Products derived from the black chokeberry, Aronia melanocarpa, are claimed to be beneficial in disorders or diseases associated with oxidative stress. The claims are based on evidence from in vitro studies and animal experiments. The active principle – a mixture of procyanidins, anthocyanins and phenolic acids – constitutes one of the most potent natural antioxidants. A systematic review was carried out of the quality of the clinical trials on chokeberry products that had been published up to December 2009, and conventionally established criteria were used to assess the strength of the evidence for their clinical effectiveness. Thirteen studies were identified. The quality of most of the trials and, correspondingly, the evidence of effectiveness for Aronia products is poor. Though laboratory and clinical data indicate that chokeberry products may well be useful as ‘functional food’ for disorders or diseases related to oxidative stress, these promising indications need to be confirmed in more rigorous studies before putative therapeutic uses can be confidently recommended for chokeberry products. Copyright © 2010 John Wiley & Sons, Ltd.

ContributorsGIW wrote and revised the manuscript in response to co-author comments. He finalized all the figures and tables, performed the literature search, and assisted with data interpretation. HJK critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. IBA performed the data analysis, constructed the figures and tables, and made important suggestions to improve the manuscript. H-CK assisted with the data analysis and also reviewed the manuscript. GRC critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. All other authors were given the opportunity to review the manuscript and make suggestions which GIW received, either revising the paper or providing explanations. All who are not deceased were involved with approval of the manuscript.

The intrarenal renin-angiotensin system (RAS) plays a key role in the development of diabetic nephropathy. Recently, we showed that combination therapy with an AT 1 receptor blocker (ARB) and an activated vitamin D analog produced excellent synergistic effects against diabetic nephropathy, as a result of blockade of the ARB-induced compensatory renin increase. Given the diversity of vitamin D analogs, here we used a pro-drug vitamin D analog, doxercalciferol (1␣-hydroxyvitamin D 2), to further test the efficacy of the combination strategy in long-term treatment. Streptozotocin-induced diabetic DBA/2J mice were treated with vehicle, losartan, doxercalciferol (0.4 and 0.6 g/kg), or losartan and doxercalciferol combinations for 20 wk. Vehicle-treated diabetic mice developed progressive albuminuria and glomerulosclerosis. Losartan alone moderately ameliorated kidney injury, with renin being drastically upregulated. A similar therapeutic effect was seen with doxercalciferol alone, which markedly suppressed renin and angiotensinogen expression. The losartan and doxercalciferol combination most effectively prevented albuminuria, restored glomerular filtration barrier structure, and dramatically reduced glomerulosclerosis in a dose-dependent manner. These effects were accompanied by blockade of intrarenal renin upregulation and ANG II accumulation. These data demonstrate an excellent therapeutic potential for doxercalciferol in diabetic renal disease and confirm the concept that blockade of the compensatory renin increase enhances the efficacy of RAS inhibition and produces synergistic therapeutic effects in combination therapy.renin-angiotensin system; compensatory renin increase; albuminuria; glomerulosclerosis DIABETIC NEPHROPATHY (DN) is the most common renal complication of diabetes mellitus and a leading cause of end-stage renal disease, accounting for 44% of new cases in 2005 (9). It is well established that the renin-angiotensin system (RAS) is a major mediator of progressive renal injury. Since renal interstitial angiotensin (ANG) II levels are much higher than in the plasma (28), the local RAS in the kidney is believed to play the major damaging role in diabetic nephropathy. Kidney cells, including mesangial cells and podocytes, are able to synthesize all components of the RAS, including renin, the (pro)renin receptor, angiotensinogen (AGT), and ANG II receptors independently of the systemic RAS, making the kidney capable of maintaining a high level of local ANG II. Intrarenal renin and AGT levels are induced in diabetic animals (4, 48). In vitro studies showed that when exposed to high glucose levels, mesangial cells and podocytes increase renin and ANG II production (13,38,42). Intrarenal ANG II promotes the progression of renal injury via multiple pathways that increase glomerular permeability, induce oxidative stress, and promote the synthesis of profibrotic and proinflammatory factors and extracellular matrix (8,15). The consequence of the progression of diabetic renal injury is the development of protein...

While quality has attracted significant attention in the past two decades, the debate is still on as to whether a firm should aim for zero defects or base its quality decisions on cost-benefit trade-offs. The continuous improvement advocates generally eschew the cost trade-off approach, but U.S. firms, after spending substantial sums on quality-related activities in the 1980s, appear to be focusing again on cost trade-offs and measures such as return on quality. This paper provides analytical support for the continuous improvement argument while relying on a cost trade-off analysis. We present a dynamic model of a monopolist making decisions on price, production, process improvement, and quality assurance efforts. The model is comprehensive and captures the effects of autonomous and induced learning on both productivity and quality and incorporates quality related costs in detail. Using this model, we show that quality improves over time, while process improvement effort and quality assurance effort decrease over time. In fact, as anecdotal and empirical evidence suggests, process improvement and quality assurance effort is high when quality level is low, and vice-versa. The optimal production rate is increasing and the optimal price is decreasing over time. We also provide valuable insights into the impact of changes in key parameters such as interest rates on production, price, process improvement effort, and quality assurance effort.Quality Improvement, Process Improvement, Learning Effects, Quality Costs, Productivity

In the general US population, serum 25-hydroxyvitamin D levels are inversely associated with several cardiovascular risk factors, including hypertension, diabetes, obesity, and hyperlipidemia.1 Low levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D [1,25(OH) 2 D 3 ] are associated with congestive heart failure and an increased rate of all-cause and cardiovascular mortality. 2-4Prospective studies have demonstrated an association between low serum 25-hydroxyvitamin D levels and increased risk of incident cardiovascular disease and myocardial infarction. 5,6 In patients with chronic kidney disease, where cardiovascular disease is the leading cause of death, therapy with activated vitamin D is associated with a reduction in mortality. 7,8 Vitamin D's cardiovascular effects may be mediated in part by regulation of the renin-angiotensin system (RAS).9,10 1,25(OH) 2 D 3 and its analogs inhibit renin expression in vivo 11 and an inverse correlation has been reported between levels of serum 1,25(OH) 2 D 3 and plasma renin activity in humans.12,13 A therapeutic effect of vitamin D in humans, however, has not been conclusively demonstrated. Pharmacological inhibition of the RAS with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) is commonly