1,354,698 research outputs found
Incipient sediment motion at high slopes in uniform flow condition,
No full textThis paper reviews the problem of the incipient motion of cohesionless particles in a
high sloping water stream. A theoretical analysis of the equilibrium of a gravel particle is
developed by a deterministic approach with the introduction of the relative degree of
exposure of the particle itself to the stream flow. The parameter, relative degree of
exposure, relates the positioning of a particle with the upstream one. The problem of
velocity distribution and the definition of drag coefficient is also revised to better account
for low submergence. The results of the theory are compared with a series of ad hoc
experiments performed by C. Gregoretti
Non-uniform suspended sediments under waves
No full textAn original mathematical formulation for suspended sediments in a two-dimensional wave boundary layer is presented. The model accounts for non-immediate adaptation of sediments to the hydrodynamic conditions, and allows to include the effect of sorting of the different diameters considered. The mathematical model is numerically solved through a finite difference scheme. It is suitable that results compare favourably with experimental data by C. Staub et al
Parametric study on the influence of jet-like inflows and outflows on fine sediment settling
No full textThis paper focuses on the dynamics of fine sediments in reservoirs exposed to hydropower cascade or pumped-storage operations. The aim is at analysing the influence of parameters such as the flow inlet and flow outlet relative position, the jet hydrodynamics, and the concentration of fine sediments on the settling process. Based on multiphase-threedimensional simulations, the results reveal a good correlation between the patterns of sediment deposition and turbulent dissipation rate. Numerical simulations were performed on the Computational Fluid Dynamic (CFD) software ANSYSCFX. These simulations cover 4 geometries, 2 jet velocities and three concentrations of sediments in the jet inflow. The results show that the deposition of fine sediment correlates with the turbulent dissipation rate. Indeed, the deposition is comparatively high in zones with high turbulent dissipation rate, such as in the vicinity of the jet-like inlet and outlet; whereas in zones with low turbulent dissipation rate the deposition is comparatively low.PL-LCH[1241
Corticosteroid receptors in lymphocytes: a possible marker of brain involution?
No full textA similarity has recently been found between the regulation of corticosteroid receptors in brain and in lymphoid tissue. We have studied the regulation of corticosteroid receptors in human mononuclear leukocytes as a possible marker of brain involution. Type I corticosteroid receptors are down regulated by excess of mineralocorticoids (primary and secondary hyperaldosteronism, pseudohyperaldosteronism) and of glucocorticoids (Cushing's syndrome). Type II corticosteroid receptors are not reduced by excess of endogenous corticosteroids (Cushing's syndrome). In normal adults there is a direct significant correlation between plasma cortisol and Type I and between plasma cortisol and Type II receptors in mononuclear leukocytes, while in Cushing's syndrome the correlation is inverse between plasma cortisol at 8 a.m. and Type II receptors. In an aged population the mean numbers of Type I and of Type II receptors are lower and plasma cortisol is higher than in adult controls, but the increase of plasma cortisol is not followed by a clinical picture of hypercorticism. Corticosteroid Type I and Type II receptors are inversely correlated with age. After dexamethasone suppression (1 mg at 11 p.m.) Type I receptors always decrease in controls while the response of Type II is not homogeneous. In an aged group of patients, both receptors are reduced by dexamethasone. We conclude that the decrease with age of corticosteroid receptors is possibly related to a physiological involution of corticosteroid receptors and that this reduction does increase plasma cortisol concentration, without affecting the glucocorticoid effector mechanism
Different pathways of degradation of SP-A and saturated phosphatidylcholine by alveolar macrophages
No full textAlveolar macrophages degrade surfactant protein (SP) A and saturated phosphatidycholine [dipalmitoylphosphatidylcholine (DPPC)]. To clarify this process, using rabbit alveolar macrophages, we analyzed the effect of drugs known to affect phagocytosis, pinocytosis, clathrin-mediated uptake, caveolae, the cytoskeleton, lysosomal pH, protein kinase C, and phosphatidylinositol 3-kinase (PI3K) on the degradation of SP-A and DPPC. We found the following: 1) SP-A binds to the plasma membrane, is rapidly internalized, and then moves toward degradative compartments. Uptake could be clathrin mediated, whereas phagocytosis, pinocytosis, or the use of caveolae are less likely. An intact cytoskeleton and an acidic milieu are necessary for the degradation of SP-A. 2) Stimulation of protein kinase C increases the degradation of SP-A. 3) PI3K influences the degradation of SP-A by regulating both the speed of internalization and subsequent intracellular steps, but its inhibition does not prevent SP-A from reaching the lysosomal compartment. 4) The degradation of DPPC is unaffected by most of the treatments able to influence the degradation of SP-A. Thus it appears that DPPC is degraded by alveolar macrophages through mechanisms very different from those utilized for the degradation of SP-A
The story of spironolactones from 1957 to now: from sodium balance to inflammation
No full textAfter the discovery of aldosterone (1953), many synthetic steroids were tested for their ability to block the sodium retaining and potassium excreting effect of synthetic mineralocorticoids in adrenalectomized rats. In the same years Kagawa discovered that 17-spirolactone steroids were effective to block mineralocorticoid effects, but when used alone they did not produce any effect in adrenalectomized rats. After the description of the first case of primary aldosteronism (1955), spironolactone (SP) was considered the main treatment before surgery to control blood pressure and kaliemia and for long-term treatment in patients with bilateral adrenal hyperplasia. SP was further used for various clinical situations, such as liver cirrhosis, idiopathic oedema, nephrosis and congestive heart failure. SP also shows an antiandrogen action, effective in polycystic ovary syndrome. In 1985 we demonstrated that human mononuclear leukocytes (MNL) possess mineralocorticoid receptors (MR) and lately we demonstrated that coincubation of MNL with canrenone blocked aldosterone mediated inflammatory, reducing the expression of PAI-1 and p22phox. It is well known that MNL and macrophages are mainly involved in vascular inflammation and atherosclerosis and we have hypothesized that the tissue invasion of MNL brings MR in the site of inflammation starting the process. Recently, aldosterone has been associated with the promotion of many organ-specific autoimmune diseases, inducing Th17 polarization of CD4+ T cells and suggesting new possible therapeutic targets for anti-mineralocorticoid drugs. In conclusion, considering all the benefits of MR-antagonists, their use should be reconsidered not only for the treatment but also for the prevention of many clinical situations
A one-way coupled hydrodynamic advection-diffusion model to simulate congested large wood transport
No full textAn advection-diffusion model is proposed to simulate large wood transport during high flows. The mathematical model is derived from the wood mass balance, taking into consideration both the wood mass concentration and the log orientation, which affects log transport and, most importantly, wood accumulation. Focusing on wood mass transport, the advection-diffusion equation is implemented in a hydrodynamic model to provide a one-way coupled solution of the flow and of the floating wood mass. The model is tested on a large series of flume experiments, involving at least 30 logs and different control parameters (flow Froude number, log length, diameter, release point). The validation through the experimental data shows that the proposed model can predict the correct displacement of the most probable position of the logs and to simulate with a sufficient accuracy the planar diffusion of the wooden mass. Transversal wood distribution is more accurate than the streamwise one, indicating that a higher control on the longitudinal diffusion needs to be implemented.Sanitary Engineerin
Choice of diuretic therapy and reconsideration for aldosterone receptors blockers.
No full textIn an interesting editorial, Kaplan1 has focused recently on the choice of thiazide diuretics and concluded that chlorthalidone, alone or in addition to other antihypertensive drugs, may replace hydrochlorothiazide (HCTZ). The author also states that HCTZ and chlorthalidone, even at low doses (12.5 to 25.0 mg), can lower serum potassium and that an addition of small doses of spironolactone or eplerenone could provide maximal antihypertensive efficacy and prevent hypokalemia, particularly in resistant patients.
A very important issue dealing with all diuretics is the volume depletion and activation of the renin-angiotensin-aldosterone system. Diuretics, with the exception of aldosterone receptor blockers, do not directly affect mineralocorticoid receptors. Recent studies of the literature have shown that aldosterone, even in situations of normal sodium intake, can enhance oxidative stress through activation of NADPH oxidase in particular clinical situations. Aldosterone is involved in inflammation atherosclerosis and heart hypertrophy and fibrosis, and the addition of aldosterone receptor blockers prevents the risk of complications in patients with heart diseases treated with other drugs (Randomized Aldactone Evaluation Study and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study).
Concerning the secondary hyperaldosteronism from diuretics, Brown and colleagues2,3 have compared the effect of HCTZ (25 mg per day) with the effect of spironolactone on the fibrinolytic balance in hypertensive subjects. Although HCTZ and spironolactone increased angiotensin II and aldosterone, only HCTZ increased plasminogen activator inhibitor 1 antigen concentration. Mineralocorticoid receptor antagonism prevents the effect of activation of the renin-angiotensin-aldosterone system on the plasminogen activator inhibitor 1 antigen in normotensive subjects and improves the fibrinolytic balance in hypertensive subjects through a potassium-independent mechanism, the same pro-oxidative effect that is evident when administering triamterene, thus supporting the concept that aldosterone increases plasminogen activator inhibitor 1 synthesis independently from the potassium concentration.2,3
We have reported studies using human mononuclear leukocytes and have found that canrenone completely blocks the pro-oxidative effect of aldosterone in these cells, as measured by the protein expression of plasminogen activator inhibitor 1 and p22phox.4 In patients treated with thiazides or furosemide, aldosterone receptors are not blocked, and the cardiovascular risk is reduced by the lowering of blood pressure but is also enhanced by the binding of high aldosterone levels to mineralocorticoid receptors at the level of target tissues and, in particular, at the level of mononuclear leukocytes, a major component of vascular inflammation. This mechanism could enhance the fibrotic and atherogenic processes. These observations further enforce the concept that the goal of therapy is not only the lowering of blood pressure and the controlling of potassium but also the prevention of the inflammatory effect of aldosterone, as specified by Kaplan1 at the end of the editorial.
Aldosterone receptor blockers do have a limited use in essential and secondary hypertension, particularly in Europe, as demonstrated by the Guidelines of the European Council of Hypertension (New Consensus Hypertension Guidelines from European Society of Hypertension/European Society of Cardiology 2007: Antihypertensive Treatment), which considers thiazides but not aldosterone receptors blockers for treatment of resistant hypertension, and maybe aldosterone receptor blockers should have a larger prescription, considering that metabolites with minimal (potassium canrenoate and canrenone) or absent (eplerenone) antiandrogenic activity are available in many countries
Aldosterone-mediated endothelial remodeling and oxidative stress
No full textThe recognition of the inflammatory and profibrotic role of aldosterone in the pathophysiology of cardiovascular disease, via its effect on endothelial dysfunction, is of growing importance, as demonstrated by the results of the recently concluded Randomized Aldactone Evaluation Study (RALES)1, and the EPlerenone neuroHormonal Efficacy and SUrvival Study (EPHESUS)2. These studies have, in fact, indicated the reduction of aldosterone effects through receptor blocking as additional benefit to patients with cardiovascular diseases.
In a paper published in the May issue Kidney International, Oberleithner documented “in vitro” an aldosterone remodeling effect on human endothelium through induction of cell stiffness due to a presumably aldosterone induced oxidative stress via modulation of NAD(P)H oxidase3. We would like to provide further support to the contention of a specific remodeling and profibrotic action of aldosterone with the demonstration “ex vivo” in human mononuclear cells, recently published by our laboratory4, that indicates that aldosterone has a direct effect on oxidative stress through its ability to increase the levels of p22phox, an important subunit of NADPH oxidase, essential for superoxide anion generation. It, in fact, functions as an integral subunit of the final electron transport from NADPH to heme and molecular oxygen in generating superoxide anions. The aldosterone-induced increased level of PAI-1, a recognized profibrotic protein, we have shown in the same study4, may also provide a direct link to the cardiovascular profibrotic and remodeling action of aldosterone. Our findings were further strengthened by similar effects shown by glycyrrhetinic acid4, a constituent of licorice root, which is known to have a direct mineralocorticoid-like effect5. Thus, the report of Oberleithner3 in combination with the results of our study provides clear evidence for the aldosterone-related vascular remodeling effects through its induction of oxidative stress and oxidative stress-related profibrotic molecules, such as PAI-1
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