Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

Background: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST).

Determination of Levetiracetam in Human Plasma by Dispersive Liquid-Liquid Microextraction Followed by Gas Chromatography-Mass Spectrometry.

Levetiracetam (LEV) is an antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes. The use of this drug has been increasing in clinical practice and intra- or -interindividual variability has been exhibited for special population. For this reason, bioanalytical methods are required for drug monitoring in biological matrices.

A three phase hollow fiber liquid-phase microextraction for quantification of lamotrigine in plasma of epileptic patients by capillary electrophoresis.

A three phase hollow fiber liquid-phase microextraction technique combined with capillary electrophoresis was developed to quantify lamotrigine (LTG) in plasma samples. The analyte was extracted from 4.0 mL of a basic donor phase (composed of 0.

An investigation of the influence of patient-related factors and comedications on lamotrigine clearance in patients with epilepsy.

Lamotrigine (LTG) is one of the most widely used antiepileptic drugs. Confusion still exists in the literature as to the relative influence of age, body weight, and concomitant drug therapy on LTG pharmacokinetics. So, the objective of this study is to evaluate the influence of patient-related factors and comedication on LTG apparent oral clearance (CL/F).

The neuroprotection of cannabidiol against MPP⁺-induced toxicity in PC12 cells involves trkA receptors, upregulation of axonal and synaptic proteins, neuritogenesis, and might be relevant to Parkinson's disease.

Cannabidiol (CBD) is a non-psychoactive constituent of Cannabis sativa with potential to treat neurodegenerative diseases. Its neuroprotection has been mainly associated with anti-inflammatory and antioxidant events; however, other mechanisms might be involved. We investigated the involvement of neuritogenesis, NGF receptors (trkA), NGF, and neuronal proteins in the mechanism of neuroprotection of CBD against MPP(+) toxicity in PC12 cells.

Plasma Cannabinoid Pharmacokinetics After Controlled Smoking and Ad libitum Cannabis Smoking in Chronic Frequent Users.

More Americans are dependent on cannabis than any other illicit drug. The main analytes for cannabis testing include the primary psychoactive constituent, Δ(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent cannabis smokers resided on a closed research unit with unlimited access to 5.

Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment.

Hydroxycarbamide modulates components involved in the regulation of adenosine levels in blood cells from sickle-cell anemia patients.

Recent studies have demonstrated the role of adenosine (ADO) in sickle-cell anemia (SCA). ADO is produced by CD39 and CD73 and converted to inosine by adenosine deaminase (ADA). We evaluated the effects of hydroxycarbamide (HU) treatment on the modulation of adenosine levels in SCA patients.

Stress alone or associated with ethanol induces prostanoid release in rat aorta via alpha2-Adrenoceptor.

Background: Stress and ethanol are both, independently, important cardiovascular risk factors.

Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats.

Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol.

Olanzapine, weight change and metabolic effects: a naturalistic 12-month follow up.

Objective: Olanzapine is an atypical antipsychotic drug used to treat schizophrenia. Some of the adverse effects related to its use are obesity, hyperlipidemia, type 2 diabetes and hypertension, which may result in development of metabolic syndrome. This study aimed to investigate a possible increase in some anthropometric and biochemical parameters, and the existence of any correlation between them in Brazilian patients with schizophrenia treated with olanzapine in the mid term.

Rimonabant effects on anxiety induced by simulated public speaking in healthy humans: a preliminary report.

Objective: We investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test.

Methods: Participants were randomly allocated to receive oral placebo or 90 mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scale.

Impact of enzymatic and alkaline hydrolysis on CBD concentration in urine.

A sensitive and specific analytical method for cannabidiol (CBD) in urine was needed to define urinary CBD pharmacokinetics after controlled CBD administration, and to confirm compliance with CBD medications including Sativex-a cannabis plant extract containing 1:1 ∆(9)-tetrahydrocannabinol (THC) and CBD. Non-psychoactive CBD has a wide range of therapeutic applications and may also influence psychotropic smoked cannabis effects. Few methods exist for the quantification of CBD excretion in urine, and no data are available for phase II metabolism of CBD to CBD-glucuronide or CBD-sulfate.

Impact of prolonged cannabinoid excretion in chronic daily cannabis smokers' blood on per se drugged driving laws.

Background: Cannabis is the illicit drug most frequently reported with impaired driving and motor vehicle accidents. Some "per se" laws make it illegal to drive with any amount of drug in the body, while others establish blood, saliva, or urine concentrations above which it is illegal to drive. The persistence of Δ(9)-tetrahydrocannabinol (THC) in chronic daily cannabis smokers' blood is unknown.

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline.

Quantification of nicotine in commercial brand cigarettes: How much is inhaled by the smoker?

The main objective of this experiment is to determine the amount of nicotine in commercial brand cigarettes by means of a nonaqueous acid-base titration. A simple glass device simulating a smoker is proposed, which allows the determination of the volatilized, filter retained, and inhaled portions. Students will readily see that the amount of nicotine/cigarette stated on the label (∼0.

Anxiolytic-like effect of oxytocin in the simulated public speaking test.

Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test.

Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes.

Mesenchymal stromal cells (MSCs) suppress T cell responses through mechanisms not completely understood. Adenosine is a strong immunosuppressant that acts mainly through its receptor A(2a) (ADORA2A). Extracellular adenosine levels are a net result of its production (mediated by CD39 and CD73), and of its conversion into inosine by Adenosine Deaminase (ADA).

The effects of dietary supplementation of methionine on genomic stability and p53 gene promoter methylation in rats.

Methionine is a component of one-carbon metabolism and a precursor of S-adenosylmethionine (SAM), the methyl donor for DNA methylation. When methionine intake is high, an increase of S-adenosylmethionine (SAM) is expected. DNA methyltransferases convert SAM to S-adenosylhomocysteine (SAH).

Curcumin could prevent methemoglobinemia induced by dapsone in rats.

The curcumin's effect given orally by gavage in single- or multiple-dose regimens on methemoglobinemia induced by dapsone (DDS) was investigated in male Wistar rats. In the single-dose regimen, groups of 10 rats received either vehicle alone, or curcumin at 0.1, 1.

Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo.

[Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits].

Introduction: Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge.

Rifampicin determination in plasma by stir bar-sorptive extraction and liquid chromatography.

A sensitive and reproducible stir bar-sorptive extraction and high performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of rifampicin in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. This miniaturized method can result in faster analysis, higher sample throughput, lower solvent consumption and less workload per sample while maintaining or even improving sensitivity. Important factors in the optimization of SBSE efficiency such as pH, temperature, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) were optimized recoveries ranging from 75 to 80%.

Socioeconomic differences in preferences and willingness-to-pay for insulin delivery systems in type 1 and type 2 diabetes.

Background: An evaluation of patients' preferences is necessary to understand the demand for different insulin delivery systems. The aim of this study was to investigate the association between socioeconomic status (SES) and patients' preferences and willingness to pay (WTP) for various attributes of insulin administration for diabetes management.

Methods: We conducted a discrete choice experiment (DCE) to determine patients; preferences and their WTP for hypothetical insulin treatments.

A valuation of patients' willingness-to-pay for insulin delivery in diabetes.

Objectives: The aim of this study was to determine the insulin-delivery system and the attributes of insulin therapy that best meet patients' preferences, and to estimate patients' willingness-to-pay (WTP) for them.

Methods: This was a cross-sectional discrete choice experiment (DCE) study involving 378 Canadian patients with type 1 or type 2 diabetes. Patients were asked to choose between two hypothetical insulin treatment options made up of different combinations of the attribute levels.

[Hematological, hemostatic and biochemical alterations induced by clofazimine and clarithromycin, in single and multiple doses, in rats].

Clarithromycin and clofazimine have been used to treat leprosy, tuberculosis and infections caused by the Mycobacterium avium complex. Since there is a scarcity of data on the toxicity of therapeutic regimens that include these drugs, this study had the aim of determining the adverse effects of these therapies, through evaluation of hematological, hemostatic and biochemical parameters. The drugs were administered to male Wistar rats, as monotherapy, in regimens of single and multiple doses.