Functional Recovery Caused by Human Adipose Tissue Mesenchymal Stem Cell-Derived Extracellular Vesicles Administered 24 h after Stroke in Rats.

Ischemic stroke is a major cause of death and disability, intensely demanding innovative and accessible therapeutic strategies. Approaches presenting a prolonged period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. Here, we evaluated the potential neuroprotective properties of nasally administered human adipose tissue mesenchymal stem cell (hAT-MSC)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. After a single intranasal EV (200 µg/kg) administered 24 h after a focal permanent ischemic stroke in rats, a higher number of EVs, improvement of the blood-brain barrier, and re-stabilization of vascularization were observed in the recoverable peri-infarct zone, as well as a significant decrease in infarct volume. In addition, EV treatment recovered long-term motor (front paws symmetry) and behavioral impairment (short- and long-term memory and anxiety-like behavior) induced by ischemic stroke. In line with these findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.

Monoolein-based nanoparticles containing indinavir: a taste-masked drug delivery system.

OBJECTIVE: This study developed a novel child-friendly drug delivery system for pediatric HIV treatment: a liquid, taste-masked, and solvent-free monoolein-based nanoparticles formulation containing indinavir (0.1%). SIGNIFICANCE: Adherence to antiretroviral therapy by pediatric patients is difficult because of the lack of dosage forms adequate for children. METHODS: Monoolein-based nanoparticles were developed. The particle size, zeta potential, pH, drug content, small angle X-ray scattering, stability, in vitro drug release profile, biocompatibility, toxicity, and taste-masking properties were evaluated. RESULTS: Monoolein-based formulations containing indinavir had nanosized particles with 155 ± 7 nm, unimodal particle size distribution, and polydispersity index of 0.16 ± 0.03. The zeta potential was negative (-31.3 ± 0.3 mV) and pH was neutral (7.78 ± 0.01). A 96% drug incorporation efficiency was achieved, and the indinavir concentration remained constant for 30 days. Polarized light microscopy revealed isotropic characteristics. Transmission electron microscopy images showed spherical shaped morphology. Small-angle X-ray scattering displayed a form factor broad peak. Indinavir had a sustained release from the nanoparticles. The system was nonirritant and was able to mask drug bitter taste. CONCLUSIONS: Monoolein-based nanoparticles represent a suitable therapeutic strategy for antiretroviral treatment with the potential to reduce the frequency of drug administration and promote pediatric adherence.

Characterization and antiproliferative activity of glioma-derived extracellular vesicles.

Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment.

Solid Dispersion of Kaempferol: Formulation Development, Characterization, and Oral Bioavailability Assessment.

Kaempferol (KPF), an important flavonoid, has been reported to exert antioxidant, anti-inflammatory, and anticancer activity. However, this compound has low water solubility and hence poor oral bioavailability. This work aims to prepare a solid dispersion (SD) of KPF using Poloxamer 407 in order to improve the water solubility, dissolution rate, and pharmacokinetic properties KPF. After optimization, SDs were prepared at a 1:5 weight ratio of KPF:carrier using the solvent method (SDSM) and melting method (SDMM). Formulations were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) analysis, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The solubility in water of carried-KPF was about 4000-fold greater than that of free KPF. Compared with free KPF or the physical mixture, solid dispersions significantly increased the extent of drug release (approximately 100% within 120 min) and the dissolution rate. Furthermore, after oral administration of SDMM in rats, the area under the curve (AUC) and the peak plasma concentration (Cmax) of KPF from SDMM were twofold greater than those of free KPF (p < 0.05). In conclusion, SD with Poloxamer 407 is a feasible pharmacotechnical strategy to ameliorate the dissolution and bioavailability of KPF.

Nanoemulsion-Loaded Hydrogels for Topical Administration of Pentyl Gallate.

The aim of this study is to describe the development of nanoemulsion-loaded hydrogels to deliver pentyl gallate (PG), a gallic acid n-alkyl ester, through the skin. PG is an antioxidant agent; however, it seems to be a promising agent for herpis labialis treatment. Aristoflex AVC® and chitosan were used as gelling agents for nanoemulsion thickening. The developed formulations presented suitable PG content (94.4-100.3% w/w), nanometric droplet sizes (162-297 nm), high zeta potentials, and a non-Newtonian pseudoplastic behavior. Both vehicles neither enhanced PG penetration nor delayed its release from the nanoemulsion. Formulations remained physically stable at 8°C during 3 months of storage.

Kaempferol-loaded mucoadhesive nanoemulsion for intranasal administration reduces glioma growth in vitro.

In order to search for new approaches to treat glioma, intranasal administration has been proposed as an alternative route to deliver drugs into the brain. Among the drug alternatives, kaempferol (KPF) has been reported to induce glioma cell death. This study aimed to prepare nanoemulsions containing KPF with and without chitosan to investigate their potential for brain delivery following intranasal administration, and to evaluate their antitumor activity against glioma cells. KPF-loaded nanoemulsion (KPF-NE) and KPF-loaded mucoadhesive nanoemulsion (KPF-MNE) were prepared by high-pressure homogenization technique and were characterized for their globule size, zeta potential, drug content, pH, viscosity, mucoadhesive strength and morphology. KPF from KPF-MNE showed significantly higher permeation across the mucosa in ex vivo diffusion studies. Histopathological examination suggests both nanoemulsions to be safe for the nasal mucosa and able to preserve KPF antioxidant capability. KPF-MNE enhanced significantly the amount of drug into rat's brain following intranasal administration (5- and 4.5-fold higher than free drug and KPF-NE, respectively). In addition, KPF-MNE reduced C6 glioma cell viability through induction of apoptosis to a greater extent than either free KPF or KPF-NE. The mucoadhesive nanoemulsion developed for intranasal administration may be a promising system for delivery to the brain, and KPF-MNE is a candidate for further antiglioma trials.

Validation of an HPLC-UV method for analysis of Kaempferol-loaded nanoemulsion and its application to in vitro and in vivo tests.

A simple and reliable HPLC-UV method for Kaempferol (KPF) determination in a Kaempferol-loaded nanoemulsion (KPF-NE), samples from mucosa permeation/retention studies, and murine brain was developed and validated according to international guidelines. The analyses were performed on a reversed-phase C18 column at 35°C and under UV detection at 368nm. The mobile phase was composed of methanol:formic acid 0.1% (75:25, v/v) and was eluted at an isocratic flow rate of 1.0mL/min. The method was selective and sensitive for KPF analysis in matrix extracts, and linear in the range of 0.25-7.5µg/mL. The method was also considered precise, accurate, and robust. The recovery rates of KPF from the porcine nasal mucosa and murine brain were higher than 85%. Low matrix effect was observed to determine KPF, including biological matrices. The applicability of the method was confirmed in all different approaches, i.e., quantification of KPF in nanoemulsion, in vitro permeation/retention of KPF across porcine nasal mucosa, and in vivo quantification of KPF in brain samples after nasal administration in rats. Thus, the method is effective and reliable to determine KPF in different real samples. The proposed method, therefore, provides a useful quantification approach to routine processes, to the development of drug delivery systems, and to KPF quantification in different biological matrices. Furthermore, the method is applicable in bioavailability studies and the developed formulation (KPF-NE) is suitable for preclinical trials in different brain disorders.

Pilates training improves pain and quality of life of women with fibromyalgia syndrome / A prática de Pilates melhora a dor e a qualidade de vida em mulheres com síndrome fibromiálgica

ABSTRACT BACKGROUND AND OBJECTIVES: There is still lack of evidence that supports Pilates training in women with fibromyalgia syndrome. Hence, the aim of the present study was to assess the effects of Pilates on pain, quality of life, depression and anxiety in women with fibromyalgia syndrome. METHODS: Twenty female volunteers diagnosed with fibromyalgia took part on this study. Thirteen women were assigned for the treatment group and seven, for the control group. All 20 patients were evaluated before and immediately after 8 weeks. Along with the anamnesis, volunteers were assessed for the 18 tender points described by the American College of Rheumatology, for number of painful regions, pain intensity with the visual analogue scale, quality of life with the Fibromyalgia Impact Questionnaire, for depression with the Beck Depression Inventory and for anxiety with the Beck Anxiety Inventory. The treated group underwent a 1-hour Pilates session twice a week for 8 weeks. The control group remained with prior treatment interventions and therapies unchanged. RESULTS: Statistically significant improvement was observed in pain intensity and number of painful regions (p<0.05) in the treated group, whereas no statistical differences were found in other variables (p>0.05) or for the control group (p>0.05). Strong correlations were found mostly between number of active tender points and Fibromyalgia Impact Questionnaire (r>0.8, p<0.05). CONCLUSION: The results support Pilates as a safe physical therapy resource in improving pain for fibromyalgia patients.

RESUMO JUSTIFICATIVA E OBJETIVOS: Ainda faltam evidências que apoiem o treino de Pilates em mulheres com fibromialgia. O objetivo deste estudo foi avaliar os efeitos do Pilates na dor, qualidade de vida, depressão e ansiedade em mulheres com fibromialgia. MÉTODOS: Vinte mulheres com diagnóstico de fibromialgia foram voluntárias do estudo. Treze foram aleatoriamente alocadas para o grupo tratamento e sete para o grupo controle. Todas as 20 pacientes foram avaliadas antes e imediatamente após o tratamento de 8 semanas. Junto com a anamnese, avaliaram-se os 18 tender points descritos pelo American College of Rheumatology para classificação da fibromialgia. Além disso, avaliou-se o número de regiões dolorosas, a intensidade da dor com a escala analógica visual, a qualidade de vida pelo Questionário de Impacto da Fibromialgia, a depressão pelo Inventário de Depressão de Beck e a ansiedade pelo Inventário de Ansiedade de Beck. O grupo tratamento realizou sessões de 1h de Pilates duas vezes por semana por 8 semanas. O grupo controle continuou com seus tratamentos anteriores ao estudo sem modificações. RESULTADOS: Melhora estatisticamente significativa foi observada na intensidade da dor e no número de regiões dolorosas (p<0,05) no grupo tratado, ao passo que não há diferenças estatísticas para outras variáveis (p>0,05) ou para o grupo controle (p>0,05). Foram encontradas fortes correlações principalmente entre o número de tender points ativos e o Questionário de Impacto da Fibromialgia (r>0,8, p<0,05). CONCLUSÃO: Os resultados obtidos apoiam o Pilates como um recurso fisioterapêutico seguro para melhorar a dor em pacientes com fibromialgia.

Pentyl Gallate Nanoemulsions as Potential Topical Treatment of Herpes Labialis.

Previous studies have demonstrated the antiherpes activity of pentyl gallate (PG), suggesting that it could be a promising candidate for the topical treatment of human herpes labialis. PG low aqueous solubility represents a major drawback to its incorporation in topical dosage forms. Hence, the feasibility of incorporating PG into nanoemulsions, the ability to penetrate the skin, to inhibit herpes simplex virus (HSV)-1 replication, and to cause dermal sensitization or toxicity were evaluated. Oil/water nanoemulsions containing 0.5% PG were prepared by spontaneous emulsification. The in vitro PG distribution into porcine ear skin after topical application of nanoemulsions was assessed, and the in vitro antiviral activity against HSV-1 replication was evaluated. Acute dermal toxicity and risk of dermal sensitization were evaluated in rat model. Nanoemulsions presented nanometric particle size (from 124.8 to 143.7 nm), high zeta potential (from -50.1 to -66.1 mV), loading efficiency above 99%, and adequate stability during 12 months. All formulations presented anti-HSV-1 activity. PG was able to reach deeper into the dermis more efficiently from the nanoemulsion F4. This formulation as well as PG were considered safe for topical use. Nanoemulsions seem to be a safe and effective approach for topically delivering PG in the treatment of human herpes labialis infection.

Optimization of headspace solid-phase microextraction for analysis of ß-caryophyllene in a nanoemulsion dosage form prepared with copaiba (Copaifera multijuga Hayne) oil.

Recent studies have shown the anti-inflammatory activity of Copaiba oils may be addressed to the high content of ß-caryophyllene, the most common sesquiterpene detected, especially in the Copaifera multijuga Hayne species. In the present study, nanoemulsions were proposed as a delivery system for copaiba oil in view to treat locally inflamed skin. This article describes the optimization and validation of a stability-indicating SPME-GC method, for ß-caryophyllene analysis in the nanoemulsions produced by high pressure homogenization. SPME methods are performed with PDMS (polydimethylsiloxane) fiber (100 µm). Three SPME parameters were evaluated by a three-level-three-factor Box-Behnken factorial design as potentially affecting the technique efficiency. According to the results obtained, the best conditions to extract ß-caryophyllene were: (i) sampling temperature of 45°C, (ii) sampling time of 20 min and (iii) no NaCl addition. Results coming from the forced degradation tests showed a reduction of ß-caryophyllene peak area when both caryophyllene methanolic solution and nanoemulsions were exposed to acid hydrolysis, UV-A irradiation, oxidative (H(2)O(2)) and thermolitic (60°C) conditions. Such reduction occurred in lower extent in the nanoemulsions, suggesting a protective effect of the formulation to ß-caryophyllene content. Since no degradation products were detected in the same retention time of ß-caryophyllene, the specificity of the method was demonstrated. The method was linear in the range of 0.14-0.68 µg mL(-1) of ß-caryophyllene (r(2)>0.999), and was also validated for precision (R.S.D.≤5.0%), accuracy (97.85-101.87%) and robustness. Finally, the method was applied to quantification of ß-caryophyllene content in the developed formulations.

Estudio descriptivo sobre algunos aspectos del proceso de atención fonoaudiológica: Instituto Médico Regional: Gálvez, 1998/99 / Description study of some aspects of the process of atention phonoaudiologic: Regional Medical Institute: Galvez, 1998/99

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)

Estudio descriptivo sobre algunos aspectos del proceso de atención fonoaudiológica: Instituto Médico Regional: Gálvez, 1998/99 / Description study of some aspects of the process of atention phonoaudiologic: Regional Medical Institute: Galvez, 1998/99

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)

Estudio descriptivo sobre algunos aspectos del proceso de atención fonoaudiológica: Instituto Médico Regional: Gálvez, 1998/99 / Description study of some aspects of the process of atention phonoaudiologic: Regional Medical Institute: Galvez, 1998/99

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)

Estudio descriptivo sobre algunos aspectos del proceso de atención fonoaudiológica: Instituto Médico Regional: Gálvez, 1998/99 / Description study of some aspects of the process of atention phonoaudiologic: Regional Medical Institute: Galvez, 1998/99

El objetivo de este estudio de tipo descriptivo y transversal fue observar los motivos de consulta a fonoaudiología, los diagnósticos fonoaudiológicos, los tipos de consulta fonoaudiológica y los agentes de derivación, en una población de pacientes de diversas edades que asistieron al consultorio de fonoaudiología del Instituto Médico Regional de la ciudad de Gálvez en el período comprendido entre enero de 1998 ydiciembre de 1999. Se trabajó con fuente secundaria de datos, historias clínicas de 99 pacientes confeccionadas por la fonoaudióloga a cargo del consultorio: 77 menores de 18 años y 22 de 18 años o más. El 77,8 por ciento de consultas fueron realizadas por pacientes menores de 18 años de edad. En este grupo etáreo las alteraciones en el habla son el motivo de consulta más frecuente (42,9 por ciento), mientras que en los pacientes de 18 años o más, las alteraciones de la voz son las que ocupan el primer lugar (72,7 por ciento). El diagnóstico fonoaudiológico, que presenta el mayor porcentaje en pacientes menores de 18 años es el de insuficiencia respiratoria nasal (35 por ciento) y en los de 18 añois o más, disfonía (72,8 por ciento). Se observó que en el grupo de pacientes menores de 18 años el 50,6 por ciento consulta en forma derivada y en el de 18 años o más, el 68,2 por cientolo hace de igual manera. El pediatra es el agente de derivación que ocupa el primer lugar entre aquellos pacientes menores de 18 años (41,0 por ciento), mientras que en pacientes de 18 años o más es el otorrinolaringólogo el que ocupa dicho lugar (73,3 por ciento)(AU)