Mark E. Cooper

Bio: Mark E. Cooper is an academic researcher from University of Queensland. The author has contributed to research in topics: Diabetes mellitus & Diabetic nephropathy. The author has an hindex of 158, co-authored 1463 publications receiving 124887 citations. Previous affiliations of Mark E. Cooper include University of Cambridge & University of Adelaide.

The role of AGEs in cardiovascular disease.

Abstract: Advanced glycation end-products (AGEs) are generated in the diabetic milieu, as a result of chronic hyperglycemia and enhanced oxidative stress. These AGEs, via direct and receptor dependent pathways promote the development and progression of cardiovascular disease. AGEs accumulate at many sites of the body including the heart and large blood vessels in diabetes. These modified proteins interact with receptors such as RAGE to induce oxidative stress, increase inflammation by promoting NFkappaB activation and enhance extracellular matrix accumulation. These biological effects translate to accelerated plaque formation in diabetes as well as increased cardiac fibrosis with consequent effects on cardiac function. Strategies to reduce the ligation of AGEs to their receptors such as agents which reduce AGE accumulation, soluble RAGE which acts as a competitive antagonist to the binding of AGEs to RAGE and genetic deletions of RAGE appear to attenuate diabetes associated atherosclerosis. Benefits on cardiac dysfunction with these inhibitors of the AGE/RAGE axis are not as well characterised. In conclusion, therapeutic strategies targeting AGEs appear to have significant clinical potential, often in combination with currently used agents such as inhibitors of the renin-angiotensin system, to reduce the major burden of diabetes, its associated cardiovascular complications.

Nitroimidazoles: Molecular Fireworks That Combat a Broad Spectrum of Infectious Diseases

Abstract: Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis. In this review, we summarize different classes of nitroimidazoles that have been described in the literature in the past five years, from approved drugs and clinical candidates to examples undergoing preclinical or early stage development. The relatively "nonspecific" mode of action and resistance mechanisms of nitromidazoles are discussed, and contemporary strategies to facilitate nitroimidazole drug development are highlighted.

Nephropathy and Elevated BP in Mice with Podocyte-Specific NADPH Oxidase 5 Expression

Abstract: NADPH oxidase (Nox) enzymes are a significant source of reactive oxygen species, which contribute to glomerular podocyte dysfunction. Although studies have implicated Nox1, -2, and -4 in several glomerulopathies, including diabetic nephropathy, little is known regarding the role of Nox5 in this context. We examined Nox5 expression and regulation in kidney biopsies from diabetic patients, cultured human podocytes, and a novel mouse model. Nox5 expression increased in human diabetic glomeruli compared with nondiabetic glomeruli. Stimulation with angiotensin II upregulated Nox5 expression in human podocyte cultures and increased reactive oxygen species generation. siRNA-mediated Nox5 knockdown inhibited angiotensin II-stimulated production of reactive oxygen species and altered podocyte cytoskeletal dynamics, resulting in an Rac-mediated motile phenotype. Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+)). Nox5(pod+) mice exhibited early onset albuminuria, podocyte foot process effacement, and elevated systolic BP. Subjecting Nox5(pod+) mice to streptozotocin-induced diabetes further exacerbated these changes. Our data show that renal Nox5 is upregulated in human diabetic nephropathy and may alter filtration barrier function and systolic BP through the production of reactive oxygen species. These findings provide the first evidence that podocyte Nox5 has an important role in impaired renal function and hypertension.

Hypertension and diabetes.

Abstract: Hypertension is often associated clinically with diabetes either as part of the insulin resistance syndrome or as a manifestation of renal disease. Elevated systemic blood pressure accelerates the progression of both microvascular and macrovascular complications in diabetes. Agents that interrupt the renin-angiotensin system confer renoprotection via a range of hemodynamic and nonhemodynamic mechanisms. Recent clinical trials confirm that these agents confer renoprotection in type 1 and type 2 diabetic patients with early or advanced renal disease. Hypertension also appears to accelerate vascular and cardiac abnormalities in diabetes, including increased atherosclerosis, arterial stiffness, left ventricular hypertrophy and diastolic dysfunction. A number of recently published and ongoing trials are exploring the role of aggressive antihypertensive treatment with a range of antihypertensive drugs in diabetic subjects at risk of or with macrovascular disease.

Genotype by environment interactions affecting grain sorghum. III. Temporal sequences and spatial patterns in the target population of environments

Abstract: The variable nature of rainfall in north-eastern Australia confounds the process of selecting sorghum hybrids that are broadly adapted. This paper uses a crop simulation model to characterise the drought environment types (ET) that occur in the target population of environments (TPE) for dryland sorghum. Seventy seasons (1921-1990) of simulations of the yield of a sorghum genotype and the associated within-season sequence of a stress index were conducted for a small TPE of 6 locations and also for a large TPE of 211 locations that attempted to represent the entire sorghum region. Previously, using the small dataset of 6 locations, pattern analysis enabled us to group seasonal stress indices from each trial into major ETs: 'low terminal stress' (ET1), severe terminal stress (ET2), and intermediate mid-season/terminal stress (ET3) in the ratio 33 : 38 : 29. When the dataset was broken into a sequence of 16 multi-environment trials (METs), each of 3 years and 6 locations, the ratios of ET1 : ET2 : ET3 differed greatly among METs, i.e. any single MET was not randomly sampling the TPE. Hence, for any MET, the average yield (GV(u)) was not the same as the overall mean of the entire 70-year dataset. If the trial yields were weighted according to the ratio of ET1 : ET2 : ET3 in the overall TPE, then GV(w) (s.d. = 0.13) for a single MET was much closer to the overall mean than was GV(u) (0.38). For different METs, the values of GV(w) were up to 30% higher or 15% lower than GV(u). Across METs, the difference between GV(u) and GV(w) was positively correlated (r = 0.88, n = 16, P < 0.05) with the frequency of ET1 ('low terminal stress') encountered within the MET and negatively correlated (r = -0.82) with the frequency of ET2. The value of weighting was confirmed by its ability to verify that two simulated genotypes had the same mean yield over many trials, even though they differed in their specific adaptation to the different ETs. The large TPE consisted of more than 15 000 simulations and was classified in 2 stages (within/among locations), repeated for each of 3 soil types. In years in which the simulation sowing criteria were met, the ratios of ET1 : ET2 : ET3 were about 4 : 2 : 4, 4 : 5 : 1, and 6 : 3 : 1 in the shallow, intermediate, and deep soils, respectively. Hence, over all soil types and locations, the sorghum TPE for northern Australia consists of at least 30% each of low terminal stress (ET1) or severe terminal stress (ET2) and these environment types need to be sampled. The incidence and nature of the 'intermediate midseason/terminal stress' environment type (ET3) varies with soil type and location. Weighting genotype performance should improve the precision of the estimate of its broadly adapted value, and be of practical use in breeding programs in these variable environments. Although the 'boundary conditions' of the TPE are not yet resolved, this paper also shows that simulation and pattern analyses can be used to determine the structure of the abiotic TPE. Taking other factors into account (e.g. soil type distribution, shire production levels, and farm profit), selection trials could be weighted to improve selection for narrow or broad adaptation, depending on the purpose of the breeding program.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …