scholarly journals Diabetes concomitant to aortic stenosis is associated with increased expression of NF-κB and more pronounced valve calcification

Diabetologia ◽  
2021 ◽  
Author(s):  
Magdalena Kopytek ◽  
Piotr Mazur ◽  
Michał Ząbczyk ◽  
Anetta Undas ◽  
Joanna Natorska
Keyword(s):  
Type 2 Diabetes ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Aortic Valve Area ◽  
Coagulation Activation ◽  
Valve Calcification

Abstract Aims/hypothesis Type 2 diabetes has been demonstrated to predispose to aortic valve calcification. We investigated whether type 2 diabetes concomitant to aortic stenosis (AS) enhances valvular inflammation and coagulation activation via upregulated expression of NF-κB, with subsequent increased expression of bone morphogenetic protein 2 (BMP-2). Methods In this case–control study, 50 individuals with severe isolated AS and concomitant type 2 diabetes were compared with a control group of 100 individuals without diabetes. The median (IQR) duration of diabetes since diagnosis was 11 (7–18) years, and 36 (72%) individuals had HbA1c ≥48 mmol/mol (≥6.5%). Stenotic aortic valves obtained during valve replacement surgery served for in loco NF-κB, BMP-2, prothrombin (FII) and active factor X (FXa) immunostaining. In vitro cultures of valve interstitial cells (VICs), isolated from obtained valves were used for mechanistic experiments and PCR investigations. Results Diabetic compared with non-diabetic individuals displayed enhanced valvular expression of NF-κB, BMP-2, FII and FXa (all p ≤ 0.001). Moreover, the expression of NF-κB and BMP-2 positively correlated with amounts of valvular FII and FXa. Only in diabetic participants, valvular NF-κB expression was strongly associated with serum levels of HbA1c, and moderately with fructosamine. Of importance, in diabetic participants, valvular expression of NF-κB correlated with aortic valve area (AVA) and maximal transvalvular pressure gradient. In vitro experiments conducted using VIC cultures revealed that glucose (11 mmol/l) upregulated expression of both NF-κB and BMP-2 (p < 0.001). In VIC cultures treated with glucose in combination with reactive oxygen species (ROS) inhibitor (N-acetyl-l-cysteine), the expression of NF-κB and BMP-2 was significantly suppressed. A comparable effect was observed for VICs cultured with glucose in combination with NF-κB inhibitor (BAY 11–7082), suggesting that high doses of glucose activate oxidative stress leading to proinflammatory actions in VICs. Analysis of mRNA expression in VICs confirmed these findings; glucose caused a 6.9-fold increase in expression of RELA (NF-κB p65 subunit), with the ROS and NF-κB inhibitor reducing the raised expression of RELA by 1.8- and 3.2-fold, respectively. Conclusions/interpretation Type 2 diabetes enhances in loco inflammation and coagulation activation within stenotic valve leaflets. Increased valvular expression of NF-κB in diabetic individuals is associated not only with serum HbA1c and fructosamine levels but also with AVA and transvalvular gradient, indicating that strict long-term glycaemic control is needed in AS patients with concomitant type 2 diabetes. This study suggests that maintaining these variables within the normal range may slow the rate of AS progression. Graphical abstract

P5991Cellular mechanisms of aortic valve calcification in primary human valvular interstitial cell culture

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zhiduleva ◽  
O Irtyuga ◽  
P Murtazalieva ◽  
J Sibagatullina ◽  
A Shishkova ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Osteogenic Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Orthotopic Heart Transplantation ◽  
Control Group ◽  
Alizarin Red ◽  
Valve Calcification ◽  
Tricuspid Aortic Valve

Abstract Background Aortic stenosis (AS) is the most common acquired valvular heart disease. Calcification of the aortic valve (AV) cusps is the main pathogenetic mechanism of AS formation, however triggering and progression mechanisms of it are not fully understood. Aortic valve interstitial cells (AVIC) are one of the main cell populations responsible for the AV structure and homeostasis. The aim of the study was to characterize the ability of AVIC to osteogenic differentiation using the model of the primary culture of AVIC of patients with aortic stenosis and assess the expression of genes involved in osteogenesis (RUNX2, BMPG2, SPRY1, SOX9, CTNNB1, POSTN, OPG and OPN). Materials and methods The study was carried out on primary human AVIC culture obtained by enzymatic dissociation of experimental valve specimens from patients with AS (n=15) and the control specimens from the orthotopic heart transplantation recipients (n=10). To assess the osteogenic potential of AVIC, the routine stem cell osteodifferentiation protocol based on the culture medium with addition of inductors (10 mM β-glycerophosphate, 0.1 μM dexamethasone, and 50 μg/ml ascorbic acid) was used. Calcium deposits were demonstrated by Alizarin Red staining. Analysis of the expression of osteogenic differentiation genes, such as RUNX2 (runtrelated transcription factor 2), BMP2 (bone morphogenetic protein 2), SPRY1 (Sprouty RTK signaling antagonist 1), SOX-9 (SRY-box9), CTNNB1 (β-catenin1), POSTN (periostin), OPG (osteoprotegerin), and OPN (osteopontin), was performed by real-time PCR. Results The inductors of osteogenic differentiation provoked greater mineralization of AVIC cultures derived from the patients with AS than that observed in control group (p=0.0003). The expression of RUNX2 and SPRY1 in non-differentiated cells was reduced compared with control cells in patients with bicuspid AV (p=0.02). After 21 days of the osteogenic induction, the expression of RUNX2 and SPRY1 increased in all three groups. At the same time, the expression of SPRY1 was lower in the group with bicuspid AV compared with tricuspid AV (p=0.007). The expression level of BMP2 did not differ between groups in unstimulated AVIC, however, it increased after osteogenic differentiation in the group of patients with tricuspid AV (p=0.017). OPN expression was higher in cells from tricuspid AV, while OPG expression was reduced in patients with both bicuspid and tricuspid AV (p<0.01), No differences were found between the groups) for the remaining genes (POSTIN, CTNNB1, SOX9) before and after stimulation with an osteogenic medium. Conclusions The osteogenic potential of AVIC is increased in patients with aortic stenosis. The gene expression profile of osteogenic differentiation differs in patients with a bicuspid and tricuspid aortic valve. Damage of protective mechanisms may be a potential mechanism for accelerated valve calcification mostly in patients with tricuspid aortic valve. Acknowledgement/Funding Russian Foundation for Basic Research, project 18-015-00016

Abstract 6143: Regression of Aortic Valve Stenosis by ApoA-I Mimetic Peptide Infusions in Rabbits

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
David Busseuil ◽  
Yanfen Shi ◽  
Mélanie Mecteau ◽  
Geneviéve Brand ◽  
Teodora Avram ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Stenosis ◽  
White Male ◽  
Treated Group ◽  
Saline Control ◽  
Control Group ◽  
Clinical Approach ◽  
Aortic Valve Area ◽  
Mimetic Peptide

Purpose : Aortic valve stenosis is the most common valvular heart disease, and standard curative therapy remains open-heart surgical valve replacement. The aim of our experimental study was to determine if ApoA-I mimetic peptide infusions could induce regression of aortic valve stenosis. Methods : Twenty-seven New-Zealand White male rabbits received a cholesterol-enriched diet and vitamin D 2 until significant aortic valve stenosis was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were randomized to receive saline (control group, n =14) or an ApoA-I mimetic peptide (treated group, n =13), 3 times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Results : Aortic valve area improved significantly in the treated group compared to controls after 7 days (20.9±0.9 mm 2 vs. 18.2±0.6 mm 2 , P <0.0001) (corresponding to increases of 15.9% and 1.9%), 10 days (21.5±1.0 mm 2 vs. 19.5±0.6 mm 2 , P =0.0032) (increases of 19.2% vs. 9.1%), and 14 days of treatment (22.4±0.9 mm 2 vs. 20.4±0.6 mm 2 , P =0.0028) (increases of 24.4% vs. 14.2%). Likewise, aortic valve thickness decreased by 19% after 14 days of treatment in the treated group (0.951±0.070 mm at baseline vs. 0.768±0.074 mm at follow-up) whereas it was unchanged in controls ( P <0.0001). Histological analysis revealed that lesion extent at the base of valve leaflets and sinuses of Valsalva was smaller in the treated compared to control group (52.8±12.5% vs. 66.7±9.9%, P =0.032). The ApoA-I mimetic peptide treatment also leads to a reduction in aortic valve calcifications as revealed by the loss of the positive relationship observed in the control group ( r =0.87, P =0.004) between calcifications area and aortic valve thickness. Conclusions : Infusions of an ApoA-I mimetic peptide lead to regression of experimental aortic valve stenosis. These positive results justify the further testing of HDL-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform our clinical approach of this disease.

P1829Accumulation of advanced glycoxidation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kopytek ◽  
M Zabczyk ◽  
A Undas ◽  
J Natorska
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Area ◽  
Science Center ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
End Products

Abstract Background Accumulation of advanced glycoxidation end products (AGEs) leads to chronic inflammation, glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). Purpose To evaluate whether increased valvular accumulation of AGEs in patients with aortic stenosis (AS) and concomitant diabetes (AS-DM) is associated with enhanced valvular inflammation, increased oxidative stress and AS progression. Methods We enrolled 50 patients (28 women), aged 67.2±7.9 years with severe AS (transvalvular gradients: PGmean=52.9±13.4 mmHg, PGmax=84.9±18.7 mmHg), including 30 subjects with type 2 DM (glycaemia 6.3±1.9 mM/l, glycated haemoglobin [HbA1c] 6.9±1.4%), who underwent aortic valve replacement. Valvular expression of AGEs, AGE receptors (RAGE), interleukin-6 (IL-6), prothrombin (FII), C-reactive protein (CRP), and reactive oxygen species (ROS) were evaluated ex vivo by single/double-immunostaining. The percentage of immuno-positive areas was analyzed for each valve. Results There were no differences with regard to age and AS severity between AS and AS-DM patients. Subjects with AS-DM had elevated valvular expression of both AGE and RAGE (41.3±15.2% and 17.6±7.1%, respectively) as compared to non-DM (9.4±3.9% and 3.4±2.4%, respectively; all p<0.001). In AS-DM patients AGE/RAGE showed co-expression in 51.5% of areas. The percentage of ROS-, CRP-, and IL-6-positive areas was elevated within AS-DM compared to AS valves (10.9±2.4%, 6±0.3%, and 5.7±1.4% vs 4.8±1.7%, 2.5±0.1%, and 1.6±0.9%, respectively; all p<0.05). Valvular expression of FII was elevated in AS-DM patients compared to those with AS (17.3±2.5% vs. 11±2%, p<0.05). In AS-DM patients the percentage of valvular AGE-positive areas correlated with HbA1c (r=0.44, p<0.05) and blood glucose levels (r=0.57, p<0,05). The amount of valvular RAGE correlated with HbA1c (r=0.63, p=0.009) but not with blood glucose levels. In AS-DM patients we found positive associations between the amount of valvular AGE and IL-6 with disease severity measured as aortic valve area (AVA; r=−0.83, p<0.0001; r=−0.64, p<0.001, respectively) and PGmax (r=0.54, p<0.05; r=0.52, p<0.05, respectively) but not with PGmean. There were no associations between PGmax/PGmean and HbA1c levels in the whole AS-DM group. However, patients with HbA1c >6.5% (n=19) or ≤6.5% (n=11) were characterized by higher PGmax and PGmean compared to those with HbA1c ≤6.5% (93.3±8.9 mmHg vs 67.5±7.2 mmHg and 63.6±6.5 mmHg vs 52±77 mmHg, respectively, all p<0.05). Conclusions Patients with AS-DM compared to those with AS demonstrate enhanced valvular AGEs accumulation and increased RAGE expression along with accelerated inflammation and oxidative stress. The accumulation of valvular AGE correlated with both hyperglycaemia and AS severity. Acknowledgement/Funding This work was supported by the grant from the Polish National Science Center (UMO-2015/19/B/NZ5/00647 to J.N).

scholarly journals The effects of insulin and liraglutide on osteoprotegerin and vascular calcification in vitro and in patients with type 2 diabetes

2015 ◽  
Vol 173 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Colin Davenport ◽  
Wan A Mahmood ◽  
Hannah Forde ◽  
David T Ashley ◽  
Amar Agha ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
Vascular Calcification ◽  
Statistical Significance ◽  
Control Group ◽  
Oral Hypoglycemics ◽  
Osteogenic Gene Expression

ObjectiveVascular calcification (VC) is inhibited by the glycoprotein osteoprotegerin (OPG). It is unclear whether treatments for type 2 diabetes are capable of promoting or inhibiting VC. The present study examined the effects of insulin and liraglutide on i) the production of OPG and ii) the emergence of VC, bothin vitroin human aortic smooth muscle cells (HASMCs) andin vivoin type 2 diabetes.Design/methodsHASMCs were exposed to insulin glargine or liraglutide, after which OPG production, alkaline phosphatase (ALP) activity and levels ofRunx2,ALPand bone sialoprotein (BSP) mRNA were measured. A prospective, nonrandomised human subject study was also conducted, in which OPG levels and coronary artery calcification (CAC) were measured in a type 2 diabetes population before and 16 months after the commencement of either insulin or liraglutide treatment and in a control group that took oral hypoglycemics only.ResultsExposure to insulin glargine, but not liraglutide, was associated with significantly decreased OPG production (11 913±1409 pg/104cells vs 282±13 pg/104cells, control vs 10 nmol/l insulin,P<0.0001), increasedALPactivity (0.82±0.06 IU/104cells vs 2.40±0.16 IU/104cells, control vs 10 nmol/l insulin,P<0.0001) and increased osteogenic gene expression by HASMCs. In the clinical study (n=101), insulin treatment was associated with a significant reduction in OPG levels and, despite not achieving full statistical significance, a trend towards increased CAC in patients.ConclusionExogenous insulin down-regulated OPGin vitroandin vivoand promoted VCin vitro. Although neither insulin nor liraglutide significantly affected CAC in the present pilot study, these data support the establishment of randomised trials to investigate medications and VC in diabetes.

scholarly journals Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System

10.2196/13186 ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. e13186 ◽  
Author(s):  
Suresh Giritharan ◽  
Felino Cagampang ◽  
Christopher Torrens ◽  
Kareem Salhiyyah ◽  
Simon Duggan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Replacement ◽  
Aortic Valve Disease ◽  
Serum Biomarkers ◽  
Rate Of Progression ◽  
One Stop ◽  
Ct And Mri

Background Type 2 diabetes mellitus (T2DM) has been established as an important independent risk factor for aortic stenosis. T2DM patients present with a higher degree of valve calcification and left ventricular dysfunction compared to patients without diabetes. This may be due to an increase in incidence and severity of myocardial fibrosis. Currently, there is no reliable method of determining the optimal timing of intervention for a patient with asymptomatic aortic stenosis or predicting when a patient will become symptomatic. Research into serum biomarkers to predict subclinical onset and track progression of aortic stenosis is hampered by the multimodal nature of the pathological processes ultimately responsible for aortic stenosis. Objective The aim of this study is to prove that an approach using a combination of serum biomarkers and the echocardiographic parameter global longitudinal strain (GLS) can be used to establish baseline status of fibrocalcific aortic valve disease, predict rate of progression, and quantitatively assess any regression of these processes following aortic valve replacement in patients with T2DM. Methods Validated serum biomarkers for the separate processes of calcification, inflammation, oxidative stress and fibrosis can be used to quantify onset and rate of progression of aortic stenosis. This, in combination with the echocardiographic parameter GLS, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, noninvasive one-stop assessment of aortic stenosis in patients with T2DM. The serum biomarkers BNP (B-type natriuretic peptide), Gal-3 (Galectin-3), GDF-15 (growth differentiation factor-15), sST2 (soluble suppression of tumorigenicity 2), OPG (osteoprotegerin), and microRNA 19b and 21 will be sampled from patients undergoing aortic valve replacement (with and without T2DM), patients with T2DM but without aortic valve disease and healthy volunteers. These patients will also undergo computed tomography (CT) scans for calcium scoring, magnetic resonance imaging (MRI) to quantify myocardial fibrosis, and myocardial strain imaging with speckle-tracking echocardiography. Samples of calcified native aortic valve and a biopsy of ventricular myocardium will be examined histologically to determine the quantity and distribution of calcification and fibrosis, and the secretome of these tissue samples will also be analyzed for levels of the same biomarkers as in the serum samples. All patients will be followed up with in 3 months and 12 months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis and CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment. Results Using all of the information gathered throughout the study will yield a ranking scale for use in the clinic, which will provide each patient with a fibrocalcific profile. This can then be used to recommend an optimal time for intervention. Conclusion A reliable, validated set of serum biomarkers combined with an inexpensive bedside echocardiographic examination can now form the basis of a one-stop outpatient-based assessment service, which will provide an accurate risk assessment in patients with aortic stenosis at first contact. International Registered Report Identifier (IRRID) PRR1-10.2196/13186

scholarly journals Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Bai ◽  
Ke Mo ◽  
Guirong Wang ◽  
Wanling Chen ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Receptors ◽  
Control Group ◽  
Sensitivity Index

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was to investigate the effects and possible mechanisms of gastrodin on the treatment of T2DM. In vivo, after treatment with gastrodin for 6 weeks, fasting blood glucose levels, blood lipid metabolism, and insulin sensitivity index values were remarkably reduced compared with those of the diabetic control group. The values of aspartate aminotransferase and alanine aminotransferase also showed that gastrodin alleviates liver toxicity caused by diabetes. Moreover, gastrodin relieved pathological damage to the pancreas in T2DM rats. In vitro, gastrodin alleviated insulin resistance by increasing glucose consumption, glucose uptake, and glycogen content in dexamethasone-induced HepG2 cells. The Western blotting results showed that gastrodin upregulated the expression of insulin receptors and ubiquitin-specific protease 4 (USP4) and increased the phosphorylation of GATA binding protein 1 (GATA1) and protein kinase B (AKT) in vivo and in vitro. Furthermore, gastrodin decreased the ubiquitin level of the insulin receptor via UPS4 and increased the binding of GATA1 to the USP4 promoter. Additionally, administration of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway inhibitors MK-2206 and LY294002 abolished the beneficial effects of gastrodin. Our results indicate that gastrodin promotes the phosphorylation of GATA1 via the PI3K/AKT pathway, enhances the transcriptional activity of GATA1, and then increases the expression level of USP4, thereby reducing the ubiquitination and degradation of insulin receptors and ultimately improving insulin resistance. Our study provides scientific evidence for the beneficial actions and underlying mechanism of gastrodin in the treatment of T2DM.

scholarly journals COMPARISION OF INDEXED PROJECTED AORTIC VALVE AREA AND AORTIC VALVE CALCIFICATION DENSITY IN PATIENTS WITH LOW FLOW, LOW GRADIENT AORTIC STENOSIS

2019 ◽  
Vol 35 (10) ◽  
pp. S24
Author(s):  
J. Grenier-Delaney ◽  
M. Annabi ◽  
I. Burwash ◽  
J. Bergler-Klein ◽  
J. Mascherbauer ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Low Flow ◽  
Aortic Valve Area ◽  
Aortic Valve Calcification ◽  
Valve Calcification ◽  
Valve Area

P3369Impact of global left ventricular afterload, aortic stenosis severity and left ventricular hypertrophy on global myocardial work

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Ilardi ◽  
S Marchetta ◽  
R E Dulgheru ◽  
S Cimino ◽  
G D'Amico ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Stroke Volume ◽  
Speckle Tracking ◽  
Left Ventricular ◽  
Low Flow ◽  
Control Group ◽  
Aortic Valve Area ◽  
Global Work ◽  
Valve Area

Abstract Background Myocardial work (MW) is an innovative tool, that derives from myocardial strain with the advantage to incorporate measurement of deformation and load. Therefore, it could be useful in conditions of increased afterload, such as aortic stenosis (AS). To date, little is known about the changes in MW related to AS severity, left ventricle (LV) geometry and arterial compliance. Purpose We investigated the effect of valvulo-arterial impedance (Zva), stroke volume and LV hypertrophy in patients with AS and preserved LV ejection fraction (EF). Methods We retrospectively analyzed 283 patients (60% males, mean age 71±12 years old) with AS (aortic valve area ≤1.5 cm2) and LVEF≥50%. Exclusion criteria were more than mild associated cardiac valve lesion, left bundle branch block, and suboptimal quality of speckle-tracking image analysis. The control group included 50 patients matched for age and sex. Clinical, demographic and resting echocardiographic data were recorded, including quantification of 2D global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Results Patients with AS had higher systolic (p=0.017) and diastolic arterial pressure (p=0.007), increased LV wall thickness, mass index (p<0.001) and volumes (p=0.045) compared to controls. Greater indexed left atrial volume, E/e' and trans-tricuspid gradient were also observed in the AS group (p<0.001). As expected, speckle tracking analysis revealed significant lower GLS in AS than in control group (18.7±3.2 vs 20.7±2.1%, p<0.001). Conversely, increased values of GCW and GWI (respectively 2965±647 vs 2360±353 mmHg%, and 2535±559 vs 2005±302 mmHg%, p<0.001) were observed in patients with AS. Besides, GWW was significantly increased in AS vs controls (147±108 vs 90±49 mmHg%, p=0.001), with no changes in terms of GWE (95±4 vs 96±2%, p=0.110). When patients were stratified according to the AS severity, the analysis of variance revealed that GCW, GWI and GWW significantly increased with higher transaortic mean gradient and lower aortic valve area (p<0.001). Also Zva demonstrated to impact on CGW (p=0.040) and GWW (p<0.001), with increased values in presence of increased global LV afterload (Zva>4.5 mmHg/ml/m2). Conversely, patients with low-flow AS (stroke volume index <35 ml/m2) showed lowers values of GCW (p=0.014) and GWI (p=0.001) compared to normal flow AS, but increased GWW (p=0.041) and reduced GWE (93±7 vs 95±4%, p=0.010). Finally, LV geometry didn't influence significantly GCW and GWE, only an increase of GWW was observed in patients with eccentric hypertrophy (p=0.031). Conclusion In patients with AS and preserved LVEF, GLS reduction is accompanied by an increase of GCW, GWI and GWW, without affecting the GWE. These modifications seem to be correlated to the severity of AS, low-flow state and increased global LV afterload but not on the grade of LV hypertrophy.

scholarly journals Hypoglycemic Activity of Medicinal Plants Used among the Cakchiquels in Guatemala for the Treatment of Type 2 Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Adolfo Andrade-Cetto ◽  
Elda Carola Cruz ◽  
Christian Alan Cabello-Hernández ◽  
René Cárdenas-Vázquez
Keyword(s):  
Type 2 Diabetes ◽  
Hypoglycemic Effect ◽  
Hypoglycemic Agents ◽  
Limb Amputation ◽  
Control Group ◽  
High Blood Glucose ◽  
Major Health Problem ◽  
Control Drug

Type 2 diabetes (T2D) is a major health problem worldwide. In this condition, the organism can produce insulin but becomes resistant to it; thus the insulin is ineffective. High blood glucose levels are a result of insulin resistance and insulin deficiency; they produce diabetes-associated complications such as kidney failure, blindness, cardiovascular disease, and lower-limb amputation. In Guatemala, there were over 752.700 cases of the disease in 2017 with prevalence of 8.4 (IDF, 2017). The use of plants for medicinal purposes has been practiced in the country since pre-Hispanic times. Among the Cakchiquels, the aerial parts of Hamelia patens Jacq., Neurolaena lobata (L.) R.Br. ex Cass., and Solanum americanum Mill. and the cortex of Croton guatemalensis Lotsy are used to treat type 2 diabetes. The aim of the present study was to confirm the hypoglycemic effect of the plants under normal conditions and under maltose and sucrose tolerance tests, as well as to test the activity of the plant extracts in vitro against alpha-glucosidases types I and II. In agreement with the traditional usage of the plants, in normal conditions without a sugar load, the extracts produced a statistically significant hypoglycemic effect similar to the control drug glibenclamide. When the sugar load was maltose, only Croton and Solanum produced a statistically significant (p < 0.05) hypoglycemic effect compared to the control drug, but when the sugar was sucrose, Croton and Hamelia produced a statistically significant effect (p < 0.05) beginning at 30 min compared to the control group, while Solanum did so at 60 min and Neurolaena at 90 min. In vitro assays showed that the extracts inhibited yeast alpha-glucosidases but not the rat intestinal ones. Of the tested plants, Croton exert an effect both under sugars' tests and under a normal tolerance test; these results suggest the potential use of this plant. The results presented here provided evidence based on the use of these plants as hypoglycemic agents in the treatment of type 2 diabetes.

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