Etomidate as an anesthetic in Colossoma macropomum: Behavioral and electrophysiological data complement each other as a tool to assess anesthetic safety.

The use of anesthetic agents in the management of fish in fish farming or ornamental fish breeding aims to minimize stress and promote animal welfare. Therefore, this study aims to investigate behavioral, electrocardiographic, and ventilatory characteristics of tambaquis exposed to anesthetic baths with etomidate. The study was conducted with juvenile tambaquis (27.38 ± 3.5g) n = 99, at etomidate concentrations of 2-4 mg.L -1, analyzing induction and anesthetic recovery behavior (experiment I), electrocardiogram (experiment II), and opercular movement (experiment III). Fish exposed to high concentrations of etomidate reached the stage of general anesthesia faster, however, the recovery time was longer, characterizing a dose-dependent relationship. Cardiorespiratory analyzes demonstrated a reduction in heart rate (69.19%) and respiratory rate (40.70%) depending on the concentration of etomidate used during anesthetic induction. During the recovery period, there was cardiorespiratory reversibility to normality. Therefore, etomidate proved to be safe as an anesthetic agent for this species at concentrations of 2 to 3 mg.L -1 for short-term anesthesia, but at higher doses the animals showed slow reversibility of anesthesia in a gradual manner and without excitability. The hemodynamic effect due to the rapid decrease in heart rate includes a negative factor of using higher concentrations of etomidate for Colossome macropomum anesthesia.

Dexamethasone attenuates low-frequency brainwave disturbances following acute seizures induced by pentylenetetrazol in Wistar rats.

Seizures are neurological disorders triggered by an imbalance in the activity of excitatory and inhibitory neurotransmitters in the brain. When triggered chronically, this imbalance can lead to epilepsy. Critically, many of the affected individuals are refractory to treatment. Given this, anti-inflammatory drugs, in particular glucocorticoids, have been considered as a potential antiepileptogenic therapy. Glucocorticoids are currently used in the treatment of refractory patients, although there have been contradictory results in terms of their use in association with antiepileptic drugs, which reinforces the need for a more thorough investigation of their effects. In this context, the present study evaluated the effects of dexamethasone (DEX, 0.6 mg/kg) on the electroencephalographic (EEG) and histopathological parameters of male Wistar rats submitted to acute seizure induced by pentylenetetrazol (PTZ). The EEG monitoring revealed that DEX reduced the total brainwave power, in comparison with PTZ, in 12 h after the convulsive episode, exerting this effect in up to 36 h (p < 0.05 for all comparisons). An increase in the accommodation of the oscillations of the delta, alpha, and gamma frequencies was also observed from the first 12 h onwards, with the accommodation of the theta frequency occurring after 36 h, and that of the beta frequency 24 h after the seizure. The histopathological analyses showed that the CA3 region and hilum of the hippocampus suffered cell loss after the PTZ-induced seizure (control vs. PTZ, p < 0.05), although DEX was not able to protect these regions against cell death (PTZ vs. DEX + PTZ, p > 0.05). While DEX did not reverse the cell damage caused by PTZ, the data indicate that DEX has beneficial properties in the EEG analysis, which makes it a promising candidate for the attenuation of the epileptiform wave patterns that can precipitate refractory seizures.

Recording of hippocampal activity on the effect of convulsant doses of caffeine.

Seizures occur when there is a hyper-excitation of the outer layer of the brain, with subsequent excessive synchrony in a group of neurons. According to the World Health Organization (WHO), an estimated 50 million people are affected by this disease, a third of whom are resistant to the treatments available on the market. Caffeine (1,3,7-trimethylxanthine), which belongs to the purine alkaloid family, is the most widely consumed psychoactive drug in the world. It is ingested by people through drinks containing this substance, such as coffee, and as an adjuvant in analgesic therapy with non-steroidal antiflammatory drugs. The present study evaluated the electrocorticographic changes observed in the hippocampus of Wistar rats subjected to acute doses of caffeine (150 mg/kg i.p), which represents a toxic dose of caffeine corresponding to an estimated acute intake of more than 12 cups of coffee to record its convulsant activity. Our results showed, for the first time, that the administration of high doses of caffeine (150 mg/kg i.p.) in rats caused an increase in the spectral distribution of power in all frequency bands and suggested the appearance of periods of ictal and interictal peaks in the electrocorticogram (ECog). We have also shown that the anticonvulsants phenytoin, diazepam and phenobarbital have a satisfactory response when associated with caffeine.

Hypoglycemic and hypolipidemic effects of Lippia origanoides Kunth in diabetic rats.

Diabetes mellitus is a metabolic disorder commonly associated with atherosclerosis. Plants with therapeutic potential, such as Lippia origanoides Kunth, emerge as effective alternatives for treating these diseases. Therefore, this work aims to analyze the antihyperglycemic and antidyslipidemic potential of the hydroalcoholic extract of Lippia origanoides Kunth (ELo) in alloxan-diabetic rats. Animals were treated orally: normal control, hyperglycemic control, positive control glibenclamide (5 mg/kg), and groups treated with ELo (75, 150, and 250 mg/kg). Preclinical evaluation of ELo showed hypoglycemic, hypolipidemic, hepatic, and renal protective effects. At all doses, ELo significantly reduced hyperglycemia, triglycerides, total cholesterol, low-density lipoprotein, atherogenic index, atherogenic coefficient, and cardiovascular risk index (p < .05). Elo at different doses promoted an increase in insulin release compared to untreated animals (p < .05) and showed α-glucosidase inhibitory activity (p < .05). Also, ELo (250 mg/kg group) showed maximum reduction of hyperglycemia, alanine transaminase, aspartate aminotransferase, malonaldehyde, and urea compared to the hyperglycemic and glibenclamide groups, and creatinine only compared to the hyperglycemic groups (p < .05). The promising action of ELo in the context of diabetes may be related to the synergistic action of flavonoid compounds identified in liquid chromatography, whose pharmacological capabilities have already been documented in previous studies. The mechanisms may be the stimulation of insulin release; the inhibitory activity of α-glucosidase; improving general clinical conditions; and the antioxidant effects of the extract. These findings pave the way for the future development of an herbal presentation of L. origanoides Kunth as a hypoglycemic and cardiovascular protector with a lipid-lowering effect.

Behavioral and electrophysiological study in Colossoma macropomum treated with different concentrations of Nepeta cataria oil in an immersion bath revealed a therapeutic window for anesthesia.

The purpose of this study was to characterize the activity of essential oils from Nepeta Cataria (EON) at concentrations of 125 µ L  L-1, 150 µ L  L-1, 175 µ L  L-1, and 200 µ L  L-1 on the behavior of loss of the posture reflex and recovery of the posture reflex and electrocardiographic activity and recording of the opercular beat of Colossoma macropomum during immersion bathing for a period of 5 min, in order to obtain a window for safe use during anesthesia. The fish (23.38 ± 3.5 g) were assigned to the following experiments: experiment 1 (latency to loss and recovery of the posture reflex): (a) 125 µ L  L-1, (b) 150 µ L  L-1, (c) 175 µ L  L-1, and (d) 200 µ L  L-1 (n = 9) per group. Experiment 2 (electrocardiographic and heartbeat recordings): (a) control group; (b) vehicle control group (2 ml of alcohol per liter of water), (c) 125 µ L  L-1, (d) 150 µ L  L-1, (e) 175 µ L  L-1, and (f) 200 µ L  L-1 (n = 9), per group. All the concentrations used showed efficacy in inducing loss of the posture reflex and reversibility with recovery of the posture reflex, but the electrocardiographic recordings indicated morphographic changes such as bradycardia during induction and p wave apiculation during recovery at the highest concentrations tested. In this way, we suggest a safe use window for short-term anesthesia with EON in the concentration range of 125 to 150 µ L  L-1 for juvenile Colossoma macropomum.

Potentiation of the depressant effect of alcohol by flunitrazepam in rats: an electrocorticographic, respiratory and electrocardiographic study.

Alcohol, a widely commercialized psychotropic drug, and the benzodiazepine Flunitrazepam, an anxiolytic widely prescribed for patients with anxiety and insomnia problems, are well known drugs and both act on the central nervous system. The misuse and the association of these two drugs are public health concerns in several countries and could cause momentary, long-lasting and even lethal neurophysiological problems due to the potentiation of their adverse effects in synergy. The present study observed the result of the association of these drugs on electrophysiological responses in the brain, heart, and respiratory rate in Wistar rats. 8 experimental groups were determined: control, one alcohol group (20% at a dose of 1 ml/100 g VO), three Flunitrazepam groups (doses 0.1; 0.2 and 0.3 mg/kg) and three alcohol-Flunitrazepam groups (20% at a dose of 1 ml/100 g VO of alcohol, combined with 0.1; 0.2 and 0.3 mg/kg of Flunitrazepam, respectively). The results showed that there was a more pronounced reduction in alpha and theta wave power in the alcohol-Flunitrazepam groups, a decrease in the power of beta oscillations and greater sedation. There was a progressive decrease in respiratory rate linked to the increase of Flunitrazepam dose in the alcohol-Flunitrazepam associated administration. It was observed alteration in heart rate and Q-T interval in high doses of Flunitrazepam. Therefore, we conclude that the association alcohol-Flunitrazepam presented deepening of depressant synergistic effects according to the increase in the dose of the benzodiazepine, and this could cause alterations in low frequency brain oscillations, breathing, and hemodynamics of the patient.

Establishing a safe anesthesia concentration window for Nile tilapia (Oreochromis niloticus) (Linnaeus 1758) by monitoring cardiac activity in eugenol immersion baths.

Nile tilapia, Oreochromis niloticus, is the most cultivated fish species in the world, due to its low cost, high growth rate, environmental adaptability, and resistance to disease and stress. Anesthetics for fish become necessary in management because they minimize mortality during transport and maintenance of ponds, one of the most used anesthetics is clove oil, which has eugenol as the major substance, representing 90-95 % of clove oil. The present study evaluates the effect of eugenol on cardiac activity in Oreochromis niloticus specimens and relates it to behavioral data to determine a concentration window for safe anesthesia. For the comportamental analysis, was used five treatments (50, 75, 100, 125, and 150 µL·L-1) were evaluated and for the eletrocardiographic test was used seven groups (Control, Vehicle, 50, 75, 100, 125, and 150 µL·L-1), n = 9/treatment, totaling 108 animals. Behavioral and electrocardiographic tests were performed on all treatments during induction and recovery. The results of the behavioral tests demonstrated the reversibility of the effects with recovery of the posture reflex, varying according to the concentration. The ECG results showed a slow recovery because, at concentrations above 100 µL·L-1, there was no full reversibility of the cardiac effects in the observed experiment time, which could cause greater changes in the tilapia hemodynamics, which led us to identify a window for safe anesthesia. Eugenol is an effective anesthetic in Nile tilapia juveniles when used in concentrations ranging from 50 to 100 µL·L-1, if there is a need for anesthetic deepening, doses above 100 µL·L-1, however, the animals must be monitored due to hemodynamic changes.

Lippia origanoides essential oil possesses anticonvulsant effect in pentylenetetrazol-induced seizures in rats: a behavioral, electroencephalographic, and electromyographic study.

Epilepsy is a neuronal disorder characterized by abnormal excitability of the brain, leading to seizures. Only around 66% of the epileptic patients respond adequately to treatment with existing conventional anticonvulsants, making it necessary to investigate new antiepileptic drugs. The growing research into natural products and their pharmacological properties has become increasingly promising, particularly in the study of essential oils, which are already widely used in popular culture for treating various diseases. The present study evaluated the anticonvulsant effects of Lippia origanoides essential oil (LOEO) (100 mg/kg i. p.) compared to diazepam (DZP) (5 mg/kg i. p.), and the combined administration of these two substances to control convulsions induced by pentylenetetrazol (PTZ) (60 mg/kg i. p.). This evaluation was carried out using 108 male Wistar rats, which were divided into two experiments. Experiment 1-Behavioral assessment: The animals were divided into 4 groups (n = 9): (I) saline solution + PTZ, (II) DZP + PTZ, (III) LOEO + PTZ, (IV) LOEO + DZP + PTZ. The convulsive behavior was induced 30 min after the administration of the tested anticonvulsant drugs, and the observation period lasted 30 min. Experiment 2- Electrocorticographic evaluation: The animals were divided into 8 groups (n = 9): (I) saline solution; (II) LOEO; (III) DZP; (IV) LOEO + DZP; (V) saline + PTZ, (VI) DZP + PTZ (VII) LOEO + PTZ, (VIII) LOEO + DZP + PTZ. PTZ was administered 30 min after LOEO and DZP treatments and electrocorticographic activity was assessed for 15 min. For the control groups, electromyographic recordings were performed in the 10th intercostal space to assess respiratory rate. The results demonstrated that Lippia origanoides essential oil increased the latency time for the appearance of isolated clonic seizures without loss of the postural reflex. The animals had a more intense decrease in respiratory rate when combined with LOEO + DZP. EEG recordings showed a reduction in firing amplitude in the LOEO-treated groups. The combining treatment with diazepam resulted in increased anticonvulsant effects. Therefore, treatment with Lippia origanoides essential oil was effective in controlling seizures, and its combination with diazepam may represent a future option for the treatment of difficult-to-control seizures.

Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous system effects, that can cause seizures in susceptible patients. This study aims to describe the changes caused by the use of Sildenafil and Tadalafil through the analysis of abnormalities expressed in the electrocorticogram (ECoG) of rats and evaluate the seizure threshold response and treatment of seizures with anticonvulsants. MATERIALS AND METHODS: The study used 108 rats (Wistar). Before surgery for electrode placement in dura mater, the animals were randomly separated into 3 experiments for electrocorticogram analysis. Experiment 1: ECoG response to using PD5i (Sildenafil 20mg/kg and Tadalafil 2.6mg/kg p.o.). Experiment 2: ECoG response to the use of PD5i in association with Pentylenetetrazole (PTZ-30 mg/kg i.p.), a convulsive model. Experiment 3: ECoG response to anticonvulsant treatment (Phenytoin, Phenobarbital and Diazepam) of seizures induced by association IPDE5 + PTZ. All recordings were made thirty minutes after administration of the medication and analyzed for ten minutes, only once. We considered statistical significance level of *p<0.05, **p<0.01 and ***p < 0.001. RESULTS: After administration of Sildenafil and Tadalafil, there were increases in the power of recordings in the frequency bands in oscillations in alpha (p = 0.0920) and beta (p = 0.602) when compared to the control group (p<0.001). After the use of Sildenafil and Tadalafil associated with PTZ, greater potency was observed in the recordings during seizures (p<0.001), however, the Sildenafil group showed greater potency when compared to Tadalafil (p<0.05). Phenobarbital and Diazepam showed a better response in controlling discharges triggered by the association between proconvulsant drugs. CONCLUSIONS: PDE5i altered the ECoG recordings in the rats' motor cortexes, demonstrating cerebral asynchrony and potentiating the action of PTZ. These findings demonstrate that PDE5i can lower the seizure threshold.

First Records of Heartbeats via ECG in a Stingless Bee, Melipona flavolineata (Apidae, Meliponini), during Contention Stress Using Isoflurane as an Anesthetic.

The hemodynamic activity of Melipona flavolineata workers was evaluated during restraint stress for a period of 30 min. The observed parameters were power variation in the elapsed time, and subsequently, six periods of one second were divided and called A, B, C, D, E and F; in each period, the electrocardiographic parameters were evaluated: spike frequency, amplitude, spike intervals and spike duration. The experiment was carried out with eight worker bees of M. flavolineata, for which electrodes of a nickel-chromium alloy were made. The bees were previously anesthetized with isoflurane and properly contained and fixed in a base for stereotaxis in which the electrode was implanted. All these procedures were performed inside a Faraday cage. The results showed power oscillations during the recording, with the highest energy level being between 300 and 600 s. Spike frequency, spike amplitude, interval between spikes and spike duration parameters underwent changes during the restraint stress period. Thus, the cardiac activity of M. flavolineata can be used as a biomarker and can be used to clarify physiological issues or alterations caused by toxic agents and indicate risk factors for these animals.

The GPER1 agonist G1 reduces brain injury and improves the qEEG and behavioral outcome of experimental ischemic stroke.

Stroke is one of the principal cerebrovascular diseases in human populations and contributes to a majority of the functional impairments in the elderly. Recent discoveries have led to the inclusion of electroencephalography (EEG) in the complementary prognostic evaluation of patients. The present study describes the EEG, behavioral, and histological changes that occur following cerebral ischemia associated with treatment by G1, a potent and selective G protein-coupled estrogen receptor 1 (GPER1) agonist in a rat model. Treatment with G1 attenuated the neurological deficits induced by ischemic stroke from the second day onward, and reduced areas of infarction. Treatment with G1 also improved the total brainwave power, as well as the theta and alpha wave activity, specifically, and restored the delta band power to levels similar to those observed in the controls. Treatment with G1 also attenuated the peaks of harmful activity observed in the EEG indices. These improvements in brainwave activity indicate that GPER1 plays a fundamental role in the mediation of cerebral injury and in the behavioral outcome of ischemic brain injuries, which points to treatment with G1 as a potential pharmacological strategy for the therapy of stroke.

Behavioral, electrocorticographic and electrocardiologic changes in Colossoma macropomum (Tambaqui) in the effect of cunaniol.

The Clibadium spp. is a shrub of occurrence in the Amazon, popularly known as Cunambi. The compounds in the leaves demonstrate ichthyotoxic properties, and its major substance, cunaniol, is a powerful central nervous system stimulant with proconvulsant activity. Few current studies relate behavioral changes to the electrophysiological profile of fish poisoning. This study aimed to describe the behavioral, electromyographic, electroencephalographic, electrocardiographic, and seizure control characteristics of anticonvulsant drugs in Colossoma macropomum submitted to cunaniol intoxication during bathing containing 0.3 µg/L cunaniol. The behavioral test showed rapid evolution presenting excitability and spasms, which were confirmed by the analysis of Electroencephalogram (EEG), Electromyogram (EMG), and changes in cardiac function detected in the ECG. Cunaniol-induced excitability control was evaluated using three anticonvulsant agents: Phenytoin, Phenobarbital, and Diazepam. While phenytoin was not effective in seizure control, diazepam proved to be the most efficient. These results demonstrate the susceptibility of Colossoma macropomum to cunaniol poisoning, given that the central nervous system and electrocardiographic changes were considered severe.

Oral Treatment with the Extract of Euterpe oleracea Mart. Improves Motor Dysfunction and Reduces Brain Injury in Rats Subjected to Ischemic Stroke.

Ischemic stroke is one of the principal causes of morbidity and mortality around the world. The pathophysiological mechanisms that lead to the formation of the stroke lesions range from the bioenergetic failure of the cells and the intense production of reactive oxygen species to neuroinflammation. The fruit of the açaí palm, Euterpe oleracea Mart. (EO), is consumed by traditional populations in the Brazilian Amazon region, and it is known to have antioxidant and anti-inflammatory properties. We evaluated whether the clarified extract of EO was capable of reducing the area of lesion and promoting neuronal survival following ischemic stroke in rats. Animals submitted to ischemic stroke and treated with EO extract presented a significant improvement in their neurological deficit from the ninth day onward. We also observed a reduction in the extent of the cerebral injury and the preservation of the neurons of the cortical layers. Taken together, our findings indicate that treatment with EO extract in the acute phase following a stroke can trigger signaling pathways that culminate in neuronal survival and promote the partial recovery of neurological scores. However, further detailed studies of the intracellular signaling pathways are needed to better understand the mechanisms involved.

Electroencephalographic Response in Juvenile Tambaqui, Colossoma macropomum, Exposed to Short-Term Anaesthetic Baths with Geraniol and Citronellol.

The aim of this study was to evaluate the level of neuronal depression in juvenile tambaqui, Colossoma macropomum, exposed to geraniol (GRL) and citronellol (CTL) in immersion baths. A total of 36 juveniles weighing 35.2 ± 9.4 g were used, organised into six experimental groups: I-control (clean water); II-ethanol (water containing the highest volume of ethanol used in the anaesthetic pre-dilution); III-GRL induction (70 µL·L-1); IV-CTL induction (90 µL·L-1); V-GRL recovery; VI-CTL recovery. Electroencephalographic (EEG) recordings were performed for 300 s in each group. EEG tracings of the control and ethanol groups showed regular and similar activity. Upon exposure to the anaesthetics, irregularities were observed in the tracings showing neuronal excitability and increased amplitudes, mainly in the case of CTL. Overall, GRL-exposed fish showed depression of the central nervous system with low and regular tracings throughout induction, presenting a gradual recovery and stable tracings, which were consistent with an adequate general anaesthetic effect. On the other hand, fish exposed to CTL showed altered EEG activity during induction, that could be considered incompatible with an appropriate anaesthetic effect and smooth recovery, presenting high and irregular EEG tracing amplitudes.

BmooMPα-I, a Metalloproteinase Isolated from Bothrops moojeni Venom, Reduces Blood Pressure, Reverses Left Ventricular Remodeling and Improves Cardiac Electrical Conduction in Rats with Renovascular Hypertension.

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, p < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, p < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, p > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, p < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, p < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

Caffeine intoxication: Behavioral and electrocorticographic patterns in Wistar rats.

Caffeine is a psychoactive substance used worldwide. The present study analyzes the seizure-related behavior and electrocorticographic (ECoG) patterns observed in rats following of a toxic dose of caffeine (150 mg/kg; intraperitoneal). Sixty-three rats were divided into three experiments: 1-Behavior's Description associated with caffeine-induced convulsion; 2- Comparison of the electrocorticographic patterns induced by caffeine and pentylenetetrazole, and 3- Assessment of the electrocorticographic response to antiepileptic drugs (diazepam, phenytoin, and phenobarbital). The behavioral analysis demonstrated tonic-clonic seizures with a loss of postural reflex and a latency of 365.8 s after the caffeine's administration. Caffeine-induced changes in the ECoG were consistent with the development of seizures with rapid evolution and burst potential consistent with the behavioral patterns observed during the caffeine-induced seizure. The ECoG of the brainwaves varied significantly between the seizures caused by caffeine and pentylenetetrazole. The predominant brain forces observed during the seizures were beta-band oscillations. The caffeine-induced seizures were resistant to attempted control with phenytoin and phenobarbital, but responded well to diazepam, which is consistent with a study of Pilocarpine, which showed that diazepam has anticonvulsant effects. These findings are important for the development of effective treatments for caffeine intoxication, in particular for individuals with a low seizure threshold.

Cardiac response in tambaqui Colossoma macropomum anaesthetised with Piper divaricatum essential oil.

The aim of this study was to evaluate the electrocardiographic responses of Colossoma macropomum exposed to short-term baths using the essential oil of Piper divaricatum (EOPD) as an anaesthetic-like agent in different doses (40, 60, and 80 µL L-1). Cardiac responses throughout and after exposure to EOPD were monitored and evaluated through mean heart rate (HR), duration and amplitude of the QRS complex (ventricular depolarization), and Q-T (ventricular contraction) and R-R (time between two successive QRS complexes) wave intervals. Across all doses, there was a marked depression of the HR, mainly at 80 µL L-1 EOPD. Mean amplitudes recorded for the QRS complex and Q-T interval at 40 µL L-1 EOPD were indistinguishable from the control, which could reinforce this concentration as sufficient and safe to promote fast anaesthesia without affecting cardiac function. Recovery from bradycardia, duration of the R-R interval, and QRS complex were similar at 60 and 80 µL L-1 EOPD; however, the Q-T interval at 80 µL L-1 EOPD revealed a more pronounced cardiac depression in relation to the controls and fish exposed to 60 µL L-1 EOPD. Thus, we conclude that 40 µL L-1 EOPD should suffice to induce fast, deep, and safe anaesthesia in tambaqui juveniles, whereas the concentration of 80 µL L-1 led to a greater depression of the cardiac function, albeit showing effect reversibility.

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration.

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

Cardiac responses in Crassostrea gasar: An experimental approach of how the tidal cycle influences the heart function of the mangrove oyster.

Cardiac physiological studies in oysters are scarce and these kinds of responses can be key issues for understanding behavioral and baseline adaptive responses. In this study we characterized the electrocardiogram (ECG) tracing patterns, wave intervals (RR; QT), and complex duration (QRS) of Crassostrea gasar during immersion followed by air exposure, simulating what occurs in a tide cycle. Initially, the ECG was analyzed in the oysters under immersion for 30 min to evaluate the basal recordings (immersion exposure condition). Then, the same animals were removed from the water and the ECG was analyzed for another 30 min to assess cardiac activity under air exposure (air exposure condition). For this, a technique of cardiac recordings was developed, allowing us to analyze, beyond ECG, other cardiac parameters such as the heart rate (HR) in beats per minute, the spectral power of HR, and the amplitude. The basal cardiac parameters analyzed in oysters in the immerse condition clearly show the waves and intervals (R-R: 11.03 ± 0.63 s, P-Q: 2.09 ± 0.06 s), with a normal and regular electrocardiographic tracing and sinus rhythm without alterations. When in the air exposure condition, oysters maintained the ECG tracing of sinus rhythm, but with changes in intervals and a prolonged isoelectric period. Moreover, in this condition, oysters presented a biphasic response: initially (phase I), heart rate increased (9.83 ± 0.98 BPM), and consequently the R-R and P-Q intervals decreased (5.86 ± 2.01 s e 1.91 ± 0.13 s, respectively); in phase II, heart rate (3.68 ± 0.82 BPM) and spectral power (21.26 ± 5.44 mV2/Hz x 10-3) decreased and consequently, the R-R interval increased (14.83 ± 2.92 s). But, the P-Q interval remained (2.45 ± 0.65 s) in phase II. The QRS complex of oysters in both phases decreased (Phase I: 0.57 ± 0.13 s; Phase II: 0.62 ± 0.05 s) compared to the immersion exposure condition (0.79 ± 0.09 s). We conclude that air exposure affected cardiac function in C. gasar leading to arrhythmia in response to the beginning of air exposure, as a means of maintaining oxygen supply, followed by bradycardia to decrease metabolism as a survival strategy. The basal responses of the mangrove oyster in the physiological modulation against the environmental factors of the tidal regime provide information about the species for possible application as model organisms in studies of toxicological evaluation of chemical products and in conservation and sustainability studies.

The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

Seizures and epilepsy are some of the most common serious neurological disorders, with approximately 80% of patients living in developing/underdeveloped countries. However, about one in three patients do not respond to currently available pharmacological treatments, indicating the need for research into new anticonvulsant drugs (ACDs). The GABAergic system is the main inhibitory system of the brain and has a central role in seizures and the screening of new ACD candidates. It has been demonstrated that the action of agents on endocannabinoid receptors modulates the balance between excitatory and inhibitory neurotransmitters; however, studies on the anticonvulsant properties of endocannabinoids from plant oils are relatively scarce. The Amazon region is an important source of plant oils that can be used for the synthesis of new fatty acid amides, which are compounds analogous to endocannabinoids. The synthesis of such compounds represents an important approach for the development of new anticonvulsant therapies.