4.1. The effects of adding pulses to calorie-restricted diets on metabolic health and inflammation in diet-induced C57Bl/6 obese male mice.
Ryan Zanganeh (1), Salma Mahmoodianfard (1), Alexane Rodrigue (2), Lalit Kishore (3), Krista A. Power (3)
(1) School of Human Kinetics, Faculty of Health Science, University of Ottawa, Ottawa ON, Canada.
(2)Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa ON, Canada.
(3) School of Nutrition Sciences, Faculty of Health Science, University of Ottawa, Ottawa ON, Canada.
Obesity is a chronic disease that is associated with intestinal and metabolic dysfunctions. Caloric restricted (CR) diets are a primary dietary approach for weight loss. In addition to CR, dietary pulses including beans, may have the potential to improve metabolic health and inflammation, due to their high content of non-digestible fermentable carbohydrates and phenolic compounds, . The objectives of this study were to determine if: 1) supplementing white or dark red kidney beans into CR diets would improve biomarkers of glucose homeostasis, appetite regulation, and inflammation in obese mice; 2) outcomes are differently affected by kidney bean variety (white vs dark red) potentially driven by increased phenolics within dark-colored beans. 5-week-old male C57Bl/6 mice were fed a high-fat diet (HFD, 60% fat) for 10 weeks (n=48) to develop an obese phenotype. Afterwards, obese mice were randomly assigned to four dietary intervention groups: 1) HFD control; 2) CR diet (13.5% fat) control; 3) CR + 15% (w/w) white kidney beans (CRWB); and 4) CR + 15% (w/w) dark red kidney beans (CRDB) for 8 weeks (n=12/group). At the end of the intervention, fasted blood samples were collected to measure blood glucose, insulin, insulin resistance (HOMA-IR), adipokines (adiponectin, leptin, PAI-1, and resistin) and appetite-related hormones (ghrelin, GIP, GLP-1, and glucagon) using Bio-Plex assays. All CR diets significantly improved metabolic health and inflammation as indicated by reduced serum leptin, insulin, and HOMA-IR biomarkers. Furthermore, mice fed CRWB diet had significantly lower blood glucose compared to HFD, while mice fed CRDB diet had significantly lower serum resistin compared to HFD. Results suggest that mice consuming CR diets supplemented with kidney beans have greater improvements in obesity-associated serum metabolic and inflammatory biomarkers, compared to mice consuming CR control diet. Moreover, differences observed between kidney bean varieties requires further investigation to elucidate mechanisms of action.
Keyword: Pulses, Calorie Restriction, Weight Loss, Inflammation, Metabolic Profile.
4.2. Impact of pectin as a soluble fibre on intestinal health in C57Bl/6 male mice.
Zeynep Cildir (1), Maisha Islam (2), Lalit Kishore (3), Krista A. Power (3)
(1) Honours BSc in Biomedical Sciences, Faculty of Science, University of Ottawa, Ottawa ON, Canada.
(2)Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa ON, Canada.
(3)School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.
Introduction: It is recommended to consume a high fibre diet, however not all fibres are equal with regards to their health benefits. Compared to insoluble fibres (e.g. cellulose), soluble fibres (e.g. pectin) are fermented by the gut microbiome resulting in the production of short-chain fatty acids which are known to improve intestinal health. In spite of this, purified rodent diets (e.g. AIN-93G) commonly used as “control” diets in nutrition-based research, contain only cellulose which may inadvertently lower baseline intestinal health in control animals. Objective: To determine the impact of purified diets containing both soluble and insoluble fibre on colon barrier integrity in mice, compared to insoluble fibre-based control diets. Methodology: 6-week-old male C57B1/6 mice were randomized to 4 groups (n=6-9 mice) and fed their respective diets for 6-weeks: 1) Low-fat (LF) diet; 17% kcal fat, 7% cellulose; 2) LF + pectin (LF+P); 5% cellulose and 2% pectin 3) High fat (HF) diet; 60% kcal fat; 7% cellulose; and 4) HF + pectin (HF+P); 5% cellulose and 2% pectin. Formalin-fixed paraffin-embedded colon sections were stained with hematoxylin and eosin or Alcian Blue and crypt height and goblet cell density, and epithelium mucus content were measured using ImageJ software. Results: Mice consuming LF+P diet, had higher proximal and distal colon crypt height and goblet cell density, but not mucus content, compared to mice consuming LF (P<0.05). On the other hand, these parameters were not modified by pectin in mice consuming HF diets. Conclusion: The outcomes of this study indicate that mice consuming cellulose as the sole source of fibre, had lower baseline intestinal health, compared to mice consuming both insoluble and soluble fibre. Interestingly, this effect is dependent on the composition of the control diet, such that the addition of pectin to HF diets, did not modify colon barrier integrity.
Keyword: Pectin, cellulose, mucus content, goblet cells, crypt height
4.3. Photo Elicitation to Explore Health and Social Exclusion with Rooming House Residents.
Joanna Binch(1) Chantal Backman(2) Erin Dej(3) Lynne Leonard(4) and J. Craig Phillips(2).
(1)PhD(c) student, School of Nursing, Faculty of Health Sciences, University of Ottawa, Ottawa, ON.
(2)School of Nursing, Faculty of Health Sciences, University of Ottawa, Ottawa, ON.
(3)Department of Criminology, Wilford Laurier University, Waterloo, ON.
(4)School of Epidemiology and Public Health, University of Ottawa.
Introduction: Compared to other Canadians, residents of rooming houses have a disproportionate burden of chronic illness and increased mortality compared to the general population. Despite potential negative health consequences, many people have no other affordable option for rental housing, and rooming houses play a unique and pivotal role. Rooming houses offer private single-occupancy accommodation where rooms are rented individually, and residents share a bathroom and/or kitchen. Without rooming houses, the transition into sheltered homelessness would be precipitous and the exit from sheltered homelessness more problematic. Little research specific to rooming house residents exists, and even less from the perspective of residents about how rooming houses are linked to their health Objective: Developed with a social exclusion framework, the aim of this study was to investigate how rooming houses are linked to health and asked what aspects of a rooming house, the behaviors and characteristics of the people who live in a rooming house, or the resources that are accessible to those who live in a rooming house, influence health outcomes? Methods: Case study methodology, photo elicitation, which included data from focus groups, photos and field notes Results: Two broad themes were identified: Housing is Health care, and Just Managing Today. The project was framed to consider health inequalities as due to structural inequalities, broadening the lens through which health practitioners conceptualize the determinants of health. Conclusion: The themes showed the silos of health care that rooming house residents negotiate and the edge of the precipitous drop along which rooming house residents balance.
Keyword: Rooming houses, social inclusion, photo elicitation, social determinants of health
4.4. “It is good for women and women need to know more about it”: Exploring women’s experiences with the community-based distribution of misoprostol for early abortion in Pakistan.
Kassandre Messier* (1,2), Muhammad Aslam (3), Najma Shabir (3), Angel Foster (1,2).
(1) Faculty of Health Sciences, University of Ottawa.
(2)Cambridge Reproductive Health Consultants.
(3) Peace Foundation Pakistan.
Introduction: Unsafe abortion directly contributes to 8%-15% of maternal deaths worldwide and there is a significant need to implement new strategies to improve access to safe services, particularly in low resource and legally restricted settings such as Southeastern Pakistan. Expanding access to misoprostol has the potential to reduce harm from unsafe abortion practices. Objective: In 2019, a local non-governmental organization developed and implemented a community-based distribution program of misoprostol for early abortion to reduce harm from unsafe abortion in the Sindh region and expand access to safe abortion care. We undertook this qualitative study to explore women’s experiences with this program. Methods: In October-December 2019, we conducted 30 in-depth interviews with women who had obtained misoprostol through this program. We audio-recorded, transcribed, and translated to English all interviews and used ATLAS.ti to manage our data. We analyzed the interviews for content and themes using deductive and inductive techniques. Results: Overall, women felt positively about their experiences with the program and the overall initiative. Women remained certain of their decisions to have an abortion and were satisfied the misoprostol-only regimen and the abortion process. Women reported that the program filled a significant need and that they would recommend the program to others. Conclusion: The community-based distribution of misoprostol is a culturally resonant and acceptable strategy for improving access to safe abortion care in Sindh, Pakistan. Expanding the reach of the program and engaging in efforts to increase awareness of and provide women with accurate information about safe abortion care appears warranted.
Keyword: Abortion; fragile settings; low resource settings; medication abortion; misoprostol
4.5. Analysis of the Antigenic Composition and Differential Incorporation of Host Membrane Proteins into Moloney Murine Leukemia Virus by Flow Virometry.
Mariam Maltseva (1), Dr Marc-André Langlois
(1)Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, ON Canada.
The analysis of viral heterogeneity has been primarily limited by the inability of traditional analytical methods to analyze viruses at an individual particle level. Flow virometry (FVM) is an emerging technique based on flow cytometry principles that enables a high throughput, multiparametric, and phenotypic characterization of viruses at a single particle resolution. Here we performed FVM to analyze surface markers found on wildtype Murine Leukemia Virus (MLV) and glycosylated Gag-deficient (glycogag) MLV. Glycogag accessory protein exhibits several roles in the MLV viral replication cycle including directing retroviral assembly and release at lipid rafts. We hypothesize that glycogag modulates host protein incorporation during viral assembly and release. Here, using FVM we revealed that glycogag is associated with an increased incorporation of the host-derived tetraspanins CD81 and CD63 along with the lipid raft and immune antigen Thy1.2 during the assembly and release of viral particles from NIH 3T3, EL4, and primary CD4+ T cells. Moreover, we showed differential uptake of host proteins between the two cell lines and primary lymphocytes that reflect the cell’s phenotype. Finally, on an individual viral particle level, we observed a high degree of heterogeneity in both the presence and abundance of host-derived antigens within the viral envelope. Aside from possible evolutionary implications of glycogag, we demonstrated that although the antigenic composition of the MLV envelope correlates to the producer cell phenotype, certain abundant cellular antigens were not conserved, alluding to a selective mechanism of protein incorporation.
Keyword: Flow Virometry, Flow cytometry , Nano Scale Flow Cytometry, Virology
4.6. Quinazoline-2-carboxamides Are Potent and Selective Inhibitors of Matrix Metalloproteinase-13.
Christina Bi* (1, 2), Ariel Buchler (1, 2), Dr. Benjamin Rotstein (1, 2).
(1) Faculty of Science, University of Ottawa, Ottawa, ON.
(2)Molecular Imaging Probes and Radiochemistry Laboratory, University of Ottawa Heart Institute, Ottawa, ON.
Introduction: Matrix metalloproteinases (MMPs), a class of zinc-containing endopeptidases, play an important role in modulating the extracellular matrix (ECM), the dysregulation of which is associated with destructive vascular remodeling in inflammatory cardiovascular diseases, such as atherosclerosis. MMP-13 is a predominant contributor to plaque destabilization through degradation of collagen within the fibrous cap. Thus, selective radiolabeled inhibitors of MMP-13 could be useful for molecular imaging of high-risk atherosclerosis and diagnosis. Objective: To test the inhibition potency and selectivity of previously synthesized novel quinazoline-2-carboxamides towards MMP-13 and inform selection of a candidate for tracer development. Methodology: Inhibitors were characterized by in vitro assay to measure potency and selectivity (IC50) against activated MMPs (-13, -1, -2, -8, -9, and -10) at varying concentrations. Control experiments were run to detect interference associated with evaluated inhibitors and fluorogenic substrate. Significance: This approach selectively targets an enzyme which increases susceptibility to plaque rupture for identification of high-risk disease. Currently, MMP-targeted radiotracers have been poorly selective and thus unsuccessful. The MMP-13 selective PET radiotracer, to be developed herein, is well-positioned to improve upon imaging sensitivity for stratification of atherosclerotic disease severity. Results: Quinazoline derivatives are potent inhibitors of MMP-13. Half of the novel compounds possessed IC50s below 50 nM. Carboxylate-containing inhibitors are 100 times more potent than inhibitors without. Conclusion/future directions: These data will be used to identify a highly selective and sensitive radiolabeling candidate to assess atherosclerotic plaque vulnerability. Future studies include evaluating Carbon-11 analogs in vivo and determining selectivity profiles of inhibitors with IC50s below 50 nM.
Keyword: Matrix metalloproteinase-13, atherosclerosis, radiotracer, enzyme- inhibition assay, positron emission tomography