Effect of Cardioxane and Selenium on Lipoperoxidation and Levels of Dopamine in Rat Brain and Heart

Background: Cardioxane has been probed in patients with advanced malignancies to protect the heart. Selenium, an essential micronutrient exerts varieties of functions such as antioxidant. The aim of this study was to test if cardioxane (CDX) and selenium (Se) have additive antioxidant protective effect on brain and heart, and their relation with dopamine levels. Methods: Thirty-six male Wistar rats divided in groups of 6 animals each, were treated as follows: G1, saline solution 0.9% (control);G2, 100 mg/kg of CDX;G3, 60 μg/kg of Se;G4, 20 mg/kg of 3-nitropropionic acid (3NP);G5, 3NP + CDX and G6, 3NP + Se. 3NP was used as an oxidative stress inducer. Drugs were administered intraperitoneally for 5 days. The animals were sacrificed on the last day of treatment and the brain and heart were extracted and used to measure lipid peroxidation, dopamine, glutathione (GSH), ATPase, calcium, and H2O2. Results: In G2 and G5, dopamine decreased in cortex and striatum while GSH increased in heart, cortex and cerebellum/medulla oblongata. ATPase activity increased in heart and cortex of groups 2, 3, 5 and 6. Lipoperoxidation and H2O2 increased in cortex of animals treated with 3NP. Conclusion: These results suggest that CDX increases antioxidant capacity in the brain and heart while selenium promotes alteration in dopamine metabolism in view of the capacity of 3NP to generate free radicals.

Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use

Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL-1. The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.

Effect of Nicotine on Dopamine and Glutathione Levels in Presence of Oligoelements in Brain Regions of Young Rats——Effect of Nicotine on Brain Regions of Rat

Aim: The purpose of this study was to understand the mechanism of nicotine mediated addiction and the role of oligoelements in reducing its effect. Methods: Male Wistar rats (weight 80 g) were treated with single and repeated doses of nicotine and/or oligoelements as follows: group 1 (control) NaCl 0.9%;group 2, nicotine (1 mg/kg);group 3, oligoelements (50 μl/rat);and group 4, nicotine (1 mg/kg) + oligoelements (50 μl/rat). All drugs were intraperitoneally administered for 4 days. Blood for the measurement of glucose was obtained from all the animals. Samples of the brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were obtained and used to measure the concentrations of dopamine, GSH levels, and lipid peroxidation (TBARS) using fluorescence and spectrophotometric methods. Results: Glucose level increased in rats treated with nicotine and oligoelements (p < 0.05), while GSH level decreased in cerebellum/medulla oblongata and hemispheres (p < 0.05) of the same animals. TBARS levels increased in cerebellum/medulla oblongata and hemispheres of animals treated with nicotine and oligoelements, but decreased in the same regions (p < 0.05) in rats treated only with oligoelements. The levels of dopamine decreased in cortex and hemispheres, but increased in cerebellum/medulla and oblongata regions of rats treated with both compounds (p < 0.05). Conclusions: Nicotine and oligoelements are associated with increase in the level of glucose, an effect that was more pronounced in the group treated with both drugs. Reduction of oxidative stress and dopamine metabolism may be involved in this effect.

Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension

Background:Recently,sildenafil was introduced to treat pulmonary arterial hypertension (PAH);however,there are currently few studies on the pharmacokinetics of sildenalfil in children.Therefore,we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose.Methods:Twelve children diagnosed with PAH,consisting of with ten males and two females,were recruited for the study after obtaining written consent from their parents or guardians.Blood samples were obtained predose and at 0.25,0.5,1,2,4,8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory.The samples were analyzed using a previously validated high performance liquid chromatography method.Results:A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for sdecting a more adjustable model was performed.The following pharmacokinetic parameters were obtained:maximal concentration (Cmax):366+179 ng/mL,time to maximal concentration:0.92±0.30 hours,elimination half-life (t1/2):2.41±1.18 hours,total clearance (CLto/F):5.85±2.81 L/hour,volume of distribution (Vd/F):20.13±14.5 L,absorption rate constants (Ka):0.343 hour-1,elimination rate (Ke):0.35 hour-1,area under curve from zero to infinity:2061±618 ng/mL/hour.The data of all patients adjusted to the model of one compartment were corroborated using AIC.Conclusions:The parameters Ka,Ke and t1/2 were found to be similar to those reported in adults;however,the values of Cmax and Vd/F were significantly higher.Based on these findings,we propose that treatment regimen of sildenafil be adjusted in children with PAH.