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1.
Indian J Dent Res ; 30(5): 692-696, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31854358

RESUMO

Introduction: Despite the enhancing effects of hyaluronidase (HYAL) over duration of anesthesia, this enzyme could cause adverse effects when injected concomitantly with local anesthetics in dental blocks. Objective: This study aimed to assess the tissue alterations caused by a local anesthetic protocol consisting of a late HYAL injection and confirm its functional effectiveness. Materials and Methods: The protocol efficacy was proved by evaluating sensory and motor functions in rats. The sciatic nerve was blocked with 2% lidocaine (LID) with epinephrine (n = 25). Thirty minutes later, 75 TRU/ml HYAL was injected into the same site (experimental group, LID/HYAL). One week later, this protocol was repeated in the contralateral hindlimb, injecting only HYAL's vehicle (control group, LID/vehicle [LID/V]). To observe the integrity of the local tissues, histological specimens were obtained 1, 24, 48, and 72 h after treatment with LID/HYAL or LID/V (n = 16 each) and stained with hematoxylin/eosin and picrosirius red. Results: Local inflammation was similar in both groups. The integrity of the nerve fibers was preserved, in spite of some inflammation-associated injuries in the surrounding tissues. The reversible tissue disorganization caused by HYAL, probably facilitated the diffusion of the residual anesthetic to the nerve, resulting in a prolonged anesthetic effect (P < 0.05). Conclusions: No irreversible morphological alterations are caused by the administration of HYAL prior the end of the LID-induced block. Moreover, this protocol prolongs LID's anesthetic effect.


Assuntos
Anestesia Local , Bloqueio Nervoso , Animais , Hialuronoglucosaminidase , Lidocaína , Ratos , Nervo Isquiático
2.
J Mass Spectrom ; 54(7): 600-611, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31066158

RESUMO

A fast and simple approach to overcome challenges in emergency toxicological analysis, using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed, for the detection of analytes in blood and urine samples from the following drug classes: analgesics, benzodiazepines, antidepressants, anticonvulsants, drugs of abuse, and pesticides. These substances are relevant in the context of emergency toxicology in Brazil. The sample preparation procedure was relatively easy and fast to perform. The method was fully validated giving limits of in the range of 0.5 and 20 ng mL-1 for blood and urine samples. The intraday and interday precision and accuracy were considered adequate for all analytes once the relative standard deviation (RSD) (%) was lower than 20% for quality control (QC) low and lower than 15% for CQ medium and high. The developed method was successfully applied to 320 real samples collected at the Poison Control Center of São Paulo, and 89.1% have shown to be positive for some of the analytes. This confirms its applicability and importance to emergency toxicological analysis, and it could be very useful in both fields of clinical and forensic toxicology.


Assuntos
/sangue , Praguicidas/sangue , Praguicidas/urina , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/urina , Analgésicos/sangue , Analgésicos/urina , Anticonvulsivantes/sangue , Anticonvulsivantes/urina , Antidepressivos/sangue , Antidepressivos/urina , Benzodiazepinas/sangue , Benzodiazepinas/urina , Brasil , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem
3.
Traffic Inj Prev ; 20(2): 122-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933546

RESUMO

OBJECTIVE: Truck drivers represent a group that is susceptible to the use of stimulant substances to reduce the symptoms of fatigue, which may be caused by a stressful and exhausting work environment. The use of psychoactive substances may increase the risk for involvement in road traffic crashes. Previous studies have demonstrated that amphetamine, cocaine, and cannabis are the 3 main drugs used by Brazilian truck drivers. We studied the prevalence of amphetamine, benzoylecgonine (indicating use of cocaine), and Δ-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH; indicating use of cannabis) in urine samples from truck drivers in the state of São Paulo, Brazil, using the same methodology during 8 years (2009-2016). METHODS: Samples were collected during a health program supported by the Federal Highway Police. Toxicological analyses were performed using immunoassays and gas chromatography-mass spectrometry. RESULTS: The total prevalence of illicit drugs was 7.8%. Benzoylecgonine was the most prevalent substance (3.6%), followed by amphetamine (3.4%) and THC-COOH (1.6%). We found the highest drug prevalence in 2010 (11.3%) and the lowest in 2011 (6.1%). We could detect a slight change in the pattern of stimulant use: until 2010, amphetamine was the most prevalent substance; however, in 2011 benzoylecgonine became the most frequently detected substance. This lasted until 2015, probably due to changes in Brazilian legislation regarding appetite suppressants; the most common one is metabolized to amphetamine. CONCLUSION: These data show that the use of psychoactive substances by truck drivers in Brazil did not decrease during the study period. This reinforces the need for further preventive measures to reduce drug use among drivers, which could lead to a decrease in traffic crashes in Brazil.


Assuntos
Estimulantes do Sistema Nervoso Central , Dirigir sob a Influência/estatística & dados numéricos , Psicotrópicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Acidentes de Trânsito/prevenção & controle , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
4.
Atherosclerosis ; 283: 100-105, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30826541

RESUMO

BACKGROUND AND AIMS: Anabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. METHODS: Twenty strength-trained AAS users (AASU) age 29 ±â€¯5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by 14C-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. RESULTS: Cholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. CONCLUSIONS: This study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.

5.
Bioanalysis ; 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30663322

RESUMO

The sample preparation is the most critical step involved in the bioanalytical process. When dealing with green analytical chemistry, sample preparation can be even more challenging. To fit the green analytical chemistry principles, efforts should be made toward the elimination or reduction of the use of toxic reagents and solvents, minimization of energy consumption and increased operator safety. The simplest sample preparations are more appropriate for liquid biological matrices with little interfering compounds such as urine, plasma and oral fluid. The same does not usually occur with complex matrices that require more laborious procedures. The present review discusses green analytical approaches for the analyses of drugs of abuse in complex biological matrices, such as whole blood, breast milk, meconium and hair.

6.
Scand J Med Sci Sports ; 29(3): 422-429, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30387184

RESUMO

Disturbed shear rate (SR), characterized by increased retrograde and oscillatory SR in the brachial artery, is associated with inflammation, atherosclerosis, endothelial dysfunction, and sympathetic hyperactivity. Young subjects do not have disturbed SR; however, elderly subjects do, which seems to be associated with sympathetic hyperactivity. Anabolic androgenic steroids (AAS) abuse in young is associated with increased muscle sympathetic nerve activity (MSNA). We hypothesized that AAS users might have disturbed SR. We tested the association between retrograde and oscillatory SR with MSNA. In addition, we measured the high-sensitivity C-reactive protein (hs-CRP). We evaluated 10 male AAS users, age 27 ± 4 years, and 10 age-matched AAS nonusers, age 29 ± 5 years. At rest, retrograde and oscillatory SR were evaluated by Doppler ultrasound, MSNA was measured with microneurography, and hs-CRP was measured in blood sample. Flow-mediated dilation (FMD) was also assessed. AAS users had higher retrograde SR (24.42 ± 17.25 vs 9.15 ± 6.62 s- 1 , P = 0.01), oscillatory SR (0.22 ± 0.13 vs 0.09 ± 0.07 au P = 0.01), and MSNA (42 ± 9 vs 32 ± 4 bursts/100 heart beats, P = 0.018) than nonusers. MSNA (bursts/100 heart beats) was correlated with retrograde SR (r = 0.50, P = 0.050) and oscillatory SR (r = 0.51, P = 0.042). AAS users had higher hs-CRP [1.17 (0.44-3.63) vs 0.29 (0.17-0.70) mg/L, P = 0.015] and decreased FMD (6.42 ± 2.07 vs 8.28% ± 1.53%, P = 0.035) than nonusers. In conclusion, AAS abuse is associated with retrograde and oscillatory SR which were associated with augmented sympathetic outflow. In addition, AAS seems to lead to inflammation characterized by increased hs-CRP. These alterations may have the potential of increasing the early risk of atherosclerotic disease in young AAS users.


Assuntos
Anabolizantes/efeitos adversos , Artéria Braquial/fisiopatologia , Esteroides/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Aterosclerose , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Frequência Cardíaca , Humanos , Masculino , Oscilometria , Fatores de Risco , Sistema Nervoso Simpático , Adulto Jovem
7.
Psychol Med ; 49(4): 655-663, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29903051

RESUMO

BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). CONCLUSIONS: To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

9.
J Forensic Leg Med ; 60: 3-8, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30189409

RESUMO

Violence is a dreadful phenomenon spread throughout the world, resulting in unfortunate events that can ultimately cause death. It is known that some countries play a much worrying role in this scenario than others. Brazil is one of them. The present work has focused on identifying the use of cocaine in 105 postmortem cases arriving at the Institute of Legal Medicine of Sao Paulo (IML-SP), the largest Brazilian city. Both blood and hair samples have been analyzed through ultra-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) in order to distinguish between recent or chronic cocaine use. The purpose of this work was to evaluate the proportion of cocaine use amongst violent individuals whose violence has ultimately led to their death. In order to do so, two previous methods, validated in-house, based on methanolic extraction for hair and protein precipitation for blood, have been used for this purpose and the final residue was analyzed through UPLC-ESI-MS/MS system. When looking at the demographics from the 105 postmortem cases analyzed, the results have shown the most critical age range to be between 18 and 25 years old and the least frequent between 37 and 45 years old. Gender wise, a rather extreme difference was found as 97 of the individuals were men and finally, considering the manner of death, the four-category criteria established appear to be fairly similar with 34 cases related to general violence and risk behavior, 26 to drug abuse suspicion, 23 to homicide resulting from opposition to police intervention and 22 to possible suicide.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Cocaína/análise , Homicídio/estatística & dados numéricos , Entorpecentes/análise , Suicídio/estatística & dados numéricos , Violência/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Cromatografia Líquida , Feminino , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Adulto Jovem
10.
Biomed Chromatogr ; 32(12): e4360, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30109709

RESUMO

This work describes a simple approach to overcome challenges in emergency toxicological analysis, using liquid-liquid extraction and high-performance liquid chromatography coupled with a diode-array detector (HPLC-DAD). A rapid procedure has been developed, for the extraction and detection of 19 analytes from the following drug classes: analgesics, benzodiazepines, antidepressants, anticonvulsants and drugs of abuse. These substances are relevant in the context of emergency toxicology in Brazil. The method has been validated according to international guidelines by establishing parameters such as lower limit of quantification, sensitivity, linearity, accuracy and precision. The intra and inter-day precision values, at the lowest concentration levels, have always been less than 20% considering its relative standard deviation. As for accuracy values, these have also been satisfactory (above 81.3%). This method was successfully applied in 201 blood samples from patients with suspected poisoning of the Poison Control Center of São Paulo (PCC-SP), Brazil. Finally, the developed method has shown to be relevant for emergency toxicology due to its high sensitivity and it could be also very useful in both fields of clinical and forensic toxicology.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Toxicologia Forense/métodos , Preparações Farmacêuticas/análise , Centros de Controle de Intoxicações , Envenenamento/diagnóstico , Adulto , Brasil , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes
11.
Clinics (Sao Paulo) ; 73: e226, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29791601

RESUMO

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.


Assuntos
Anabolizantes/efeitos adversos , Androgênios/efeitos adversos , Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Adulto , Sistema Nervoso Autônomo/fisiologia , Barorreflexo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Estudos Transversais , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Exercícios de Alongamento Muscular , Análise de Onda de Pulso , Taxa Respiratória/efeitos dos fármacos , Fatores de Risco , Estatísticas não Paramétricas , Nervo Vago/fisiologia , Rigidez Vascular/efeitos dos fármacos
13.
Artigo em Inglês | MEDLINE | ID: mdl-29329090

RESUMO

Cannabis misuse during pregnancy is associated with severe impacts on the mother and baby health, such as newborn low birth weight, growth restriction, pre-term birth, neurobehavioral and developmental deficits. In most of the cases, drug abuse is omitted or denied by the mothers. Thus, toxicological analyzes using maternal-fetal matrices takes place as a suitable tool to assess drug use. Herein, meconium was the chosen matrix to evaluate cannabis exposure through identification and quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic (THCCOOH). Accelerated solvent extraction (ASE) was applied for sample preparation technique to simultaneously extract and hydrolyze conjugated THCCOOH from meconium, followed by a solid-phase extraction (SPE) procedure. The method was developed and validated for gas chromatography-mass spectrometry (GC-MS), reaching hydrolysis efficiency of 98%. Limits of detection (LOD) and quantification (LOQ) were, respectively, 5 and 10 ng/g. The range of linearity was LOQ to 500 ng/g. Inter and intra-batch coefficients of variation were <8.4% for all concentration levels. Accuracy was in 101.7-108.9% range. Recovery was on average 60.3%. Carryover effect was not observed. The procedure was applied in six meconium samples from babies whose mothers were drug users and showed satisfactory performance to confirm fetal cannabis exposure.


Assuntos
Dronabinol/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas/métodos , Mecônio/química , Dronabinol/análise , Dronabinol/química , Dronabinol/isolamento & purificação , Dronabinol/metabolismo , Feminino , Glucuronídeos , Humanos , Hidrólise , Recém-Nascido , Modelos Lineares , Abuso de Maconha/metabolismo , Gravidez , Complicações na Gravidez/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Med Sci Sports Exerc ; 50(3): 596-602, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29040222

RESUMO

PURPOSE: Increased resting muscle sympathetic nerve activity (MSNA) and lower forearm blood flow (FBF) were observed in young men who use anabolic androgenic steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by muscle mechanoreflex and central command has never been tested. In addition, we evaluated the blood pressure (BP) and heart rate (HR) responses during these maneuvers. METHODS: Nineteen AAS users (AASU) 31 ± 6 yr of age and 18 AAS nonusers (AASNU) 29 ± 4 yr of age were recruited. All participants were involved in strength training. AAS use was determined using a urine test (liquid chromatography with tandem mass spectrometry). MSNA was measured using the microneurography technique. FBF was measured by using venous occlusion plethysmography. BP was measured using an automatic oscillometric device. HR was recorded continuously through ECG. Isometric handgrip exercise was performed at 30% of the maximal voluntary contraction for 3 min, and mental stress was elicited by the Stroop color-word test for 4 min. RESULTS: The MSNA and FBF responses during exercise were similar between AASU and AASNU, with a trend toward higher MSNA (bursts per minute; P = 0.084) and lower forearm vascular conductance (FVC; units; P = 0.084) in AASU than in AASNU. During mental stress, AASU showed a significantly higher MSNA (P < 0.05) and lower FBF (P < 0.05) compared with AASNU. During both maneuvers, HR and BP increased linearly in both groups; however, AASU showed a significantly higher HR compared with AASNU. CONCLUSIONS: During muscle mechanoreflex activation (isometric exercise), AASU have normal MSNA and FBF responses, whereas during central command (mental stress) stimulation, AASU have exacerbated MSNA and blunted vasodilation. Therefore, mental stress seems to exacerbate neurovascular control throughout stress reaction situations in AASU.


Assuntos
Exercício/fisiologia , Hemodinâmica , Estresse Psicológico , Sistema Nervoso Simpático , Congêneres da Testosterona/administração & dosagem , Adulto , Pressão Sanguínea , Antebraço/irrigação sanguínea , Força da Mão , Frequência Cardíaca , Humanos , Masculino , Pletismografia , Fluxo Sanguíneo Regional , Vasodilatação
16.
Clinics ; 73: e226, 2018. tab
Artigo em Inglês | LILACS-Express | ID: biblio-890749

RESUMO

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population.

17.
Braz. J. Pharm. Sci. (Online) ; 54(1): e17174, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951914

RESUMO

ABSTRACT Ayahuasca is a beverage with psychoactive properties used in religious and ceremonial rituals by some religious groups. The main active components of ayahuasca are dimethyltryptamine and the harmala alkaloids with ß-carboline structure acting as monoamine oxidase A inhibitors. This combination produces a pronounced activation of serotonergic pathways and presents potential interaction with other psychotropics. The objective of this study was to investigate the possible interactions between ayahuasca and agents employed in general anesthesia. The pharmacological interactions between ayahuasca and morphine or propofol were evaluated in mice using doses of 12, 120 and 1200 mg/kg (0.1 to 10 times the average dose consumed by humans in religious rituals). Ayahuasca alone showed an antinociceptive effect in the writhing and formalin tests, and intensified the analgesic effect of morphine in the hot plate test. Concerning the pharmacological interactions between ayahuasca and propofol, the results were opposite; ayahuasca intensified the depressant effect of propofol in the rotarod test, but decreased the sleeping time induced by propofol. These set of results showed the occurrence of some interactions between ayahuasca and the drugs morphine and propofol, possibly by both pharmacokinetics and pharmacodynamics mechanisms


Assuntos
Animais , Masculino , Camundongos , Interações de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Morfina/análise , Bebidas/efeitos adversos , Propofol/análise , Banisteriopsis/efeitos adversos , Psychotria/efeitos adversos , Analgésicos/efeitos adversos
18.
Front Behav Neurosci ; 11: 139, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804451

RESUMO

The combined infusion of Banisteriopsis caapi stem and Psychotria viridis leaves, known as ayahuasca, has been used for centuries by indigenous tribes. The infusion is rich in N, N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors, with properties similar to those of serotonin. Despite substantial progress in the development of new drugs to treat anxiety and depression, current treatments have several limitations. Alternative drugs, such as ayahuasca, may shed light on these disorders. Here, we present time-course behavioral changes induced by ayahuasca in zebrafish, as first step toward establishing an ideal concentration for pre-clinical evaluations. We exposed adult zebrafish to five concentrations of the ayahuasca infusion: 0 (control), 0.1, 0.5, 1, and 3 ml/L (n = 14 each group), and behavior was recorded for 60 min. We evaluated swimming speed, distance traveled, freezing and bottom dwelling every min for 60 min. Swimming speed and distance traveled decreased with an increase in ayahuasca concentration while freezing increased with 1 and 3 ml/L. Bottom dwelling increased with 1 and 3 ml/L, but declined with 0.1 ml/L. Our data suggest that small amounts of ayahuasca do not affect locomotion and reduce anxiety-like behavior in zebrafish, while increased doses of the drug lead to crescent anxiogenic effects. We conclude that the temporal analysis of zebrafish behavior is a sensitive method for the study of ayahuasca-induced functional changes in the vertebrate brain.

19.
Forensic Sci Int ; 273: 140-143, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28273545

RESUMO

Traffic accidents are responsible for 1.25 million deaths worldwide and are the most common cause of death among those aged 15-29 years. In Brazil, traffic accidents caused more than 44,000 deaths in 2014. The use of psychoactive drugs is an important risk factor for being involved in traffic accidents. Previous studies have found that psychoactive substances are commonly used by truck drivers in Brazil to maintain their extensive work schedule and stay awake while driving during nighttime hours. The state of Sao Paulo is one of the most important states regarding goods transportation. Important highways cross through Sao Paulo to other regions from Brazil and to other countries in Latin America. This study aims to determine the prevalence of illicit drug use by truck drivers in the state of Sao Paulo through toxicological analyses of oral fluid. Truck drivers were randomly stopped by police officers on federal roads during morning hours. Oral fluid samples were collected using the Quantisal™ device. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Oral fluid samples were screened for amphetamine, cocaine, and tetrahydrocannabinol (Δ9-THC) by ELISA and the confirmation was performed using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Of the 764 drivers stopped, 762 agreed to participate. The participants were driving an average of 614km and 9.4h a day. Of the total samples, 5.2% (n=40) tested positive for drugs. Cocaine was the most frequently found drug (n=21), followed by amphetamine (n=16) and Δ9-THC (n=8). All drivers were men with an average age of 42.5 years. With these results we were able to verify that many truck drivers were still consuming psychoactive drugs while driving, and cocaine was the most prevalent one. This reinforces the need for preventive measures aimed at controlling the use of illicit drugs by truck drivers in Brazil.


Assuntos
Dirigir sob a Influência/estatística & dados numéricos , Veículos Automotores , Ocupações , Saliva/química , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Brasil/epidemiologia , Humanos , Masculino , Detecção do Abuso de Substâncias
20.
Toxicology ; 376: 44-50, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27129946

RESUMO

Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaine's pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M1- and M3-muscarinic acetylcholine receptor and an antagonist at the remaining subtypes. No reports have assessed AEME's role in addiction. Adult male Wistar rats were intraperitoneally administered with saline, 3mg/kg AEME, 15mg/kg cocaine, or a cocaine-AEME combination on every other day during a period of 9 days. After a 7-days withdrawal period, a challenge injection of the respective drugs was performed on the 17th day. The locomotor activity was evaluated on days 1, 3, 5, 7, 9 and 17, as well as dopamine levels (9th day) and dopaminergic receptors proteins (D1R and D2R on the 17th day) in the caudate-putamen (CPu) and nucleus accumbens (NAc). AEME was not able to induce the expression of behavioral sensitization, but it substantially potentiates cocaine-effects, with cocaine-AEME combination presenting higher expression than cocaine alone. An increase in the dopamine levels in the CPu in all non-saline groups was observed, with the highest levels in the cocaine-AEME group. There was a decrease in D1R protein level in this brain region only for cocaine and cocaine-AEME groups. In the NAc, an increase in the dopamine levels was only observed for cocaine and cocaine-AEME groups, with no changes in both D1R and D2R protein levels. These behavioral and neurochemical data indicate that AEME alone does not elicit behavioral sensitization but it significantly potentiates cocaine effects when co-administered, resulting in dopamine increase in CPu and NAc, brain regions where dopamine release is mediated by cholinergic activity.


Assuntos
Cocaína/análogos & derivados , Cocaína/administração & dosagem , Cocaína/metabolismo , Dopamina/metabolismo , Atividade Motora/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Sinergismo Farmacológico , Masculino , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Receptores Dopaminérgicos/metabolismo
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