High Intensity Physical Exercise before the Brain Ischemia Promotes Increase in Brain Injury.

Studies have demonstrated the beneficial effects of light- and moderate-intensity physical exercise on the nervous system of animals with cerebral ischemia. To investigate the effects of two high-intensity physical exercise protocols, standardized for resistance and strength gain, in rats trained before cerebral ischemia induced by Bilateral Common Carotid Artery Occlusion (BCCAO). Forty-eight male Wistar rats were divided into two groups: with ischemia and without ischemia (sham). Both groups were subdivided into animals that performed high-intensity exercises in the muscle strength modality (I+Ex2; Sham+Ex2; n=16); animals submitted to high-intensity exercises in the aerobic modality (I+Ex1; Sham+Ex1; n=16), and animals that did not practice physical exercises - sedentary (I+Sed; Sham+Sed, n=16). Cerebral ischemia was induced using the BCCAO model. The physical training program used before the procedure was of high intensity, in the aerobic and muscular strength modalities, and was performed using a vertical ladder, for 4 weeks, 5 days per week. In order to process and stain the brain tissue, the Nissl method was used for neuron labeling and quantification in the cortex, striatum, and hippocampus. As for the animals' body weight and the heart weight differences were found between the groups I+Ex2 and Sham+Ex2 (p<0.05). Data on neuron quantification in the cerebral cortex, dentate gyrus, and right and left striatum revealed significant differences between groups. High-intensity physical training in the strength gain modality promotes significant damage to the animal's brain when performed prior to BCCAO-induced cerebral ischemia.

Efficacy of curcumin in the treatment of experimental vulvovaginal candidiasis / Eficacia de la curcumina en el tratamiento de la candidiasis vulvovaginal experimental

Background: Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. Aims: Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. Methods: The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. Results: Curcumin showed minimum inhibitory concentration values of 125-1000μg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. Conclusions: Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis

Antecedentes: Candida albicans es la principal causante de la candidiasis vulvovaginal y algunos aislamientos pueden presentar resistencia a los antifúngicos azólicos. Objetivos: Debido al conocido potencial antifúngico de la curcumina, el objetivo de este trabajo fue evaluar su actividad anti-Candidain vitro y su efecto en el tratamiento de la candidiasis vulvovaginal experimental. Métodos: La actividad anti-Candida de la curcumina se evaluó frente a ocho cepas de Candida mediante un ensayo de microdilución en caldo, y su mecanismo de acción se estudió por una prueba de unión a ergosterol. Posteriormente se evaluó el efecto de la curcumina en el tratamiento de la candidiasis vulvovaginal con un modelo de rata inmunosuprimida, tratada con estrógenos. Resultados: La curcumina mostró valores de concentración inhibitoria mínima de 125-1.000μg/ml, y el mejor resultado se observó frente a Candida glabrata. El compuesto demostró ser capaz de unirse al ergosterol de la membrana, lo que podría ser su mecanismo de acción. Además, en el modelo in vivo de candidiasis vulvovaginal con C. albicans, los tratamientos redujeron la carga fúngica vaginal en ratas infectadas después de siete días de tratamiento con diferentes dosis. Conclusiones: La curcumina podría considerarse un agente antifúngico eficaz prometedor en el tratamiento de la candidiasis vulvovaginal

Efficacy of curcumin in the treatment of experimental vulvovaginal candidiasis.

BACKGROUND: Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. AIMS: Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. METHODS: The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. RESULTS: Curcumin showed minimum inhibitory concentration values of 125-1000µg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. CONCLUSIONS: Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis.

Effects of high fat diet on kidney lipid content and the Na, K-ATPase activity

ABSTRACT It is widely known that high fat diet (HFD) can contribute to the advent of health problems. Recent studies have indicated that obesity imposes a hemodynamic overload to the kidneys. In order to further investigate such injuries, two groups of six Swiss mice each were fed with a controlled AIN93G diet or a high fat (AIN93G modified) diet for eight weeks. Blood samples were collected to determine the hormonal, lipid profile, glucose, urea, and creatinine levels. Histopathological and immunohistochemical analysis were carried out to analysis the kidney damage. Fractions of renal membranes were prepared to assess the Na,K-ATPase activity, lipid peroxidation, total cholesterol, and phospholipid content. The results indicated that the blood lipid profile, urea and creatinine was not altered by the HFD. On the other hand, it was observed in HFD diet mice elevated glucose blood levels along with an augment on insulin and a decrease on corticosterone release. HFD provoked a reduction in the diameter of the convoluted tubules and cell volume in Bowman's capsule and an increased number of positive cells with Na,K-ATPase, but reduced the Na,K-ATPase activity and the cholesterol content in the kidney cell membrane but favored the lipid peroxidation.

Anti-inflammatory effects of the butanolic fraction of Byrsonima verbascifolia leaves: Mechanisms involving inhibition of tumor necrosis factor alpha, prostaglandin E(2) production and migration of polymorphonuclear leucocyte in vivo experimentation.

The leaves of Byrsonima verbascifolia (Malpighiaceae) are traditionally used to treat various diseases including inflammatory conditions. The main goal of this study was to evaluate the in vivo anti-inflammatory activity of the polar constituents from the butanolic fraction of B. verbascifolia leaves (BvBF), as well as to investigate the mechanisms involved in the anti-inflammatory activity. The polar constituents were identified by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD­MS) and matrix-assisted laser desorption/ionization ­ time-of-flight mass spectrometry (MALDI-TOF MS) to obtain a complete chemical profile of the fraction. Forty-five compounds were detected in the BvBF by LC-DAD­MS/MS, including condensed tannins, phenolic acids, flavonoids (flavones and flavonols) and other compounds. In addition, several condensed tannins were identified by MALDI-MS/MS, which are composed predominantly by procyanidin units (PCY) and up to six flavan-3-ol units. The BvBF exhibited significant antioxidant and anti-inflammatory activities. The BvBF inhibited paw edema and polymorphonuclear (PMN) leukocyte migration to the footpad and pleural cavity induced by carrageenan. Furthermore, a minor dose (12.50 mg/kg) of BvBF effectively decreased tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) levels in the footpad. These findings suggest that the mechanism of the anti-inflammatory action in the BvBF is linked to the inhibition of the production of inflammatory mediators such as TNF-α and PGE2 and the PMN cell migration.

Efeito da administração oral de extrato etanólico de Rosmarinus officinalis L. (alecrim) no desenvolvimento do Tumor Sólido de Ehrlich / Effect of oral administration of the ethanol extract of Rosmarinus officinalis L. (alecrim) in the development of Ehrlich Solid Tumor

objetivo deste estudo foi avaliar os efeitos da administração oral diária de extrato etanólico de R.officinalis no desenvolvimento do Tumor Sólido de Ehrlich. Camundongos Swiss foram separados em três grupos A, B e C (n=6). Os animais do grupo A (controle) ingeriram solução salina durante todo o experimento. Os animais do grupo B, a partir do 1º dia, receberam diariamente, por gavagem, uma dose de 100 mg/kg do extrato etanólico de R.officinalis. Os animais do grupo C iniciaram, no 21º dia, a ingestão diária desse extrato. No 21º dia, todos os camundongos foram inoculados subcutaneamente no coxim plantar esquerdo com 2 x 106 células do Tumor de Ehrlich. No 42º dia, os animais foram sacrificados e suas patas foram removidas para análise histopatológica. Os resultados obtidos, através da mensuração da espessura das patas, mostraram que o grupo controle e os grupos que receberam o extrato, apresentaram o mesmo crescimento tumoral. Nas análises histopatológicas, não foram observadas diferenças na morfologia das células tumorais entre os grupos. A administração oral diária de 100 mg/kg de extrato etanólico de Rosmarinus officinalis não afetou o potencial proliferativo de tumor. Outras concentrações do extrato etanólico de Rosmarinus officinalis serão estudadas em experimentos futuros.(AU)

The aim of this study was to evaluate the effects of daily oral administration of ethanol extract of R.officinalis in the development of Ehrlich solid tumor. Swiss mice were divided into three groups A, B and C (n = 6). The animals of group A (control) received saline throughout the experiment. The animals of group B, from day 1, received daily by gavage, a dose of 100 mg/kg of R.officinalis ethanol extract. The animals of group C, on day 21, began the daily intake of this extract. At day 21, all mice were inoculated with 2 x 106 Ehrlich tumor cells in the left footpad. On day 42, the animals were sacrificed; their footpads were measured and removed for histopathological analysis. The results showed that the control group and the groups receiving the extract, before and after tumor inoculation, presented the same tumor growth. Furthermore, the histopathological analysis showed no differences in the morphology of tumor cells between groups. The daily oral administration of 100 mg/kg ethanol extract of Rosmarinus officinalis did not affect the proliferative potential of tumor. Other concentrations this ethanol extract times will be studied in future experiments.(AU)

Efficacy of methotrexate-loaded poly(ε-caprolactone) implants in Ehrlich solid tumor-bearing mice.

CONTEXT: Methotrexate (MTX) is used in the treatment of malignancies; however, its clinical application is limited by its toxic dose-related side effects. An alternative to overcome the toxicity of the MTX in healthy tissues is the design of an implantable device capable of controlling the delivery of this drug for an extended period within the tumor site. OBJECTIVE: To develop methotrexate-loaded poly(ε-caprolactone) implants (MTX PCL implants) and to demonstrate their efficacy as local drug delivery systems capable of inhibiting Ehrlich solid tumor bearing mice. MATERIALS AND METHODS: MTX PCL implants were produced by the melt-molding technique and were characterized by FTIR, WAXS, DSC and SEM. The in vitro and in vivo release of MTX from the PCL implants was also evaluated. The efficacy of implants in inhibiting tumor cells in culture and the solid tumor in a murine model was revealed. RESULTS AND DISCUSSION: The chemical and morphological integrity of the drug was preserved into the polymeric matrix. The in vitro and in vivo release processes of the MTX from the PCL implants were modulated by diffusion. MTX diffused from the implants revealed an antiproliferative effect on tumor cells. Finally, MTX controlled and sustained released from the polymeric implants efficiently reduced 42.7% of the solid tumor in mice paw. CONCLUSION: These implantable devices represented a contribution to improve the efficacy and safety of chemotherapy treatments, promoting long-term local drug accumulation in the targeted site.

Development and evaluation of sustained-release etoposide-loaded poly(ε-caprolactone) implants.

Poly(ε-caprolactone) implants containing etoposide, an important chemotherapeutic agent and topoisomerase II inhibitor, were fabricated by a melt method and characterized in terms of content uniformity, morphology, drug physical state, and sterility. In vitro and in vivo drug release from the implants was also evaluated. The cytotoxic activity of implants against HeLa cells was studied. The short-term tolerance of the implants was investigated after subcutaneous implantation in mice. The original chemical structure of etoposide was preserved after incorporation into the polymeric matrix, in which the drug was dispersed uniformly. Etoposide was present in crystalline form in the polymeric implant. In vitro release study showed prolonged and controlled release of etoposide, which showed cytotoxicity activity against HeLa cells. After implantation, good correlation between in vitro and in vivo drug release was found. The implants demonstrated good short-term tolerance in mice. These results tend to show that etoposide-loaded implants could be potentially applied as a local etoposide delivery system.

Controlled release of triamcinolone acetonide from polyurethane implantable devices: application for inhibition of inflammatory-angiogenesis.

The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.