Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice.

Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/kg, MLE (4, 20, or 100 mg/kg), fractions (F1 to F6), lupeol 10 mg/kg or diazepam (3 mg/kg). Methanolic leaf extract preserved neuron viability as well as the relative organ weight, and hematological and biochemical parameters. The behavioral endpoints, neuromuscular coordination, and sensory response parameters revealed a dose-dependent effect of methanolic leaf extract. This extract, active fractions, lupeol, and diazepam potentiated the hypno-sedative effect of the barbiturate and attenuated PTZ-induced acute seizure. This antiseizure effect was completely reversed by flumazenil 2 mg/kg (benzodiazepine site antagonist). Altogether, the benzodiazepine site-mediated anticonvulsant effects of methanolic leaf extract, active fractions, and lupeol corroborate traditional application of T. globiferus against epilepsy.

Forced internal desynchrony induces cardiometabolic alterations in adult rats.

Disruptions in circadian rhythms have been associated with several diseases, including cardiovascular and metabolic disorders. Forced internal desynchronization induced by a period of T-cycles of 22 h (T22 protocol) reaches the lower limit of entrainment and dissociates the circadian rhythmicity of the locomotor activity into two components, driven by different outputs from the suprachiasmatic nucleus (SCN). The main goal of this study was to evaluate the cardiovascular and metabolic response in rats submitted to internal desynchronization by T22 protocol. Male Wistar rats were assigned to either a control group subjected to a usual T-cycles of 24 h (12 h-12 h) or an experimental group subjected to the T22 protocol involving a 22-h symmetric light-dark cycle (11 h-11 h). After 8 weeks, rats subjected to the T22 exhibited desynchrony in their locomotor activity. Although plasma glucose and insulin levels were similar in both groups, desynchronized rats demonstrated dyslipidemia, significant hypertrophy of the fasciculate zone of the adrenal gland, low IRB, IRS2, PI3K, AKT, SOD and CAT protein expression and an increased expression of phosphoenolpyruvate carboxykinase in the liver. Furthermore, though they maintained normal baseline heart rates and mean arterial pressure levels, they also presented reduced baroreflex sensitivity. The findings indicate that circadian timing desynchrony following the T22 protocol can induce cardiometabolic disruptions. Early hepatic metabolism dysfunction can trigger other disorders, though additional studies are needed to clarify the causes.

Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats.

The infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DßH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABAA receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.

Median preoptic nucleus mediates the cardiovascular recovery induced by hypertonic saline in hemorrhagic shock.

Changes in plasma osmolarity, through central and peripheral osmoreceptors, activate the median preoptic nucleus (MnPO) that modulates autonomic and neuroendocrine adjustments. The present study sought to determine the participation of MnPO in the cardiovascular recovery induced by hypertonic saline infusion (HSI) in rats submitted to hemorrhagic shock. The recordings of mean arterial pressure (MAP) and renal vascular conductance (RVC) were carried out on male Wistar rats (250-300 g). Hemorrhagic shock was induced by blood withdrawal over 20 min until the MAP values of approximately 60 mmHg were attained. The nanoinjection (100 nL) of GABAA agonist (Muscimol 4 mM; experimental group (EXP)) or isotonic saline (NaCl 150 mM; control (CONT)) into MnPO was performed 2 min prior to intravenous overload of sodium through HSI (3 M NaCl, 1.8 mL/kg, b.wt.). Hemorrhagic shock reduced the MAP in control (62 ± 1.1 mmHg) and EXP (61 ± 0.4 mmHg) equipotently. The inhibition of MnPO impaired MAP (CONT: 104 ± 4.2 versus EXP: 60 ± 6.2 mmHg) and RVC (CONT: 6.4 ± 11.4 versus EXP: -53.5 ± 10.0) recovery 10 min after HSI. The overall results in this study demonstrated, for the first time, that the MnPO plays an essential role in the HSI induced resuscitation during hypovolemic hemorrhagic shock.

A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats.

Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-ß-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1)) or free saporin (sham, 0.021 ng.nL(-1)) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1), b.wt., for longer than 1 min). In the sham-group (n = 8), HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-DßH-saporin-treated rats (n = 11)were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DßH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

Prevalence of eating disorder attitudes among men and women with exercise dependence symptoms: a non-athlete population study / Prevalência de transtornos alimentares entre homens e mulheres com sintomas de dependência de exercícios: um estudo na população de não atletas / Prevalencia de los trastornos alimentarios entre hombres y mujeres con síntomas de dependencia de ejercicios: estudio de la población no deportista

The present study sought to describe the prevalence of Secondary Exercise Dependence (ScED, i.e. eating disorders attitudes along with exercise dependence symptoms) may differ between men and women in a broader exercising population. In this study, 174 regularly exerciser, aged 18-62 years old, who were invited to respond the Exercise Dependence Scale (EDS) and the Eating Attitudes Test (EAT-26). There were more women than men with ScED. However, only men in the sample presented exercise dependence symptoms without eating disorders attitudes. Eating disorders may or may not exist in those who are exercise dependent in the broad exercising population, although there is a higher prevalence of ScED in women than men.

O presente estudo buscou descrever a prevalência da Dependência de Exercícios Secundário (DESc, ou seja, atitudes alimentares de risco associadas com sintomas de dependência de exercícios) entre homens e mulheres em uma população não-atleta. Neste trabalho, 174 praticantes regulares de exercícios físicos, entre 18 e 62 anos, quando abordados responderam à Escala de Dependência de Exercícios (EDE) e ao Eating Attitudes Test (EAT-26). Houve mais mulheres do que homens com DESc. Contudo, somente os homens apresentaram sintomas de dependência de exercícios com ausência de atitudes alimentares de risco. Os transtornos alimentares podem ou não ocorrer entre não-atletas dependentes de exercícios físicos, embora haja uma maior prevalência de DESc entre as mulheres.

El estudio tiene como objetivo describir la prevalencia de la Dependencia de Ejercicio Secundaria (DESc, a saber riesgo de trastornos alimentarios asociado con los síntomas de dependencia de ejercicios) entre hombres y mujeres en una población no atleta. En este trabajo, 174 practicantes de ejercicios físicos regulares, entre 18 y 62 años, cuando abordados respondieron a la Escala de Dependencia del Ejercicio (EDE) y Eating Attitudes Test (EAT-26). Hubo más mujeres que hombres con DESc. Todavía, sólo los hombres mostraron síntomas de dependencia de ejercicios desasociado de los riesgos de trastorno alimentarios. Trastornos alimentarios pueden existir entre los practicantes de ejercicios no deportistas, aunque hay una mayor prevalencia de mujeres con DESc.

A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats.

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280-350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6) or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were anesthetized (urethane 1.2 g⋅kg(-1) b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml⋅kg(-1) b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (-45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition.

Renal sympathoinhibition induced by hypernatremia: involvement of A1 noradrenergic neurons.

Several findings suggest that A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. Recently we demonstrated that the renal vasodilation induced by infusion of hypertonic saline (HS) depends on the integrity of the A1 neurons. Here we determined the effect of lesions of these neurons on the inhibition of the renal sympathetic nerve activity (RSNA) induced by HS infusion. All experiments were performed in Wistar rats (280-350 g). A1 neurons were lesioned by microinjections of antidopamine-beta-hydroxylase-saporin (6.3 ng in 60 nl) into the CVLM (n=5), whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n=10). Two weeks later, rats were anesthetized (urethane 1.2 g/kg, iv), and instrumented for recording of arterial pressure and RSNA. In sham rats, HS infusion (3 M NaCl, 0.18 ml/100 g bw, iv) induced a transient (

Mood changes after maximal exercise testing in subjects with symptoms of exercise dependence.

Considering exercise has positive and negative reinforcing properties, the mood states of sedentary, nonexercise-dependent and exercise-dependent volunteers were compared after maximal exercise testing. Mood status was evaluated by the Beck Depression Inventory, Trait-State Anxiety Inventory, and Profile of Mood States (POMS). No differences were detected before the test or after it, indicating little possibility of positive reinforcement. However, a significant reduction in the POMS Tension-Anxiety scores was observed in both exerciser groups (greater in the exercise-dependent group) but not in the sedentary group. Only in the exercise-dependent group were significant reductions in Anger and Total Mood Disorders scores observed compared with their pre-exercise scores. These data suggest that exercising has stronger negative reinforcement properties for exercise-dependent volunteers and is a factor which could increase the odds of their becoming dependent on exercise.

Dependência da prática de exercícios físicos: estudo com maratonistas brasileiros / Exercise dependence: a study with Brazilian marathon runners

O presente estudo teve como objetivo testar, numa amostra de maratonistas brasileiros, a versão em português da adaptaçäo da Escala de Dependência de Corrida proposta por Hailey e Bailey (1982). Métodos e resultados:59 maratonistas de uma equipe da cidade de São Paulo foram abordados e orientados a preencher a Escala de Dependência de Corrida (EDC). A amostra foi composta, na sua maior parte, por homens (72 por cento) com média de 34 ± 7 anos, sendo que 77 por cento corriam habitualmente havia cerca de dois a oito anos; 42,5 por cento corriam de quatro a cinco vezes/semana e 81 por cento dedicavam-se de uma a duas horas/dia em média para seus treinos. A média na pontuaçäo total da EDC foi de 5 ± 2,5 pontos (escala 0-14 pontos). A correlaçäo entre a pontuaçäo total da EDC com cada uma das 23 questöes que compöem o instrumento revelou que 10 questöes apresentaram níveis de correlaçäo significativos. As respostas positivas que apresentaram maior sensibilidade foram: "Sinto que me falta algo quando näo corro" (r = 0,61); "A corrida tem influenciado meu estilo de vida" (r = 0,58) e "Experimento grande prazer quando corro" (r = 0,56). Conclusäo: Observamos na amostra brasileira níveis médios de pontuaçäo na escala semelhantes aos descritos pelos autores do instrumento original, sugerindo que a traduçäo näo alterou a sensibilidade da escala e que este instrumento possa ser útil no estudo da dependência da prática de corrida (ou exercícios físicos) em desportistas brasileiros