Lalita Bharadwaj

MECHANISM OF HYDROXYL RADICAL-INDUCED MODULATION OF VASCULAR TONE

We investigated the effects of hydroxyl radicals (OH) generated by a .OH-generating system (dihydroxyfumarate [DHF], adenosine diphosphate [ADP], and FeCl3) on isolated rabbit aorta suspended in Krebs-Ringer solution. The .OH-generating system produced a concentration-dependent generation of .OH. .OH relaxed rabbit aorta and norepinephrine (NE)-precontracted aorta in a concentration-dependent manner. Mannitol completely prevented this relaxation. Relaxation was completely absent in preparations denuded of endothelium. The relaxant effect was reduced by 62% by an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), by 58% by an inhibitor of guanylate cyclase (methylene blue), by 48% by an inhibitor of cyclooxygenase (indomethacin), and by 83% by an adenosine triphosphate (ATP)-sensitive K+ channel blocker (glyburide). The inhibition of .OH-induced relaxation by a combination of indomethacin, methylene blue, and glyburide was not greater than by each of the individual agents. These results indicate that .OH produces a relaxation of the aorta that is completely endothelium-dependent and is partly mediated by an endothelium-derived relaxing factor (nitric oxide), vasodilatory arachidonic acid metabolites, and an ATP-sensitive K+ channel.

Cardiac Depressant Effects of Oxygen Free Radicals

In many clinical situations, including cardiac ischemia/reperfusion, elective cardiac arrest, and renal dialysis, the chances of increased production of oxygen free radicals (OFR) exist. OFR have been implicated as a causative factor of cell damage in several pathologic conditions. The effects of exogenous OFR, gener ated by xanthine plus xanthine oxidase, in the absence and in the presence of OFR scavenger (superoxide dismutase [SOD]) on the contractility of isolated perfused heart of rabbit were studied. OFR produced concentration-dependent decreases in the contractility of perfused heart. SOD prevented the OFR-in duced decreases in the left ventricular contractility. Xanthine produced an in crease in the contractility of isolated perfused rabbits heart. Xanthine oxidase produced a marked decrease in the left ventricular contractility. Repeated ad ministration of xanthine oxidase produced accelerated and greater decreases in the contractility of perfused heart when compared with that of the initial admin istration of the drug. Effects of xanthine or xanthine oxidase on the cardiac function and contractility were also studied in anesthetized dogs. Xanthine alone had no significant effect on the cardiac function and indices of myocardial contractility. However, xanthine oxidase produced a marked decrease in the mean aortic pressure, left ventricular work index, heart rate, cardiac index, left ventricular systolic pressure, left ventricular end-diastolic pressure, (+) and ( — ) dp/dt of left ventricular pressure, and other indices of myocardial contrac tility [(dp/dt)/PAW (pulmonary arterial wedge pressure)]; and an increase in the total systemic and pulmonary vascular resistance. Repeated administration of xanthine oxidase in anesthetized dogs had lesser effects on the cardiovascular system when compared with those from the initial dose of the drug. These results suggest that OFR are cardiac depressant. Clinical situations wherein there is an increased production of OFR or increased formation of xanthine and xanthine oxidase may be associated with decreased cardiac func tion and contractility. Scavengers of OFR may protect the heart from the delete rious effects of OFR in such clinical conditions.

Drinking Water Management: Health Risk Perceptions and Choices in First Nations and Non-First Nations Communities in Canada

The relationship between tap water and health has been a topic of public concern and calls for better management in Canada since well-publicized contamination events in two provinces (Ontario and Saskatchewan) in 2000–2001. This study reports the perspectives on health risks from tap water and corresponding use of, and spending on, bottled water in a number of different communities in Canada. In 2009–2010, four First Nations communities (three from Ontario and one from Saskatchewan) and a geographically diverse sample of non-First Nations Canadians were surveyed about their beliefs concerning health risks from tap water and their spending practices for bottled water as a substitute. Responses to five identical questions were examined, revealing that survey respondents from Ontario First Nations communities were more likely than non-First Nations Canadians to believe bottled water is safer than tap water (OR 1.6); more likely to report someone became ill from tap water (OR 3.6); more likely to express water and health concerns related to tap water consumption (OR 2.4); and more likely to spend more on bottled water (OR 4.9). On the other hand, participants from one Saskatchewan First Nations community were less likely than non-First Nations Canadians to believe that someone had become ill from drinking tap water (OR 3.8), less likely to believe bottled water is safer than tap (OR 2.0), and less likely to have health concerns with tap water (OR 1.5). These differences, however, did not translate into differences in the likelihood of high bottled water expenditures or being a 100% bottled water consumer. The paper discusses how the differences observed may be related to water supply and regulation, trust, perceived control, cultural background, location, and past experience.

A Framework for Building Research Partnerships with First Nations Communities

Solutions to complex health and environmental issues experienced by First Nations communities in Canada require the adoption of collaborative modes of research. The traditional “helicopter” approach to research applied in communities has led to disenchantment on the part of First Nations people and has impeded their willingness to participate in research. University researchers have tended to develop projects without community input and to adopt short term approaches to the entire process, perhaps a reflection of granting and publication cycles and other realities of academia. Researchers often enter communities, collect data without respect for local culture, and then exit, having had little or no community interaction or consideration of how results generated could benefit communities or lead to sustainable solutions. Community-based participatory research (CBPR) has emerged as an alternative to the helicopter approach and is promoted here as a method to research that will meet the objectives of both First Nations and research communities. CBPR is a collaborative approach that equitably involves all partners in the research process. Although the benefits of CBPR have been recognized by segments of the University research community, there exists a need for comprehensive changes in approaches to First Nations centered research, and additional guidance to researchers on how to establish respectful and productive partnerships with First Nations communities beyond a single funded research project. This article provides a brief overview of ethical guidelines developed for researchers planning studies involving Aboriginal people as well as the historical context and principles of CBPR. A framework for building research partnerships with First Nations communities that incorporates and builds upon the guidelines and principles of CBPR is then presented. The framework was based on 10 years’ experience working with First Nations communities in Saskatchewan. The framework for research partnership is composed of five phases. They are categorized as the pre-research, community consultation, community entry, research and research dissemination phases. These phases are cyclical, non-linear and interconnected. Elements of, and opportunities for, exploration, discussion, engagement, consultation, relationship building, partnership development, community involvement, and information sharing are key components of the five phases within the framework. The phases and elements within this proposed framework have been utilized to build and implement sustainable collaborative environmental health research projects with Saskatchewan First Nations communities.

Quantifiable progress of the First Nations Water Management Strategy, 2001–2013: Ready for regulation?

Drinking water security is a serious issue for many First Nations reserve communities in Canada. Over the last decade, CAD

Risk factors associated with the choice to drink bottled water and tap water in rural Saskatchewan.

2 billion has been invested to improve the situation by way of several key policies. Though action plans have been developed, expert panels have been struck and commissioned assessments have occurred, little progress has been reported, and on-reserve communities suffering through drinking water emergencies continue to be featured in the media. This paper presents an evidence-based critical analysis of federal policies related to drinking water on First Nations lands, and their associated follow-up progress reports and commissioned assessments. The goals and outcomes of policies since 2001 are noted, and the scope and outcomes of each are compared. This study uses an exploratory analysis of government-documented quantifiable indicators to assess the progress made through the implementation of varied policies and expert panel recommendations. The analysis highlights shortfalls in the collection of indicator data that show that communities have the technical capacities to meet policy requirements. The effectiveness of government policies to prepare communities for the imposition of regulations introduced through the passing of Bill S-8, The Safe Drinking Water for First Nations Act (2012), is discussed.

Drinking water quality in Indigenous communities in Canada and health outcomes: a scoping review.

A cross-sectional study investigated risk factors associated with choices to drink bottled water and tap water in rural Saskatchewan. Of 7,500 anonymous postal questionnaires mailed out, 2,065 responses were analyzed using generalized linear mixed models. Those who reported a water advisory (p < 0.001) or living in the area for ≤10 years (p = 0.01) were more likely to choose bottled water. Those who reported tap water was not safe to drink were more likely to choose bottled water, an effect greater for those who had no aesthetic complaints (p ≤ 0.001), while those with aesthetic complaints were more likely to choose bottled water if they believed the water was safe (p < 0.001). Respondents who treated their water and did not use a community supply were more likely to choose bottled water (p < 0.001), while those who did not treat their water were more likely to choose bottled water regardless of whether a community supply was used (p < 0.001). A similar pattern of risk factors was associated with a decreased likelihood of consuming tap water daily; however, the use of a community water supply was not significant. Understanding the factors involved in drinking water choices could inform public health education efforts regarding water management in rural areas.

Whiteboard animation for knowledge mobilization: a test case from the Slave River and Delta, Canada

Background Many Indigenous communities in Canada live with high-risk drinking water systems and drinking water advisories and experience health status and water quality below that of the general population. A scoping review of research examining drinking water quality and its relationship to Indigenous health was conducted. Objective The study was undertaken to identify the extent of the literature, summarize current reports and identify research needs. Design A scoping review was designed to identify peer-reviewed literature that examined challenges related to drinking water and health in Indigenous communities in Canada. Key search terms were developed and mapped on five bibliographic databases (MEDLINE/PubMED, Web of Knowledge, SciVerse Scopus, Taylor and Francis online journal and Google Scholar). Online searches for grey literature using relevant government websites were completed. Results Sixteen articles (of 518; 156 bibliographic search engines, 362 grey literature) met criteria for inclusion (contained keywords; publication year 2000–2015; peer-reviewed and from Canada). Studies were quantitative (8), qualitative (5) or mixed (3) and included case, cohort, cross-sectional and participatory designs. In most articles, no definition of “health” was given (14/16), and the primary health issue described was gastrointestinal illness (12/16). Challenges to the study of health and well-being with respect to drinking water in Indigenous communities included irregular funding, remote locations, ethical approval processes, small sample sizes and missing data. Conclusions Research on drinking water and health outcomes in Indigenous communities in Canada is limited and occurs on an opportunistic basis. There is a need for more research funding, and inquiry to inform policy decisions for improvements of water quality and health-related outcomes in Indigenous communities. A coordinated network looking at First Nations water and health outcomes, a database to store and create access to research findings, increased funding and time frames for funding, and more decolonizing and community-based participatory research aimed at understanding the relationship between drinking water quality and health outcomes in First Nations communities in Canada are needed.

Perspectives on past and present waste disposal practices: a community-based participatory research project in three Saskatchewan first nations communities.

Objective To present the co-creation of a whiteboard animation video, an enhanced e-storytelling technique for relaying traditional knowledge interview results as narratives. Design We present a design for translating interview results into a script and accompanying series of figures, followed by technical steps to create a whiteboard animation product. Method Our project used content analysis and researcher triangulation, followed by a collaborative process to develop an animated video to disseminate research findings. A 13-minute long whiteboard animation video was produced from a research study about changing environments in northern Canadian communities and was distributed to local people. Three challenging issues in the video creation process including communication issues, technical difficulties and contextual debate were resolved among the supporting agencies and researchers. Conclusions Dissemination of findings is a crucial step in the research process. Whiteboard animation video products may be a viable and culturally-appropriate form of relaying research results back to Indigenous communities in a storytelling format.

Troglitazone reduces heat shock protein 70 content in primary rat hepatocytes by a ubiquitin proteasome independent mechanism

The impact of current and historical waste disposal practices on the environment and human health of Indigenous people in First Nations communities has yet to be adequately addressed. Solid waste disposal has been identified as a major environmental threat to First Nations Communities. A community-based participatory research project (CBPR) was initiated by the Saskatoon Tribal Council Health and Family Services Incorporated to investigate concerns related to waste disposal in three Saskatchewan First Nations Communities. Utilizing a qualitative approach, we aimed to gain an understanding of past and present waste disposal practices and to identify any human and environmental health concerns related to these practices. One to one interviews and sharing circles were conducted with Elders. Elders were asked to share their perspectives on past and present waste disposal practices and to comment on the possible impacts these practices may have on the environment and community health. Historically waste disposal practices were similar among communities. The homeowner generated small volumes of waste, was exclusively responsible for disposal and utilized a backyard pit. Overtime waste disposal evolved to weekly pick-up of un-segregated garbage with waste disposal and open trash burning in a community dump site. Dump site locations and open trash burning were identified as significant health issues related to waste disposal practices in these communities. This research raises issues of inequity in the management of waste in First Nations Communities. It highlights the need for long-term sustainable funding to support community-based waste disposal and management strategies and the development of First Nations centered and delivered educational programs to encourage the adoption and implementation of waste reduction, reutilization and recycling activities in these communities.