Spironolactone improves angiotensin-induced vascular changes and oxidative stress

Angiotensin II plays an important role in vascular remodeling. We investigated the role of aldosterone, which is stimulated by angiotensin II, as a mediator of angiotensin II-induced vascular structural and functional alterations. Sprague-Dawley rats (n=8 to 12/group) received angiotensin II (120 ng/kg per minute, subcutaneously) for 14 days +/- spironolactone or hydralazine (25 mg/kg per day). An additional group received aldosterone (750 ng/h, subcutaneously) +/- spironolactone. Systolic blood pressure was increased by angiotensin II (P<0.001) and reduced by spironolactone and hydralazine (P<0.001). Aldosterone-induced increase of blood pressure was reduced by spironolactone (P<0.05). In mesenteric small arteries studied on a pressurized myograph, media/lumen ratio was increased (P<0.001) and acetylcholine-mediated relaxation was impaired in angiotensin II-infused rats (P<0.001); both were partially improved by spironolactone (P<0.05) but not by hydralazine. Aldosterone-induced increase of media/lumen ratio (P<0.001) and impaired response to acetylcholine (P<0.001) were normalized by spironolactone. Response to sodium nitroprusside was similar in all groups. Aortic NADPH oxidase activity was increased (P<0.01) by angiotensin II and reduced by spironolactone and hydralazine. Aldosterone also increased (P<0.05) activation of NADPH oxidase, an effect abolished by spironolactone. Plasma thiobarbituric acid-reactive substances (a marker of oxidative stress), higher in angiotensin II and aldosterone rats (P<0.001), were normalized by spironolactone. In conclusion, spironolactone, which inhibited aldosterone actions, partially corrected structural and functional angiotensin II-induced abnormalities. These effects were associated with reduced vascular NADPH oxidase activity and decreased plasma markers of oxidative stress. Our findings suggest that aldosterone may mediate some of angiotensin II-induced vascular effects in hypertension, in part via increased oxidative stress.     

An ultrasonographic investigation of deep neck flexor muscles cross-sectional area in forward and normal head posture

Background

As one of the most common work-related musculoskeletal disorders and postural deviations, forward head posture (FHP), is considered to lead to muscle imbalance.

Effect of Resveratrol Supplementation on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Purpose

The evidence has suggested that resveratrol has anti-inflammatory effect; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol supplementation on the levels of inflammatory markers through a systematic review and meta-analysis of available randomized controlled trials (RCTs).

Administration of Selenium Nanoparticles Reverses Streptozotocin-Induced Neurotoxicity in the male rats

Metabolic Brain Disease - Alzheimer’s disease is the most common neurodegenerative disease associated with deposition of amyloid-beta and the increased oxidative stress. High free radical...     

Boceprevir and telaprevir‐based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end‐stage liver disease score

Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)‐NS3/NS4A protease inhibitors (PI)] in association with PEG‐IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow‐up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty‐one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non‐response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non‐responders to 59.1% in partial non‐responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P < 0.001). The model for end‐stage liver disease (MELD) score was significantly increased at W12 for telaprevir (P = 0.008) and at W24 for boceprevir (P = 0.027). PI‐based triple therapy leads to high rates of virological response even in previously non‐responder patients. Renal function after triple therapy is impaired as well as MELD score in all patients. Cautious clinical monitoring should focus not only on haematological and dermatological side effects but also on renal function.     

Echocardiographic estimation of left ventricular filling pressures in patients with mitral valve stenosis

Mitral stenosis (MS) is prevalent in developing countries. By improving healthcare systems, it could be expected that the incidence of new cases would decrease and therefore the mean age of mitral stenosis patients would increase. This increase in age of MS patients is accompanied by the occurrence of other diseases, such as coronary artery disease, hypertension, diabetes mellitus and chronic obstructive pulmonary disease.In a number of patients with MS, the question arises of the impact of mitral valve disease (MVD) on the presenting symptom. For example, in patients presenting with dyspnea, with both significant MS and hypertension, increased left ventricular (LV) filling pressure due to hypertension could influence assessment of the severity of MS. In these patients, severity of MS could be underestimated because the increased diastolic pressure reduces the mitral valve gradient, and the increased LV stiffness shortens pressure half-time (PHT).Similarly, patients with both pulmonary disease and MS may have dyspnoea because of pulmonary rather than cardiac cause. It is therefore advantageous to assess LV filling pressure in these cases in an attempt to prove or refute a cardiac cause for dyspnoea.Using Doppler measurements to estimate LV filling pressures is desirable. However, conventional Doppler measurements have limitations in the prediction of left ventricular end-diastolic pressure (LVEDP) in this group of patients. For example, in patients with MS, the left atrium (LA) is enlarged to compensate for the increase in LA pressure. Similarly, mitral inflow peak early diastolic velocity (E) is highly dependent on LA pressure1 and also preload.2 Pulmonary venous (PV) flow also has a blunted pattern in most patients with MS.3 Therefore, in MS patients, LA size, mitral inflow pattern and pulmonary venous pattern are all altered, making these measurements unreliable for the estimation of LVEDPHowever, other Doppler and tissue Doppler echocardiographic indices and time intervals, such as peak early diastolic velocity of mitral annulus (Ea), E/Ea ratio, mitral inflow propagation velocity (VP), E/VP, pulmonary vein velocities, Tei index and the ratio of isovolumic relaxation time (IVRT) to interval between the onset of mitral E and annular Ea (TE–Ea), which have shown promising values in the prediction of LV filling pressure in a variety of diseases,4-11 have not been assessed in the setting of mitral stenosis.The aim of this study was to analyse the components of mitral and pulmonary waves in patients with mitral stenosis and to construct a Doppler-derived LVEDP prediction model based on the combined analysis of transmitral and pulmonary venous flow velocity curves.     

Association between MIF gene variation and Meniere's disease

Several pieces of evidence support the involvement of immune system in Menière's disease (MD). Macrophage migration inhibitory factor (MIF) plays a key role in immune‐mediated reactions. Several studies have shown an association between MIF gene polymorphisms and susceptibility to various inflammatory and autoimmune disorders. The aim of this study was to explore the association between MIF‐173 G/C polymorphism and MD in an Iranian population. In this case–control association study, MD cases (N = 72) were recruited and were comprised of definitive MD (N = 58) and probable MD (N = 14) subjects. Normal healthy subjects (N = 100) were also included. Genotyping for MIF‐173 G/C polymorphism was carried out using PCR‐RFLP technique. There was a significant increase in genotype GG in patients with MD compared with the control group. (GG vs. GC + CC, P = 0.02, OR = 2.08, 95% CI: 1.02–4.3). This was more significant when definitive MD was stratified and compared with the controls (GG vs. GC + CC, P = 0.009, OR = 2.6, 95% CI = 1.19–6.18). This study's result indicates the potential role of MIF in MD of which further evaluation is required. Also, the more significant association between MIF gene polymorphism and definitive MD designates the involvement of specific pathogenic mechanisms which may be considered as a marker for diagnosis.