Evaluation of left and right ventricular functions pre and post balloon mitral Valvuloplasty using speckled tracking echocardiography

Background: Rheumatic heart disease remains a considerable cause of cardiovascular morbidity and mortality in developing countries such as India. The aim of the present study was to compare ventricular (LV and RV) function in patients with severe mitral stenosis (MS) undergoing balloon mitral Valvuloplasty (BMV) with those on medical management and also with healthy controls and to assess the burden of ventricular (LV and RV) systolic dysfunction, its determinants, and its reversibility with percutaneous balloon mitral Valvuloplasty using speckle tracking echocardiography in patients with severe MS.Methods: This prospective study was performed in a tertiary care center, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow in patients with severe MS, from September 2014 to September 2015. A total of 60 were divided into three groups. Cases (n=30), patients with severe MS undergoing BMV; case controls (n=20), patients with severe MS who did not give consent for BMV and chose medical management and healthy controls (n=10). Cases who underwent BMV were analyzed pre and post BMV and detailed echocardiographic and speckle-tracking echocardiography (STE) was done at baseline, 24-48 hours after BMV and at post one month after BMV. Appropriate statistical analysis was applied and different parameters were compared.Results: Most of the cases (56.7%) control (65%) and healthy controls (40%) were between 21-30 years of age. Female preponderance was observed in the study. A significant (p=0.01) decrease in the LA size, PASP (p=0.0001), MV PG area (p=0.0001) and significant (p=0.0001) increase in the LVEF, MVA area was observed from baseline to post 24-48 hours and at post one month after BMV among cases. Significant improvement was noticed in longitudinal strain and regional rotation in different LV segments as assessed by STE at post 24-48 hours and post one month after BMV (p value 0.001) among cases. No significant (p>0.05) difference in the 2D echo parameters was seen from baseline to follow-ups among the case controls. No significant improvement was observed in regional rotation, global rotation in different LV and RV segments after one month as assessed by STE among case controls whereas significant improvement was seen in cases.Conclusions: BMV results in marked improvement in LV and RV GLS immediately post BMV with improvement towards normalization at follow up after one month and the same can be easily assessed by Speckle tracking echocardiography

Evaluation of coronary microcirculation by myocardial contrast echocardiography in patients of ST elevation myocardial infarction

Background: No reflow phenomenon observed during catheter intervention has been associated with poor cardiovascular outcomes. Assessment of filling defect by myocardial contrast echocardiography (MCE) correlates with no reflow. Limited studies are available for the same. This study was designed to look for impact of type of therapy for revascularization (whether percutaneous coronary intervention or thrombolysis) and its evaluation by MCE and follow up echocardiography parameters.Methods: Total 50 consecutive patients of ST-elevation myocardial infarction (STEMI) were taken study including recent STEMI (within 7 days). After all routine investigations patient underwent coronary angiography and percutaneous coronary intervention (PCI) procedure. Following completion of procedure, thrombolysis in myocardial infarction (TIMI) flow, TIMI frame count, and myocardial blush grade were calculated and noted. Post revascularization contrast echocardiography was done after patient stabilization. Findings were correlated with cath-lab parameters applying appropriate statistical tests. Follow up was planned after 30 days.Results: 50 consecutive patients admitted with acute myocardial infarction (MI) or recent MI (0-7 day) who underwent primary PCI - 82% (n=41) or thrombolysed with various thrombolytic agents - 18% (n=9). Mean age of the study group was 55.02±12.65 years. There was significant association in between TIMI 3 flow and absence of filling defect in MCE (p=0.03), but no significant association found in between revascularization therapy (Either PCI or Thrombolysis) and filling defect in MCE (p=0.08).Conclusions: Our study found good correlation between myocardial contrast score with angiographically measured TIMI flow and improved echocardiographic findings on follow up

Coronary angiographic abnormalities in patients of diabetes mellitus and metabolic syndrome

Background: Diabetes mellitus and Metabolic syndrome, both are established risk factors for CAD. In our study, we tried to compare the effects of these two diseases individually as well as their combined effect.Methods: we performed an Observational, cross-sectional, hospital-based, single center study on 240 patients presenting at our hospital with chest pain. we assessed the severity of CAD with Syntax score and divided the study population into three groups with SS of =33.Results: statistically significant difference was found in each of the first three groups of combined MS plus DM, only MS without DM, only DM without MS when compared with the fourth group of nondiabetics nonmetabolic syndrome patients. Strongest difference was found between patients with combined diabetes and metabolic syndrome with those who had none of these (<0.001). Thus, complexity of CAD is much severe in patients who have diabetes and/or metabolic syndrome.Conclusions: Patients having diabetes mellitus and/or metabolic syndrome are found to have more severe form of coronary artery disease than those who don’t have either of these. However, presence of both diabetes and metabolic syndrome has not been found to impose any significant additional risk than their isolated presence

Geraniol attenuates osteoclast differentiation by suppressingNF-kB activity and expression of osteoclastogenic genes

Osteoporotic patients have lower bone mass due to increased bone resorption by osteoclasts. The aim of this study was to investigate the cytotoxic and antiosteoclastogenic effects of geraniol, a natural monoterpene on human CD14+ monocytes (ex vivo) and murine RAW264.7 macrophages (in vitro) using alamar blue and tartrate resistant acid phosphatase staining respectively. The anti-osteoclastogenic activity of geraniol was further explored by analyzing its effects on actin ring formation and bone resorptive function of osteoclasts. Geraniol significantly (p < 0.001) inhibited osteoclast formation in CD14+ monocytes and RAW264.7 macrophages without cytotoxicity. Moreover, reduced osteoclastogenesis in these cells led to an arrest in actin ring formation and diminished bone resorption. Analysis of underlying molecular mechanisms revealed that geraniol alleviated NF-kB activity, an indispensable upstream modulator of osteoclast formation. Furthermore, expression of key osteoclastogenic genes such as dendritic cell-specific transmembrane protein (DC-STAMP) involved in cell-cell fusion and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor essential for osteoclast differentiation was downregulated by geraniol. These observations indicate that inhibition of osteoclast differentiation is presumably one of the pharmacological properties of geraniol.Grants from the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship; RESCOM, University of Pretoria and the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being.http://link.springer.com/journal/442017-12-31hb2016Food ScienceHuman NutritionPhysiolog

Inhibitory effects of eugenol on RANKL-induced osteoclast formation via attenuation of NF-kappa B and MAPK pathways

Bone loss diseases are often associated with increased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. Compounds that can attenuate RANKL-mediated osteoclast formation are of great biomedical interest. Eugenol, a phenolic constituent of clove oil possesses medicinal properties; however, its anti-osteoclastogenic potential is unexplored hitherto. Here, we found that eugenol dose-dependently inhibited the RANKL-induced multinucleated osteoclast formation and TRAP activity in RAW264.7 macrophages. The underlying molecular mechanisms included the attenuation of RANKL-mediated degradation of IκBα and subsequent activation of NF-κB pathway. Furthermore, increase in phosphorylation and activation of RANKL-induced mitogen-activated protein kinase pathways (MAPK) was perturbed by eugenol. RANKL-induced expression of osteoclast-specific marker genes such as TRAP, cathepsin K (CtsK) and matrix metalloproteinase-9 (MMP-9) was remarkably downregulated by eugenol. These findings provide the first line of evidence that eugenol mediated attenuation of RANKL-induced NF-κB and MAPK pathways could synergistically contribute to the inhibition of osteoclast formation. Eugenol could be developed as therapeutic agent against diseases with excessive osteoclast activity.The Vice Chancellor’s Postdoctoral Research Fellowship and Institute for Food, Nutrition and Well-being, University of Pretoria.http://informahealthcare.com/journal/cts2016-06-30hb201

Piperine alleviates osteoclast formation through the p38/c-Fos/NFATc1 signaling axis

Increased bone fracture is one of the health risk factors in patients with bone loss related disorders such as osteoporosis and breast cancer metastasis to bone. Over activity of osteoclasts leads to uncoupling of bone remodeling favoring bone loss over bone formation. Receptor activator of nuclear factor-κβ ligand (RANKL) triggers the differentiation pathway leading to multinucleated osteoclast formation. Modulation of RANKL or its downstream signaling pathways involved in osteoclast formation is of significant interest in the development of anti-resorptive agents. In this study, we investigated the effects of piperine, an alkaloid present in Piper nigrum L. on osteoclast formation. Piperine inhibited tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast formation in murine RAW264.7 macrophages and human CD14+ monocytes induced by RANKL and breast cancer cells. Piperine attenuated the p38-mitogen activated protein kinase (MAPK) pathway activation, while the extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) or NF-κβ pathways downstream of RANKL remained unaffected. Concomitantly, expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcription factors involved in osteoclastogenesis were remarkably inhibited by piperine. Furthermore, piperine disrupted the actin ring structure and bone resorption, a characteristic hallmark of osteoclasts. Collectively, these results suggest that piperine inhibits osteoclast differentiation by suppressing the p38/NFATc1/c-Fos signaling axis.RESCOM, University of Pretoria, the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship, the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being and the Struwig-Germeshuysen Research Trust, South Africa.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1872-80812016-11-30hb201

Arachidonic acid and Docosahexaenoic acid suppress osteoclast formation and activity in human CD14+ monocytes, in vitro

An unbalanced diet can have adverse effects on health. Long chain polyunsaturated fatty acids (LCPUFAs) have been the focus of research owing to their necessity of inclusion in a healthy diet. However, the effects of LCPUFAs on human osteoclast formation and function have not been explored before. A human CD14+ monocyte differentiation model was used to elucidate the effects of an ω-3 LCPUFA, docosahexaenoic acid (DHA), and an ω-6 LCPUFA, arachidonic acid (AA), on osteoclast formation and activity. CD14+ monocytes were isolated from peripheral blood of healthy donors and stimulated with macrophage colony stimulating factor and receptor activator of nuclear factor kappa-B ligand to generate osteoclasts. Data from this study revealed that both the LCPUFAs decreased osteoclast formation potential of CD14+ monocytes in a dose-dependent manner when treated at an early stage of differentiation. Moreover, when exposed at a late stage of osteoclast differentiation AA and DHA impaired the bone resorptive potential of mature osteoclasts without affecting osteoclast numbers. AA and DHA abrogated vitronectin receptor expression in differentiating as well as mature osteoclasts. In contrast, the degree of inhibition for calcitonin receptor expression varied between the LCPUFAs with only AA causing inhibition during osteoclast differentiation. Furthermore, AA and DHA down regulated the expression of key osteoclast-specific genes in differentiating as well as mature osteoclasts. This study demonstrates for the first time that LCPUFAs can modulate osteoclast formation and function in a human primary osteoclast cell line.S1 Fig. Effects of AA and DHA on cell viability. CD14+ monocytes were treated with indicated concentrations of AA and DHA for 48 h and cell viability was measured by alamar blue assay. The results are representative of two independent experiments conducted in triplicate and expressed as percentage cell viability relative to the control.The South African Medical Research Council (MRC), the University of Pretoria School of Medicine Research Committee (RESCOM) and the University of Pretoria Postgraduate Study Abroad Programme.http://www.plosone.orgam201

Study of coronary artery disease in young population of Central India

Background: Coronary heart disease is the most common indication among cardiovascular diseases (CVD) and a major cause of mortality and morbidity. According to global burden of disease study estimates, nearly 24.8% of all deaths in India are attributable to CVD. Objectives of the current research study were to establish a correlation between varied risk factors and coronary artery disease (CAD), to determine angiographic characteristics individually in patients with multiple risk factors and to evaluate number of vessels involved in CAD.Methods: Present study was a prospective study conducted on 50 patients with acute coronary syndrome below 40 yrs of age admitted at the department of cardiology, Superspeciality hospital, NSCB medical college, Jabalpur. All patients included in the study were subjected to coronary angiography. The angiographic characteristics such as extent of CAD (characterized by the number of vessels with angiographic lesions) were determined.Results: Current study findings depicted that most of CAD patients were in age group of 36-40 years. Proportion of males was higher than females. One-fifth of patients were diabetics and 34.0% were hypertensive. It was observed that 54.0% CAD patients had history of smoking and 32.0% had history of premature CAD. Most of patients exhibited single vessel disease in CAG and left anterior descending (LAD) was the most commonly involved artery.Conclusions: Smoking was concluded as one of the major risk factor associated with CAD and most of patients exhibited single vessel disease, LAD being the most commonly involved artery. Significant number of patients with family history depicted high risk for CAD. Males were concluded to be more prone to CAD at younger age

Ellagic acid inhibits RANKL-induced osteoclast differentiation by suppressing the p38 MAP kinase pathway

Bone undergoes continuous remodeling by a coupled action between osteoblasts and osteoclasts. During osteoporosis, osteoclast activity is often elevated leading to increased bone destruction. Hence, osteoclasts are deemed as potential therapeutic targets to alleviate bone loss. Ellagic acid (EA) is a polyphenol reported to possess anticancer, antioxidant and anti-inflammatory properties. However, its effects on osteoclast formation and function have not yet been examined. Here, we explored the effects of EA on RANKL-induced osteoclast differentiation in RAW264.7 murine macrophages (in vitro) and human CD14+monocytes (ex vivo). EA dose-dependently attenuated RANKL-induced TRAP+ osteoclast formation in osteoclast progenitors with maximal inhibition seen at 1 µM concentration without cytotoxicity. Moreover, owing to perturbed osteoclastogenesis, EA disrupted actin ring formation and bone resorptive function of osteoclasts. Analysis of the underlying molecular mechanisms revealed that EA suppressed the phosphorylation and activation of the p38 MAP kinase pathway which subsequently impaired the RANKL-induced differentiation of osteoclast progenitors. Taken together, these novel results indicate that EA alleviates osteoclastogenesis by suppressing the p38 signaling pathway downstream of RANKL and exerts inhibitory effects on bone resorption and actin ring formation.RESCOM, University of Pretoria; the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being; and in part by the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship.http://link.springer.com/journal/122722018-01-31hb2017Human NutritionPhysiolog

Ferulic acid impairs osteoclast fusion and exacerbates survival of mature osteoclasts

Elevated bone loss induced by osteoclasts is a critical and most commonly observed pathological complication during osteolytic diseases such as osteoporosis. Hence, attenuation of osteoclast formation or function is a classical therapeutic approach to regulate bone loss. In this study, we found that ferulic acid (FA), a natural compound potently inhibited osteoclast formation in human CD14+ peripheral blood monocytes (PBMCs) ex vivo with an IC50 of 39 μM.Moreover, due to impaired differentiation of osteoclast progenitors, actin ring formation and bone resorption activity were also perturbed. Investigation of underlying molecular mechanisms revealed that FA inhibited the RANKL-induced expression of dendritic cell-specific transmembrane protein (DC-STAMP), a critical regulator of osteoclast fusion. In addition, expression of matrix metalloproteinase-9 (MMP-9) and cathepsin K (CTSK), the key osteoclast specific lysosomal proteases involved in bone matrix resorption were severely aggravated by FA. A significant reduction in mature osteoclast numbers was detected in the presence of FA accompanied by increased caspase-3 activity and DNA-fragmentation, a characteristic hallmark of apoptosis. Collectively, these results suggested that FA inhibited osteoclast fusion by suppressing the expression of DC-STAMP and induced apoptosis in mature osteoclasts by the caspase-3 pathway.Grants from RESCOM, University of Pretoria; the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being; and in part by the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship.http://link.springer.com/journal/106162017-10-31hb2016Human NutritionPhysiolog