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.

Ovarian Puncture Triggers an Inflammatory Response that did not Affect Late Folliculogenesis, Ovulation Rate, and Fertility.

Ovarian puncture has been widely used in assisted reproduction, but there are still gaps about its effects on ovarian morphophysiology, as well as the relationship between inflammation caused by this procedure and the follicular growth and fertility. The aim of this study was to investigate the effects of ovarian puncture on folliculogenesis and fertility. Mice (n = 24) were divided into two groups: (1) SHAM-both ovaries were exposed and repositioned and (2) Punctured-ovaries were exposed, punctured, and repositioned. After 96 h of surgery, ovaries were collected for morphofunctional analysis. New females were used for the superovulation (n = 10) and fertility assays (n = 10). Increased volumetric density of inflammatory cells-p = 0.0005, p = 0.0013; hemorrhagic foci-p < 0.0001; and inflammatory exudate-p < 0.0001 could be noticed on the punctured group, compared to SHAM. The percentage of primordial follicles was lower on the punctured ovaries (p = 0.00294). Ovarian puncture has also induced an increase in the proliferation of granulosa cells of primary (p = 0.0321) and antral follicles (p = 0.0395), and an increased apoptotic index of antral follicles (p = 0.0100). There was no influence on expression of some genes related to inflammation, collagen deposition and folliculogenesis progression. The reproductive aspects (oocyte retrieval and number of fetuses per female) were not altered (p > 0.05). Taken together, our findings strongly suggest that ovarian puncture results in a local inflammation that affects follicular growth and atresia. However, it does not affect female fertility, which strengthens the safety of this procedure.

Ocimum basilicum L. (basil) presents pro-apoptotic activity in an Ehrlich's experimental tumor murine model.

PURPOSE: This study aimed to evaluate the therapeutic effect of an ethanol extract of Ocimum basilicum L. (EEOb) aerial parts against Ehrlich's experimental tumor (EET) in mice. METHODS: Swiss mice were divided into two groups (control and treated; n = 6). On day 21, all mice were inoculated subcutaneously with 2 × 106 (0.05 mL) EET cells in the left paw for solid tumor development. This study lasted 28 days. Treatment began 24 hours after inoculation with EET. Measurements of dorsoplantar thickness were used to assess tumor growth. The paw pad was collected for histopathological analysis and stained using the argyrophilic nucleolar organizing regions (AgNOR) technique and immunohistochemistry for proliferating cell nuclear antigen, Bcl-2 and Bax. RESULTS: The treatment of animals with EEOb at 100 mg/kg intraperitoneally was able to reduce the growth (Control = 3.7 ± 0.1 mm vs. EEOb = 5.7 ± 0.2 mm) and the number of AgNORs of solid Ehrlich tumor. The antitumor effect of EEOb was associated with the induction of apoptosis of tumoral cell, as suggested by the reduction of the content of Bcl-2 induced by extract. CONCLUSIONS: The study demonstrated that daily administration of EEOb is able to reduce the growth of EET by induce apoptosis of tumoral cells.

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.

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.

Ocimum basilicum L. (basil) presents pro-apoptotic activity in an Ehrlich's experimental tumor murine model

ABSTRACT Purpose: This study aimed to evaluate the therapeutic effect of an ethanol extract of Ocimum basilicum L. (EEOb) aerial parts against Ehrlich's experimental tumor (EET) in mice. Methods: Swiss mice were divided into two groups (control and treated; n = 6). On day 21, all mice were inoculated subcutaneously with 2 × 106 (0.05 mL) EET cells in the left paw for solid tumor development. This study lasted 28 days. Treatment began 24 hours after inoculation with EET. Measurements of dorsoplantar thickness were used to assess tumor growth. The paw pad was collected for histopathological analysis and stained using the argyrophilic nucleolar organizing regions (AgNOR) technique and immunohistochemistry for proliferating cell nuclear antigen, Bcl-2 and Bax. Results: The treatment of animals with EEOb at 100 mg/kg intraperitoneally was able to reduce the growth (Control = 3.7 ± 0.1 mm vs. EEOb = 5.7 ± 0.2 mm) and the number of AgNORs of solid Ehrlich tumor. The antitumor effect of EEOb was associated with the induction of apoptosis of tumoral cell, as suggested by the reduction of the content of Bcl-2 induced by extract. Conclusions: The study demonstrated that daily administration of EEOb is able to reduce the growth of EET by induce apoptosis of tumoral cells.

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.

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.

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.