RESUMO
Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.
Assuntos
Aminofilina , Catalepsia , Modelos Animais de Doenças , Marcha , Haloperidol , Doença de Parkinson , Animais , Catalepsia/tratamento farmacológico , Catalepsia/induzido quimicamente , Camundongos , Masculino , Aminofilina/administração & dosagem , Aminofilina/farmacologia , Aminofilina/uso terapêutico , Marcha/efeitos dos fármacos , Haloperidol/administração & dosagem , Haloperidol/farmacologia , Doença de Parkinson/tratamento farmacológicoRESUMO
Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of ß2-adrenergic receptors/AC/cAMP pathway.
Assuntos
Asma , Broncodilatadores , AMP Cíclico , Modelos Animais de Doenças , Inibidores da Fosfodiesterase 4 , Traqueia , Animais , Cobaias , Inibidores da Fosfodiesterase 4/farmacologia , Asma/tratamento farmacológico , Asma/fisiopatologia , Traqueia/efeitos dos fármacos , Masculino , Broncodilatadores/farmacologia , AMP Cíclico/metabolismo , Músculo Liso/efeitos dos fármacos , Ovalbumina , Relaxamento Muscular/efeitos dos fármacos , Aminofilina/farmacologiaRESUMO
Introdução: A analgesia epidural oferece uma das formas mais eficazes de alívio da dor durante o trabalho de parto, e em países de alta e média renda, seu uso aumentou nas últimas décadas. A cefaleia pós-punção dural (CPPD) é descrita como uma cefaleia ortostática causada pela baixa pressão do líquido cefalorraquidiano (LCR), geralmente acompanhada de dor cervical, zumbido, alterações na audição, fotofobia e/ou náusea. É uma complicação relativamente frequente após bloqueios neuroaxiais, e pode se apresentar na punção dural que ocorre intencionalmente na raquianestesia, ou não intencionalmente como complicação da anestesia peridural. Objetivo: Por meio de uma revisão de ensaios clínicos publicados nos últimos dez anos, propor um protocolo de tratamento da CPPD para ser aplicado no Hospital do Servidor Público Municipal (HSPM) de São Paulo - SP. Método: Trata-se de um estudo exploratório baseado no método de revisão da literatura com síntese de evidências. A base de dados escolhida para seleção dos artigos foi a PUBMED, utilizando a seguinte estratégia de busca: "post-dural puncture headache"[title]. Foram selecionados ensaios clínicos publicados nos últimos dez anos (2012 - 2022). Resultados: Doze trabalhos foram selecionados, resumidos e apresentados em ordem cronológica de publicação. Além disso, as diretrizes apontadas pelos artigos foram utilizadas para sugerir um protocolo hospitalar no tratamento da CPPD. Conclusão: Segundo os trabalhos consultados, um bom protocolo de tratamento para CPPD começaria pela escolha do tipo de agulha, sendo as mais indicadas a 25S e 25G atraumáticas. Como tratamento farmacológico pós-anestesia para a CPPD temos o uso de teofilina, aminofilina, ondansetrona e dexmedetomidina como opções não invasivas de controle dos sintomas da CPPD, além do bloqueio do gânglio esfenopalatino. Ainda, a associação entre neostigmina e atropina também se mostrou eficaz no tratamento da CPPD. Palavras-Chave: Cefaleia Pós-Punção Dural. Raquianestesia. Anestesiologia.
Assuntos
Humanos , Feminino , Gravidez , Dor , Atropina , Teofilina , Trabalho de Parto , Analgesia Epidural , Pressão do Líquido Cefalorraquidiano , Protocolos Clínicos , Dexmedetomidina , Cefaleia Pós-Punção Dural , Aminofilina , Anestesia , Anestesia Epidural , Raquianestesia , Anestesiologia , AgulhasRESUMO
Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.
Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Asma , Sociedades Médicas , Terapêutica , Alergia e Imunologia , Pacientes , Pediatria , Encaminhamento e Consulta , Teofilina , Espasmo Brônquico , Epinefrina , Corticosteroides , Ipratrópio , Anestésicos Inalatórios , Serviços Médicos de Emergência , Agonistas de Receptores Adrenérgicos beta 2 , Ventilação não Invasiva , Aminofilina , Hospitalização , Ketamina , Sulfato de Magnésio , Hipóxia , AntibacterianosRESUMO
INTRODUCTION: Second-line drugs for acute asthma, such as salbutamol, magnesium sulfate, and aminophylline, are generally intravenously administered. OBJECTIVE: To compare the efficacy and safety of using mag nesium sulfate or aminophylline in children who did not respond to initial treatment. PATIENTS AND METHOD: Randomized clinical trial. Children who did not improve the Modified Pulmonary Index Score (mPSI) receive at random magnesium sulfate (50 mg/kg/single dose) or aminophylline (5 mg/ kg/dose followed by continuous infusion at 1 mg/kg/hour for 3 hours). Primary endpoints were changes in mPSI and oxygen saturation; secondary endpoints: hospitalization rate, need for transfer to the intensive care unit, use of a third intervention, and adverse effects. RESULTS: 131 patients were studied (66 patients in the aminophylline group and 65 MgSO4). The mean age was 5 ± 2.3 years, the demographic and clinical parameters did not differ between the groups. In the group that received magnesium sulfate, the mPSI and oxygen saturation changed significantly in favor from 13.1 ± 1.3 to 4.9 ± 2.5 (p < 0.001) and from 3.3 ± 2.5; (p 0.021), respectively, and their risk of hospital admission (RR 0.68 95% CI [0.56, 0.82]) and of secondary failure (0.16 95% CI 95% [0 , 07; 0.38]) decreased. Only one adverse event (tachycardia) was recorded. CONCLUSION: The administration of a single dose of magnesium sulfate proved to be more effective and safe than the use of aminophylline as a second- line drug.
Assuntos
Aminofilina/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Doença Aguda , Asma/diagnóstico , Criança , Pré-Escolar , Esquema de Medicação , Quimioterapia Combinada , Serviço Hospitalar de Emergência , Feminino , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
In the field of experimental pharmacology, researchers continuously investigate new relaxant agents of the airway smooth muscle cells (ASMCs), since the pathophysiology of respiratory illnesses, such as asthma, involves hyperresponsiveness and changes in ASMC homeostasis. In this scenario, labdane-type diterpenes, like forskolin (FSK), are a class of compounds known for their relaxing action on smooth muscle cells (SMCs), being this phenomenon related to the direct activation of AC-cAMP-PKA pathway. Considering the continuous effort of our group to study the mechanism of action and prospecting for compounds isolated from natural sources, in this paper, we presented how the diterpene 8(17),12E,14-labdatrien-18-oic acid (LBD) promotes relaxant effect on ASMC, performing in vitro experiments using isolated guinea pig trachea and in silico molecular docking/dynamics simulations. In vitro experiments showed that in the presence of aminophylline, FSK and LBD had their relaxant effect potentiated (EC50 from 1.4 ± 0.2 × 10-5 M to 1.5 ± 0.3 × 10-6 M for LBD and from 2.0 ± 0.2 × 10-7 M to 6.4 ± 0.4 × 10-8 M for FSK) while in the presence of Rp-cAMPS this effect was attenuated (EC50 from 1.4 ± 0.2 × 10-5 M to 3 × 10-4 M for LBD and from 2.0 ± 0.2 × 10-7 to 3.1 ± 1.0 × 10-6 M for FSK). Additionally, in silico simulations evidenced that the lipophilic character of LBD is probably responsible for its stability on AC binding site. LBD presented two preferential orientations, where the double bonds of the isoprene moiety as well as the unique polar group (carboxylic acid) in this compound form important anchoring points. In this sense, we consider that the LBD can interact stabilizing the catalytic dimmer of AC as the FSK, although less efficiently.
Assuntos
Diterpenos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Aminofilina/farmacologia , Animais , Sítios de Ligação , Colforsina/farmacologia , Simulação por Computador , Diterpenos/administração & dosagem , Diterpenos/química , Feminino , Cobaias , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Miócitos de Músculo Liso/metabolismo , Traqueia/citologiaRESUMO
BACKGROUND: Care variability for children with severe acute asthma has been well documented in high-income countries, yet data from low- and middle-income regions are lacking. We sought to characterize the magnitude of practice variability in the care of Latin American children to identify opportunities for standardization of care. METHODS: A cross-sectional study performed through a retrospective analysis of contemporaneously collected data of children with severe acute asthma admitted to a center contributing to the LARed Network registry between May 2017 and May 2019. Centers were grouped by geographic location: Atlantic (AT), South Pacific (SP), and North Central (NC). RESULTS: Among 434 children, most received care in hospitals in the AT group (54% [235/434]), followed by the NC (23% [101/434]) and SP (23% [98/434]) groups. The majority of children in the AT (92% [215/235]) and SP (91% [89/98]) groups received nebulized salbutamol/albuterol, while metered-dose inhalers were preferred in the NC group (72% [73/101]). There was a wide variation in the use of antibiotics: AT (57% [135/235]), SP (48% [47/98]), and NC (14% [14/101]). The same was true for ipratropium bromide: AT (67% [157/235]), SP (90% [88/98]), and NC (17% [17/101]), and aminophylline: AT (57% [135/235]), NC (5% [5/101]), and SP (0% [0/98]). High-flow nasal cannula was the preferred respiratory support modality in the AT (60% [141/235]) and NC (40% [40/101]) groups, while bilevel positive airway pressure (BiPAP) use was more common in the SP group (80% [78/98]). CONCLUSION: We identified significant variability in care for severe acute asthma. Our findings will help to inform the design of future studies, quality improvement initiatives, and development of practice guidelines within Latin America.
Assuntos
Asma/terapia , Adolescente , Albuterol/uso terapêutico , Aminofilina/uso terapêutico , Antibacterianos/uso terapêutico , Broncodilatadores/uso terapêutico , Cânula , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitalização , Humanos , Ipratrópio/uso terapêutico , Masculino , Inaladores Dosimetrados , Estudos RetrospectivosRESUMO
Fundamento: O fluxo coronariano com predomínio diastólico aumenta duas a cinco vezes na hiperemia, mediada por vasodilatação (reserva de fluxo coronariano), podendo, na hipertrofia, ocorrer isquemia relativa. Na hipertrofia secundária, o fluxo em repouso torna-se isquêmico pelo aumento da demanda. Na cardiomiopatia hipertrófica com fibrose perivascular, há funcionalização de vasos colaterais, para aumentar a irrigação dos segmentos hipertrofiados. Objetivo: Determinar o padrão do fluxo coronariano em pacientes com hipertrofia secundária e cardiomiopatia hipertrófica, avaliando a reserva de fluxo coronariano. Métodos: Avaliamos o fluxo coronariano em 34 pacientes com hipertrofia secundária, em 24 com cardiomiopatia hipertrófica e em 16 controles. A artéria descendente anterior foi detectada com Doppler transtorácico com calibração adequada do equipamento. Nos grupos controle e com hipertrofia secundária, foi calculada a reserva de fluxo coronariano com dipiridamol (0,84 mg/kg) endovenoso. O mesmo procedimento foi realizado em seis pacientes do grupo com cardiomiopatia hipertrófica, nos quais também foi avaliado o fluxo das colaterais da região hipertrófica. Os dados foram comparados por variância com significância de 5%. Resultados: Na hipertrofia secundária, houve aumento do índice de massa e, na cardiomiopatia hipertrófica, predominou o aumento da espessura relativa. A fração de ejeção e a disfunção diastólica foram maiores no grupo com cardiomiopatia hipertrófica. A reserva de fluxo coronariano foi menor no grupo com cardiomiopatia hipertrófica, sendo detectado, também, fluxo de colaterais com redução da reserva de fluxo coronariano. Conclusão: A análise da circulação coronariana com Doppler transtorácico é possível em indivíduos normais e hipertróficos. Pacientes com hipertrofia secundária e cardiomiopatia hipertrófica apresentam diminuição da reserva de fluxo coronariano, e aqueles com cardiomiopatia hipertrófica mostram fluxo de vasos colaterais dilatados observados na região hipertrófica, com diminuição da reserva de fluxo coronariano.(AU)
Background: Coronary flow with a diastolic predominance increases two to five times in hyperemia, mediated by vasodilation (coronary flow reserve, CFR) and, in hypertrophy, relative ischemia may occur. In secondary hypertrophy (LVH), the flow, normal at rest, becomes ischemic due to increased demand. In hypertrophic cardiomyopathy (HCM) with perivascular fibrosis, collateral vessels appear to increase the irrigation of hypertrophied segments. Objective: To determine the coronary flow pattern in patients with secondary hypertrophy and hypertrophic cardiomyopathy, evaluating the coronary flow reserve. Methods: Coronary flow was evaluated in 34 patients with secondary hypertrophy, 24 with hypertrophic cardiomyopathy and in 16 controls. The anterior descending artery was detected with transthoracic Doppler with adequate equipment calibration. In the hypertrophic cardiomyopathy group, the flow of collaterals from the hypertrophic region was evaluated. In the control and secondary hypertrophy groups and in six patients in the hypertrophic cardiomyopathy group, the intravenous dipyridamole (0.84 mg) coronary flow reserve was calculated. The data were compared by variance with a significance of 5%Results: In secondary hypertrophy there was an increase in mass index and blood pressure, and in hypertrophic cardiomyopathy an increase in relative thickness predominated. Ejection fraction and diastolic dysfunction were higher in the hypertrophic cardiomyopathy group. The coronary flow reserve was lower in the hypertrophic cardiomyopathy group, and flow of collaterals was also detected, with a reduction in the coronary flow reserve. Conclusion: the analysis of coronary circulation with transthoracic Doppler is possible in normal and hypertrophic individuals. Patients with secondary hypertrophy and hypertrophic cardiomyopathy have a decrease in the coronary flow reserve, and patients with hypertrophic cardiomyopathy show a hyper flow of dilated collateral vessels observed in the hypertrophic region, with a decrease in the coronary flow reserve.(AU)