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The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.

O conteúdo de dopamina nas estruturas cerebrais tem sido relacionado à excitabilidade neuronal e várias abordagens têm sido utilizadas para estudar este fenômeno durante o período de vulnerabilidade às crises. No presente trabalho, descrevemos os efeitos da depleção de dopamina após a administração de 6-hidroxidopamina (6-OHDA) na região pars compacta da substância negra de ratos submetidos ao modelo de epilepsia com pilocarpina. A susceptibilidade ao estado de mal epiléptico induzido pela pilocarpina, bem como a frequência de crises espontâneas e recorrentes durante o período crônico do modelo foi determinada. Sendo o hipocampo uma das principais estruturas afetadas no desenvolvimento desse modelo experimental de epilepsia, os níveis de dopamina nessa região foram determinados após a administração da droga. No primeiro experimento, 62% (15/24) dos ratos pré-tratados com 6-OHDA e 45% (11/24) daqueles que receberam ácido ascórbico como solução controle evoluíram para crises límbicas motoras e para o estado de mal epiléptico, após a administração de pilocarpina. A gravidade das crises durante o período agudo do modelo foi significativamente maior nos ratos epilépticos experimentais (56,52%) do que nos ratos controle (4,16%). No segundo experimento, não houve diferença significante entre os grupos quanto à frequência de crises na fase crônica do modelo. Nossos dados mostraram que a dopamina pode desempenhar um papel importante na gravidade das crises na fase aguda da pilo, o que parece ser exercido por sua ação inibitória da dopamina sobre a expressão motora das crises.

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The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

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The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.

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The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

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AIMS: 1) Characterize the progression of exercise intolerance in monocrotaline-induced pulmonary hypertension (PH) in mice and 2) evaluate the therapeutic effect of aerobic exercise training (AET) on counteracting skeletal and cardiac dysfunction in PH. MAIN METHODS: Wild type C57BL6/J mice were studied in two different time points: 2 months and 4 months. Exercise tolerance was evaluated by graded treadmill exercise test. The AET was performed in the last month of treatment of 4 months' time point. Cardiac function was evaluated by echocardiography. Skeletal muscle cross-sectional area was assessed by immunofluorescence. The diameter of cardiomyocytes and pulmonary edema were quantified by staining with hematoxylin-eosin. The variables were compared among the groups by two-way ANOVA or non-paired Student's t-test. Significance level was set at p < 0.05. KEY FINDINGS: After 2 months of MCT treatment, mice presented pulmonary edema, right cardiac dysfunction and left ventricle hypertrophy. After 4 months of MCT treatment, mice showed pulmonary edema, right and left cardiac dysfunction and remodeling associated with exercise intolerance and skeletal muscle atrophy. AET was able to reverse cardiac left ventricle dysfunction and remodeling, prevent exercise intolerance and skeletal muscle dysfunction. Thus, our data provide evidence of skeletal muscle abnormalities on advanced PH. AET was efficient in inducing an anti-cardiac remodeling effect besides preventing exercise intolerance. SIGNIFICANCE: Our study provides a robust model of PH in mice, as well as highlights the importance of AET as a preventive strategy for exercise intolerance and, skeletal and cardiac muscle abnormalities in PH.

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Cleft palate is a common malformation of craniofacial development, and postnatal deficiencies in palate formation may occur. The aim of this study was to determine whether alendronate treatment could induce maxillary mineralization and thus reduce the need for surgical procedures. The effects of alendronate on maxillary bone development, the midpalatal suture, and the levels of transforming growth factor beta-1 (TGF-ß1), bone morphogenetic protein 2 (BMP-2), collagen I and II, and V-ATPase were evaluated in newborn rats. Thirty newborn rats were placed in a control group and 30 in a group that received intraperitoneal alendronate (2.5 mg/kg/day). The animals were euthanized on day 7 or 12, and the heads were subjected to histological and immunohistochemical analyses. Specimens from rats that received alendronate presented larger bone matrix deposition in areas of intramembranous ossification of the maxillary bone when compared to controls. Furthermore, higher levels of TGF-ß1, BMP-2, and collagen I were observed, whereas osteoclasts showed no V-ATPase. The alendronate group also showed higher levels of TGF-ß1 and collagen II in the midpalatal suture, whereas BMP-2 levels were lower than in controls. These results coincided with an expansion of the chondroid. In conclusion, alendronate increased the intramembranous ossification in the maxillary bone in association with increased expression of TGF-ß1, BMP-2, and collagen I and decreased V-ATPase. The drug induced an expansion of chondrocytes and a decrease in mineral bone deposition despite the high levels of TGF-ß1 in this area. Alendronate may therefore be useful in the treatment of diseases affecting bone growth.

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Fresh frozen allograft bone is routinely used in orthopedic surgery for the reconstruction of large bone defects, and its use in oral and maxillofacial surgery is increasing. The purpose of this case was to demonstrate the installation of dental implants and the use of fresh frozen bone for reconstruction of anterior maxilla in the same surgery. This case report presents the insertion of dental implants followed immediately by a placement of fresh frozen allograft in block and particle for a reconstruction of atrophic anterior maxillary in the same surgery. Ten months subsequent to this procedure, provisional fixed prosthesis was installed on the implants. Four months later (postoperative month 14), the final fixed prosthesis was installed and the clinical success was observed. The insertion of dental implants followed immediately by a placement of fresh frozen allograft is a safe and efficient process that results in the successful return of dental function and aesthetic rehabilitation for the patient.

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We aimed to evaluate the effects of acute heat stress (HS) and age on the redox state in broilers aged 21 and 42 days. We evaluated the expression of genes related to antioxidant capacity, the production of hydrogen peroxide (H2O2), and the activity of antioxidant enzymes in the liver, as well as oxidative stress markers in the liver and plasma. The experiment had a completely randomized factorial design with two thermal environments (thermoneutral and HS, 38°C for 24 h) and two ages (21 and 42 days). Twenty-one-day-old animals exposed to HS showed the highest thioredoxin reductase 1 (TrxR1) (P<0.0001) and glutathione synthetase (GSS) (P<0.0001) gene expression levels. Age influenced the expression of the thioredoxin (Trx) (P=0.0090), superoxide dismutase (SOD) (P=0.0194), glutathione reductase (GSR) (P<0.0001) and glutathione peroxidase 7 (GPx7) (P<0.0001) genes; we observed greater expression in birds at 21 days than at 42 days. Forty-two-day-old HS birds showed the highest H2O2 production (222.31 pmol dichlorofluorescein produced/min×mg mitochondrial protein). We also verified the effects of age and environment on the liver content of Glutathione (GSH) (P<0.0001 and P=0.0039, respectively) and catalase (CAT) enzyme activity (P=0.0007 and P=0.0004, respectively). Higher GSH content and lower CAT activity were observed in animals from the thermoneutral environment compared with the HS environment and in animals at 21 days compared with 42 days. Broilers at 42 days of age had higher plasma creatinine content (0.05 v. 0.01 mg/dl) and higher aspartate aminotransferase activity (546.50 v. 230.67 U/l) than chickens at 21 days of age. Our results suggest that under HS conditions, in which there is higher H2O2 production, 21-day-old broilers have greater antioxidant capacity than 42-day-old animals.

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