Moderate Antiproteinuric Effect of Add-On Aldosterone Blockade with Eplerenone in Non-Diabetic Chronic Kidney Disease. A Randomized Cross-Over Study

Reduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD.Open randomized cross-over trial.Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours.Eight weeks of once-daily administration of add-on 25–50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade.24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance.The mean urinary albumin excretion was 22% [CI: 14,28], P<0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia.Open label, no wash-out period and a moderate sample size.In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium

Reporäntans effekt på aktiemarknaden

Syftet med uppsatsen är att studera och analysera hur en räntehöjning respektive -sänkning påverkar aktiekursen samt om det föreligger någon skillnad mellan olika branscher och soliditetsnivåer. Vi har genomfört en kvantitativ studie, en händelsestudie, av totalt 60 svenska företag fördelade på sex olika branscher, alla noterade på Stockholmsbörsen. Vi har beräknat den onormala avkastningen för alla aktier under perioden fem dagar före till fem dagar efter de reporänteförändringar som skett mellan åren 1994-2004. Vi har testat ett antal uppställda hypoteser och använder oss därför av en hypotetiskt-deduktiv teoribildning. Vi har funnit att en höjning respektive en sänkning av reporäntan leder till en negativ respektive en positiv onormal avkastning på företagens underliggande aktie. Vad gäller branschskillnader så uppvisar branscherna finans, IT, material och industri större känslighet gentemot ränteändringar än branscherna konsument och hälsovård. Vidare finner vi inget bevis för att en låg soliditet leder till större känslighet för ränteändringar

Validation of guidelines for cfd modelling of a single tube row and in-line tube bundles

This paper questions and improves commonly used guidelines for modelling a tube bundle in cross-flow at ReD = 3.4 · 104 and ReD = 1.1 · 105. Especially, when the locations of flow separation are of high interest. A major conclusion of this paper is that near-wall modelling (y+ &lt; 5) is preferable and use of wall functions with y+ &gt; 5 should be avoided in relation to flow separation behind tubes in cross-flow. CFD modelling of a tube bundle may be simplified with the use of symmetric or periodic boundary conditions to account for the full geometry. The present work reveals periodicity in vorticity formation between a double cylinder row, though the wake region behind a single cylinder row is neither characterised as in-phase nor reversed phase. Likewise, periodic boundary conditions may result in a modelling with large wake deflections for a full tube bundle. Furthermore, since there is no unequivocal answer to which turbulence model to apply for tubes in cross-flow, the RNG k-ε, Realizable k-ε, SST k-ω, and RSM turbulence models are tested and compared.</jats:p

Amplification of EDHF-type vasodilatations in TRPC1-deficient mice

BACKGROUND AND PURPOSE: TRPC1 channels are expressed in the vasculature and are putative candidates for intracellular Ca(2+) handling. However, little is known about their role in endothelium-dependent vasodilatations including endothelium-derived hyperpolarizing factor (EDHF) vasodilatations, which require activation of Ca(2+)-activated K(+) channels (K(Ca)). To provide molecular information on the role of TRPC1 for K(Ca) function and the EDHF signalling complex, we examined endothelium-dependent and independent vasodilatations, K(Ca) currents and smooth muscle contractility in TRPC1-deficient mice (TRPC1-/-). EXPERIMENTAL APPROACH: Vascular responses were studied using pressure/wire myography and intravital microscopy. We performed electrophysiological measurements, and confocal Ca(2+) imaging for studying K(Ca) channel functions and Ca(2+) sparks. KEY RESULTS: TRPC1 deficiency in carotid arteries produced a twofold augmentation of TRAM-34- and UCL1684-sensitive EDHF-type vasodilatations and of endothelial hyperpolarization to acetylcholine. NO-mediated vasodilatations were unchanged. TRPC1-/- exhibited enhanced EDHF-type vasodilatations in resistance-sized arterioles in vivo associated with reduced spontaneous tone. Endothelial IK(Ca)/SK(Ca)-type K(Ca) currents, smooth muscle cell Ca(2+) sparks and associated BK(Ca)-mediated spontaneous transient outward currents were unchanged in TRPC1-/-. Smooth muscle contractility induced by receptor-operated Ca(2+) influx or Ca(2+) release and endothelium-independent vasodilatations were unaltered in TRPC1-/-. TRPC1-/- exhibited lower systolic blood pressure as determined by tail-cuff blood pressure measurements. CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that TRPC1 acts as a negative regulator of endothelial K(Ca) channel-dependent EDHF-type vasodilatations and thereby contributes to blood pressure regulation. Thus, we propose a specific role of TRPC1 in the EDHF–K(Ca) signalling complex and suggest that pharmacological inhibition of TRPC1, by enhancing EDHF vasodilatations, may be a novel strategy for lowering blood pressure