Anti-inflammatory effects of Mangifera indica L. extract in a model of colitis

AIM:To investigate the effect of aqueous extract from Mangifera indica L.(MIE)on dextran sulfate sodium (DSS)-induced colitis in rats.METHODS:MIE(150 mg/kg)was administered in two different protocols:(1)rectally,over 7 d at the same time as DSS administration;and(2)once daily over 14 d (by oral gavage,7 d before starting DSS,and rectally for 7 d during DSS administration).General observations of clinical signs were performed.Anti-inflammatory activity of MIE was assessed by myeloperoxidase(MPO)activity. Colonic lipid peroxidation was determined by measuring the levels of thiobarbituric acid reactive substances (TBARS).Reduced glutathione(GSH)levels,expression of inflammatory related mediators[inducible isoforms of nitric oxide synthase(iNOS)and cyclooxygenase (COX)-2,respectively]and cytokines[tumor necrosis factor(TNF)-αand TNF receptors 1 and 2]in colonic tissue were also assessed.Interleukin(IL)-6 and TNF-α serum levels were also measured. RESULTS:The results demonstrated that MIE has anti-inflammatory properties by improvement of clinical signs,reduction of ulceration and reduced MPO activity when administered before DSS.In addition,administration of MIE for 14 d resulted in an increase in GSH and reduction of TBARS levels and iNOS,COX-2, TNF-αand TNF R-2 expression in colonic tissue,and a decrease in IL-6 and TNF-αserum levels. CONCLUSION:MIE has anti-inflammatory activity in a DSS-induced rat colitis model and preventive administration(prior to DSS)seems to be a more effective protocol.     

Carvedilol administration in acute myocardial infarction results in stronger inhibition of early markers of left ventricular remodeling than metoprolol

Background

The structural secuelae of acute myocardial infarction (AMI) is mostly dictated by left ventricular (LV) remodelling, leading to heart failure. Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a critical role in LV remodelling.β-blockers are first line therapy for AMI and heart failure; however, the mechanisms responsible for their benefits remain poorly understood. Different β-blocker agents have been shown to exert beneficial activities both in AMI and heart failure, however, their role in early remodelling after ischemia/reperfusion is to be fully elucidated.We sought to compare the effect of 2 of the most prescribed β-blocker agents in early markers of LV remodelling after AMI.

Methods

A reperfused AMI was induced in Yorshire pigs, being randomized to early intravenous carvedilol, metoprolol or placebo. Twenty-four hours after reperfusion markers of early remodelling were addressed in the LV.

Results

The early administration of both β-blockers is able to significantly reduce macrophage infiltration as well as the expression and activity of MCP-1 and MMP-2 compared to placebo. The effects of carvedilol were much stronger than those of metoprolol. Conversely, carvedilol upregulated the expression TIMP-2 to a greater extent than metoprolol.

Conclusions

In an AMI model closely mimicking human pathophysiology, the early administration of carvedilol reduced the expression of markers associated with early LV remodelling to greater extent than metoprolol. These findings may explain the superior clinical benefits exerted by carvedilol in heart failure.     

Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes

BackgroundThe metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale).ObjectivesThe purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs).MethodsA cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography.ResultsAfter adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335). Relative risk estimations using Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease predictors confirmed that inclusion of HbA1c modified the risk of multiterritorial SA in most risk categories.ConclusionsRoutine use of HbA1c can identify asymptomatic individuals at higher risk of SA on top of traditional CVRFs. Lifestyle interventions and novel antidiabetic medications might be considered to reduce both HbA1c levels and SA in individuals without diabetes.     

Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough

Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.     

Vascular reactivity in patients with undifferentiated connective tissue diseases

Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested.We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI).MethodsRabbits (n = 12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I_Milano, n = 8) or placebo (n = 4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5 cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI.ResultsMDCT detected a significant decrease in plaque burden caused by recombinant apoA-I_Milano (464 [423–535] to 405 [363–435] mm³, p = 0.03) that was confirmed by MRI (324 [286–412] to 298 [282–399] mm³, p = 0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r = 0.750, p < 0.001) and change in plaque burden (r = 0.657, p = 0.020). MDCT overestimated plaque burden compared to MRI.On MDCT, the mean interobserver variability for plaque burden was 2.5 ± 0.4%.ConclusionsIn an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.     

Online Hemodiafiltration Reduces Bisphenol A Levels

Several uremic toxins have been identified and related to higher rates of morbidity and mortality in dialysis patients. Bisphenol A (BPA) accumulates in patients with chronic kidney disease. The aim of this study is to demonstrate the usefulness of online hemodiafiltration (OL‐HDF) in reducing BPA levels. Thirty stable hemodialysis patients were selected to participate in this paired study. During three periods of 3 weeks each, patients were switched from high‐flux hemodialysis (HF‐HD) to OL‐HDF, and back to HF‐HD. BPA levels were measured in the last session of each period (pre‐ and post‐dialysis) using ELISA and HPLC. Twenty‐two patients (mean age 73 ± 14 years; 86.4% males) were included. Measurements of BPA levels by HPLC and ELISA assays showed a weak but significant correlation (r = 0.218, P = 0.012). BPA levels decreased in the OL‐HDF period of hemodialysis, in contrast to the HF‐HD period when they remained stable (P = 0.002). In conclusion, OL‐HDF reduced BPA levels in dialysis patients.