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Biomedical subjects

M J MacLean

Publications and source records attributed to M J MacLean.

9 recordsLinked to original sources

Methylglyoxal production in bacteria: suicide or survival?

Methylglyoxal is a toxic electrophile. In Escherichia coli cells, the principal route of methylglyoxal production is from dihydroxyacetone phosphate by the action of methylglyoxal synthase. The toxicity of methylglyoxal is believed to be due to its ability to interact with the nucleophilic centres of macromolecules such as DNA. Bacteria possess an array of detoxification pathways for methylglyoxal. In E. coli, glutathione-based detoxification is central to survival of exposure to methylglyoxal. The glutathione-dependent glyoxalase I-II pathway is the primary route of methylglyoxal detoxification, and the glutathione conjugates formed can activate the KefB and KefC potassium channels. The activation of these channels leads to a lowering of the intracellular pH of the bacterial cell, which protects against the toxic effects of electrophiles. In addition to the KefB and KefC systems, E. coli cells are equipped with a number of independent protective mechanisms whose purpose appears to be directed at ensuring the integrity of the DNA. A model of how these protective mechanisms function will be presented. The production of methylglyoxal by cells is a paradox that can be resolved by assigning an important role in adaptation to conditions of nutrient imbalance. Analysis of a methylglyoxal synthase-deficient mutant provides evidence that methylglyoxal production is required to allow growth under certain environmental conditions. The production of methylglyoxal may represent a high-risk strategy that facilitates adaptation, but which on failure leads to cell death. New strategies for antibacterial therapy may be based on undermining the detoxification and defence mechanisms coupled with deregulation of methylglyoxal synthesis.

Antiporters↗

The role of glyoxalase I in the detoxification of methylglyoxal and in the activation of the KefB K+ efflux system in Escherichia coli.

The glyoxalase I gene (gloA) of Escherichia coli has been cloned and used to create a null mutant. Cells overexpressing glyoxalase I exhibit enhanced tolerance of methylglyoxal (MG) and exhibit elevated rates of detoxification, although the increase is not stoichiometric with the change in enzyme activity. Potassium efflux via KefB is also enhanced in the overexpressing strain. Analysis of the physiology of the mutant has revealed that growth and viability are quite normal, unless the cell is challenged with MG either added exogenously or synthesized by the cells. The mutant strain has a low rate of detoxification of MG, and cells rapidly lose viability when exposed to this electrophile. Activation of KefB and KefC is diminished in the absence of functional glyoxalase I. These data suggest that the glutathione-dependent glyoxalase I is the dominant detoxification pathway for MG in E. coli and that the product of glyoxalase I activity, S-lactoylglutathione, is the activator of KefB and KefC.

Antiporters↗

I want to live here for rest of my life. The challenge of case management for rural seniors.

The research on long-term care for seniors clearly demonstrates that efforts to integrate urban case management services with elderly people living in rural settings have not been successful. Presenting findings of the Rural Seniors Assisted Living Study conducted in northwestern Ontario, Canada, this article demonstrates the complexity of providing health and social services for seniors living in small rural communities, services that are often vastly different from those provided in urban communities. The article proposes a specialized Rural Case Management approach with rural elderly clients and identifies four intervention roles: providing direct service, consulting extensively with specialists of other disciplines, constructing and supporting natural helping networks, and resource management. The approach also requires that the rural case manager assume a leadership role at the community level in the development of services for seniors. Having a locally based case manager rather that a case manager who travels out to rural areas from an urban center is essential to the success of this rural case management approach. Finally, the article contends that rural case management differs from urban case management by requiring specialized knowledge, skills and educational programs.

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Changing the way we talk with elders: promoting health using the communication enhancement model.

Good communication is an essential component of optimal delivery of health care and health promotion efforts. In this article, we address the communication predicament faced by older adults when their opportunities for optimal care are limited by inappropriate communication with formal care providers. We then introduce the Communication Enhancement Model which promotes health in old age by stressing recognition of individualized cues, modification of communication to suit individual needs and situations, appropriate assessment of the health/social problems, and empowerment of both elders and providers. Applications of the Communication Enhancement Model are discussed for two high-risk groups (elders from ethnocultural communities and elders with dementia) to show how it can function as a guide for the development and evaluation of educational interventions with health and social professionals working with elders.

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Time course of myocardial bloodflow changes during healing of myocardial infarct in pigs.

OBJECTIVE: To define the time course of changes in bloodflow and microsphere content at intervals between one and 28 days after surgical ligation of the circumflex coronary artery. SUBJECTS AND METHODS: After the ligation, pigs were assigned to six groups; all pigs in a group were reanesthetized at either one, three, seven, 14, 21 or 28 days post ligation to determine myocardial bloodflow distribution using radionuclide-labelled (15 +/- 2 microns) microspheres. RESULTS: Bloodflow to the infarct zone, 10 mins post ligation, was 7.3 +/- 1.4% of the normal flow. At one and three days post occlusion, infarct bloodflow was about 50% of the 'normal', declining after day 7 to between 20 and 25%. Bloodflow in the noninfarct zone was significantly elevated during the initial 14 days, declining thereafter to within the normal range. Microspheres in the infarct zone injected prior to the occlusion became concentrated and were diluted in the noninfarct zone; the ratio of infarct:noninfarct microsphere content rose progressively, reaching a 2.5-fold rise by day 28. CONCLUSIONS: The initial stages of infarct healing are associated with a marked rise in bloodflow with a subsequent fall. A more prolonged augmentation of flow is evident in the noninfarct zone. Microspheres are useful in estimating the relative magnitude of changes in the myocardium accompanying the healing (shrinkage) of the infarct and hypertrophy occurring in the noninfarct zone after a coronary occlusion.

Animals↗

Just World beliefs and attitudes toward helping elderly people: a comparison of British and Canadian university students.

Social science students from a British university and a Canadian university were studied to determine the relationship between their beliefs in a just world and their attitudes toward helping elderly people who have social, economic or health needs. Approximately 30 percent of the British students (N = 71) and 50 percent of the Canadian students (N = 124) expressed a belief in a just world. In both groups, just world believers blamed elderly people for being in poor health or financial circumstances, and the Canadian just world believers also tended to dismiss the needs of elderly people for the convenience of society. These and other differences in the attitudes of the British and Canadian students toward elderly people are discussed from a social and historical context. Implications of a belief in a just world by social science students are discussed in relation to the provision of social services to elderly people.

Adolescent↗

The normalization principle and the institutionalized elderly.

As a large percentage of the elderly population will spend some time in long-term facilities such as nursing homes, it is important to ensure the best possible conditions for residents and staff of these facilities. The authors describe the application of the eight components of the "normalization principle" to the institutionalized elderly as a valuable, systematic approach to maintaining the quality of life in long-term facilities. They suggest methods of promoting normal daily, weekly, and yearly rhythms, normal life-cycle experiences, and normal social, sexual, economic and environmental conditions within the framework of the long-term facility.

Activities of Daily Living↗

Aspects of preventive health care for older persons.

Preventive health care for older persons is considered in terms of primary, secondary and tertiary prevention and examples of relevant services are provided both from Canada and from other countries. Three areas of concern are identified, namely communication, quality assurance and funding. It is suggested that various approaches used in other countries, such as Home Visitor Programs, be examined and more generally that comparisons with health care services in other countries be carried out, particularly with respect to evaluations and possible economic steering effects.

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