Marcos Antônio Fernandes Brandão

Toxicology of Lapachol in rats: embryolethality

Lapachol is a naphtoquinone with therapeutic potential against enterovirus, Chagas disease and is also used as an antimalarial and antiinflamatory agent. In order to study teratogenic potential of Lapachol, pregnant Wistar rats were treated with 0.5 ml of distilled water (control group); 0.5 ml of hydroalcoholic solution (vehicle group) and 10 mg of Lapachol in 0.5 ml of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, l5 and 21 and food intake on days 2, 6, 15 and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA-one way, Dunnett test and the chi square test. Significance level test alpha = 0.05. Results have shown that mothers were unaffected but there were a 99.2% of fetus mortality, indicative of a strong abortifacient effect of Lapachol in rats.

Interceptive effect of Lapachol in rats.

Lapachol is a naphtoquinone with therapeutic potential against Chagas disease and is also used as an antimalarial agent. To study the reproductive toxicity potential of Lapachol, pregnant Wistar rats were treated with 0.5 mL of distilled water (control group), 0.5 mL of hydroalcoholic solution (vehicle group), or 20 mg of Lapachol in 0.5 mL of hydroalcoholic solution (treated group) by oral gavage from the 8th to the 12th day of pregnancy. The following variables were observed: maternal body weight on days 1, 6, 15, and 21; food intake on days 2, 6, 15, and 21 of pregnancy. The number of live and dead fetuses and the sites of resorptions were counted. The ovaries were weighed and the corpora lutea were counted. Data were analyzed by ANOVA one-way Dunnett test and chi 2 test. Results showed that mothers were uneffected but there was 100% fetal/embryo mortality, indicative of a strong interceptive effect of Lapachol in rats.

Mushroom tyrosinase inhibitory activity and major fatty acid constituents of Amazonian native flora oils

In order to treat hyperpigmentation-related problems, there has been a global trend in developing cosmetics claiming to have skin-whitening properties, which act by inhibiting melanin biosynthesis. The objective of this work was to evaluate the in vitro mushroom tyrosinase inhibitory activity of five Amazonian native flora oils, and so to verify the possibility of their incorporation into cosmetic products. In addition, the fatty acid composition of the essential oils was determined by gas chromatography-flame ionisation detection in order to determine the main components of these oils. The tyrosinase inhibitory activity of the tested oils was found to be in the following order: acai (IA50 = 66.08 µg mL-1) > tucuma > pataua > pracaxi > castanha do Brasil. This study suggests that acai oil has great potential in the treatment of hyperpigmentation and other related disorders, due to its considerable tyrosinase inhibitory activity.

Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: A double-blind, randomised study

OBJECTIVE This study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women. DESIGN This study was a prospective, randomised, double-blind, comparative trial with a control group. SETTING The study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil. POPULATION A total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy. INTERVENTIONS The patients were randomised into three groups: (1) daily treatment with 2.5mg tibolone (n=64), (2) 50mg calcium carbonate+200 IU vitamin D3 (Ca/Vit D3, n=54) or (3) 1mg oestradiol+0.5mg norethindrone acetate (E2/NETA, n=56) for 12 weeks. PRIMARY OUTCOME MEASURES The primary outcome was the evaluation of QoL using the Womens Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment. RESULTS A total of 130 women in the following groups completed the study: tibolone (n=42), Ca/Vit D3 (n=44) and E2/NETA (n=44). An improved QoL based on the WHQ was observed at T0 (80.12±14.04, 77.73±15.3, 77.45±15.4) and T12 (57.0±15.5, 55.7±16.7, 58.4±12.6) for the tibolone, E2+NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2±26, 5.6±2.8, 5.4±2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2±1.5, 4.0±1.8, 4.3±2.0, respectively, p values <0.05). Adverse effects were few and mild. CONCLUSIONS An improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend® SF PH4 oral suspensions

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

A natural broad-spectrum sunscreen formulated from the dried extract of Brazilian Lippia sericea as a single UV filter

Despite the challenges in producing plant-derived photoprotective products, novel natural, broad-spectrum sunscreens have gained momentum in the cosmetic industry in the past few years. Traditionally, most of these products have been derived from plants producing polyphenolic and flavonoid compounds. In this study, we focused on plants belonging to the genus Lippia. The study aimed to develop a natural broad-spectrum sunscreen from a Lippia species that could be used as a single UV filter in formulation. Initially, UV transmission of sunscreens (10%, w/w) derived from four different Lippia species was determined to estimate their UVB protection factor (SPF). Next, the extract from species showing the best result was subjected to in vivo SPF and in vitro UVA radiation protection factor (UVAPF) determination using diffuse transmittance spectroscopy. The natural sunscreens obtained in vitro SPF values ranging from 1.7 to 7.6. The higher SPF was obtained with L. sericea species; the in vivo SPF of this sunscreen was 7.5 and its UVAPF was 2.97 when used as a single UV filter in a lotion. The photoprotective activity of this sunscreen was found to be related to the total polyphenolic content of the plant and not to its flavonoid content or antioxidant capacity. Thus, the results of this study suggested that the natural sunscreen from L. sericea has the potential to be used commercially.

In vitro drug release and ex vivo percutaneous absorption of resveratrol cream using HPLC with zirconized silica stationary phase.

Since the designs of optimal formulations for resveratrol permeation via the skin are lacking, the aim of this study was to establish the profile of resveratrol permeability into and across human skin. For that, a laboratory-made chromatographic column was used (Zr-PMODS), with its performance being compared to a traditional C18 column. In vitro drug release was conducted with polysulfone membranes, and the flux (JS) was 30.49 μg cm(-2) h(-1)), with a lag time (LT) of 0.04 h, following a pseudo-first-order kinetics. For ex vivo percutaneous absorption using excised female human skin, the kinetic profile was the same, but JS was 0.87 μg cm(-2) h(-1) and LT was 0.97 h. From the initials 49.30 μg applied to the skin, 9.50 μg were quantified in the receptor medium, 20.48 μg was retained at the stratum corneum (do not account as permeated) and 21.41 μg was retained at the viable epidermis+dermis (account as permeated), totalizing 30.90 μg of resveratrol permeated after 24 h of application (62.6%). From these results, one can conclude that a person using the 1-g emulsion dose released by the pump containing 20mg of resveratrol will have, theoretically, 12.53 mg of it liberated into his bloodstream, gradually and continuously for 24 h.

Optimization of a new dissolution test for oxcarbazepine capsules using mixed-level factorial design

Neste trabalho foi desenvolvido e validado um teste de dissolucao para capsulas de oxcarbazepina. Para o estudo de triagem, foi utilizado um planejamento experimental de niveis mistos composto de fatores com dois e tres niveis (32 × 2), de modo a selecionar a velocidade de agitacao, o meio de dissolucao e o aparato. Esta estrategia e util, pois reduz o tempo de desenvolvimento do metodo e tambem gera resultados mais exatos. A melhor porcentagem de dissolucao foi obtida utilizando o aparato pa a 80 rpm e com solucao aquosa de laurilsulfato de sodio a 1% m/v como meio de dissolucao. A quantificacao da massa dissolvida foi realizada por analise espectrofotometrica UV-Vis a 304 nm. Os resultados do estudo da validacao demonstraram que o metodo e preciso e linear no intervalo de 83-249 µg mL-1 de oxcarbazepina. Os resultados evidenciaram que o metodo apresenta utilidade e adequabilidade para o estudo da dissolucao de capsulas de oxcarbazepina, uma vez que nao existe metodo oficial com este proposito.

Fetal growth in rats treated with lapachol

Lapachol is a naphthoquinone well known for its therapeutic potential. Previous studies have shown that lapachol does not interfere with embryonic development during the pre-implantation period. However, when administered during the organogenic period at the same dose level, it induces a high fetal death incidence. To evaluate the effect of lapachol during fetogenesis, 20 pregnant Wistar rats were randomly divided into two groups: vehicle (10 mL of a 50% aqueous ethanol solution/kg body weight) and treated (100 mg of lapachol/kg body weight). Lapachol was administered from the 17th to 20th day of pregnancy. The following variables were analyzed: maternal body weight from 16th to 21st day of pregnancy, food intake from 17th to 21st day of pregnancy, clinical signs of physical discomfort, ovarian weights, implantations, resorptions and mortality indices, fetal and placenta weights, external malformations, and fetal organ weights. Results indicated that lapachol was not toxic to mothers, although it was fetotoxic leading to fetal growth retardation.

Fatty acid and phospholipase A2 plasma levels in children with autism

OBJECTIVE To evaluate fatty acid plasma levels, phospholipase A2 activity, and the developmental profiles of children with autism vs. control subjects. METHODS Twenty four children with autism underwent laboratory analysis for fatty acid quantification using gas chromatography and PLA2 activity determination by fluorometric assay. RESULTS No correlation was observed between the developmental quotient and fatty acid plasma levels. Phospholipase A2 activity was significantly higher among autistic children compared with controls. CONCLUSION The study did not show a correlation between fatty acid and phospholipase A2 plasma levels and the developmental profile of children with autism.