Animal Experimentation and Research Commons^™

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

Arkansas Animal Science Department Report 2011, David L. Kreider

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein

Pharmacy Faculty Articles and Research

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Arkansas Animal Science Department Report 2010, David L. Kreider

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Arkansas Animal Science Department Report 2010, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Arkansas Animal Science Department Report 2008, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Arkansas Animal Science Department Report 2006, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Arkansas Animal Science Department Report 2004, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Arkansas Animal Science Department Report 2003, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

The faculty and staff of the Animal Science Program are pleased to present the sixth edition of the Arkansas Animal Science Report. As with virtually all programs in the country, budget constraints presented serious challenges to teaching, research, and extension programming. However, the faculty and staff responded with innovation, good management, and hard work to maintain a productive program designed to benefit the students of the University and the citizens of the state. We are committed to remaining faithful to our Land-Grant mission. A sincere thank you is owed to Dr. Zelpha Johnson and Dr. Wayne Kellogg for editing this …

Arkansas Animal Science Department Report 2002, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Il-10 And Alveolar Bone Loss, Abdulaziz Saud Al-Rasheed

Loma Linda University Electronic Theses, Dissertations & Projects

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory activities. IL-10 knockout (KO) mice exhibit severe intestinal inflammation in the presence of normal gut flora. We hypothesized that IL-10 KO mice would also be susceptible to inflammatory periodontal disease resulting in alveolar bone loss (ABL). The purpose of this study was to compare naturally occurring ABL in IL-10 KO and wild type (WT) mice. Twelve IL-10 KO and 12 WT mice, age-(7 months) and sex-(male) matched, were used. Half of the mice were on 129/SvEv and half on C57BL/6J background. Animal heads were defleshed and treated to remove all organic material. ABL …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Arkansas Animal Science Department Report 2000, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

Animal Science is very much devoted to youth education and development. During the past year, over 20,000 youth were involved in 4-H livestock projects. Two very successful activities that took place last year were the Mid-American Grassland Evaluation Contest and Livestock Judging Camps. The Grassland Contest is designed to teach students about grassland resource management for livestock and wildlife uses. The contest was held in Cape Girardeau, Missouri. Firstplace honors in the 4-H division went to White County, and second place honors went to Van Buren County. Two Livestock Judging Camps (Fayetteville and Hope) were conducted this past year. A …

Periradicular Response Of Immunodeficient Rats To Mechanical Pulpal Exposure, James E. Stich

Loma Linda University Electronic Theses, Dissertations & Projects

Periradicular lesions develop as a result of the interaction between root canal irritants and the immune system. The purpose of this study was to investigate the periradicular response of immunodeficient rats to their oral flora. Twenty Sprague-Dawley rats received a total body irradiation dose of 750 cGy one week prior to the investigation. The pulps of the mandibular first molars of these animals and six nonirradiated rats were exposed mechanically with a ½ round bur and left open to the oral cavity. Additional irradiation (350 cGy) was administered bi-weekly to maintain immunosuppression. Periradicular specimens were obtained after two and four …

Arkansas Animal Science Department Report 1999, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Neuronal And Metabolic Increases In Pedunculopontine Nucleus Of Parkinson's Rats, Jonathan Dennis Carlson

Loma Linda University Electronic Theses, Dissertations & Projects

The theoretical mechanisms underlying the symptoms of Parkinson’s disease are based on dysfunctional output from the basal ganglia projected to the cortex via the thalamus. However, the subthalamic nucleus (STN) and substantia nigra pars reticularis (SNr) as part of the basal ganglia, also project to the brainstem, in particular to the pedunculopontine nucleus (PPN). Both the STN and SNr have altered neuronal activity in the 6-hydroxydopamine (6-OHDA) Parkinson’s model rat. Thus, it is hypothesized that the PPN is altered in this model of Parkinson’s disease.

This hypothesis was examined by comparing the rates of glucose metabolism and spontaneous neuronal activity …

Arkansas Animal Science Department Report 1998, Stacey Gunter

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Periodontal Repair In Dogs : Effect Of Recombinant Human Transforming Growth Factor Beta-1 On Guided Tissue Regeneration, Saghi Shayan Razi

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to evaluate bone and cementum regeneration in the critical size, supraalveolar, periodontal defect model following surgical implantation of recombinant human transforming growth factor beta-1 (rhTGFß-1) in conjunction with guided tissue regeneration (GTR). Five male beagle dogs were used in a split-mouth design. Alternate jaw quadrants in consecutive animals received GTR with rhTGFß-1 in a resorbable calcium carbonate carrier. Contralateral jaw quadrants received GTR with carrier only (control). The healing interval was 4 weeks. Clinical healing was generally uneventful, however, minor membrane exposures were observed for both treatments with limited gingival inflammation. All defects with …

The Effect Of Guidor™ And Hop-1 On Hard Tissue Healing : Following Periradicular Surgery In Cats, Hugh Maguire

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to evaluate the effects of the resorbable membrane Guidor™ and the osteogenic protein hOP-1 on hard tissue healing following periradicular surgery in cats.

Surgical endodontic therapy was performed on the maxillary canine teeth of twelve cats. After orthograde root canal therapy, flap reflection, osteotomy, resection of the root end, root end cavity preparation and the placement of a root end filling, eight of the surgical sites were treated with Guidor™ and eight with hOP-1. The remaining eight sites received no further treatment and served as controls.

The animals were sacrificed at twelve weeks following …

Periodontal Repair In Dogs : Part I : Evaluation Of The Natural Disease Model ; Part Ii : Eptfe Barrier Membranes Support Wound Stabilization And Enhance Bone Regeneration, James Marc Haney

Loma Linda University Electronic Theses, Dissertations & Projects

Animal models are frequently consulted for histometric analysis of reconstructive periodontal therapy. Statistical analysis of induced lesion defects and surgically created defects from our laboratory suggest defect size homogeneity is critical for the model to discriminate treatment effects. This study characterizes natural disease defects in beagle dogs. Buccal-lingual histologic sections from the 2nd, 3rd, and 4th mandibular premolar teeth (P2, P3, P4) from 6 aged beagle dogs with natural disease defects were evaluated for variation in defect height between pair matched tooth types, and jaw quadrants, as well as estimated confidence intervals for treatment differences between left and right pair …

Suppressive Effects Of Transforming Factor-Β And Interleukin-10 On The Cytolytic Activity Of Murine Macrophages And Reversal By Cytokines, Chin-Hung Lin

Loma Linda University Electronic Theses, Dissertations & Projects

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of ³H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was …

Development Of Periapical Lesions In Immunosuppressed Rats, Phillip A. Waterman Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

The pathogenesis of periapical lesions is the interaction of the oral flora with the existing host defenses. The role of bacteria has been established in endodontic disease but the contribution of the host defenses in periapical lesion formation is less clear. The purpose of this study was to compare periapical lesion development in immunosuppressed rats with that in normal rats. Thirty-five, eight-week old Sprague-Dawley rats were equally divided into seven groups. Groups 1, 2, and 3 were given weekly injections of Cytoxan, an immunosuppressive agent. Groups 4, 5, and 6 received no immunosuppressive therapy. Group 7 served as a control, …

Arkansas Cooperative Beef Bull Performance Test 1991, M. W. Eaton, A. E. Brown Jr., J. A. Hornsby, R. W. Parham, J. D. Shockey, W. C. Loe

Arkansas Agricultural Experiment Station Research Series

Performance testing of beef bulls was initiated to improve productivity of Arkansas beef cattle through breeding. This cooperative testing program provides cattlemen with reliable information for identifying animals with superior breeding value for the traits of production measured in the test. By using the information as a basis for herd sire selection, a breeder can greatly increase the chances of obtaining a bull that will sire rapid-gaining, more efficient, highquality calves. Such calves can increase profits for both the breeder and the feeder. This testing program provides information that is useful to financial institutes in arranging their lending programs and …

The Role Of T Cells In The Pathogenesis Of Periapical Lesions, John B. Wallstrom

Loma Linda University Electronic Theses, Dissertations & Projects

The pulps of mandibular molars of 15 athymic and 15 conventional rats were surgically exposed and left open to their oral flora. Each group was divided into 3 subgroups of 5 animals each. The rats were sacrificed after their pulps were exposed for 2, 4, or 8 weeks. After fixing, decalcifying, and embedding, the specimens were sectioned and stained with H and E. They were then examined under a microscopic grid and quantified by percentages of surface areas of bone, connective tissue, bone marrow, intrabony spaces, periapical lesions, and numbers of osteoclasts. This was done using a DataVoice computerized data …

In Vitro Evaluation Of Cancer Patient Immune Responses Following Infusion Of Radiolabeled Murine Monoclonal Antibody, Kelly A. King

Loma Linda University Electronic Theses, Dissertations & Projects

Several monoclonal antibody (MAb) types derived from mice have been developed specifically for the use of targeting human tumors. The specificity of these murine MAb’s for their respective tumor antigens is very high making them potentially good immunotherapeutic agents for cancer treatment and diagnosis. A limiting factor in using these murine MAb’s in patients is the development of human anti-mouse antibody (HAMA). The presence of HAMA may reduce the effectiveness of MAb for tumor targeting. If patient sensitization could be quickly detected following the initial infusion of MAb, then future infusion could be altered or terminated to prevent further sensitization. …

Enhancement Of Intratumor Antibody Distribution With A Bifunctional Antibody Delivery System And With Hyperthermia, Karen Lynn King

Loma Linda University Electronic Theses, Dissertations & Projects

The intratumor distribution of a new monoclonal antibody-hapten-based delivery system was examined. From two marine antibodies, Hybritech, Inc. has developed a bifunctional antibody (BPA) with specificities against CEA (ZCE-025 or GEM 231) and against one of two derivatives of [¹¹¹In]-benzyl-EDTA (CHA 255), EOTUBE or BLEDTA IV, to form ZCE/CHA or CEM/CHA. BFA accumulates in CEA-expressing tissue and clears from non-antigenic tissues prior to administration of an [¹¹¹In]-hapten.

Using five groups of nude mice bearing human colon tumor xenografts (T380), we evaluated different carriers of [¹¹¹In]-EOTUBE to prelocalized ZCE/CHA. We administered all antibodies and haptens …

Autonomic Nervous System And Cholesterol Transport, Yuan-Line Hung

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL₂ cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order …