Seven chromium-containing complexes were tested for effects on blood glucose regulation, serum cholesterol levels, serum triglyceride levels, and body composition. The compounds included Cr picolinate, Cr chelidonate, chromate, Cr chelidamate, Cr arginate, nichrome, and Cr chloride. The study was divided into two major sections, a rat study and a chicken study. In the rat study all seven chromium-containing complexes were tested. They were administered to the rats in four different testing periods at 1 ppm, 5 ppm, and 25 ppm of chromium. Methods of administration varied for each testing period. After the chromium compounds were administered, a glucose tolerance test (GTT) was conducted on the rats in each of the four experiments. No consistent, significant findings were observed in blood glucose or insulin levels or in blood glucose or insulin change during the GTI. Tissue and blood samples were collected at the end of the study. Liver tissue weights were significantly reduced as the level of chromium supplementation increased. A similar trend was noted in the epididymal fat pad weight, but was not statistically significant. In the chicken study the partitioning effects of Cr picolinate, chromate, Cr chelidamate, Cr arginate, nichrome, and Cr chloride were more closely examined. The chickens were supplemented at 3, 15, and 75 ppm for 8 weeks. No beneficial effects from the supplementation were noted in feed efficiency, total intake, fasting blood glucose and insulin levels, HDL and total cholesterol levels, or serum triglycerides. At the end of 3 weeks the birds supplemented at 3 ppm were heavier than the other treatment birds. At the end of the 8 weeks the birds were sectioned into primal cuts and weighed. No beneficial effects of chromium supplementation were noted in any of the cuts when expressed as a raw weight, percent of dressed weight, or percent of live bird weight. Kidney chromium levels were significantly increased as the level of chromium supplementation increased in the picolinate-, arginate-, and chelidamate-treated groups. Chromium chloride-, picolinate-, arginate-, and chelidamate-treated groups all showed significant increases in liver chromium levels as the level of chromium supplementation increased.

La producción de haploides y haploides duplicados es una herramienta empleada en una gran cantidad de especies que permitiría acortar sustancialmente el tiempo requerido para la obtención de nuevos individuos homocigotas. El desarrollo y la optimización de nuevas tecnologías en este sentido es de gran interés para el avance en investigación básica así como para acelerar programas de mejoramiento genético vegetal. En el presente trabajo se evaluó la producción de plantas potencialmente haploides de maíz (Zea mays L.) para su utilización en programas de mejoramiento e investigación genética. Se trabajó con la técnica de inducción de potencialmente haploides in vivo mediante el empleo de polinizadores inductores de haploidía. Estos polinizadores se destacan por su aptitud de generar un número significativo de granos potencialmente haploides al fecundar distintos parentales femeninos. Se utilizaron cinco polinizadores y se evaluó su capacidad para la inducción de granos potencialmente haploides in vivo en porcentaje. La capacidad de inducción de plantas potencialmente haploides de los diferentes polinizadores fue cuantificada en diferentes ambientes de cultivo de los parentales y utilizando diferente germoplasma como progenitor femenino. Los experimentos se realizaron en 4 ambientes, a saber, Venado Tuerto, en dos fechas de siembra (VT1, VT2), Balcarce y Rancagua (Chile). La detección de granos potencialmente haploides se basó en la expresión de un gen marcador de color, R-nj (Rojo navajo), tanto en endosperma como en embrión. Dicho marcador permite seleccionar aquellos embriones en los cuales la fecundación no tuvo lugar. La ausencia de coloración en el embrión indica la ausencia de fecundación, evidenciando la condición haploide materna de dicho individuo. No obstante la presencia de inhibidores de color estaría afectando dicha expresión en algunos de los germoplasmas evaluados en este trabajo. Se lograron identificar polinizadores inductores de haploidía con comportamiento estadísticamente superior. Dicha capacidad fue corroborada en diferentes ambientes sin encontrarse interacción entre los mismos. Los polinizadores inductores HIND 2 (X1-B1/G3-64) y HIND 4 (M4-B3/G3-64) presentaron porcentajes de inducción de haploides potenciales superiores al 8%. En este estudio los valores más elevados de inducción fueron registrados en el ambiente de Balcarce (13,8%). El ambiente en el cual se realiza la polinización es una fuente de variabilidad que debe considerarse en el momento de implementar la técnica de obtención de individuos potencialmente haploides. La técnica de obtención de haploides de maíz in vivo optimizada en esta tesis permite la obtención de estimativamente 10 granos potencialmente haploides a ser duplicados por cada 100 granos obtenidos en el cruzamiento de inducción. Esta relación permite una aplicación directa en programas de mejoramiento de maíz comerciales. / The production of haploids and double haploids is a widely used strategy in many species allowing the reduction of the time to the generation of a complete homocigous individual. The development and optimization of new technologies is of mayor interest for the basic research and to hasten processes in breeding programs. In the present work maize (Zea mays L.) haploid plants production for breeding and research purposes was evaluated. The in vivo haploid induction technique was performed by using male haploid inducers. Five haploid inducers were tested in their ability to generate haploid kernels. The inducer pollinators were selected for their ability to generate a significant number of haploid kernels over different females pollinated. The induction of haploid plants was tested for the different pollinators as affected by parental growing environment and female germplasm. Female parental material and inducers were planted in Venado Tuerto, two sowing dates (VT1, VT2), Balcarce and Rancagua (Chile). Haploid kernels detection was based on the expression of color markers, R-nj, in endosperm and embryo. Such marker allows the selection of embryos in which fertilization was not effective. The lack of color on embryo is an evidence for incomplete fecundation, leading to a putative maternal haploid kernel. However the presence of color inhibitors in some of the female germplasms evaluated in this work may be affecting the expression of the markers. It was possible to identify haploid inducers with statistically superior performance. There was no interaction between inducers and the environments tested in this work. The maternal haploid inducers HIND 2 (X1-B1/G3-64) and HIND 4 (M4-B3/G3-64) presented haploid induction rates over 8%. In the present evaluation the highest induction rates were obtained in Balcarce environment (13.8 %). The environmental condition in which pollination takes place is a source of variability that must be taken into consideration while developing the in vivo haploid induction technique. This maize haploid in vivo process produces c.a. 10 haploids to be doubled per 100 kernels obtained in the crossing between the inducers and the female parents. This efficiency rate is large enough for a direct application in commercial maize breeding programs.

Breast cancer has the highest incidence rate in women, accounting for more than 22% of all cancers and possessing a strong disposition to metastasize to bone. These skeletal metastases become a significant cause of morbidity and mortality in patients with the primary symptom being pain. Pain is a major concern in determining a patient’s quality of life and there have been many attempts to understand and control bone pain with little success. Previous studies have shown that glutamate plays a role in bone cancer pain, with an excess in free glutamate able to cause pain either directly through excitotoxic pathways or indirectly though the dysregulation of osteoclasts and osteoblasts, causing bone dysregulation. TRPV-1 receptors have also has been implicated in the mechanisms of bone cancer pain, as osteoclasts release protons during bone remodeling which can elicit a TRPV-1-related nociceptive response from neurons in the surrounding periosteum. Capsazepine was identified during a high throughput screen of 30,000 compounds to be a potent inhibitor of breast cancer cell-mediated glutamate release, a neurotransmitter with known associations in neural signaling, bone homeostasis, and pain. Capsazepine also has antagonistic effects on transient receptor potential vanilloid type 1 (TRPV-1) receptors which act as key players in both heat and vanilloid-induced nociception. These findings suggest that Capsazepine may provide a multi-site effect for the treatment of cancer-induced bone pain. An animal model of breast cancer-induced bone pain involved intrafemorally injecting MDA-MB-231 cancer cells to measure pain. Behavioural tests are then performed measuring dynamic weight bearing and paw withdrawal thresholds. These measurements are used to demonstrate both movement-evoked and spontaneous pain-related behaviour of the affected limb. Using Capsazepine, we demonstrate a dose-dependent attenuation of pain behaviour in vivo, while confirming tumour presence using immunohistochemistry (IHC). We show that TRPV-1 and glutamate play an important role in the onset and severity of bone cancer pain and blocking these pain pathways provide relief from pain commonly associated with cancer in the bone. / Thesis / Master of Health Sciences (MSc)

No description available.

ABSTRACT COMPLETION OF AN IN VIVO DIGESTIBILITY TRIAL IN HORSES AND IN VITRO DIGESTIBILITY ASSAY DEVELOPMENT Cassandra Renee Sweeney In vivo analysis of equine feed digestibility has been the gold standard since the late 1800's, although it can be time consuming, costly, and labor intensive. In vitro digestibility analysis may be more economical and beneficial to both feed manufacturers and consumers. The availability of accurate in vivo data is crucial for critical evaluation and validation of any potential in vitro method (Coles et al., 2005). Ten adult American quarter horse geldings were used in the in vivo digestibility evaluation of two complete pelleted feeds fed as 100% of intake. The ingredients of the two treatments were similar: wheat middlings, rice hulls, alfalfa and beet pulp. The treatments differed in added mineral sources, yeast, direct fed microbials, and Yucca schidigera extract, added to enhance dry matter digestibility of the test diet. The in vivo evaluation consisted of two phases in a randomized crossover design. Total daily dry matter intake (DMI) and daily dry matter excretion (DME) were measured. Apparent digestibility (aDig) of % DM, % NDF, % ADF, % ADLom, and % OM (DM) were also calculated. No differences were seen in aDig of NDF, ADF, ADLOM or OM between the two experimental diets (P > 0.05). There was also no difference in DMI or DME, as a percentage of body weight (BW), between the two experimental diets. The effect of phase was not significant for all tests run on aDig, DMI, and DME (P > 0.05). BW was not significantly different (P > 0.05) between diets, however there was a trend for v heavier BW during phase 2 (P = 0.073). In vitro digestibility assay development followed the in vivo evaluation. A three-stage batch system as briefly described by Boisen and Fernandez (1997) was utilized. Through literature review, trial and error, personal communication with other labs and product and chemical manufactures, careful documentation of the methods were detailed. Using the control feed from the in vivo evaluation, variation in the methods was significantly reduced, and estimations of DML began to approach those seen in vivo throughout method development. Although further method development may be needed for species-specific use, the methods described here can provide the foundation for future in vitro digestibility studies.

Bronchopulmonary dysplasia (BPD), the chronic lung disease that develops in premature babies following mechanical ventilation and oxygen exposure, is the most common complication of extreme prematurity. Currently, there is no cure for BPD. Increasing evidence indicates early-onset emphysema and pulmonary vascular disease in survivors with BPD (Aukland et al., 2006; Wong et al., 2008), suggesting an irreversible arrest in lung growth and/or premature lung aging resulting in life-long health problems (J. Sucre et al., 2021). Transient in vivo cellular reprogramming through the activation of the Yamanaka reprogramming factors Oct4, Sox2, Klf4, c-Myc (OSKM), ameliorate cellular and physiological hallmarks of aging and to promote tissue regeneration and improve organ function after injury. (Chen et al., 2021a; Hishida et al., 2022b; Lu et al., 2020) This thesis focuses on determining if transient in vivo cellular reprogramming can regenerate an established lung injury in a BPD mouse model. Two strategies, (a) Adeno-Associated virus (AAV) mediated transient overexpression of the OSK factors and (b) using a transgenic reprogrammable mouse line to overexpress the OSKM factors were employed to test the efficiency of in vivo cellular reprogramming in regenerating the lungs. Both the strategies, under the conditions tested, did not regenerate established lung injury in a BPD mouse model but the feasibility of both these strategies was established here laying a foundation for the next phase of the study.

Das Ziel der experimentellen Studie war die Erprobung der (bereits in vitro erfolgreich getesteten) Ca(OH)2-Beschichtung In vivo unter dem Aspekt, ob und inwieweit die antibakteriellen und somit auch antiinflammatorischen bzw. entzündungsmoderierenden Eigenschaften der Ca(OH)2-Beschichtung eine sinnvolle und effektive Ergänzung zu den bisher erfolgreich eingesetzten Calciumphosphat(CaP)-Beschichtungen mit bewiesenen, guten proosseointegrativen Eigenschaften bei lasttragenden Implantaten sein können. Zusammenfassend kann festgestellt werden, dass die Ergebnisse der In vitro Untersuchung durch die In vivo Versuche in den Bereichen 0-100 KBE grundsätzlich als gestützt gelten können. Die Zuverlässigkeit der Wirkung durch Ca(OH)2 nimmt jedoch mit steigender KBE-Zahl ab, sodass weitere Testreihen sinnvoll sind. / The aim of the experimental study was to test the Ca(OH)2-coating (which has already been successfully tested in vitro) in vivo under the aspect of whether and to what extent the antibacterial and thus also anti-inflammatory or inflammation-moderating properties of the Ca(OH)2-coating can be a useful and effective addition to the common successfully used calcium phosphate (CaP)-coatings with proven, good proosseointegrative properties in load-bearing implants. In summary, it can be stated that the results of the in vitro investigation can generally be considered supported through the in vivo tests in the range of 0 -100 CFU. However, the reliability of the effect caused by Ca(OH)2 decreases as the CFU number increases, so further series of tests make sense.

No description available.

No description available.

It is well known that lead is toxic. Since the full effects, particularly of long term, low level exposure are not well understood, further knowledge of lead metabolism has significant public health implications. Traditionally, clinical studies of lead's effect on health have relied heavily on blood lead levels as an indicator of lead exposure. However, this is unsatisfactory, because blood lead levels principally reflect only recent exposure and lead in serum is more readily bioavailable than whole blood. Over 90% of the lead body burden is in bone, where it has a long residence time. Therefore, bone lead measurements are reflective of cumulative exposure. The bone lead detection system at McMaster University uses a ¹⁰⁹Cd source, which is positioned at the centre of the detector face (HPGE). This arrangement allows great flexibility, since one can sample lead in a range of different bone sites due to a robust normalization technique that eliminates the need to correct for bone geometry, thickness of overlying tissue, and other related factors. Lead in both the tibia and the calcaneus, whole blood lead, and serum lead have been measured in a group of 49 active lead workers (Nova Pb bone lead survey). Before studying the interrelationships between the above measurements, work was done to improve the programs which fit the bone lead spectra. That is, work was done to link the amplitudes of the alpha and beta peaks and to investigate the sensitivity of the analysis on the channel ranges and start parameters. The main goal of this project was to carefully study the interrelationships between the major components of any human lead metabolism model, bone, whole blood, and serum, in order to establish a solid basis for computer modelling of lead metabolism. / Thesis / Master of Science (MSc)