7 research outputs found
The Role of the Frank–Starling Law in the Transduction of Cellular Work to Whole Organ Pump Function: A Computational Modeling Analysis
We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain
Plant-mediated synthesis of zinc oxide and copper oxide nanoparticles by using ferulago angulata (schlecht) boiss extract and comparison of their photocatalytic degradation of Rhodamine B (RhB) under visible light irradiation
Petrogenesis of gem sapphire in a pegmatite-aplite vein from the Alvand batholith, Western Iran
Geochemistry of garnet in pegmatites from the Boroujerd Intrusive Complex, Sanandaj-Sirjan Zone, western Iran: implications for the origin of pegmatite melts
Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study
In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod
Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.
BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator
that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and
improvement on imaging in a phase 2 study involving patients with multiple
sclerosis.
METHODS: In this 12-month, double-blind, double-dummy study, we randomly assigned
1292 patients with relapsing-remitting multiple sclerosis who had a recent
history of at least one relapse to receive either oral fingolimod at a daily dose
of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established
therapy for multiple sclerosis) at a weekly dose of 30 microg. The primary end
point was the annualized relapse rate. Key secondary end points were the number
of new or enlarged lesions on T(2)-weighted magnetic resonance imaging (MRI)
scans at 12 months and progression of disability that was sustained for at least
3 months.
RESULTS: A total of 1153 patients (89%) completed the study. The annualized
relapse rate was significantly lower in both groups receiving fingolimod--0.20
(95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95%
CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon group (0.33; 95%
CI, 0.26 to 0.42; P<0.001 for both comparisons). MRI findings supported the
primary results. No significant differences were seen among the study groups with
respect to progression of disability. Two fatal infections occurred in the group
that received the 1.25-mg dose of fingolimod: disseminated primary varicella
zoster and herpes simplex encephalitis. Other adverse events among patients
receiving fingolimod were nonfatal herpesvirus infections, bradycardia and
atrioventricular block, hypertension, macular edema, skin cancer, and elevated
liver-enzyme levels.
CONCLUSIONS: This trial showed the superior efficacy of oral fingolimod with
respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as
compared with intramuscular interferon beta-1a. Longer studies are needed to
assess the safety and efficacy of treatment beyond 1 year. (ClinicalTrials.gov
number, NCT00340834.