Apocynin as an antidepressant agent: in vivo behavior and oxidative parameters modulation.

Depression is one of the most common mood disorders, which affects one in six people at some point in life. However, the treatment of this disease is still a challenge. Chronic corticosterone administration (CCA) is a widely used animal model to study the mechanisms involved, as well as possible therapeutic strategies for the treatment of depression. Moreover, elevated oxidative stress has been observed in psychiatric disorders, including major depression and, in this context, antioxidant therapy may be a potential therapeutic alternative. In this study, we investigated the effect of seven days of treatment with apocynin, an antioxidant of natural origin, on depressive-like behavior and oxidative parameters in mice submitted to CCA. After 21 days of corticosterone administration (20 mg/Kg/day, subcutaneously, s.c.), we observed the development of depressive-like behavior with an increase in immobility time on tail suspension test and forced swimming test and reduction in total grooming time on splash test. Also, we found high superoxide dismutase activity and hydrogen peroxide levels whereas catalase activity was reduced in the prefrontal cortex, hippocampus and striatum. Seven days of treatment with apocynin (100 mg/Kg/day orally, p.o), performed immediately after corticosterone administration in the last week of protocol, was able to reverse the most of these changes, revealing its antidepressant-like effect. In conclusion, our results suggest apocynin as an antidepressant-like agent with a mechanism of action based on the attenuation of oxidative changes induced by CCA.

Evaluation of oxidative stress and brain-derived neurotrophic factor levels related to crack-use detoxification.

Crack is a central nervous system stimulant extracted from the Erythroxylum coca plant. It is considered the most potent and addictive form of cocaine, and its euphoric effects are attained within a few seconds after consumption. Alteration of biological markers of oxidative stress and brain-derived neurotrophic factor (BDNF) could be related to the severity of crack withdrawal symptoms in patients undergoing rehabilitation. Thus, the objective of this study was to evaluate if the crack consumption and the drug detoxification process during 14 days in hospitalization regime was able to modify the oxidative status and BDNF levels, in male crack-abstinent patients. The crack detoxification process increased the glutathione (GSH), total thiol content (GST), nitric oxide (NO), and superoxide dismutase (SOD) levels, and reduced the mean BDNF levels. Moreover, a positive correlation was found between the number of hospital admission days and SOD values and between the GST levels and crack-use time after 14 days of detoxification. Furthermore, a negative correlation between the frequency of crack use and NO levels on the first day of hospitalization was also found. In conclusion, the results of this study indicated that crack consumption causes increased oxidative stress in drug users and that the detoxification process during 14 days was sufficient to improve oxidative parameters and antioxidant defenses of the patients, which could positively contribute to rehabilitation process. In addition, we also observed a great variability in the BDNF levels of the patients during the detoxification process, resulting in a reduction in the mean values of this neurotrophin.

A grazing height target to minimize tiller stem elongation rate in annual ryegrass swards / Altura limite de pastejo para minimizar o alongamento de colmos em pastos de azevém anual

ABSTRACT: Italian ryegrass (Lolium multiflorum Lam) is one of the most cultivated temperate annual forage crop around the world. Despite that, there is little information about the process of stem elongation during its vegetative growth. This information would be useful for grazing management purposes. Thus, the aim of this study was to assess the herbage accumulation and stem elongation rates in annual ryegrass pastures submitted to intermittent stocking. The experimental design used was a completely randomized 2x2 factorial with three replications. The treatments were defined by the combination of two pre-grazing heights (15 and 25cm) associated with two post-grazing heights (4 and 8cm). The herbage accumulation rates were higher in pastures with 25cm pre-grazing associated with post-grazing heights of 8cm. However, leaf production rate was only affected by post-grazing height, with higher values being recorded for stubbles heights of 8cm, regardless of pre-grazing height. Stem elongation rates in annual ryegrass tillers increased rapidly when pastures reached around 18cm, a condition where there was a relatively low competition for light, suggesting that; 1) pre-grazing heights of 18 to 20cm in annual ryegrass could be used as a upper limit for grazing management purposes whether the objective is to minimize stem contribution in accumulated herbage and 2) It seems that stem elongation is as inevitable process (independently of competition for light) and that this could be related to the necessary strength of stems, pseudostems and sheaths to support larger and heavier leaves.

RESUMO: O azevém anual (Lolium multuflorum Lam) é uma das plantas forrageiras de clima temperado mais cultivadas no mundo. Apesar disso, há poucas informações sobre o processo de alongamento de colmos para essa espécie durante seu crescimento vegetativo. Tal informação seria útil para o manejo mais adequado desta espécie. Assim, o objetivo do presente trabalho foi avaliar o acúmulo de forragem e as taxas de alongamento de colmos em pastos de azevém anual submetidos à lotação intermitente. O delineamento experimental foi completamente casualizado em arranjo factorial 2x2, com três repetições. Os tratamentos consistiram na combinação de duas alturas em pré-pastejo (15 e 25cm), associadas com duas alturas de resíduo (4 e 8cm). A maior taxa de acúmulo de forragem foi observada nos pastos manejadas com 25cm, associadas com alturas de resíduo de 8cm. Entretanto, a taxa de acúmulo de folhas foi similar para pastos manejados com 8cm de resíduo, independente da altura em pré-pastejo (15 ou 25cm). A taxa de alongamento de colmos em perfilhos de azevém anual aumentaram rapidamente quando os pastos atingiram uma altura de 18cm, condição onde havia uma relativa baixa competição por luz, sugerindo que: 1) alturas em pré-pastejo entre 18 e 20cm em pastos de azevém anual poderia ser usada como um limite máximo de altura quando o objetivo for minimizar a contribuição de colmos na forragem acumulada; e 2) parece que o alongamento de colmos é um processo inevitável (independente de competição por luz) e isso poderia estar relacionado com a força necessária de colmos, pseudocolmos e bainhas para suportar o peso de folhas cada vez maiores e mais pesadas.

Estudo da emissão de luz por diodoinfravermelho na dor neuropática em ratos / Study of infrared light emitting diodes infraredon neuropathic pain in rats

Introdução: A lesão nervosa periférica pode causar alteraçõesfuncionais tanto sensitivas quanto motoras, podendo promoverimportantes comprometimentos, especialmente a dor neuropática.Dentre os vários tratamentos propostos está o emprego da luz monocromáticade baixa intensidade, como o diodo de emissão de luz(LED). Objetivo: Avaliar o efeito analgésico do LED no espectroinfravermelho em modelo experimental de dor neuropática porconstrição do nervo ciático em ratos. Material e métodos: Foramutilizados 24 ratos machos Wistar, randomizados em 4 grupos (n =6). Grupo I: animais neuropáticos e tratados com LED; grupo II:animais neuropáticos e tratados com o LED desligado (placebo);grupo III: animais Sham e tratados com LED; grupo IV: animaisSham e tratados com LED desligado (placebo). Para avaliar a eficáciado tratamento, foram empregados parâmetros de nocicepção comoalodínia mecânica estática, dinâmica e térmica ao frio; hiperalgesiatérmica ao calor e nocicepção espontânea. Resultados: Os animaisneuropáticos desenvolveram alodínia e hiperalgesia ao estímulomecânico, térmico e nocicepção espontânea em 7 dias (Tempo 0)contados a partir da indução da neuropatia, mantendo essas manifestaçõesaté o 14º dia. Conclusão: O tratamento contínuo com LED noespectro infravermelho promoveu efeito analgésico em um modeloexperimental de dor neuropática em ratos. Os resultados obtidosneste estudo sugerem que esse recurso físico pode ser utilizado notratamento de pacientes com dor neuropática.

Introduction: The peripheral nerve injury can cause sensory andmotor functional changes, promoting important damages, especiallyneuropathic pain. The use of monochromatic light of low intensity,such as light-emitting diode (LED) is among different treatmentsoptions. Objective: This study proposes an evaluation of analgesiceffect of LED in the infrared spectrum in experimental model ofneuropathic pain induced by constriction of the sciatic nerve in rats.Methods: We used 24 male Wistar rats randomized into 4 groups (n= 6). Group I: neuropathic animals, treated with LED; group II:neuropathic animals, treated with LED (placebo); group III: Shamanimals treated with LED, group IV: Sham animals treated withLED turned off (placebo). We used nociception parameters suchas static mechanical allodynia, thermal (cold) dynamics, thermal(heat) hyperalgesia and spontaneous nociceptive in order to evaluatetreatment efficacy. Results: All animals developed neuropathicallodynia and hyperalgesia to mechanical stimulation, thermal andspontaneous nociception in 7 days (time 0), starting on inductionof neuropathy, maintaining these conditions until the 14th day.Conclusion: Continuous LED treatment with infrared spectrumpromotes analgesic effect in experimental model of neuropathic painin rats. The results of this study suggest that this treatment may beused to treat patients with neuropathic pain.

Distribuição de colmo na estrutura vertical de pastos de capim Aruana e azevém anual submetidos a pastejo intermitente por ovinos / Distribution of stem in the vertical structure of Aruana guineagrass and Annual ryegrass pastures subjected to rotational grazing by sheep

O objetivo deste estudo foi determinar a participação relativa de colmo na estrutura vertical de pastos de capim Aruana e azevém anual submetidos a estratégias de pastejo intermitente por ovinos. Os tratamentos para o capim Aruana corresponderam a pastejos realizados quando os pastos atingiam 95 e 98% de interceptação da luz incidente (IL) até as alturas pós-pastejo de 10 e 15cm. Para o azevém anual, os tratamentos corresponderam a pastejos realizados quando os pastos atingiam 15 e 25cm de altura pré-pastejo até as alturas pós-pastejo de 4 e 8cm. O delineamento experimental utilizado para as duas espécies foi inteiramente casualizado, em arranjo fatorial 2x2, com três repetições. Para quantificação da massa de colmo na estrutura vertical dos pastos, foram realizadas duas amostragens no pré-pastejo por unidade experimental (piquetes de 196m²) utilizando-se um quadrado de 25cm x 25cm de lado, em cada ciclo de pastejo. As amostras foram coletadas de forma estratificada a cada 5cm até o nível do solo. Após o corte estratificado, o material foi separado em colmo, folhas e material morto. Independente da espécie vegetal ou da altura de entrada, aproximadamente 90% de todo o colmo dos pastos encontra-se presente até 50% da altura do pasto, indicando que possíveis reduções em consumo a partir desse momento no rebaixamento podem ser atribuídas a dificuldades em manipulação e apreensão da forragem.

The aim of this study was to determine the relative contribution of stem in the vertical structure of Aruana guineagrass and annual ryegrass pastures submitted to strategies of rotational grazing by sheep. Treatments for Aruana guineagrass corresponded to grazing when the swards intercepted 95 and 98% of the incident light (LI) until the post-grazing heights of 10 and 15cm. For annual ryegrass, treatments corresponded to grazing when the swards reached 15 and 25cm (pre-grazing heights) until the post-grazing of 4 and 8cm. The experimental design for two species was a completely randomized in a 2x2 factorial scheme, with three replications. To quantify the stem mass present at each 5cm in the vertical structure of the pastures two samples were taken per experimental unit (paddocks of 196m²) using a square of 25cmx25cm. Cut samples was separated in leaves, stem and dead material. Regardless of plant species or pre-grazing height, approximately 90% of the stem is present up to 50% of sward height, suggesting that reported intake reduction beyond this point can be attributed to difficulties in forage manipulation and apprehension.

Contribution of peripheral vanilloid receptor to the nociception induced by injection of spermine in mice.

Polyamines (putrescine, spermidine and spermine) are important endogenous regulators of ion channels, such as vanilloid (TRPV1), glutamatergic (NMDA or AMPA/kainate) and acid-sensitive (ASIC) receptors. In the present study, we have investigated the possible nociceptive effect induced by polyamines and the mechanisms involved in this nociception in vivo. The subcutaneous (s.c.) injection of capsaicin (as positive control), spermine, spermidine or putrescine produced nociception with ED(50) of 0.16 (0.07-0.39)nmol/paw, 0.4 (0.2-0.7) µmol/paw, 0.3 (0.1-0.9) µmol/paw and 3.2 (0.9-11.5) µmol/paw, respectively. The antagonists of NMDA (MK801, 1 nmol/paw), AMPA/kainate (DNQX, 1 nmol/paw) or ASIC receptors (amiloride, 100 nmol/paw) failed to reduce the spermine-trigged nociception. However, the TRPV1 antagonists capsazepine or SB366791 (1 nmol/paw) reduced spermine-induced nociception, with inhibition of 81 ± 10 and 68 ± 9%, respectively. The previous desensitization with resiniferatoxin (RTX) largely reduced the spermine-induced nociception and TRPV1 expression in the sciatic nerve, with reductions of 82 ± 9% and 67 ± 11%, respectively. Furthermore, the combination of spermine (100 nmol/paw) and RTX (0.005 fmol/paw), in doses which alone were not capable of inducing nociception, produced nociceptive behaviors. Moreover, different concentrations of spermine (3-300 µM) enhanced the specific binding of [(3)H]-RTX to TRPV1 receptor. Altogether, polyamines produce spontaneous nociceptive effect through the stimulation of TRPV1, but not of ionotropic glutamate or ASIC receptors.