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

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

Constitutive L-Sox5 overexpression delays differentiation of ATDC5 cells into chondrocytes and correlates with reduced expression of differentiation markers

L-Sox5 is a member of sex-determining region Y-type high mobility group box (SOX) family of transcription factors. We assessed the effects of retroviral overexpression of L-Sox5 on chondrocyte differentiation using the clonal murine cell line ATDC5. We observed a temporal-restricted expression pattern of L-Sox5 in insulininduced ATDC5 cells differentiating toward chondrocyte lineage. The protein expression levels of L-Sox5 showed a drastic decrease in contrast to unaltered mRNA levels during differentiation. L-Sox5 delayed the differentiation of ATDC5 cells as evidenced by Alcian blue staining for proteoglycan synthesis. The mRNA levels of chondrocyte and hypertrophic/osteoarthritic markers were markedly decreased or delayed in L-Sox5 overexpressing cells. L-Sox5 abrogated the promoter activity of Runx2. These results suggest that L-Sox5 protein expression may diminish along with the progress of chondrogenic differentiation. L-Sox5 may act as a negative regulator if expressed aberrantly at least in part by regulating the critical fate of chondrogenesis.National Natural Science Foundation of China (30270660), the Jilin Province Science and Technology Development Project (20040114), the Fok Ying Tung Education Foundation (91025), and the Training Fund of NENU’S Scientific Innovation Project NENUSTC08015).http://link.springer.com/journal/110102016-03-31hb201

Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3

Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. TSP-1 is highly upregulated during early stage of osteogenesis, whereas it inhibits terminal osteoblast differentiation. Expression of TSP-1 is downregulated in cancer cells, and its ectopic expression has been shown to restrain tumor growth. Transcriptional regulation of TSP-1 in osteogenesis and cancer is poorly understood; this prompted us to study its regulation by the two key regulators of the aforementioned processes: Runx2 and Runx3. Through a PCR-based cDNA subtraction technique, we identified and cloned a cDNA fragment for mouse TSP-1, whose expression was dramatically upregulated in response to Runx2 expression in mesenchymal stem cells. Moreover, TSP-1 expression was considerably reduced in the lung of Runx2 knockout mouse. On the other hand, TSP-1 gene expression drastically increased at both the transcriptional and translational levels in response to Runx3 expression in B16-F10 melanoma cells. In line with this, Runx2 and Runx3 bound to the TSP-1 promoter and stimulated its activity. Hence, these results provide first line of evidence that TSP-1 is a transcriptional target gene of Runx2 and Runx3