Medicine and Health Sciences Commons^™

Lipiodol Versus Methylene Blue For Prevention Of Postsurgical Adhesion Formation In A Rat Model., E. Duran, Esra Kuscu, Hulusi Zeyneloglu, Esra Saygili, Sertac Batioglu

Eyup Hakan Duran

OBJECTIVE: To determine the effects of intraperitoneal Lipiodol and methylene blue in prevention of postsurgical adhesion formation. STUDY DESIGN: Thirty female rats were divided into three equal groups and a standard damage to provoke adhesion formation was made by laparotomy to each of them. Methylene blue and Lipiodol was administered intraperitoneally to the first and second groups, respectively; while the third group was taken as control and no additional intervention was made. Adhesions were scored by a second look laparotomy which was made 21 days after the first operation. RESULTS: Adhesion scores of the second group (i.e. Lipiodol group) were …

Expression And Localization Of Inducible And Endothelial Nitric Oxide Synthase In The Rat Ovary. Effects Of Gonadotropin Stimulation In Vivo, Bradley Van Voorhis, K. Moore, P. Strijbos, S. Nelson, S. Baylis, D. Grzybicki, C. Weiner

Bradley J Van Voorhis

Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine++ if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to …

Autoantibodies And Infertility: A Review Of The Literature, Bradley Van Voorhis, D. Stovall

Bradley J Van Voorhis

The role that autoantibodies play in infertility remains uncertain. There are conflicting data regarding the prevalence of autoantibodies in women with endometriosis. Certainly no one has demonstrated an association between the presence of antibodies in women with endometriosis and infertility. Despite intensive study, there is also no consensus on a role of autoantibodies to the zona pellucida as a cause of infertility. Recently, much attention has been focused on autoantibodies and infertility particularly with regards to phospholipid antibodies and their effect on IVF success rates. The literature suggests that women with infertility have an increased prevalence of phospholipid antibodies compared …

Comparison Of In Vivo Bioavailability Of Progestational Agents Into The Rat Uterus And Liver And The Effect Of Plasma Protein Binding, Bradley Van Voorhis, D. Matt, M. Tedeschi, K. Steingold

Bradley J Van Voorhis

The in vivo bioavailabilities of three clinically available progestational agents were evaluated with a previously described rat model. With this model a single-injection, double-isotope technique was performed to calculate and compare the unidirectional extractions of progesterone, 19-nortestosterone, and medroxyprogesterone acetate into the rat uterus and liver. To assess the role of plasma protein binding in the extraction of these agents, steroids were presented in four different vehicles: (1) Ringer's solution, 0.1% bovine serum albumin; (2) Ringer's solution, 4% bovine serum albumin; (3) Ringer's solution, 0.8 mg/ml, alpha 1-acid glycoprotein; (4) human pregnancy serum. The results revealed that liver extraction always …

Effect Of Hydrogen Peroxide On Prostaglandin Production And Contractions Of The Pregnant Rat Uterus, P. Cherouny, R. Ghodgaonkar, Jennifer Niebyl, N. Dubin

Jennifer R Niebyl

Although evidence for a role for prostaglandins in parturition is abundant, less is known about how prostaglandin levels are regulated at term. Conditions occurring peripartum in the uteroplacental unit can result in reactive oxygen production. We investigated the effect of one reactive oxygen product, hydrogen peroxide, on in vitro activity of uterine segments from the 18-day-pregnant rat. H2O2 (0.3 mmol/L) was found to elicit rhythmic contractions and increase prostaglandins F2 alpha and E2 release by uterine tissue. Indomethacin blocked both of these effects. We conclude that H2O2 stimulates uterine contractions through a prostaglandin release mechanism. A speculative hypothesis of peripartum …

Drugs For Inhibition Of Premature Labor, Jennifer Niebyl

Jennifer R Niebyl

Effective inhibition of premature labor depends on prompt initiation of treatment. The author discusses factors initiating parturition, and the benefits and risks for mother and child of administration of alcohol, beta adrenergic agents, magnesium sulfate, and other agents that may counteract them.

The Pharmacologic Inhibition Of Premature Labor, Jennifer Niebyl, D. Blake, J. Johnson, T. King

Jennifer R Niebyl

Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to …

Preterm Parturition. Prostaglandin Synthetase Inhibitors, Jennifer Niebyl

Jennifer R Niebyl

No abstract provided.

Encapsulated Beta-Islet Cells As A Bioartificial Pancreas To Treat Insulin-Dependent Diabetes During Pregnancy, Stephen Hunter, Y. Wang, C. Weiner, Jennifer Niebyl

Jennifer R Niebyl

OBJECTIVE: Our purpose was to determine the effectiveness of the bioartificial pancreas technique in correcting (1) maternal carbohydrate metabolism and (2) fetal malformation rates in a pregnant diabetic animal model. STUDY DESIGN: Insulin secretion from encapsulated rat islets cultured in the presence of homologous rat prolactin was determined and compared with that of controls. Streptozotocin-induced diabetic Balb/c mice were then transplanted with rat islet cells encapsulated within alginate microbeads and were then bred. Blood glucose determinations were made after transplantation and throughout gestation. Pups were delivered by cesarean section on day 19 of gestation. Outcome parameters from the transplanted study …

Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai

Xiangbing Meng

Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …

Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie

Xiangbing Meng

Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …

Biodegradable Microspheres Containing Group B Streptococcus Vaccine: Immune Response In Mice, Stephen Hunter, M. Andracki, A. Krieg

Stephen K. Hunter

OBJECTIVE: This study seeks to show the feasibility of producing a group B Streptococcus (GBS) vaccine, which is capable of producing both a local IgA immune response at the mucosal surface where GBS is colonized and a humoral IgG response, which is capable of transplacental passive immunization. STUDY DESIGN: Inactivated GBS antigen was microencapsulated in poly (D, L-lactic-co-glycolic acid) (PLG) with a water-in-oil-in-water double emulsion technique. Immunostimulatory synthetic oligodeoxynucleotides containing cytidine-phosphate-guanosine (CpG) motifs were coencapsulated as a potent adjuvant. The ICR strain of mouse was used in these studies. Female mice with normal immune systems were immunized with the PLG …

From Molecules To Medicine: A Future Cure For Preeclampsia?, Mark Santillan, Donna Santillan, Curt Sigmund, Stephen Hunter

Stephen K. Hunter

In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of …

In Vivo Biocompatibility Evaluation Of Cibacron Blue-Agarose, J. Kao, R. Rose, M. Yousef, Stephen Hunter, V. Rodgers

Stephen K. Hunter

This study investigated the biocompatibility of Cibacron blue-agarose as a biomaterial for microencapsulation. Cibacron blue-agarose is known to have an affinity for albumin under certain pH conditions and in the proper steric environment. Thus it was postulated that the material's high affinity for host albumin might reduce a secondary immune response and reduce the fibrotic overgrowth that often accompanies transplanted foreign materials. In vivo tests were performed using the Lewis rat model. Both Cibacron blue-agarose and plain agarose disks were prepared, with some disks from each group being pre-exposed to sera from Lewis rats. The disks were transplanted into the …

Promotion Of Neovascularization Around Hollow Fiber Bioartificial Organs Using Biologically Active Substances, Stephen Hunter, J. Kao, Y. Wang, J. Benda, V. Rodgers

Stephen K. Hunter

A limiting factor of the long-term function of bioartificial organs is oxygen delivery to the encapsulated tissue. This study determined whether incorporation of endothelial cell growth factor (ECGF) into the alginate core of a hollow fiber bioartificial organ will induce neovascularization around the hollow fiber. Polyethersulfone (PES) and polyvinylidine difluoride (PVDF) hollow fibers were examined. Endothelial cell growth factor was incorporated into sodium alginate, extruded into the lumen of hollow fibers, and cured in calcium chloride. Samples without ECGF were fabricated and used as controls. Hollow fibers were implanted into 16 rats. For each rat, two implants were placed subcutaneously …

Encapsulated Beta-Islet Cells As A Bioartificial Pancreas To Treat Insulin-Dependent Diabetes During Pregnancy, Stephen Hunter, Y. Wang, C. Weiner, Jennifer Niebyl

Stephen K. Hunter

OBJECTIVE: Our purpose was to determine the effectiveness of the bioartificial pancreas technique in correcting (1) maternal carbohydrate metabolism and (2) fetal malformation rates in a pregnant diabetic animal model. STUDY DESIGN: Insulin secretion from encapsulated rat islets cultured in the presence of homologous rat prolactin was determined and compared with that of controls. Streptozotocin-induced diabetic Balb/c mice were then transplanted with rat islet cells encapsulated within alginate microbeads and were then bred. Blood glucose determinations were made after transplantation and throughout gestation. Pups were delivered by cesarean section on day 19 of gestation. Outcome parameters from the transplanted study …

Efficacy Of Polymeric Encapsulated C5a Peptidase-Based Group B Streptococcus Vaccines In A Murine Model., Donna Santillan, Karishma K Rai, Mark Santillan, Yogita Krishnamachari, Aliasger K Salem, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 μg of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at …

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 …

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 …

Effects Of Bevacizumab In Mouse Model Of Endometrial Cancer: Defining The Molecular Basis For Resistance, S. Davies, Donghai Dai, G. Pickett, K. Thiel, V. Korovkina, Kimberly Leslie

Donghai Dai

Endometrial cancer is the most frequent gynecologic cancer in women. Long-term outcomes for patients with advanced stage or recurrent disease are poor. Targeted molecular therapy against the vascular endothelial growth factor (VEGF) and its receptors constitute a new therapeutic option for these patients. The goal of our study was to assess the potential effectiveness of inhibition of VEGF/VEGFR signaling in a xenograft model of endometrial cancer using bevacizumab (Avastin, a humanized antibody against VEGFA). We also aimed to identify molecular markers of sensitivity or resistance to this agent. We show that bevacizumab retards tumor growth in athymic mice by inhibiting …

A Potential Synergistic Anticancer Effect Of Paclitaxel And Amifostine On Endometrial Cancer, Donghai Dai, A. Holmes, T. Nguyen, S. Davies, D. Theele, C. Verschraegen, Kimberly Leslie

Donghai Dai

Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G1 phase …

Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai

Donghai Dai

Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …

A Therapeutic Model For Advanced Endometrial Cancer: Systemic Progestin In Combination With Local Adenoviral-Mediated Progesterone Receptor Expression, Donghai Dai, L. Albitar, T. Nguyen, L. Laidler, M. Singh, Kimberly Leslie

Donghai Dai

Cancer of the uterine endometrium is a frequent gynecologic malignant disease for which few therapeutic options are available for advanced disease. Progesterone is the normal female hormone that limits growth and proliferation of endometrial cancers; however, progesterone receptors are frequently down-regulated, leading to treatment failures. The current studies explored the effectiveness of adenoviral-mediated progesterone receptor gene transduction in combination with progestin therapy in mouse xenograft models. Pretreatment of cells with progesterone receptor-encoding adenovirus and progestin inhibited the development of s.c. tumors in athymic mice. In the i.p. xenograft model, replacement of both isoforms of progesterone receptor, PRA and PRB, in …

Gestational Trophoblastic Diseases: 1. Pathophysiology Of Hyperglycosylated Hcg, L. Cole, Donghai Dai, S. Butler, Kimberly Leslie, E. Kohorn

Donghai Dai

OBJECTIVE: Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. METHODS AND RESULTS: hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma …

The Nitric Oxide-Cyclic Gmp Pathway Plays An Essential Role In Both Promoting Cell Survival Of Cerebellar Granule Cells In Culture And Protecting The Cells Against Ethanol Neurotoxicity, N. Pantazis, J. West, Donghai Dai

Donghai Dai

NMDA has two beneficial effects on primary neuronal cultures of cerebellar granule cells (CGCs) established from 10-day-old rat pups. First, NMDA is neurotrophic and will enhance survival of CGCs in culture in the absence of ethanol. Second, ethanol exposure will induce cell death in CGC cultures, and NMDA can lessen this ethanol-induced cell loss, i.e., NMDA is neuroprotective. Because NMDA can stimulate production of nitric oxide (NO), which can in turn enhance synthesis of cyclic GMP, this study tested the hypothesis that the NO-cyclic GMP pathway is essential for NMDA-mediated neurotrophism and neuroprotection. Inhibiting the synthesis of NO with N(G)-nitro-L-arginine …

Mrna Expression In Rabbit Experimental Aneurysms: A Study Using Gene Chip Microarrays, W. Mangrum, F. Farassati, R. Kadirvel, C. Kolbert, S. Raghavakaimal, Donghai Dai, Y. Ding, D. Grill, V. Khurana, D. Kallmes

Donghai Dai

BACKGROUND AND PURPOSE: The molecular characteristics of intracranial aneurysms are still poorly documented. A rabbit elastase aneurysm model has been helpful in the evaluation of devices and strategies involved in endovascular treatment of aneurysms. The goal of this project was to document the molecular changes, assessed by gene chip microarrays, associated with the creation of aneurysms in this model compared with the contralateral carotid artery. MATERIALS AND METHODS: A microarray of rabbit genes of interest was constructed using rabbit nucleotide sequences from GenBank. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 4 rabbits. …