A new phage-display tumor-homing peptide fused to antiangiogenic peptide generates a novel bioactive molecule with antimelanoma activity

Phage-display peptide libraries have been widely used to identify specific peptides targeting in vivo tumor cells and the tumor vasculature and playing an important role in the discovery of antitumor bioactive peptides. In the present work, we identified a new melanoma-homing peptide, (-CVNHPAFAC-), using a C7C phage-display library directed to the developing tumor in syngeneic mice. Phage were able to preferentially target melanoma in vivo, with an affinity about 50-fold greater than that with normal tissue, and the respective synthesized peptide displaced the corresponding phage from the tumor. A preferential binding to endothelial cells rather than to melanoma cells was seen in cell ELISA, suggesting that the peptide is directed to the melanoma vasculature. Furthermore, the peptide was able to bind to human sonic hedgehog, a protein involved in the development of many types of human cancers. Using a new peptide approach therapy, we coupled the cyclic peptide to another peptide, HTMYYHHYQHHL-NH(2), a known antagonist of VEGFR-2 receptor, using the GYG linker. The full peptide CVNHPAFACGYGHTMYYHHYQHHL-NH(2) was effective in delaying tumor growth (P < 0.05) and increasing animal survival when injected systemically, whereas a scramble-homing peptide containing the same antagonist did not have any effect. This is the first report on the synthesis of a tumor-homing peptide coupled to antiangiogenic peptide as a new anticancer therapeutics

REALMS Study: Real-World Effectiveness and Safety of Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis in Portugal

Background: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). Objectives: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. Methods: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. Results: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. Conclusions: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.info:eu-repo/semantics/publishedVersio

Women’s pelvic floor muscle strength and urinary and anal incontinence after childbirth: a cross-sectional study

Abstract OBJECTIVE To analyse pelvic floor muscle strength (PFMS) and urinary and anal incontinence (UI and AI) in the postpartum period. METHOD Cross-sectional study carried out with women in their first seven months after child birth. Data were collected through interviews, perineometry (Peritron™), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS 128 women participated in the study. The PFMS mean was 33.1 (SD=16.0) cmH2O and the prevalence of UI and AI was 7.8% and 5.5%, respectively. In the multiple analyses, the variables associated with PFMS were type of birth and cohabitation with a partner. Newborn’s weight, previous pregnancy, UI during pregnancy, and sexual activity showed an association with UI after child birth. Only AI prior to pregnancy was associated with AI after childbirth. CONCLUSION Vaginal birth predisposes to the reduction of PFMS, and caesarean section had a protective effect to its reduction. The occurrence of UI during pregnancy is a predictor of UI after childbirth, and women with previous pregnancies and newborns with higher weights are more likely to have UI after childbirth.AI prior to pregnancy is the only risk factor for its occurrence after childbirth. Associations between PFMS and cohabitation with a partner, and between UI and sexual activity do not make possible to conclude that these variables are directly associated

The latent stem cell population is retained in the hippocampus of transgenic Huntington's disease mice but not wild-type mice

The demonstration of the brain's ability to initiate repair in response to disease or injury has sparked considerable interest in therapeutic strategies to stimulate adult neurogenesis. In this study we examined the effect of a progressive neurodegenerative condition on neural precursor activity in the subventricular zone (SVZ) and hippocampus of the R6/1 transgenic mouse model of Huntington's disease (HD). Our results revealed an age-related decline in SVZ precursor numbers in both wild-type (WT) and HD mice. Interestingly, hippocampal precursor numbers declined with age in WT mice, although we observed maintenance in hippocampal precursor number in the HD animals in response to advancement of the disease. This maintenance was consistent with activation of a recently identified latent hippocampal precursor population. We found that the small latent stem cell population was also maintained in the HD hippocampus at 33 weeks, whereas it was not present in the WT. Our findings demonstrate that, despite a loss of neurogenesis in the HD hippocampus in vivo, there is a unique maintenance of the precursor and stem cells, which may potentially be activated to ameliorate disease symptoms