Browsing by Author "Worley, Deanna, committee member"

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Open Access
Kinematic and kinetic analysis of canine pelvic limb amputees at a trot
(Colorado State University. Libraries, 2011) Hogy, Sara, author; Reiser, Raoul, advisor; Worley, Deanna, committee member; Haussler, Kevin, committee member
Osteosarcoma is the most common form of bone tumors in dogs. Treatment options include palliative or curative-intent options. Of the curative-intent treatments, the most common is amputation, due to lower cost and the ability to perform the procedure on all osteosarcoma patients irrespective of tumor location, as opposed to limb-sparing options which can only be used when the tumor is located at the distal radius or ulna of the thoracic limb. Overall, dogs with amputations adjust well to the loss of the limb; however, there still remains a subset of patients which do not. In this study, the ground reaction force kinetics and joint angular kinematics of pelvic limb amputees and four-legged dogs were compared to identify compensation strategies adopted by amputees after the loss of a pelvic limb. It was hypothesized that there would be increased flexion and extension of all limbs within the amputees, as well as increased spinal motion. In addition, it was hypothesized that there would be decreased vertical impulses in all limbs of amputees, as well as, decreased propulsion forces within the thoracic limbs of amputees, as compared to controls. The four-legged control population consisted of 24 dogs and the pelvic limb amputee population consisted of 12 dogs. Both populations had dogs of varying breeds. Ground reaction force data were captured using three serial force platforms while dogs were trotted down an over-ground walkway. Concurrently, joint angular kinematic data were captured by motion capture software using retroflective markers affixed to bony landmarks along the limbs and axial skeleton. Peak ground reaction forces and impulses were slightly different between pelvic limb amputees and four-legged dogs. Pelvic limb amputees had increased peak braking forces in the contralateral thoracic limb and increased peak propulsion in both the ipsilateral thoracic limb and remaining pelvic limb. In addition, amputees had increased peak vertical force and propulsion impulse in the remaining pelvic limb. Time to peak braking force was significantly decreased in all limbs of the amputees, while time to peak propulsion ground reaction force was increased in all limbs of the amputees. Limb kinematics of pelvic limb amputees were very similar to the kinematics of four-legged dogs. The only compensatory strategy adopted within the limbs of the amputee was increased range of motion of the hock joint within the remaining pelvic limb. However, the pelvic limb amputees had various spinal compensatory changes within the sagittal plane. Amputees had increased regional spinal motion about both the T1 and T13 markers and increased extension about the L7 marker, compared to four-legged controls. The motion of the spine in the horizontal plane varied only in the regional angular motion about the L7 marker. Overall, ground reaction force kinetic and joint angular kinematic gait analysis of pelvic limb amputees showed that there are various compensation strategies adopted by pelvic limb amputees to adjust for the loss of a limb. Combined, these compensation strategies allow for successful adaptation to a three-legged gait pattern after the removal of a pelvic limb. Clinically, this information will be valuable for determining factors related to adaptive strategies with pelvic limb amputees. This information can also be used to create a set of quantitative measures needed to classify canine amputees into adapted or poorly adapted gait parameters.
Open Access
Kinematic and kinetic analysis of canine thoracic limb amputees at a trot
(Colorado State University. Libraries, 2011) Jarvis, Sarah, author; Reiser, Raoul, advisor; Worley, Deanna, committee member; Haussler, Kevin, committee member
Most dogs appear to adapt well to the removal of a thoracic limb, but clinically there is a particular subset of dogs that still have problems with gait that seem to be unrelated to age, weight, or breed. The purpose of this study was to objectively characterize biomechanical changes in gait associated with amputation of a thoracic limb. Sixteen amputees and 24 control dogs of various breeds with similar stature and mass greater than 14 kg were recruited and participated in the study. Dogs were trotted across three in-series force platforms as spatial kinematic and ground reaction force data were recorded during the stance phase. Ground reaction forces, impulses, and stance durations were computed as well as stance widths, stride lengths, limb and spinal joint angles. Kinetic results show that thoracic limb amputees have increased stance times and vertical impulses. The remaining thoracic limb and pelvic limb ipsilateral to the side of amputation compensate for the loss of braking, and the ipsilateral pelvic limb also compensates the most for the loss of propulsion. The carpus, and ipsilateral hip and stifle joints are more flexed during stance, and the T1, T13, and L7 joints experience significant differences in spinal motion in both the sagittal and horizontal planes throughout the gait cycle stance phases. The spine, carpus, and ipsilateral hip and stifle joints are of most concern when considering the biomechanical impact that a thoracic limb amputation may have for a given dog.
Open Access
Markers and mechanisms of resistance to Toceranib phosphate (Palladia®) in canine cutaneous mast cell tumor
(Colorado State University. Libraries, 2014) Halsey, Charles H. C., author; Gustafson, Daniel, advisor; Thamm, Douglas, committee member; Ehrhart, EJ, committee member; Worley, Deanna, committee member
To view the abstract, please see the full text of the document.
Open Access
Metal organic frameworks as heterogenous nitric oxide catalysts for use in the development of therapeutic polymer materials
(Colorado State University. Libraries, 2014) Harding, Jacqueline L., author; Reynolds, Melissa, advisor; Prieto, Amy, committee member; Crans, Debbie, committee member; Bailey, Travis, committee member; Worley, Deanna, committee member
Implantable polymeric medical devices are subject to surface biofouling due to the deposition of microbial agents and the accumulation of proteins at the material interface. Consequently, medical devices which are intended for beneficial functions can become a potentially fatal threat. As a result biofouling resistant materials are vigorously sought through the manipulation of material surface properties and by eluting therapeutics on the material surface. Nitric oxide (NO) is a bioactive agent generated by most nucleated cells in the human body and is known to mediate antimicrobial and antithrombus effects while maintain the capacity to promote the proliferation of healthy tissues. As such, the development of NO releasing biomaterials is known to reduce incidences of surface biofouling. However, current NO releasing materials are limited to short lifetimes of used based on limited capacity of exogenous NO which can be incorporated into the material. In order to circumvent this problem the goal of this research is to develop a biomaterial which generates NO from an endogenously supplied source. Metal organic frameworks (MOFs) were selected for investigation as heterogeneous catalysts for the generation of NO from bioavailable NO donors, S-nitrosothiols (RSNOS). MOFs were evaluated as NO catalysts based on their capacity to react with various RSNO substrates and their maintained structural integrity under reaction conditions. Presented herein is the successful demonstration of a Cu-MOF for the catalytic generation of NO from bioavailable RSNOs donors. However, the limited stability of this proof of principle MOF in aqueous solution prompted the development of a MOF-NO catalyst that is suitable for physiological applications through tuning the organic ligands used in the construction of the framework. Finally a two-fold demonstration of the feasibility towards designing composite MOF based biomaterials is presented as blended materials prepared via commercial manufacturing processes and via surface growth of MOFs on flexible polymeric substrates.
Embargo
Synthesis and characterization of biologically relevant redox-active molecules
(Colorado State University. Libraries, 2023) Kostenkova, Kateryna, author; Crans, Debbie, advisor; Zadrozny, Joseph, committee member; Paton, Robert, committee member; Worley, Deanna, committee member
Redox chemistry is fundamental to several essential life processes, such as energy metabolism, respiration, and free radical formation. Many redox-active inorganic and organic molecules are promising agents to combat difficult-to-treat diseases, including cancer and tuberculosis. This dissertation covers the syntheses, studies of the fundamental chemical and biological properties of two vastly different classes of redox-active molecules, inorganic and organic molecules. Most of this work has investigated the fundamental development of hydrophilic, hydrophobic and amphiphilic redox-active vanadium complexes for the treatment of different types of cancer. The last chapter of this dissertation describes the studies of the fundamental properties of demethylmenaquinones which are biosynthetic precursors to menaquinones, lipid electron carriers essential for anaerobic bacterial respiration of several types of bacteria, including Escherichia coli, Actinomadura madurae and pathogenic Mycobacterium tuberculosis. Targeting bacterial electron transport chain disrupts respiration of pathogenic Mycobacterium tuberculosis, thus, studying the properties of demethylmenaquinone analogs is of great interest. Chapter one, an introductory chapter, presents a comprehensive review of the developments in vanadium anticancer therapeutics over the last five years. The structural diversity of the vanadium-containing anticancer compounds, potential applications to various cancer cell lines, and different modes of delivery of highly cytotoxic vanadium species are described in detail. Vanadium gained interest for its anticancer applications after bis(maltolato)oxovanadium(IV), an antidiabetic complexes studied in Phase II clinical trials, went off patent in September 2011. Previous studies with vanadium antidiabetic complexes, however, provided valuable information to understand the action of novel vanadium anticancer complexes, as cancer and diabetes target the same metabolic pathways. Chapters two and three describe the syntheses, spectroscopic characterization, and cytotoxic studies of novel vanadium(V) catecholate complexes with pyridine-containing Schiff base ligands. According to previous reports, vanadium(V) Schiff base catecholate complexes are promising agents for glioblastoma treatment, and herein we investigated whether the presence of the pyridine ring on the Schiff base scaffold improves cytotoxicity and hydrolytic stability of the vanadium catecholato complexes. The studies showed that the presence of the pyridine ring improves hydrolytic stability of the V(V) catecholate complexes, yet it decreases their uptake into glioblastoma cells which result in the decrease of cytotoxicity of the complexes. Even though the stability increased and the compounds have enough time to get into cells, the efficacy of these complexes decreased. Chapter three further explores the redox properties and the redox reaction mechanism of vanadium(V) Schiff base catecholate complexes with pyridine-scaffolds and tert- butyl substituted catecholate ligands. Chapter four describes the speciation studies and testing of vanadium(V) dipicolinate that enhance the effects of oncolytic viruses, non-pathogenic viruses that can infect and kill cancer cells. Additionally, the chapter describes 1H and 51V NMR studies carried out in model membrane interfaces. The data show that V(V) dipicolinates hydrolyze under physiological conditions and generate vanadate which ultimately enhances the spread of the oncolytic viruses. V(V) dipicolinates are located on the interface of the aqueous pool and hydrophobic region of model membranes which also contributes to their hydrolysis. Chapter five describes PtIV and MoVI monosubstituted decavanadates, monoplatino(IV)nonavanadate(V) ([H2PtIVVV9O28]5-, V9Pt), and monomolybdo(VI)-nonavanadate(V) ([MoVIVV9O28]5-, V9Mo), and their ability to initiate signal transduction on the luteinizing hormone receptor (LHR) in CHO cells and their speciation chemistry under the biological experiments. The PtIV and MoVI monosubstituted decavanadates are large vanadium- oxo clusters that are structurally similar to decavanadate but have different charges. The results showed that both V9Mo and V9Pt affect LHR expression and do not inhibit cell growth which is different than the decavanadate ([V10O28]6−, abbreviated V10). Although all the clusters hydrolyze under the assay conditions lifetimes are different, and this was characterized using spectroscopic methods. Using the washing experiments, we were able to show that the V9Pt and V9Mo monosubstituted decavanadates do not associate with the cells and, hence, do not negatively affect cell growth, however, they are more effective in initiating signaling. Chapter six describes initial efforts to study the fundamental properties of two truncated demethylmenaquinones, biosynthetic precursors for menaquinones. The studies are important to understand the fundamental differences between the chemical properties of menaquinones and demethylmenaquines which include 3D conformation and redox potential. Indeed, the development of inhibitors of MenG, a methyltransferase enzyme that coverts demethylmenaquines to form menaquinones, is a known target for drug development for antitubercular applications. Therefore, we investigated whether non-native demethylmenaquines would convert to menaquinones by the relevant enzymes present in the membrane preparations. In summary, the first five chapters demonstrate 1) the diversity of applications of vanadium compounds for treatment of different types of cancer and 2) the efforts to develop vanadium- based anticancer therapeutics to treat different types of cancer. The final chapter describes efforts in fundamental studies preparing and characterizing the chemical properties the truncated demethylmenaquinones. In addition, we demonstrated that the membrane preparations of mycobacteria concerted the synthesized truncated demethylmenaquinone-2 and demethylmenaquinone-3 are processed to form menquinone-2 and menaquinone-3.