UPLC-MS-ESI-QTOF analysis and antifungal activity of the spondias tuberosa arruda leaf and root hydroalcoholic extracts

The aim of this study was to identify and evaluate the chemical compositions and effects of the S. tuberosa leaf and root hydroalcoholic extracts (HELST and HERST) against different strains of Candida. Chemical analysis was performed by Ultra-Performance Liquid Chromatography Coupled to Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF). The Inhibitory Concentration of 50% of the growth (IC50) as well as the intrinsic and combined action of the extracts with the antifungal fluconazole (FCZ) were determined by the microdilution method while the minimum fungicidal concentrations (MFCs) and the effect on fungal morphological transitions were analyzed by subculture and in humid chambers, respectively. From the preliminary phytochemical analysis, the phenols and flavonoids were the most abundant. The intrinsic IC50 values for HELST ranged from 5716.3 to 7805.8 \ub5g/mL and from 6175.4 to 51070.9 \ub5g/mL for the HERST, whereas the combination of the extracts with fluconazole presented IC50 values from 2.65 to 278.41 \ub5g/mL. The MFC of the extracts, individually, for all the tested strains was 6516384 \ub5g/mL. When fluconazole was combined with each extract, the MFC against CA URM 5974 was reduced (HELST: 2048 and HERST: 4096 \ub5g/mL). Synergism was observed against standard C. albicans (CA) and C. tropicalis (CT) strains and with the root extract against the CT isolate. The leaf extract inhibited the morphological transition of all strains while the root extract inhibited only CT strains

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis [a Experiência Da Vida Real Com Complicações Cardiovasculares Na Primeira Dose De Fingolimode]

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.729712714Thomas, K., Ziemssen, T., Management of fingolimod in clinical practice (2013) Clin Neurol Neurosurg., 115, pp. S60-S64Ontaneda, D., Hara-Cleaver, C., Rudick, R.A., Cohen, J.A., Bermel, R.A., Early tolerability and safety of fingolimod in clinical practice (2012) J Neurol Sci., 323, pp. 167-172Bünemann, M., Liliom, K., Brandts, B.K., A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes (1996) EMBO J., 15, pp. 5527-5534Sanna, M., Liao, J., Jo, E., Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate (2004) J Biol Chem, 279, pp. 13839-13848Laroni, A., Brogi, D., Morra, V.B., Safety of the first dose of fingolimod for multiple sclerosis: Results of an open-label clinical trial (2014) BMC Neurol, 14, p. 65Polman, C.H.R., Reingold, S.C., Banwell, B., Dianosticcriteria for multiple sclerosis: 2010 Revisions to the Mac Donald criteria (2011) Ann Neurol, 69, pp. 292-302Espinosa, P.S., Berger, J.R., Delayed fingolimod-associated asystole (2011) Mult Scler, 17, pp. 1387-1389Kappos, L., Radue, E.W., O'Connor, P., A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis (2010) N Engl J Med, 362, pp. 387-401Singer, B.A., Initiating oral fingolimod treatment in patients with multiple sclerosis (2013) Ther Adv Neurol Disord, 6, pp. 269-27