Evaluación preclínica de la actividad antiinflamatoria de un gel con aceite de árbol de té / Preclinical evaluation of the anti-inflammatory activity of a gel with tea tree oil

Objetivo: Evaluar la actividad antiinflamatoria de una formulación semisólida que contiene Aceite de Árbol de Té (AAT), a dos concentraciones (2 % y 2,5 %), para futuro tratamiento de enfermedad periodontal.Método: Prueba preclínica de edema auricular por aceite de crotón, con una muestra de 30 ratones, para ser com-parados con Indometacina y Diclofenaco.Resultados: La concentración al 2 % mostró un 51,21 % de inhibición de la actividad inflamatoria, mientras que para la concentración del 2,5 %, fue de 54,74 %. Las pruebas estadísticas para conocer la eficacia de los tratamien-tos demostraron que no existen diferencias significativas entre las combinaciones de tratamientos, indicando que todos tratamientos son similares (p>0,05).Conclusiones: Los resultados de este estudio demuestran que la forma semi solida de AAT, en los estudios preclíni-cos en la fase de ensayos in vivo con animales no humanos demostró poseer una actividad antiinflamatoria. (AU)

Objective: To evaluate the anti-inflammatory activity of a semi-solid Tea Tree Oil (TTO) form at 2 % and 2,5% con-centrations for treating periodontal disease.Method: A preclinical test in a sample of 30 mice with ear edema induced by croton oil was divided into two groups to compare treatment with Indomethacin and Diclofenac.Results: TTO at 2,5 % concentration showed a higher inhibition activity of inflammation (54,74 %) than TTO at 2 % (51,21 %). Statistical analysis showed no significative differences between treatment combinations (p>0,05).Conclusions: The tea tree oil in semi-solid form, applied in 2 - 2,5 % concentration in this preclinical study, showed consistent anti-inflammatory activity. (AU)

Pharmacokinetic-Pharmacodynamic Modeling of Midazolam in Pediatric Surgery.

Midazolam (MDZ) is used for sedation in surgical procedures; its clinical effect is related to its receptor affinity and the dose administered. Therefore, a pharmacokinetic-pharmacodynamic (PK-PD) population model of MDZ in pediatric patients undergoing minor surgery is proposed. A descriptive, observational, prospective, and longitudinal, study that included patients of both sexes, aged 2-17 years, ASA I/II, who received MDZ in IV doses (0.05 mg/kg) before surgery. Three blood samples were randomly taken between 5-120 min; both sedation by the Bispectral Index Scale (BIS) and its adverse effects were recorded. The PK-PD relationship was determined using a nonlinear mixed-effects, bicompartmental first-order elimination model using Monolix Suite™. Concentrations and the BIS were fitted to the sigmoid Emax PK-PD population and sigmoid Emax PK/PD indirect binding models, obtaining drug concentrations at the effect site (biophase). The relationship of concentrations and BIS showed a clockwise hysteresis loop, probably indicating time-dependent protein binding. Of note, at half the dose used in pediatric patients, adequate sedation without adverse effects was demonstrated. Further PK-PD studies are needed to optimize dosing schedules and avoid overdosing or possible adverse effects.

Influence of Age and Sex on the Pharmacokinetics of Midazolam and the Depth of Sedation in Pediatric Patients Undergoing Minor Surgeries.

Whether age and sex influence the depth of sedation and the pharmacokinetics of midazolam is currently unknown. The influence of age and sex was investigated in 117 children (2 to 17 years) who required intravenous sedation for minor surgery (0.05 mg/kg). Plasma concentrations and sedation effects were simultaneously measured. The measured concentrations were analyzed using a two-compartment model with first-order elimination. Among the age ranges, significant differences were found (p < 0.05) between the volume of distribution (Vd) of the first compartment (V1) and that of the second (V2). With respect to sex, differences in V2 were found between age groups. At the administered dose, in patients younger than 6 years, a profound sedative effect (40-60 BIS) was observed for up to 120 min, while in older children, the effect lasted only half as long. The differences found in the Vd and bispectral index (BIS) in patients younger than 6 years compared to older patients may be due to immature CYP3A activity and body fat content; furthermore, the Vd varies with age due to changes in body composition and protein binding. Patients younger than 6 years require intravenous (IV) doses <0.05 mg/kg of midazolam for deep sedation. Dosage adjustments according to age group are suggested.

Sedation level with midazolam: A pediatric surgery approach.

Midazolam (MDZ) is a short-acting benzodiazepine that is widely used to induce and maintain general anesthesia during diagnostic and therapeutic procedures in pediatric patients due to its sedative properties. The aim of this study was to perform a systematic review without a meta-analysis to identify scientific articles and clinical assays concerning MDZ-induced sedation for a pediatric surgery approach. One hundred and twenty-eight results were obtained. After critical reading, 37 articles were eliminated, yielding 91 publications. Additional items were identified, and the final review was performed with a total of 106 publications. In conclusion, to use MDZ accurately, individual patient characteristics, the base disease state, comorbidities, the treatment burden and other drugs with possible pharmacological interactions or adverse reactions must be considered to avoid direct alterations in the pharmacokinetics and pharmacodynamics of MDZ to obtain the desired effects and avoid overdosing in the pediatric population.