Wastewater surveillance to assess cocaine and methylenedioxymethamphetamine use trends during a major music festival in Brazil.

Wastewater-based epidemiology was applied in northeastern Brazil during a dance festival, revealing that cocaine consumption doubled during the event days. The daily drug loads were 0.95 ± 0.03 to 11.4 ± 0.4 g/day for BE, 1.8 ± 0.4 to 7.6 ± 0.3 g/day for COC, 0.04 ± 0.02 to 0.19 ± 0.02 g/day for COE, and 0.08 ± 0.02 to 0.80 ± 0.02 g/day for MDMA.

This study employed the wastewater­based epidemiology (WBE) strategy to investigate cocaine (COC) and ecstasy (MDMA) usage during Carnatal festival in Rio Grande do Norte, Brazil. Wastewater samples were collected over the four festival days (December 12­15, 2019), as well as during corresponding days before and after the event. The samples underwent filtration, acidification, solid­phase extraction (SPE) for pre­concentration, and analysis using ultra­high­performance liquid chromatography­tandem mass spectrometry (UHPLC­MS/MS) with calibration using deuterated internal standards. The measured concentration ranges in the wastewater samples were as follows: benzoylecgonine (BE, a metabolite of COC use) ranged from 760 ± 30 to 8914 ± 252 ng/L, COC (non­metabolized or directly discharged) ranged from 1182 ± 25 to 6,760 ± 95 ng/L, cocaethylene (COE, a metabolite of alcohol­COC use) ranged from 21 ± 10 to 161 ± 10 ng/L, and MDMA (ecstasy) ranged from 18 ± 5 to 613 ± 15 ng/L. Daily wastewater loads were estimated as 0.81 ± 0.03 to 11.69 ± 0.33 g/day for BE, 1.42 ± 0.03 to 8.06 ± 0.11 g/day for COC, 0.02 ± 0.01 to 0.21 ± 0.01 g/day for COE, and 0.02 ± 0.01 to 0.80 ± 0.02 g/day for MDMA. Notably, COE and MDMA were only detected above the quantification limit during the festival days. The data enable estimating that COC consumption doubled during the event days. The COC/BE ratio indicated likely drug disposals on the event's last day and the subsequent week. The study's findings shed light on illicit substance consumption, assisting in public health programs and combating drug trafficking efforts.

Inhibition of murine colorectal cancer metastasis by targeting M2-TAM through STAT3/NF-kB/AKT signaling using macrophage 1-derived extracellular vesicles loaded with oxaliplatin, retinoic acid, and Libidibia ferrea.

Colorectal cancer is still unmanageable despite advances in target therapy. However, extracellular vesicles (EVs) have shown potential in nanomedicine as drug delivery systems, especially for modulating the immune cells in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), alone or in combination (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines and prevent metastasis in mice of allograft and peritoneal colorectal cancer models. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or particularly M1EV4 downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastasis in the peritoneum, liver, and lungs. STAT3, NF-kB, and AKT were the major genes downregulated by of M1EV systems. Tumor-associated macrophages (TAMs) shifted from an M2 phenotype (CD163) to an M1 phenotype (CD68) reducing levels of IL-10, TGF-ß and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR1, survivin, vimentin, and PD-L1 after treatment with systems of M1EVs. The study shows that EVs from M1 antitumor macrophages can transport drugs and enhance their immunomodulatory and antitumor activity by modulating pathways associated with cell proliferation, migration, survival, and drug resistance.

A Metformin-Ferulic Acid Salt with Improved Biopharmaceutical Parameters.

Though ferulic acid presents great hypoglycemic potential, it possesses limited aqueous solubility, and low oral bioavailability. When associated with metformin, the first-choice drug in Type 2 diabetes treatment, FA demonstrates synergistic hypoglycemic effects, however, it also causes certain undesirable dose-related effects. This study aimed to develop a new ferulic acid - metformin multicomponent system, and incorporate it into a solid dosage form with improved biopharmaceutical parameters. A novel metformin: ferulate (1:1) salt (MFS) was produced, which was properly characterized using differing analytical techniques, including single crystal analysis. Also during the course of the study, a new polymorph of the metformin free base was observed. The MFS was obtained using solvent evaporation methods, which achieved high yields in reproducible process, as well as a 740-fold increase in ferulic acid aqueous solubility. The MFS tablets developed met quality control requirements for this dosage form, as well as revealing excellent performance in vitro dissolution tests, presenting dissolution efficiency values of 95.4 ± 0.5%. Additionally, physicochemical instability was not observed in a study at 40 °C for 3 months for both MFS powder and its tablet form. The MFS product developed is a promising candidate for further Type 2 diabetes clinical study.

A high-performance liquid chromatography method for simultaneous quantification of metformin and ferulic acid in solid dosage forms.

Metformin is one of the most commonly used drugs in the world for the treatment of type 2 diabetes, while ferulic acid is a molecule that stands out for its antioxidant potential. Recent studies demonstrate hypoglycemic synergy between these molecules. The objective of this study is to develop and validate an analytical methodology by high-performance liquid chromatography for the simultaneous quantification of these drugs in pharmaceutical formulations. The method used an octadecylsilane column and a mobile phase composed of 6 mM sodium lauryl sulfate in 15 mM phosphate buffer:ACN (65:35). Ferulic acid and metformin were monitored at 232 nm, with a mobile phase flow rate of 1 ml/min and oven temperature at 40°C. The method was linear in the range of 5-25 µg/ml for both molecules. In the presence of degradation products, satisfactory selectivity was achieved. Accuracy values were close to 100% and standard deviations in precision were less than 2%. In the robustness evaluation, the proposed variations did not interfere with the quantification. Therefore, it is concluded that the present method can be safely applied to the quality control of ferulic acid and metformin raw materials, as well as when they are combined in pharmaceutical formulations.

Antioxidant Activities of Commiphora leptophloeos (Mart.) J. B. Gillett) (Burseraceae) Leaf Extracts Using In Vitro and In Vivo Assays.

Commiphora leptophloeos is widely used in folk medicine without any scientific basis. Considering this, the aim of this study was to evaluate the chemical profile and the antioxidant activity of C. leptophloeos leaf extracts using in vitro and in vivo assays. Six extracts were obtained from fresh leaves using a serial extraction (nonpolar to polar solvents). These extracts were first evaluated with the presence of phytochemical compounds using the methods thin layer chromatography (TLC), ultrahigh performance liquid chromatography (UHPLC-DAD), and high performance liquid chromatography, both with diode array detection (HPLC-DAD). Based on the compounds identified, it was used some bioinformatics tools in order to identify possible pathway and gene targets. After that, the antioxidant capacity from these extracts was analysed by in vitro assays and in vivo assays using Caenorhabditis elegans model. Phytochemical analyses showed the presence of polyphenols, such as rutin, vitexin, and quercetin diglycosides in all extracts, especially in ethanol extract (EE) and methanol extract (EM). Bioinformatics analysis showed these polyphenols linked to antioxidant pathways. Furthermore, EE and EM displayed a high antioxidant capacity in DPPH and superoxide radical scavenging assays. They also had no effect on cell viability for 3T3 nontumour cell. However, for B16-F10 tumour cell lines, these extracts had toxicity effect. In vivo assays using C. elegans N2 showed that EE was not toxic, and it did not affect its viability nor its development. Besides, EE increased worm survival under oxidative stress and reduced intracellular reactive oxygen species (ROS) levels by 50%. Thus, C. leptophloeos EE displayed an important in vitro and in vivo antioxidant capacity. The EE extract has polyphenols, suggesting that these compounds may be responsible for a myriad of biological activities having this potential to be used in various biotechnological applications.

Influência do uso da proantocianidina em um adesivo autocondicionante: avaliação da resistência de união / Influence of the use of proanthocyanidinin a self-etching adhesive: evaluation of bond strength / Influenciadel uso de proantocianidinaem um adesivo autograbante: evaluación de la fuerza de unión

Introdução:Os sistemas adesivos possibilitama execução de restaurações estéticas e minimamente invasivas, sendo, portanto,objeto de pesquisas para contornar os problemas que se apresentam no procedimento restaurador.Objetivo:Avaliar in vitroa resistência de união de um sistema adesivo autocondicionante, e deste modificado com soluções extrativas de semente de uva.Metodologia:Duas soluções extrativas foram preparadas comextrato de semente de uva em pó dissolvido em acetona e etanol. A partir delas e de umadesivo,seis sistemas adesivos autocondicionantes experimentais foram preparados, diferindo quanto aosolvente utilizado eàsproporções entre adesivo puro e solução extrativa(7,5%, 15% e 30%). Setenta incisivos bovinos hígidos tiveram as raízes removidas com disco de carborundum e as faces vestibulares desgastadas comlixas d'água de granulação 120, 240, 600 e 1200 sob refrigeração até expor a dentina superficial. Os dentes foram distribuídos aleatoriamenteem sete grupos distintos: Controle; A7,5; A15; A30; E7,5; E15; e E30, contendo 10 elementos cada. A aplicação dos adesivos foi executada de acordo com as recomendações do fabricante do adesivo controle. A restauração foi realizada com uma matriz de silicone com dimensões 2mm de altura e 4mm de diâmetro e inserido o material restaurador em incremento único e fotopolimerizado por 40s. Após três meses armazenados em água destilada, os espécimes foram submetidos ao teste de resistência de união. Foi empregado ométodo estatísticoTeste Paramétrico Anova 1 Fator e pós-teste de Tamhane (p<0,05). Resultados:Os grupos A7,5, E7,5 e E30 não apresentaram diferença em relação ao grupo Controle; A15 e A30 mostraram desempenho estatisticamente semelhante entre si; e E15 não apresentou diferença estatística em relação aos outros adesivos.Conclusões:A adição de proantocianidina teve efeitos diferentes,dependendodos solventes e das concentrações utilizadas, mas sem alterar significativamente o desempenho do adesivo (AU).

Introduction:Adhesive systems make it possible to perform aestheticand minimally invasive restorations, being the subject of research to circumvent the problems that arise in the restorative procedure.Objective:Evaluate in vitrothe bond strength of a self-etching adhesive system,and modified with extractive grape seed solutions. Methodology:Two extractive solutions were prepared with powdered grape seed extract dissolved in acetone and ethanol. From them and an adhesive, six experimental self-etching adhesive systems were prepared, differing in terms of the solvent used and the proportions between pure adhesive and extractive solution(7.5%, 15% and 30%). Seventy healthy bovine incisors had their roots removed with carborundum disc and the vestibular faces were worn with sandpaper with granulation water 120, 240, 600 and 1200 under refrigeration until the superficial dentin was exposed. The teeth were randomly assigned to seven different groups: Control; A7.5; A15; A30; E7.5; E15; and E30, containing 10 elements each. The application of the adhesives was carried out according to the recommendations of the manufacturer of the control adhesive. The restoration was performed with a silicone matrix with dimensions 2mm high and 4mm indiameter and the restorative material was inserted in a single increment and light cured for 40s. After three months stored in distilled water, the specimens were submitted to the bond strength test. The statistical method Parametric Test Anova 1 Factor and Tamhane post-test (p<0.05) were used. Results:Groups A7.5, E7.5 and E30 showed no difference in relation to the Control group; A15 and A30 showed a statistically similar performance; and E15 showed no statistical difference in relation to the other adhesives. Conclusions:The addition of proanthocyanidin had different effects, depending on the solvents and concentrations used, but without significantly altering the performance ofthe adhesive (AU).

Introducción: Sistemas adhesivos permiten realizar restauraciones estéticas y mínimamente invasivas, siendo objeto de investigación para sortear problemas que surgen en elprocedimiento restaurador. Objetivo: Evaluar in vitrola fuerza de unión de un sistema adhesivoautograbante y modificado con soluciones extractivas de semilla de uva. Metodología: Se prepararon dos soluciones extractivas con extracto de semilla de uva en polvo disuelto en acetona y etanol. A partir de ellos y de un adhesivo, se prepararon seis sistemas experimentales de adhesivos autograbantes, que se diferencian en cuanto al solvente utilizado y las proporciones entre adhesivo puro y solución extractiva (7,5%, 15% y 30%). Setenta incisivos bovinos sanos fueron removidos con un disco de carborundo y las caras vestibulares fueron usadas com lija de agua de granulación 120, 240, 600 y 1200 bajo refrigeración hasta que la dentina superficial quedo expuesta. Los dientes se asignaron aleatoriamente a siete grupos diferentes: Control; A7,5; A15; A30; E7,5; E15; y E30, que contiene 10 elementos cada uno. La aplicación de los adhesivos se realizó siguiendo las recomendaciones del fabricante del adhesivo de control. La restauración se realizó con matriz de silicona con 2mm de altura y 4mm de diámetro y el material restaurador se insertó en un solo incremento y se fotopolimerizó durante 40s. Tres meses después, almacenados em agua destilada, las muestras se sometieron a la prueba de resistencia de la unión. Se utilizó el método estadístico Prueba Paramétrica Factor Anova 1 y post-prueba de Tamhane (p<0,05). Resultados: Los grupos A7,5, E7,5 y E30 no mostraron diferencias em relación con el grupo Control; A15 y A30 mostraron un desempeño estadísticamente similar; y E15 no mostró diferencia estadística en relación con los otros adhesivos. Conclusiones: La adición de proantocianidina tuvo diferentes efectos, dependiendo de los disolventes y concentraciones utilizadas, pero sin alterar significativamente el rendimiento del adhesivo (AU).

Antioxidant stability enhancement of carotenoid rich-extract from Cantaloupe melon (Cucumis melo L.) nanoencapsulated in gelatin under different storage conditions.

The study evaluated the potential and antioxidant stability of nanoencapsulated carotenoid-rich extract (CE) from Cantaloupe melon (EPG). DPPH and ABTS radical scavenging assays were used to investigate the nanoencapsulation effect on antioxidant potential. CE and EPG stability were evaluated at 25 °C and 5 °C, with and without light (1600 lx) for 60 days, determining the ß-carotene concentration by UHPLC and antioxidant potential by ABTS. The antioxidant potential of carotenoids increased after nanoencapsulation (57-59%). After 60 days, there was low retention of ß-carotene (0-43.6%) in the CE, mainly at 25 °C light (0.00%) and dark (10.0%), and total loss of activity in the four conditions. EPG preserved the ß-carotene concentration in the dark at 25 °C (99.0%) and in the light (83.1%) and dark (99.0%) at 5 °C, maintaining the antioxidant potential (68.7-48.3%). Therefore, EPG enhanced and stabilized the antioxidant potential of carotenoids, beneficial to human health.

Laboratory-Scale Preparation and Characterization of Dried Extract of Muirapuama (Ptychopetalumolacoides Benth) by Green Analytical Techniques.

This work reports on the preparation of a drying process from the ethanolic extract of Muirapuama and its characterization through green analytical techniques. The spray-drying processes were performed by using ethanolic extract in a ratio of 1:1 extract/excipient and 32 factorial design. The properties of dried powder were investigated in terms of total flavonoid content, moisture content, powder yield, and particle size distribution. An analytical eco-scale was applied to assess the greenness of the developed protocol. Ultra-high performance liquid chromatography (UHPLC)with reduced solvent consumption in the analysis was compared to the conventional HPLC method. A Fourier transform near-infrared (FT-NIR) spectroscopic method was applied based on the principal component scores for the prediction of extract/excipient mixtures and partial least squares regression model for quantitative analysis. NIR spectroscopy is an economic, powerful, and fast methodology for the detection of excipient in muirapuama dried extracts, generating no residue in the analysis. Scanning electron microscopy (SEM) images showed samples with a higher concentration of excipient, presenting better morphological characteristics and a lower moisture absorption rate. An eco-scale score value of 85 was achieved for UHPLC and 100 was achieved for NIR (excellent green analysis). Above all, these methods are rapid and green for the routine analysis of herbal medicines based on dried extracts.

A New Ferulic Acid-Nicotinamide Cocrystal With Improved Solubility and Dissolution Performance.

Among the various strategies for increasing aqueous solubility of pharmaceutical substances, cocrystals have been emerging as a promising alternative. The ferulic acid (FEA) is a molecule with limited aqueous solubility, but with an interesting pharmacological activity, highlighting its antitumor potential. This study presents the characterization and physicochemical properties of a new cocrystal based on FEA and nicotinamide (NIC). The FEA-NIC cocrystal was obtained by solvent evaporation technique and physicochemically characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance and scanning electron microscopy. The content determination and dissolution profile in different media were analyzed by high-performance liquid chromatography. The results obtained with the characterization techniques indicated the obtainment of an anhydrous cocrystal of FEA and NIC at a 1:1 molar ratio. The method was reproducible and obtained a high yield, of approximately 99%. In addition, a 70% increase in the FEA solubility in the cocrystal and a better dissolution performance than the physical mixture in pH 6.8 were achieved.

Myrciaria tenella (DC.) O. Berg (Myrtaceae) Leaves as a Source of Antioxidant Compounds.

Myrciaria species are widely studied to identify their chemical composition and evaluate their biological activity. Since evidence supporting the potential antioxidant and antiproliferative activity of Myrciaria tenella is lacking, the aim of this work was to evaluate these activities in six different leaf extracts: hexane (CHE), chloroform (CCE), ethanolic (CEE), methanolic (CME), aqueous final (CFAE), and only aqueous (CAE). The presence of phenolic compounds, tannin, saponin, and ursolic acid was determined by thin layer chromatography (TLC). CEE, CME, and CFAE showed in vitro antioxidant activity at the initiation, propagation, and termination stages of oxidative damage. Moreover, no toxicity was observed in the 3T3 non-cancerous cell line. On the other hand, all extracts promoted cell death in the tumor cell lines human cervical adenocarcinoma cell line (HeLa) and human stomach gastric adenocarcinoma cell line (AGS). Based on these results, the effect of CEE on the AGS cell line was analyzed using flow cytometry, and necrosis and late apoptosis were observed. Finally, the Caenorhabditis elegans model showed that CEE was able to reduce the basal reactive oxygen species (ROS) level. Ultra-performance liquid chromatography (UPLC) analysis showed rutin as the major compound in CEE. Therefore, Myrciaria tenella fresh leaves may be potential sources of molecules possessing antioxidant and antiproliferative activities.

Nanoencapsulation improved water solubility and color stability of carotenoids extracted from Cantaloupe melon (Cucumis melo L.).

Cantaloupe melon carotenoids were encapsulated in porcine gelatin, whey protein isolate and concentrate by emulsification O/W to evaluate which agent could promote an increase in water solubility, and color stability in yogurt. The average particle size obtained was 59.3 (2.60) nm-161.0 (27.30) nm. Encapsulated crude extract in porcine gelatin presented the smallest size and polydispersity index [0.4 (0.04)], and showed sphericity, smooth surface and low agglomeration in SEM. These results associated to the good chemical interaction between the raw materials shown by FTIR, justify the increase in water solubility [0.072 (0.007) mg.mL-1] compared to the crude extract [0.026 (0.003) mg.mL-1]. The yogurt added with this nanoencapsulate remained stable for 60 days, unlike the crude extract. The results show that the nanoencapsulation using gelatin increased water solubility and the potential of application of melon carotenoids in food as natural dyes.

Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves.

Genipa americana is a medicinal plant popularly known as "jenipapo", which occurs in Brazil and belongs to the Rubiaceae family. It is a species widely distributed in the tropical Central and South America, especially in the Cerrado biome. Their leaves and fruits are used as food and popularly in folk medicine to treat anemias, as an antidiarrheal, and anti-syphilitic. Iridoids are the main secondary metabolites described from G. americana, but few studies have been conducted with their leaves. In this study, the aim was to chemical approach for identify the main compounds present at the extract of G. americana leaves. The powdered leaves were extracted by maceration with EtOH: water (70:30, v/v), following liquid-liquid partition with petroleum ether, chloroform, ethyl acetate and n-butanol. A total of 13 compounds were identified. In addition three flavonoids were isolated from the ethyl acetate fraction: quercetin-3-O-robinoside (GAF 1), kaempferol-3-O-robinoside (GAF 2) and isorhamnetin-3-O-robinoside (GAF 3) and, from n-butanol fraction more two flavonoids were isolated, kaempferol-3-O-robinoside-7-O-rhamnoside (robinin) (GAF 4) and isorhamnetin-3-O-robinoside-7-rhamnoside (GAF 5). Chemical structures of these five flavonoids were elucidated using spectroscopic methods (MS, ¹H and 13C-NMR 1D and 2D). These flavonoids glycosides were described for the first time in G. americana.

Physical-Mechanical Properties and Micromorphology of Calcium Cements Exposed to Polyacrylic and Phosphoric Acids.

OBJECTIVE: To evaluate if physical and mechanical properties of self-curing calcium hydroxide cements were affected by contact with polyacrylic and phosphoric acids. MATERIALS AND METHODS: Resin-containing (Life (LF)) and resin-free (Hydro C (HyC)) materials were subjected to polyacrylic acid conditioning and rinsing (POL); phosphoric acid conditioning and rinsing (PHO); rinsing only; and no treatment (n = 10). Water sorption/solubility, release of hydroxyl ions (pH), roughness (Ra), and impact resistance were evaluated. Additional samples (n = 1) were prepared for scanning electron microscopy (SEM) analysis of the surface morphology. Data were analyzed by two-way ANOVA and Tukey post hoc test (P < 0.05). RESULTS: Water sorption was significantly higher for LF when in contact with PHO and lower for POL (P < 0.05). The mean solubility was higher with POL for both cements (P < 0.05). PHO increased the mean surface roughness for HyC (P < 0.01); a significant decrease was noted for LF after contact with both acids (P < 0.01). PHO promoted lower release of hydroxyl ions on both cements (P < 0.05). For LF, rinsing, PHO, and POL presented similar morphology, differing from the control group. For HyC, PHO and POL presented similar morphology, differing from the control group. CONCLUSIONS: PHO had a negative effect on the physical properties of the cements tested, except for the solubility test. POL affected roughness and solubility of HyC cement. CLINICAL RELEVANCE: Clinical procedures that require polyacrylic and phosphoric acid conditioning must be done carefully on self-curing calcium hydroxide cements in order to avoid negative impact on their properties.

Development and validation of an UHPLC method for the determination of betamethasone valerate in cream, gel, ointment and lotion.

An ultra high performance liquid chromatographic method has been developed and validated for the determination of betamethasone valerate (BMV) in topical dermatologic formulations. For the development of the method, response surface methodology based on a three-level full factorial design was used. The eluent composition, the column dimension and the flow rate were chosen as relevant experimental parameters to investigate. The response surface plots revealed an optimum separation by using a RP column (30 mm × 2 mm i.d., 2.2 µm particle size), at 30 °C; isocratic mobile phase consisting of acetonitrile:water (60:40) at a flow rate of 0.2 mL min(-1) and a wavelength set at 254 nm. The proposed method was validated for four types of matrices according to ICH guidelines requirements. Dexamethasone acetate (DMA) was used as internal standard. Linearity was studied in the range of 5-200 µg mL(-1) for BMV in spiked matrix samples. Recoveries were in the range of 95-105% and precision was better than 5% for both analytes, either in cream, gel, ointment, or lotion formulations, when using simple sample preparation. Retention times were 0.95 min for DMA and 1.40 min for BMV, demonstrating a short method run time. The method was successfully applied for routine analysis of dermatological formulations containing betamethasone valerate.

Clinical safety evaluation of a tea containing Cissampelos sympodialis in healthy volunteers

ABSTRACTCissampelos sympodialis Eichler, Menispermaceae, is widely used by Indian tribes and folk medicine to treat various inflammatory disorders, including asthma. Clinical toxicological trials were made with the tea of C. sympodialis, a medicinal plant. The study took place at Lauro Wanderley Hospital/UFPB-PB, where seventeen healthy volunteers were chosen, among those six men and eleven women who orally ingested, during four weeks uninterruptedly, 150 ml of the tea, once a day. Before the first ingestion and after the last one, the participants were subjected to clinical and laboratorial tests for their overall conditions in order to analyze the toxicity of the plant. The results demonstrated that the volunteers neither experience clinical nor laboratorial alterations, as well as no significant adverse effects, apart from little change detected in their hematological tests. Nevertheless, none demonstrated any pathological conditions, just alterations of the normal human being physiology. Therefore, it is concluded that these data complement that obtained during pre-clinical studies and confirm a low toxicity of this plant.

Development of O/W emulsions containing Euterpe oleracea extract and evaluation of photoprotective efficacy

Euterpe oleracea Mart. is a palm tree popularly known as açai, which is primarily found in northern Brazil. The açai's fruits contain anthocyanins, a class of polyphenols to which antioxidant properties have been attributed. The aim of this work was to develop O/W sunscreens emulsions containing açai glycolic extract (AGE) and to evaluate both their physical stability and photoprotective efficacy. Emulsions containing AGE and sunscreens were formulated using different types and concentrations of polymeric surfactant (acrylates/C 10-30 alkyl acrylate crosspolymer and sodium polyacrylate). The influence of two rheology modifiers (polyacrylamide (and) C13-14/isoparaffin (and) Laureth-7 and Carbomer) on the stability was also investigated. Physical stability was evaluated by preliminary and accelerated studies. Emulsions with 1.0% sodium polyacrylate were stable and exhibited non-newtonian pseudoplastic behavior and thixotropy. Photoprotective efficacy was evaluated by in vivo Sun Protection Factor (SPF) and determination of Protection Factor of UVA (PF-UVA). When AGE was added to the sunscreen emulsion, no significant increase in the in vivo SPF value was observed. The emulsion containing AGE showed PF-UVA = 14.97, 1.69 of the SPF/PF-UVA ratio and a critical wavelength value of 378 nm, and may therefore be considered a sunscreen with UVA and UVB protection.

Euterpe oleracea Mart. é uma palmeira popularmente conhecida como açaí, encontrada no norte do Brasil. O fruto do açaí apresenta em sua composição antocianinas, uma classe de polifenóis à qual é atribuída propriedade antioxidante. Os objetivos desse trabalho foram desenvolver emulsões fotoprotetoras O/A contendo extrato glicólico de açaí (AGE), avaliar a estabilidade física e avaliar a eficácia fotoprotetora. Emulsões contendo AGE e filtros solares foram formuladas utilizando diferentes tipos e concentrações de tensoativo polimérico (acrilates/C 10-30 alquil acrilato polímero cruzado e polilacrilato sódico). A influência de dois modificadores reológicos (poliacrilamida (e) C13-14/isoparafina (e) Laureth-7 e Carbomer) na estabilidade foi avaliada. A estabilidade física das emulsões foi avaliada por meio de estudos de estabilidade preliminar e acelerada. Emulsões com 1,0% poliacrilato sódico foram estáveis, exibiram comportamento não-newtoniano pseudoplástico e tixotrópico. A eficácia fotoprotetora foi avaliada pelo teste in vivo de Fator de Proteção Solar (FPS) e pela determinação do Fator de Proteção UVA (FP-UVA). Quando adicionado o AGE na emulsão contendo filtros solares, não se observou aumento significativo no valor do FPS. A emulsão contendo o AGE apresentou FP-UVA=14,97, a razão FPS/FP-UVA = 1,69 e o comprimento de onda crítico igual a 378 nm, podendo ser considerado um protetor solar com proteção UVA e UVB.

Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.

Isoniazida e rifampicina são fármacos de primeira escolha para a prevenção e tratamento da tuberculose. A rifampicina degrada-se em condições ácidas do estômago, principalmente na presença da isoniazida, o que contribui para a falha do tratamento. O presente trabalho teve como objetivo a obtenção de péletes de isoniazida gastrorresistentes, visando a evitar contato da rifampicina com isoniazida e consequente degradação no meio ácido estomacal. Os péletes foram produzidos pela técnica de extrusão-esferonização. O processo de revestimento foi conduzido em leito fluidizado com solução orgânica de Acrycoat L 100(r). Os péletes obtidos foram submetidos ao teste de dissolução em HCl 0,1 N e tampão fosfato. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada completamente no meio tampão fosfato. A quantidade de rifampicina dissolvida em meio ácido, quando associada a péletes de isoniazida não revestidos, foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100(r) mostrou-se eficiente para o recobrimento com a função de gastrorresistência, indicando que a instabilidade da rifampicina pode ser reduzida nas associações com a isoniazida através do revestimento entérico da isoniazida.

Validation of a method for determination of ampicillin in human plasma using LC-DAD.

We describe the validation data of a simple but selective chromatographic method for determination of ampicillin in human plasma using liquid chromatography-diode array detector. Blank plasma free of drugs was transferred to eppendorf's tubes and spiked with ampicillin stock solution to obtain quality control samples at 1.00, 2.50, 5.00, and 10.00 microg/mL. Extraction of ampicillin and cephalexin (internal standard) from plasma samples (250 microL) was investigated using three different methods: precipitation with perchloric acid, ultra-filtration and solid-phase extraction. Chromatographic separation was achieved using a Shimpak C(18) column (300 mm x 4.6 mm i.d.; 5 microm), and detection was done at 215 nm with a diode array UV-Vis detector. The mobile phase consisted of dihydrogen phosphate (pH 3.5)-acetonitrile (87.5:12.5, v/v) delivered at a flow rate of 1.00 mL/min. Selectivity was evaluated with different pools of human plasma. Perchloric acid precipitation showed an excellent selectivity for normal plasma. The precipitation method presented recoveries above 84.0 +/- 3.3% and 82.0 +/- 1.6%, (n = 3) for ampicillin and cephalexin, respectively. The method has a limit of detection of 0.15 microg/mL and is linear in the range of 0.30 to 100.00 microg/mL. Standardized residue analysis demonstrated normality and homocedasticity. Inter-day precision was 4.5%, and accuracy was 11.1% (n = 9). Stability studies demonstrated instability of b-lactamics in human plasma at 20 and 2 degrees C after 6 and 360 h of storage, respectively.

Avaliação de parâmetros de extração da Cinchona Vahl por métodos farmacopéicos e não farmacopéicos / Extraction parameters from Cinchona pubescens Vahl using pharmacopeia and no pharmacopeia methods

O presente estudo teve como objetivo a otimização de parâmetros cinéticos de extração da Cinchona pubescens Vahl por ultra-som, usando métodos farmacopéicos e não farmacopéicos. Na extração por ultrasom variaram-se o tempo, a massa, a faixa granulométrica, o volume de solvente e o tipo de solvente. Na decocção, as extrações foram feitas no tempo e temperatura descrita na Farmacopéia Brasileira IV, variando-se o sistema solvente. Na extração por maceração variaram-se o tempo e o sistema solvente. O teor de alcalóides quinolínicos foi monitorado por espectrofotometria no UV a 325 nm. O método decocção foi o que apresentou o maior rendimento na extração dos alcalóides, dados equivalentes foram conseguidos com o método ultra-som, no tempo de 5 min e solvente acidificado pH 4, com um rendimento maior ao da maceração. Pela aplicação do planejamento fatorial para o método do ultra-som foi visto que há uma interação entre as variáveis, necessitando de um melhor ajuste entre elas a fim de melhorar a eficiência extrativa do método do ultra-som.

The present study for ultrasound had as objective the optimization of kinetic parameters of extraction of the Cinchona pubescens Vahl, using pharmacopeia and no pharmacopeia methods. In the extraction for ultrasound they had varied the time, the solvent type, the mass, the volume of solvent and grain size of the sample. In the decoction, the extractions had been made according to the time and temperature described in Brazilian Pharmacopeia IV, varying the solvent system. In the extraction for maceration the time and the solvent system had varied. The alkali of the Cinchona pubescens Vahl, was monitored by spectrophotometry in UV 325 nm. The method decoction was the one that presented the biggest income in the alkaloids extraction, given equivalent data had been obtained with the method ultrasound, in the solvent acidified pH 4 and time of 5 min, with a bigger income than the one of the maceration.

Evaluation of the leishmanicide action of ethanol extracts of Crotalaria retusa L (Fabaceae) / Avaliação da ação leishmanicida do extrato etanólico da Crotalaria retusa L (Fabaceae)

The purpose of the present work is to conduct an evaluation of the cytotoxicity of ethanol extracts and the total alkaloid fraction (TAF) from Crotalaria retusa for procyclic promastigotes cells of Leishmania chagasi. The kinetic study of extraction assisted by ultrasound of the total alkaloids present in Crotalaria retusa made it possible the optimization of the extraction parameters. It was evaluated the leishmanicide action of the TAF which did not show toxic activity for cells of the parasite in high concentrations. It was observed a powerful leishmanicide action of the ethanol extracts (10 and 30 percent) after the concentration of 5.6 mg/mL of Crotalaria retusa, and the ethanol present in the extractive solution (10 and 30 percent) in the concentration from 70 and 210 x 10-4 percent, respectively. These results suggest that the cytotoxicity of the ethanol extract of Crotalaria retusa at 10 and 30 percent for cells of Leishmania chagasi, can be associated only to the concentration of the alcohol present in the extract.

O presente trabalho se propõe avaliar a atividade citotóxica do extrato etanólico bruto e da fração dos alcalóides totais (FAT) da planta Crotalaria retusa para células promastigotas metacíclicas de Leishmania chagasi. O estudo da cinética de extração por ultra-som para os alcalóides totais da Crotalaria retusa, tornou possível a otimização dos parâmetros de extração. Foi avaliada a ação leishmanicida da FAT da planta em estudo, a qual não mostrou atividade citotóxica em altas concentrações. Foi observado uma potente ação leishmanicida para os extratos etanólicos (10 e 30 por cento) após a concentração de 5,6 mg/mL de Crotalaria retusa e do etanol presente na solução extrativa (10 e 30 por cento) nas concentrações de 70 e 210 x 10-4 por cento, respectivamente. Estes resultados sugerem a citotoxicidade do extrato etanólico da Crotalaria retusa de 10 a 30 por cento para células de Leishmania chagasi, associada possivelmente à concentração do etanol presente no extrato.