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1.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34067981

RESUMO

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.


Assuntos
Broncodilatadores/uso terapêutico , Metanfetamina/efeitos adversos , Pseudoefedrina/uso terapêutico , Medição de Risco/métodos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Humanos , Metanfetamina/química , Transtornos Relacionados ao Uso de Substâncias/etiologia
2.
BMJ Open ; 11(5): e044696, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006547

RESUMO

OBJECTIVES: To examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence. DESIGN: A dose-escalating, phase-2, open-label, single-group study of oral LDX at two Australian drug treatment services. SETTING: The study was conducted at two Australian stimulant use disorder treatment clinics. PARTICIPANTS: There were 16 participants: at least 18 years old, MA dependent for at least the preceding 2 years using ICD-10 criteria, reporting use of MA on at least 14 of the preceding 28 days. INTERVENTIONS: Daily, supervised LDX of 100-250 mg, single-blinded to dose, ascending-descending regimen over 8 weeks (100-250 mg over 4 weeks; followed by 4-week dose reduction regimen, 250-100 mg). Participants were followed through to week 12. OUTCOMES: Primary outcomes were safety, drug tolerability and regimen completion at the end of week 4. Participants were followed to week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence and neurocognitive functioning. RESULTS: Fourteen of 16 participants (87.5%) completed escalation to 250 mg/day. Two participants withdrew from the trial in the first week: one relocated away from the study site, the other self-withdrew due to a possible, known side effect of LDX (agitation). There was one serious adverse event of suicidal ideation which resolved. All other adverse events were mild or moderate in severity and known side effects of LDX. No participant was withdrawn due to adverse events. MA use decreased from a median of 21 days (IQR: 16-23) to 13 days (IQR: 11-17) over the 4-week escalation period (p=0.013). CONCLUSIONS: LDX at a dose of up to 250 mg/day was safe and well tolerated by study participants, warranting larger trials as a pharmacotherapy for MA dependence. TRIAL REGISTRATION NUMBER: ACTRN12615000391572.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Austrália , Estimulantes do Sistema Nervoso Central/efeitos adversos , Método Duplo-Cego , Humanos , Dimesilato de Lisdexanfetamina , Metanfetamina/efeitos adversos , Resultado do Tratamento
4.
Curr Opin Psychiatry ; 34(4): 344-350, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965972

RESUMO

PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.


Assuntos
Analgésicos Opioides/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Fentanila/envenenamento , Overdose de Opiáceos/epidemiologia , Epidemia de Opioides/estatística & dados numéricos , Cocaína/envenenamento , Comorbidade , Overdose de Drogas/epidemiologia , Humanos , Drogas Ilícitas/envenenamento , Metanfetamina/envenenamento
5.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946401

RESUMO

The deposition of amyloid-beta (Aß) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer's disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the "Molecule Activity Predictor" feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Proteína HMGB1/metabolismo , Metanfetamina/farmacologia , Doença de Alzheimer/metabolismo , Animais , Estimulantes do Sistema Nervoso Central/uso terapêutico , Humanos , Metanfetamina/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
Analyst ; 146(10): 3336-3345, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33999061

RESUMO

The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current approaches require complex sample purification strategies alongside significant analysis time. Given the high prevalence of MA within the global drug market, there remains a need for rapid, portable and alternative screening approaches appropriate for direct detection within biological matrices for employment across the forensic and clinical environments. This contribution illustrates the use of an electrochemiluminescence (ECL) strategy for the screening of MA, amphetamine (AMP) and para hydroxy-methamphetamine (pOH-MA) for such applications. The sensing system showed ideal analytical performance with linear ranges at forensically relevant concentrations of 0.1 µM to 0.5 mM for MA, 10 µM to 1 mM AMP and 10 µM to 5 mM for pOH-MA, and superb detection limits of 74.6 nM, 6 µM and 82. µM for MA, AMP and pOH-MA respectively. Furthermore, the sensor was successful in the detection of MA, AMP and pOH-AMP within human pooled serum, artificial urine and saliva, without any prior purification strategies. Here a portable ECL sensor is detailed for the successful employment of the direct screening of these amphetamine type substances and their corresponding metabolites at clinically and forensically relevant concentrations within a range of biological matrices. This approach successfully represents a strong proof-of-concept, for a novel, simple and rapid screening method with significant potential for high-throughput screening of biological samples for drug metabolites, widening the avenues where ECL sensors could be employed.


Assuntos
Metanfetamina , Anfetamina , Humanos , Medições Luminescentes , Saliva , Detecção do Abuso de Substâncias
7.
Water Res ; 197: 117007, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813169

RESUMO

The article presented by Wang et al. (2020) intends to elucidate the possible ecological effects of low (0.05-25 µg L-1) and higher (100 µg L-1) concentrations of methamphetamine on adult Oryzias latipes through a battery of assays, including histopathology. However, we found several mistakes and inaccuracies in the findings by means of this method. Given the increasing research effort in the field, the authors' paper may become highly influential in future toxicological research. Despite the authors' undoubted effort invested in their experiment, they did not employ standardized methods for histopathological assessment in the key laboratory experiment presented in their paper.


Assuntos
Metanfetamina , Oryzias , Poluentes Químicos da Água , Animais , Ecossistema , Metanfetamina/toxicidade , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Sci Total Environ ; 782: 146839, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836378

RESUMO

Consumption of methamphetamine has primarily been estimated in wastewater-based epidemiology by measuring the parent compound. However, this could lead to overestimation when methamphetamine is directly disposed into the sewer system. In this respect, it would be advantageous to measure a specific metabolite of methamphetamine instead. We identified 4-hydroxymethamphetamine (pholedrine) as a potential marker. Stability experiments were performed in both filtered and unfiltered wastewater. Correlations with relative loads in wastewater were used to establish its potential as a marker of direct disposal of methamphetamine, or even as a wastewater-based epidemiology biomarker of methamphetamine consumption. This study then investigated the use of pholedrine in combination with methamphetamine to better detect direct disposal events and its potential as a marker of methamphetamine consumption. Examples from both South Australia and New Zealand exemplify the use of pholedrine to identify potential instances of direct disposal of methamphetamine.


Assuntos
Metanfetamina , Poluentes Químicos da Água , Biomarcadores , Metanfetamina/análogos & derivados , Nova Zelândia , Austrália do Sul , Detecção do Abuso de Substâncias , Águas Residuárias , Poluentes Químicos da Água/análise
9.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803075

RESUMO

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A2A receptor (A2AR). First, we noticed that methamphetamine does not affect A2A functionality if the receptor is expressed in a heterologous system. However, A2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB1 receptor (CB1R) and the sigma 1 receptor (σ1R). Signaling via both adenosine A2AR and cannabinoid CB1R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A2AR-CB1R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A2AR- and the CB1R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ1R, alters the expression and function of two interacting receptors, A2AR, which is a therapeutic target for neuroprotection, and CB1R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.


Assuntos
Antagonistas do Receptor A2 de Adenosina/farmacologia , Corpo Estriado/metabolismo , Metanfetamina/farmacologia , Neurônios/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptores sigma/metabolismo , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos
10.
J Med Case Rep ; 15(1): 183, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810803

RESUMO

BACKGROUND: Urinary retention is a condition in which impaired emptying of the bladder results in postvoid residual urine. It can be acute or chronic urinary retention. There have been only scattered case studies that have described urinary retention resulting from methamphetamine use. This case report is aimed at raising awareness about methamphetamine abuse as an important factor in the aetiological considerations when evaluating cases of urinary retention among healthy younger age groups. CASE PRESENTATION: We report a patient who had acute urinary retention after brief amphetamine use. A 26-year-old Nigerian man presented at the emergency room on account of an inability to pass urine and lower abdominal pain. Before this incident, the patient reported a recent ingestion of amphetamine to achieve weight reduction and a fit body. A week after use, he started to experience difficulty passing out urine hence necessitating a visit to the emergency department. After a brief assessment, physical examination revealed a man in painful distress with mild suprapubic fullness. He had a successful passage of a urethral catheter for continuous bladder drainage with dramatic improvement in his symptoms. He was subsequently discontinued on methamphetamine use and referred to a urologist for further evaluation. CONCLUSION: Most cases of urinary retention are diagnosed clinically and are rarely missed. But because urinary retention is associated with a wide range of aetiological factors, clinicians need to be aware of the effects of certain drugs in the aetiology of urinary retention. In the management of a case of urinary retention in the younger age group, clinicians should enquire about a history of drug use, the drug of particular interest being methamphetamine, and also employ the use of urodynamic studies in the evaluation of such cases.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Retenção Urinária , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Humanos , Masculino , Metanfetamina/efeitos adversos , Bexiga Urinária , Retenção Urinária/induzido quimicamente
11.
BMC Genomics ; 22(1): 259, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845768

RESUMO

BACKGROUND: Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine. RESULTS: Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts than male hearts both in terms of the number of genes affected and the magnitude of the changes. The largest changes in female hearts involved genes that regulate the circadian clock (Dbp, Per3, Per2, BMal1, and Npas2) which are known to impact myocardial ischemic injury. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. CONCLUSIONS: These data demonstrate that female rats are more sensitive than males to methamphetamine-induced changes in the myocardial transcriptome and that methamphetamine does not induce changes in myocardial transcription that persist long term after exposure to the drug has been discontinued.


Assuntos
Relógios Circadianos , Metanfetamina , Animais , Ritmo Circadiano , Feminino , Coração , Masculino , Miocárdio , Ratos , Transcrição Genética
12.
Chemosphere ; 278: 130393, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33823350

RESUMO

Recognition of misused stimulant drugs has always been a hot topic from a medical and judicial perspective. Methamphetamine (MAMP) is an addictive and illegal drug that profoundly affects the central nervous system. Like other illicit drugs, the detection of MAMP in biological and street samples is vital for several organizations such as forensic medicine, anti-drug headquarters and diagnostic clinics. By emerging nanotechnology and exploiting nanomaterials in sensing applications, a great deal of attention has been given to the design of analytical sensors in MAMP tracing. For the first time, this study has briefly reviewed all the optical and electrochemical sensors in MAMP detection from earlier so far. How various receptors with engineering nanomaterials allow developing novel approaches to measure MAMP have been studied. Fundamental concepts related to optical and electrochemical recognition assays in which nanomaterials have been used and relevant MAMP sensing applications have been comprehensively covered. Challenges, opportunities and future outlooks of this field have also been discussed at the end.


Assuntos
Técnicas Biossensoriais , Drogas Ilícitas , Metanfetamina , Nanoestruturas , Técnicas Eletroquímicas , Nanotecnologia
13.
J Stud Alcohol Drugs ; 82(2): 197-203, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823966

RESUMO

OBJECTIVE: Inhibitory deficits contribute to impulsive drug-seeking behavior in individuals with methamphetamine use disorder (MUD). Whether abstinent individuals with MUD exhibit greater cognitive disinhibition when the suppressed response is associated with drug-related images is not fully known. This study evaluated the potency of drug-associated cue exposure in this process. METHOD: We recruited 54 abstinent men with MUD and 46 healthy control (HC) subjects to complete a novel go/no-go task in which drug-associated cues were presented in 240 trials. RESULTS: Upon exposure to drug-associated cues, the numbers of commission errors increased significantly only in the abstinent MUD group (p < .001), and the abstinent MUD group produced higher levels of commission errors than the HC group (p = .009). When drug-associated cues were not available (in scrambled trials), the abstinent MUD group produced similar levels of commission errors when compared with the HC group (p = .336). The reaction times in drug cue exposure trials were longer than in scrambled trials across groups (p < .001), whereas the abstinent MUD group produced shorter reaction times than HCs, regardless of trial conditions (p = .004). CONCLUSIONS: The novel go/no-go task is a useful method for detecting impulsivity in abstinent individuals with MUD. Cue exposure triggers impairment of inhibitory control in individuals with MUD at abstinence.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Sinais (Psicologia) , Metanfetamina/administração & dosagem , Adulto , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Pessoa de Meia-Idade , Tempo de Reação , Adulto Jovem
14.
ACS Chem Neurosci ; 12(9): 1552-1562, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33871963

RESUMO

Methamphetamine (MA), a potent central nervous system stimulant, mainly affects the brain dopaminergic and serotoninergic systems. Monoamine oxidase, catechol-O-methyltransferase, and aldehyde dehydrogenase 2 (ALDH2) are important enzymes in the metabolism of dopamine (DA) and serotonin (5-HT); however, the role of ALDH2 in MA addiction remains unclear. This study focused on the real-time changes in DA, 5-HT, and their metabolites, including 3,4-dihydroxyphenylacetic aldehyde and salsolinol, which are metabolites directly related to ALDH2, to examine the effects of the inhibition of ALDH2 on hyperlocomotion induced by MA. Locomotor activity was evaluated in rats after administration of MA and/or CVT-10216 (a selective ALDH2 inhibitor). Moreover, the simultaneous quantification of DA, 5-HT, and their metabolites in brain microdialysates of the rats was performed using a derivatization-assisted LC-MS/MS method after full validation. The validation results proved the method to be selective, sensitive, accurate, and precise, with acceptable linearity within calibration ranges. Intraperitoneal (i.p.) administration of 10 or 20 mg/kg of CVT-10216 significantly decreased MA-induced hyperlocomotion (1 mg/kg, i.p.). The analytical results of rat brain microdialysates demonstrated that the administration of CVT-10216 significantly downregulated DA levels, which were increased upon exposure to MA. Moreover, the increase in 3-methoxytyramine levels following coadministration of CVT-10216 and MA could play a potential role in antagonizing the hyperlocomotion induced by MA. All of these findings suggest that the inhibition of ALDH2 protects against MA-induced hyperlocomotion and has therapeutic potential in MA addiction.


Assuntos
Metanfetamina , Aldeído Desidrogenase , Aldeído-Desidrogenase Mitocondrial , Animais , Encéfalo , Catecol O-Metiltransferase , Cromatografia Líquida , Isoflavonas , Microdiálise , Ratos , Espectrometria de Massas em Tandem
15.
Molecules ; 26(9)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922144

RESUMO

Methamphetamine (METH) is a synthetic psychostimulant drug that has detrimental effects on the health of its users. Although it has been investigated as a cause of neurodegenerative disease due to its neurotoxicity, whether small molecules derived from natural products attenuate these side effects remains elusive. 6,7,4'-trihydroxyflavanone (THF) is a flavanone family that possesses various pharmacological activities, including anti-rheumatic, anti-ischemic, anti-inflammatory, anti-osteoclastogenic, and protective effects against METH-induced deactivation of T cells. However, little is known about whether THF protects neuronal cells from METH-induced neurotoxicity. Here, we investigated the protective effects of THF on neurotoxicity induced by METH exposure by enhancing the Nrf2/HO-1 and PI3K/Akt/mTOR signaling pathways in SH-SY5y cells. Treatment with THF did not lead to cytotoxicity, but attenuated METH-induced neurotoxicity by modulating the expression of apoptosis-related proteins, METH-induced oxidative stress, and PI3K/Akt/mTOR phosphorylation in METH-exposed SH-SY5y cells. Moreover, we found THF induced Nrf2 nuclear translocation and HO-1 expression. An inhibitor assay confirmed that the induction of HO-1 by THF attenuates METH-induced neurotoxicity. Therefore, we suggest that THF preserves neuronal cells from METH-induced neurotoxicity by upregulating HO-1 expression through the Nrf2 and PI3K/Akt/mTOR signaling pathways. Thus, THF has therapeutic potential for use in the treatment of METH-addicts suffering from neurodegenerative diseases.


Assuntos
Flavanonas/farmacologia , Heme Oxigenase-1/metabolismo , Metanfetamina/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo , Fosforilação , Transdução de Sinais/efeitos dos fármacos
17.
Molecules ; 26(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923340

RESUMO

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophagy.


Assuntos
Curcumina/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Curcuma/química , Curcumina/química , Humanos , Metanfetamina/toxicidade , Fármacos Neuroprotetores/química , Síndromes Neurotóxicas/patologia , Células PC12 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos
18.
BMJ Case Rep ; 14(3)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785605

RESUMO

We report a case of a 20-year-old man who was diagnosed with spontaneous spinal cord infarction after abusing methamphetamine for a year. He presented with sudden onset of bilateral upper and lower limb weakness. His MRI spine showed a long segment of high signal intensity seen predominantly in the anterior spinal cord from medulla to mid thoracic level as well as a pencil-like hyperintensity seen postcontrast suggestive of spinal cord ischaemia or infarct. Thus, he was empirically treated for presumed anterior spinal cord infarction. He then developed autonomic dysfunction and went into respiratory distress, which required invasive mechanical ventilation support. Subsequently, he developed cardiac arrythmia with supraventricular tachycardiac followed by asystole and succumbed to illness on day 9 despite maximal resuscitative efforts. This case report illustrates a rare spinal cord infarction caused by methamphetamine intoxication and the importance of identifying and treating it early.


Assuntos
Metanfetamina , Isquemia do Cordão Espinal , Adulto , Humanos , Infarto/induzido quimicamente , Infarto/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Metanfetamina/efeitos adversos , Medula Espinal , Isquemia do Cordão Espinal/diagnóstico , Isquemia do Cordão Espinal/etiologia , Adulto Jovem
19.
Eur J Pharmacol ; 900: 174066, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33789156

RESUMO

Methamphetamine (MA) abuse is associated with the development of pulmonary arterial hypertension (PAH) and subsequent right ventricular failure. A recent clinical study demonstrated that female sex is a major risk factor for MA-induced PAH. The mechanisms associated with increased prevalence and severity of MA-induced PAH in females are still unclear. We hypothesized that MA may promote changes in gene expression in the right ventricle contributing to the development and/or worsening of PAH in females. Male and female C57BL/6 mice were treated with either MA or vehicle. Right and left ventricular systolic pressures (RVSP and LVSP, respectively) were assessed and tissue samples were collected for gene expression and histology. LVSP and RVSP were not affected by MA in either males or females. Right ventricular hypertrophy was significantly increased by MA in females but it was not affected by MA in males. In the female mice, MA-induced right ventricular hypertrophy was associated with increased expression of brain natriuretic peptide gene and members of the TGF-ß receptor signaling pathway such as TGF-ß receptor-1, smad3 and smad7. In male mice, there were no changes in right ventricular gene expression. Our results suggest that MA caused right ventricular hypertrophy in female mice, but not in males and that this was associated with an increase in hypertrophic genes. The right ventricular hypertrophy was not dependent on increased RVSP suggesting a direct effect of MA on the right ventricle. If this translates to PAH patients, it might explain the poor outcome observed in MA-associated female PAH patients.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Hipertrofia Ventricular Direita/genética , Metanfetamina/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/genética , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hipertensão Arterial Pulmonar/genética , Receptores de Fatores de Crescimento Transformadores beta/efeitos dos fármacos , Caracteres Sexuais , Transdução de Sinais/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
20.
Int J Mol Sci ; 22(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668155

RESUMO

Although traumatic brain injury (TBI) causes hospitalizations and mortality worldwide, there are no approved neuroprotective treatments, partly due to a poor understanding of the molecular mechanisms underlying TBI neuropathology and neuroprotection. We previously reported that the administration of low-dose methamphetamine (MA) induced significant functional/cognitive improvements following severe TBI in rats. We further demonstrated that MA mediates neuroprotection in part, via dopamine-dependent activation of the PI3K-AKT pathway. Here, we further investigated the proteomic changes within the rat cortex and hippocampus following mild TBI (TM), severe TBI (TS), or severe TBI plus MA treatment (TSm) compared to sham operated controls. We identified 402 and 801 altered proteins (APs) with high confidence in cortical and hippocampal tissues, respectively. The overall profile of APs observed in TSm rats more closely resembled those seen in TM rather than TS rats. Pathway analysis suggested beneficial roles for acute signaling through IL-6, TGFß, and IL-1ß. Moreover, changes in fibrinogen levels observed in TSm rats suggested a potential role for these proteins in reducing/preventing TBI-induced coagulopathies. These data facilitate further investigations to identify specific pathways and proteins that may serve as key targets for the development of neuroprotective therapies.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Dopaminérgicos/farmacologia , Espectrometria de Massas/métodos , Metanfetamina/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteoma/metabolismo , Animais , Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Masculino , Proteoma/análise , Ratos , Ratos Wistar , Transdução de Sinais
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