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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: 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
BACKGROUND: Patients undergoing high-risk surgeries with acid-based disorders are associated with poor outcomes. The screening of mixed acid-based metabolic disorders by calculating delta anion gap (AG)/delta bicarbonate (Bic) has a clinically relevant role in patients with high AG metabolic acidosis (MA), however its utility in individuals facing high-risk surgical procedures remains unclear. OBJECTIVE: Characterize metabolic acidosis using delta-AG/delta-Bic and its associations in patients undergoing high-risk surgeries with possible outcome-related complications. DESIGN: Prospective observational multicentric study. SETTING: Three tertiary hospitals in Brazil. PATIENTS: Patients undergoing high-risk surgeries, aged 18 years or older, requiring postoperative critical care. MAIN OUTCOME MEASURES: Patients undergoing high-risk surgeries monitored during the postoperative phase across three distinct intensive care units (ICUs), with assessment encompassing laboratory analyses upon admission and 24 h thereafter. Patients with MA and with elevated AG within 24 h were separated into 3 subgroups: [G1 - delta-AG/delta-Bic < 1.0] MA associated with hyperchloremia; [G2 - delta-AG/delta-Bic between 1.0 and 1.6] MA and no mixed disorders; and [G3 - delta-AG/delta-Bic > 1.6] MA associated with alkalosis. Primary endpoint was 30-day mortality. The secondary endpoints were cardiovascular, respiratory, renal, neurological, coagulation and infective complications. RESULTS: From the 621 surgical patients admitted to ICU, 421 (51.7%) had any type of acidosis. After 24 h, 140 patients remained with MA with elevated AG (G1: 101, G2: 18, and G3: 21). When compared to patients from subgroups 1 and 3, the subgroup with no mixed disorders 2 showed higher 30-day mortality (adjusted HR = 3.72; 95% CI 1.11-12.89, p = 0.001), cardiovascular complications (p = 0.001), ICU mortality (p = 0.03) and sum of all complications during the ICU period (p = 0.021). CONCLUSION: In the postoperative time, patients with metabolic acidosis and no mixed disorders present higher ICU-Mortality and higher cardiovascular postoperative complications when compared with patients with combined hyperchloremia or alkalosis. Delta-AG/delta-Bic can be a useful tool to evaluate major clinical outcomes in this population.
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Equilíbrio Ácido-Base , Acidose , Bicarbonatos , Unidades de Terapia Intensiva , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Acidose/sangue , Bicarbonatos/sangue , Idoso , Complicações Pós-Operatórias/epidemiologia , Brasil/epidemiologia , AdultoRESUMO
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
The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.
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Cisto Dentígero , Mucopolissacaridose I , Humanos , Cisto Dentígero/cirurgia , Cisto Dentígero/diagnóstico , Mucopolissacaridose I/complicações , Mucopolissacaridose I/diagnóstico , Mucopolissacaridose I/terapia , Masculino , Doenças Mandibulares/cirurgia , Doenças Mandibulares/diagnóstico , FemininoRESUMO
This study aimed to describe and compare specific matchdays sessions and playing positions external load during congested fixtures in elite football when combining the objectives from two different training days in one session. Data was collected from 27 players from the 1st Brazilian division (28.7 ± 18.61 years) that participated in the following training days during congested fixtures (n = 16 weeks): a) Match day+1 (MD+1MD-2, session 1 day after the game with tasks from MD+1 and MD-2 sessions, n = 9); b) Matchday-2 (MD-2MD+2, session 2 days prior to subsequent match with tasks from MD-2 and MD+2 sessions, n = 11); c) Matchday-1 (MD-1MD+2, session 1 day prior to subsequent match with tasks from MD-1 and MD+2 sessions, n = 12); and d) Matchday-1 (MD-1MD+3, session 1 day prior to subsequent match with tasks from MD-1 and MD+3 sessions, n = 11). External load was collected with global positioning systems, while internal load with the rating of perceived exertion (RPE). The MD+1MD-2 showed higher total distance covered (F = 116.92, p < 0.001) and player load (F = 56.67, p < 0.001) values than the other three training days, while both the MD+1MD-2 and MD-2MD+2 revealed higher distance covered at high-speed running (F = 22.43, p < 0.001) and high metabolic load distance covered (F = 75.98, p < 0.001) than both MD-1 sessions. Fullbacks covered higher high-speed running distance (F = 3.6, p = 0.033) than center backs, while midfielders reported higher RPE (F = 5.29, p = 0.003) values than defensive midfielders and fullbacks. Coaches may use the MD+1MD-2 to emphasize total distance covered, while both MD+1MD-2 and MD-2MD+2 to promote HSR and HML distance compared to MD-1 sessions. In addition, combining training sessions allows to normalize external load across playing positions with the exception of fullbacks that are exposed to higher stimulus.
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Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolites' variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.
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Antitussígenos , Cannabis , Plantas Medicinais , Camundongos , Animais , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Expectorantes/farmacologia , Expectorantes/uso terapêutico , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Brasil , Fenolsulfonaftaleína , Cromatografia Líquida , Dronabinol/uso terapêutico , Espectrometria de Massas em Tandem , Plantas Medicinais/química , Ácido Cítrico/toxicidade , Ácido Cítrico/uso terapêuticoRESUMO
BACKGROUND: Several studies suggest that hemodynamic optimization therapies can reduce complications, the length of hospital stay and costs. However, Brazilian data are scarce. Therefore, the objective of this analysis was to evaluate whether the improvement demonstrated by hemodynamic optimization therapy in surgical patients could result in lower costs from the perspective of the Brazilian public unified health system. METHODS: A meta-analysis was performed comparing surgical patients who underwent hemodynamic optimization therapy (intervention) with patients who underwent standard therapy (control) in terms of complications and hospital costs. The cost-effectiveness analysis evaluated the clinical and financial benefits of hemodynamic optimization protocols for surgical patients. The analysis considered the clinical outcomes of randomized studies published in the last 20 years that involved surgeries and hemodynamic optimization therapy. Indirect costs (equipment depreciation, estate and management activities) were not included in the analysis. RESULTS: A total of 21 clinical trials with a total of 4872 surgical patients were selected. Comparison of the intervention and control groups showed lower rates of infectious (RR = 0.66; 95% CI = 0.58-0.74), renal (RR = 0.68; 95% CI = 0.54-0.87), and cardiovascular (RR = 0.87; 95% CI = 0.76-0.99) complications and a nonstatistically significant lower rate of respiratory complications (RR = 0.82; 95% CI = 0.67-1.02). There was no difference in mortality (RR = 1.02; 95% CI = 0.80-1.3) between groups. In the analysis of total costs, the intervention group showed a cost reduction of R$396,024.83-BRL ($90,161.38-USD) for every 1000 patients treated compared to the control group. The patients in the intervention group showed greater effectiveness, with 1.0 fewer days in the intensive care unit and hospital. In addition, there were 333 fewer patients with complications, with a consequent reduction of R$1,630,341.47-BRL ($371,173.27-USD) for every 1000 patients treated. CONCLUSIONS: Hemodynamic optimization therapy is cost-effective and would increase the efficiency of and decrease the burden of the Brazilian public health system.
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Análise Custo-Benefício/métodos , Hemodinâmica/fisiologia , Assistência Perioperatória/economia , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Operatórios , Brasil , Análise Custo-Benefício/economia , Análise Custo-Benefício/estatística & dados numéricos , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricosRESUMO
CONTEXT: Lippia thymoides Mart. & Schauer (Verbenaceae) is used in folk medicine to treat wounds, fever, bronchitis, rheumatism, headaches, and weakness. OBJECTIVE: This study determinates the chemical composition of essential oils from L. thymoides, obtained at during each of the four seasons and correlates with pharmacological properties. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and analyzed by gas chromatography coupled to mass spectroscopy (GC-MS). Antioxidant activity was determined by DPPH free radical scavenging and ß-carotene bleaching methods. The antimicrobial assays were performed by minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) methods. Isolated rat aorta and uterus, and guinea-pig trachea were utilized to evaluate relaxant potential in pre-contracted smooth muscle. RESULTS AND DISCUSSION: Essential oils from leaves of L. thymoides had the sesquiterpene ß-caryophyllene (17.22-26.27%) as the major constituent followed by borneol (4.45-7.36%), camphor (3.22-8.61%), camphene (2.64-5.66%), and germacrene D (4.72-6.18%). In vitro assays showed that these essential oils do not have antioxidant activity, have antimicrobial selectivity to Gram-positive bacteria Staphylococcus aureus (MIC = 0.004 mg/mL and MMC = 0.26-10.19 mg/mL) and Micrococcus luteus (MIC = 0.03 mg/mL and MMC = 8.43 mg/mL), relax isolated rat aorta (EC50 = 305-544 µg/mL, with endothelium; and EC50 = 150-283 µg/mL, without endothelium), and uterus (EC50 = 74-257 µg/mL), and minor potency, isolated guinea-pig trachea. CONCLUSIONS: Lippia thymoides is a source of natural products of pharmaceutical interest, being necessary additional studies to determine the substances involved in the biological activities.
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Lippia/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Estações do Ano , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Compostos de Bifenilo/química , Relação Dose-Resposta a Droga , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cobaias , Masculino , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Oxirredução , Fitoterapia , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tocolíticos/química , Tocolíticos/isolamento & purificação , Tocolíticos/farmacologia , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , beta Caroteno/químicaRESUMO
Introduction The study of electrophysiological auditory measures with different types of masking makes it possible to understand temporal processing skills and the processes involved in speech recognition in noise situations. The use of modulated masking in cortical measures of hearing enables the obtainment of analysis parameters of the masking release and its impact on neural auditory processing. Objective To investigate the behavior of cortical auditory evoked potentials (CAEPs) with modulated masking in the normal hearing population. Data synthesis A total of 2,159 articles were identified in the initial search; of these, 12 were selected for full reading. After excluding studies that did not meet the eligibility criteria, six articles were included in the present systematic review. The results show that the type of masking has an influence on cortical auditory behavior, indicating a different effect on neural posture rergarding CAEP responses. Modulated noise as masking in the CAEP record generated statistically higher and earlier responses compared with non-modulated/steady noise, evidenced by the results obtained in the meta-analysis with subgroup analysis. These responses may indicate an influence of the type of noise in the neural auditory coding. Conclusion Better responses were observed in modulated masking in terms of the behavior of CAEPs. Decreased latency and increased amplitude of cortical measurements with the use of modulated noise indicate a lower masking effect of this noise in cortical auditory processing, evidencing the masking release phenomenon.
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OBJECTIVE: To analyze the Benefit of Modulated Masking (BMM) on hearing in young, adult and elderly normal-hearing individuals. METHODS: The sample included 60 normal-hearing individuals aged 18-75 years who underwent behavioral assessment (sentence recognition test in the presence of steady and modulated noise) and electrophysiological assessment (cortical Auditory Evoked Potential) to investigate BMM. The results were analyzed comparatively using the paired t-test and ANOVA for repeated measures, followed by the Bonferroni post-hoc test (p-valueâ¯<â¯0.05). RESULTS: A decrease in latencies and an increase in amplitudes of cortical components (P1-N1-P2) was observed due to noise modulation in all age groups. Modulated noise generated better auditory threshold responses (electrophysiological and behavioral), compared to steady noise. The elderly presented a higher threshold in both hearing domains, compared to the other participants, as well as a lower BMM magnitude. CONCLUSION: It was possible to conclude that the modulated noise generated less interference in the magnitude of the neural response (smaller latencies) and in the neural processing time (larger amplitudes) for the speech stimulus in all participants. The higher auditory thresholds (electrophysiological and behavioral) and the lower BMM magnitude observed in the elderly group, even in the face of noise modulation, suggest a lower temporal auditory performance in this population, and may indicate a deficit in the temporal resolution capacity, associated with the process of aging.
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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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(-)-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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Monoterpenos Cicloexânicos , Monoterpenos , Ocitocina , Útero , Animais , Ocitocina/farmacologia , Feminino , Monoterpenos Cicloexânicos/farmacologia , Camundongos , Útero/efeitos dos fármacos , Monoterpenos/farmacologia , Contração Uterina/efeitos dos fármacos , Ratos , Ratos Wistar , Parassimpatolíticos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Carbacol/farmacologiaRESUMO
Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump-less recirculating organ-on-chip platform that combines human pluripotent stem cell (sc)-derived sc-liver and sc-islet organoids is presented. The platform reproduces key aspects of the metabolic cross-talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc-islet and sc-liver organoids while preserving a reduced release of pro-inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc-liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc-islets produce pro-inflammatory cytokines on-chip. Finally, the platform reproduces known effects of anti-diabetic drugs on-chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on-chip, as well as for testing potential therapeutic interventions.
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Ilhotas Pancreáticas , Dispositivos Lab-On-A-Chip , Fígado , Organoides , Humanos , Fígado/metabolismo , Organoides/metabolismo , Ilhotas Pancreáticas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Glucose/metabolismoRESUMO
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.
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RATIONALE, AIMS AND OBJECTIVES: Implementation of clinical pharmacy services, such as drug dispensing, is a complex process. It is necessary to understand the challenges associated with this practice from the perspective of the actors involved to help ensure optimal service provision. Thus, this study aimed to understand the factors that may influence the implementation of drug dispensing in community pharmacies, according to the perceptions of pharmacists. METHOD: This qualitative study was based on semistructured, face-to-face interviews. The participants were pharmacists who worked in a chain of community pharmacies in Brazil, selected based on their direct participation in the implementation process. The interview recordings were transcribed full verbatim and were independently analyzed using thematic analysis, followed by consensus meetings between researchers. The factors identified by the participants were classified according to the Apoteca framework. This study was approved by the Committee of Ethics in Research and all participants signed an informed consent form. RESULTS: We conducted 18 interviews, with 47 factors that may influence the implementation of drug dispensing in community pharmacies being identified. These factors were allocated to seven categories: support from community pharmacy chain (4), pharmacy infrastructure (11), characteristics of the pharmacy, medicines and other health products (4), pharmacist (16), dispensing work process (2), pharmacy team (2) and patient (8). The classification of factors according to the Apoteca framework allocated most of them to administrative (14) and technical (15) domains, followed by attitudinal (13) and political (5) domains. CONCLUSION(S): This study identified several factors that can influence the implementation of drug dispensing and classified them according to the domains of the Apoteca framework, highlighting the multifactorial nature of the implementation process. The results of this study can guide the planning of strategies aimed at providing efficient drug dispensing in community pharmacies.
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Serviços Comunitários de Farmácia , Farmácias , Serviço de Farmácia Hospitalar , Humanos , Farmacêuticos , Pesquisa QualitativaRESUMO
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
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.
Assuntos
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
Introduction Auditory-evoked potentials are influenced by several factors, including polarity, filter, stimulus intensity and stimulation rate. The presentation of higher rates of stimuli per second enables the collection of a greater number of responses in a given period of time, promoting a shorter testing time; however, the collected recordings are subject to changes related to wave morphology. Objectives To compare the brainstem auditory-evoked-potential responses with click stimulus with the most commonly used stimulation rates in the clinical practice. Methods The present cross-sectional analytical study was performed with fifteen participants of both genders and normal hearing thresholds. The brainstem auditory-evoked potential was performed at four different stimulation rates (21.1, 26.7, and 27.7 stimuli/s, and a rate determined based on a mathematical calculation using the a measurement of the transmission frequency of the power grid at the time of the examination). Results We observed that the rate of 21.1 stimuli/s showed the highest amplitudes for waves I, III, and V when compared with the other rates. The rate of 26.7 stimuli/s, when compared with 27.7 stimuli/s, showed a higher amplitude for wave V. The latency if wave V was significantly lower with the rate of 21.1 stimuli/s than with 27.7 stimuli/s. Conclusions The stimulation rate interferes with wave latencies and amplitudes; its decrease from 27.7 to 21.1 stimuli/s decreases the latency of wave V and increases the amplitues and improves the morphology of waves I, III and V. In addition, we found evidence that suggests an improvement in the visualization of wave III by adjusting the stimulation rate based on a measurement of the local transmission frequency of the power grid.
RESUMO
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.