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Sialorrhea, defined as an excess flow of saliva or excessive secretions, is common in patients with cerebral palsy and other neurologic disorders and is associated with clinical complications such as increased risk of local skin reactions, infections, aspiration, pneumonia, and dehydration. Upon failure of non-pharmacologic measures, clinicians have several noninvasive pharmacologic options available to manage sialorrhea. This review of the literature provides detailed descriptions of medications used, efficacy, safety, and practical considerations for use of non-injectable pharmacologic agents. The literature search included published -human studies in the English language in PubMed and Google Scholar from 1997 to 2022. Relevant citations within articles were also screened. A total of 15 studies representing 719 pediatric patients were included. Glycopyrrolate, atropine, scopolamine, and trihexyphenidyl all have a potential role for sialorrhea management in children; however, glycopyrrolate remains the most studied option with 374 (n = 52.0%) of the 719 patients included in the systematic review receiving this medication. Overall, glycopyrrolate showed similar efficacy but higher tolerability than its comparators in 2 comparative studies and is often considered the first-line agent. Patient-specific (age, route of administration) and medication-specific (dosage formulation, medication strength) considerations must be weighed when initiating a new therapy or switching to another medication upon treatment failure. Owing to the high propensity of adverse events with all agents, clinicians should consider initiating doses at the lower end of the dosage range, as previous studies have noted a dose-dependent relationship.
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ABSTRACT Purpose: To explore the therapeutic effects of orthokeratology lens combined with 0.01% atropine eye drops on juvenile myopia. Methods: A total of 340 patients with juvenile myopia (340 eyes) treated from 2018 to December 2020 were divided into the control group (170 cases with 170 eyes, orthokeratology lens) and observation group (170 cases with 170 eyes, orthokeratology lens combined with 0.01% atropine eye drops). The best-corrected distance visual acuity, best-corrected near visual acuity, diopter, axial length, amplitude of accommodation, bright pupil diameter, dark pupil diameter, tear-film lipid layer thickness, and tear break-up time were measured before treatment and after 1 year of treatment. The incidence of adverse reactions was observed. Results: Compared with the values before treatment, the spherical equivalent degree was significantly improved by 0.22 (0.06, 0.55) D and 0.40 (0.15, 0.72) D in the observation and control groups after the treatment, respectively (p<0.01). After the treatment, the axial length was significantly increased by (0.15 ± 0.12) mm and (0.24 ± 0.11) mm in the observation and control groups, respectively, (p<0.01). After the treatment, the amplitude of accommodation significantly declined in the observation group and was lower than that in the control group, whereas both bright and dark pupil diameters significantly increase and were larger than those in the control group (p<0.01). After the treatment, the tear-film lipid layer thickness and tear break-up time significantly declined in the two groups (p<0.01). Conclusions: Orthokeratology lens combined with 0.01% atropine eye drops can synergistically enhance the control effect on juvenile myopia with high safety.
RESUMO Objetivo: Explorar os efeitos terapêuticos das lentes de ortoceratologia combinados com colírio atropina 0,01% em miopia juvenil. Métodos: Um total de 340 pacientes com miopia juvenil (340 olhos) tratados entre 2018 e Dezembro de 2020 foram divididos em Grupo Controle (170 casos com 170 olhos, lentes de ortoceratologia) e Grupo Observação (170 casos com 170 olhos, lentes de ortoceratologia combinadas com colírio atropina 0,01%). A acuidade visual melhor corrigida para longe, acuidade visual melhor corrigida para perto, dioptria, comprimento axial, amplitude de acomodação, diâmetro da pupila brilhante, diâmetro da pupila escura, espessura da camada lipídica da película lacrimal e tempo de ruptura do rasgo foram medidos antes do tratamento e 1 ano depois. A incidência de reações adversas foi observada. Resultados: Antes do tratamento, o grau esférico equivalente foi significativamente melhorado em 0,22 (0,06, 0,55) D e 0,40 (0,15, 0,72) D respectivamente no Grupo Observação e no Grupo Controle após o tratamento (p<0,01). Após tratamento, o comprimento axial foi significativamente aumentado em (0,15 ± 0,12) mm e (0,24 ± 0,11) mm respectivamente nos Grupos Observação e controle (p<0,01), enquanto, no grupo de observação, a amplitude de acomodação diminuiu significativamente e foi inferior a do Grupo Controle, e o diâmetro da pupila brilhante e o diâmetro da pupila escura aumentaram significativamente e foram maiores do que os do Grupo Controle (p<0,01). A espessura da camada lipídica da película lacrimal e o tempo de ruptura do rasgo diminuíram significativamente nos dois grupos (p<0,01) após o tratamento. Conclusões: As lentes de ortoceratologia combinadas com colírio atropina 0,01% podem melhorar significativamente o efeito controle em miopia juvenil com elevada segurança.
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ABSTRACT This document on myopia control is derived from a compilation of medical literature and the collective clinical expertise of an expert committee comprising members from the Brazilian Society of Pediatric Ophthalmology and the Brazilian Society of Contact Lenses and Cornea. To manage myopia in children, the committee recommends corneal topography and biannual visits with cycloplegic refraction, along with annual optical biometry. For fast-progressing myopia, biannual biometry should be considered. Myopic progression is defined as an annual increase in spherical equivalent greater than 0.50 D/year or in axial length greater than 0.3 mm (until 10 years old) or 0.2 mm (above 11 years). The proposed treatments for myopia progression include environmental control, low concentration atropine, defocus glasses, contact lenses, or Ortho-K lenses, and combinations of these methods may be necessary for uncontrolled cases. Treatment should be sustained for at least 2 years. This document serves as a comprehensive guideline for diagnosing, treating, and monitoring pre-myopic and myopic children in Brazil.
RESUMO Esta revisão foi baseada na literatura médica e na experiência clínica de um comitê de especialistas membros da Sociedade Brasileira de Oftalmologia Pediátrica e da Sociedade Brasileira de Lentes de Contato e Córnea. Rotineiramente as crianças devem ser submetidas a topografia da córnea no primeiro exame e visitas semestrais com refração cicloplegiada e biometria óptica anual. A progressão da miopia foi definida como um aumento anual no equivalente esférico maior que 0,50 D/ano ou do comprimento axial maior que 0,3 mm (até 10 anos) ou 0,2 mm (mais de 11 anos). Os tratamentos propostos para a progressão são controle ambiental, atropina em baixa concentração, óculos com defocus, lentes de contato ou ortoceratologia, devendo-se considerar associações para casos não controlados. O tratamento deve ser realizado por pelo menos 2 anos. O presente documento é uma diretriz para diagnóstico, tratamento e acompanhamento de crianças pré-míopes e míopes no Brasil.
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ABSTRACT Objective: The benefit of atropine in pediatric tracheal intubation is not well established. The objective of this study was to evaluate the effect of atropine on the incidence of hypoxemia and bradycardia during tracheal intubations in the pediatric emergency department. Methods: This is a single-center observational study in a tertiary pediatric emergency department. Data were collected on all tracheal intubations in patients from 31 days to incomplete 20 years old, performed between January 2016 and September 2020. Procedures were divided into two groups according to the use or not of atropine as a premedication during intubation. Records with missing data, patients with cardiorespiratory arrest, cyanotic congenital heart diseases, and those with chronic lung diseases with baseline hypoxemia were excluded. The primary outcome was hypoxemia (peripheral oxygen saturation ≤88%), while the secondary outcomes were bradycardia (decrease in heart rate >20% between the maximum and minimum values) and critical bradycardia (heart rate <60 bpm) during intubation procedure. Results: A total of 151 tracheal intubations were identified during the study period, of which 126 were eligible. Of those, 77% had complex, chronic underlying diseases. Atropine was administered to 43 (34.1%) patients and was associated with greater odds of hypoxemia in univariable analysis (OR: 2.62; 95%CI 1.15-6.16; p=0.027) but not in multivariable analysis (OR: 2.07; 95%CI 0.42-10.32; p=0.37). Critical bradycardia occurred in only three patients, being two in the atropine group (p=0.26). Bradycardia was analyzed in only 42 procedures. Atropine use was associated with higher odds of bradycardia in multivariable analysis (OR: 11.00; 95%CI 1.3-92.8; p=0.028). Conclusions: Atropine as a premedication in tracheal intubation did not prevent the occurrence of hypoxemia or bradycardia during intubation procedures in pediatric emergency.
RESUMO Objetivo: Avaliar o efeito da atropina na incidência de hipoxemia e bradicardia durante a intubação orotraqueal no departamento de emergência pediátrica. Métodos: Estudo observacional, realizado em departamento de emergência pediátrica terciário em que foram analisados os registros de intubações orotraqueais de pacientes com 31 dias a 20 anos incompletos, entre janeiro de 2016 e setembro de 2020. Os procedimentos foram divididos em dois grupos de acordo com o uso ou não da atropina como pré-medicação durante a intubação. Foram excluídos os procedimentos com falhas no preenchimento dos dados, pacientes com parada cardiorrespiratória, cardiopatias congênitas cianóticas, e aqueles com pneumopatias crônicas com hipoxemia basal. O desfecho primário foi hipoxemia (saturação periférica de oxigênio ≤88%), enquanto os desfechos secundários foram bradicardia (queda >20% entre a frequência cardíaca máxima e mínima) e bradicardia crítica (frequência cardíaca <60 bpm) durante o procedimento de intubação Resultados: Foram identificados 151 procedimentos de intubação orotraqueal, sendo 126 elegíveis para o estudo. Desses, 77% tinham doenças subjacentes complexas e crônicas. A atropina foi administrada em 43 (34,1%) pacientes e foi associada a maiores chances de hipoxemia na análise univariada (OR: 2,62; IC95% 1,15-6,16; p=0,027), porém, não na análise multivariada (OR: 2,073; IC95% 0,416-10,32; p=0,373). A bradicardia crítica ocorreu em apenas três pacientes, sendo dois no grupo atropina (p=0,268). A bradicardia foi analisada em apenas 42 procedimentos. O uso de atropina foi associado a maior probabilidade de bradicardia (OR: 11,00; IC95% 1,3-92,8; p=0,028) na análise multivariável. Conclusões: Atropina como pré-medicação na intubação orotraqueal não evitou a ocorrência de hipoxemia ou bradicardia durante os procedimentos de intubação na emergência pediátrica.
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Objetivo: Comparar la efectividad del tratamiento de atropina versus oclusión ocular en pacientes con ambliopía refractiva moderada unilateral. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo de una serie de casos que acudieron a la consulta de Oftalmología Pediátrica del Instituto Cubano de Oftalmología Ramón Pando Ferrer durante el período comprendido de septiembre del 2019 a septiembre de 2021. La muestra quedó conformada por 44 pacientes, los cuales se dividieron de forma aleatoria en dos grupos de estudio, 22 casos al grupo de oclusiones e igual número al grupo de atropina, que cumplían los criterios de inclusión. Se analizaron las variables edad, sexo, defecto refractivo, agudeza visual mejor corregida, sensibilidad al contraste y estereopsis. Resultados: Predominó el astigmatismo hipermetrópico en ambos grupos de estudio. La media de la agudeza visual mejor corregida inicial en ambos grupos fue de 0,4 LogMAR y mejoró a 0,1 LogMAR al finalizar el tratamiento. La media de la sensibilidad al contraste inicial fue de 1,48 (±19,75) para el grupo de oclusiones y de 1,47 (±20,5) para el grupo atropina, al finalizar alcanzaron 1,59 (±10,1) y 1,57 (±10,0) por orden de mención. La estereopsis inicial fue subnormal en ambos grupos, al finalizar el tratamiento fue normal en el 77,3 por ciento grupo oclusión y el 68,2 por ciento grupo atropina. Conclusiones: La efectividad del tratamiento en pacientes con ambliopía refractiva moderada unilateral con atropina es similar a la que se alcanza con la aplicación de la oclusión ocular(AU)
Objective: To compare the effectiveness of atropine treatment versus ocular occlusion in patients with unilateral moderate refractive amblyopia. Methods: A descriptive, longitudinal and prospective study of a series of cases that attended the Pediatric Ophthalmology office of the Ramón Pando Ferrer Cuban Institute of Ophthalmology during the period from September 2019 to September 2021 was carried out. The sample consisted of 44 patients, who were randomly divided into two study groups, 22 cases to the occlusion group and the same number to the atropine group, who met the inclusion criteria. The variables age, gender, refractive defect, best corrected visual acuity, contrast sensitivity and stereopsis were analyzed. Results: Hypermetropic astigmatism predominated in both study groups. Average initial best-corrected visual acuity in both groups was 0.4 LogMAR and improved to 0.1 LogMAR at the end of treatment. Average initial contrast sensitivity was 1.48 (±19.75) for the occlusion group and 1.47 (±20.5) for the atropine group, at completion reaching 1.59 (±10.1) and 1.57 (±10.0) in order of mention. Initial stereopsis was subnormal in both groups, at the end of treatment it was normal in 77.3 percent occlusion group and 68.2 percent atropine group. Conclusions: The effectiveness of treatment in patients with unilateral moderate refractive amblyopia with atropine is similar to that achieved with the application of ocular occlusion(AU)
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Humanos , Criança , Atropina/uso terapêutico , Ambliopia/etiologia , Epidemiologia Descritiva , Estudos LongitudinaisRESUMO
6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from the rat isolated vas deferens, and has been characterized as a major modulator of the contractility of rat isolated epididymal vas deferens (RIEVD). Drugs such as tricyclic antidepressants, α1 and ß1ß2 adrenoceptor blockers, act as selective antagonists of the 6-ND receptor in the RIEVD. In the rat isolated atria, 6-ND has a potent positive chronotropic action and causes remarkable potentiation of the positive chronotropic effects induced by dopamine, noradrenaline, and adrenaline. Here, whether 6-ND interacts with the classical catecholamines in the rat isolated vas deferens was investigated. Incubation with 6-ND (0.1 and 1 nM; 30min) caused no contractions in the RIEVD but provoked significant leftward shifts in the concentration-response curves to noradrenaline, adrenaline, and dopamine. Pre-incubation of the RIEVD with 6-ND (1 nM), potentiated the contractions induced by electric-field stimulation (EFS), whereas pre-incubation with 1 nM of dopamine, noradrenaline or adrenaline, did not affect EFS-induced contractions. In tetrodotoxin (1 µM) pre-treated (30 min) RIEVD, pre-incubation with 6-ND (0.1 nM) did not cause leftward shifts in the concentration-dependent contractions induced by noradrenaline, adrenaline, or dopamine. Pre-incubation of the RIEVD with the α2A-adrenoceptor antagonist idazoxan (30 min, 10 nM) did not affect dopamine, noradrenaline, adrenaline, and EFS-induced contractions. However, when idazoxan (10 nM) and 6-ND (0.1 nM) were simultaneously pre-incubated (30 min), a significant potentiation of the EFS-induced contractions of the RIEVD was observed. 6-nitrodopamine causes remarkable potentiation of dopamine, noradrenaline, and adrenaline contractions on the RIEVD, due to activation of adrenergic terminals, possibly via pre-synaptic adrenoceptors.
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Norepinefrina , Ducto Deferente , Masculino , Ratos , Animais , Norepinefrina/farmacologia , Epinefrina/farmacologia , Dopamina/farmacologia , Idazoxano/farmacologia , Catecolaminas/farmacologia , Receptores Adrenérgicos , Estimulação Elétrica , Contração MuscularRESUMO
6-Nitrodopamine (6-ND) is released by rat vas deferens and exerts a potent contractile response that is antagonized by tricyclic antidepressants and α1-, ß1- and ß1/ß2-adrenoceptor antagonists. The release of 6-ND, noradrenaline, adrenaline and dopamine from rat isolated right atria was assessed by tandem mass spectrometry. The effects of the catecholamines were evaluated in both rat isolated right atria and in anaesthetized rats. 6-ND was the major catecholamine released from the isolated atria and the release was significantly reduced in nitric oxide synthase inhibitor L-NAME pre-treated atria or in atria obtained from L-NAME chronically treated animals, but unaffected by tetrodotoxin. 6-ND (1 pM) significantly increased the atrial frequency, being 100 times more potent than noradrenaline and adrenaline. Selective ß1-blockers reduced the atrial frequency only at concentrations that prevented the increases in atrial frequency induced by 6-ND 1pM. Conversely, ß1-blockade did not affect dopamine (10 nM), noradrenaline (100 pM) or adrenaline (100 pM) effect. The reductions in atrial frequency induced by the ß1-adrenoceptor antagonists were absent in L-NAME pre-treated atria and in atria obtained from chronic L-NAME-treated animals. Tetrodotoxin did not prevent the reduction in atrial frequency induced by L-NAME or by ß1-blockers treated preparations. In anaesthetized rats, at 1 pmol/kg, only 6-ND caused a significant increase in heart rate. Inhibition of 6-ND synthesis by chronic L-NAME treatment reduced both atrial frequency and heart rate. The results indicate that 6-ND is a major modulator of rat heart chronotropism and the reduction in heart rate caused by ß1-blockers are due to selective blockade of 6-ND receptor.
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Antidepressivos Tricíclicos , Dopamina , Antagonistas Adrenérgicos beta/farmacologia , Animais , Antidepressivos Tricíclicos/farmacologia , Catecolaminas , Dopamina/análogos & derivados , Dopamina/farmacologia , Epinefrina/farmacologia , Átrios do Coração , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase , Norepinefrina/farmacologia , Ratos , Receptores Adrenérgicos , Tetrodotoxina/farmacologiaRESUMO
This study sought to evaluate the histological damage to the respiratory tract caused by inhaling an aqueous solution of 50% malathion, as well as the protective effects of sublingually-applied 1% atropine sulfate eye drops in rats. We searched the literature for the signs and symptoms associated with malathion inhalation for rats, humans, and livestock. We divide 24 female Wistar rats into three groups exposed to distilled water, malathion, and plastic boxes coupled to nebulizers kept at 22- 24°C. At the end of the experiment, the mice were sacrificed and their lungs and trachea were harvested. Histopathological examination revealed that the trachea in the treatment group is similar to that of the control group.
Este experimento buscou estudar e avaliar os danos histológicos ao aparelho respiratório, pela inalação de solução aquosa de Malation a 50% em ratas e o tratamento pela via sublingual com colírio de sulfato de atropina a 1%. Buscamos na literatura os sinais e danos não somente nesta espécie como também em animais domésticos e de produção além de estendermos para seres humanos que eventualmente são intoxicados pela substância. Foram utilizadas 24 ratas, fêmeas, da espécie Wistar em três grupos expostos a água destilada ou malation e outro tratado por 21 dias, utilizando caixas plásticas acopladas a nebulizadores, com controle da temperatura da sala entre 22° e 24°C. Ao final do experimento e eutanásia seguindo as normas de bem-estar dos animais, foram coletados os pulmões e traquéias de todos os grupos, e a partir do exame histopatológico constatou-se recuperação do parênquima de traquéia no grupo tratado, semelhante ao grupo controle.
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BACKGROUND: The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate (OAS) in New Zealand white (NZW) rabbits. METHODS: OAS (1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21, and 30 (OAS group). A second group (n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were: Schirmer I test, tear break-up time (TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated. RESULTS: While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control (p < 0.001), and versus basal production (p < 0.001). TBUT showed statistically significant differences between groups (days 3 and 10; p = 0.001) and versus basal values (day 3; p < 0.001). Fluorescein staining showed a statistically significant difference (day 3; p = 0.001). The most frequent clinical finding was conjunctival hyperemia (76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation (86.7% minimal; 13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference. CONCLUSIONS: The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention; it is not a viable model after OAS administration is suspended.
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Síndromes do Olho Seco , Aparelho Lacrimal , Animais , Atropina/farmacologia , Síndromes do Olho Seco/tratamento farmacológico , Fluoresceína , Inflamação , Aparelho Lacrimal/patologia , CoelhosRESUMO
In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.
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Síndrome do Ovário Policístico , Progesterona , Animais , Atropina/farmacologia , Estradiol , Feminino , Ovulação/efeitos dos fármacos , RatosRESUMO
Breast cancer is a major health problem and accounted for 11.6% of all new cancer cases and 6.6% of all cancer deaths among women worldwide in 2018. However, its etiology has remained elusive. According to epidemiological studies, environmental factors are influencing the increase in the incidence of breast cancer risk. Components such as chemicals, including pesticides, are agents that produce deleterious effects on wildlife and humans. Among them, the organophosphorus pesticides, such as malathion, have largely been considered in this etiology. The epithelial-mesenchymal transition serves a key role in tumor progression and it is proposed that malathion is closely associated with the origin of this transition, among other causes. Moreover, proteins participating in this process are primordial in the transformation of a normal cell to a malignant tumor cell. The aim of the current study was to evaluate markers that indicated oncogenic properties. The results indicated greater expression levels of proteins associated with the epithelial-to-mesenchymal transition, including E-cadherin, Vimentin, Axl, and Slug in the rat mammary glands treated with malathion alone and combined with estrogen. Atropine was demonstrated to counteract the malathion effect as a muscarinic antagonist. The understanding of the use of markers in experimental models is crucial to identify different stages in the cancer process. The alteration of these markers may serve as a predicting factor that can be used to indicate whether a person has altered ducts or lobules in breast tissue within biopsies of individuals exposed to OPs or other environmental substances.
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ABSTRACT A rare case of bilateral congenital microcoria associated with antimetropia in a 47-year-old man is here described. The patient presented with a chief complaint of progressive vision loss in his right eye over the past five years. A slit-lamp examination and ultrasound biomicroscopy confirmed congenital microcoria and cataracts. Phacoemulsification was performed using an iris expansion device and the anterior capsule was stained using the "trypan down under" technique. Preoperative considerations, the surgical approach, and postoperative management are discussed.
RESUMO Um caso raro de microcoria congênita bilateral associada à antimetropia em um homem de 47 anos de idade é descrito aqui. O paciente queixava-se de perda visual progressiva em seu olho direito nos últimos 5 anos. Um exame com lâmpada de fenda e biomicroscopia ultrassônica confirmaram microcoria congênita e catarata. A facoemulsificação foi realizada usando dispositivo de expansão iriana, e a cápsula anterior foi corada através da técnica "trypan down under". Considerações pré-operatórias, abordagem cirúrgica e manejo pós-operatório são discutidos.
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Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Atropina/administração & dosagem , Catarata/complicações , Extração de Catarata , Distúrbios Pupilares/congênito , Facoemulsificação/métodos , Distúrbios Pupilares/cirurgia , Distúrbios Pupilares/complicações , Microscopia AcústicaRESUMO
BACKGROUND: different Solanaceae and Erythroxylaceae species produce tropane alkaloids. These alkaloids are the starting material in the production of different pharmaceuticals. The commercial demand for tropane alkaloids is covered by extracting them from cultivated plants. Datura stramonium is cultivated under greenhouse conditions as a source of tropane alkaloids. Here we investigate the effect of different levels of water availability in the soil on the production of tropane alkaloids by D. stramonium. METHODS: We tested four irrigation levels on the accumulation of tropane alkaloids. We analyzed the profile of tropane alkaloids using an untargeted liquid chromatography/mass spectrometry method. RESULTS: Using a combination of informatics and manual interpretation of mass spectra, we generated several structure hypotheses for signals in D. stramonium extracts that we assign as putative tropane alkaloids. Quantitation of mass spectrometry signals for our structure hypotheses across different anatomical organs allowed us to identify patterns of tropane alkaloids associated with different levels of irrigation. Furthermore, we identified anatomic partitioning of tropane alkaloid isomers with pharmaceutical applications. CONCLUSIONS: Our results show that soil water availability is an effective method for maximizing the production of specific tropane alkaloids for industrial applications.
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Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes. A sub-lethal dose of commercial chlorpyrifos (20â¯mg/kg, i.p.) elicited signs of acute toxicosis during the first hours after its injection in rats. Twenty-four hours after treatment, this single dose of chlorpyrifos induced a depressive-like behaviour in the rat forced swimming test without impairing locomotor activity. At this time (24â¯h), chlorpyrifos decreased plasma butyrylcholinesterase (BChE) activity and hippocampal, striatal and prefrontal cortical AChE activity in rats. The behavioural and biochemical consequences of acute chlorpyrifos poisoning do not seem to be long lasting, since 30â¯days later they were absent. We evaluated whether these behavioural and biochemical consequences of acute chlorpyrifos treatment would be reversed by the antidotes atropine (10â¯mg/kgâ¯i.p.) and/or pralidoxime (40â¯mg/kg; i.p.) given 1â¯h after poisoning. Pralidoxime partially reactivated the AChE activity in the prefrontal cortex, but not in the hippocampus and striatum. Atropine attenuated the depressive-like behaviour induced by chlorpyrifos in rats. Our results suggest that acute chlorpyrifos poisoning induces a transient depressive-like behaviour possible related to hippocampal AChE inhibition. They suggest that treatment with atropine and pralidoxime seems to be insufficient to counteract all the effects of OP acute poisoning, at least in rats.
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Antídotos/farmacologia , Atropina/farmacologia , Encéfalo/efeitos dos fármacos , Clorpirifos/toxicidade , Depressão/prevenção & controle , Intoxicação por Organofosfatos/prevenção & controle , Acetilcolinesterase/metabolismo , Animais , Antídotos/administração & dosagem , Atropina/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Depressão/induzido quimicamente , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Masculino , Intoxicação por Organofosfatos/etiologia , Compostos de Pralidoxima/administração & dosagem , Compostos de Pralidoxima/farmacologia , Ratos , Ratos WistarRESUMO
Mesopontine and basal forebrain cholinergic neurons are involved in the control of behavioral states and cognitive functions. Animals treated with cholinergic muscarinic receptor antagonists display a dissociated state characterized by behavioral wakefulness (W) associated with high amplitude slow oscillations and spindles in the electroencephalogram (EEG), similar to those that occur during non-REM (NREM) sleep. Oscillations in the gamma frequency band (≈ 40 Hz) of the EEG also play a critical role during W and cognition. Hence, the present study was conducted to determine the effect of muscarinic antagonists on the EEG gamma band power and coherence. Five cats were implanted with electrodes in different cortices to monitor the EEG. The effects of atropine and scopolamine on power and coherence within the low gamma frequency band (30-45 Hz) from pairs of EEG recordings were analyzed and compared to gamma activity during sleep and W. Muscarinic antagonists induced a NREM sleep-like EEG profile that was accompanied by a large increase in gamma power and coherence. The values of gamma coherence were similar to that occurring during alert W (AW), and greater than in quiet W, NREM and REM sleep. We conclude that under atropine or scopolamine, functional interactions between cortical areas in the gamma frequency band remain high, as they are during AW. This significant functional connectivity at high frequency may explain why the animals remain awake in spite of the presence of slow waves and spindles.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Eletroencefalografia , Antagonistas Muscarínicos/farmacologia , Animais , Atropina/farmacologia , Gatos , Eletrodos Implantados , Escopolamina/farmacologia , Sono/efeitos dos fármacos , Sono/fisiologia , Vigília/efeitos dos fármacos , Vigília/fisiologiaRESUMO
Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Time-related parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice.
Assuntos
Animais , Masculino , Camundongos , Xilazina/agonistas , Ketamina/agonistas , Atropina/antagonistas & inibidores , Anestesia/classificaçãoAssuntos
Atropina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Compostos Organofosforados/sangue , Compostos de Pralidoxima/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
Resumo Objetivo: Demonstrar a eficácia do uso do colírio de atropina 0,025% em crianças míopes, no Brasil, para a diminuição da progressão da miopia. Métodos: Realizou-se estudo prospectivo em 60 pacientes do Hospital Geral Universitário e Oftalmocenter Santa Rosa - Cuiabá - MT, com idades entre 6 e 12 anos, com equivalente esférico da refração entre -1,00 a -6,00 DE, refração cilíndrica < -1,00 DC e taxa de progressão anual de 0,50 DE (ou maior). Efetuou-se exame oftalmológico geral, topografia corneana e a medida do diâmetro anteroposterior do globo ocular (DAP). Os pacientes foram divididos em dois grupos: em que o Grupo 1 recebeu colírio de atropina 0,025%, todas as noites, e prescreveu-se a refração total com lentes com antirreflexo de multicamadas; e, no Grupo 2, somente a refração total. Nova avaliação foi realizada dois anos após. O teste T Student pareado foi utilizado para comparações das refrações, DAP e ceratometrias, medidas no exame inicial e no exame com 2 anos de seguimento. Resultados: Das 60 crianças, 30 eram do Grupo 1 com idade média de 8,21 ± 1,72 anos, e as do grupo controle com idade média de 8,17 ± 1,73 anos. Quatorze (46,66%) e 16 (53,33%) eram do sexo masculino nos Grupos 1 e 2, respectivamente. O Grupo 1 revelou menor progressão da miopia (Grupo 1: 0,43 ± 0,19D, Grupo 2: 1,24 ± 0,37D) e menor crescimento do DAP em relação ao grupo controle (Grupo 1: 0,19 ± 0,09mm, Grupo 2: 0,48 ± 0,12mm). Houve diferença estatisticamente significativa (P<0,05) entre o grupo tratado e o controle em relação à refração e ao crescimento DAP. A topografia não teve mudança estatisticamente significativa. Conclusão: A atropina em baixas concentrações foi eficaz em diminuir a progressão da miopia em 65% desta população estudada, por 2 anos. No entanto estudos com maior número de participantes e em diversas regiões do Brasil poderiam demonstrar melhor esse fato.
Abstract Purpose: To demonstrate the efficacy of 0.025% atropine eyedrops in myopic children in Brazil for decreasing myopia progression Methods: This was a prospective study with 60 children from Hospital Geral Universitário and Oftalmocenter Santa Rosa in Cuiabá, MT, Brazil, aged between 6 to 12 years, with spherical equivalent refractive error of -1.00 to -6.00 diopters (D) and astigmatism of -1.00 D or smaller. They underwent a complete ophthalmological examination, corneal topography and optical biometry. Children were assigned into two groups: group 1 used 0.025% atropine drop, once-nightly dosing, and it was prescribed total refraction in anti-reflective coating lens; and group 2 was prescribed just total refraction. A new evaluation was conducted 2 years after that. Paired student's t-test was used to compare refractions, axial length and keratometry which were measured in an initial exam and after a two-year follow-up. Results: Of the 60 children, the 30 in group 1 had an age mean and SD 8.21 +/- 1.72, and of the control group were 8.17 +/- 1.73 years. Fourteen (46,66%) and 16 (53,33%) were male, respectively. Myopic progression was significantly lower in group 1 (-0.43 +/- 0.19 D) than in group 2 (-1.24 +/- 0.37 D) and axial length increase was also significantly smaller in group 1(0.19 +/- 0.09 mm) than in group 2 (0.48 +/- 0.12 mm). There were no significant statistical differences regarding keratometry between groups. Conclusions: Low dose atropine eyedrops were effective in decreasing myopia progression in 65% of this population studied for 2 years. Furthermore, a larger scale randomized controlled study with longer follow-up seems warranted.
Assuntos
Humanos , Masculino , Feminino , Criança , Atropina/administração & dosagem , Atropina/uso terapêutico , Miopia/prevenção & controle , Miopia/tratamento farmacológico , Soluções Oftálmicas , Oftalmoscopia , Refração Ocular , Erros de Refração , Tonometria Ocular , Acuidade Visual , Estudos Prospectivos , Estudos Longitudinais , Biometria , Progressão da Doença , Topografia da Córnea , Técnicas de Diagnóstico Oftalmológico , Administração Oftálmica , Instituições de Assistência Ambulatorial , Miopia/diagnósticoRESUMO
RESUMO A nicotina é uma substância perigosa, extraída das folhas de fumo. Quando absorvida em quantidade excessiva, ela pode levar à insuficiência respiratória e à parada cardíaca. A comercialização de cigarros eletrônicos (e-cigarros) permite que os usuários manuseiem diretamente o líquido, com consequente aumento do risco de exposição à nicotina líquida. Descrevemos nossa experiência no tratamento do caso de um paciente que ingeriu elevada concentração de nicotina líquida contida em líquido para e-cigarros. O paciente apresentava bradicardia e hipotensão, que são sintomas de estimulação parassimpática, além de comprometimento da consciência. O paciente teve recuperação após tratamento com atropina e vasopressor.
ABSTRACT Nicotine is a dangerous substance extracted from tobacco leaves. When nicotine is absorbed in excessive amounts, it can lead to respiratory failure and cardiac arrest. The commercialization of electronic cigarettes (e-cigarettes) has allowed users to directly handle e-cigarette liquid. Consequently, the risk of liquid nicotine exposure has increased. We describe our experience of managing the case of a patient who orally ingested a high concentration of liquid nicotine from e-cigarette liquid. The patient presented with bradycardia and hypotension, which are symptoms of parasympathetic stimulation, together with impaired consciousness. He recovered following treatment with atropine and a vasopressor.
Assuntos
Humanos , Masculino , Bradicardia/etiologia , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/intoxicação , Atropina/uso terapêutico , Vasoconstritores/uso terapêutico , Bradicardia/tratamento farmacológico , Hipotensão/etiologia , Hipotensão/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
In the right atrium (RA), adenosine and acetylcholine inhibit the pacemaker function of the sinoatrial node and induce cardiac arrest. Pre-incubation of receptor antagonists is known to inhibit the cardiac arrest induced by these agonists; however, the effect of antagonist administration after established cardiac arrest has not been described. Therefore, we assessed whether specific receptor antagonists could revert cardiac arrest induced by adenosine and muscarinic receptors activation. RA isolated from adults Wistar rats were mounted in an organ bath containing Krebs solution. Cardiac arrest was induced by adenosine or ATP (1mM), the A1 adenosine receptor agonist CPA (0.1-1µM), and muscarinic receptor agonists, carbachol (0.3-1µM) and acetylcholine (1mM). After establishing the cardiac arrest, the A1 adenosine receptor antagonist DPCPX (0.3-30µM), the muscarinic receptor antagonist atropine (10nM to 100µM) or the phosphodiesterase inhibitor IBMX (10-300µM) were incubated in order to check for the return of spontaneous contractions. DPCPX reversed the cardiac arrest induced by adenosine, ATP and CPA. In addition, atropine reversed the cardiac arrest induced by carbachol. Unexpectedly, DPCPX also reversed the cardiac arrest induced by carbachol. Similarly to DPCPX, the phosphodiesterase inhibitor IBMX reversed the cardiac arrest induced by adenosine, CPA and carbachol. The antagonism of adenosine and acetylcholine receptors activation, as well as phosphodiesterase inhibition, are able to revert cardiac arrest. DPCPX restore spontaneous contractions via the selective antagonism of A1 adenosine receptor and through a secondary mechanism likely related to phosphodiesterase inhibition.