Alterations in salivary biochemical composition and redox state disruption induced by the anticonvulsant valproic acid in male rat salivary glands.

OBJECTIVE: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters. MATERIALS AND METHODS: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands. RESULTS: Salivary flow rate, pH, buffering capacity, total protein, potassium, sodium, and chloride were similar between groups. However, phosphate and calcium were reduced in VPA400, while amylase was increased in both VPA100 and VPA400. We did not detect significant differences in the areas of acini, ducts, and connective tissue in the salivary glands between the groups. There were no significant changes in the redox status of the submandibular glands. In turn, in the parotid glands we detected reduced total oxidizing capacity and lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARs) and higher uric acid concentration in both the VPA100 and VPA400 groups, and increased superoxide dismutase (SOD) in the VPA400 group. CONCLUSION: Chronic treatment with VPA modified the salivary biochemical composition and caused disruption in the redox state of the parotid gland in rats.

Exercise behavior, practice, injury, and symptoms of respiratory tract infection of 502 Brazilian adults during lockdown oscillations in two years (2021-2022) of the COVID-19 pandemic.

BACKGROUND: In the period between 2020 and 2023, during the COVID-19 (coronavirus disease 2019) pandemic, many countries released their restriction measures so that individuals were able to begin practicing physical exercises and outdoor sports again. The purpose of the current study was to evaluate the physical exercise behavior, symptoms of respiratory tract infection, and training practice, as well as aspects of pain and injuries in the lower limbs of adults during periods of lockdown oscillations in the two years of the COVID-19 pandemic in Brazil. METHODS: Cross-sectional study. PARTICIPANTS: A total of 502 adults were evaluated during two consecutive years of the COVID-19 pandemic, corresponding to the years 2021 and 2022. A virtual questionnaire was applied using the Google Forms platform through a link, or a Quick Response Code available in social media environments. The variables collected were: anthropometric characteristics, presence of comorbidities, clinical history for the diagnosis of COVID-19, and behavior related to physical exercise practices, divided into five topics: (1) physical exercise habits; (2) symptoms and health care utilization; (3) habit of practicing physical exercise in relation to the prevention of COVID-19; (4) preventive measures for COVID-19; and (5) feelings and reasons for practicing exercises. RESULTS: A total 79.0% of the participants returned to the practice of physical exercise after a period of social isolation due to COVID-19, with running (30.0%) and muscle strength training (50.0%) being the most prevalent modalities, in which 62.0% of practitioners carried out the activity individually, without any professional or technical monitoring. With regard to physical preparation, 61.0% reported performing pre-training stretching, 64.0% associated with muscular resistance training. Of these, 89% did not report current injuries or pain symptoms when returning to exercise (69.0%). Total of 60.5% reported experiencing respiratory tract symptoms of COVID-19 and seeking a consultation with a doctor, and 61.0% performed diagnostic test, with RT-PCR (Real time-polymerase chain reaction) being the most common test. Of those tested, 55.0% were positive for COVID-19, without the need for hospitalization (95.0%). The most commonly used measures for the prevention of COVID-19 were the fabric or surgical mask. The predominant feeling in the pandemic was anxiety (50.5%) and the reasons for practicing sports were: physical conditioning (30.9%), a feeling of pleasure (21.3%), and weight loss (20.3%). CONCLUSION: After two years of the COVID-19 pandemic (2021-2022), with periods of lockdown, there were low reports of injuries and pain symptoms after exercising on the return to physical exercise practices of running and strength training. However, the restrictions negatively affected the exercise behavior due to respiratory tract symptoms of COVID-19 and a reduction in training intensity, performed without any professional or technical supervision. The participants reported the use of a fabric or surgical mask for the prevention of COVID-19, and an increased feeling of anxiety. The reasons given for practicing physical exercise were physical conditioning, a feeling of pleasure, and weight loss.

Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats.

Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.

Emerging role of microglia and astrocyte in the affective-motivational response induced by a rat model of persistent orofacial pain.

Few studies are approaching the neural basis underlying the aggregation of emotional disorders in orofacial pain despite the stress, depression, and anxiety are some of the most commonly reported risk factors. Using a persistent orofacial pain rat model induced by complete Freund's adjuvant (CFA) injection into the temporomandibular joint, we have investigated the plasticity astrocytes and microglia key brain regions for the affective-emotional component of pain. We measured the expression and morphologic pattern of reactivation of glial fibrillary acidic protein (GFAP, astrocyte marker) and Iba-1 (microglial marker) by western blotting and immunohistochemistry analysis. The results showed no alterations on motor activity during inflammatory pain, indicating an exclusive effect of nociceptive behavior on the plasticity of limbic regions. CFA-induced temporomandibular inflammation changed GFAP and Iba-1 expression in distinct regions related to emotional behavior in a time-dependent manner. A significant increase in GFAP and Iba-1 expression was observed in the central nucleus of the amygdala, hippocampus and periaqueductal grey matter from day 3 to day 10 post-CFA injection. Moreover, a positive correlation between GFAP and Iba-1 upregulation and an increased mechanical hypersensitivity was observed. Conversely, no change on GFAP and Iba-1 expression was observed in the hypothalamus and colliculus during orofacial inflammatory pain. Our data suggest an important role for glial cells in the affective-motivational dimension of orofacial pain beyond their well-explored role in the traditional nociceptive transmission circuits.

Lesões bucais em idosos usuários de prótese dentária: uma revisão de escopo / Oral lesions in elderly dental prosthesis wearers: a scoping review / Lesiones orales en usuarios de prótesis dentales de edad avanzada: una revisión de alcance

Objetivo: Mapear as evidências científicas disponíveis acerca das lesões bucais prevalentes em idosos que fazem uso de próteses dentárias. Métodos: Trata-se de uma revisão de escopo na qual os estudos foram selecionados em abril de 2022, a partir de buscas nas bases Cochrane, Lilacs, PubMed, Scopus e Web of Science. Incluíram-se estudos publicados de 1997 a 2021 e não houve restrição de idioma. Resultados: Foram incluídos 18 artigos, sendo dezesseis (88,9%) estudos transversais e dois (11,1%) estudos de coorte, de diferentes países. A estomatite protética foi a lesão mais prevalente nos idosos na maior parte dos achados, seguida por úlceras, queilite angular, hiperplasias e candidíase eritematosa. Conclusões: Os estudos analisados apontam uma maior ocorrência da estomatite protética em mulheres, sendo o uso de próteses removíveis mais propício a lesões. Sugere-se que outros protocolos de pesquisa sejam desenvolvidos a fim de evidenciar novos achados sobre a temática, em diferentes regiões. (AU).

Objective: To identify the scientific evidence available on the prevalent oral lesions in the elderly who use dental prostheses. Methods: This is a scoping review in which studies were selected in April 2022, from searches in Cochrane, Lilacs, PubMed, Scopus and Web of Science databases. Studies published from 1997 to 2021 were included, and there was no language restriction. Results: Eighteen articles were included, of which sixteen (88.9%) were cross-sectional studies and two (11.1%) were cohort studies, from different countries. Prosthetic stomatitis was the most prevalent lesion in the elderly in most findings, followed by ulcers, angular cheilitis, hyperplasia and erythematous candidiasis. Conclusions: The studies analyzed point to a higher occurrence of prosthetic stomatitis in women, with the use of removable prostheses being more prone to lesions. It is suggested that other research protocols be developed in order to highlight new findings on the subject in different regions. (AU).

Objetivo: Mapear la evidencia científica disponible sobre las lesiones orales prevalentes en los ancianos que utilizan prótesis dentales. Métodos: Se trata de una revisión de la investigación en la que los estudios fueron seleccionados en abril de 2022, a partir de búsquedas en las bases Cochrane, Lilacs, PubMed, Scopus y Web of Science. Se incluyeron los estudios publicados entre 1997 y 2021 y no hubo restricción de idioma. Resultados: Se incluyeron dieciocho artículos, de los cuales dieciséis (88,9%) eran estudios transversales y dos (11,1%) eran estudios de cohortes, procedentes de diferentes países. La estomatitis fue la lesión más prevalente en los ancianos en la mayoría de los hallazgos, seguida de las úlceras, la queilitis angular, la hiperplasia y la candidiasis eritematosa. Conclusiones: Los estudios analizados señalan una mayor ocurrencia de estomatitis protésica en las mujeres, siendo el uso de prótesis removibles más propenso a las lesiones. Se sugiere que se desarrollen otros protocolos de investigación con el fin de evidenciar nuevos hallazgos sobre el tema, en diferentes regiones. (AU).

A Comparative Analysis Applied to the Partial Discharges Identification in Dry-Type Transformers by Hall and Acoustic Emission Sensors.

Dry-type insulated transformers stand out for their higher applicability in substations, high-voltage instrumentation systems, and electrical installations. In this machine, the insulation system is constituted of dielectric materials such as epoxy resin and Nomex paper. Some critical issues in the operation of this equipment, such as overload, moisture, or heat, can induce a slow degradation of the physical-chemical properties of the dielectric materials, which can culminate in the total failure of the transformer. However, before the transformer's shutdown, it is common to detect discharge activity in the insulation system. Based on this issue, this work proposes an experimental and comparative analysis between acoustic emission and Hall-effect sensors, aiming at differentiating discharges in epoxy resin and Nomex paper, materials that constitute the insulation of the dry-type insulated transformers. Two signal processing techniques were studied: traditional frequency analysis and discrete wavelet transform. The objective is to develop signal processing techniques to differentiate each type of discharge since different discharges require different maintenance actions. The results obtained indicate that acoustic emission sensors and Hall sensors are promising in differentiating discharge in epoxy resin and Nomex paper. Furthermore, the pattern recognition tools presented by this work, which associated the wavelet levels energies and the energy of the full signals with the average band and the equivalent bandwidth, were effective to perform feature extraction of power transformer condition.

Exercise-Induced MicroRNA Regulation in the Mice Nervous System is Maintained After Activity Cessation.

BACKGROUND: Physical exercise can improve synaptic function and protect the nervous system against many diseases by altering gene regulation. MicroRNAs (miRs) have emerged as vital regulators of gene expression and protein synthesis not only in the muscular system, but also in the brain. OBJECTIVE: Here we investigated whether exercise-induced miRs expression in the nervous and muscular systems is activity-dependent or it remains regulated even after exercise cessation. METHODS: The expression profile of miR-1, -16, and -206 was monitored by RT-PCR in the dorsal root ganglion, in the spinal cord dorsal and ventral horn, and in the soleus muscle of mice after 5 weeks of swimming training and after swimming exercise followed by 4 weeks of sedentary conditions. Control animals consisted of mice that swan daily for 30s during the 5-weeks training period, returning to the non-swimming activity for additional 4 weeks. RESULTS: After exercise, miR-1 was upregulated in all tissues investigated. However, the upregulation of miR-1 continued significantly high in both aspects of the spinal cord and in the soleus muscle. The expression profiles of miR-16, and -206 were increased only in the nervous system. However, miR-16 upregulation persisted in the DRG and in the spinal cord after exercise interruption, whereas miR-206 continued upregulated only in the spinal cord ventral horn. CONCLUSION: Exercise training can cause long-lasting changes in the expression of miRs independently of exercise maintenance. Spatial and temporal expression of miRs is to some extent dependent on this activity. The data raised a new conceptual hypothesis on the biogenesis of miRs, indicating that long-lasting and systematic exercise can potentially cause irreversible miR regulation after activity cessation.

Peripheral oxytocin is inversely correlated with cognitive, but not emotional empathy in schizophrenia.

Endogenous oxytocin has been associated with different aspects of social cognition in healthy subjects and patients with schizophrenia. In this pilot study, we investigated the relationship between plasma oxytocin and oxytocin level changes induced by empathy-eliciting, attachment-related movie scenes with correlates of cognitive and emotional empathy in patients and healthy controls. The Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) were administered to patients with schizophrenia (N = 35, 12 females) and healthy controls (N = 35, 12 females) to estimate dimensions of cognitive and emotional empathy. Peripheral basal oxytocin concentrations and oxytocin responses to movie-based emotional stimuli were assessed using radioimmunoassay with sample extraction. In patients, induced oxytocin level changes were inversely correlated with MET cognitive empathy regarding negative emotional states. Controlling for non-social cognition and age revealed a significant negative association between basal oxytocin levels and MET cognitive empathy for positive emotions. In healthy subjects, oxytocin reactivity was inversely correlated with the IRI subscale "fantasy". Oxytocin was not related to any measure of emotional empathy. A hyper-reactive oxytocin system might be linked to impaired cognitive empathy as a part of a dysfunctional regulative circuit of attachment-related emotions and interpersonal stressors or threats by attribution of meaning. Healthy adults with a disposition to identify with fictional characters showed lower oxytocin reactivity, possibly indicating familiarity with movie-based stimuli. The oxytocinergic system may be involved in maladaptive coping mechanisms in the framework of impaired mentalizing and associated dysfunctional responses to interpersonal challenges in schizophrenia.

S100A9 plays a pivotal role in a mouse model of herpetic neuralgia via TLR4/TNF pathway.

Herpetic neuralgia is a painful condition following herpes zoster disease, which results from Varicella-zoster virus reactivation in the dorsal or trigeminal sensory ganglia. Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not well understood. Recently, we identified, that neuroimmune-glia interactions in the sensory ganglion is a critical mechanism for the development of herpetic neuralgia. Here, we investigate the contribution of S100A9, a well-known pro-inflammatory molecule produced by myeloid cells, for the development of herpetic neuralgia using a murine model of HSV-1 infection. We found that cutaneous HSV-1 infection results in an increase of S100A9 expression in the Dorsal Root Ganglia (DRGs). Infiltrating neutrophils into the DRGs were the main source of S100A9 post HSV-1 infection. Functionally, genetic or pharmacological inhibition of S100A9 impairs the development of HSV-1 infection-induced mechanical pain hypersensitivity. Finally, we found that the pronociceptive role of S100A9 in herpetic neuralgia depends on the TLR4/TNF pathway. These results unraveled previously unknown mechanisms involved in the pathophysiology of herpetic neuralgia and indicate that S100A9 might be an important target for novel therapies aiming acute herpetic neuralgia.

Chronic uphill and downhill exercise protocols do not lead to sarcomerogenesis in mouse skeletal muscle.

It has been suggested that eccentric contraction (EC) is associated with increases in serially arranged sarcomeres (sarcomerogenesis), while concentric contraction (CC) has been associated with serial sarcomeres decrease. Sarcomerogenesis following EC is thought to be a protective muscle adaptation, preventing muscle injury in future eccentric exercise bouts (repeated bout effect). However, the mechanisms underlying sarcomerogenesis in EC remain unknown, and the sarcomerogenic responses observed in response to EC and CC are contradictory. We measured sarcomere length, sarcomere length uniformity, serial sarcomere number, and fascicle length in gastrocnemius medialis, tibialis anterior, vastus medialis and vastus lateralis in sedentary (SED) mice, and in mice following protocols of moderate uphill (TRU) and downhill (TRD) training and uphill (OTU) and downhill (OTD) overtraining. We found pain sensitivity after the first bout of EC exercise on TRD and OTD followed by a normalized sensory response after four weeks of training, indicating a repeated bout effect. However, these findings were not associated with sarcomerogenesis, as serial sarcomere numbers did not increase in TRD and OTD skeletal muscle samples compared to controls (SED). However, we found a decrease in serial sarcomere number in VL and TA in OTU group mice, which was associated with a decrease in fascicle length and no change of sarcomere length at the tested joint configuration. We conclude that excessive concentric muscle contraction (OTU group mice), leads to a decrease in serial sarcomere number, while moderate or excessive eccentric training, did not result in sarcomerogenesis, as reported in the literature.

Dynamic expression of glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 in the mouse spinal cord dorsal horn under pathological pain states.

Objective: Animal models of chronic pain have demonstrated that glial cells are promising target for development of analgesic drugs. However, preclinical studies on glial response under chronic pain conditions vary depending on the cellular markers, the species used, the experimental design and model. Therefore, we investigate the expression profile of GFAP and Iba-1 during the behavioral manifestation of sensory disorder in inflammatory and neuropathic pain models. Methods: the expression profile of fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) were quantitated in the spinal dorsal horn of Balb/C mice submitted to six models of chronic pain. Protein analysis was performed by western blot and the results colligated with pain-related behavior. Results: Using the same method to quantitate proteins we observed that while GFAP is upregulated after axotomy, partial nerve injury and cutaneous inflammation, its expression is not changed during muscle inflammation, non-inflammatory muscle pain, and in a viral-associated pain. Differently, Iba-1 is downregulated after axotomy but upregulated after partial lesion of peripheral nerve as well as after virus inoculation and during non-inflammatory muscle pain. Cutaneous and muscle inflammation induced no change in Iba-1 expression in the dorsal horn.In spite of a marked time-dependent variation in protein expression, mechanical allodynia was present at any time of all the models investigated. Discussion: Under distinct pain conditions, GFAP and Iba-1 expression is dependent on the origin of the stimulus, disease progression and tissue affected. Moreover, their expression and is not necessarily associated to the behavior manifestation of pain.

Effect of swimming training on nerve morphological recovery after compressive injury.

OBJECTIVE: This study aims to investigate morphological alterations caused by partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity swimming training as therapeutic strategy for nerve regeneration. METHODS: A number of 30 male adult mice were equally divided in control, 14 days after PNL (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days) and 5-week exercise training after 7 days post-lesion (PNL trained 35 days) groups. PNL trained 35 days group began with a 10-min session for 3 days and this time was gradually increased by 10 min every three sessions until the animals had swum for 50 min per session. Morphoquantitative analysis was carried out to assess nerve regeneration in each group. RESULTS: PNL 14 days group exhibited less degenerating signs than PNL 42 days group, where most post-lesion alterations were visualized. Nerve area and minimum diameter were significantly lower (p < 0.05) than control group. PNL 70 days group showed a greater degree of regenerating fibers and similar morphometric parameters to control group. PNL trained 35 days demonstrated signs of regeneration, reaching control group values in the morphometric analysis. DISCUSSION: PNL promotes great histopathological changes, which became more visible at 42 post-injury days. A natural nerve-regeneration tendency was observed throughout time, as observed in PNL 70 days group; nevertheless, moderate swimming training was found to be a therapeutic resource for nerve regeneration, accelerating such process from a morphoquantitative perspective. ABBREVIATIONS: ANOVA: One-way analysis of variance; BDNF: Brain-derived neurotrophic factor; FGF-2: Fibroblast growth factor 2; GDNF: Glial cell line derived neurotrophic factor; IGF: Insulin-link growth factor; IL-1ß: Interleukin-1ß; NGF: Neural growth factor; PBS: Phosphate-buffered saline; PNL: Partial sciatic nerve ligation.

Neuroimmune-Glia Interactions in the Sensory Ganglia Account for the Development of Acute Herpetic Neuralgia.

Herpetic neuralgia is the most important symptom of herpes zoster disease, which is caused by Varicella zoster Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not totally elucidated. Here, we examined the neuroimmune interactions at the sensory ganglia that account for the genesis of herpetic neuralgia using a murine model of Herpes Simplex Virus Type-1 (HSV-1) infection. The cutaneous HSV-1 infection of mice results in the development of a zosteriform-like skin lesion followed by a time-dependent increase in pain-like responses (mechanical allodynia). Leukocytes composed mainly of macrophages and neutrophils infiltrate infected DRGs and account for the development of herpetic neuralgia. Infiltrating leukocytes are responsible for driving the production of TNF, which in turn mediates the development of herpetic neuralgia through downregulation of the inwardly rectifying K+ channel Kir4.1 in satellite glial cells. These results revealed that neuroimmune-glia interactions at the sensory ganglia play a critical role in the genesis of herpetic neuralgia. In conclusion, the present study elucidates novel mechanisms involved in the genesis of acute herpetic pain and open new avenues for its control.SIGNIFICANCE STATEMENT Acute herpetic neuralgia is the most important symptom of herpes zoster disease and it is very difficult to treat. Using a model of peripheral infection of mice with HSV-1, we have characterized for the first time the neuroimmune-glia interactions in the sensory ganglia that account for the development of acute herpetic neuralgia. Among these mechanisms, leukocytes composed mainly of macrophages and neutrophils infiltrate infected sensory ganglia and are responsible for driving the production of TNF. TNF, via TNFR1, mediates herpetic neuralgia development through downregulation of the inwardly rectifying K+ channel Kir4.1 in satellite glial cells. This study elucidates novel mechanisms involved in the genesis of acute herpetic neuralgia and open new avenues for its control.

BDNF-TRKB signaling system of the dorsal periaqueductal gray matter is implicated in the panicolytic-like effect of antidepressant drugs.

A wealth of evidence implicates the BDNF-TRKB system in the therapeutic effects of antidepressant drugs (ADs) on mood disorders. However, little is known about the involvement of this system in the panicolytic property also exerted by these compounds. In the present study we evaluated the participation of the BDNF-TRKB system of the dorsal periaqueductal gray matter (DPAG), a core structure involved in the pathophysiology of panic disorder, in AD-induced panicolytic-like effects in rats. The results showed that short- (3 days) or long-term (21 days) systemic treatment with the tricyclic ADs imipramine, clomipramine or desipramine increased BDNF levels in the DPAG. Only longterm treatment with the selective serotonin reuptake inhibitor fluoxetine was able to increase BDNF levels in this structure. After 21-day treatment, fluoxetine and the three tricyclic ADs used also increased BDNF concentration in the hippocampus, a key area implicated in their mood-related actions. Neither in the DPAG nor hippocampus did long-term treatment with the standard anxiolytics diazepam, clonazepam or buspirone affect BDNF levels. Imipramine, both after short and long-term administration, and fluoxetine under the latter regimen, raised the levels of phosphorylated TRKB in the DPAG. Short-term treatment with imipramine or BDNF microinjection inhibited escape expression in rats exposed to the elevated T maze, considered as a panicolytic-like effect. This anti-escape effect was attenuated by the intra-DPAG administration of the TRK receptor antagonist k252a. Altogether, our data suggests that facilitation of the BDNF-TRKB system in the DPAG is implicated in the panicolytic effect of ADs.

Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.

Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain.

Cultivo consorciado de soja com braquiária / Intercropping of braquiária with soybean

Objetivou-se nesse trabalho estudar o cultivo consorciado da Brachiaria brizantha cv. Marandu com a soja. O experimento foi implantado em área sob sistema plantio direto vigente há 3 anos, em Latossolo Vermelho eutroférrico, no município de Maripá - PR. O delineamento experimental foi de blocos casualizados com cinco repetições. A produção e o valor nutricional do capim Marandú foram estudados em quatro tratamentos que consistiram de épocas de semeadura da braquiária em relação á semeadura da soja: antecipada (sete dias antes da semeadura da soja), conjunta (mesmo dia da semeadura da soja), e defasada (nos estádios V3 e R1 da soja). No estudo da produtivividade, teor de nitrogênio e teor de óleo nos grãos da cultura da soja foram adotados seis tratamentos que constaram de épocas de semeadura do capim Marandu, [antecipada (sete dias antes da semeadura da soja), conjunta (mesmo dia da semeadura da soja), após (estádio V3, R1 e R5 da soja) em relação à data de semeadura da soja, mais o cultivo exclusivo da leguminosa (solteira)]. A maior produtividade de massa seca pela forrageira ocorre com a semeadura antecipada, entretanto, nesse caso ocorre a maior redução de produtividade da soja. A época de semeadura da braquiária até o R5 da soja não tem influência sobre o valor nutricional da forrageira. O cultivo consorciado da soja com Brachiaria brizantha cv. Marandu não tem influência sobre o teor de nitrogênio foliar, teor de óleo e atividade de enzima peroxidase da soja. A maior produtividade da soja ocorre quando a mesma é cultivada solteira ou quando a braquiária for semeada no estádio R5. O teor de proteína bruta dos grãos da soja é reduzido quando a semeadura da braquiária ocorre antecipadamente ou em conjunto com a soja em relação ao cultivo solteiro.

The objective of this work was to study the intercropping of Brachiaria brizantha. Marandu with soybeans. The experiment has been planted in a 3 year prevailing area with no-tillage, in eutrophic Oxisol at Maripá ­ PR. The experimental design was a randomized block with five replications. For the forage study, four treatments were performed which consisted of seeding times brachiaria [early (seven days before planting soybeans) joint (same day of soybean planting) and after (at stages V3 and R1 culture)] intercropping with soybean. To study the yield and crude protein and oil levels of the grain were adopted six treatments, which consisted of sowing dates of "capim Marandu" [early (seven days before planting soybeans), joint (same day of soybean planting ) after (V3, R1 and R5 soybean) and in single culture (single)]. The forager higher productivity of dry matter occurs with early sowing, however, the greatest reduction in soybean yield also occurs in this case. The sowing of Brachiaria until R5 soy has no influence on the nutritional value of the forage. The intercropped of soybean with Brachiaria brizantha. Marandu has no impact on the leaf Nitrogen content, oil content and enzyme activity of soybean peroxidase. The highest yield of soybeans occurs when it is grown single or Brachiaria is sown in stage R5. The crude protein content of soybean grain is reduced when brachiaria seeding is early or together with soybeans compared to single culture.

Substituição da adubação nitrogenada mineral pela cama de frango na sucessão aveia/milho / Mineral nitrogen substitution by chicken litter in succession oat/corn

A busca constante pela sustentabilidade dos sistemas de produção têm direcionado as pesquisas a buscar alternativas aos problemas oriundos da intensificação dos sistemas produtivos. Nesse contexto o presente trabalho teve como objetivo estudar os efeitos da substituição da adubação nitrogenada mineral pela cama de frango sucessão aveia-milho e nas características químicas do solo. O trabalho foi desenvolvido durante o período de maio de 2009 a março de 2010 em área de Latossolo Vermelho eutroférrico. O delineamento foi de blocos ao acaso com quatro repetições. Os seis tratamentos foram obtidos com a combinação de diferentes quantidades de cama de frango (0, 1500, 3000, 4500, 6000 e 7500 kg ha-1) aplicadas 30 dias antes da semeadura da aveia combinadas com a adubação nitrogenada mineral de cobertura aplicada na cultura do milho (311,1; 257,8; 202,2; 148,9; 95,6; 42,2 kg ha-1 de uréia), visando o fornecimento total de 140 kg ha-1 de nitrogênio (N). A aplicação de cama de frango na cultura da aveia favorece o aumento da produção de massa seca, teor e acúmulo de N. A substituição da adubação nitrogenada mineral pela cama de frango eleva os índices de produtividade da cultura do milho. A utilização de cama de frango altera as propriedades químicas do solo, elevando os teores de matéria orgânica, alumínio trocável e a acidez potencial. Entretanto reduz o pH, K, Ca, Mg, soma de bases e saturação por bases.

The constant search for sustainability of production systems have driven research to find alternatives to the problems arising from the intensified use such systems. In this context the present work aimed study the effects of substitution of mineral nitrogen by chicken litter in oat and corn crop in succession and the chemical characteristics of soil. The study was conducted during the period May 2009 to March 2010 in area of Oxisol. The design was of randomized block with four replications. The six treatments were obtained by a combination of different amounts of chicken litter (0, 1500, 3000, 4500, 6000 and 7500 kg ha-1) applied 30 days before the sowing of oats combined with the mineral nitrogen applied in coverage in corn (311.1, 257.8, 202.2, 148.9, 95.6, 42.2 kg ha-1 of urea), for the total supply of 140 kg ha-1 of nitrogen (N). The application of poultry litter in oat promotes increased the production of dry matter, and content and accumulation of N. The mineral nitrogen substitution by chicken litter increases the yield of corn crop. The use of poultry litter alters the chemical properties of soil, increasing the levels of organic matter, exchangeable Al and acidity potential. However lowers the pH, K, Ca, Mg, sum of bases and base saturation.

Long-term antidepressant treatment inhibits neuropathic pain-induced CREB and PLCγ-1 phosphorylation in the mouse spinal cord dorsal horn.

UNLABELLED: The effect of long-term administration of imipramine, a tricyclic antidepressant, on the phosphorylation status of cyclic adenosine monophosphate-responsive element-binding protein (CREB), mitogen-activated protein kinase family members, and phospholipase γ-1 (PLCγ-1) was investigated in the dorsal horn of the spinal cord following peripheral nerve lesion. Nerve injury induced an ipsilateral long-lasting increased phosphorylation of CREB and PLCγ-1 but not extracellular signal-regulated kinase (ERK1,2), p38, and c-Jun N-terminal kinase. Daily administration of imipramine (5, 10, or 30 mg/kg) for 21 days progressively reduced both tactile-induced neuropathic pain hypersensitivity and thermal hyperalgesia. After withdrawal of treatment, the antinociceptive effect of imipramine was gradually abolished but still remained for at least 3 weeks. Conversely, no analgesic effect was observed with short-term imipramine treatment. Moreover, imipramine therapy reversed nerve injury-induced CREB and PLCγ-1 phosphorylation but had no effect on ERK1,2, p38, and c-Jun N-terminal kinase activity. These results indicate that long-term administration of imipramine may prevent some of the harmful changes in the spinal cord dorsal horn following nerve injury. However, imipramine analgesic effect takes time to develop and mature, which might explain in part why the clinical analgesic effect of tricyclic antidepressants develops with a delay after the beginning of treatment. Our data also provide evidence that prolonged imipramine treatment may induce antinociception in neuropathic pain conditions because of its action on the PLCγ-1/CREB-signaling pathway. PERSPECTIVE: This article demonstrates that long-term treatment with imipramine reverses some of the marked effects induced by peripheral nerve injury in the spinal dorsal horn that contribute to long-term maintenance of sensory disorder, providing a new view to the mechanisms of action of these drugs.

Differential expression of microRNAs in mouse pain models.

BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs. The expression of numerous brain-specific miRNAs with a high degree of temporal and spatial specificity suggests that miRNAs play an important role in gene regulation in health and disease. Here we investigate the time course gene expression profile of miR-1, -16, and -206 in mouse dorsal root ganglion (DRG), and spinal cord dorsal horn under inflammatory and neuropathic pain conditions as well as following acute noxious stimulation. RESULTS: Quantitative real-time polymerase chain reaction analyses showed that the mature form of miR-1, -16 and -206, is expressed in DRG and the dorsal horn of the spinal cord. Moreover, CFA-induced inflammation significantly reduced miRs-1 and -16 expression in DRG whereas miR-206 was downregulated in a time dependent manner. Conversely, in the spinal dorsal horn all three miRNAs monitored were upregulated. After sciatic nerve partial ligation, miR-1 and -206 were downregulated in DRG with no change in the spinal dorsal horn. On the other hand, axotomy increases the relative expression of miR-1, -16, and 206 in a time-dependent fashion while in the dorsal horn there was a significant downregulation of miR-1. Acute noxious stimulation with capsaicin also increased the expression of miR-1 and -16 in DRG cells but, on the other hand, in the spinal dorsal horn only a high dose of capsaicin was able to downregulate miR-206 expression. CONCLUSIONS: Our results indicate that miRNAs may participate in the regulatory mechanisms of genes associated with the pathophysiology of chronic pain as well as the nociceptive processing following acute noxious stimulation. We found substantial evidence that miRNAs are differentially regulated in DRG and the dorsal horn of the spinal cord under different pain states. Therefore, miRNA expression in the nociceptive system shows not only temporal and spatial specificity but is also stimulus-dependent.