BNT162b2 mRNA COVID-19 against symptomatic Omicron infection following a mass vaccination campaign in southern Brazil: A prospective test-negative design study.

BACKGROUND: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant. METHODS: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19. RESULTS: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days. CONCLUSION: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).

Lafoensia pacari alleviates intestinal damage by modulating cyclooxygenase-2: In silico and in vivo evaluation in a colitis model.

BACKGROUND: Inflammatory bowel diseases (IBD) are a worldwide health problem and mainly affect young people, consequently affecting the workforce. Available treatments are often associated with side effects, and new therapeutic options are needed. For centuries, plants have represented important substrates in the field of drug development. Lafoensia pacari (L. pacari) is a plant whose pharmaceutical potential has been described, and may have biological activity relevant to the treatment of IBD symptoms. AIM: To investigate the activity of keto-alcoholic extracts of L. pacari with respect to ameliorating the inflammatory and nociceptive symptoms of acute experimental colitis in mice. METHODS: Keto-alcoholic extracts of L. pacari leaves and bark were administered to male and female Swiss mice weighing 25 g to 30 g (n = 8 male mice and n = 8 female mice). The effect of these extracts was observed in an acetic acid-induced acute experimental model of colitis with regard to antinociception/analgesia and inflammatory tissue damage. Recorded macroscopic indices included the Wallace score and the colon weight obtained using a precision scale. Mechanical hyperalgesia was determined using an electronic analgesimeter. Behavior related to overt pain was determined by quantifying the number of writhing instances within 20 min of administration of acetic acid. Molecular docking was performed using human and murine cyclooxygenase-2 (COX-2) with 3 flavonoids (ellagic acid, kaempferol, and quercetin) on the AutoDock Vina software. Analysis of variance followed by Tukey's posttest was used with P < 0.05 indicating significance. RESULTS: In this murine model of colitis, administration of extracts from L. pacari ameliorated acetic acid-induced writhing and colitis-associated inflammatory pain. These improvements may be attributable to the reduction in edema, inflammation (e.g., ulcers, hyperemia, and bowel wall damage), and the intensity of abdominal hyperalgesia. The keto-alcoholic extracts of L. pacari leaves and bark administered at a dose of either 100 mg/kg or 300 mg/kg significantly reduced the number of writhing events when compared to the negative control (P < 0.05). Additionally, extracts of L. pacari bark also performed better than Dipyrone. Leaf extracts administered at 10 mg/kg, 30 mg/kg, and 100 mg/kg and bark extracts administered at 30 mg/kg significantly reduced or prevented the development of edema in the colon of treated mice, while mesalazine did not. Moreover, using molecular docking, we observed that the flavonoids present in L. pacari extracts bind to COX-2, an event not unique to ellagic acid. CONCLUSION: The results of this study demonstrate a potential novel application of L. pacari extracts for the reduction of inflammation and promotion of antinociception/analgesia as demonstrated by our findings in a murine model of colitis. These findings were also corroborated by in silico analyses, and suggest that L. pacari extracts may be a promising therapeutic agent in the treatment of IBD.

Efeitos sedativos da administração intranasal ou intramuscular de midazolam associado ou não ao butorfanol em periquito autraliano (Melopsitacus undulatus) / Sedative effects of intranasal or intramuscular administration of midazolam with or without butorphanol in budgerigards (Melopsitacus undulatus)

Frequentemente o médico-veterinário é requisitado para realização de diversos procedimentos em aves, os quais geralmente necessitam de sedação ou anestesia geral. Este trabalho teve como objetivo comparar os efeitos sedativos do midazolam (5 mg.kg-1) associado ou não ao butorfanol (1 mg.kg-1) pelas vias de administração intranasal ou intramuscular. Sete periquitos australianos foram submetidos a quatro tratamentos em delineamento do tipo crossover com 15 dias de intervalo. Foram avaliados os períodos de latência, tempos de decúbito dorsal, tempos de sedação, tempos de recuperação, grau de sedação e qualidade de recuperação. Os resultados paramétricos foram avaliados por análise de variância de uma via seguida por teste de Student- Newman-Keuls e os dados não paramétricos foram submetidos ao teste Kruskal-Wallis ambos com 5% de significância. A técnica intranasal demonstrou melhores graus de sedação; no entanto, concluiu-se que ambos os protocolos e as vias de administração avaliados são seguras e viáveis para sedação em periquito australiano.

Often veterinarians have attended various species of birds to perform clinical procedures, which require sedation or general anesthesia. The aim of this study was compare the intranasal or intramuscular sedative effects of midazolam (5 mg.kg-1) with or without butorphanol (1 mg.kg-1). Seven budgerigards (Melopsitacus undulates) were submitted in a crossover design to four treatments. The procedures were performed with 15 days washout. Were evaluated the on set time, dorsal recumbency time duration, total sedation period, total recovery time, sedation degree and recovery quality. The parametric results were analised by one way ANOVA following Student-Newman-Keuls test and non-parametric datas were submitted to Kruskal-Wallis test, both with 5% significance. The intranasal technical demonstrates best degrees of sedation, however, this study concluded that both protocols and the administration routes are safe and viable for sedation in budgerigards

Farmacocinética do propofol em nanoemulsão em cães / Pharmacokinetics of propofol nanoemulsion in dogs

O propofol em nanoemulsão é uma nova formulação constituída por sistemas nanoemulsionados, caracterizado pela ausência do veículo lipídico. A modificação do veículo pode acarretar alterações farmacocinéticas, resultando em diferentes taxas de distribuição e excreção do propofol. O objetivo deste estudo foi avaliar a farmacocinética de uma nova formulação de propofol em nanoemulsão do tipo óleo em água, comparando com a formulação tradicional em emulsão lipídica. Foram utilizadas seis cadelas sem raça definida, castradas (10,7±1,5kg), em estudo aleatório e de autocontrole, que receberam as duas formulações de propofol com intervalo de 30 dias entre os tratamentos, sendo administrada uma dose bolus de 8mg kg-1, seguida de infusão contínua por 60 minutos na taxa de 0,4mg kg-1 min-1. Amostras de sangue arterial foram colhidas momentos antes da indução (0), 2, 5, 10, 15, 30 e 60 minutos após a dose bolus e após o término da infusão nos tempos 5, 10, 15, 30, 60 e 90 minutos e 2, 3, 4, 6, 10 e 24 horas. Não foram encontradas diferenças significativas entre os parâmetros farmacocinéticos de volume de distribuição, clearance, constante de eliminação, meia-vida e constantes de distribuição, demonstrando que o propofol em nanoemulsão não apresenta alteração farmacocinética em relação à formulação tradicional.

Propofol nanoemulsion is a new formulation consisting of nanoemulsified systems, characterized by the absence of lipid vehicle. Changes in drug vehicle may alter the pharmacokinetics and result in different distribution and elimination rates of propofol. The aim of this study was to evaluate the pharmacokinetics of a new oil in water propofol nanoemulsion formulation, compared to the traditional lipid emulsion. Six neutered female mixed-breed dogs were used (10.7±1.5kg) in a randomized and self control trial with 30 days interval. They received both propofol formulations administered as a bolus dose of 8mg kg-1 followed by 60 minutes continuous infusion at 0.4mg kg-1 min-1 rate. Arterial blood samples were collected just before induction (0), 2, 5, 10, 15, 30, and 60 minutes after the bolus dose, and after the end of the infusion at five, 10, 15, 30, 60, and 90 minutes and 2, 3, 4, 6, 10, and 24 hours. There were no significant differences in the evaluated pharmacokinetics parameters that included volume of distribution, clearance, elimination rate constant, half-life, and distribution constants, demonstrating that propofol nanoemulsion has no pharmacokinetics differences when compared to the traditional formulation.

Farmacocinética do propofol em nanoemulsão em gatos / Pharmacokinetic of propofol in nanoemulsion in cats

Os felinos são deficientes na biotransformação do propofol e os dados em relação à farmacocinética nessa espécie são escassos. O objetivo deste estudo foi determinar o perfil farmacocinético da infusão contínua de propofol em nanoemulsão juntamente com a emulsão lipídica em felinos. Utilizaram-se seis gatos sem raça definida (SRD), adultos, machos, castrados, com peso médio de 4,2±0,8kg, em estudo aleatório e de autocontrole. Os animais receberam 10mg kg-1 min-1 de propofol a 1% em emulsão lipídica (EMU) ou em nanoemulsão (NANO) durante 30 segundos e, imediatamente após, iniciou-se a infusão de 0,3 mg kg-1 min-1 da mesma formulação durante 60 minutos. Após 15 dias, receberam o mesmo tratamento com a formulação oposta. Amostras de 3mL de sangue venoso foram coletadas nos tempos 0 (basal), 2, 5, 10, 15, 30 e 60 minutos de infusão e aos 5, 10, 15, 30, 60, 90, 120, 180, 240, 360, 600 e 1440 minutos após o final da infusão. Os parâmetros farmacocinéticos foram determinados a partir da curva de decaimento da concentração plasmática versus tempo ao final da infusão. A análise estatística foi realizada através de ANOVA-RM com posterior teste t pareado entre os grupos. Não houve diferença entre as formulações em relação a todos os parâmetros. Os volumes de distribuição foram altos com Vdss de 23,23±12,30 litros kg-1 para a nanoemulsão e de 18,12±8,54 litros kg-1 para a emulsão lipídica. Os Cls foram baixos com um Cl central de 22,20±10,83mL kg-1 min-1 para a nanoemulsão e de 23,42±13,50mL kg-1 min-1 para emulsão lipídica. Conclui-se que a farmacocinética do propofol em gatos após infusão contínua caracteriza-se por uma ampla distribuição tecidual e uma lenta eliminação, com possível efeito cumulativo. A formulação em nanoemulsão apresenta características farmacocinéticas semelhantes às da emulsão lipídica.

Cats are deficient in the metabolism of propofol and the data on the pharmacokinetics in this species are scarce. The aim of this study was to determine the pharmacokinetic profile of continuous infusion of propofol in lipid emulsion and compare with the nanoemulsion formulation, in cats. Domestic cats, short hair, adults, male, castrated, weighting 4.2±0.8kg in a randomized and self control trial were used. The animals received 10mg kg-1 of 1% propofol in lipid emulsion or nanoemulsion for 30 seconds and immediately after that, a continuous rate infusion of 0.3mg kg-1 min-1 of the same formulation was administered for 60 minutes. After 15 days the cats received the same treatment with the opposite formulation. Samples of 3mL of venous blood were collected by a central venous catheter inserted in the jugular vein at 0 (baseline), 2, 5, 10, 15, 30, and 60 minutes of infusion and at 5, 10, 15, 30, 60, 90, 120, 180, 240, 360, 600 and 1440 minutes after the end of the infusion. The pharmacokinetic parameters were determined from the decay curve of plasma concentration versus time at the end of the infusion. Statistical analysis was performed using RM-ANOVA with subsequent paired t-test between groups. There was no difference between the formulations with respect to all parameters. The volumes of distribution were high with Vdss of 23.23±12.30 liters kg-1 for the nanoemulsion and 18.12±8.54 liters kg-1 for lipid emulsion. The Cls were low with a Cl central to 22.20±10.83mL kg-1 min-1 for the nanoemulsion and 23.42±13.50mL kg-1 min-1 for lipid emulsion. The conclusion is that the pharmacokinetics of propofol in cats after infusion is characterized by a broad tissue distribution and a slow elimination, with possible cumulative effect. The formulation nanoemulsion has pharmacokinetic properties similar to the lipid emulsion.