Animal Experimentation and Research Commons^™

Harry F. Harlow And Animal Research: Reflection On The Ethical Paradox, John P. Gluck

Experimentation Collection

With respect to the ethical debate about the treatment of animals in biomedical and behavioral research, Harry F. Harlow represents a paradox. On the one hand, his work on monkey cognition and social development fostered a view of the animals as having rich subjective lives filled with intention and emotion. On the other, he has been criticized for the conduct of research that seemed to ignore the ethical implications of his own discoveries. The basis of this contradiction is discussed and propositions for current research practice are presented.

An Animal Model For Development Of Pulpal Inflammation, John W. Masters

Loma Linda University Electronic Theses, Dissertations & Projects

Several animal models have been proposed to develop pulpal inflammation. Procedures recommended in these models have many variables and have not produced consistent results. The purpose of this study was to create pulpal inflammation using the Nd:YAG laser.

Forty-five cuspids of 12-18 month old beagle dogs were lased at 5, 7.5, and 10 watts (W) for 20 seconds with a 600 micron contact probe. Five cuspids were not lased but were used as controls. Following laser application, the teeth were extracted at intervals of 3, 7, and 30 days. They were then fixed in 10% formalin, decalcified, sectioned, and stained …

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 …

Bone Morphogenetic Proteins And Periodontal Repair, Michael B. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

For over thirty years now, research has been carried out to isolate and purify bone morphogenetic protein (BMP), a substance which has been shown to induce heterotopic bone formation in various animal species. Recent advances in the fields of developmental biology, molecular biology and genetics, have shown that the BMPs not only are responsible for postfetal bone induction (including normal bone remodeling, healing and repair), but are also critical during embryogenesis - not only in regards to the skeletal system, but quite possibly in the morphogenesis and pattern formation of other tissues and organs as well.

Due to their bone …

Regulation Of Melanogenesis In B16 Mouse Melanoma Cells By Protein Kinase C (Pkc), Harish Mahalingam

Theses, Dissertations and Capstones

The pigment cell-specific expression of tyrosinase and TRP1 has been shown to be important for the production of melanin in pigmented cells. Using a pigmented cell line, B16 mouse melanoma, we obtained evidence that PKC plays a major role in regulating melanogenesis. Chronic treatment with phorbol dibutyrate (PDBu) leads to downregulation of PKC activity and protein levels. This is accompanied by a loss of pigmentation which is correlated with a 50% reduction and a complete loss of TRP1 and tyrosinase respectively. Similar results were obtained with Northern and Western blotting indicating that PKC may regulate the steady state levels of …

A Rodent For Your Thoughts: The Animal Model Strategy In Psychology, Kenneth J. Shapiro

Experimentation Collection

In this second of three essays, I describe how the early modern psychologists adopted the strategy of further transforming rats and other species into models of human thought, feeling, and behavior, and, particularly, of disorders of these - in effect taking "a rodent for your thoughts." In the third essay I will provide a critique and empirically-based evaluation of animal model research. Here I indicate what the model strategy in the biomedical sciences, properly understand, is intended to achieve and how, by contrast, particular models are presented to the public and funding agencies. Finally, I describe how they are utilized …

The Ingrown World Of Animal Model Research In Psychology, Kenneth J. Shapiro

Experimentation Collection

In the previous essay, I described the proper function of models in science as heuristic, as a way of generating hypotheses about the actual object of study. Turning to animal models in psychology, I offered a general characterization of that enterprise using sham feeding, an animal model of the eating disorder called bulimia, as an example. In this final of three essays, I offer an evaluation of this animal model strategy that largely employs the tools of social science. I close with a recommendation and a prediction.

Alveolar Bone And Cementum Regeneration Following Periodontal Reconstructive Therapy : A Review Of Histologic Observations In Man And Experimental Animals, Karen E. Rodden

Loma Linda University Electronic Theses, Dissertations & Projects

Periodontal regeneration includes the formation of both alveolar bone and cementum. Studies reporting histologic evidence of healing following periodontal reconstructive therapy were reviewed to determine whether regeneration of these structures improves with increasing healing interval, and whether they regenerate independently or whether regeneration of one structure is dependent upon regeneration of the other. Additionally, the review addresses whether specific reconstructive modalities predictably yield increased amounts of regeneration. Differences in regenerative potential between humans, nonhuman primates, and canines were also examined. Results of over a decade of studies of periodontal reconstructive therapy were tabulated by family (human, nonhuman primate, and canine) …

Evaluation Of Nitric Oxide In Respiratory Distress Syndrome, Kimberly S. Myruski

Loma Linda University Electronic Theses, Dissertations & Projects

Little is known of the effects of low concentrations of inhaled nitric oxide (NO) on pulmonary mechanics and lung volumes in premature newborn infants with lung disease. Cardiopulmonary function tests including blood gas analyses were obtained from eleven premature lamb models with respiratory distress syndrome to determine if compliance, airways resistance, tidal volume, functional residual capacity, and gas exchange were affected. The effect of inhaled NO on the direction of shunting through the ductus arteriosus was determined using echocardiography.

Twin lambs were cannulated with arterial and venous catheters and intubated with an endotracheal tube before delivery on gestational day 126-130 …

Ornithine Decarboxylase And Polyamines In Perinatal Hypoxia, Satyaseelan Packianathan

Loma Linda University Electronic Theses, Dissertations & Projects

Hypoxic and hypoxic/ischemic episodes contribute to various neurological aberrations, learning disabilities, et cetera in surviving infants. Despite major advances in understanding the pathophysiology of hypoxia, the cellular basis for hypoxic-mediated injury remains poorly understood. In addition, the role of developmentally essential enzymes vis á vis their contributions, or lack thereof, to hypoxic-mediated injury has not been adequately investigated. In the series of studies comprising this dissertation, we tested the hypothesis that acute and/or chronic hypoxia affect the activity of omithine decarboxylase (ODC; E.C. 4.1.1.17), the developmentally essential enzyme in polyamine biosynthesis, in the fetal and newborn rat brain. Fetal and …

Periodontal Repair In Dogs : Evaluation Of Rhbmp-2 Carriers, Lauralee Nygaard

Loma Linda University Electronic Theses, Dissertations & Projects

This study evaluated candidate carriers for recombinant human bone morphogenic protein-2 (rhBMP-2) in periodontal reconstructive surgery.

Canine demineralized bone matrix (DBM), bovine inorganic crystallene bone matrix (Bio-Oss), bovine derived microfibrillar collagen matrix (Helistat), poly (D,L-lactide-coglycolide) micropaiticles (PLGA), and polylactic acid granules (Drilac) were used with rhBMP-2 (20 (µg/100 µl implant volume) in routine critical size canine supraalveolar periodontal defects. Contralateral defects in six beagle dogs were randomly assigned to receive: DBM/rhBMP-2, DBM-control, Bio-Oss/rhBMP-2, Helistat/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2, all with autologous blood except for Helistat and PLGA. Animals were sacrificed eight weeks post-surgery and block sections of the defects were processed …

Experimental Peri-Implant Tissue Breakdown In Rhesus Monkeys, Oliver Hanisch

Loma Linda University Electronic Theses, Dissertations & Projects

The aim of this investigation was to characterize peri-implant tissue breakdown following ligature-induced plaque accumulation around osseointegrated implants in the rhesus monkey. Two hydroxyapatite-coated cylindrical implants were inserted bilaterally in the second premolar and first molar region of both mandible and maxilla in four non-human primates (Macaca mulatto). The implants were left submerged to osseointegrate for one year. Eight weeks after healing abutment connection, a two-month plaque control program was initiated. At the end of this period, clinical and radiographic recordings were carried out, and peri-implant subgingival microbial samples were obtained (baseline). Subsequently, cotton ligatures were placed around …

How The Rat Turned White, Kenneth J. Shapiro

Experimentation Collection

This is the first in a three-part series on the use of animals in psychological research. In it, I describe how animals got into laboratories in the first place, and their purpose and life there. In the second, I will describe animal model research, the strategy whereby psychologists' develop nonhuman animal models to study human psychopathology. In the concluding piece, I will present a critique of this enterprise, using original data I gathered. The three articles are based on a forthcoming book, Animal Models of Human Psychology: Science, Ethics, and Policy.

The Animal Research Controversy: Protest, Process & Public Policy, Andrew N. Rowan, Franklin M. Loew, Joan C. Weer

eBooks

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups …

Stab Wounds To Rat Brains : Demyelination, Remyelination And The Cellular Response, Particularly Of Oligodendrocytes, Xie Dangci

Loma Linda University Electronic Theses, Dissertations & Projects

The present body of knowledge concerning the results of central nervous system injury is incomplete and controversial. The role of oligodendrocytes, the cells involved in phagocytosis, the stages of demyelination, and the evidence for remyelination are of interest. Following stab wounds to rat brain cortex, corpus callosum and hippocampus, the animals were examined at 4,7,11,18,23,29,45,60 and 70 days postoperation (dpo). To help in the identification of cells immunocytochemical markers for astrocytes and immature oligodendrocytes were used. These were labels for glial fibrillary acidic protein (GFAP) and myelin/oligodendrocyte specific protein (MOSP) respectively. Light and electron microscopy were correlated using conventionally prepared …

The Production And Characterization Of A Monoclonal Antibody To A Naturally Occurring Aminomalonic Acid Epitope And A Comparison With An Antibody To A Synthetically Derived Aminomalonic Acid Epitope, James L. Gulley

Loma Linda University Electronic Theses, Dissertations & Projects

The goal for this project is to undertake the first step in the study of blocking metastasis by a monoclonal antibody. The long range goal of this line of research is to study a novel mechanism for the blocking of tumor metastasis in general and prostatic cancer metastasis in particular. The problem that this addresses is the growing number of cases of prostatic cancer in the increasingly aging male population. This cancer is not lethal unless it metastasizes, yet there is no cure for the metastatic disease. The inherent specificity of a monoclonal antibody combined with the uniqueness of the …

Short And Long Term Effects Of Proton Microbeam Irradiation : In The Lateral Geniculate Nucleus Of Felis Domesticus, Chad Sherwood Reder

Loma Linda University Electronic Theses, Dissertations & Projects

Little is known of the effects of proton irradiation on neural tissue. A 1.0 mm microbeam was used on the cat lateral geniculate nucleus (LGN) to quantify the short term (< 3 months) and long term (< 9 months) effects of radiation damage. The LGN is a large structure with well defined afferent, efferent, and receptive field properties.

Electrophysiological and histological techniques were used to examine the effects of the microbeam at 60, 40, and 16 Gy, administered as a single bolus. Recordings of light evoked responses in the LGN were obtained using microelectrodes in nine animals within 12 weeks of irradiation, and 6 animals within 36 weeks of irradiation. Receptive fields were mapped onto a tangent screen using standard receptive field techniques. Histological measures included afferent …

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Healing Potential Of Osteotomies Of The Nasal Sinus In The Dog, Roderick W. Tataryn

Loma Linda University Electronic Theses, Dissertations & Projects

Maxillary sinus osteotomy is sometimes indicated for transantral surgical approaches to palatal roots of maxillary molars. A search of the literature showed an absence of any report on the healing potential of such defects. The purpose of this study was to determine histologically the reparative process of the nasal sinus of dogs following small and large surgical antral perforations. After anesthetizing six beagle dogs, full thickness periosteal flaps were raised overlying the maxillary buccal cortical plates. A 5x5 mm diameter perforation was created with a trephine bur above the second maxillary premolar on one side of each animal. On the …

Measurement Of Blood Flow In Reflected Muco-Gingival Tissue Flaps In Cats : Using The Radiolabeled Microsphere Method, Gary T. Wuchenrich

Loma Linda University Electronic Theses, Dissertations & Projects

Blood flow to the maxilla and mandible may vary due to differences in vascular supply and in physiologic, metabolic and pathologic conditions. In general it is accepted that oral tissues have an abundant blood supply; however, there is little information quantifying blood flow to these regions. In this study, the maxillary tissues were chosen to measure the blood flow in attached and reflected gingival tissue in adult cats using the radiolabeled microsphere method.

Sixteen cats with permanent dentition, clean mouths, and without inflamed gingiva upon visual inspection were used and divided into two groups. Group 1 consisted of six cats …

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 …

The Next Decade: A Shifting Focus, Henry Spira

Commentaries and Editorials

No abstract provided.

Concepts Of Animal Well-Being And Predicting The Impact Of Procedures On Experimental Animals, D. J. Mellor, C. S. W. Reid

Experimental Research and Animal Welfare Collection

1. We argue that:

• in their application to non-human animals, 'welfare' and 'well-being' are interchangeable words; and that

• good welfare/well-being is the state of being manifest in an animal when its nutritional, environmental, health, behavioural and mental needs are met.

2. These latter are essentially the 'five freedoms' formulated by the Farm Animal Welfare Council of the United Kingdom.

3. Using the five freedoms as a basis, we have developed a system for assessing the impact of a proposed animal experiment or usage. The freedoms are now transformed into 'domains of potential compromise' and are redefined better to …

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 …

A Non-Human Primate Model For Evaluating A Fenestration Corticotomy Technique, Philip G. M. Khng

Loma Linda University Electronic Theses, Dissertations & Projects

A study model has been designed to evaluate the effectiveness of a new fenestration corticotomy procedure in two non-human primates Macaca fasicularis.

The objective of this study was to evaluate the efficacy of a new conservative corticotomy procedure to facilitate dental translation using fenestrations. This pilot study compared treatment and control quadrants of each individual animal's maxilla and mandible with both having the same retraction appliance and force on the 2nd premolar following extraction of the 1st molars. The null hypothesis stated that there was no significant statistical difference between the new conservative corticotomy procedure (fenestrations) when compared with …

Alternatives In The 90'S: What's Next?, Henry Spira

Conference Presentations

The 80's was a decade of remarkable and innovative research and development of alternatives. We see the 90’s as the decade of validation and implementation.

From an activist's perspective, the 80's was very encouraging,-- alternatives gained acceptance, legitimacy and credibility within the toxicology, corporate and regulatory communities. And The Center for Alternatives to Animal Testing (CAAT) at Johns Hopkins University played a significant role in making this acceptance possible.

But these new technologies have yet to realize their full potential; the focus to date has been on development more than on bringing these technologies into routine usage. And the public, …

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, …

Transforming Growth Factor-Beta 1 Expression In Developing Ovine Teeth As Visualized By In Situ Hybridization, Søren Jepsen

Loma Linda University Electronic Theses, Dissertations & Projects

Recently we demonstrated that human dentin contained relatively high amounts of transforming growth factor beta (TGF-ß) and proposed that dentin TGF-ß originated from odontoblasts. Because of the suggested role of TGF-ß in mediating cellular interactions in dental cell development by paracrine mechanisms, we studied the expression of TGF-ß message in developing teeth by in situ hybridization. 5 µm serial sections of neonatal sheep mandibular third molars that had been fixed in glutaraldehyde and paraffin-embedded were used for in situ analysis. An [³⁵S]-labeled cRNA probe, complementary to TGF-ß1 mRNA, was constructed from human TGF-ß1 cDNA. Northern analysis of total …

Modulation Of Rat Hepatic S9-Dependent Mutagenesis, Dna Binding, And Metabolism Of Aflatoxin B1 And Benzo[A]Pyrene By Four Chinese Medicinal Herbs, Brian Yuen Yau Wong

Loma Linda University Electronic Theses, Dissertations & Projects

Extracts of the herbs Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumors while extracts of Astragalus membranaceus (AM) and Ligustrum lucidum (LL) are often used as adjuncts in cancer therapy. In this study, we determined the effects of aqueous extracts of these four herbs on aflatoxin B₁ (AFB₁) benzo[a]pyrene (BaP), benzo[a]pyrene 7,8-dihydrodiol (BaP 7,8-DHD) and benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE)-induced mutagenesis, mediated by enzymes in rat hepatic 9000 x g supernatant (S9), in Salmonella typhimurium TA100. We also studied the effects of these four herbs on …