Effects of Dietary Energy Concentration and Feed Intake on Growth Performance of Newly Received Growing Cattle Fed Diets Based on Corn and Corn Co-Products

Objective:This study’s focus was to evaluate if feeding equal amounts of energy from a high-energy limit-fed diet has an effect on growth performance of growing beef cattle when compared to traditional high-roughagead libitumdiets. Study Description:A total of 392 crossbred heifers were fed one of four experimental diets for a 70-day receiving period. Treatments included a high-roughage diet formulated to provide 45 Mcal of net energy for gain (NEg) per 100 lb of dry matter (DM) and fed forad libitumintake (AL) or a high-energy diet formulated to provide 60 Mcal of NEgper 100 lb of DM and fed at 75% (LIM-75), 80% (LIM-80), or 85% (LIM-85) ofad libitumintake. Treatments were designed to equalize for energy intake between calves assigned to AL and LIM-75. The Bottom Line:Restricting feed intake while maintaining energy intake does not negatively influence growth performance of newly received growing beef cattle. In times of high forage cost or shortened growing periods producers could program gains based on their own financial and personal needs

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation

Background: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Methods: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Results: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6–12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Conclusions: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations

Enhanced Oxygen Supply Improves Islet Viability in a New Bioartificial Pancreas

<p>The current epidemic of diabetes with its overwhelming burden on our healthcare system requires better therapeutic strategies. Here we present a promising novel approach for a curative strategy that may be accessible for all insulin-dependent diabetes patients. We designed a subcutaneous implantable bioartificial pancreas (BAP)-the "beta-Air" that is able to overcome critical challenges in current clinical islet transplantation protocols: adequate oxygen supply to the graft and protection of donor islets against the host immune system. The system consists of islets of Langerhans immobilized in an alginate hydrogel, a gas chamber, a gas permeable membrane, an external membrane, and a mechanical support. The minimally invasive implantable device, refueled with oxygen via subdermally implanted access ports, completely normalized diabetic indicators of glycemic control (blood glucose intravenous glucose tolerance test and HbA1c) in streptozotocin-induced diabetic rats for periods up to 6 months. The functionality of the device was dependent on oxygen supply to the device as the grafts failed when oxygen supply was ceased. In addition, we showed that the device is immuno-protective as it allowed for survival of not only isografts but also of allografts. Histological examination of the explanted devices demonstrated morphologically and functionally intact islets; the surrounding tissue was without signs of inflammation and showed visual evidence of vasculature at the site of implantation. Further increase in islets loading density will justify the translation of the system to clinical trials, opening up the potential for a novel approach in diabetes therapy.</p>

Overlap and correlation of islet characterization methods with clinical transplant outcome.

<p>Data from our study illustrating that membrane integrity staining (based on FDA/PI), oxygen consumption rate (OCR) normalized to DNA content (OCR/DNA), and OCR/DNA normalized to the islet size index (ISI) (OCR/DNA/ISI) are not correlated with the clinical outcome [insulin independence vs. dependence] at 6–12 months following islet autotransplant (IAT). However, both <i>islet equivalent</i> (IE) <i>dose</i> and the <i>OCR dose</i> were correlated with post-IAT outcome. The gray region indicates the range of <i>IE</i> and <i>OCR doses</i> that is associated with uncertain IAT outcome. Note that the width of the gray region is much narrower with the <i>OCR dose</i>. The black dotted line represents the calculated cut-off point for clinical outcome (<i>IE dose</i>: 5,794 and <i>OCR dose</i>: 6.23). The second column of graphs represents receiver operating characteristic (ROC) curves for each of the five islet product characteristics from this data set. The area-under-the-curve (AUC) has been calculated for each islet product characteristic and these values are shown above each ROC curve.</p

Previously published data showing overlap and correlation of islet equivalent dose with clinical transplant outcome.

<p>Data from Anazawa <i>et al</i>. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134428#pone.0134428.ref010" target="_blank">10</a>] illustrating that the <i>islet equivalent</i> (<i>IE</i>) <i>dose</i> correlates with the clinical outcome [insulin independence vs. dependence] at 6–12 months following islet autotransplant (IAT). However, the gray region indicates a wide range of <i>IE dose</i> (IE/kg of recipient) that is associated with an uncertain IAT outcome. The second graph shows the receiver operating characteristic (ROC) curve for this previously published data set with the area-under-the-curve (AUC) above.</p

Summary of cases where <i>OCR dose</i> correctly predicted clinical transplant outcome, whereas <i>IE dose</i> did not.

<p>Summary of cases where <i>OCR dose</i> correctly predicted clinical transplant outcome, whereas <i>IE dose</i> did not.</p

Comparison of demographic, isolation, and quality assessment variables between insulin dependent and independent clinical transplant outcome 6–12 months post-transplant.

<p>Data are means ± standard error or percentage.</p><p>^asignificant difference (p< 0.05) between groups as calculated by a Mann Whitney non-parametric test.</p><p>Comparison of demographic, isolation, and quality assessment variables between insulin dependent and independent clinical transplant outcome 6–12 months post-transplant.</p