RESUMO
The ivermectin (IVM), as a broad-spectrum antiparasitic drug, was widely prescribed to treat COVID-19 during the pandemic, despite lacking proven efficacy in combating this disease. Therefore, it is important to establish affordable devices in laboratories with minimal infrastructure. The laser engraving technology has been revolutionary in sensor manufacturing, primarily attributed to the diversity of substrates that can be employed and the freedom it provides in creating sensor models. In this work, electrochemical sensors based on graphene were developed using the laser engraving technology for IVM sensing. Through, the studies that used the techniques of cyclic voltammetry and differential pulse voltammetry, following parameter optimization, for the laser-induced graphene electrode demonstrated a mass transport governed by adsorption of the species and exhibited a linear working range of 10-100 (µmol L-1), a limit of detection (LOD) of 1.6 × 10-6 (mol L-1), a limit of quantification (LOQ) of 4.8 × 10-6 (mol L-1), and a sensitivity of 0.139 (µA µmol L-1). The developed method was successfully applied to direct analysis of pharmaceutical tablets, tap water (recovery of 94%) and synthetic urine samples (recovery between 97% and 113%). These results demonstrate the feasibility of the method for routine analyses involving environmental samples.
Assuntos
Técnicas Eletroquímicas , Grafite , Ivermectina , Lasers , Ivermectina/análise , Ivermectina/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Grafite/química , Humanos , Limite de Detecção , Antiparasitários/urina , Antiparasitários/análise , Antiparasitários/química , Eletrodos , COVID-19 , SARS-CoV-2RESUMO
Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.
Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.
Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ivermectina/análise , Eficácia , Sulfato de Atazanavir/análise , COVID-19/complicações , COVID-19/tratamento farmacológico , Pacientes Ambulatoriais , Estudos Prospectivos , Estudos de Coortes , Ensaios Clínicos como Assunto/métodos , Estudos Observacionais como Assunto/métodosRESUMO
Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.
Assuntos
Antiprotozoários , Curcumina , Leishmania mexicana , Leishmania , Antiprotozoários/química , Antiprotozoários/farmacologia , Membrana Celular/metabolismo , Curcumina/metabolismo , Curcumina/farmacologia , Ivermectina/análise , Ivermectina/metabolismo , Ivermectina/farmacologia , Estresse OxidativoRESUMO
This study aimed at determining the plasma disposition kinetics of eprinomectin (EPM) and EPM excretion pattern through milk after topical administration to dairy cattle at the recommended dose of 0.5 mg/kg and at 1 and 1.5 mg/kg. A high variability in the plasma concentration profiles was observed among animals, particularly in the Cmax values, with a coefficient of variation between 39 and 53%. The Cmax and AUC values were significantly affected by the dose administered at 1.5 mg/kg. However, such differences did not seem to follow a linear pattern among treatments. These parameters did not differ among dose rates after dose normalization; nevertheless, the simulation of a linear kinetic disposition showed a mean plasma AUC value of 254 ng.d/ml instead of the observed value of 165 ng.d/ml. EPM concentration profiles in milk were significantly lower than those measured in plasma. The Cmax and AUC milk-to-plasma ratios ranged from 0.14 to 0.26 and 0.16 to 0.21, respectively (p>0.05). The low milk-to-plasma ratio of EPM accounted for a low percentage of the fraction of the administered dose excreted through milk, being significantly higher at a dose rate of 0.5 mg/kg (0.07%) of EPM than at 1.5 mg/kg (0.04%) (p<0.05). The topical administration of EPM to lactating dairy cows at higher doses than that recommended for gastrointestinal nematodes showed a milk excretion pattern with a zero milk withdrawal period. In conclusion, the administration of topical EPM formulation at 1 or 1.5 mg/kg may be a valuable tool to be used in regional strategic deworming programs aimed to control ectoparasite infections in dairy production systems.
Assuntos
Lactação , Leite , Administração Tópica , Animais , Bovinos , Feminino , Ivermectina/análogos & derivados , Ivermectina/análise , Leite/químicaRESUMO
The presence of antibiotic residues in drinking water may be a source of contamination, which could affect the diffusion of polyphenols into the wine must during the traditional fermentation process. Antibiotic residues such as ivermectin, hydroxychloroquine, ciprofloxacin, and azithromycin on the diffusion of polyphenols and anthocyanins during wine fermentation were studied. Different samples were taken at different periods (0, 48, 96, and 168 h) to analyse the total polyphenols, anthocyanin content, and antioxidant capacity, which were correlated with Peleg's equation to establish the diffusion kinetics of these compounds. The results indicated that the presence of antibiotics reduced between 40 and 50% the diffusion of the total polyphenols and monomeric anthocyanins in red wine. The use of ivermectin showed the highest kinetic parameter k1 compared with the use of other antibiotics. This suggested that the chemical structure and molecular weight of the antibiotics could play an important role in inhibiting the metabolism of yeasts affecting the ethanol and CO2 production. Consequently, cell membranes would be impermeable and would not allow the release of polyphenols and anthocyanins. Therefore, it is necessary to establish strategies that allow future water quality control in wine production companies.
Assuntos
Água Potável , Vinho , Antioxidantes/química , Vinho/análise , Antocianinas/química , Água Potável/análise , Antibacterianos/farmacologia , Antibacterianos/análise , Ivermectina/análise , Polifenóis/análiseRESUMO
O descobrimento, o sucesso comercial e os benefícios sociais da ivermectina (IVM) sempre foram mundialmente reconhecidos e deu aos seus autores o prêmio Nobel de Medicina/Fisiologia, em 2015. Sua exclusiva ação endectocida e alta segurança permitiram que a IVM fosse imediatamente integrada em vários protocolos sanitários para praticamente todas as espécies animais, incluindo humanos. Entretanto, uso da IVM em larga escala e em alta frequência, acarretou a seleção de parasitos resistentes. Mais recentemente, a IVM vem sendo pesquisada e reposicionada para atuar contra o novo RNA beta-corona vírus SARS-CoV-2, principalmente em países da América Latina. Em outra frente, os impactos ambientais também devem ser considerados, pois a eliminação da IVM em grandes quantidades por animais e humanos pode afetar frágeis ecossistemas aquáticos (ex. sedimentos, crustáceos), assim como, comunidades com baixo desenvolvimento social e pouco acesso a redes de água tratada. O objetivo da presente revisão foi abordar os potenciais novos usos da IVM, reconhecendo a importância do medicamento e sua atuação na Saúde Única, durante a pandemia COVID-19. Médicos-veterinários podem participar desde momento, orientando o seu uso de maneira cuidadosa para mitigar problemas sanitários em humanos e animais. A avaliação criteriosa pode evitar o uso excessivo da IVM, protegendo organismos não-alvo em todo o ecossistema.
The discovery, the commercial success, and the social benefits of ivermectin (IVM) were always recognized worldwide and gave the authors the Nobel price of Medicine/Physiology in 2015. Itsexclusive endectocide activity and great safety allowed IVM to be immediately integrated in various health protocols to practically all animal species, including humans. Even tough, the large-scale and the high frequency of use of IVM has caused the selection of resistant parasites. More recently, IVM is being searched and repositioned to act against the new SARS-CoV-2 virus, mainly in Latin American countries. In another front, environmental protection must also be considered, as the large IVM elimination by humans and animals may affect fragile marine ecosystems (ex. sediments, crustaceans) as well as, unassisted communities with low social development with low access to safe water. The objective of the present review was to cover the potential new uses of IVM recognizing the importance of the compound to One Health, during the COVID-19 pandemic. Veterinarians can participate in this moment by advising its correct use to mitigate health problems in humans and animals. A careful evaluation may avoid the excessive use of IVM protecting non-target organisms on the entire ecosystem.
Assuntos
Animais , Doenças Parasitárias em Animais , Ivermectina/análise , Ivermectina/normas , Meio Ambiente , Saúde ÚnicaRESUMO
O descobrimento, o sucesso comercial e os benefícios sociais da ivermectina (IVM) sempre foram mundialmente reconhecidos e deu aos seus autores o prêmio Nobel de Medicina/Fisiologia, em 2015. Sua exclusiva ação endectocida e alta segurança permitiram que a IVM fosse imediatamente integrada em vários protocolos sanitários para praticamente todas as espécies animais, incluindo humanos. Entretanto, uso da IVM em larga escala e em alta frequência, acarretou a seleção de parasitos resistentes. Mais recentemente, a IVM vem sendo pesquisada e reposicionada para atuar contra o novo RNA beta-corona vírus SARS-CoV-2, principalmente em países da América Latina. Em outra frente, os impactos ambientais também devem ser considerados, pois a eliminação da IVM em grandes quantidades por animais e humanos pode afetar frágeis ecossistemas aquáticos (ex. sedimentos, crustáceos), assim como, comunidades com baixo desenvolvimento social e pouco acesso a redes de água tratada. O objetivo da presente revisão foi abordar os potenciais novos usos da IVM, reconhecendo a importância do medicamento e sua atuação na Saúde Única, durante a pandemia COVID-19. Médicos-veterinários podem participar desde momento, orientando o seu uso de maneira cuidadosa para mitigar problemas sanitários em humanos e animais. A avaliação criteriosa pode evitar o uso excessivo da IVM, protegendo organismos não-alvo em todo o ecossistema.(AU)
The discovery, the commercial success, and the social benefits of ivermectin (IVM) were always recognized worldwide and gave the authors the Nobel price of Medicine/Physiology in 2015. Itsexclusive endectocide activity and great safety allowed IVM to be immediately integrated in various health protocols to practically all animal species, including humans. Even tough, the large-scale and the high frequency of use of IVM has caused the selection of resistant parasites. More recently, IVM is being searched and repositioned to act against the new SARS-CoV-2 virus, mainly in Latin American countries. In another front, environmental protection must also be considered, as the large IVM elimination by humans and animals may affect fragile marine ecosystems (ex. sediments, crustaceans) as well as, unassisted communities with low social development with low access to safe water. The objective of the present review was to cover the potential new uses of IVM recognizing the importance of the compound to One Health, during the COVID-19 pandemic. Veterinarians can participate in this moment by advising its correct use to mitigate health problems in humans and animals. A careful evaluation may avoid the excessive use of IVM protecting non-target organisms on the entire ecosystem.(AU)
Assuntos
Animais , Ivermectina/análise , Ivermectina/normas , Saúde Única , Meio Ambiente , Doenças Parasitárias em AnimaisRESUMO
Southern cattle tick resistance to pour-on and injectable acaricides has yet to be evaluated on a broader scope, and the paucity of information on the subject may hinder efforts to control this parasite. The objective of this study was to evaluate the resistance profile of ten populations of Rhipicephalus microplus to the acaricides fluazuron, fipronil and ivermectin in cattle herds in Mato Grosso do Sul, Brazil. The larval immersion test (LIT) was used to evaluate susceptibility to ivermectin and fipronil and the adult immersion test (AIT) was performed to evaluate fluazuron. Samples were randomly obtained in ten farms, and in general, we found resistance in five samples to fluazuron and in four samples to ivermectin and fipronil. Six samples showed incipient resistance to ivermectin and fipronil. Five of the ten evaluated samples showed resistance and/or incipient resistance to all the active ingredients, and the other five to two active ingredients. Among the samples classified as resistant, the average resistance ratio for ivermectin was 2.75 and 3.26 for fipronil. These results demonstrate the advanced status of resistance to the most modern chemical groups for the control of R. microplus in the state of Mato Grosso do Sul.(AU)
A resistência do carrapato-do-boi a acaricidas com modo de aplicação "pour-on" e injetáveis é pouco avaliada em estudos mais abrangentes, e essa escassez de informação pode resultar falhas no seu controle. Este estudo teve como objetivo avaliar o perfil de resistência em dez populações de Rhipicephalus microplus aos acaricidas fluazuron, fipronil e ivermectina, em rebanhos bovinos em Mato Grosso do Sul, Brasil. A caracterização fenotípica da resistência foi realizada por meio do teste de imersão de adultos (AIT) para o fluazuron, e teste de imersão de larvas (LIT) para fipronil e ivermectina. As amostras foram obtidas aleatoriamente em dez fazendas, sendo diagnosticada resistência em cinco amostras ao fluazuron e em quatro amostras à ivermectina e fipronil. Seis amostras apresentaram resistência incipiente à ivermectina e fipronil. Cinco das dez amostras avaliadas apresentaram resistência e / ou resistência incipiente a todos os princípios ativos, e as outras cinco a dois princípios ativos. Entre as amostras classificadas como resistentes, a média do fator de resistência para ivermectina foi de 2,75 e de 3,26 para fipronil. Esses resultados demonstram o avançado estado de resistência aos mais modernos grupos químicos para o controle de R. microplus em Mato Grosso do Sul.(AU)
Assuntos
Rhipicephalus/imunologia , Rhipicephalus/parasitologia , Ivermectina/efeitos adversos , Ivermectina/análise , Acaricidas/imunologiaRESUMO
Avermectins and moxidectin are antiparasitics widely used as active pharmaceutical ingredients in veterinary medicine, as well as in pesticide formulations for pest control in agriculture. Although the use of these compounds provides benefits to agribusiness, they can impact the environment, since a large part of these substances may reach the soil and water from the excreta of treated animals and following direct applications to crops. The present work had the objective of evaluating the dissipation behaviors of abamectin, doramectin, eprinomectin, ivermectin, and moxidectin in four native Brazilian soils of different textural classes (clay, sandy-clay, sandy, and sandy-clay-loam), following OECD Guideline 307. The studies were conducted in a climate chamber at 22⯰C, 71% relative humidity, and protected from light. The dissipation studies were carried out with all drugs together, since no difference was verified when studies were done with each drug separately. The concentrations of the drugs in the soils were determined using an ultra-high performance liquid chromatograph coupled to a fluorescence detector or a tandem mass spectrometer. The dissipation half-life (DT50) values ranged from 9 to 16 days and the calculated GUS index values were in the range from -1.10 to 0.08, indicating low mobility of the drugs in the soils evaluated and low tendency for leaching. In addition, a field study was carried out to evaluate the dissipation of abamectin after application of a foliar pesticide in an orange crop. A DT50 of 9 days was determined, which was similar to that obtained under controlled conditions in the climate chamber (12 days), indicating that biotransformation was the primary process influencing the overall dissipation.
Assuntos
Antiparasitários/química , Ivermectina/análogos & derivados , Macrolídeos/metabolismo , Praguicidas/química , Poluentes do Solo/química , Solo/química , Antiparasitários/análise , Brasil , Monitoramento Ambiental , Meia-Vida , Ivermectina/análise , Ivermectina/química , Ivermectina/metabolismo , Macrolídeos/análise , Macrolídeos/química , Praguicidas/análise , Poluentes do Solo/análiseRESUMO
Due to the lack of regulated drugs for aquaculture, the present study considered specific issues relating to environmental and food safety aspects concerning the potential use of emamectin benzoate (EMA) in freshwater fishes such as tilapia (Oreochromis niloticus) - an important commercial fish species worldwide. The residual depletion of EMA (EMA-B1a) in fillet (muscle plus skin in natural proportions) of tilapia treated with a daily dose of 50⯵g/kg BW during seven consecutive days was evaluated. To facilitate this, analytical methods for quantitation of EMA in fish feed and in fish fillet employing LC-MS/MS were developed and validated. To eliminate the risk of EMA leaching from feed into the aquatic environment during fish medication via oral administration, a promising procedure for drug incorporation into feed involving the coating of feed pellets with ethyl cellulose polymer containing EMA was evaluated. The medicated feed exhibited good homogeneity (CVâ¯<â¯2.1%) with negligible EMA release (< LOQ) when the medicated feed remained in the water for up to 20â¯min. Depletion study analysis revealed the highest EMA concentration obtained in fish fillet to be 13.3â¯ng/g. Therefore, under the employed rearing conditions of this study, the obtained results did not evidence requirement for a minimum withdrawal period to be proposed considering the maximum residue limit of 100⯵g/g for fish muscle. In response to the well-recognized demands and need for new alternative veterinary drugs for use within aquaculture, this study offers impetus for consideration of EMA use in tilapia taking into account environmental contamination and food safety issues.