3-(2,4-Dibromo­anilino)-2,2-dimethyl-2,3-dihydro­naphtho[1,2-b]furan-4,5-dione: a new substituted aryl­amino nor-β-lapachone derivative

The title compound, C20H15Br2NO3, shows the furan ring to adopt a half-chair conformation and the two ring systems to be approximately perpendicular [dihedral angle = 71.0 (2)°]. In the crystal structure, inter­molecular C—H⋯O contacts link the mol­ecules

Modafinil induces rapid-onset behavioral sensitization and cross-sensitization with cocaine in mice: implications for the addictive potential of modafinil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on aro7FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)2014/24277-4sem informaçãosem informaçã

The influence of aerobic fitness status on ventilatory efficiency in patients with coronary artery disease

OBJECTIVE: To test the hypotheses that 1) coronary artery disease patients with lower aerobic fitness exhibit a lower ventilatory efficiency and 2) coronary artery disease patients with lower initial aerobic fitness exhibit greater improvements in ventilatory efficiency with aerobic exercise training. METHOD: A total of 123 patients (61.0±0.7 years) with coronary artery disease were divided according to aerobic fitness status into 3 groups: group 1 (n = 34, peak VO2;17.5 and ;24.5 ml/kg/min). All patients performed a cardiorespiratory exercise test on a treadmill. Ventilatory efficiency was determined by the lowest VE/VCO2 ratio observed. The exercise training program comprised moderate-intensity aerobic exercise performed 3 times per week for 3 months. Clinicaltrials.gov: NCT02106533 RESULTS: Before intervention, group 1 exhibited both lower peak VO2 and lower ventilatory efficiency compared with the other 2 groups (

Chemoselective oxidation of benzophenazines by m-CPBA: n-oxidation vs. oxidative cleavage

Chemoselectivity is observed when a pyran-benzo[a]phenazine and a furan-benzo[a]phenazine from beta-lapachone and nor-beta-lapachone, respectively, were submitted to oxidation by m-CPBA. The pyran phenazine furnished mainly macrolactones, while the furan one led exclusively to a phenazine N-8 oxide. To understand this difference in reactivity, we synthesized a new furan phenazine, with the reactive double bond site less hindered than that of the derivative from nor-beta-lapachone. This furan phenazine, upon oxidation with m-CPBA, furnished mainly the expected macrolactone. These experimental results, along with preliminary analysis based on mechanical molecular calculations of the ground state of the substrates, allowed us to suggest that the observed chemoselectivity has a steric oxidant approach control origin, related to the presence of the geminal methyl groups in the phenazine structure. Several of the synthesized compounds are, herein, reported for the first time

Specificity and selectivity improvement in doping analysis using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry

Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry was used for the identification of forty doping agents. The improvement in the specificity was remarkable, allowing the resolution of analytes that could not be done by one-dimensional chromatographic systems. The sensitivity observed for different classes of prohibited substances was clearly below the value required by the World Anti-Doping Agency. In addition time-of-flight mass spectrometry gives full spectrum for all analytes without any interference from the matrix, resulting in selectivity improvements. These results could support the implementation of an exhaustive monitoring approach for hundreds of doping agents in a single injection

Participation of Dopamine D1 and D2 Receptors in the Rapid-Onset Behavioral Sensitization to Modafinil

Studies on the abuse potential of modafinil, a psychostimulant-like drug used to treat narcolepsy, are still controversial. While some studies claim no potential for abuse, increasing evidence suggests that modafinil induces abuse-related effects, including rapid-onset behavioral sensitization (i.e., a type of sensitization that develops within hours from the drug priming administration). The rapid-onset sensitization paradigm is a valuable tool to study the neuroplastic changes that occur quickly after drug administration, and shares neuroadaptations with drug abuse in humans. However, the mechanisms involved in the rapid-onset behavioral sensitization induced by modafinil are uncertain. Our aim was to investigate the possible involvement of dopamine D1 and D2 receptors on acute modafinil-induced hyperlocomotion and on the induction and expression of rapid-onset behavioral sensitization induced by modafinil in male Swiss mice. Treatment with the D1 receptor antagonist SCH 23390 or the D2 receptor antagonist sulpiride attenuated the acute modafinil-induced hyperlocomotion in a dose-dependent manner. Pretreatment with either antagonist before the priming injection of modafinil prevented the development of sensitization in response to a modafinil challenge 4 h later. However, only SCH 23390 decreased the expression of modafinil-induced rapid-onset behavioral sensitization. Taken together, the present findings provide evidence of the participation of D1 and D2 receptors on the development of rapid-onset behavioral sensitization to modafinil, and point to a prominent role of D1 receptors on the expression of this phenomenon

Effects of Ibuprofen intake in muscle damage, body temperature and muscle power in Paralympic powerlifting athletes

The aim of this study is to evaluate the effect of ingesting ibuprofen on post-workout recovery of muscle damage, body temperature and muscle power indicators in Paralympic powerlifting athletes. The study was carried out with eight Paralympic powerlifting athletes (aged 27.0 ± 5.3 years and 79.9 ± 25.5 kg of body mass) competing at the national level, with a minimum training experience of 12 months, who all submitted to two experimental conditions: Ibuprofen (2 × 00 mg) and control. The maximal isometric force of the upper limbs and rate of force development, thermography, and serum biochemical analyzes of creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were measured before, after, 24 h after and 48 h after the intervention. Maximal isometric force only decreased in the placebo condition, which increased back to baseline levels, while no substantial decline in baseline force was seen in the ibuprofen condition, although no effect for exercise condition was detected. After the exercise, the rate of force development decreased significantly for both conditions and did not exceed baseline levels again after 48 h. Muscle temperature decreased significantly at 48-h post-exercise in the placebo condition, when compared with the previous day of measurement; and deltoid muscle temperature at 48-h post-exercise was higher with the ibuprofen condition. Although the results indicate some positive effects of ibuprofen use, they do not enable a clear statement regarding its positive effects on muscle function and muscle damage. Ibuprofen seems to have caused a delay in the anti-inflammatory response following exercise.publishedVersio

Effects of High-Intensity Warm-Up on 5000-Meter Performance Time in Trained Long-Distance Runners

Warm-up protocols with high intensities before continuous running provide potential benefits for middle-distance runners. Nevertheless, the effect of high-intensity warm-ups on long-distance runners remains unclear. The purpose of this study was to verify the effect of a high-intensity warm-up protocol on 5000 m performance in trained runners. Thirteen male runners (34 ± 10 years, 62 ± 6 kg, 62.7 ± 5.5 ml/kg/min) performed two 5000 m time trials, preceded by two different warm-ups. One high-intensity warm up (HIWU: 1x 500 m (70% of the running intensity) + 3x 250 m (100% of the running intensity) and one low-intensity warm up (LIWU: 1x 500 m (70% of the running intensity) + 3x 250 m (70% of the running intensity)), where the running intensities were calculated using the results obtained in the Cooper test. Physiological and metabolic responses, and endurance running performance parameters, were evaluated by the Counter Movement Jump (CMJ), running rating of perceived exertion (RPE), blood lactate concentration (BLa), and performance running. Total time for the 5000 m was lower using HIWU when compared to LIWU (1141.4 ± 110.4 s vs. 1147.8 ± 111.0 s; p = 0.03; Hedges' g = 0.66). The HIWU warm-up led to an improvement in pacing strategy during the time trial. After warm-up protocols, the performance on the CMJ was improved only when applying HIWU (p = 0.008). Post warm-up BLa was significantly higher for HIWU vs. LIWU (3.5 ± 1.0 mmol·L-1 vs. 2.3 ± 1.0 mmol·L-1; p = 0.02), with similar behavior for the RPE (p = 0.002), internal load of the session (p = 0.03). The study showed that a high-intensity warm-up protocol can improve performance in the 5000 m in trained endurance runners

A voz dos bandos: colectivos de justiça e ritos da palavra portuguesa em Timor Leste colonial

Este artigo examina as relações entre o discurso da justiça e a prática do ritual nos bandos do governo colonial português em Timor Leste, entre a segunda metade do século XIX e as primeiras décadas do século XX. Os bandos consistiam em ordens e instruções de comando emanadas pelo governador português em Díli, e comunicadas de forma cerimonial por oficiais às populações dos diversos reinos timorenses dispersos pelo país. Bandos eram um instrumento por excelência de governação colonial dos assuntos indígenas, servindo para arbitrar conflitos, punir transgressões e, em geral, instituir realidades no mundo timorense. Contudo, esta instituição assumiu igualmente uma singular expressão nos usos timorenses, servindo bandos para comunicar também as ordens de autoridades tradicionais, os liurais. O artigo acompanha as variações coloniais e indígenas que os bandos adquiriram em Timor Leste, conceptualizando-os enquanto colectivos de justiça. Ao considerar assim os bandos como colectivos – formações heterogéneas em que elementos linguísticos e não linguísticos se combinam na produção de efeitos de poder sobre as populações – o artigo propõe uma via conceptual alternativa às perspectivas linguísticas e literárias de análise do discurso colonial