Cross-Linked Alginate Film Pore Size Determination Using Atomic Force Microscopy and Validation Using Diffusivity Determinations

The deficit of organ donors has fueled the need for advances in tissue engineering and regenerative medicine. Microencapsulation in alginate immuno-isolation membranes has been used to treat many disabling metabolic disorders, namely, phenylketonuria, kidney failure and diabetes mellitus. Systematic nutrient flux determinations are hindered by the lack of experimental data on alginate-based membrane topography and the pore size thus preventing the full therapeutic potential of the bio-membranes to be reached. In this study, samples of cross-linked alginate membranes were subjected to the following analytical characterization: 1) pore size characterization using atomic force microscopy operated in contact mode to detect and measure pore size; 2) differential scanning calorimetry to confirm biopolymer cross-linking; and 3) diffusivity measurements using spectrophotometry and fluorescence microscopy to confirm the presence of through pores and to calculate reflection coefficients. The pore sizes for the pre-clinical standard formulation of 1.5% (w/v) medium viscosity alginate cross-linked with 1.5% CaCl2 and 0.5% (w/v) alginate and chitosan cross-linked with 20% CaCl2 are 5.2 nm ± 0.9 nm and 7.0 nm ± 3.1 nm, respectively. An increase in the glass transition temperatures as a function of cross-linker concentration was observed. Diffusivity values obtained from the inward diffusivity of creatinine into macrocapsules (d = 1000 μm ± 75 μm) and the outward diffusivity of FITC dextrans from macrocapsules (d = 1000 μm ± 75 μm) and microcapsules (d = 40 μm ± 5 μm) were shown to correlate strongly (R2 = 0.9835) with the ratio of solute to pore sizes, confirming the presence of through pores. Reflection coefficients approaching and exceeding unity correlate with the lack of permeability of the membranes to MW markers that are 70 kDa and greater

The Grizzly, October 4, 2012

Campus Crime Rates • Banners Call for Student Power • UC Prepares to Vote • Professors up for Tenure • Resumania Offers Resume Aid • Phoenixville To-Dos • Marisa Roman Joins Ursinus Faculty • Grad School Guru Returns to Offer Tips and Advice • Opinion: We Should Distance Ourselves from Technology; Give CAB Events a Chance; Grizzly Staff Editorial • 3-0 UC Rugby Looks to Extend Streak • UC Recap: Mixed Week for the Bears • Coach Profile: Joe Groff, Volleyballhttps://digitalcommons.ursinus.edu/grizzlynews/1865/thumbnail.jp

The Grizzly, September 27, 2012

Ursinus Partners With Columbia • Family Day Coming Soon • Berman Search • Bi-Textual Poetry Series Kicked Off Sept. 18 • Big Brothers, Sisters Program • Internship Event • Services at Wellness • Opinion: Ursinus Should Disclose Annual Budget; Changes in Dining Services are Justified • UC Recap: Field Hockey Falls to F&M • Behind the Scenes: Kip and Sean Lacyhttps://digitalcommons.ursinus.edu/grizzlynews/1864/thumbnail.jp

The Grizzly, January 24, 2013

Distinguished Retirees Leave Ursinus • New Deans Take Office • Plans for Library\u27s Future • Resident Adviser Recruitment Continues • UC Welcomes New RD • Intervarsity Christian Fellowship Strives for Change • Students Create Their Own Wismer Masterpieces • How to Form a New Student Club on Campus • Opinion: Sexual Assault Absent in Media Coverage; Birthright Trip to Israel Provides New Insights • Senior Abitz Attends FFCA Academy • Senior Spotlight: Amber Yacenda, Basketball • Draper Drops 33, Swarthmore in OThttps://digitalcommons.ursinus.edu/grizzlynews/1872/thumbnail.jp

The Grizzly, September 6, 2012

Ursinus Welcomes New Dean • Wismer Changes • Orientation Update • Dr. Heinzl Lecture • Gary Hodgson\u27s Tenure as Campus Safety Officer • Meet Mike Mullin, New R.D. • Gender-Neutral Bathrooms Arrive on UC Campus • Residence Life Offers Support for the Class of 2016 • Opinion: Athletes Frustrated by Dining Changes; Senator Rubio Would Have Been a Better V.P. Choice for the GOP • Field Hockey Looks to Keep Tradition • Under New Coach, Volleyball Begins 2012 Season • Lofty Expectations for Bears Footballhttps://digitalcommons.ursinus.edu/grizzlynews/1861/thumbnail.jp

A Randomized Placebo-Controlled Trial of \u3cem\u3eN\u3c/em\u3e-Acetylcysteine for Cannabis Use Disorder in Adults

Background—Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods—In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results—There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions—In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors

PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. METHODS: LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. RESULTS: Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c(+/-)). Resting membrane potential was more depolarized in Pitx2c(+/-) atria, and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. CONCLUSIONS: PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF