Coculture of bladder urothelial and smooth muscle cells on small intestinal submucosa: potential applications for tissue engineering technology.

PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich membrane with inherent growth factors that has previously been shown to promote in vivo bladder regeneration. We evaluate in vitro use of small intestinal submucosa to support the individual and combined growth of bladder urothelial cells and smooth muscle cells for potential use in tissue engineering techniques, and in vitro study of the cellular mechanisms involved in bladder regeneration. MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and smooth muscle cells were established using standard enzymatic digestion or explant techniques. Cultured cells were then seeded on small intestinal submucosa at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and 28 days. The 5 separate culture methods evaluated were urothelial cells seeded alone on the mucosal surface of small intestinal submucosa, smooth muscle cells seeded alone on the mucosal surface, layered coculture of smooth muscle cells seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich coculture of smooth muscle cells seeded on the serosal surface followed by seeding of urothelial cells on the mucosal surface 24 hours later, and mixed coculture of urothelial cells and smooth muscle cells mixed and seeded together on the mucosal surface. Following harvesting at the designated time points small intestinal submucosa cell constructs were formalin fixed and processed for routine histology including Masson trichrome staining. Specific cell growth characteristics were studied with particular attention to cell morphology, cell proliferation and layering, cell sorting, presence of a pseudostratified urothelium and matrix penetrance. To aid in the identification of smooth muscle cells and urothelial cells in the coculture groups, immunohistochemical analysis was performed with antibodies to alpha-smooth muscle actin and cytokeratins AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth muscle cells occurred in vitro on small intestinal submucosa. When seeded alone urothelial cells and smooth muscle cells grew in several layers with minimal to no matrix penetration. In contrast, layered, mixed and sandwich coculture methods demonstrated significant enhancement of smooth muscle cell penetration of the membrane. The layered and sandwich coculture techniques resulted in organized cell sorting, formation of a well-defined pseudostratified urothelium and multilayered smooth muscle cells with enhanced matrix penetration. With the mixed coculture technique there was no evidence of cell sorting although matrix penetrance by the smooth muscle cells was evident. Immunohistochemical studies demonstrated that urothelial cells and smooth muscle cells maintain the expression of the phenotypic markers of differentiation alpha-smooth muscle actin and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3-dimensional growth of human bladder cells in vitro. Successful combined growth of bladder cells on small intestinal submucosa with different seeding techniques has important future clinical implications with respect to tissue engineering technology. The results of our study demonstrate that there are important smooth muscle cell-epithelial cell interactions involved in determining the type of in vitro cell growth that occurs on small intestinal submucosa. Small intestinal submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix interactions that are involved in regeneration and various disease processes of the bladder.

Pharmaceutical care in an inpatient pediatric intensive care unit: an international multicentric study

Introduction Pediatric intensive care patient represent a population athigh risk for drug-related problems. Our objective is to describe drugrelated problems and intervention of four decentralized pharmacists inpediatric and cardiac intensive care unit.Materials & Methods Multicentric, descriptive and prospectivestudy over a six-month period (August 1st 2009-January 31st 2010).Drug-related problems and clinical interventions were compiled infour pediatric centers using a tool developed by the Socie´te´ Franc¸aisede Pharmacie Clinique. Data concerning patients, drugs, intervention,documentation, approval (if needed), and estimated impact werecompiled. The four pharmacists participating were from Belgium (B),France (F), Quebec (Q) and Switzerland (S).Results A total of 996 interventions were collected: 129 (13%) in B,238 (24%) in F, 278 (28%) in Q and 351 (35%) in S. These interventionstargeted 269 patients (median 22 month-old, 52% male): 69(26%) in B, 88 (33%) in F, 56 (21%) in Q and in S. These data werecollected during 28 non consecutive days in the clinical unit in B, 59days in F, 42 days in Q and 63 days in S. The main drug-relatedproblems were inappropriate administration technique (293, 29%),untreated indication (254, 25%) and supra therapeutic dosage (106,11%). The pharmacist's interventions concerned mainly administrationmode optimization (223, 22%), dose adjustment (200, 20%) andtherapeutic monitoring (164, 16%). The three major drug classesleading to interventions were anti-infectives for systemic use (233,23%) and alimentary tract and metabolism drugs (218, 22%). Interventionsconcerned mainly residents and all clinical staff (209, 21%).Among the 879 (88%) interventions requiring a physician's approval,731 (83%) were accepted. Interventions were considered as having amoderate (51%) or major (17%) clinical impact. Among the interventionsprovided, 10% were considered to have an economicalpositive impact. Differences and similarities between countries willbe presented at the poster session.Discussion & Conclusion Decentralized pharmacist at patient bedsideis a pre-requisite for pharmaceutical care. There are limitedstudies comparing the activity of clinical pharmacists betweencountries. This descriptive study illustrates the ability of clinicalpharmacist to identify and solve drug-related problems in pediatricintensive care unit in four different francophone countries.

Report of Recommendations to Iowa State University of Science and Technology, Ames, Iowa, for the year ended June 30, 2010

Report on Iowa State University of Science and Technology, Ames, Iowa, for the year ended June 30, 2010

Audit report on the Student Health Facility Revenue Bond Funds of Iowa State University of Science and Technology for the year ended June 30, 2011

Audit report on the Student Health Facility Revenue Bond Funds of Iowa State University of Science and Technology for the year ended June 30, 2011

Agreed-upon procedures report on the Iowa State Center Business Office of Iowa State University of Science and Technology for the year ended June 30, 2011

Agreed-upon procedures report on the Iowa State Center Business Office of Iowa State University of Science and Technology for the year ended June 30, 2011

Prediction markets supporting technology assessment

In this thesis, we study the use of prediction markets for technology assessment. We particularly focus on their ability to assess complex issues, the design constraints required for such applications and their efficacy compared to traditional techniques. To achieve this, we followed a design science research paradigm, iteratively developing, instantiating, evaluating and refining the design of our artifacts. This allowed us to make multiple contributions, both practical and theoretical. We first showed that prediction markets are adequate for properly assessing complex issues. We also developed a typology of design factors and design propositions for using these markets in a technology assessment context. Then, we showed that they are able to solve some issues related to the R&D portfolio management process and we proposed a roadmap for their implementation. Finally, by comparing the instantiation and the results of a multi-criteria decision method and a prediction market, we showed that the latter are more efficient, while offering similar results. We also proposed a framework for comparing forecasting methods, to identify the constraints based on contingency factors. In conclusion, our research opens a new field of application of prediction markets and should help hasten their adoption by enterprises. Résumé français: Dans cette thèse, nous étudions l'utilisation de marchés de prédictions pour l'évaluation de nouvelles technologies. Nous nous intéressons plus particulièrement aux capacités des marchés de prédictions à évaluer des problématiques complexes, aux contraintes de conception pour une telle utilisation et à leur efficacité par rapport à des techniques traditionnelles. Pour ce faire, nous avons suivi une approche Design Science, développant itérativement plusieurs prototypes, les instanciant, puis les évaluant avant d'en raffiner la conception. Ceci nous a permis de faire de multiples contributions tant pratiques que théoriques. Nous avons tout d'abord montré que les marchés de prédictions étaient adaptés pour correctement apprécier des problématiques complexes. Nous avons également développé une typologie de facteurs de conception ainsi que des propositions de conception pour l'utilisation de ces marchés dans des contextes d'évaluation technologique. Ensuite, nous avons montré que ces marchés pouvaient résoudre une partie des problèmes liés à la gestion des portes-feuille de projets de recherche et développement et proposons une feuille de route pour leur mise en oeuvre. Finalement, en comparant la mise en oeuvre et les résultats d'une méthode de décision multi-critère et d'un marché de prédiction, nous avons montré que ces derniers étaient plus efficaces, tout en offrant des résultats semblables. Nous proposons également un cadre de comparaison des méthodes d'évaluation technologiques, permettant de cerner au mieux les besoins en fonction de facteurs de contingence. En conclusion, notre recherche ouvre un nouveau champ d'application des marchés de prédiction et devrait permettre d'accélérer leur adoption par les entreprises.

Audit report of the accompanying Schedule of Debt Service and Coverage for Iowa State University of Science and Technology as of February 10, 2012 for the Athletic Facilities Revenue Bond Funds

Audit report of the accompanying Schedule of Debt Service and Coverage for Iowa State University of Science and Technology as of February 10, 2012 for the Athletic Facilities Revenue Bond Funds

Agency Fact Sheet, Department of Information Technology, FY2002

This document produced by the Iowa Department of Administrative Services has been developed to provide a multitude of information about executive branch agencies/department on a single sheet of paper. The facts provides general information, contact information, workforce data, leave and benefits information and affirmative action data.

Testosterone and doping control.

BACKGROUND AND OBJECTIVES: Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone. METHODS: Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids. RESULTS: Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone. CONCLUSIONS: Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.

Agency Fact Sheet, Department of Information Technology, FY2003

This document produced by the Iowa Department of Administrative Services has been developed to provide a multitude of information about executive branch agencies/department on a single sheet of paper. The facts provides general information, contact information, workforce data, leave and benefits information and affirmative action data.

Report on a review of selected application controls over the Iowa State University of Science and Technology Facilities Planning and Management - Facilities Administrative Management Information System for the period of April 18, 2011 through May 16, 2011

Report on a review of selected application controls over the Iowa State University of Science and Technology Facilities Planning and Management - Facilities Administrative Management Information System for the period of April 18, 2011 through May 16, 2011

Comparative sensitivity of tumor and non-tumor cell lines as reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC50-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

Report of Recommendations to Iowa State University of Science and Technology, Ames, Iowa, for the year ended June 30, 2011

Report on Iowa State University of Science and Technology, Ames, Iowa, for the year ended June 30, 2011