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(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.
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The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300â mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300â mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
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Antipiréticos , Antitussígenos , Etanol , Expectorantes , Momordica charantia , Extratos Vegetais , Folhas de Planta , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Camundongos , Antitussígenos/farmacologia , Antitussígenos/química , Antitussígenos/isolamento & purificação , Folhas de Planta/química , Ratos , Etanol/química , Antipiréticos/farmacologia , Antipiréticos/química , Antipiréticos/isolamento & purificação , Masculino , Momordica charantia/química , Expectorantes/farmacologia , Expectorantes/isolamento & purificação , Expectorantes/química , Tosse/tratamento farmacológico , Ratos Wistar , Relação Dose-Resposta a Droga , Saccharomyces cerevisiae/efeitos dos fármacos , Febre/tratamento farmacológicoRESUMO
OBJECTIVES: Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS). DESIGN: Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS ( M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children ( M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3. RESULTS: Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs. CONCLUSIONS: Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.
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Potenciais Evocados Auditivos do Tronco Encefálico , Microcefalia , Infecção por Zika virus , Humanos , Feminino , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/complicações , Infecção por Zika virus/congênito , Masculino , Microcefalia/fisiopatologia , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Criança , Estudos de Casos e Controles , Potenciais Evocados Auditivos/fisiologia , BrasilRESUMO
Introduction Noise obscures speech signal, causing auditory masking. The effects of this masking can be observed through the cortical auditory evoked potentials (CAEPs). White noise, in turn, has an effect on the auditory cortex, interfering, for example, with lexical decision making. Objective To analyze the effect of simultaneous masking by contralateral white noise on CAEPs elicited by speech stimuli. Methods Cross-sectional observational analytical study carried out with 15 participants of both sexes, who were submitted to CAEPs in two conditions: 1) without noise; 2) with white noise at 100 dBSPL intensity, contralaterally and simultaneously. To compare these conditions, the Student t test or the Wilcoxon test were used, depending on the sample normality. Differences with p values < 0.05 were considered significant. Results : When white noise was presented contralaterally and simultaneously to the CAEPs with speech stimulus, an increase in P1, N1 and P2 wave latencies was observed. P1 and P2 amplitudes and N1-P2 peak to peak amplitude also increased, unlike N1 amplitude, which decreased. The differences were significant for P1 and P2 wave latencies and for P2 wave amplitude. Conclusion The simultaneous masking effect was observed from the morphological alterations of the CAEPs with speech stimulus when white noise was presented in the contralateral ear. There was a significant increase in P1 and P2 wave latencies, as well as in P2 wave amplitude.
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INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.
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Cimenos , Dismenorreia , Tocolíticos , Ratos , Animais , Feminino , Humanos , Dismenorreia/tratamento farmacológico , Dismenorreia/induzido quimicamente , Dismenorreia/metabolismo , Tocolíticos/efeitos adversos , Ocitocina/efeitos adversos , RoedoresRESUMO
Abstract Introduction Noise obscures speech signal, causing auditory masking. The effects of this masking can be observed through the cortical auditory evoked potentials (CAEPs). White noise, in turn, has an effect on the auditory cortex, interfering, for example, with lexical decision making. Objective To analyze the effect of simultaneous masking by contralateral white noise on CAEPs elicited by speech stimuli. Methods Cross-sectional observational analytical study carried out with 15 participants of both sexes, who were submitted to CAEPs in two conditions: 1) without noise; 2) with white noise at 100 dBSPL intensity, contralaterally and simultaneously. To compare these conditions, the Student t test or the Wilcoxon test were used, depending on the sample normality. Differences with p values < 0.05 were considered significant. Results: When white noise was presented contralaterally and simultaneously to the CAEPs with speech stimulus, an increase in P1, N1 and P2 wave latencies was observed. P1 and P2 amplitudes and N1-P2 peak to peak amplitude also increased, unlike N1 amplitude, which decreased. The differences were significant for P1 and P2 wave latencies and for P2 wave amplitude. Conclusion The simultaneous masking effect was observed from the morphological alterations of the CAEPs with speech stimulus when white noise was presented in the contralateral ear. There was a significant increase in P1 and P2 wave latencies, as well as in P2 wave amplitude.
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Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.
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Transtorno Depressivo Maior , Ketamina , Humanos , Camundongos , Animais , Natação , Ketamina/farmacologia , Ketamina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Elevação dos Membros Posteriores , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Modelos Animais de Doenças , Dexametasona/uso terapêutico , Depressão/tratamento farmacológicoRESUMO
OBJECTIVE: Investigate the auditory function of the elderly using the middle latency potentials. METHODOLOGY: Group 1 (G1): 20 healthy individuals of both genders, older than 60 years, without hearing loss. Group 2 (G2): 20 healthy individuals of both sexes, older than 60 years, with hearing loss in frequencies from 4 to 8 kHz. Potential recording was performed with unilateral and bilateral stimulation and the Binaural Interaction Component was calculated. RESULTS: Na latency in C3A1 was greater in the stimulation of the right ear in G2 and the amplitude of Na-Pa was greater in the stimulation of the right ear and recording in C3A1 in G1. The latency of the Pa component was higher in the stimulation of the right ear recorded in C4A2. The Pb component in G2 by bilateral stimulation and recorded in C4A2 had higher latency. The first and second negative and positive peaks presented greater amplitude in G1. In C3A1, the 1st negative peak was more negative in G1 and the 2nd positive peak showed greater amplitude in C4A2 in both groups. CONCLUSION: The transmission of auditory information to the primary auditory cortex is impaired with aging, especially in unilateral stimulation, reinforced by losses in elderly people with peripheral hearing loss, such as in the binaural interaction at the cortical and subcortical levels. Thus, the AMLR has shown to be a sensitive examination to investigate neuroauditory disorders in the elderly, especially related to high-frequency hearing loss and primary auditory cortex dysfunctions caused by the aging process.
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Córtex Auditivo , Perda Auditiva , Idoso , Humanos , Masculino , Feminino , Potenciais Evocados Auditivos/fisiologia , Audição , Envelhecimento/fisiologia , Orelha , Estimulação Acústica , Córtex Auditivo/fisiologiaRESUMO
Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.
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Hipertermia Induzida , MicroRNAs , Convulsões Febris , Humanos , Pré-Escolar , Ratos , Animais , Convulsões Febris/genética , Transcriptoma , Hipocampo , MicroRNAs/genética , Suscetibilidade a DoençasRESUMO
Based on brain magnetic resonance imaging results, the second and third most frequent causes of central pontine myelinolysis (CPM) were liver transplant (LT) and cirrhosis, which together accounted for 13.7% and 12.5% of all diagnoses of CPM. Medical diseases including cirrhosis, LT, malnutrition, and alcoholism are well-known conditions associated with CPM in addition to hyponatremia. The prognosis is poor and depends on early diagnosis and treatment to achieve better outcomes. This is a case report of CPM occurring after a deceased donor LT in a patient presenting many risk factors such as chronic hyponatremia, previous episodes of encephalopathy, and tacrolimus immunosuppression. We briefly discuss the pathophysiology, risk factors, diagnosis, and treatment, highlighting the role and challenges of the anesthesiologist in managing this kind of patient and preventing the syndrome in the context of major surgery.