Analysis of the cognitive and functional behavior of female rats in the periestropause after hormone therapy with estrogen.

Perimenopause is a critical period, with severe cycle irregularity and lower estrogen secretion altering redox state biomarkers, leading to behavioral changes. The estrogen hormonal therapy (EHT) being commonly used to alleviate climacteric effects. Therefore, the aim of this study was to analyze anxiolytic profile, recognition memory (short and long term), ambulation, redox status, cell synaptic activity in locus coeruleus and hippocampus of Wistar rats in the periestropause after EHT. Forty rats participated in the study; 20 were treated with corn oil (group 21Mo/Veh; corn oil/0.2 mL/sc; 2x/week) and 20 were submitted to EHT (group 21Mo/E2; 17ß-estradiol/15 µg/Kg/sc; 2x/week) for 120 days. Open field, elevated plus maze, object recognition (RO), and footprint tests were performed immediately before and at the end of the treatment period. From the decapitated brains, isolated hippocampus were destined for biochemical analysis, in turn, perfused brains were destined for histological analysis. The 21Mo/E2 group had a significantly greater total time in the central region and a significantly greater number of entries into the open arms compared to the 21Mo/Veh group, as in crossing, rearing and grooming behaviors, evidencing an anxiolytic profile. In the RO test, the 21Mo/Veh group decreased long-term memory, and the 21Mo/E2 group maintained the same index as at 17 months of age, in addition to a better balance of the hippocampal redox state, prevention of neuronal cell loss and better gait. Based on the results, it appears that exogenous E2 supplementation during periestropause may help preserve neurological functions and potentially prevent neuropsychological and neurodegenerative disorders.

Antimicrobial, Antibiofilm Activities and Synergic Effect of Triterpene 3ß,6ß,16ß-trihydroxyilup-20(29)-ene Isolated from Combretum leprosum Leaves Against Staphylococcus Strains.

Antimicrobial resistance is a natural phenomenon and is becoming a huge global public health problem, since some microorganisms not respond to the treatment of several classes of antibiotics. The objective of the present study was to evaluate the antibacterial, antibiofilm, and synergistic effect of triterpene 3ß,6ß,16ß-trihydroxyilup-20(29)-ene (CLF1) against Staphylococcus aureus and Staphylococcus epidermidis strains. Bacterial susceptibility to CLF1 was evaluated by minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assay. In addition, the effect combined with antibiotics (ampicillin and tetracycline) was verified by the checkerboard method. The biofilms susceptibility was assessed by enumeration of colony-forming units (CFUs) and quantification of total biomass by crystal violet staining. The compound showed bacteriostatic and bactericidal activity against all Staphylococcal strains tested. The synergistic effect with ampicillin was observed only for S. epidermidis strains. Moreover, CLF1 significantly inhibited the biofilm formation and disrupted preformed biofilm of the all strains. Scanning electron microscopy (SEM) images showed changes in the cell morphology and structure of S. aureus ATCC 700698 biofilms (a methicillin-resistant S. aureus strain). Molecular docking simulations showed that CLF1 has a more favorable interaction energy than the antibiotic ampicillin on penicillin-binding protein (PBP) 2a of MRSA, coupled in different regions of the protein. Based on the results obtained, CLF1 proved to be a promising antimicrobial compound against Staphylococcus biofilms.

Synthesis and Antimicrobial Activity of Ursolic Acid Ester Derivatives.

Infections caused by microorganisms are a major cause of morbidity and mortality worldwide, and natural products continue to be important sources for the discovery of new antimicrobial agents. Ursolic acid is a triterpene with known antibacterial action, being naturally found in plants, such as Jaracanda oxyphylla and Jacaranda caroba (Bignoniaceae). Ursolic acid derivative esters have revealed potential biological activities, such as antitumor, antiviral, and antibacterial activity. In this study, sixteen esters (1-16) were synthesized from ursolic acid using DIC/DMAP and characterized by infrared (IR), nuclear magnetic resonance (1 H- and 13 C-NMR) and mass spectrometry. All ursolic acid esters were evaluated against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and the yeast Candida albicans. Six compounds are herein described for the first time (3, 9, 11, 13, 14 and 16) with yields up to 91.6 %. Compounds 11 (3ß-(3,4-dimethoxybenzoyl)ursolic acid) and 15 (3ß-nicotinoylursolic acid) displayed promising antifungal activity, with inhibition of C. albicans growth of 93.1 and 95.9 %, respectively.

Photodynamic therapy associated final irrigation in root canals of the primary teeth.

The aim of this study was to analyze, in vitro, the reduction of Enterococcus faecalis in root canals of primary teeth after final irrigation and photodynamic therapy (PDT) use. Twenty primary molars were contaminated with Enterococcus faecalis. The teeth were randomly distributed into four groups according to the irrigation solutions and PDT use: G1 (Saline solution and no PDT use), G2 (17 % EDTA and no PDT use), G3 (Saline solution and PDT use) and G4 (17 % EDTA and PDT use). For PDT, 0.005 % toluidine blue was chosen as the photosensitizer, which was inserted in the canals with sterile paper cones. Bacterial counts were performed with a BHI test in blood agar plate, where bacteria were collected inside the canal for 30 s using sterile paper cones. The collection took place before and after the irrigation and PDT protocols. The samples were diluted, spread onto a blood agar plate and then incubated at 37 °C for 24 h. There was a reduction of the microbiota from the irrigation solutions before and after the final irrigation for all groups. It was observed a statistically significant reduction (p < 0,05) when PDT was used (97.6 % at the saline solution and 89.8 % at the 17 % EDTA) when compared to the groups with no PDT use. Our data demonstrated that PDT, according to the parameters used, increased the disinfection performance of the solutions tested in the root canals of primary teeth.

Annona Genus: Traditional Uses, Phytochemistry and Biological Activities.

Species from the Annona (Anonaceae) genus are used in traditional medicine for the treatment of various diseases. Ethnobotanical studies provide information regarding the plant part and the preparation method being used, while scientific studies such as in vitro, in vivo, and clinical tests can provide evidence supporting ethnopharmacological reports, directing studies towards the isolation of compounds which may be active for specific pathologies. Annona muricata and Annona squamosa were the most commonly reported species from those studied, with Annona cherimola and Annona classiflora also standing out. Acetogenins were the most commonly isolated metabolite class due to their cytotoxic properties, with flavonoids, alkaloids, steroids, and peptides also being reported. Many species from the Annona genus have proven biological activities, such as antitumor, antioxidant, antimicrobial and antifungal. The present review had as its objective to facilitate access to ethnobotanical, chemical and biological information in order to direct future researches.

Evaluation of the antimicrobial and antioxidant activity of 7-hydroxy-4', 6-dimethoxy-isoflavone and essential oil from Myroxylon peruiferum L.f.

This study evaluated the antibacterial, antifungal, and antioxidant effect of 7-hydroxy-4',6-dimethoxy-isoflavone and essential oil of Myroxylon peruiferum. The compound was isolated and its structure elucidated by NMR. The chemical composition of essential oil determined by GC-MS analysis. To evaluation of antimicrobial activity, the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) were performed. In addition to analysis of antioxidant activity, DPPH radical scavenging tests, iron chelating assay (FIC), antioxidant reducing power assay (FRAP) and ß-carotene bleaching assay (BCB) were performed. For the essential oil were identified 24 organized compounds having as main constituents; Germacrene D (17.2%), α-pinene (14.8%) and E-caryophyllene (10.8%). The results showed that isoflavone (2000 to 156 µg/mL) and essential oil (5.0 to 1.25%) present antibacterial and antifungal activity against Gram-positive bacteria and filamentous fungi. The isoflavone and the essential oil also presented antioxidant activity in all the tests, mainly on inhibition of the oxidation of ß-carotene test concentrations ranging from 60 to 100%. In conclusion, isoflavone and essential oil from M. peruiferum present an antimicrobial alternative against Gram-positive bacteria, especially of the genus Staphylococcus and dermatophyte fungi of the genus Trichophyton, as well as a natural compound antioxidant.

Photobiomodulation can alter mRNA levels cell death-related.

Photobiomodulation (PBM) by low-level laser has demonstrated excellent results for inflammatory treatments, promoting repair of injured tissues. Knowledge regarding the molecular mechanisms involved in this process has been increasing, but its effect on cell death/survival-related gene expression after laser irradiation with different doses is not well understood. So, it is important to know these effects in order to guarantee the safety of therapeutic protocols based on PBM. This study aimed to investigate the mRNA levels of genes related to proteins involved in cell death/survival pathways of healthy tissues from talocrural joint of mice after PBM. Mice were divided into three groups: control, PBM at 3 J cm-2, and PBM at 30 J cm-2. Laser irradiation was performed on talocrural joint during four consecutive days. Morphological analyses, immunocytochemistry, FasL, Fas, Bax, Apaf1, Caspase9, Caspase3, Caspase6, Bcl2 mRNA levels, and DNA fragmentation were performed to verify cell death induction after laser irradiation. PBM can increase mRNA levels of almost genes pro-apoptotic. On the other hand, mRNA level of anti-apoptotic protein Bcl-2 gene was not significantly altered. Bcl-2/Bax ratio (indicator of protective molecular response) was decreased after PBM at 30 J cm-2, trending to DNA fragmentation. Results obtained in this study indicate that PBM by low-level infrared laser alters mRNA relative levels of genes involved in cell death pathways. However, these molecular alterations were not able to cause DNA fragmentation in cells in talocrural joint tissues, indicating that infrared laser was not enough to cause cell death.

L-Arginine supplementation does not enhance blood flow and muscle performance in healthy and physically active older women.

PURPOSE: The purpose of this study was to examine the effects of acute L-arginine (L-arg) supplementation on peripheral vasodilatation and muscle performance in older women. METHODS: In a double-blind, randomized, placebo-controlled study, 20 elderly women were randomly assigned in a double-blind fashion to either an L-arg (ARG, N = 10) or placebo (PLA, N = 10) group. During the first visit, both groups underwent a Doppler ultrasound exam (to assess the femoral artery vasodilatation) at rest (baseline), and immediately before and after the isokinetic strength test (performed at 80 min after supplementation). On the second and third visits, the groups completed a battery of muscle performance tests (to assess the isometric and functional strength), initiated at the same time point (80 min after supplementation). RESULTS: The femoral artery blood flow (ARG: 443.9 ± 42.8 vs. PLA: 373.1 ± 40.8 ml/min; P > 0.05) and area (ARG: 0.45 ± 0.03 vs. PLA: 0.41 ± 0.02 cm(2); P > 0.05) were similar between the groups at basal conditions, and they remained unchanged after supplementation. Following exercise, blood flow increased ~160 % above the basal level, and there was no significant (P > 0.05) difference between the ARG and PLA groups. Additionally, there were no significant (P > 0.05) differences between the ARG and PLA groups for any strength variable (isokinetic, isometric, and functional). CONCLUSION: These results show that acute L-arg supplementation provides no ergogenic effect on blood flow and muscle performance in older women.

Light-emitting diode phototherapy improves muscle recovery after a damaging exercise.

The goal of the present study was to determine the effect of light-emitting diode phototherapy (LEDT) at 630 nm on muscle recovery after a damaging eccentric exercise bout. Seventeen healthy young male volunteers, without previous experience with eccentric exercise, were included in a randomized double-blinded placebo-controlled trial. They were divided into a LEDT (n = 8) and a PLACEBO group (n = 9). To induce muscle damage, subjects performed 30 eccentric contractions with a load of 100 % of maximal voluntary isometric contraction strength of the elbow flexors of the non-dominant arm. LEDT group subjects received biceps brachii phototherapy (λ 630 nm; total energy density, 20.4 J/cm2) immediately after the exercise bout. The LEDT in the placebo group was aimed at the muscle, but it remained turned off. Isometric muscle strength, muscle soreness, and elbow range of motion (ROM) were measured before and at 24, 48, 72, and 96 h the after eccentric exercise bout and compared between groups. Our results showed that the muscle soreness, muscle strength loss, and ROM impairments were significantly reduced up to 96 h after a damaging eccentric exercise bout for the LEDT group compared with the PLACEBO group. A single LEDT (630 nm) intervention immediately after a damaging eccentric exercise bout was effective in terms of attenuating the muscle soreness and muscle strength loss and ROM impairments.

Development and evaluation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and polycaprolactone microparticles of nimodipine.

Polymeric microparticles containing the calcium channel blocker nimodipine were successfully obtained through simple emulsion/ organic solvent evaporating method. The extended release formulations, composed by the polymers poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) and polycaprolactone (PCL), were submitted to characterization through X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared analysis (FT-IR) and determination of the mean particle diameter. All formulations obtained revealed an amorphous characteristic, proven through XRPD and DSC results. Besides, no chemical interaction was observed between drug and polymer in polymeric microparticles. PHBV-NMP formulation showed a higher drug entrapment, a larger particle size, a thermal degradation behavior similar to that observed for nimodipine and a longer drug release time, being selected for in vivo evaluation. The PHBV-NMP polymeric microparticles were able to keep the pharmacological antihypertensive effect for a longer period of time, becoming a good alternative to control nimodipine release in hypertension treatment.

Creatine supplementation: effects on blood creatine kinase activity responses to resistance exercise and creatine kinase activity measurement / A suplementação de creatina: efeitos sobre o sangue de creatina quinase respostas ao exercício de resistência e de medida da atividade da creatina quinase

The purpose of this study was to determine the effects of creatine supplementation and exercise on the integrity of muscle fiber, as well as the effect of the supplementation on the creatine kinase (CK) assay measurement. Forty-nine sedentary individuals participated in a double-blind study and were divided into two groups: C (n=26) received 4x5-day packages of 0.6 g.kg-1 of body weight contained 50 percent of creatine + 50 percent of dextrose, and P (n=23) received packages containing only dextrose. On the first day the groups performed a 1RM test for bench press, seated row, leg extension, leg curl and leg press. On D7 they received the supplements. On the fourteenth day, they performed a training session of five exercises, each in three sets of ten repetitions at 75 percent of 1RM. Blood was collected before (D14) and after the exercise session (D15). Differing levels of blood creatine were tested to determine the influence on the assay measurements of CK. ANOVA and Tukey's post-hoc tests were used to compare groups and different times of study protocol (P<0.05). No changes were observed in CK activity of the groups from D0, D7 and D14. On D15 CK activity increases 140 percent (women) and 200 percent (men). There was no difference in CK activity between groups. Blood creatine levels up to 5mM produced no significant effect on CK assay results. CK activity increased after resistance exercise, while creatine supplementation produced no difference in the muscle cellular integrity nor compromised assay methodology.

O objetivo do presente estudo foi determinar o efeito da suplementação de creatina e do exercício na integridade das fibras musculares e, também, o efeito da suplementação na técnica de mensuração da atividade da creatina kinase (CK). Quarenta e nove sedentários participaram de um estudo duplo-cego e foram divididos em dois grupos: C (n=26) que receberam 4x5 dias embalagens com 0,6 g.kg-1 de massa corporal com 50 por cento de creatina + 50 por cento de dextrose, e P (n=23) que receberam embalagens contendo apenas dextrose. No primeiro dia, eles realizaram o teste de 1RM para os exercícios supino reto, remada sentada, cadeira extensora, mesa flexora, e leg press. No D7 receberam os suplementos. No décimo quarto dia eles realizaram uma sessão de treinos com os cinco exercícios, cada um com 3x10 repetições a 75 por cento de 1RM. Sangue foi coletado antes (D14) e depois da sessão de exercícios (D15). Diferentes concentrações de creatina no sangue foram testadas para determinar a influência nos métodos de medida da atividade de CK. ANOVA e o teste post-hoc de Tukey foram usados para comparar os grupos e as diferentes coletas (P<0,05). Não foram observadas mudanças significativas na atividade de CK nos grupos em D0, D7 e D14. Em D15 a atividade de CK aumentou 140 por cento (mulheres) e 200 por cento (homens). Não houve diferenças na atividade de CK entre os grupos. Concentrações sanguíneas de creatina até 5 mM não produziram efeitos significativos nos resultados de CK. A atividade de CK aumenta após o exercício, mas a creatina não tem influência na integridade da fibra muscular ou compromete o método de análise da CK.