Valsartan in the Treatment of Heart Attack Survivors

Survivors of myocardial infarction (MI) are at high risk of disability and death. This is due to infarct-related complications such as heart failure, cardiac remodeling with progressive ventricular dilation, dysfunction, and hypertrophy, and arrhythmias including ventricular and atrial fibrillation. Angiotensin (Ang) II, the major effector molecule of the renin–angiotensin–aldosterone system (RAAS) is a major contributor to these complications. RAAS inhibition, with angiotensin-converting enzyme (ACE) inhibitors were first shown to reduce mortality and morbidity after MI. Subsequently, angiotensin receptor blockers (ARBs), that produce more complete blockade of the effects of Ang II at the Ang II type 1 (AT1) receptor, were introduced and the ARB valsartan was shown to be as effective as an ACE inhibitor in reducing mortality and morbidity in high-risk post-MI suvivors with left ventricular (LV) systolic dysfunction and and/or heart failure and in heart failure patients, respectively, in two major trials (VALIANT and Val-HeFT). Both these trials used an ACE inhibitor as comparator on top of background therapy. Evidence favoring the use of valsartan for secondary prevention in post-MI survivors is reviewed

Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly

Elderly patients (age ≥65 years) with hypertension are at high risk for vascular complications, especially when diabetes is present. Antihypertensive drugs that inhibit the renin-angiotensin system have been shown to be effective for controlling blood pressure in adult and elderly patients. Importantly, renin-angiotensin system inhibitors were shown to have benefits beyond their classic cardioprotective and vasculoprotective effects, including reducing the risk of new-onset diabetes and associated cardiovascular effects. The discovery that the renin-angiotensin system inhibitor and angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan, can selectively activate the peroxisome proliferator-activated receptor-γ (PPARγ, an established antidiabetic drug target) provides the unique opportunity to prevent and treat cardiovascular complications in high-risk elderly patients with hypertension and new-onset diabetes. Two large clinical trials, ONTARGET (Ongoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular disease) have assessed the cardioprotective and antidiabetic effects of telmisartan. The collective data suggest that telmisartan is a promising drug for controlling hypertension and reducing vascular risk in high-risk elderly patients with new-onset diabetes

Soil quality as affected by agroforestry and grass buffers in grazed pasture and row crop systems

Title from PDF of title page (University of Missouri--Columbia, viewed on August 27, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Thesis advisors: Drs. Ranjith P. Udawatta, Stephen H. Anderson and Robert J. KremerIncludes bibliographical references.Vita.M.S. University of Missouri--Columbia 2011."May 2011"Establishment of agroforestry and grass buffers within agroecosystems is believed to improve soil quality. Soil enzyme activities and water stable aggregates have been identified as sensitive soil quality indicators to evaluate early responses to soil management. However, only a few studies compared these parameters among buffers, grazing pastures, and row crop systems. The objective of this study was to compare the activities of selected enzymes, water stable aggregates (WSA), soil organic carbon (SOC), total nitrogen (TN), and bulk density (Db) as soil quality parameters among four management treatments: grazed pasture (GP), agroforestry buffer (AgB), grass buffer (GB) and row crop (RC). Two soil depths (0-10 and 10-20 cm) were analyzed in all treatments for two consecutive years, 2009 and 2010. The enzyme activities, WSA, SOC, TN, and Db were determined by standard procedures. Most of the soil quality indicators were significantly greater in perennial vegetation treatments compared to row crop management indicating that perennial vegetation provides favorable conditions for greater enzyme activities and other soil quality indicators. Although there were numerical variations, the trends in response of quality parameters were consistent between years. Soil enzyme activities were significantly correlated with soil organic carbon content. Assessing changes in selected soil quality indicators appears to be a useful tool to determine soil management effects as well as trends in soil degradation

Healing after myocardial infarction in the dog: Changes in infarct hydroxyproline and topography

Temporal changes in infarct collagen and left ventricular topography during healing after myocardial infarction were studied in 132 dogs with coronary artery ligation: 8 sham dogs and 13 with no infarction (controls) and 111 with infarction (3 at 1 day, 54 at 2 days, 25 at 7 days, 3 at 2 weeks, 9 at 4 weeks and 17 at 6 weeks). Myocardial hydroxyproline (a marker of collagen) was measured by spectrophotometry and pathologic infarct size, arteriographic occluded bed size and topography by computerized planimetry of weighed left ventricular rings. Over 6 weeks, hydroxyproline was unchanged in normal regions (average 4.20 mg/g dry weight) but increased progressively between 7 days and 6 weeks (9.94 versus 55.55 mg/g, p < 0.001) in infarct zones. Progressive infarct contraction occurred over 6 weeks, with infarct size at 6 weeks being 40% less than at 2 days (9.7 versus 16.3% of the left ventricle, p < 0.001), although total infarct hydroxyproline was directly related to infarct size at each time period (r = 0.73 to 0.81, p ≤ 0.05).Significant (p ≤ 0.05) left ventricular topographic changes in infarct hearts compared with control hearts included: 1) increase in cavity area (5.0 versus 3.9 cm2), endocardial circumference (8.8 versus 7.4 cm) and expansion index (infarct/normal endocardial segment length, 1.21 versus 1.02) by 7 days; and 2) decrease in thinning ratio (infarct/normal wall thickness, 0.71 versus 0.98) by 6 weeks. Also, compared with 2 day infarcts, by 6 weeks infarct area was decreased (1.8 versus 3.4 cm2) and the noninfarcted segment length increased (6.9 versus 5.4 cm). Changes in hydroxyproline and topography were similar for anterior (n = 54) and posterior (n = 57) infarcts.Thus, healing in canine infarcts is associated with cavity dilation and infarct expansion within 7 days followed by infarct contraction and thinning by 6 weeks, whereas collagen increases between 7 days and 6 weeks. Collagen deposition in expanded and thinned infarct segments explains the permanent regional shape distortion associated with ventricular aneurysms

Maximal sets of points in finite projective space, no t-linearly dependent

AbstractConsider a finite (t + r − 1)-dimensional projective space PG(t + r − 1, s) based on the Galois field GF(s), where s is prime or power of a prime. A set of k distinct points in PG(t + r − 1, s), no t-linearly dependent, is called a (k, t)-set and such a set is said to be maximal if it is not contained in any other (k∗, t)-set with k∗ > k. The number of points in a maximal (k, t)-set with the largest k is denoted by mt(t + r, s). Our purpose in the paper is to investigate the conditions under which two or more points can be adjoined to the basic set of Ei, i = 1, 2, …, t + r, where Ei is a point with one in i-th position and zeros elsewhere. The problem has several applications in the theory of fractionally replicated designs and information theory

Different Relations Between Infarct Size and Occluded Bed Size in Barbiturate-Anesthetized Versus Conscious Dogs

The relation between infarct size and occluded bed size in barbiturate-anesthetized (n = 32) and conscious (n = 34) dogs was compared using models of the left anterior descending (n = 43) and circumflex (n = 23) coronary arteries with 2 day old infarcts. Infarct and occluded bed (postmortem coronary arteriography) masses were measured by computerized planimetry of weighed left ventricular rings. For either type of occlusion, infarcts were larger in anesthetized than in conscious dogs (56 versus 33% occluded bed, p < 0.001), with greater slopes of the linear regressions between infarct size and occluded bed size (p < 0,001) and less epicardial sparing (p < 0.05) on topographic mapping. Although arterial and left atrial pressures were similar in the two groups, heart rates were higher in the anesthetized dogs, both before (127 versus 88 beats/min, p < 0.001) and after (151 versus 109 beats/min, p < 0.001) occlusion. Myocardial blood flow distribution (radioactive microspheres, n = 33) favored the epicardium in anesthetized dogs, with lower endocardial-epicardial flow ratios pre- and postocclusion. Also, the level of total plasma catecholamines (radioenzymatic assay) was higher in barbiturate-anesthetized (n = 5) than in conscious (n = 5) dogs. Increasing the heart rate in conscious dogs (n = 18) to that of the anesthetized group (139 beats/min) by pacing produced larger infarcts and greater linear regression slopes, as seen in anesthetized dogs. Decreasing the heart rate in anesthetized dogs (n = 7) to that of the conscious group (98 beats/min) by sinoatrial node destruction and pacing resulted in smaller infarcts and lower linear regression slope, as seen in conscious dogs. Thus, the larger infarcts in barbiturate-anesthetized dogs appeared to be related mainly to the tachycardia, although transmural maldistribution of flow and increased circulating catecholamines might have contributed

Modification of left ventricular geometry and function during healing after acute myocardial infarction

Increased left ventricular (LV) size and deformation of LV geometry are associated with LV dysfunction. Regional shape distortion (RSD), detected on two-dimensional echocardiography (2D-Echo) after acute myocardial infarction (MI), is associated with poor outcome. Two hypotheses were tested: i) early RSD of the asynergic infarct zone after MI is followed by progressive global LV dilatation, remodelling towards a spheroidal shape, and more LV dysfunction; and ii) the progressive remodelling of LV geometry spans the phases of early infarction and healing and may be modified by early and prolonged therapies applied over the phases of infarction and healing. A bench to bedside approach was used, with concurrent studies in a dog model of healing over 6 weeks after MI and patients with first MI's. Computer- assisted analysis of the 2D-Echo images with 3D reconstruction was used to quantify LV asynergy (akinesis + dyskinesis), LV volumes, LV ejection fraction, RSD bulge and global LV shape. The animal studies showed that collagen deposition during healing after MI increases progressively, reaching a plateau around 2 weeks, and deposition of collagen in already dilated infarct zones is followed by late thinning and further RSD associated with LV aneurysms. Importantly, serial 2D-Echo tracked the in- vivo changes in LV geometry and function and showed greater RSD and LV dysfunction with anterior than inferior MI, and with transmural MI than nontransmural MI. Other studies showed: i) lower LV resistance to distension and rupture in infarcted hearts; ii) marked extracellular matrix (ECM) disruption and RSD in transmural MI; ill) delayed effects on LV remodelling after infarct-limiting therapies given during acute MI; iv) loss of beneficial effects of the vasodilator nitroglycerin (NTG) with hypotension induced by high doses during acute MI; v) decreased wall stress by prolonged LV unloading after MI, with nitrates (eccentric dosing) and angiotensin-converting enzyme (ACE) inhibitors, limited early RSD and progressive LV remodelling and dysfunction; this effect was greater with therapy over 6-weeks than just over the first 2 weeks; vi) late reperfusion limited early RSD and adverse LV remodelling, and preserved ECM in the epicardial rim; vii) the resistance of the healed left ventricle to distension and rupture was further reduced by prolonged anti-inflammatory therapy (ibuprofen); viii) prolonged ACE inhibitor therapy decreases infarct collagen, which may be harmful under certain conditions. The clinical studies with serial 2D-Echo showed that systematic tomographic imaging could provide quantitative data on regional and global LV geometry and function including the degree of RSD (depth, area, and volume). An early 2D-Echo not only provided diagnostic data on LV thrombi and complications of MI, but the extent of LV asynergy on the initial 2D-Echo predicted outcome at 3 months and 1 year. Importantly, the degree of RSD on the initial 2D-Echo predicted patients at high risk of adverse remodelling with infarct expansion, greater LV dysfunction, progressive LV dilatation, and poor outcome at 1 year. Survivors of MI with > 18% LV asynergy and significant RSD on a baseline 2D Echo were at increased risk of topographic deterioration on exercise programs. Anti-inflammatory therapy after MI resulted in more RSD and adverse remodelling. Short-term LV unloading with low-dose intravenous NTG therapy during the acute MI, as well as prolonged nitrate (eccentric dosing) and captopril therapy during healing over 6 weeks after MI, improved 2D-Echo indexes of LV geometry and function, decreased complications and improved outcome. Acute thrombolytic therapy also limited LV remodelling after MI. In all these studies, the degree of RSD and severity of LV dysfunction were greater with anterior than inferior MI, and with Q-wave than non-Q wave MI. In Conclusion, the overall results indicate that early RSD in the infarct zone leads to progressive global LV dilatation, LV dysfunction and poor outcome and the changes in LV geometry and function can be quantified by serial quantitative 2D-Echo imaging. Marked RSD is associated with early ECM disruption and aneurysm formation after transmural MI. During healing, infarct zones may be thinned and dilated before the collagen plateau, and collagen deposition into these zones result in further RSD and chronic aneurysms. Prolonged anti-remodelling therapy during healing, with agents that decrease wall stress without damaging the ECM, or decreasing infarct collagen, or causing infarct thinning, or impairing healing, might be more effective for reducing RSD, LV aneurysm, global dilatation and poor outcome. The 2D-Echo measurement of RSD early after MI might be potentially important for stratifying patients according to their topographic status and for the objective assessment of the effects of anti-remodelling strategies during healing after MI

Nation, Nationalism and the Partition of India Two Moments from Hindi Fiction

Este artículo estudia la presencia del Islam en India en las cuatro décadas siguientes a la Independencia, según dos novelas en hindi, Adha Gaon, de Rahi Masoom Reza y Sookha Bargad, de Manzoor Ehtesham. En ambas la Partición es el eje central de la identidad musulmana, que en todo caso mantiene su fidelidad a la nación india. Sin embargo, el discurso del fundamentalismo hindú desde la década de 1980 ha ido alienando a esta comunidad, que no solo rechazó la idea de Paquistán como patria de los musulmanes, sino que fue fundamental para mantener la neutralidad religiosa del estado en India.This paper traces the trajectory of Muslims in India over roughly four decades after Independence through a study of two Hindi novels, Rahi Masoom Reza’s Adha Gaon and Manzoor Ehtesham’s Sookha Bargad. It explores the centrality of Partition to issues of Muslim identity, their commitment to the Indian nation, and how a resurgent Hindu communal discourse particularly from the 1980s onwards “otherizes” a community that not only rejected the idea of Pakistan as the homeland for Muslims, but was also critical to the construction of a secular Indian nation

Soil quality parameters for row-crop systems and grazed pastures with agroforestry buffers

Paper presented at the 12th North American Agroforesty Conference, which was held June 4-9, 2011 in Athens, Georgia.In Ashton, S. F., S.W. Workman, W.G. Hubbard and D.J. Moorhead, eds. Agroforestry: A Profitable Land Use. Proceedings, 12th North American Agroforestry Conference, Athens, GA, June 4-9, 2011.Incorporation of trees and establishment of buffer are believed to enhance soil quality. Soil enzyme activities and water stable aggregates have been identified as good indices for assessing soil quality to evaluate early responses to changes in soil management. However, studies comparing these parameters for grazing pastures and row crop systems are limited. The objective of this study is to examine the activities of selected enzymes (fluorescein diacetate (FDA) hydrolase, dehydrogenase, [beta]-glucosidase and [beta]-glucosaminidase), the percentage of water stable aggregates (WSA), and soil organic carbon and nitrogen as soil quality parameters for grazed pasture and row-crop systems. The study consisted of four management treatments: grazed pasture (GP), agroforestry buffer (AgB), grass buffer (GB) and row-crop (RC). Soil organic carbon (SOC), total nitrogen (TN) contents and soil bulk density were also determined. Two soil depths (0-10 and 10-20 cm) were analyzed for all treatments for two consecutive years, 2009 and 2010. The row-crop treatment showed significantly lower [beta]-glucosidase and [beta]-glucosaminidase activity and significantly lower WSA compared to all other treatments. The FDA hydrolase activities were not significant in 2009 but were significant in 2010. There were numerical variations of parameters in two years but the pattern was consistent. Surface soil revealed higher enzyme activities and higher WSA than the sub-surface soil. The treatment by depth interactions were significant for [beta]-glucosidase and [beta]-glucosaminidase enzymes in 2009 but the interactions were significant for dehydrogenase and [beta]-glucosaminidase enzymes in 2010. Implications can be made that permanent vegetation will improve soil quality by enhancing organic matter accumulation in the soil and increasing microbial activity with minimum soil disturbance which will have a positive effect on the ecosystems.Bodh Paudel (1), Ranjith Udawatta (1,2), Stephen H. Anderson (1) and Robert Kremer (3) ; 1. Soil, Environmental and Atmospheric Sciences, 302 Anheuser-Busch Natural Resources Building, University of Missouri, Columbia, MO, USA. 2. Center for Agroforestry, 203 Anheuser-Busch Natural Resources Building, University of Missouri, Columbia, MO, USA. 3. USDA-ARS Cropping Systems and Water Quality Unit, University of Missouri, Columbia, MO, USA.Includes bibliographical references

Effect of Silver Addition on the Ethanol-Sensing Properties of Indium Oxide Nanoparticle Layers: Optical Absorption Study

In2O3 and In2O3:Ag nanoparticle layers have been deposited using a two-step method consisting of chemical capping and dip coating techniques. The result of optical absorption analysis of In2O3:Ag samples shows the presence of Ag2O and Ag in air-annealed and vacuum-annealed samples, respectively. These results have been correlated with the gas sensing properties of these layers towards ethanol and support the proposed mechanism that increase in sensor response on Ag addition is due to the conversion of Ag2O to Ag in the presence of ethanol