Exosome-Enriched Plasma Analysis as a Tool for the Early Detection of Hypertensive Gestations.

Hypertensive disorders of pregnancy are closely associated with prematurity, stillbirth, and maternal morbidity and mortality. The onset of hypertensive disorders of pregnancy (HDP) is generally noticed after the 20th week of gestation, limiting earlier intervention. The placenta is directly responsible for modulating local and systemic physiology by communicating using mechanisms such as the release of extracellular vesicles, especially exosomes. In this study, we postulated that an analysis of exosome-enriched maternal plasma could provide a more focused and applicable approach for diagnosing HDP earlier in pregnancy. Therefore, the peripheral blood plasma of 24 pregnant women (11 controls, 13 HDP) was collected between 20th and 24th gestational weeks and centrifuged for exosome enrichment. Exosome-enriched plasma samples were analyzed by Raman spectroscopy and by proton nuclear magnetic resonance metabolomics (1H NMR). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the Raman data, from the spectral region of 600-1,800 cm-1, to determine its potential to discriminate between groups. Using principal component analysis, we were able to differentiate the two groups, with 89% of all variances found in the first three principal components. In patients with HDP, most significant differences in Raman bands intensity were found for sphingomyelin, acetyl CoA, methionine, DNA, RNA, phenylalanine, tryptophan, carotenoids, tyrosine, arginine, leucine, amide I and III, and phospholipids. The 1H NMR analysis showed reduced levels of D-glucose, L-proline, L-tyrosine, glycine, and anserine in HDP, while levels of 2-hydroxyvalerate, polyunsaturated fatty acids, and very-low-density lipoprotein (VLDL) were increased. 1H NMR results were able to assign an unknown sample to either the control or HDP groups at a precision of 88.3% using orthogonal partial least squares discriminant analysis and 87% using logistic regression analysis. Our results suggested that an analysis of exosome-enriched plasma could provide an initial assessment of placental function at the maternal-fetal interface and aid HDP diagnosis, prognosis, and treatment, as well as to detect novel, early biomarkers for HDP.

Dynamic Electroporation Model Evaluation on Rabbit Tissues.

Biological electroporation is a process of opening pores in the cell membrane when exposed to intense electric fields. This work provides results for validation of a dynamic model of electroporation on biological tissues. Computational simulations were carried out and results for the electrical current through the tissue and increase of the tissue temperature were compared to experimental results. Two calculation methods were used: Equivalent Circuit Method and Finite Element Method. With Equivalent Circuit Method the dielectric dispersion present in biological tissues was included. Liver, kidney and heart of rabbit were used in the experiments. Voltage pulse protocols and voltage ramps were applied using stainless steel needles electrodes. There is good agreement between the simulated and experimental results with mean errors below 15%, with the simulated results within the experimental standard deviation. Only for the protocol with fundamental frequency of 50 kHz, the simulation performed by the Finite Element Method using a commercial software did not correctly represent the current, with errors reaching 50%. The justification for the error found is due to the dielectric dispersion that was not included in this simulator.

Hypolipidemic, hipoglycemiant and antioxidant effects of Myrcia splendens (Sw) DC in an animal type 2 diabetes model induced by streptozotocin / Efectos hipolipemiante, hipoglucemiante y antioxidante de Myrcia splendens (Sw) DC en un modelo animal de diabetes tipo 2 inducido por estreptozotocina

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.

Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.

Estudo retrospectivo da prevalência de perfurações gastrointestinais em pacientes submetidos a colonoscopias no Hospital Regional Hans Dieter Schmidt / Retrospective study of the prevalence of gastrointestinal perforation in patients submitted to colonoscopies at Hans Dieter Schmidt Regional Hospital

Introdução: A colonoscopia é um instrumento padrão ouro para triagem e identificação precoce do câncer colorretal. Embora relativamente segura, está sujeita a complicações, como a perfuração de cólon, vinculando-se com altas taxas de morbidade e mortalidade. Objetivos: Avaliar a prevalência de perfuração intestinal em realização de colonoscopias entre os anos de 2012 e 2017 no Hospital Regional Hans Dieter Schmidt, em Joinville-SC e traçar um perfil dos sujeitos que sofreram perfuração, fatores de risco associados, caracterização do exame (diagnóstico ou terapêutico) e seus respectivos desfechos clínicos. Métodos: Estudo quantitativo, descritivo, retrospectivo e transversal, com coleta de dados realizada por análise de prontuários eletrônicos, resultados de colonoscopias e laudos anatomopatológicos. Resultados: Entre 2012 e 2017 foram realizadas 898 colonoscopias, sendo registradas 9 perfurações (1,00%), sendo 4 em mulheres e 5 em homens. Destas, 8 (0,89%) foram com intuito diagnóstico e 1 (0,11%) teve objetivo terapêutico. As faixas etárias variavam entre 46 e 76 anos, sendo a hipertensão arterial sistêmica (55,55%) e a realização de cirurgias prévias (55,55%) os fatores de risco mais encontrados. Os diagnósticos das perfurações foram realizados por meio de laparotomia, e o tratamento foi realizado conjuntamente ao diagnóstico. Cinco casos evoluíram a óbito após a realização do tratamento, um para sepse e outro para peritonite fecal. Conclusão: Perfurações secundárias a exame de colonoscopia apesar de escassas, porém cursar com complicações graves, como sepse, peritonite fecal e até mesmo óbito.

câncer diagnosis. Though it is a relatively safe exam, it is not free of complications, such as colon perforation, which presents a high morbimortality rate. Objectives: Investigate the prevalence of perforation in subjetcs who went through colonoscopy in the Regional Hospital Hans Dieter Schmidt, located in Joinville (SC) during 2012-2017 and their epidemiologic profile, including risk factors, exam intention (therapeutic or diagnosis) and respective outcomes. Methods: Cross-sectional, descriptive, quantitative and retrospective study, whose data were collected from medical registers of colonoscopy outcomes and anatomopathologic reports. Results: During 2012-2017 period, 898 colonoscopies were conducted and 9 perforations (1,00%) cases were observed, four in men and five in women. Among those, eight (0,89%) aimed diagnosis and one (0,11%) was therapeutic. Age of subjects who suffered perforation ranged from 46 to 76 years and systemic arterial hypertension and previous surgery were the most present risk factors (55,55% each). Perforation cases were detected by laparotomy and the management was instituted right after diagnosis. Five cases resulted in death after treatment, one progressed to sepsis and other to fecal peritonitis. Conclusion: Perforation due to colonoscopy, though rare, might progress to serious complications, like sepsis, fecal peritonitis and even death.

Effects of aerobic exercise training on oxidative stress in the skeletal muscles of obese rats / Efeitos do treinamento aeróbico sobre o estresse oxidativo em músculos esqueléticos de ratos obesos / Efectos del entrenamiento aeróbico sobre el estrés oxidativo en músculos esqueléticos de ratones obesos

ABSTRACT Introduction Obesity is a complex and multifactorial metabolic disorder characterized by the accumulation of body fat; physical exercise increases energy expenditure and promotes a reparative effect through modulation of endogenous antioxidant defenses. Objective To evaluate the effects of the high-fat diet (HFD) on oxidative stress parameters in skeletal muscles of rats using aerobic exercise training protocols (AETP), moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). Methods The study was quantitative and experimental. Animals received 8 weeks of HFD or normal diet (ND), followed by 9 weeks of HFD or ND and the two AETPs. Results HFD did not alter the formation of thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl and protein carbonyl content in the soleus and plantaris muscles; in contrast, the protocols caused a decrease in TBA-RS levels in the plantaris muscle and increased the sulfhydryl content in the soleus muscle, while MICT increased the sulfhydryl content in the plantaris muscle and reduced protein carbonyl content in both muscles. HFD reduced SOD activity in the plantaris muscle while the MICT protocol enhanced SOD in the soleus muscle and both protocols reversed the decrease in SOD in the plantaris muscle. HFD increased CAT activity in the soleus muscle, the HIIT protocol prevented this alteration and both protocols increased CAT in the plantaris muscle. HFD reduced GSH-Px activity in both muscles, and the MICT protocol prevented this reduction in the soleus muscle, while the HIIT protocol partially prevented this decrease. The MICT protocol did not prevent the reduction of GSH-Px and the HIIT protocol partially prevented this decrease in the plantaris muscle. Conclusions HFD elicited oxidative stress in the skeletal muscle of rats, and both protocols were able to prevent most of the alterations in oxidative stress parameters caused by the HFD. Level of evidence IV; Investigation of treatment outcomes.

RESUMO Introdução Obesidade é uma desordem metabólica complexa e multifatorial, caracterizada pelo acúmulo de gordura corporal. O exercício físico tem a capacidade de aumentar o gasto energético e promover efeito reparador por meio da modulação das defesas antioxidantes endógenas. Objetivo Avaliar os efeitos da dieta hiperlipídica (DHL) sobre parâmetros de estresse oxidativo em músculos esqueléticos de ratos, por protocolos de treinamento físico aeróbico (TFA), treinamento contínuo de intensidade moderada (TCIM) e treinamento intervalo de alta intensidade (HIIT). Métodos O estudo foi quantitativo e experimental. Animais receberam 8 semanas de DHL ou dieta normal (DN), seguidas por 9 semanas de DHL ou DN e os dois TFA. Resultados A DHL não alterou a formação de substâncias reativas ao ácido tiobarbitúrico (TBA-RS), conteúdo total de sulfidrilas e de proteínas carboniladas nos músculos sóleo e plantar. Em contraste, os protocolos diminuíram TBA-RS no músculo plantar e aumentaram o conteúdo de sulfidrilas no músculo sóleo. TCIM aumentou o conteúdo de sulfidrilas no músculo plantar e reduziu o conteúdo de proteínas carboniladas em ambos os músculos. A DHL reduziu a atividade da SOD no músculo plantar; o TCIM aumentou a SOD no músculo sóleo e ambos os protocolos reverteram a diminuição da SOD no músculo plantar. A DHL aumentou a CAT no músculo sóleo, o HIIT preveniu essa alteração e ambos os protocolos aumentaram a CAT no músculo plantar. A DHL diminuiu a atividade da GSH-Px em ambos os músculos, e o TCIM preveniu esta diminuição no músculo sóleo, enquanto que o HIIT preveniu parcialmente esta diminuição. O TCIM não preveniu a redução da GSH-Px, e o HIIT preveniu parcialmente esta diminuição no músculo plantar. Conclusão A DHL causou estresse oxidativo nos músculos esqueléticos de ratos, e ambos os protocolos foram capazes de prevenir a maioria das alterações nos parâmetros de estresse oxidativo causadas pela DHL. Nível de evidência IV; Investigação dos resultados do tratamento.

RESUMEN Introducción La obesidad es un desorden metabólico complejo y multifactorial caracterizado por la acumulación de grasa corporal. El ejercicio físico tiene la capacidad de aumentar el gasto energético y promover efecto reparador por medio de la modulación de las defensas antioxidantes endógenas. Objetivos Evaluar los efectos de la dieta hiperlipídica (DHL) sobre parámetros de estrés oxidativo en los músculos esqueléticos de las ratas, por protocolos de entrenamiento físico aeróbico (TFA), entrenamiento continuo de intensidad moderada (TCIM) y entrenamiento de intervalo de alta intensidad (HIIT). Métodos El estudio fue cuantitativo y experimental. Los animales recibieron ocho semanas de DHL o dieta normal (DN), seguidas por nueve semanas de DHL o DN y los dos TFA. Resultados La DHL no alteró la formación de sustancias reactivas al ácido tiobarbitúrico (TBA-RS), contenido total de sulfhidrilos y de proteínas carboniladas en los músculos sóleo y plantar. En contraste, los protocolos disminuyeron TBA-RS en el músculo plantar y aumentaron el contenido de sulfhidrilos en el músculo sóleo. TCIM aumentó el contenido de sulfhidrilos en el músculo plantar y redujo el contenido de proteínas carboniladas en ambos músculos. La DHL redujo la actividad de la SOD en el músculo plantar, el TCIM aumentó la SOD en el músculo sóleo y ambos protocolos revirtieron la disminución de la SOD en el músculo plantar. La DHL aumentó la CAT en el músculo sóleo, el HIIT previno esa alteración y ambos protocolos aumentaron la CAT en el músculo plantar. La DHL disminuyó la actividad de GSH-Px en ambos músculos, y el TCIM previno esta disminución en el músculo sóleo, mientras que el HIIT previno parcialmente esta disminución. El TCIM no previno la reducción de la GSH-Px y el HIIT previno parcialmente esta disminución en el músculo plantar. Conclusión La DHL causó estrés oxidativo en los músculos esqueléticos de ratones y ambos protocolos fueron capaces de prevenir la mayoría de las alteraciones en los parámetros de estrés oxidativo causados por DHL. Nivel de evidencia IV; Investigación de los resultados del tratamiento.

Hypolipemiant and antioxidant effects of Eugenia brasiliensis in an animal model of coconut oil-induced hypertriglyceridemia.

We investigated the effects of chronic administration of crude hydroalcoholic extract (CHE) and crude acetone extract (CAE) obtained from leaves of Eugenia brasiliensis species on hypertriglyceridemia and oxidative stress caused by the chronic administration of coconut oil. Rats received CHE or CAE (50, 100 or 150mg/kg, orally) for 30days, plus coconut oil (2mL, orally) or saline for 15th. Triglyceride levels, liver cell lipid accumulation, thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activities of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in the blood and liver of rats. Results showed that chronic administration of CHE or CAE was able to prevent hypertriglyceridemia and decrease the lipid droplets in liver cells, as well as the increase in TBA-RS, the reduction in total sulfhydryl content and CAT activity in the blood and prevent total or partial the increase in CAT and reduction in SOD and GSH-Px activities in the liver. These findings indicate that both extracts may have hypolipidemic and antioxidant effects.

Argininic acid alters markers of cellular oxidative damage in vitro: Protective role of antioxidants.

We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0mM) trolox and ascorbic acid, as well as of NG-nitro-l-arginine methyl ester (L-NAME) at 1.0mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10vol (1:10w/v) of 20mM sodium phosphate buffer, pH 7.4, containing 140mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1h at 37°C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0µM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0µM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology.

Galactose alters markers of oxidative stress and acetylcholinesterase activity in the cerebrum of rats: protective role of antioxidants.

We evaluated the in vitro effects of galactose at 0.1, 3.0, 5.0 and 10.0 mM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content, protein carbonyl content, on the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum and hippocampus of rats. We also investigated the influence of the antioxidants (each at 1 mM), α-tocopherol, ascorbic acid and glutathione, on the effects elicited by galactose on the parameters tested. Results showed that galactose, at a concentration of 3.0 mM, enhanced TBA-RS levels in the hippocampus, cerebral cortex and cerebellum of rats. In the cerebral cortex, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and protein carbonyl content, and at 10.0 mM increased CAT activity and decreased AChE activity. In the cerebellum, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS, SOD and GSH-Px activities. In the hippocampus, galactose at concentrations of 5.0 and 10.0 mM increased TBA-RS and CAT activity and at 10.0 mM decreased GSH-Px. Data showed that at the pathologically high concentration (greater than 5.0 mM), galactose induces lipid peroxidation, protein carbonylation, alters antioxidant defenses in the cerebrum, and also alters cholinesterase activity. Trolox, ascorbic acid and glutathione addition prevented the majority of alterations in oxidative stress parameters and the decrease in AChE activity that were caused by galactose. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by galactose.

Differential in vitro effects of homoarginine on oxidative stress in plasma, erythrocytes, kidney and liver of rats in the absence and in the presence α-tocopherol, ascorbic acid or L-NAME.

In the present study, we evaluated the in vitro effects of homoarginine (hArg) at 1, 10 and 20 µM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma, erythrocytes, kidney and liver of rats (60 days old). We also investigated the influence of the antioxidants (each at 1 mM) α-tocopherol and ascorbic acid, as well as of the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) at 1 mM, on the effects elicited by hArg on the parameters tested. In plasma, hArg at concentrations of 10 and 20 µM decreased moderately the total sulfhydryl content. At 20 µM, hArg enhanced moderately TBA-RS in the plasma. In plasma, the effects of hArg (20 µM) on TBA-RS and total thiol content were abolished by α-tocopherol, ascorbic acid and L-NAME. At all concentrations tested, hArg did not exert any effect on CAT, SOD or GSH-Px activity in the erythrocytes. In the kidney, hArg exerted effects only at 20 µM and in a different manner: TBA-RS levels increased and total thiol content and CAT activity decreased, while SOD and GSH-Px activity increased. In the renal medulla, α-tocopherol and ascorbic acid but not L-NAME abolished the effects of hArg (20 µM) on TBA-RS, while all agents inhibited the hArg-induced increase in SOD activity. In the renal cortex, α-tocopherol, ascorbic acid and L-NAME abolished the effects of hArg (20 µM) on the total sulfhydryl content and GSH-Px activity, but L-NAME did not reverse the inhibitory effects of hArg on CAT activity. In the liver, no effects of hArg were observed of all biomarkers measured. At the pathologically high concentration of 20 µM, as it may occur in plasma in hyperargininemia, hArg may enhance lipid peroxidation and thiol oxidation and inhibit CAT activity, but may increase SOD and GSH-Px activity predominantly in the kidney.

Pharmacodynamic and Pharmacokinetic Studies of β-Cyclodextrin:Dexamethasone Acetate Complexes in Mice

The aim of this study was to evaluate the in vivo activity of the anti-inflammatory and analgesic effects of a suspension of the complex composed of dexamethasone acetate (DMA) with β-cyclodextrin in comparison to a suspension of the pure DMA. Solid complexes prepared by different methods were evaluated in pharmacodynamics and pharmacokinetics studies. The pharmacodynamic effect was investigated although the capacity of the inhibited the inflammation. Models of abdominal constriction, carrageenan-induced paw oedema and formalin induced licking were used. The study of the pharmacodynamic comparison of free DMA and products of β-CD:DMA demonstrated no significant difference in the majority of the tests performed. Plasma concentrations of DMA and DMA:β-CD were assayed by HPLC. A significant (p > 0.05) decrease in the relative bioavailability was obtained with the suspension containing the DMA:β-CD complex as measured by DMA plasma levels. The area under the curve (AUC) of the suspension of DMA was higher than that obtained with the suspension of the complexes. The pharmacokinetic evaluation of dexamethasone carried out on mice in the present study showed that complexed DMA with β-cyclodextrin modifieds some parameters related to the phases of absorption and elimination of this drug.

Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: in vitro drug release and in vivo evaluation

In this study, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(l-lactide) (PLA) microspheres containing ibuprofen were prepared with the aim of prolonging the drug release. The oil-in-water (O/W) emulsion solvent evaporation technique was used, varying the polymer ratio. All formulations provided spherical particles with drug crystals on the surface and a porous and rough polymeric matrix when PHBV was used and smooth external surface when prepared with PLA. The in vitro dissolution profiles show that the formulation containing PHBV/PLA at the proportion of 30/70 presented the best results in terms of prolonging the ibuprofen release. The analysis of the concentration of ibuprofen in the blood of rats showed that maximum levels were achieved at between one and two hours after administration of the immediate-release form (pure drug), while the prolonged microspheres led to a small amount of the drug being released within the first two hours and reached the maximum level after six hours of administration. It was concluded that it is possible to prolong the release of ibuprofen through its incorporation into PHBV/PLA microspheres.

No presente estudo foram preparadas microesferas de poli(hidroxibutirato-co-hidroxivalerato) (PHBV) e poli(ácido láctico) (PLA) com o objetivo de prolongar a liberação do ibuprofeno, utilizado como fármaco modelo. Empregou-se o método de emulsificação e evaporação do solvente óleo em água (O/A), variando-se a proporção entre os polímeros. Todas as formulações originaram partículas esféricas com cristais de fármaco aderidos à superfície externa. As microesferas apresentaram superfície rugosa e porosa, quando o PHBV foi utilizado, e superfície externa lisa, quando preparadas com o PLA. Os perfis de dissolução in vitro evidenciaram que a formulação que continha PHBV/PLA na proporção de 30/70 apresentou melhores resultados para prolongar a liberação do ibuprofeno. Através da análise da concentração de ibuprofeno no plasma de ratos, após administração oral, verificou-se que os níveis máximos ocorreram entre 1 e 2 horas após a administração de ibuprofeno não encapsulado, enquanto o fármaco presente nas microesferas atingiu um pico máximo após 6 horas da administração. Conclui-se, portanto, que é possível prolongar a liberação do ibuprofeno após a sua incorporação às microesferas preparadas com os polímeros PHBV e PLA, especialmente na proporção de 30/70.