1 The e ect of dexamethasone, lipocorton-1 2 ± 26 and an antiserum to lipocortin-1 2 ± 26 (LCPS1) upon the hyperalgesic activities in rats of carrageenin, bradykinin, tumour necrosis factor a (TNFa), interleukin-1 2 , interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin Eb (PGE 2 ) and dopamine were investigated in a model of mechanical hyperalgesia. 2 Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin (100 mg), bradykinin (500 ng), TNFa (2.5 pg), IL-1b (0.5 pg), and IL-6 (1.0 ng), but not responses to IL-8 (0.1 ng), PGE 2 (100 ng) and dopamine (10 mg), were inhibited by pretreatment with dexamethasone (0.5 mg kg 71 , subcutaneously, s.c., or 0.04 ± 5.0 mg/paw). 3 Inhibition of hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng) and IL-1b (0.5 pg) by dexamethasone (0.5 mg kg 71 , s.c.) was reversed by LCPS1 (0.5 ml kg 71 , injected s.c., 24 h and 1 h before hyperalgesic substances) and hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng), TNFa (2.5 pg) and IL-1b (0.5 pg), but not responses to PGE 2 (100 ng), were inhibited by pretreatment with lipocortin-1 2 ± 26 (100 mg/paw). Also, lipocortin-1 2 ± 26 (30 and 100 mg ml 71 and dexamethasone (10 mg ml 71 ) inhibited TNFa release by cells of the J774 (murine macrophage-like) cell-line stimulated with LPS (3 mg ml 71 ), and LCPS1 partially reversed the inhibition by dexamethasone. These data are consistent with an important role for endogenous lipocortin-1 2 ± 26 in mediating the anti-hyperalgesic e ect of dexamethasone, with inhibiton of TNFa production by lipocortin-1 2 ± 26 contributing, in part, to this role. 4 Although arachidonic acid by itself was not hyperalgesic, the hyperalgesic response to IL-1b (0.25 pg, i.pl.) was potentiated by arachidonic acid (50 mg) and the potentiated response was inhibited by dexamethasone (50 mg, i.pl.) and lipocortin-1 2 ± 26 (100 mg, i.pl.). Also, lipocortin-1 2 ± 26 (30 and 100 mg ml 71 ) inhibited/abolished PGE 2 release by J774 cells stimulated with LPS (3 mg ml 71 ). These data suggest that, in in¯ammatory hyperalgesia, inhibition of the induction of cyclo-oxygenase 2 (COX-2), rather than phospholipase A 2 , by dexamethasone and lipocortin-1 2 ± 26 accounts for the antihyperalgesic e ects of these agents. 5 The above data support the notion that induction of lipocortin by dexamethasone plays a major role in the inhibition by dexamethasone of in¯ammatory hyperalgesia evoked by carrageenin, bradykinin and the cytokines TNFa, IL-1b and IL-6, and provides additional evidence that the biological activity of lipocortin resides within the peptide lipocortin-1 2 ± 26 . Further, the data suggest that inhibition of lipocortin-1 2 ± 26 of eicosanoid production by COX-2 also contributes to the anti-hyperalgesic e ect of lipocortin-1.

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Objectives: This study compared the effects of high-intensity interval training (HIIT) with effects of combined training (CT) on physical function, body composition, and muscle strength in obese postmenopausal women (PW) (trial registration: NCT03200639). Methods: PW were randomized to CT (n = 12) and HIIT (n = 12). The CT group performed 30 minutes of moderate walking at 70% of maximum heart rate (MHR) and five resistance exercises at 70% of one repetition maximum (1RM) for 12 weeks. The HIIT group performed 10 sets of vigorous exercises (30 seconds (s) of stair climbing and 30 s of body weight squats) at >80% MHR interspersed by a light walk (recovery period at 60% MHR). Results: Both groups reduced body fat percentage (0.5%), chair stand (3 s) and increased leg lean mass (0.3 kg). Only the CT, however, increased muscle strength (29%) and fast walking speed (5%) compared with HIIT. The fast walking speed changes were partially explained by the muscle strength changes (36%, r = 0.60, P = 0.027) in the CT group. Conclusions: These results suggest that HIIT is an alternative time-efficient protocol for improving chair stand and body composition when compared with CT, whereas only CT is an efficient protocol for improving muscular strength and fast walking speed in obese PW. Thus, CT must be prioritized when the increase of muscular strength and fast walking speed are the goals of training. Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A443.

This study aimed to investigate the influence of physical activity in innate immunity to conduce to an effective antitumoral immune response analyzing the phenotype and activation status of infiltrating cells. We analysed the intracellular cytokines and the transcription factors of tumor infiltrating lymphocytes (TILS) and spleen leukocytes. The Nos2 gene expression was evaluated in spleen cells and futhermore the ROS production was measured and spleen cells; another cell evaluated was dendritic cells (TIDCs), their cytokines expression and membrane molecules; finally to understood the results obtained, we analysed the dendritic cells obtained from bone marrow. Were used female Balb/c mice divided into 4 groups: two controls without tumor, sedentary (GI) and trained (GII) and two groups with tumor, sedentary (GIII) or trained (GIV). The physical activity (PA) was realized acoording swimming protocol. Tumor was induced by injection of 4T1 cells. All experiments were performed in biological triplicate. After the experimental period, the tumor was removed and the cells were identified by flow cytometry with labeling to CD4, CD8, CD11c, CD11b, CD80, CD86 and Ia, and intracelular staining IL-10, IL-12, TNF-α, IFN-γ, IL-17, Tbet, GATA3, RORγt and FoxP3. The bone marrow of the animals was obtained to analyse the derivated DCs by flow cytometry and culture cells to obtain the supernatant to measure the cytokines. Our results demonstrated that the PA inhibit the tumoral growth although not to change the number of TILS, but reduced expression of GATA-3, ROR-γT, related with poor prognosis, and TNF-α intracellular; however occur one significantly reduction in TIDCS, but these cells expressed more co-stimulatory and presentation molecules. Furthermore, we observed that the induced PA stimulated the gene expression of Tbet and the production of inflammatory cytokines suggesting an increase of Th1 systemic response. The results evaluating the systemic influence in DCs showed that the PA improve significantly the number of those cells in bone marrow as well the number of co-stimulatory molecules. Therefore, we could conclude that PA influence the innate immunity by interfering to promote in process of maturation of DCs both in tumor and systemically, that by its turn promote a modification in acquired immune cells, representing by T helper to induce an important alteration transcription factors that are responsible to maintain a suppressive microenviroment, and thereby, allowing the latter cells can thus activate antitumor immune response. The PA was able improve the Th1 systemic response by enhance to Tbet gene expression, promote a slightly increased of Th1-type cytokines and decrease Gata3 and Foxp3 gene expression in which can inhibit the Th1 immune response.

Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN.