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1.
PLoS One ; 15(3): e0227044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203565

RESUMO

Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels.


Assuntos
Comportamento Animal/efeitos dos fármacos , Cocaína/efeitos adversos , Etanol/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Animais , Cocaína/administração & dosagem , Modelos Animais de Doenças , Etanol/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Ratos , Reforço Psicológico , Autoadministração/efeitos adversos , Autoadministração/psicologia , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tirosina/sangue
2.
Forensic Sci Int ; 305: 110004, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707239

RESUMO

This study aims to investigate the prevalence of alcohol and drugs of abuse in Italian drivers involved in road traffic crashes between 2011 and 2018. Toxicological analyses were performed on the whole blood of 7593 injured drivers. Alcohol and illicit drugs, namely tetrahydrocannabinol (THC; cut-off 2ng/ml), cocaine (cut-off 10ng/ml), illicit opiates (cut-off 10ng/ml) and amphetamines (amphetamine, methamphetamine, MDMA, MDA; cut-off 20ng/ml) were investigated. The age and gender of the driver, the time of the crash (weekend/weekday and day/night), the road crash year and Blood Alcohol Concentration (BAC) were also considered. The 16.2% of samples tested positive for alcohol, 2.5% for cocaine, followed by opiates (2.0%), cannabinoids (1.5%), and amphetamines (0.5%). The overall prevalence of alcohol and drugs was lower than those reported in previous epidemiological studies of the DRUID project. The year 2011 showed the highest prevalence of drug-positive cases (24.1%), while the lowest prevalence was found in 2016 (16.8%), after the update of the Road Traffic Law (RTL) that increased punishments for driving under the influence. A progressive increase in the number of alcohol-positive female drivers was observed from 2011 to 2018, and the highest prevalence was found in the 26-35-year-old age range. Illicit drugs showed the highest overall prevalence in drivers <26 years of age but, if considering single drugs, cocaine and opiates were mostly found in subjects older than 36 years of age. A higher percentage of drug-positive drivers was found on weekend nights for alcohol and on both weekend and weekday nights for drugs. The types of drugs used by drivers did not change during the studied period.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Concentração Alcoólica no Sangue , Dirigir sob a Influência/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Distribuição por Idade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(9): 1134-1138, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31594160

RESUMO

Objective: To understand the serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), and thyroxine (T4) and identify the related influencing factors of thyroid dysfunction in drug users. Methods: From June to August 2018, a face-to-face questionnaire survey was conducted in 788 male drug users in a drug rehabilitation center in Jiangsu province to collect their socio-demographic information. Then, venous blood sample was collected from each participant for the detection of various hematological indicators, such as thyroid hormones. Results: The abnormal rates of T3, T4, FT3, FT4 and TSH were 4.57%, 1.27%, 0.51%, 0.38% and 0.89%, respectively, in the male drug users. HCV infection was an influencing factor for abnormal T3 level in the male drug users (OR=8.52, 95%CI: 2.36-30.74, P=0.001). And serum T3 (P<0.001) and T4 (P=0.048) levels increased with increasing HCV viral load. Conclusions: HCV infection was an influencing factor for the abnormality of serum T3 level in drug users. Therefore, thyroid-related knowledge should be added in the health education for drug users, and the monitoring of thyroid function should be strengthened for drug users infected with HCV.


Assuntos
Usuários de Drogas , Centros de Tratamento de Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Hormônios Tireóideos/sangue , China , Humanos , Masculino , Tireotropina , Tiroxina , Tri-Iodotironina
4.
Intern Med ; 58(18): 2627-2632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527368

RESUMO

Objective In the management of patients with suspected acute drug poisoning, a screening test using the patient's urine is usually performed. The Triage DOA® and INSTANT-VIEW M-1® kits are two commonly used point-of-care screening kits in Japan. However, the relationship between the results of these screening kits and the blood concentration of the poisoning drug is not clear. In this study, we evaluated which kit is more useful for acute drug poisoning screening based on a comparison of their results with the results of a serum drug analysis. Methods This prospective cross-sectional study investigated all patients with acute drug poisoning admitted to a general hospital in Tokyo, Japan, over a nine-month period. The Triage DOA® and INSTANT-VIEW M-1® screening kits were used, and a qualitative serum analysis was conducted simultaneously in all cases. We compared the kits for use in screening patients with acute drug poisoning and evaluated the utility of the kits. Results For the 117 patients enrolled in this study, the 2 kits showed different sensitivities to benzodiazepines (Triage®, 78.6%; INSTANT-VIEW®, 90.5%). Both kits showed high sensitivity to barbiturates (Triage®, 87.0%; INSTANT-VIEW®, 91.3%) but low sensitivity to tricyclic antidepressants (Triage®, 25.0%; INSTANT-VIEW®, 45.8%). Conclusion Because the sensitivity varies depending on the kind of drug, it is difficult to discuss the superiority of these kits. However, this study compared the results of two types of urinary drug screening kits with the results of qualitative analysis of drugs in serum as a gold standard, providing important reference data.


Assuntos
Programas de Rastreamento/métodos , Kit de Reagentes para Diagnóstico , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Triagem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos Tricíclicos/sangue , Antidepressivos Tricíclicos/urina , Barbitúricos/sangue , Barbitúricos/urina , Benzodiazepinas/sangue , Benzodiazepinas/urina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tóquio , Adulto Jovem
5.
Forensic Sci Int ; 303: 109958, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31542401

RESUMO

The routine analysis of driver specimens for gamma-hydroxybutyrate (GHB) is rarely performed by toxicology laboratories as the physical and chemical properties of GHB make it unamenable to the screening methods usually employed. The prevalence of the drug in driver populations has therefore only rarely been reported. This study outlines the results of the routine analysis for GHB in the blood of motor vehicle drivers in Queensland, Australia, over an eight-year period (2011-2018). The methodology for GHB analysis was updated over the course of the study; screening for GHB was conducted using GC/FID or GC/MS between 2011 and 2016 and by LC/MS/MS from 2017 onwards. Due to the endogenous nature of GHB, any specimens containing greater than 5mg/kg GHB were subjected to quantitative analysis by either; GC/MS after liquid-liquid extraction and derivatisation with BSTFA+1%TMCS (2011-2016), or by LC/MS/MS analysis after solvent precipitation from 2017 onwards. Of the 15,061 specimens analysed, 160 were positive for GHB (1.1% of all cases, range 0.4-1.8%). GHB positive drivers were 66.9% male (33.1% female) and had an average age of 32 years. The mean GHB concentration identified was 89mg/kg (range 6-354mg/kg). GHB was found to be closely associated with amphetamine type substances (ATS), particularly methylamphetamine. Though GHB was present in only 2.2% of all ATS positive specimens submitted to the laboratory, 91.2% of all GHB positive cases contained an ATS. Other drugs commonly co-administered with GHB were THC, cocaine, benzodiazepines and erectile dysfunction drugs. GHB was found to be more commonly identified in drivers from city areas and a geographical localisation of the use of the drug was identified in the Gold Coast region of Queensland.


Assuntos
Anfetaminas/sangue , Dirigir sob a Influência , Oxibato de Sódio/sangue , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Austrália/epidemiologia , Benzodiazepinas/sangue , Feminino , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Entorpecentes/sangue , Inibidores da Fosfodiesterase 5/sangue , Citrato de Sildenafila/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Tadalafila/sangue
6.
Hum Exp Toxicol ; 38(11): 1244-1253, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31319705

RESUMO

Prolactin (PRL) levels can usually be controlled by PRL-inhibiting psychiatric drugs that include anti-dopamine agents. However, the use of dopamine (DA) antagonists may lead to hyperprolactinemia under certain clinical conditions. The aim of this study was to investigate postmortem PRL levels as potential markers of drug abuse, especially that of DA antagonists, in autopsy cases. We examined 121 autopsy cases, excluding cases involving acute hypoxia/ischemia, such as asphyxia, because PRL concentrations are reportedly increased under acute hypoxic conditions. Detected drugs were classified as either DA antagonists, stimulants, psychotropic drugs other than DA antagonists, or other non-psychotropic drugs, and many cases had no detected drugs. Samples comprised blood collected from the right heart chamber and cerebrospinal fluid (CSF). PRL protein level was measured by chemiluminescent immunoassay, and PRL gene expression in the anterior pituitary of autopsy cases was analyzed by reverse transcription-polymerase chain reaction. The PRL-positive cell ratio in the anterior pituitary gland was also measured by immunohistochemical analysis. The results indicated that PRL levels in the serum and CSF were higher in DA antagonist cases than in other cases. PRL levels in the serum and CSF also correlated with the PRL gene expression in cases with abuse of DA antagonists. However, no significant difference in the PRL-positive cell ratio in the anterior pituitary gland was evident between any of the classes of drug-detected and drug-undetected cases. These results suggest that postmortem measurements of PRL transcription levels may be useful for diagnosing cases of DA antagonist use.


Assuntos
Antagonistas de Dopamina , Prolactina/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Dopamina/sangue , Feminino , Expressão Gênica , Ginecomastia/sangue , Ginecomastia/líquido cefalorraquidiano , Ginecomastia/diagnóstico por imagem , Ginecomastia/genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Prolactina/sangue , Prolactina/líquido cefalorraquidiano , Psicotrópicos , RNA Mensageiro/metabolismo , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/líquido cefalorraquidiano , Adulto Jovem
7.
J Clin Neurosci ; 65: 11-16, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076249

RESUMO

Schizophrenia (SCH) and drug addiction are chronic disorders that are frequently accompanied by physical diseases, poor nutrition and reduced self-care, all of which are likely to result in vitamin deficiencies. The objective of this study was to compare vitamin levels in SCH patients, substance use disorder (SUD) patients and healthy controls (HCs). The study included 189 SCH patients, 119 SUD patients and 109 HCs. Information on vitamin B12, folic acid and vitamin D levels were retrieved from the hospital's database, and mean values and deficiency/insufficiency were evaluated. Vitamin D deficiency (<30 ng/ml) was more common in the SCH group than in the SUD and HC groups (88.4%, 74.8% and 86.4%, respectively). Although there were no significant differences in folic acid deficiency (<3.0 ng/ml) in the SUD and SCH groups (15.1% and 8.5%, respectively), the incidence of folic acid deficiency was significantly higher in both groups as compared with that in the HC group (5.8%). Significantly higher numbers of patients in the SCH group than in the SUD group had vitamin B12 deficiency (45.5% vs. 28.3%). The prevalence of vitamin B12 deficiency in the SUD group was significantly higher than that the HC group (28.3% vs.11.5%). As compared with the HC group, vitamin D and B12 levels were significantly lower in SCH group, and folic acid and B12 levels were significantly lower in the SUD group. Several vitamin deficiencies appear to be common in both SCH and SUD. Possible reasons should be investigated.


Assuntos
Deficiência de Ácido Fólico/epidemiologia , Esquizofrenia/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Deficiência de Vitamina B 12/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Feminino , Ácido Fólico/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Vitamina B 12/sangue , Vitamina D/sangue
8.
J Forensic Leg Med ; 65: 101-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129558

RESUMO

Structural analogs of classic drugs, also called designer drugs, are a booming market due to the easy accessibility on the internet and their legal status. One of those 'legal highs' is an analog of phencyclidine, namely 3-methoxyphencyclidine (3-MeO-PCP). Very few fatalities have been reported where 3-MeO-PCP contributed to the death of an individual. We present the first fatal case in the Netherlands and one of the few worldwide. Postmortem biological samples and the presumed abused unknown substance, sold as ant poison, were obtained. 3-MeO-PCP was detected, and the resulting concentration was 152 µg/l in whole blood. The presumed taken unknown sample was identified as 3-MeO-PCP and thus linked to the victim. The cause of death was a combination of 3-MeO-PCP, amphetamine, and alcohol. Improved diagnostic skills are necessary to face these emerging novel psychoactive substances also in light of public health and social risks.


Assuntos
Drogas Desenhadas/envenenamento , Fenciclidina/análogos & derivados , Psicotrópicos/envenenamento , Adulto , Anfetamina/sangue , Concentração Alcoólica no Sangue , Cromatografia Líquida , Drogas Desenhadas/análise , Humanos , Masculino , Espectrometria de Massas/métodos , Países Baixos , Fenciclidina/sangue , Fenciclidina/envenenamento , Psicotrópicos/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue
9.
J Forensic Leg Med ; 65: 76-80, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112932

RESUMO

According to World Health Organization (WHO) estimations, approximately 6 million people lose their lives yearly due to some kind of injury, while one-third of these incidents are due to violent acts. Violent deaths include accidents (road traffic accidents, drownings, falls, heat effects etc), suicides as well as homicides. Elderly people seem to be at greater risk due to their special characteristics as a vulnerable social group. The aim of this study was to investigate violent deaths (accidents, suicides and homicides) among elderly people in Attica, Greece, during the period 2011-2015 by examining manner of death with respect to demographic data (gender and age) and toxicological examination results. A total of 546 violent deaths among people over 65 years old were included in this study. Autopsy findings along with toxicological examination results were collected from the archives of the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens. The findings of the study showed that most of the victims were male (63.74%). The overwhelming majority of violent deaths (425 cases) were accidents, 92 cases suicides, and the remaining 29 cases homicides. Drowning was the leading cause of all accidental deaths, followed by road traffic accidents. Hangings prevailed among violent suicide methods and asphyxiation presented as a predominant homicide method.


Assuntos
Acidentes/mortalidade , Homicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Asfixia/mortalidade , Queimaduras/mortalidade , Afogamento/mortalidade , Feminino , Grécia/epidemiologia , Humanos , Masculino , Lesões do Pescoço/mortalidade , Envenenamento/mortalidade , Estudos Retrospectivos , Distribuição por Sexo , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Ferimentos não Penetrantes/mortalidade , Ferimentos Penetrantes/mortalidade
10.
Forensic Sci Int ; 299: 174-179, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31039545

RESUMO

Medical problems related to illicit drug use are frequently encountered at electronic dance music (EDM) events. In this prospective study, the medical problems and toxicological analyses on intoxicated persons and seized materials are described jointly. The aim of this study is to find out to what extent these efforts may assist in developing prevention strategies and organising on-site care at EDM events. The most frequently encountered clinical presentation in the 121 included patients was: agitation/aggression (26%), drunkenness (25%), depressed level of consciousness (24%) and hallucinations (9%). Only five patients were transported by ambulance to a hospital. In 100 of the 121 included patients (83%) an ethanolemia of at least 0.50 g/L was measured (with ethanol as the only drug found in 47 cases). 3,4-methylenedioxymethamphetamine (MDMA) was detected in 54% of the blood samples, cocaine in 11%, gamma-hydroxybutyric acid (GHB) in 11%, amphetamine in 7%, ketamine in 6% and a new psychoactive substance (NPS) in 4%. Except for 8 MDMA-users poly drug use was found in all these cases. The 178 seized samples most frequently contained MDMA (31%), cannabis (28%) or no active substance (15%). In 11 samples (6%) an NPS was detected. Of particular interest was a tablet containing 4-chloromethamphetamine (a previously unknown neurotoxic NPS), 4-chloroamphetamine, para-methoxyamphetamine, para-methoxymethamphetamine and ethylone. Our data show that at EDM events ethanol and MDMA are still the party drugs causing most health hazards and that NPS only play a minor role. Regarding the toxicological efforts, we recommend to analyse all seized materials from an EDM event, but only blood samples from the most severely intoxicated patients.


Assuntos
Intoxicação Alcoólica/epidemiologia , Concentração Alcoólica no Sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Bélgica/epidemiologia , Serviços Médicos de Emergência , Humanos , Aplicação da Lei , Comportamento de Massa , Estudos Prospectivos , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue
11.
Am J Emerg Med ; 37(4): 645-650, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30914133

RESUMO

BACKGROUND: Substance abuse is associated with traumatic injuries. Prior studies of drug use and injury have relied on urine drug of abuse screens, which have false positives, false negatives and inability to detect novel drugs. Our study characterizes the relationship between injury mechanism and drugs of abuse detected in serum via confirmatory testing. METHODS: This prospective observational study was conducted from Jan-Sept 2012 at a level 1 trauma center on trauma patients > 13 years who had blood drawn for routine tests. Demographic, injury and standard laboratory data were abstracted from patient charts. Comprehensive serum drug testing was done using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS, LC1200-TOF/MS 6230, Agilent, Santa Clara, CA). RESULTS: Of 272 patients, 71.0% were male, 30.5% had violent injury type and 32.4% had a penetrating injury mechanism. Violent injury type and penetrating injury mechanisms were more frequent in patients who were male, younger age, Black, or Hispanic (p < 0.05 for all). LC-TOF/MS showed that 46.0% were positive for at least one drug. Stimulant drugs were associated with violent injury type (OR 2.9; 95% CI 1.64-5.15) and penetrating injury mechanism (OR 3.3; 95% CI 1.86-5.82). Tobacco use was associated with violent injury type (OR 3.9; 95% CI 2.25-6.77) and penetrating injury mechanism (OR 4.14; 95%CI 2.4-7.14). CONCLUSIONS: Many drugs are present in trauma patients that are not routinely detected on urine drug of abuse tests. Both stimulant drugs and cigarette smoking are indicators of multidimensional hazardous behaviors, which were associated with more violent and penetrating trauma.


Assuntos
Estimulantes do Sistema Nervoso Central/sangue , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Violência , Ferimentos Penetrantes/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Fumar Cigarros , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , São Francisco/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/sangue , Espectrometria de Massas em Tandem , Adulto Jovem
12.
PLoS One ; 14(3): e0213791, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870525

RESUMO

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1ß, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to "Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision" (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1ß (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1ß (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1ß (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients.


Assuntos
Alcoolismo/diagnóstico , Biomarcadores/sangue , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Mediadores da Inflamação/sangue , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Alcoolismo/sangue , Alcoolismo/epidemiologia , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
13.
J Forensic Sci ; 64(4): 1105-1111, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30731020

RESUMO

Gabapentin, a GABA analogue, is a nonopioid prescribed for seizure control and neuralgic pain. Its abuse for recreational purposes has been increasing in recent years as the number of prescriptions also increases. In our series, we review 104 cases of decedents who tested positive for gabapentin in postmortem blood samples and an additional 53 nonfatal cases of motor vehicle drivers suspected of driving under the influence. In 47.1% of the fatality cases, gabapentin was directly involved in death. Most gabapentin fatalities had several other intoxicants present (opioids, over-the-counter medications, antianxiety, and antidepressant medications). In cases in which gabapentin was determined to be a cause of death, the blood concentrations ranged from 1.1 to 134.0 mg/L. Persons who died of a gabapentin-related drug death were prescribed the drug legitimately 91.4% of the time, with 84.2% of those also having a known prior history of abuse or misuse of prescription medications.


Assuntos
Gabapentina/efeitos adversos , Gabapentina/análise , Uso Indevido de Medicamentos sob Prescrição/mortalidade , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Acidentes/mortalidade , Cromatografia Líquida , Dirigir sob a Influência/estatística & dados numéricos , Overdose de Drogas , Feminino , Homicídio/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Estudos Retrospectivos , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Suicídio/estatística & dados numéricos , Espectrometria de Massas em Tandem , Virginia/epidemiologia , Corpo Vítreo/química
14.
J Anal Toxicol ; 43(5): 392-398, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30767008

RESUMO

In 2013, the Centers for Disease Control and Prevention released a warning regarding a new recreational drug, acetyl fentanyl. Acetyl fentanyl is a µ-opioid receptor agonist, and its pharmacological effects include euphoria, altered mood, miosis and central nervous system depression. The objective of this report was to develop a sensitive and specific method for the quantitation of acetyl fentanyl by gas chromatography-mass spectrometry in postmortem casework. Acetyl fentanyl was isolated from biological matrices using solid-phase extraction and acetyl fentanyl-13C6 was employed as an internal standard. The method was validated utilizing the Scientific Working Group for Forensic Toxicology's published method validation parameters, and the biological matrices used for analysis were postmortem blood and urine. In addition to the quantitation of acetyl fentanyl, a demographic study of cases obtained from the Rhode Island Office of State Medical Examiners and the University of Florida Health Pathology Laboratories-Forensic Toxicology Laboratory was performed to examine potential risk factors for acetyl fentanyl use. The results from this study found that the blood concentrations in these individuals ranged from 17 to 945 ng/mL. This suggests acetyl fentanyl is less potent than its prototype drug, fentanyl and requires an increased dose to achieve its desired effects. The demographic analysis indicated white males aged 21-40 years and individuals with a previous history of drug use have the highest risk for acetyl fentanyl abuse.


Assuntos
Fentanila/análogos & derivados , Toxicologia Forense/métodos , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Fentanila/sangue , Fentanila/urina , Toxicologia Forense/instrumentação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Limite de Detecção , Masculino , Mudanças Depois da Morte , Reprodutibilidade dos Testes , Extração em Fase Sólida , Detecção do Abuso de Substâncias/instrumentação , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto Jovem
15.
Forensic Sci Int ; 297: 189-197, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802648

RESUMO

Recently, fentanyl analogs account for significant number of opioid deaths in the United States. Routine forensic analyses are often unable to detect and differentiate these analogs due to low concentrations and presence of structural isomers. A data-independent screening method for 14 fentanyl analogs in whole blood and oral fluid was developed and validated using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Data were acquired using Time of Flight (TOF) and All Ions Fragmentation (AIF) modes. The limits of detection (LOD) in blood were 0.1-1.0 ng/mL and 0.1-1.0 ng/mL in TOF and AIF modes, respectively. In oral fluid, the LODs were 0.25 ng/mL and 0.25-2.5 ng/mL in TOF and AIF modes, respectively. Matrix effects in blood were acceptable for most analytes (1-14.4%), while the nor-metabolites exhibited ion suppression >25%. Matrix effects in oral fluid were -11.7 to 13.3%. Stability was assessed after 24 h in the autosampler (4 °C) and refrigerator (4 °C). Processed blood and oral fluid samples were considered stable with -14.6 to 4.6% and -10.1 to 2.3% bias, respectively. For refrigerated stability, bias was -23.3 to 8.2% (blood) and -20.1 to 20.0% (oral fluid). Remifentanil exhibited >20% loss in both matrices. For proof of applicability, postmortem blood (n = 30) and oral fluid samples (n = 20) were analyzed. As a result, six fentanyl analogs were detected in the blood samples with furanyl fentanyl and 4-ANPP being the most prevalent. No fentanyl analogs were detected in the oral fluid samples. This study presents a validated screening technique for fentanyl analogs in whole blood and oral fluid using LC-QTOF-MS with low limits of detection.


Assuntos
Fentanila/análogos & derivados , Fentanila/análise , Saliva/química , Detecção do Abuso de Substâncias/métodos , Alfentanil/análise , Cromatografia Líquida , Toxicologia Forense , Furanos/análise , Humanos , Limite de Detecção , Espectrometria de Massas , Remifentanil/análise , Extração em Fase Sólida , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Sufentanil/análise
16.
Clin Toxicol (Phila) ; 57(3): 149-163, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30307336

RESUMO

INTRODUCTION: γ-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths. OBJECTIVE: The aim of this review is to assist clinical and forensic practitioners with the interpretation of γ-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons. METHODS: The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords γ-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine γ-hydroxybutyric acid in blood and other biological specimens make use of gas- or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of γ-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cut-offs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All biological fluids and tissue containing water are suitable for the analysis of GHB. Examples of alternative specimens discussed in this review are CSF, saliva, hair strands, breast milk, DBS, VH, and brain tissue. CONCLUSIONS: Body fluids for the analysis of GHB must be obtained as quickly as possible after a poisoned patient is admitted to hospital or after a person is arrested for a drug-related crime to enhance chances of detecting the drug. The sampling of urine lengthens the window of detection by 3-4 h compared with blood samples, but with longer delays between last intake of GHB and obtaining specimens, hair strands, and/or nails might be the only option. In postmortem toxicology, the concentrations of drugs tend to be more stable in bladder urine, VH, and CSF compared with blood, because these sampling sites are protected from the spread of bacteria from the gut. Accordingly, the relationship between blood and urine concentrations of GHB furnishes useful information when drug intoxication deaths are investigated.


Assuntos
Toxicologia Forense/métodos , Oxibato de Sódio/análise , Adulto , Feminino , Humanos , Masculino , Oxibato de Sódio/farmacocinética , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto Jovem
17.
World J Biol Psychiatry ; 20(1): 51-63, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28532221

RESUMO

OBJECTIVES: Case reports describe neuropsychiatric manifestations associated with antiphospholipid antibodies (aPlAbs). In patients sharing the same symptoms fulfilling the antiphospholipid syndrome (APS) clinical criteria, the prevalence of common mental disorders has, however, never been studied. METHODS: We observed women with three consecutive abortions before the 10th week of gestation or one foetal loss at or beyond the 10th week. We compared the prevalence of common psychiatric disorders detected through screening using the Mini International Neuropsychiatric Interview, 10 years after inclusion, in women with APS (n = 506), women negative for aPlAbs but carrying the F5rs6025 or F2rs1799963 thrombogenic polymorphism (n = 269), and women with negative thrombophilia screening results as controls (n = 764). RESULTS: Similar prevalence values were obtained for controls and women bearing one of the two thrombogenic polymorphisms. Women with APS more frequently had mood disorders (relative risk (RR) 1.57 (1.262-1.953), P = .0001) and anxiety (RR 1.645 (1.366-1.979), P < .0001). Within the APS group, lupus anticoagulant (LA) and anti-ß2GP1 IgG, or triple positivity, were strong risk factors for mood disorders. CONCLUSIONS: Women with obstetric APS have a higher risk of positive screening for common mental disorders than women without APS.


Assuntos
Aborto Espontâneo , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica , Transtornos de Ansiedade , Transtornos do Humor , Trombofilia , Aborto Habitual/sangue , Aborto Habitual/epidemiologia , Aborto Habitual/imunologia , Aborto Espontâneo/sangue , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/imunologia , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/imunologia , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/imunologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Transtornos do Humor/epidemiologia , Transtornos do Humor/imunologia , Gravidez , Prevalência , Transtornos Psicóticos/sangue , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/imunologia , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/imunologia , Trombofilia/sangue , Trombofilia/epidemiologia , Trombofilia/imunologia
18.
J Anal Toxicol ; 43(3): 203-211, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295849

RESUMO

Suvorexant (SVR), lorcaserin (LCR) and brivaracetam (BVR) have been recently approved for the treatment of insomnia, obesity and epilepsy, respectively. Despite their clinical uses, these drugs have some abuse potential and have been enlisted under the schedule IV (SVR, LVR) and schedule V (BVR) categories of the Controlled Substances Act. A sensitive UPLC-MS-MS assay was developed for simultaneously determining SVR, LCR and BVR in human plasma. The liquid-liquid extraction method, using tert-butyl methyl ether as an extracting solvent, was used for sample preparation. Chromatographic separation was performed by using the Acquity BEH C18 column, using 10 mM ammonium acetate/acetonitrile/formic acid (15/85/0.1%; v/v/v) as the mobile phase. For sample ionization, electrospray ionization was used in the positive-ion mode. The multiple-reaction monitoring mode was used for detecting and quantifying analytes by using separate precursor-to-product ion transitions. The assay was validated following the SWGTOX guidelines, and all validation results were within the acceptable limits. The calibration curves of the analytes in the plasma were found to be linear, and the coefficient of determination (R2) was ≥ 0.992 for all the three analytes. The limit of detection values for SVR, LCR and BVR were 0.08, 0.11 and 0.26 ng/mL, respectively, whereas the limit of quantification values were 0.16, 0.27 and 0.65 ng/mL, respectively. The assay developed in this study is suitable for the identification and quantification of SVR, LCR and BVR in the forensic laboratory.


Assuntos
Azepinas/sangue , Benzazepinas/sangue , Pirrolidinonas/sangue , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/sangue , Triazóis/sangue , Calibragem , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Extração Líquido-Líquido , Medicamentos sob Prescrição , Padrões de Referência , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/instrumentação , Espectrometria de Massas em Tandem
19.
Gac Sanit ; 33(1): 4-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28784303

RESUMO

OBJECTIVE: The effect of drugs other than alcohol on severity of trauma remains unclear. Pooled data analyses in previous studies that grouped substances with opposite effects on the central nervous system (CNS) may have masked the influence of substances on injury severity. The aim was to analyze the effect of stimulant, hallucinogenic and depressant drugs other than alcohol on injury severity in trauma patients. METHODS: The presence of alcohol, stimulant drugs (cocaine, amphetamines and methamphetamines), depressant drugs (benzodiazepines, opiates, methadone and barbiturates) and hallucinogenic drugs (THC and PCP) was analyzed in 1187 patients between 16 and 70 years old admitted to a trauma hospital between November 2012 and June 2015. Injury severity was determined prospectively as the Injury Severity Score. A multivariate analysis was used to quantify the strength of association between exposure to substances and trauma severity, using the presence of alcohol as a stratification variable. RESULTS: Drugs other than alcohol were found in 371 patients (31.3%): 32 (2.7%) stimulants, 186 (15.3%) depressants, 78 (6.6%) hallucinogenics and 75 (5.6%) polydrug use. The presence of CNS depressant substances was associated with increased injury severity only in patients also exposed to alcohol, with an adjusted odds ratio of 4.63 (1.37-15.60) for moderate injuries and 7.83 (2.53-24.21) for severe. CONCLUSION: CNS depressant drugs had a strong influence on injury severity in patients who screened positive for alcohol consumption.


Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Alucinógenos/farmacologia , Escala de Gravidade do Ferimento , Transtornos Relacionados ao Uso de Substâncias , Ferimentos e Lesões , Adolescente , Adulto , Idoso , Depressores do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/sangue , Feminino , Alucinógenos/sangue , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/complicações , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Adulto Jovem
20.
J Forensic Sci ; 64(1): 304-308, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29768653

RESUMO

n-Ethyl pentylone (NEP) is a chemical substance derived from cathinone. Synthetic cathinones are an evolving group of drugs with stimulating, mind-altering effects sometimes referred to as novel or new psychoactive substances (NPS). There is scarce information in the medical literature regarding forensic cases in which NEP is detected in toxicological testing. We present four fatalities involving NEP from Alabama in 2017. Deaths were attributed to NEP toxicity in two cases (peripheral blood concentrations of 0.121 and 0.953 mg/L) and injuries caused by gunshot wounds in two cases (peripheral blood concentrations of 0.045 and 0.031 mg/L). One case involving NEP described an individual who exhibited classic CNS-stimulant induced erratic behavior before being found dead. These cases enhance the forensic literature regarding specific NPS like NEP and provide contextual reference for professionals considering the significance of NEP in toxicological interpretation.


Assuntos
Alcaloides/sangue , Psicotrópicos/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Acidentes , Adulto , Alabama , Alcaloides/envenenamento , Cromatografia Gasosa-Espectrometria de Massas , Homicídio , Humanos , Masculino , Psicotrópicos/envenenamento , Transtornos Relacionados ao Uso de Substâncias/complicações , Ferimentos por Arma de Fogo/complicações
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