Distinct Effects of Unfractionated Heparin versus Bivalirudin on Circulating Angiogenic Peptides

Background: Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. Methodology/Principal Findings: We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 26296313 % and 253654%, respectively, within 30 minutes of UFH therapy (p,0.01 for both; n = 8). VEGF levels decreased by 93.265 % in patients treated with UFH (p,0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 an

Ethnobotany in the Nepal Himalaya

<p>Abstract</p> <p>Background</p> <p>Indigenous knowledge has become recognized worldwide not only because of its intrinsic value but also because it has a potential instrumental value to science and conservation. In Nepal, the indigenous knowledge of useful and medicinal plants has roots in the remote past.</p> <p>Methods</p> <p>The present study reviews the indigenous knowledge and use of plant resources of the Nepal Himalayas along the altitudinal and longitudinal gradient. A total of 264 studies focusing on ethnobotany, ethnomedicine and diversity of medicinal and aromatic plants, carried out between 1979 and 2006 were consulted for the present analysis. In order to cross check and verify the data, seven districts of west Nepal were visited in four field campaigns.</p> <p>Results</p> <p>In contrast to an average of 21–28% ethnobotanically/ethnomedicinally important plants reported for Nepal, the present study found that up to about 55% of the flora of the study region had medicinal value. This indicates a vast amount of undocumented knowledge about important plant species that needs to be explored and documented. The richness of medicinal plants decreased with increasing altitude but the percentage of plants used as medicine steadily increased with increasing altitude. This was due to preferences given to herbal remedies in high altitude areas and a combination of having no alternative choices, poverty and trust in the effectiveness of folklore herbal remedies.</p> <p>Conclusion</p> <p>Indigenous knowledge systems are culturally valued and scientifically important. Strengthening the wise use and conservation of indigenous knowledge of useful plants may benefit and improve the living standard of poor people.</p

Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers.</p> <p>Methods</p> <p>Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months.</p> <p>Results</p> <p>In a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤ 40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months.</p> <p>Conclusions</p> <p>We identified TGFBR1 as a new candidate prognostic biomarker after acute MI.</p

Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project

Background: Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings: We tested a set of $\sim$50,000 polymorphisms from $\sim$2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance: We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans

Effects of different types of statins on lipid profile: a perspective on Asians

Context: The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. Evidence Acquisition: PubMed searches were conducted using the keywords ‘statin, effect, and lipid profile’ from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. Results: CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. Conclusions: The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary

Socialization, legitimation and the transfer of biomedical knowledge to low- and middle-income countries: analyzing the case of emergency medicine in India

BACKGROUND: Medical specialization is a key feature of biomedicine, and is a growing, but weakly understood aspect of health systems in many low- and middle-income countries (LMICs), including India. Emergency medicine is an example of a medical specialty that has been promoted in India by several high-income country stakeholders, including the Indian diaspora, through transnational and institutional partnerships. Despite the rapid evolution of emergency medicine in comparison to other specialties, this specialty has seen fragmentation in the stakeholder network and divergent training and policy objectives. Few empirical studies have examined the influence of stakeholders from high-income countries broadly, or of diasporas specifically, in transferring knowledge of medical specialization to LMICs. Using the concepts of socialization and legitimation, our goal is to examine the transfer of medical knowledge from high-income countries to LMICs through domestic, diasporic and foreign stakeholders, and the perceived impact of this knowledge on shaping health priorities in India. METHODS: This analysis was conducted as part of a broader study on the development of emergency medicine in India. We designed a qualitative case study focused on the early 1990s until 2015, analyzing data from in-depth interviewing (n = 87), document review (n = 248), and non-participant observation of conferences and meetings (n = 6). RESULTS: From the early 1990s, domestic stakeholders with exposure to emergency medicine in high-income countries began to establish Emergency Departments and initiate specialist training in the field. Their efforts were amplified by the active legitimation of emergency medicine by diasporic and foreign stakeholders, who formed transnational partnerships with domestic stakeholders and organized conferences, training programs and other activities to promote the field in India. However, despite a broad commitment to expanding specialist training, the network of domestic, diasporic and foreign stakeholders was highly fragmented, resulting in myriad unstandardized postgraduate training programs and duplicative policy agendas. Further, the focus in this time period was largely on training specialists, resulting in more emphasis on a medicalized, tertiary-level form of care. CONCLUSIONS: This analysis reveals the complexities of the roles and dynamics of domestic, diasporic and foreign stakeholders in the evolution of emergency medicine in India. More research and critical analyses are required to explore the transfer of medical knowledge, such as other medical specialties, models of clinical care, and medical technologies, from high-income countries to India