Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

Prolonged testosterone 17ß-cyclopentylpropionate exposition induces behavioral, ovarian, oviductal, uterine and reproductive disturbances in female mice.

Anabolic-androgenic steroids (AAS) abuse is often associated with metabolic disorders and infertility. However, the current evidence on AAS-induced reproductive toxicity is mainly based on male studies. Thus, AAS repercussions on female reproductive capacity remain poorly understood, despite scarce evidence that fertility determinants may be more severely impaired in females than males exposed to these drugs. Accordingly, this study used an integrated framework to investigate the impact of different testosterone 17ß-cyclopentylpropionate (TC) doses on pain sensitivity, aggressiveness, anxiety, sexual behavior, ovarian, oviductal, uterine and reproductive morphofunctional and molecular outcomes. These parameters were used to explore the reproductive capacity in female mice exposed to this synthetic testosterone ester. The animals were untreated or intraperitoneally treated with 5, 10 and 20 mg/kg TC every 48 h for 12 weeks. Our findings indicated that testosterone was upregulated while the hormones luteinizing, follicle-stimulating, estrogen and progesterone were down-regulated by TC. This AAS also exerted deleterious effects on anxiety, aggressivity, nociception, exploratory and sexual behavior in female mice. Concurrently, TC attenuated ovarian follicle maturation, interrupted the estrous cycle, induced oviductal and uterine hypotrophy. Estrous cyclicity was reestablished 60 days after AAS treatment. However, TC-treated mice still exhibited impaired reproductive capacity, a disturbance potentially related to deficiency in folliculogenesis, sex hormones production, and endometrial receptivity mediate by ER-α, PR, HOXA-10 and LIF down-regulation. Taken together, our findings indicated that in addition to female behavior, reproductive organs microstructure and function are markedly impaired by TC in a dose-dependent manner, whose time-dependent reversibility remains to be clarified.

Does 8-Week Resistance Training with Slow Movement Cadenced by Pilates Breathing Affect Muscle Strength and Balance of Older Adults? An Age-Matched Controlled Trial.

This study investigated the balance and dorsiflexion strength of older adults after eight weeks of resistance training, with the exercise velocity cadenced by the Pilates breathing technique and the volume modulated by the session duration. Forty-four older adults were divided into two groups: resistance training (TR; n = 22) and resistance training with the Pilates breathing technique cadencing all exercises (TR + P; n = 22), both during eight weeks. The total exercising volume was controlled by time of execution (50 min/session). The dorsiflexion strength and balance were assessed. The RT group showed higher dorsiflexion strength after the protocol: Right (RT = 29.1 ± 7.7 vs. RT + P = 22.9 ± 5.2, p = 0.001) and Left (RT = 29.5 ± 6.9 vs. RT + P = 24.0 ± 5.2, p = 0.001). All balance parameters were improved in RT + P group compared to its own baseline: Path Length (cm) (pre = 71.0 ± 14.3 vs. post = 59.7 ± 14.3, p = 0.003); Sway Velocity (cm/s) (pre = 3.6 ± 0.7; post = 2.9 ± 0.7; p = 0.001); Sway Area (cm2) (pre = 8.9 ± 5.3 vs. post = 5.7 ± 2.1, p = 0.003); Excursion Medio Lateral (cm) (pre = 3.0 ± 0.7 vs. post = 2.6 ± 0.5 cm, p = 0.002); and Excursion AP (cm) (pre = 3.6 ± 1.4 vs. post = 2.8 ± 0.7 cm, p = 0.010). Resistance training using slower velocity movement cadenced by Pilates breathing technique produced balance improvements compared to baseline (moderate to large effect sizes), but no between-group effect was observed at the end of the protocol. The dorsiflexion strength was higher in the RT group compared to RT + P group.

Development of novel montmorillonite-based sustained release system for oral bromopride delivery.

The drug delivery systems are an important strategy of pharmaceutical technology to modulate undesirable properties, increasing efficacy, and reducing the side effects of active pharmaceutical ingredients (API). The sustained release is a type of controlled-release system that provides a suitable drug level in the blood through a slow release rate. An interesting alternative to achieve a controlled release is the application of carrier materials such as polymers, cyclodextrins, and clays. Sodium montmorillonite (Na-MMT) is a biocompatible natural clay that allows the insertion of organic compounds in interlamellar space, owing to its high cation exchange capacity and large internal surface area. Bromopride (BPD) is an aminated compound with antiemetic properties classified as class II (low solubility, high permeability) of the Biopharmaceutical Classification System (BCS). Herein, the aim of the study was the development and investigation of a drug delivery system formed by intercalation of BPD with Na-MMT. The results indicate the successful intercalation of this API with the lamellar silicate, meanwhile, there was no evidence of BPD intercalation in organic montmorillonite. The Na-MMT/BPD molecular complex exhibits a sustained release in performed assays. Molecular dynamics simulations suggested that BPD molecules interact with the montmorillonite layer through ion-dipole interactions and also between BPD molecules, forming hydrogen bonds web into montmorillonite interlayer space. The new drug delivery system showed an alternative to achieve the BPD sustained release, which may improve its pharmacological performance in therapeutic applications.

Cytotoxicity of different concentrations of glycolic acid and its effects on root dentin microhardness - An in vitro study.

The aim of the study was to evaluate the cytotoxicity of different glycolic acid concentrations (GA) and its effects on dentinal microhardness. Cytotoxicity was evaluated after inoculation of test irrigants in the lymphocyte primary culture for 3 min. The tested substances were distilled water(DW); 17% EDTA; QMix; 10% GA; 17% GA; and 25% GA. Counting of total, live and dead cells was performed, obtaining the average percentage of dead cells of each group. For microhardness evaluation, 60 root dentin samples were divided into the same tested groups (n = 10) and immersed in test irrigants for 3 min. Dentin microhardness was evaluated by Vicker test. Specific statistical analysis was made in both tests. Results showed significant lower cytotoxicity for QMix and 10% GA (P < 0.05). Moreover, all test irrigants presented similar values of microhardness than the control group (P > 0.05). In conclusion, lower GA concentration can be an alternative for final irrigation on endodontics.

Eight-week equipment-based Pilates exercises positively affects quality of life, and functional capacity in non-active adult women: a randomized controlled trial.

BACKGROUND: The Pilates exercises are popular for muscle conditioning among women. However, the effects on conditioning of healthy non-active adult women due to Pilates practicing are not fully explained. The aim of this randomized controlled trial was to assess the effects of equipment-based Pilates exercises on the percentage of body fat, weight, body mass index (BMI), functional capacity, and quality of life of adult healthy women. METHODS: Seventy-eight non-active women were randomly assigned to 2 groups (Pilates or Control). The Pilates group performed a total of 16 exercise sessions (60 minutes each, performed twice a week for 8 consecutive weeks). The control group was instructed to perform no exercise. Percentage of body fat (DXA scans), weight, BMI, distance covered in the incremental shuttle walk test, maximal oxygen uptake (VO2max), and quality of life (SF-36 scores) were analyzed. RESULTS: There were no significant between-group differences at baseline, but significant group-by-time interaction was observed for Pilates group postintervention. Higher distance covered (P=0.01), VO2max (P=0.04), and quality of life (P=0.04) were observed after the intervention compared to the control group. No differences were observed for body composition. CONCLUSIONS: Two months of equipment-based Pilates training improved functional capacity and quality of life in healthy adult women.

Acute Effects of Single- Versus Double-Leg Postactivation Potentiation on Postural Balance of Older Women: An Age-Matched Controlled Study.

AIMS: To compare the postactivation potentiation effects of isometric contraction until failure in double- and single-leg tasks on older women's balance. METHODS: The one-legged balance test was performed before and immediately after a rise-to-toes task until the task failure. Older women were divided into two groups: a group performed the task with double leg (n = 43) and the other group with single-leg support (n = 55). RESULTS: The single-leg group showed slower velocity of sway post rise-to-toes task (pre = 4.02 ± 1; post = 3.78 ± 1.15 m/s; p = .04) without differences for the center of pressure path length (pre = 79 ± 21; post = 75 ± 23 cm; p = .08). In the double-leg group, faster velocity of sway (pre = 4 ± 1.22; post = 4.25 ± 1.13; p = .03) and increased center of pressure path length (pre = 80 ± 24; post = 85 ± 23 cm; p = .03) were observed after the task. CONCLUSIONS: The single-leg group showed improved balance outcomes due to postactivation potentiation, while the double-leg group showed worsened balance consistent with muscle fatigue.

Assessment of the Ability of Different Cleaning Protocols to Remove Eugenol-based Endodontic Sealer from the Root Dentin.

AIM: The aim of this study is to assess three protocols for removing a eugenol-based filling endodontic sealer from root dentin and the bond strength of fiberglass posts luted with resin cement. MATERIALS AND METHODS: Sixty single-rooted bovine teeth were prepared and filled with the Endofill endodontic sealer and gutta-percha cones. After 7 days, 9 mm of the filling was removed and divided into five groups (n = 12) according to the cleaning protocol: G1 (negative control), unfilled; G2 (positive control), saline solution; G3, 95% alcohol; G4, amyl acetate; and G5, Largo bur. The canals were hybridized and fiberglass posts were luted with resin cement. They were cross-sectioned in slices of 1 mm and subjected to the push-out test. The other samples were sectioned longitudinally and visualized in a scanning electron microscope (SEM), and the existing chemical elements were quantified by energy dispersive spectroscopy (EDS). The statistical analysis used variance analysis (ANOVA)-one way and Fisher's test, at a 5% significance level. RESULTS: The 95% alcohol was more effective for cleaning the canal, resulting in a clean dentinal surface and bond strength statistically similar to the negative control. The Largo bur was also statistically similar to the negative control, with only a few debris impregnated on the wall. Amyl acetate showed more sealer residues on the canal walls, with a consequent lower bond strength value than the other groups, only higher than the positive control. CONCLUSION: The 95% alcohol and Largo burs may be used after removing the canal filling, so that the bond strength is improved when using the eugenol-based sealer.

Effect of different protocols of eugenol removal on the bond strength between the fibre post and root dentin.

The aim of this study was to evaluate the bond strength between the fibre post and root dentin after different cleaning protocols to remove eugenol from dentin. The residues and elemental composition of dentin were analysed using SEM and EDS. Bovine incisor roots were obturated with eugenol-based sealer. The post space was prepared, and the roots were divided into the following groups according to the cleaning protocol: unfilled (negative control), saline solution (positive control), 70% ethanol, acetone and 70% isopropyl alcohol. The fibre posts were cemented and push-out test realised. Chemical analysis of the dentin was performed using SEM and EDS. The bond strength values were analysed by anova/Fisher's and were as follows: negative control (7.30 ± 2.77) = 70% ethanol (6.64 ± 2.91) = 70% isopropyl alcohol (5.01 ± 3.15) = acetone (4.42 ± 1.53) >positive control (1.29 ± 0.56). It was concluded that 70% ethanol may be a good cleaning protocol to remove eugenol from dentin.

Effectiveness of calcium and sodium hypochlorite in association with reciprocating instrumentation on decontamination of root canals infected with Enterococcus faecalis.

The aim of this study was to evaluate the antimicrobial activity of sodium and calcium hypochlorite utilising reciprocating instrumentation. Sixty root canals were inoculated with E. faecalis for 14 days. Samples were divided into six groups according to decontamination protocol: G1: no treatment, G2: distilled water, G3: 2.5% sodium hypochlorite, G4: 2.5% calcium hypochlorite, G5: 5.25% sodium hypochlorite and G6: 5.25% calcium hypochlorite. Instrumentation was performed with Wave One reciprocating system (Dentsply Sirona Endodontics, York, PA, USA) in groups G2 to G6. Colony-forming units (CFUs) counting was performed and the data were subjected to Anova and Tukey (α  =  0.05). Group 1 and 2 showed the highest mean contamination, with a significant difference between them (P < 0.05). Groups 3, 4, 5 and 6 showed the lowest contamination means with no significant difference between them (P < 0.05). Sodium and calcium hypochlorite, in association with reciprocating instrumentation, can be an effective decontamination protocol in root canals infected with E. faecalis.