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A comparison of doxorubicin and doxorubicinol in rat heart and liver tissue following anthracycline administration
No full textThis study examined the pharmacokinetic profile of the chemotherapeutic drug doxorubicin (DOX), and of its main metabolite doxorubicinol (DOXOL) in male Sprague-Dawley rats. HPLC was used to evaluate both the effect of dose (1.5 mg/kg vs. 4.5 mg/kg) and the effect of recovery time (24, 24, 72, 96, 120, 144, 168 and 192 hours) from the bolus intraperitoneal injection on plasma, liver and heart concentrations. Fluorescence microscopy allowed for qualitative analysis of DOX in liver and heart sections. Plasma concentrations of both drug and metabolite were relatively stable over the examination period. The pattern of response was similar in the liver, although DOX concentrations were decreased after 192 hours, preceded by a spike in DOXOL at 168 hours. The 4.5 mg/kg dose produced increased concentrations of DOX at several of the initial sampling time points in this tissue. In heart tissue, concentrations of DOX steadily decreased for both doses and a dose response was evident until 144 hours. No differences were distinguishable between time-points nor between doses beyond 144 hours. The concentration of DOXOL in this tissue was elevated after 24 hours and subsequently remained stable. Interestingly, DOX and DOXOL remained detectable at 192 hours post-injection for all samples. Fluorescence microscopy results consistently revealed sections that indicated the presence of DOX and were representative of the tissues being analyzed. It was observed that following injection, DOX entered the nuclei of cells rather rapidly and seemingly in proportion to the dose administered. This localization was less apparent as time progressed. These findings strongly suggest that DOX was rapidly absorbed, distributed and metabolized, however its elimination patterns remain unclear. The fact that concentrations remained relatively stable in plasma and liver, and fixed in heart tissue after 144 hours, implies that it is stored in cardiac
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tissue, and also potentially in other compartments, allowing for constant re-introduction and re-distribution. Remarkably, an increase in the dose administered did not produce greater accumulation of either drug or metabolite over time in any of the tissues analyzed, therefore the mechanism(s) responsible for the uptake and distribution within the tissues appear to be rate limiting (dose-independent). Nevertheless, the residual amounts of DOX and DOXOL in the heart and liver suggest the possibility of further accumulation upon repeated injections, supporting previous findings suggesting that cumulative doses of DOX are extremely damaging and can result in cardioxicity
Characterization of secreted acid phosphatase activity of a streptomyces albus clinical isolate
No full textDue to limitations in the efficacy of the current vaccines against Tuberculosis, there are efforts currently underway exploring the possibility of using the phylogenetically related Streptomycetes as heterologous vaccine vehicles against Tuberculosis. Ideal candidates for such a vaccine should be somewhat pathogenic and physiologically similar to M. tuberculosis so as to induce an immune response capable of targeting and inactivating this pathogen. Towards establishing such a physiological relatedness, previous work in our laboratory has established a similarity profile between M. tuberculosis and a clinical isolate of Streptomyces albus at the level of secreted enzymes. Amongst these was a strong secreted acid phosphatase activity. This work reports on the characterization of the secreted acid phosphatase activity in this clinical isolate of Streptomyces albus. In this work, two enzymes with sequence homology to those encoding a protein tyrosine phosphatase and an inorganic pyrophosphatase were purified from the culture supernatant of S. albus. The calculated molecular masses of these two putative phosphatases were approximately 18 and 30 kDa, respectively. The S. albus protein tyrosine phosphatase has 50% amino acid sequence identity to the protein tyrosine phosphatase of M. tuberculosis (gi|686037535). The inorganic pyrophosphatase has 68% amino acid sequence identity with M. tuberculosis inorganic pyrophosphatase (gi|625006479). Based on our knowledge of the role of acid phosphatases in pathogenic bacteria, presence of this activity in the supernatant of S. albus further supports the physiological relatedness of M. tuberculosis and S. albus and supports the proposition of using S. albus as a heterologous vaccine against Tuberculosis
A generalized electronic diabatic model applied to two-state reactions.
No full textA generalized electronic diabatic model for chemical reactions includes a physical mechanism for the transition from a reactant-like to a product-like quantum state, namely, an external field. In our model, an external electric field couples states and modifies effective potential energy surfaces thereby allowing to treat a reaction as a fully quantum process. Through semi-classical models of two-state reactions, we show that we can control the identity of the most stable nuclear configuration by varying the form and intensity of the external field’s coupling potential. We group topologically equivalent potential energy curves in phase diagrams for a manifold of simple two-state models. We also illustrate the method’s implementation in a fully quantum-mechanical approach by considering two diabatic states in the radical HBN⇄BNH isomerization. To ensure diabaticity, these states are built on a grid of floating Gaussian orbitals and the potential energy curves are constructed by moving the nuclei
Evaluating the impacts of an outdoor adventure leadership experience program in a rural aboriginal community
Get PDFThis research study stems from the findings and results of previous research conducted in collaboration with Laurentian University and Wikwemikong as it relates to youth and sport participation. An outdoor adventure leadership experience program was co-designed and implemented within the community of Wikwemikong for the youth between the ages of 12 – 18 years. The impacts of a 10-day outdoor adventure leadership experience program, five years after the initial intervention is the basis of this research study. The research findings suggest that the 10-day Outdoor Adventure Leadership Experience program has demonstrated mno-bimaadziwin (the good life) thereby having an impact on the overall health and well-being of the youth leaders and their families.
The community of Wikwemikong has demonstrated the commitment to make use of the findings as a result of the research; the findings and recommendations are tangible products used for the betterment of community programs and services.
Keywords
Talking circle, medicine wheel, mno-bimaadziwin (the good life), indigenous research, participatory action researc
Intramuscular immunization of mice with KatA (catalase) generates functional antibodies against Campylobacter jejuni invasion of gut epithelial cells in vitro
Get PDFThe high incidence of Campylobacter jejuni-associated diarrhea, increase in the frequency of drug resistance in clinical isolates, and the recent association of C. jejuni infections and Guillain-Barré syndrome has heightened the need to develop effective anti-Campylobacter vaccines. Due to the risk of auto-immunity, vaccination using inactivated whole-cells or attenuated cells cannot be considered. Subunit vaccines however are a viable alternative and have been shown to be effective against similar pathogens. The main goal of this research is to test efficacy of the catalase A (KatA) protein as vaccine candidate against this pathogen. It was determined that KatA co-fractionates with both the soluble and insoluble cell fractions and a balanced IgG1/IgG2a response could be produced against it following immunization in mice. It was demonstrated that these antibodies can mediate complement-specific bactericidal activity and reduced adhesion and invasion of human epithelial (Caco-2) cells by C. jejuni using established in vitro assays
Patterns of soil health for prime agricultural lands in the Greater City of Sudbury Area
No full textAt the regional scale, soil information regarding commonly employed land uses allows for improved negotiations between land owners, land managers and city planners, and also guides the adoption of sustainable policies and management practices to maintain the finite soil resources required for the on-going preservation of the local agricultural industry under stresses of a changing climate. The increasing management intensity of agricultural soils in the Greater Sudbury region, as elsewhere around the world, is placing negative pressure on the critical soil resource. This pressure is a result of reduced land availability from encroaching non-agricultural land uses, more powerful farming equipment, and a heavy reliance on chemical fertilizers. These diverse pressures are also intensified in the study area due to the strong local demand for topsoil and sod for urban development on the shallow rocky soils of much of the nearby urban area. In this study, a novel geo-referenced database was developed from measured soil health properties sampled in locally significant prime agricultural lands. Using Kruskal-Wallis comparisons, descriptive statistics and coefficients of variation, seven common land uses of the region were evaluated. Soil health properties were found to reflect land use cover and varied along a land use intensity gradient. The results from this study suggest that intensive land management practices in the region decreased topsoil total C concentrations, increased bulk density, narrowed the soil C to N ratio, increased total and available soil major nutrient levels, whilst triggering decreased micronutrient availability. Furthermore, in combination to contrasting soil health differences between dominant land uses, continuous predicted surfaces of soil properties created using GIS software, proved to be useful to highlight spatial patterns of soil properties influenced by local land use decisions. The results in this study confirm that soil resources in the prime agricultural lands of the region are at greater risk of ongoing loss of soil health due to management intensification
The effects of weak electromagnetic field (EMF) exposure on developing Xenopus laevis tadpoles
No full textThe effect of electromagnetic fields (EMFs) on biological systems continues to be explored in the scientific literature and is expanded upon in the present study by using Xenopus laevis tadpoles as a model for vertebrate physiology and behaviour . Previous research has shown that weak EMF exposure causes delays in tadpole metamorphosis. The current study assesses the influence of EMFs on tadpole social behaviour by quantifying the strong natural gathering instinct of the animals. EMFs that have an impact on tadpole behaviour are hypothesized to further show quantifiable differences in tadpole neuroanatomy. Results from the present study do not show a significant interaction between field exposure and tadpole growth or social behaviour. Strong limitations are discussed with respect to the data collected. How the data from this experiment coincides with the current literature on biological-EMF interaction is rationalized. Finally, aspects of the present study that can be utilized to guide future research are identified.Honours Essa
A Process for Creating the Aboriginal Children’s Health and Well-Being Measure (ACHWM)
No full textThe purpose of this study was to identify concepts of health and well-being important to Aboriginal children and youth. These concepts
were necessary for the development of a culturally appropriate measure of health