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1.
Life Sci ; 256: 117917, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525001

RESUMO

AIMS: Methamphetamine (METH) is an abused psychostimulant causing public health concern worldwide. While most studies have focused on the neurotoxic effects of METH, METH-induced cerebrovascular dysfunction has recently drawn attention as an important facet of METH-related pathophysiology. In this study, we investigated the protective role of GKT136901, a NOX1/4 inhibitor, against METH-induced blood-brain barrier (BBB) dysfunction. MAIN METHODS: Primary human brain microvascular endothelial cells (HBMECs) were used as an in vitro BBB model. HBMECs were treated with GKT136901, followed by METH exposure for 24 h. The generation of reactive oxidative species (ROS) was measured using 2',7'-dichlorofluorescin diacetate (DCF-DA) staining. To examine the BBB function, paracellular permeability of HBMEC monolayer was measured using FITC-labeled dextran. To evaluate structural properties of BBB in HBMECs, tight junction (TJ), adherent junction (AJ), and cytoskeletal proteins were stained and analyzed by confocal microscopy. KEY FINDINGS: METH treatment rapidly increased ROS generation in HBMECs but GKT136901 treatment inhibited METH-induced ROS generation. Although METH increased the permeability of HBMEC monolayer, this effect was abolished upon GKT136901 treatment. Following METH exposure, the proteins Zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) were translocalized from the cell membrane to the cytoplasm, thereby destroying intercellular tight junction (TJ) and adherent junction (AJ) structures, which were ameliorated upon GKT136901 treatment. METH exposure altered the cellular morphology of HBMECs and induced stress fiber formation. However, GKT136901 prevented METH-induced morphological and cytoskeletal changes in HBMECs. SIGNIFICANCE: These results suggest that GKT136901 prevents METH-induced BBB dysfunction in HBMECs through the inhibition of ROS generation.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Metanfetamina/efeitos adversos , NADPH Oxidases/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Pirazóis/farmacologia , Piridonas/farmacologia , Antígenos CD/metabolismo , Barreira Hematoencefálica/citologia , Caderinas/metabolismo , Capilares/citologia , Permeabilidade Capilar , Descoberta de Drogas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
3.
AIDS Behav ; 24(9): 2720-2731, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32185596

RESUMO

We studied mechanisms driving gender differences in HIV incidence among 651 women and men who inject drugs (PWID) in Tijuana, Mexico, hypothesizing that sex work will mediate the association between female gender and HIV incidence. Of 43 HIV seroconversions occurring between 2011 and 2018, 8.8% were among females and 5.2% among males. HIV incidence density was significantly higher among females versus males (1.75 per 100 person years [PY], 95% CI 1.16-2.66, vs. 0.95 per 100 PY, 95% CI 0.62-1.47). Factors significantly associated with HIV seroconversion were: sex work (adjusted hazard ratio [aHR] = 2.25, 95% CI 1.05-4.80); methamphetamine injection (aHR = 2.30, 95% CI 1.12-4.73); and methamphetamine and heroin co-injection in the past six months (aHR = 2.26, 95% CI 1.23-4.15). In mediation analyses, sex work mediated a substantial proportion (84.3%) of the association between female gender and HIV incidence. Interventions should target female PWID who engage in sex work to reduce gender-related disparities in HIV incidence.


Assuntos
Infecções por HIV/epidemiologia , Heroína/efeitos adversos , Metanfetamina/efeitos adversos , Trabalho Sexual , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Feminino , Infecções por HIV/diagnóstico , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
4.
JAMA Netw Open ; 3(3): e200910, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32167568

RESUMO

Importance: Impulsivity during periods of abstinence is a critical symptom of patients who use methamphetamine (MA). Objective: To evaluate changes in impulse inhibition elicited by repetitive transcranial magnetic stimulation (rTMS) in patients with MA addiction. Design, Setting, and Participants: This randomized clinical trial was conducted in Da Lian Shan Addiction Rehabilitation Center, Nanjing, China, from December 1, 2018, to April 20, 2019. Effects of the intervention were examined at 3 time points: after a single session (day 1), 24 hours after 10 repeated sessions (day 11), and at 3 weeks of follow-up (day 31). Men with MA addiction and healthy male control participants were recruited for this study. Data analysis was performed from March 2019 to October 2019. Interventions: Patients who use MA were randomized to undergo sham rTMS (36 patients) and or 1-Hz rTMS (37 patients) to the left prefrontal cortex, receiving daily TMS treatments for 10 consecutive days. Main Outcomes and Measures: The primary outcome was impulse inhibition, which is primarily embodied by accuracy reduction (ie, accuracy cost) from standard to deviant trials in a 2-choice oddball task (80% standard and 20% deviant trials). Result: The study included 73 men with MA addiction (mean [SD] age, 38.49 [7.69] years) and 33 male healthy control participants without MA addiction (mean [SD] age, 35.15 [9.68] years). The mean (SD) duration of abstinence for the men with MA addiction was 9.27 (4.61) months. Compared with the control group, patients with MA addiction exhibited greater impulsivity (accuracy cost, 3.3% vs 6.2%). The single session of 1-Hz rTMS over the left prefrontal cortex significantly increased accuracy from 91.4% to 95.7% (F1,36 = 9.58; P < .001) and reaction time delay from 50 milliseconds to 77 milliseconds (F1,36 = 22.66; P < .001) in deviant trials. These effects were seen consistently after 10 sessions of 1-Hz rTMS treatment (day 11 vs day 1, t26 = 1.59; P = .12), and the behavioral improvement was maintained at least for 3 weeks after treatment (day 31 vs day 1, t26 = 0.26; P = .80). These improvement effects of impulse inhibition were coupled with a reduction in addictive symptoms as measured by cue-induced craving. The pretest accuracy cost was positively correlated with the change in impulse inhibition (r = 0.615; P < .001) and change in craving (r = 0.334; P = .01), suggesting that these 2 behaviors may be modified simultaneously. Conclusions and Relevance: These findings suggest that repeated rTMS sessions have sustained effects on impulse inhibition in patients with MA addiction and provide novel data on impulsivity management strategies for addiction rehabilitation. Trial Registration: ChiCTR-ROC-16008541.


Assuntos
Comportamento Aditivo , Cognição/fisiologia , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
5.
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
6.
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
8.
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
10.
PLoS One ; 15(1): e0227774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978078

RESUMO

The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and addiction, which can powerfully and chronically worsen human health, have received relatively little attention in this regard. Therefore, the main objective of this study was to characterize how selected synthetic psychoactive cathinones (aka "Bath Salts") and amphetamine stimulants modify the gut microbiome. Mice were treated with mephedrone (40 mg/kg), methcathinone (80 mg/kg), methamphetamine (5 mg/kg) or 4-methyl-methamphetamine (40 mg/kg), following a binge regimen consisting of 4 injections at 2h intervals. These drugs were selected for study because they are structural analogs that contain a ß-keto substituent (methcathinone), a 4-methyl group (4-methyl-methamphetamine), both substituents (mephedrone) or neither (methamphetamine). Mice were sacrificed 1, 2 or 7 days after treatment and DNA from caecum contents was subjected to 16S rRNA sequencing. We found that all drugs caused significant time- and structure-dependent alterations in the diversity and taxonomic structure of the gut microbiome. The two phyla most changed by drug treatments were Firmicutes (methcathinone, 4-methyl-methamphetamine) and Bacteriodetes (methcathinone, 4-methyl-methamphetamine, methamphetamine, mephedrone). Across time, broad microbiome changes from the phylum to genus levels were characteristic of all drugs. The present results signify that these selected psychoactive drugs, which are thought to exert their primary effects within the CNS, can have profound effects on the gut microbiome. They also suggest new avenues of investigation into the possibility that gut-derived signals could modulate drug abuse and addiction via altered communication along the gut-brain axis.


Assuntos
Drogas Desenhadas/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Metanfetamina/análogos & derivados , Metanfetamina/efeitos adversos , Propiofenonas/efeitos adversos , Psicotrópicos/efeitos adversos , Animais , DNA Bacteriano/isolamento & purificação , Drogas Desenhadas/administração & dosagem , Feminino , Microbioma Gastrointestinal/genética , Metanfetamina/administração & dosagem , Camundongos , Modelos Animais , Propiofenonas/administração & dosagem , Psicotrópicos/administração & dosagem , RNA Ribossômico 16S/genética
11.
Forensic Sci Int ; 306: 110093, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816483

RESUMO

Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan (2005-2017). Chi-square/Fisher's exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson regression models were used to estimate the rate ratios ("RRs") and annual percentage changes ("APCs"). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95 % CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95 % CI, -18.9 to -10.6), whereas methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95 % CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.


Assuntos
Analgésicos Opioides/envenenamento , Ketamina/envenenamento , Metanfetamina/envenenamento , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Distribuição por Idade , Analgésicos Opioides/efeitos adversos , Intoxicação por Monóxido de Carbono/mortalidade , China/epidemiologia , Feminino , Heroína/efeitos adversos , Heroína/envenenamento , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/envenenamento , Ketamina/efeitos adversos , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Distribuição por Sexo , Suicídio/estatística & dados numéricos , Adulto Jovem
12.
J Am Acad Orthop Surg ; 28(1): e28-e33, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30985479

RESUMO

INTRODUCTION: We sought to characterize the prevalence of methamphetamine (MA) abuse and associated orthopaedic injury patterns at our level 1 trauma center. METHODS: We conducted a retrospective review of all orthopaedic consults for the year 2016. Patients were classified as MA users based on urine toxicology results and social history. RESULTS: The prevalence of MA use was 10.0%. MA users were more likely to present with hand lacerations and other infections (P < 0.05 for all). Regarding the mechanism of injury, MA users were more likely to be involved in automobile versus pedestrian, automobile versus bicycle, ballistic, knife, closed fist, other assault/altercation, and animal bite injuries (P < 0.05 for all). DISCUSSION: MA use is prevalent at our level 1 trauma center. The prevalence and injury patterns of MA abuse warrant deeper study into the effects of this drug on orthopaedic outcomes. LEVEL OF EVIDENCE: Level III.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Metanfetamina/efeitos adversos , Sistema Musculoesquelético/lesões , Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Toxicol Lett ; 321: 73-82, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31862507

RESUMO

An enterogenic infection occurs when intestinal mucosal disruption is followed by the invasion of intestinal bacteria into the blood and distant organs, which can result in severe diseases or even death. Our previous study using Rhesus monkeys as an in vivo model revealed that methamphetamine (MA) induced intestinal mucosal barrier damage, which poses a high risk of enterogenic infection. However, how methamphetamine causes intestinal mucosal barrier damage remains largely unknown. In this study, we employed an in vitro model, and found that MA treatment could inhibit the expression of miR-181c, which directly targets and regulates TNF-α, and ultimately induces apoptosis and damages the intestinal barrier. Moreover, we measured TNF-α serum levels as well as the intestinal mucosal barrier damage indicators (diamine oxidase, d-lactic acid, and exotoxin) and found that their levels were significantly higher in MA-dependents than in healthy controls (P < 0.001). To the best of our knowledge, this is the first report evidencing that miR-181c is involved in MA-induced intestinal barrier injury via TNF-α regulation, which introduces novel potential therapeutic targets for MA-dependent intestinal diseases.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Estimulantes do Sistema Nervoso Central/efeitos adversos , Células Epiteliais/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Metanfetamina/efeitos adversos , MicroRNAs/metabolismo , Junções Íntimas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/patologia , Animais , Apoptose/efeitos dos fármacos , Translocação Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Estudos de Casos e Controles , Linhagem Celular , Impedância Elétrica , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Microbioma Gastrointestinal , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Permeabilidade , Ratos , Transdução de Sinais , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
14.
Am J Cardiol ; 125(1): 127-134, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31699360

RESUMO

Anecdotal cases of reversible methamphetamine-associated cardiomyopathy (rMAC) have been reported, but not well understood. This study sought to determine the clinical characteristics, outcomes and predictors of reversibility among patients with rMAC as compared with patients with persistent MAC (pMAC). We retrospectively studied adult MAC patients with left ventricular ejection fraction (LVEF) ≤40% at a single center between 2004 and 2018. rMAC was defined as increase in LVEF by ≥20 points or to ≥50%. Those with persistent LVEF ≤40% constituted the pMAC group. 357 MAC cases were identified: 250 patients had pMAC and 107 had rMAC. After a median follow-up of 45 months (interquartile range 27 to 70), LVEF increased by 28.3 ± 6.9% in rMAC (p <0.001), whereas it was unchanged in pMAC (Δ: -0.5 ± 8.7%, p = 0.350). Heart failure hospitalizations and New York Heart Association Class III/IV heart failure were both significantly reduced for rMAC than the pMAC group. All-cause mortality was 21.6% overall, 28% in pMAC and 6.5% in the rMAC group (p <0.001). Kaplan-Meier survival curves demonstrated significantly higher cumulative survival for rMAC (Log Rank p <0.001). Multivariable logistic regression identified MA cessation (odds ratio/OR: 4.23, 95% confidence interval/CI: 2.47 to 7.38, p <0.001) and baseline right ventricular end systolic area (OR: 0.92, 95% CI: 0.87 to 0.97, p = 0.001) as strongly predictive of MAC reversal. In conclusion, MAC reversal is not uncommon and is associated with significant clinical improvement including reduced mortality. It can be facilitated by MA cessation when the cardiac chambers, especially the right ventricle, are not severely dilated.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Cardiomiopatias/induzido quimicamente , Ventrículos do Coração/diagnóstico por imagem , Metanfetamina/efeitos adversos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Transtornos Relacionados ao Uso de Anfetaminas/mortalidade , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , California/epidemiologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Causas de Morte/tendências , Dopaminérgicos/efeitos adversos , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências
15.
BMC Psychiatry ; 19(1): 416, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870339

RESUMO

BACKGROUND: Cannabis is the most widely used illicit substance by Australian young people, including those engaged with youth alcohol and other drug (AOD) systems. While recreational cannabis use in young people may be a developmental activity for some, for others, this usage becomes regular and be associated with poorer long term outcomes. This study reports on the rates of cannabis use and co-existing psychosocial complexity factors in the Youth Needs Census (2013 and 2016) where workers report on all clients in the youth AOD system, a cohort considered highly vulnerable. METHODS: Data was examined for two rounds of data collection for the Youth Needs Census, including 823 youth AOD service engaged young people in 2016 and 1000 AOD service engaged young people in 2013, to identify usage rates, psychosocial outcomes, and changes over time. RESULTS: Daily use of cannabis alone significantly exceeded daily usage rates for methamphetamines, alcohol, and cannabis used alongside other substances. Daily cannabis use was significantly associated with mental health problems, employment problems, education problems, family problems, and housing problems. Daily cannabis use was associated with most psychosocial complexity factors to the same extent as daily methamphetamine use and daily alcohol use, with daily cannabis users only showing lower incidence of the drug-related harm measure. Notably, daily cannabis use also increased from 2013 (47.5%) to 2016 (54.2%). CONCLUSIONS: It is imperative that the number of individuals using cannabis is considered alongside the severity of harm when assessing the social impact of this substance. Within cannabis users engaged with the youth AOD system, who often have high levels of psychosocial complexity, cannabis is used daily by a large proportion of these youths and may play a role in negatively impacting their lives.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Fumar Maconha/epidemiologia , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/terapia , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Transtornos Relacionados ao Uso de Anfetaminas/terapia , Austrália/epidemiologia , Cannabis , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Feminino , Humanos , Masculino , Fumar Maconha/psicologia , Fumar Maconha/terapia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Adulto Jovem
16.
Expert Opin Pharmacother ; 20(18): 2273-2293, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671001

RESUMO

Introduction: Drug use related deaths are increasing and the lack of effective treatment for psychostimulants can be largely held responsible. Particularly, no pharmacotherapy is approved for methamphetamine (METH) use disorder despite decades of research. Only psychosocial interventions are clinically used, with limited long-term recovery and relapse.Areas covered: This review aims to select and describe the most relevant findings to date. Selected clinical trials were found in PubMed using the following keywords ('methamphetamine') and ('addiction' OR 'withdrawal' OR 'treatment' OR 'pharmacotherapy'). Randomized placebo-controlled trials enrolling treatment-seeking METH-dependent subjects and inherent secondary analysis were included.Expert opinion: Overall, end-of-treatment abstinence, reduced METH use or lower relapse rates were seen on METH dependent subgroups or attained significance only following post hoc analysis, irrespective of the medication tested. For example, light and heavy METH users seem to respond differently to pharmacotherapy. This together with the heterogeneous nature of the METH dependent population strongly suggests that some drugs herein described (e.g. mirtazapine, methylphenidate) should be further tested in clinical trials focused on subgroups. Lastly, objective measures, such as urinalysis, are mandatory to include in clinical trials and early treatment response and/or medication compliance should be carefully monitored and considered as predictors of success/failure.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metanfetamina/efeitos adversos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Humanos , Masculino , Metilfenidato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Med Sci Monit ; 25: 8515-8526, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712546

RESUMO

BACKGROUND Methamphetamine (METH), a confirmed neurotoxic drug, has also reportedly caused several intestinal inflammatory injury cases. The NLRP3 (Nod-like receptor 3 protein) inflammasome can induce several inflammatory injuries by activating IL-1ß and IL-18 when overexpressed. We designed experiments to determine whether METH can cause intestinal inflammatory injury via NLRP3 inflammasome overexpression. MATERIAL AND METHODS IEC-6 cells were classified as control, METH (0.5 mM), and METH (0.5 mM)+MCC950 (100 µM) groups. C57BL/6 mice were separated into control, NS, METH (5 mg/kg), and METH (5 mg/kg)+MCC950 (10 mg/kg) groups (n=10). We detected apoptosis, transepithelial electrical resistance (TEER), and proinflammatory factors (IL-6, INF-γ, TNF-alpha, and NF-kappaB) in the METH cell model. We also assessed proinflammatory factors (IL-6, INF-γ, TNF-alpha, and NF-kappaB) and observed intestinal tissues stained with hematoxylin and eosin (HE) in the METH animal model to explore intestinal inflammatory injury due to METH. After adding MCC950 (an NLRP3 inflammasome inhibitor), we additionally detected NLRP3 inflammasome components (NLRP3, Caspase-1, and ASC), IL-1ß, and IL-18 to estimate the relationship of the NLRP3 inflammasome with intestinal inflammatory injury due to METH. RESULTS METH can lead apoptosis, increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-alpha, and NF-kappaB), and decrease TEER in the METH cell model. In the METH animal model, METH can cause obvious injury and increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-alpha, and NF-kappaB). All the intestinal inflammatory changes due to METH depended on overexpression of the NLRP3 inflammasome and could be ameliorated by MCC950, except for ASC and NF-kappaB. CONCLUSIONS METH, in addition to being a confirmed neurotoxic drug, can also cause severe intestinal inflammatory injury via NLRP3 inflammasome overexpression. NF-kappaB may be an activator of the NLRP3 inflammasome in METH intestinal inflammatory injury.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Metanfetamina/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/metabolismo , Masculino , Metanfetamina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA
18.
Psychiatry Res ; 281: 112599, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31629302

RESUMO

A continuously rising consumption of methamphetamine (MA) has been suggested to be associated with increasing cognitive dysfunction. The objective of this study was to investigate associations between cognitive functions and gender, drug using patterns and treatment-attending profiles of recently abstinent MA users over the course of six months abstinence. Data were collected from 108 participants in two inpatient rehabilitation centers. The mean duration of MA use was 11.5 years. Interviews and cognitive tests (cognitrone, Stroop, TMT, nback) were performed right after the withdrawal and again after approx. six months of abstinence. Comparisons and explorative analyses between the groups (gender, primary MA/ multidrug users, early dropouts/ completers) regarding cognitive variables were performed. At baseline a significant decline in general neuropsychological functioning and attention/concentration after ongoing years of consumption were found. After a period of six months abstinence, cognitive performances remained stable or improved significantly for cognitrone percentile and cognitive flexibility. Normal cognitive functions were measured in former MA users after acute withdrawal which remained stable and partly improved in those patients who refrained from substance abuse over six months. Continued long-term MA intake was the only identified indicator of poorer cognitive performance. These results point towards a regain of cognitive performance in patients abstinent from MA.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Transtornos Cognitivos/psicologia , Cognição/fisiologia , Metanfetamina/efeitos adversos , Síndrome de Abstinência a Substâncias/psicologia , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/epidemiologia , Fatores de Tempo , Adulto Jovem
19.
Clin Ter ; 170(5): e337-e338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612189

RESUMO

In this letter, which is meant as a response to the letter titled "Sex enhancers: challenges, threats and the need for targeted measures", the Authors discuss the evolution of Chemsex phenomenon towards at least two directions: firstly, the use of psychoactive and non-psychoactive substances usually implicated in Chemsex, such as GHB/GBL, ketamine, mephedrone and other synthetic cathinones and erectile dysfunction medications, is currently accompanied by the use of illicit opioids, which have recently been indicated as a new serious health threat for consumers. In addition, as reported by the last European Drug report, the simultaneous use of illicit benzodiazepines with non-medical opioids misuse has also been observed. Secondly, strictly linked to the rising use of non-medical opioids is the risk of transition towards heroine followed by the adoption of risky injection practices frequently accompanied by high-risk sexual behaviors. In this sense, the current definition of the phenomenon as "the voluntary intake of certain psychoactive and non- psychoactive drugs in the context of sex parties and sexual intercourses with the intention of facilitating and/or enhancing the sexual encounter mostly among men who have sex with other men (MSM)" has been expanded to "heterosexual chemsex".


Assuntos
Drogas Ilícitas/efeitos adversos , Psicotrópicos/efeitos adversos , Comportamento Sexual/estatística & dados numéricos , Sexo sem Proteção/estatística & dados numéricos , Adulto , Humanos , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Psicotrópicos/administração & dosagem , Saúde Sexual/estatística & dados numéricos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias , Inquéritos e Questionários
20.
PLoS One ; 14(10): e0220270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600226

RESUMO

BACKGROUND: Methamphetamine (MA) is a potent agonist at the trace amine-associated receptor 1 (TAAR1). This study evaluated a common variant (CV) in the human TAAR1 gene, synonymous single nucleotide polymorphism (SNP) V288V, to determine the involvement of TAAR1 in MA dependence. METHODS: Participants (n = 106) with active MA dependence (MA-ACT), in remission from MA dependence (MA-REM), with active polysubstance dependence, in remission from polysubstance dependence, and with no history of substance dependence completed neuropsychiatric symptom questionnaires and provided blood samples. In vitro expression and function of CV and wild type TAAR1 receptors were also measured. RESULTS: The V288V polymorphism demonstrated a 40% increase in TAAR1 protein expression in cell culture, but message sequence and protein function were unchanged, suggesting an increase in translation efficiency. Principal components analysis resolved neuropsychiatric symptoms into four components, PC1 (depression, anxiety, memory, and fatigue), PC2 (pain), PC3 (drug and alcohol craving), and PC4 (sleep disturbances). Analyses of study group and TAAR1 genotype revealed a significant interaction for PC3 (craving response) (p = 0.003). The control group showed no difference in PC3 associated with TAAR1, while adjusted mean craving for the MA-ACT and MA-REM groups, among those with at least one copy of V288V, was estimated to be, respectively, 1.55 (p = 0.036) and 1.77 (p = 0.071) times the adjusted mean craving for those without the TAAR1 SNP. CONCLUSIONS: Neuroadaptation to chronic MA use may be altered by TAAR1 genotype and result in increased dopamine signaling and craving in individuals with the V288V genotype.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/genética , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas-G/genética , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Transtornos Relacionados ao Uso de Anfetaminas/patologia , Linhagem Celular , Fissura , Dopamina/genética , Dopamina/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Humanos , Masculino , Metanfetamina/administração & dosagem , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas-G/biossíntese
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