Medicine and Health Sciences Commons^™

Protective Immunization In Mice Against Group B Streptococci Using Encapsulated C5a Peptidase, Donna Santillan, M. Andracki, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The purpose of the study was to test whether C5a peptidase encapsulated within a biodegradable polymer can act as a vaccine and elicit an immune response to prevent group B streptococci (GBS) infection in mice and provide protection to pups. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-co-glycolide). Female ICR mice were immunized with encapsulated C5a peptidase, free C5a peptidase, or empty microparticles. Booster doses were given at days 21 and 42. Antibody responses were measured by enzyme-linked immunosorbent assay. Challenge with GBS type III was performed 4 days after the final booster in the vaginal …

Cell Encapsulation As A Potential Nondietary Therapy For Maternal Phenylketonuria., Donna Santillan, Mark Santillan, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The objective of this work was to determine whether cells overexpressing phenylalanine (Phe) hydroxylase (PAH) can significantly reduce Phe in vitro for potential use as a therapy for preventing maternal phenylketonuria.

STUDY DESIGN: Human 293T and WRL68 cell lines were transiently and stably transfected to overexpress PAH. Cells were encapsulated within microspheres of sodium alginate. Timed measurements of Phe in media were performed using tandem mass spectrometry.

RESULTS: Both nonencapsulated and encapsulated transiently transfected cells overexpressing PAH significantly reduced the Phe concentration in media by approximately 50% in comparison to mock-transfected cells. Cell line clones stably expressing PAH significantly …

Theoretical Prediction Of Induction Period From Transient Pore Evolvement In Polyester-Based Microparticles, A. Zhao, Stephen Hunter, V. Rodgers

Stephen K. Hunter

A model was developed and compared to experimental results for prediction of the induction period during drug delivery from various compositions of biodegradable copolymer PLGA microparticles. The uniqueness of this model is that it considers transient pore evolvement and uses the kinetic parameters of polymer degradation, which are independent of experimental measurements of microparticle erosion, in its analysis. Delivery data from PLGA microparticles (50:50, 75:25, and 85:15) releasing ovalbumin (OVA, 46 kDa) and bovine serum albumin (BSA, 66 kDa) were determined and used as the model systems. Experimental measurements were carried out from 85 to 150 days depending on the …

Rotary Culture Enhances Pre-Osteoblast Aggregation And Mineralization, S. Facer, R. Zaharias, M. Andracki, J. Lafoon, Stephen Hunter, G. Schneider

Stephen K. Hunter

Three-dimensional environments have been shown to enhance cell aggregation and osteoblast differentiation. Thus, we hypothesized that three-dimensional (3D) growth environments would enhance the mineralization rate of human embryonic palatal mesenchymal (HEPM) pre-osteoblasts. The objective of this study was to investigate the potential use of rotary cell culture systems (RCCS) as a means to enhance the osteogenic potential of pre-osteoblast cells. HEPM cells were cultured in a RCCS to create 3D enviroments. Tissue culture plastic (2D) cultures served as our control. 3D environments promoted three-dimensional aggregate formations. Increased calcium and phosphorus deposition was significantly enhanced three- to 18-fold (P < 0.001) in …

Leukemia In Pregnancy And Fetal Response To Multiagent Chemotherapy, W. Hansen, P. Fretz, Stephen Hunter, J. Yankowitz

Stephen K. Hunter

BACKGROUND: Leukemia is rare in pregnancy and treatment with intensive, multiagent chemotherapy produces complete remission in most adults, but might have deleterious effects on fetuses. CASE: A 24-year-old gravida 3 para 2 presented at 24 weeks with pruritus, rash, pancytopenia, and hepatitis. A bone marrow biopsy found acute lymphocytic leukemia. She completed three cycles of intensive multiagent chemotherapy with transient oligohydramnios in each cycle. Although there was decreased fetal growth rate, umbilical artery Doppler scans were normal. She delivered a normal 2150-g male infant at 36 weeks. CONCLUSION: Pregnant women with newly diagnosed leukemia should not delay treatment, but multiagent …

Bioartificial Pancreas Use In Diabetic Pregnancy, Stephen Hunter, Y. Wang, V. Rodgers

Stephen K. Hunter

The purpose of this study was to evaluate the feasibility and effectiveness of Bioartificial Pancreas (BAP) technology use during diabetic pregnancy. In particular, the study asked 1) can microencapsulated islet cells effectively correct carbohydrate metabolism during diabetic pregnancy and 2) will such therapy, if initiated before conception, eliminate diabetes-induced congenital malformations in the fetus? Streptozotocin-induced diabetic female mice (ICR) received transplants of rat islets encapsulated within alginate microbeads. Animals were placed with male mice and bred. Random, nonfasting blood glucose (BG) determinations were made posttransplantation and throughout pregnancy. Pups were delivered by cesarean section on day 19 of gestation. Outcome …

Present And Future Perspectives On The Use Of Free Or Encapsulated Pancreatic Islet Cell Transplantation As A Treatment Of Pregnancy Complicated By Type 1 Diabetes, Stephen Hunter

Stephen K. Hunter

Pregnancies complicated by insulin-dependent diabetes mellitus (IDDM) pose significant health risks to both the mother and her developing fetus. Congenital malformations in the offspring of diabetic mothers have an incidence which is 2-5 times that seen in the background. Euglycemia in the first trimester of pregnancy can reduce this incidence, but achieving euglycemia with conventional exogenous insulin therapy is both costly and difficult. Even with intense insulin dosage adjustments, the blood glucose profile of the diabetic pregnant patient does not mimic that seen in nondiabetic patients. Both the difficulties and inadequacies of conventional therapy for IDDM-complicated pregnancy provide a stimulus …

Mathematical Modeling Of Myoglobin Facilitated Transport Of Oxygen In Devices Containing Myoglobin-Expressing Cells, H. Tilakaratne, Stephen Hunter, V. Rodgers

Stephen K. Hunter

Low pO(2) is perhaps the most significant factor in artificial pancreas failure. In these environments, not only is the beta cell production of insulin reduced, but the cell death rate is also significantly higher. Mathematical models are developed to test the feasibility of facilitated oxygen transport in enhancing O(2) flux to genetically engineered cells in a bioartificial device such as a pancreas. For this device, it is proposed that beta cells be genetically engineered to express myoglobin throughout the cell. In addition, the significance of including myoglobin throughout the alginate matrix present to provide immuno-protection for the transplanted cells is …

The Influence Of Fetal Sex On Patterns Of Change In Anti-Mullerian Hormone During Pregnancy, Ryan Empey, Donna A. Santillan, Mark Santillan, Eric M. Tyler, Stephen K. Hunter, Elaine M. Smith, Barbara J. Stegmann

Stephen K. Hunter

Maternal anti-mullerian hormone declines sharply between 13-15 weeks, likely as a result of feto-placental signaling. Fetal AMH levels are known to be widely disparate after the first trimester, with high levels in male and absent levels in female. However, it is unclear as to whether differing fetal AMH levels influence the pattern of change of maternal AMH. Our objective was to examine AMH throughout gestation to determine if the maternal concentration varies according to the gender of the fetus.