29 research outputs found
Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial
Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials.
Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.
Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.
Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049
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Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by sigma2 receptor agonists and antagonists
Some sigma receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between sigma receptor ligands and the dopamine transporter, the effects of sigma receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [3H]dopamine release at concentrations consistent with their affinities for sigma2 receptors. In contrast, BD737 (1S.2R-(-)-cis-N-¿2-(3,4-dichlorophenyl)ethyl¿-N-methyl-2-(1-pyrrolidiny l)cyclohexylamine), a sigma1 receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [3H]dopamine release under these conditions. Three antagonists at sigma receptors, one of which is non-selective for subtypes, and two of which are sigma2-selective, all blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (-)-pentazocine was similarly blocked by sigma2 receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of sigma receptors pharmacologically identified as the sigma2 subtype
Optimising the use of arsenic trioxide in 'high risk' acute promyelocytic leukaemia (APL): The UK experience.
The upgrading of the sidewalk: from traditional working-class colonisation to the squatting practices of urban middle-class families
Insights to the clarification of sugar cane juice expressed from sugar cane stalk and trash
Processing of juice expressed from green sugar cane containing all the trash (i.e., tops and leaves, the nonstalk component) of the sugar cane plant during sugar manufacture has been reported to lead to poor clarified juice (CJ) quality. Studies of different liming techniques have been conducted to identify which liming technique gives the best clarification performance from juice expressed from green cane containing half of all trash extracted (GE). Results have shown that lime saccharate addition to juice at 76 °C either continuous or batchwise gives satisfactory settling rates of calcium phosphate flocs(50−70 cm/min) and CJ with low turbidity and minimal amounts of mineral constituents. Surprisingly, the addition of phosphoric acid (≤300 mg/kg as P2O5), prior to liming to reduce juice turbidity (≤80%), increased the Mg (≤101%) and Si(≤148%) contents particularly for clarified GE juices. The increase was not proportional with increasing phosphoric acid dose. The nature of the flocs formed, including the zeta potential of the particles by the different liming techniques, has been used to account for the differences in clarification performance. Differences between the qualities of the CJ obtained with GE juice and that of burnt cane juices with all trash extracted (BE) have been discussed to provide further insights into GE processing