Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Stresses encountered during human islet isolation lead to unavoidable beta-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, beta-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less beta-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The PEPSI Exoplanet Transit Survey (PETS) I: Investigating the presence of a silicate atmosphere on the super-Earth 55 Cnc e

The study of exoplanets and especially their atmospheres can reveal key insights on their evolution by identifying specific atmospheric species. For such atmospheric investigations, high-resolution transmission spectroscopy has shown great success, especially for Jupiter-type planets. Towards the atmospheric characterization of smaller planets, the super-Earth exoplanet 55 Cnc e is one of the most promising terrestrial exoplanets studied to date. Here, we present a high-resolution spectroscopic transit observation of this planet, acquired with the PEPSI instrument at the Large Binocular Telescope. Assuming the presence of Earth-like crust species on the surface of 55 Cnc e, from which a possible silicate-vapor atmosphere could have originated, we search in its transmission spectrum for absorption of various atomic and ionized species such as Fe , Fe+, Ca , Ca+, Mg and K , among others. Not finding absorption for any of the investigated species, we are able to set absorption limits with a median value of 1.9 x RP. In conclusion, we do not find evidence of a widely extended silicate envelope on this super-Earth reaching several planetary radii.Comment: MNRAS, in pres

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

Continuous Quadrupole Magnetic Separation of Islets during Digestion Improves Purified Porcine Islet Viability

Islet transplantation (ITx) is an emerging and promising therapy for patients with uncontrolled type 1 diabetes. The islet isolation and purification processes require exposure to extended cold ischemia, warm-enzymatic digestion, mechanical agitation, and use of damaging chemicals for density gradient separation (DG), all of which reduce viable islet yield. In this paper, we describe initial proof-of-concept studies exploring quadrupole magnetic separation (QMS) of islets as an alternative to DG to reduce exposure to these harsh conditions. Three porcine pancreata were split into two parts, the splenic lobe (SPL) and the combined connecting/duodenal lobes (CDL), for paired digestions and purifications. Islets in the SPL were preferentially labeled using magnetic microparticles (MMPs) that lodge within the islet microvasculature when infused into the pancreas and were continuously separated from the exocrine tissue by QMS during the collection phase of the digestion process. Unlabeled islets from the CDL were purified by conventional DG. Islets purified by QMS exhibited significantly improved viability (measured by oxygen consumption rate per DNA, p < 0.03 ) and better morphology relative to control islets. Islet purification by QMS can reduce the detrimental effects of prolonged exposure to toxic enzymes and density gradient solutions and substantially improve islet viability after isolation.Schulze Foundation; Schulze Diabetes Institute, NIH [R44DK072647-03, R01DK068717]; Carol Olson Memorial Diabetes Research Fund; Iacocca Family Foundation; Schott Family Foundation; Kettering Family FoundationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The PEPSI exoplanet transit survey (PETS) I: investigating the presence of a silicate atmosphere on the super-earth 55 Cnc e

The study of exoplanets and especially their atmospheres can reveal key insights on their evolution by identifying specific atmospheric species. For such atmospheric investigations, high-resolution transmission spectroscopy has shown great success, especially for Jupiter-type planets. Towards the atmospheric characterization of smaller planets, the super-Earth exoplanet 55 Cnc e is one of the most promising terrestrial exoplanets studied to date. Here, we present a high-resolution spectroscopic transit observation of this planet, acquired with the PEPSI instrument at the Large Binocular Telescope. Assuming the presence of Earth-like crust species on the surface of 55 Cnc e, from which a possible silicate-vapor atmosphere could have originated, we search in its transmission spectrum for absorption of various atomic and ionized species such as Fe , Fe +, Ca , Ca +, Mg, and K , among others. Not finding absorption for any of the investigated species, we are able to set absorption limits with a median value of 1.9 × RP. In conclusion, we do not find evidence of a widely extended silicate envelope on this super-Earth reaching several planetary radii

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