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1.
Toxicol Lett ; 331: 188-199, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32569805

RESUMO

Methamphetamine (METH) is a highly addictive psychostimulant drug whose abuse can cause many health complications. Our previous studies have shown that METH exposure increases α-synuclein (α-syn) expression. Recently, it was shown that α-syn could be transferred from neurons to astrocytes via exosomes. However, the specific role of astrocytes in α-syn pathology involved in METH neurotoxicity remains unclear. The objective of this study was to determine whether exosomes derived from METH-treated neurons contain pathological α-syn and test the hypothesis that exosomes can transfer pathological α-syn from neurons to astrocytes. To this end, using animal and cell line coculture models, we show that exosomes isolated from METH-treated SH-SY5Y cells contained pathological α-syn. Furthermore, the addition of METH exosomes to the medium of primary cultured astrocytes induced α-syn aggregation and inflammatory responses in astrocytes. Then, we evaluated changes in nuclear receptor related 1 protein (Nurr1) expression and the levels of inflammatory cytokines in primary cultured astrocytes exposed to METH or α-syn. We found that METH or α-syn exposure decreased Nurr1 expression and increased proinflammatory cytokine expression in astrocytes. Our results indicate that α-syn can be transferred from neuronal cells to astrocytes through exosomes. When internalized α-syn accumulated in astrocytes, the cells produced inflammatory responses. Nurr1 may play a crucial role in this process and could be a therapeutic target for inflammatory damage caused by METH.


Assuntos
Astrócitos/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/toxicidade , Exossomos/metabolismo , Metanfetamina/toxicidade , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/metabolismo , alfa-Sinucleína/metabolismo , Animais , Astrócitos/imunologia , Astrócitos/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Citocinas/metabolismo , Hipocampo/citologia , Humanos , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos C57BL , Neurônios/imunologia , Neurônios/metabolismo , Síndromes Neurotóxicas/imunologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Cultura Primária de Células , Sinucleinopatias/imunologia , Sinucleinopatias/metabolismo
4.
Toxicol Lett ; 331: 42-52, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32464236

RESUMO

Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC >> MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N­acetyl­L­cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.


Assuntos
Alcaloides/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Drogas Ilícitas/toxicidade , Rim/efeitos dos fármacos , Alcaloides/química , Benzodioxóis/química , Benzodioxóis/toxicidade , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Rim/metabolismo , Rim/patologia , Metanfetamina/análogos & derivados , Metanfetamina/química , Metanfetamina/toxicidade , Metilaminas/química , Metilaminas/toxicidade , Pentanonas/química , Pentanonas/toxicidade , Pirrolidinas/química , Pirrolidinas/toxicidade , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
5.
PLoS One ; 15(5): e0229389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469882

RESUMO

Links between crystalline methamphetamine (CM) use and criminal offending are often drawn in the media; however, there has been little scientific research into this relationship. The aim of this study was to ascertain the prevalence and correlates of lifetime CM use among a sample of young people in detention in Australia and to examine whether an association exists between lifetime CM use and recidivism in this population.The sample included 202 young people (164 males) in youth detention in the state of Victoria, Australia. Participants were administered questionnaires related to lifetime substance use and socio-environmental experiences. Lifetime mental health data and offending data were obtained for each participant from public mental health and policing databases. More than one third (38%) of the sample reported lifetime CM use. In multivariate logistic regression analyses, older age, male gender, polysubstance use, and high levels of community disorganisation were associated with CM use. The presence of a psychiatric diagnosis over the lifetime was not significantly associated with CM use. CM use was also not significantly associated with violent recidivism. Efforts to address CM use and related harm in detained youth should include community-based strategies to reduce CM use among this vulnerable population following their release from detention. However, the findings suggest that CM use on its own is unlikely to be an important consideration for professionals concerned with determining which young people should be selected for treatment designed to reduce the risk of violent recidivism.


Assuntos
Comportamento Criminoso/efeitos dos fármacos , Delinquência Juvenil/psicologia , Metanfetamina/toxicidade , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Analgésicos Opioides/efeitos adversos , Austrália/epidemiologia , Cannabis/efeitos adversos , Comportamento Criminoso/fisiologia , Feminino , Medicina Legal , Humanos , Delinquência Juvenil/legislação & jurisprudência , Masculino , Saúde Mental , Abuso Físico/psicologia , Polícia/estatística & dados numéricos , Saúde Pública , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Adulto Jovem
6.
PLoS One ; 15(5): e0233010, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396581

RESUMO

Methamphetamine use has increased over the past decade and the first use of methamphetamine is most often when women are of reproductive age. Methamphetamine accumulates in the liver; however, little is known about the effect of methamphetamine use on hepatic drug metabolism. Methamphetamine was administered on 3 occassions to female Dunkin Hartley guinea pigs of reproductive age, mimicking recreational drug use. Low doses of test drugs caffeine and midazolam were administered after the third dose of methamphetamine to assess the functional activity of cytochrome P450 1A2 and 3A, respectively. Real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of factors involved in glucocorticoid signalling, inflammation, oxidative stress and drug transporters. This study showed that methamphetamine administration decreased hepatic CYP1A2 mRNA expression, but increased CYP1A2 enzyme activity. Methamphetamine had no effect on CYP3A enzyme activity. In addition, we found that methamphetamine may also result in changes in glucocorticoid bioavailability, as we found a decrease in 11ß-hydroxysteroid dehydrogenase 1 mRNA expression, which converts inactive cortisone into active cortisol. This study has shown that methamphetamine administration has the potential to alter drug metabolism via the CYP1A2 metabolic pathway in female guinea pigs. This may have clinical implications for drug dosing in female methamphetamine users of reproductive age.


Assuntos
Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metanfetamina/administração & dosagem , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/toxicidade , Citocromo P-450 CYP1A2/genética , Feminino , Cobaias , Humanos , Taxa de Depuração Metabólica , Redes e Vias Metabólicas/efeitos dos fármacos , Metanfetamina/sangue , Metanfetamina/toxicidade , Modelos Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Mol Immunol ; 121: 159-166, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32222586

RESUMO

Methamphetamine (METH) is a major public health and safety problem worldwide. METH is psychostimulant that activates microglia via the toll-like receptor (TLR) 4/MD2 complex, modulating the abundant production of pro-inflammatory cytokines in the central nervous system (CNS). The TLR4/MD2 complex on the surface of microglia recognizes pathogen-associated molecular patterns such as lipopolysaccharide (LPS) resulting in brain tissue inflammation and neuronal damage. Since METH has been associated with microglia-induced neurotoxicity, we hypothesized that METH impairs the expression of TLR4 and activation of NF-κB in NR-9460 microglia-like cells after LPS challenge. We demonstrated that METH decreases the distribution and expression of TLR4 receptors on the surface of microglia-like cells after incubation with endotoxin. Moreover, METH impairs the TLR4/MD2 complex signaling pathways, compromises the activation of NF-κB, and reduces the production of pro-inflammatory mediators in microglia-like cells upon LPS stimulation. Interestingly, microglia-like cells treated with METH and challenged with LPS showed considerable cellular morphological changes including enlarged nuclei and ruffled surface. Our results suggest that METH may have a significant impact on microglial-induced neuroinflammation, neurotoxicity, and the CNS defense against infection. It also highlights the importance of studying the effects of METH on the molecular and cellular components of users' CNS immunity. Finally, animal studies exploring the role of METH on the effectors functions of microglia after antigenic exposure are necessary to understand drug-related inflammation and neural damage in users.


Assuntos
Estimulantes do Sistema Nervoso Central/toxicidade , Encefalite/induzido quimicamente , Metanfetamina/toxicidade , Microglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/imunologia , Citocinas/metabolismo , Encefalite/imunologia , Encefalite/patologia , Humanos , Lipopolissacarídeos/imunologia , Camundongos , Microglia/citologia , Microglia/imunologia , NF-kappa B/imunologia , NF-kappa B/metabolismo , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
9.
Sci Total Environ ; 721: 137728, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169646

RESUMO

Methamphetamine (METH) is a central nervous system stimulant drug whose use has increased in the last few years worldwide. After the ingestion of even a single dose, METH is excreted by the organism and enters the aquatic ecosystems, whereby concentrations up to hundreds of ng/L were measured in both sewage and surface waters. Although the environmental concentrations are currently quite low, the high biological activity of METH might cause adverse effects towards non-target organisms. However, to date the information on METH toxicity towards aquatic organisms is limited. Thus, the present study aimed at investigating biochemical and behavioral effects induced by METH exposure towards the Cladoceran Daphnia magna. A 21-days exposure to two environmental concentrations of METH (50 ng/L and 500 ng/L) was performed. At selected time points (7, 14 and 21 days) the amount of pro-oxidant molecules, the activity of antioxidant enzymes (SOD, CAT, GPx) and levels of lipid peroxidation (LPO) were measured as oxidative stress-related endpoints. Changes in swimming activity and reproductive output were assessed as behavioral endpoints. METH exposure affected the oxidative status of D. magna specimens at both tested concentrations, although no oxidative damage occurred. Although METH did not modulate the swimming activity of D. magna, a significant, positive effect on reproductive output, in terms of number of offspring was found. Our results showed that low concentrations of METH might represent a threat for D. magna, affecting the health status of this aquatic species at different level of biological organization.


Assuntos
Metanfetamina , Poluentes Químicos da Água/análise , Animais , Daphnia , Ecossistema , Estresse Oxidativo
10.
Proc Natl Acad Sci U S A ; 117(14): 8126-8134, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32205443

RESUMO

We recently reported that social choice-induced voluntary abstinence prevents incubation of methamphetamine craving in rats. This inhibitory effect was associated with activation of protein kinase-Cδ (PKCδ)-expressing neurons in central amygdala lateral division (CeL). In contrast, incubation of craving after forced abstinence was associated with activation of CeL-expressing somatostatin (SOM) neurons. Here we determined the causal role of CeL PKCδ and SOM in incubation using short-hairpin RNAs against PKCδ or SOM that we developed and validated. We injected two groups with shPKCδ or shCtrlPKCδ into CeL and trained them to lever press for social interaction (6 d) and then for methamphetamine infusions (12 d). We injected two other groups with shSOM or shCtrlSOM into CeL and trained them to lever press for methamphetamine infusions (12 d). We then assessed relapse to methamphetamine seeking after 1 and 15 abstinence days. Between tests, the rats underwent either social choice-induced abstinence (shPKCδ groups) or homecage forced abstinence (shSOM groups). After test day 15, we assessed PKCδ and SOM, Fos, and double-labeled expression in CeL and central amygdala medial division (CeM). shPKCδ CeL injections decreased Fos in CeL PKCδ-expressing neurons, increased Fos in CeM output neurons, and reversed the inhibitory effect of social choice-induced abstinence on incubated drug seeking on day 15. In contrast, shSOM CeL injections decreased Fos in CeL SOM-expressing neurons, decreased Fos in CeM output neurons, and decreased incubated drug seeking after 15 forced abstinence days. Our results identify dissociable central amygdala mechanisms of abstinence-dependent expression or inhibition of incubation of craving.


Assuntos
Núcleo Central da Amígdala/fisiologia , Fissura/fisiologia , Comportamento de Procura de Droga/fisiologia , Relações Interpessoais , Animais , Comportamento Animal , Modelos Animais de Doenças , Humanos , Masculino , Metanfetamina/administração & dosagem , Metanfetamina/efeitos adversos , Neurônios/metabolismo , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/metabolismo , RNA Interferente Pequeno/administração & dosagem , Ratos , Ratos Sprague-Dawley , Autoadministração , Somatostatina/genética , Somatostatina/metabolismo
11.
MMWR Morb Mortal Wkly Rep ; 69(12): 317-323, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32214077

RESUMO

Methamphetamine is a highly addictive central nervous system stimulant. Methamphetamine use is associated with a range of health harms, including psychosis and other mental disorders, cardiovascular and renal dysfunction, infectious disease transmission, and overdose (1,2). Although overall population rates of methamphetamine use have remained relatively stable in recent years (3), methamphetamine availability and methamphetamine-related harms (e.g., methamphetamine involvement in overdose deaths and number of treatment admissions) have increased in the United States* (4,5); however, analyses examining methamphetamine use patterns and characteristics associated with its use are limited. This report uses data from the 2015-2018 National Surveys on Drug Use and Health (NSDUHs) to estimate methamphetamine use rates in the United States and to identify characteristics associated with past-year methamphetamine use. Rates (per 1,000 adults aged ≥18 years) for past-year methamphetamine use were estimated overall, by demographic group, and by state. Frequency of past-year use and prevalence of other substance use and mental illness among adults reporting past-year use were assessed. Multivariable logistic regression examined characteristics associated with past-year use. During 2015-2018, the estimated rate of past-year methamphetamine use among adults was 6.6 per 1,000. Among adults reporting past-year methamphetamine use, an estimated 27.3% reported using on ≥200 days, 52.9% had a methamphetamine use disorder, and 22.3% injected methamphetamine. Controlling for other factors, higher adjusted odds ratios for past-year use were found among men; persons aged 26-34, 35-49, and ≥50 years; and those with lower educational attainment, annual household income <$50,000, Medicaid only or no insurance, those living in small metro and nonmetro counties,† and those with co-occurring substance use and co-occurring mental illness. Additional efforts to build state and local prevention and response capacity, expand linkages to care, and enhance public health and public safety collaborations are needed to combat increasing methamphetamine harms.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Metanfetamina/administração & dosagem , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Adulto Jovem
12.
Nature ; 579(7800): 555-560, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214250

RESUMO

Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3-5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs.


Assuntos
Espinhas Dendríticas/fisiologia , Aprendizagem por Discriminação/fisiologia , Receptores de Dopamina D2/metabolismo , Animais , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Condicionamento Clássico/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Aprendizagem por Discriminação/efeitos dos fármacos , Dopamina/metabolismo , Antagonistas dos Receptores de Dopamina D2/farmacologia , Extinção Psicológica/efeitos dos fármacos , Masculino , Metanfetamina/antagonistas & inibidores , Metanfetamina/farmacologia , Camundongos , Plasticidade Neuronal , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Optogenética , Receptor A2A de Adenosina/metabolismo , Receptores de Dopamina D1/metabolismo , Recompensa , Transdução de Sinais/efeitos dos fármacos , Sinapses/metabolismo
13.
Nat Protoc ; 15(4): 1542-1559, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203485

RESUMO

It is difficult to translate results from animal research on addiction to an understanding of the behavior of human drug users. Despite decades of basic research on neurobiological mechanisms of drug addiction, treatment options remain largely unchanged. A potential reason for this is that mechanistic studies using rodent models do not incorporate a critical facet of human addiction: volitional choices between drug use and non-drug social rewards (e.g., employment and family). Recently, we developed an operant model in which rats press a lever for rewarding social interaction with a peer and then choose between an addictive drug (heroin or methamphetamine) and social interaction. Using this model, we showed that rewarding social interaction suppresses drug self-administration, relapse to drug seeking, and brain responses to drug-associated cues. Here, we describe a protocol for operant social interaction using a discrete-trial choice between drugs and social interaction that causes voluntary abstinence from the drug and tests for incubation of drug craving (the time-dependent increase in drug seeking during abstinence). This protocol is flexible but generally requires 8-9 weeks for completion. We also provide a detailed description of the technical requirements and procedures for building the social self-administration and choice apparatus. Our protocol provides a reliable way to study the role of operant social reward in addiction and addiction vulnerability in the context of choices. We propose that this protocol can be used to study brain mechanisms of operant social reward and potentially impairments in social reward in animal models of psychiatric disorders and pain.


Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Operante/fisiologia , Comportamento de Procura de Droga/fisiologia , Modelos Psicológicos , Autoadministração/métodos , Animais , Modelos Animais de Doenças , Feminino , Heroína/administração & dosagem , Masculino , Metanfetamina/administração & dosagem , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Remifentanil/administração & dosagem , Comportamento Social , Transtornos Relacionados ao Uso de Substâncias/psicologia
14.
Bratisl Lek Listy ; 121(3): 225-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115981

RESUMO

AIM: Nicotine at high concentrations induces apoptosis in trophoblastic cells through induction of cell cytotoxicity and Reactive Oxygen Species (ROS). Methamphetamine in low dose has pharmaceutical properties. It seems that this components in low dose can protect the trophoblastic cells from nicotine-induced cell death. METHOD: Trophoblastic (JEG-3) cells grown in DMEM culture medium. MTT assay test detected the cell viability and Lactate Dehydrogenase test measured the cells cytotoxicity. Griess reaction was used for NO production analysis. Cell migration traced by wounding technique. Human Cytokine Array Focused 13-plex was also used for analysis of IL-1α, IL-1ß, IL-6, INFγ, and TNFα pre-inflammatory cytokines. RESULTS: Methamphetamine, in very low dose (pM), increased the cell viability and NO production, and decreased cell cytotoxicity, IL-1α, IL-1ß, IL-6, INFγ, and TNFα pre-inflammatory cytokines of JEG-3 cell which were exposed to high dose of nicotine, respectively. Cell migration was enhanced by low dose of methamphetamine in JEG-3 cells. CONCLUSION: Methamphetamine in very low dose suppressed the JEG-3 cell death induced by high dose of nicotine (Fig. 5, Ref. 48) Keywords: methamphetamine, nicotine, cell death, NO.


Assuntos
Dopaminérgicos , Inflamação , Metanfetamina , Trofoblastos , Linhagem Celular Tumoral , Sobrevivência Celular , Dopaminérgicos/farmacologia , Humanos , Inflamação/tratamento farmacológico , Metanfetamina/farmacologia , Nicotina/toxicidade , Trofoblastos/efeitos dos fármacos
15.
Am J Public Health ; 110(4): 509-516, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32078347

RESUMO

Objectives. To evaluate trends and correlates of methamphetamine use in the United States.Methods. Data are from 15 747 334 drug-related treatment admissions among persons aged 12 years or older in the 2008-2017 Treatment Episode Data Set. We analyzed trends and used multivariable logistic regression.Results. Methamphetamine-related admissions increased from 15.1% of drug-related treatment admissions in 2008 to 23.6% in 2017. Increases occurred among nearly all demographic groups. Methamphetamine injection increased from 17.5% of admissions in 2008 to 28.4% in 2017. Among methamphetamine-related admissions, heroin use increased from 5.3% of admissions in 2008 to 23.6% in 2017. Characteristics associated with increased odds of reporting methamphetamine use at admission included female sex; admissions aged 35 to 44 years; admissions in the Midwest, South, and West; unemployment; not in labor force; living dependent; living homeless; and having a referral from criminal justice, a health care provider, or other community treatment source.Conclusions. Treatment admissions involving methamphetamine use increased significantly over the past decade and appear to be linked to the ongoing opioid crisis in the United States. Efforts to mobilize public health prevention, treatment, and response strategies to address rising methamphetamine use and overdose are needed.


Assuntos
Hospitalização/tendências , Metanfetamina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Criança , Feminino , Heroína , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
16.
Water Res ; 174: 115585, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105996

RESUMO

Ketamine (KET) and methamphetamine (METH) have been recognized as emerging contaminants in aquatic ecosystems. This paper aimed to investigate the environmental behaviour, including the degradation, distribution, and bioaccumulation, of METH, KET, and their main metabolites (amphetamine (AMP) and norketamine (NorKET)). The changes in acute toxicity in the aqueous phase and in the bacterial community in sediment were determined to assess the associated eco-risk of the drug exposure. Five types of lab-scale aquatic ecosystems were established and exposed to KET or METH for 40 days: a water- sediment- organisms- KET system (K), a water- sediment- organisms- METH system (M), a water- sediment- organism- METH- KET system (M + K), a water-sediment- KET- METH system (control), and a water- sediment- organisms system (biocontrol). The results demonstrated that much faster degradation occurred for both METH (t1/2 = 3.89 and 2.37 days in the M and M + K group, respectively) and KET(t1/2 = 5.69 days 5.39 days in the K group and M + K group, respectively) than in the control group (t1/2 = 7.83 and 86.71days for METH and KET, respectively). Rapid adsorption of KET, METH, and their metabolites was observed in the sediment, which had clay and silt as the main particle sizes. KET was observed to be absorbed by shallow-water fish (Chinese medaka, rosy bitterling and mosquito fish), while METH was dominantly ingested by bottom-dwellers (loach). Duckweed might play a crucial role in the dissipation process of METH and KET, which were mainly adsorbed by duckweed roots. During incubation, the acute toxic levels in the K and M + K groups changed from non-toxic to medium toxicity levels, and the toxicity in the M and control groups changed from non-toxic to low toxicity levels. Moreover, marked changes in the bacterial community in the sediment induced by METH or KET exposure were observed, and the most significant change in the bacterial community was observed in the group spiked with both METH and KET. This work for the first time elucidated the environmental behaviors of METH and KET in aquatic ecosystem and associated the impact on ecological system equilibrium.


Assuntos
Ketamina , Metanfetamina , Poluentes Químicos da Água , Animais , Bioacumulação , Ecossistema , Sedimentos Geológicos
17.
Cell Prolif ; 53(3): e12773, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020692

RESUMO

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Antioxidantes/uso terapêutico , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Metanfetamina/efeitos adversos , Resveratrol/uso terapêutico , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
18.
Emergencias (Sant Vicenç dels Horts) ; 32(1): 26-32, feb. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-185850

RESUMO

Objetivo: Investigar si existen diferencias clínicas y toxicológicas en pacientes intoxicados por anfetamina (ANF) y metanfetamina (MANF) atendidos en servicios de urgencias. Método: Estudio observacional retrospectivo de intoxicaciones por ANF y MANF con confirmación analítica en Baleares (2013-2018). Se compararon variables clínicas, toxicológicas y de manejo clínico entre grupos. Resultados: 1) Se incluyeron 120 pacientes, 86 (71,7%) grupo ANF y 34 (28,3%) grupo MANF. 2) La confirmación de derivados anfetamínicos se realizó por cromatografía de gases-espectrometría de masas en 787 muestras de orina previamente positivas mediante un método de cribado cualitativo. Se confirmaron 154 (19,6%) muestras. De ellas, 34 fueron excluidas. 3) Se encontraron diferencias significativas entre ANF y MANF en: edad (32,3 vs 28,4 años); sexo (72,1 vs 94,1% hombres); nacionalidad española (64,0 vs 29,4%); en motivos de admisión: alteración de conducta (15,1 vs 0%) y palpitaciones (1,2 vs 20,6%); y en características clínicas: agitación (27,9 vs 8,8%). No hubo diferencias de manejo clínico. El 76,6% de casos fueron polintoxicaciones, más comunes en ANF (82,6 vs 61,8%). En estos casos se detectó principalmente cocaína (63,0%), cannabis (48,9%), MDMA (38,0%) y alcohol (35,9%). La mayor asociación del cannabis con el grupo de ANF fue estadísticamente significativa (45,3 vs 17,6%). La causa de los falsos positivos se identificó en el 78,7% de muestras, siendo el MDMA (71,2%) la principal. Conclusiones: Se observaron diferencias entre ANF y MANF en cuanto a variables demográficas y motivo de asistencia; no obstante en esta serie hubo un alto porcentaje de polintoxicaciones


Objective: To determine whether clinical and toxicologic findings differed between cases of amphetamine (AMP) and methamphetamine (mAMP) poisoning attended in 2 Balearic Island hospital emergency departments. Methods: Retrospective observational study of AMP and mAMP cases with laboratory confirmation between 2013 and 2018. We compared clinical and toxicologic variables as well as clinical management between groups. Results: 1) A total of 120 cases were found: 86 (71.7%) with AMP poisoning and 34 (28.3%) with mAMP poisoning. 2) Drug poisoning was confirmed by gas chromatography associated with mass spectrometry (GC–MS) in 787 urine samples found to be positive during screening. One hundred fifty-four (19.6%) were confirmed by GC–MS. Thirtyfour of them did not meet the inclusion criteria. 3) Significant differences between AMP and mAMP cases were found for age (32.3 vs 28.4 y, respectively); sex (72.1% vs 94.1% men); and Spanish nationality (64.0% vs 29.4%). Reasons for admission and clinical features also differed: the reasons were aberrant behavior (15.1% in the AMP group vs 0% in the mAMP group) and palpitations (1.2% vs 20.6%); agitation was observed in 27.9% and 8.8%, respectively. Clinical management was similar in the 2 groups. Multiple drug poisoning was detected in 76.6% patients and was more common in patients in the AMP group (82.6% vs 61.8%). The additional drugs in these cases were mainly cocaine (63.0%), cannabis (48.9%), 3,4-methylenedioxy-N-methamphetamine (MDMA) (38.0%), and alcohol (35.9%). Cannabis was detected in a significantly higher proportion in the AMP group (45.3%) than in the mAMP group (17.6%). False positives were found in 78.7% of the samples. The culprit drug was most often MDMA (71.2%). Conclusions: AMP poisonings were associated with age over 30 years, Spanish nationality, aberrant behavior, agitation, multiple drug findings, and the use of cannabis. Poisonings caused by mAMP abuse were associated with age under 30 years, non-Spanish nationality, palpitations, and single-drug use


Assuntos
Humanos , Masculino , Feminino , Adulto , Anfetamina/toxicidade , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Serviços Médicos de Emergência , Metanfetamina/toxicidade , Estudos Retrospectivos , Unidades de Terapia Intensiva , Acidente Vascular Cerebral/complicações
20.
Water Res ; 172: 115495, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954935

RESUMO

Urban wastewater treatment plants (WWTPs) can be an emission source of aerosol particles to the air and this process has the potential to spread emerging pollutants into the air, where the particles can be widely transported over long distances to areas where this pollution is unexpected. This study demonstrates aeration tanks in WWTPs as a potential source of ketamine, methamphetamine and other emerging contaminant emissions into the air. Ketamine and methamphetamine are frequently detected in high concentrations (maximum of 151.8-162.8 pg/m3) in gaseous and aerosol samples along with 24 other emerging contaminants. Through correlation analysis, the common occurrence of emerging contaminants in air is attributable to their high aqueous concentrations as well as their physicochemical properties. Two simple regression models are developed to provide a practical and convenient way to estimate the steady-state concentrations in air. The gas-phase emission model illustrates the relationship between the solubility, the pKa and the aqueous concentration of compounds in the aeration basin and their gaseous concentrations in air (statistical strength of 74.1%; p value < 0.05), while the partition model establishes the ratio of a compound in the gas and particulate phases in air (statistical strength of 82.6%; p value < 0.05). The results provide a basis for assessing the risk of the inhalation exposure to airborne emerging contaminants; however, in-depth research addressing the impact of aerosols containing persistent pharmaceuticals on human health is still needed.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ketamina , Metanfetamina , Monitoramento Ambiental , Humanos , Águas Residuárias
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