

Manifestaciones y secuelas cutáneas de la drogadicción / Cutaneous manifestations and sequelae in drug addicts

Las lesiones dermatológicas producidas por la administración de drogas ilícitas y sus eventuales secuelas, tienen implicancias médico-legales y sumo valor para el diagnóstico retrospectivo de adicción. Estas lesiones son de origen multifactorial: combinan la reacción del huésped ante agentes químicos sensibilizantes e irritantes, traumatismos reiterados por técnicas de aplicación incorrectas e infección sobreagregada. Clínicamente, se observan como hiperpigmentaciones sobre trayectos vasculares indurados, cicatrices atróficas en áreas de inyección subcutánea, abscesos sépticos y granulomas por cuerpo extraño, en su mayoría provocados por excipientes y adulterantes, como lesiones más características. Se presentan casos clínicos y se hace revisión de estos procesos, enfatizando la situación particular en Argentina en relación a la bibliografía consultada, proveniente de países del Primer Mundo. Asimismo, se ilustra brevemente el léxico tan particular de los adictos, cuyos rudimentos se vuelven imposibles de obviar cuando se avanza en el estudio de estos pacientes (AU)

Expression of amphetamine-induced behavioral sensitization after short- and long-term withdrawal periods: participation of mu- and delta-opioid receptors.

Repeated amphetamine administration results in behavioral sensitization, an enduring behavioral transformation expressed after short and long periods of withdrawal. To investigate the participation of the opioid system in amphetamine-induced behavioral sensitization, we studied the effect of naloxone, an opioid receptor antagonist, on the expression of behavioral sensitization tested after short- (2 days) and long-term (14 days) withdrawal periods. In addition, using quantitative competitive RT-PCR, we examined the levels of mu-opioid receptor (MOR) and delta-opioid receptor (DOR) mRNA in the nucleus accumbens shell (NAcSh) and ventral tegmental area (VTA) of behaviorally sensitized rats, at these two withdrawal times. This study showed that whereas naloxone did not modify the expression of behavioral sensitization tested after 2 days of withdrawal, it completely blocked the expression when tested after 14 days of withdrawal. DOR and MOR mRNA levels were not modified in the NAcSh of rats expressing behavioral sensitization after 2 or 14 days of withdrawal. Conversely, DOR and MOR mRNA levels were elevated in the VTA of animals expressing behavioral sensitization after 2 days of withdrawal. However, whereas DOR mRNA returned to control levels, MOR mRNA levels remained elevated in animals expressing behavioral sensitization after 14 days of withdrawal. These results indicate a striking difference between the role played by opioid receptors in the expression of amphetamine-induced behavioral sensitization, when tested after short- or long-term withdrawal periods. In addition, our results support the notion that repeated amphetamine-induced changes in opioid receptor expression may contribute to the perpetuation of psychostimulant abuse and/or relapse.

El modelo de la fenciclidina en la esquizofrenia / The phencyclidine model of schizophrenia

La fenciclidina (PCP) produce psicosis muy similares a la esquizofrenia. Mientras las psicosis inducidas por anfetamina presentan sólo síntomas positivos como delirio y alucinaciones, las psicosis inducidas por PCP presentan tanto síntomas positivos como negativos (aplanamiento afectivo, retardo psicomotor, empobrecimiento del discurso). De este modo las psicosis anfetamínicas se ajustan a un modelo schneideriano y las psicosis por PCP a un modelo bleuleriano de esquizofrenia. La PCP se une selectivamente a un sitio de unión específico, el receptor a aminoácidos excitatorios N-metil-D-aspaertato (NMDA). Estos hallazgos sugieren que una disfunción de la neurotransmisión mediada por el receptor NMDA puede contribuir a la etiopatogenia de la esquizofrenia

Linfadenopatía angioinmunoblástica por ingestión prolongada de anfetamina / Angioimmunoblastic lymphadenopathy due to protractred amphetamine intake

Se presenta un paciente de 58 años con una linfadenopatía angioinmunoblástica (LAI) que ha ingerido 3 tabletas diarias de anfetamina durante 8 años.La ingestión prolongada de grandes dosis de anfetamina produce daños microvasculares un rasgo característico de la LAI. Con sólo medidas generales se observó una tendencia a la regresión de las adenopatías. El empleo del interferón alfa leucocitario pareció efectivo en el control de algunas adenopatías inguinales persistentes (AU)

Linfadenopatía angioinmunoblástica por ingestión prolongada de anfetamina / Angioimmunoblastic lymphadenopathy due to protractred amphetamine intake

Se presenta un paciente de 58 años con una linfadenopatía angioinmunoblástica (LAI) que ha ingerido 3 tabletas diarias de anfetamina durante 8 años.La ingestión prolongada de grandes dosis de anfetamina produce daños microvasculares un rasgo característico de la LAI. Con sólo medidas generales se observó una tendencia a la regresión de las adenopatías. El empleo del interferón alfa leucocitario pareció efectivo en el control de algunas adenopatías inguinales persistentes