Glucocorticoids and the skin

Glucocorticoids are the most effective anti -inflammatory agents currently available, but a variety of adverse effects limit their clinical usefulness. This work explores further two facets of the interaction between glucocorticoids and the skin, with the aim of identifying means of reducing glucocorticoid toxicity.(a) Metabolism of glucocorticoids by skin: Human skin is active in the terminal metabolism of cortisol to cortisone, but the biological implications of this process in skin are uncertain. Because there are technical difficulties in dealing with human skin, an animal model, the nude mouse, has been evaluated for its suitability to the study of the metabolism of corticosterone to 11B- dehydrocorticosterone (the homologous reaction in rodents of cortisol to cortisone conversion in man); a process mediated by 1 l ß- hydroxysteroid dehydrogenase. The skin of the nude mouse has previously been shown to be appropriate for pharmacokinetic and phannacodynamic studies of glucocorticoids. In this model, skin 11B- hydroxysteroid dehydrogenase had an apparent Km for corticosterone of 37 p.M. Skin 11B- hydroxysteroid dehydrogenase was up- regulated, in -vivo, by active glucocorticoids and was NADP dependent. By comparison, kidney 1 Iß- hydroxysteroid dehydrogenasé had a higher apparent Km (120 μM) for corticosterone, used NAD and NADP with equal facility and was not regulated in- vivo by glucocorticoids. These data suggest that the skin may possess an isoform distinct from that of the kidney. Immunohistochemical studies demonstrated that 11ß -hydroxysteroid dehydrogenase was most abundant in the epidermis. In- vitro, this enzyme was markedly inhibited by glycyrrhetinic acid, the active principle in liquorice. Using the classic bioassay of glucocorticoid activity (skin vasoconstrictor assay), it was found that co- application of glycyrrhetinic acid and hydrocortisone resulted in potentiation of skin vasoconstrictor activity of hydrocortisone. This suggests that inhibition of hydrocortisone metabolism might explain the long recognised but poorly understood anti - inflammatory action of liquorice and its congeners and may represent a novel means of targeting glucocorticoid therapy.(b) Skin vasoconstrictor response (blanching) to topical glucocorticoids: Glucocorticoids applied topically to human skin produce vasoconstriction in dermal vessels, the degree of which correlates closely with the potency and clinically efficacy of these compounds. Although previous workers had noted heterogeneity in blanching responses to glucocorticoids, this was never systematically studied. In qualitative studies, it was shown that skin blanching was inducible by RU- 28362, a specific glucocorticoid receptor (type II) agonist and blocked by RU- 38486, a glucocorticoid antagonist. Moreover, aldosterone (type I receptor agonist) failed to produce blanching. In addition blanching was observed in an individual with clinical and biochemical features of aldosterone receptor deficiency. These data therefore suggest that blanching is a glucocorticoid specific phenomenon mediated via the classical glucocorticoid receptor. To test whether skin vasoconstrictor response might reflect glucocorticoid sensitivity, blanching responses was tested in a clinical model of glucocorticoid resistance. In patients with glucocorticoid resistant asthma, skin responsiveness was also found to be diminished. Responsiveness was also somewhat diminished in a cohort of asthmatics on long term prednisolone. Skin vasoconstrictor responsiveness might therefore reflect systemic sensitivity to glucocorticoids and previous glucocorticoid use might reduce skin responsiveness. When tested against other parameter indicating systemic glucocorticoid effects, acute systemic glucocorticoid exposure over 10 days did not affect skin responsiveness. It is possible that resistance to the anti -inflammatory effects of glucocorticoids might accrue from long term exposure and it might therefore be possible to use the skin vasoconstrictor assay a marker for glucocorticoid sensitivity - a novel purpose for this long used assay

European Forests and Carbon Sequestration Services: An Economic Assessment of Climate Change Impacts

This paper reports an original economic valuation of the impact of climate change on the provision of forest regulating services in Europe. To the authors’ knowledge the current paper represents the first systematic attempt to estimate human well-being losses with respect to changes in biodiversity and forest regulating services that are directly driven by climate change. First, selected 34 European countries are grouped by their latitude intervals to capture the differentiated regional effects of forests in response to climate change. Moreover, the future trends of forest areas and stocked carbon in 2050 are projected through the construction and simulation of global circulation models such as HADMC3 following four different future developing paths described by the four IPCC scenarios. Finally, the valuation exercise is anchored in an ecosystem service based approach, involving the use of general circulation models and integrated assessment models. Our findings address two dimensions in the evaluation of climate impacts on European forests: Firstly, future projections yield different states of the world depending upon the IPCC scenario adopted. Secondly, spatial issues matter in an assessment of the distributional impacts of climate change, as these impacts are not distributed in a uniform way across the European countries under consideration.Economic Valuation, Forest Ecosystem, Carbon Sequestration, Climate Change Impacts

Recreational, Cultural and Aesthetic Services from Estuarine and Coastal Ecosystems

The role of economic analysis in guiding the sustainable development of estuarine and coastal ecosystems is investigated based on a comprehensive review of the literature on the valuation of the recreation, cultural and aesthetic services. The implications of the findings for the sustainable management of coral reefs, Marine Protected Areas, and Small Island Developing States are discussed. Finally, the potential of meta-analytical benefit transfer and scaling up of values at various aggregation levels is demonstrated in the context of coastal tourism and recreation in Europe. The results of the study support the conclusion that the non-material values provided by coastal and estuarine ecosystems in terms of recreational, cultural and aesthetic services represent a substantial component of human well-being.Aesthetic Values, Coastal Recreation, Coral Reefs, Cultural Values, Ecosystem Services Valuation, Ecosystem Services, Estuarine Ecosystems, Marine Protected Areas, Non-market Valuation, Non-use Values, Passive Values, Recreational Fishing, Small Island Developing States, Spiritual and Religious Values.

Environmental Justice, Transit Equity and the Place for Immigrants in Toronto

In response to population growth and events, Toronto is currently in the midst of debates about transportation planning. However, the perspectives of immigrants, especially women, who depend heavily on public transit, are often missing from academic and policy debates on transportation planning in Toronto. Due to Toronto’s changing demographic landscape, a transit planning strategy that is based on a deeper understanding of how immigrant groups travel across the city can further social equity in transportation. Drawing on qualitative interviews with immigrants on their experiences of public transit in Toronto, the paper proposes an environmental justice framework in order to consider the equity and sustainability issues inherent in Toronto stakeholders’ focus on transit expansion. The research fi ndings highlight the limited aff ordability of public transit, the poor servicing and connectivity of transit networks, and the resulting barriers to accessing work opportunities across the region. The paper concludes by highlighting the need for new directions in transit policy and planning that can better address the changing demographics and social and spatial divisions in the city

Assessments of Childhood Apraxia of Speech Disorder

Speech communication is important for every human being. Whether the communication is verbal or non-verbal, everyone goes through a specific process to formulate speech. The specific process is known as the speech chain model. As the speaker, the speech communication chain consists of six stages. These are intention, meaning, utterance, articulatory planning, articulatory production, and sound. As the listener, the speech communication chain continues with the auditory response, word sequence, meaning, and then understanding the information that was received. To put this in play, an idea or thought is formed first. The brain then assigns meanings to words and the brain categorizes those words through the mental lexicon. After those words have been assigned, the brain starts planning how to produce thoughts. The brain then sends those plans to the articulatory muscles and produces phonetic sounds to form a meaningful sentence (Denes & Pinson, 1993)

Energy Solutions, Neo-Liberalism, and Social Diversity in Toronto, Canada

In response to the dominance of green capitalist discourses in Canada’s environmental movement, in this paper, we argue that strategies to improve energy policy must also provide mechanisms to address social conflicts and social disparities. Environmental justice is proposed as an alternative to mainstream environmentalism, one that seeks to address systemic social and spatial exclusion encountered by many racialized immigrants in Toronto as a result of neo-liberal and green capitalist municipal policy and that seeks to position marginalized communities as valued contributors to energy solutions. We examine Toronto-based municipal state initiatives aimed at reducing energy use while concurrently stimulating growth (specifically, green economy/green jobs and ‘smart growth’). By treating these as instruments of green capitalism, we illustrate the utility of environmental justice applied to energy-related problems and as a means to analyze stakeholders’ positions in the context of neo-liberalism and green capitalism, and as opening possibilities for resistance

Glucometric Guardianship

This communication conceptualizes, defines and describes glucometric guardianship, as a means of ensuring optimal glycemic management. We define glucometric guardianship as the process of ensuring appropriate measurement, monitoring and analysis of glucose levels, so as to ensure alertness in glycemic management, and agility in anticipating and detecting suboptimal glycemic parameters, and responding to them. This paper hopes to draw attention to the need for glucometric science, encourage debate and discussion and facilitate research on the topic

Does insulin resistance co-exist with glucocorticoid resistance in the metabolic syndrome? Studies comparing skin sensitivity to glucocorticoids in individuals with and without acanthosis nigricans

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome is associated with increased risk for both diabetes and coronary artery disease, which insulin resistance alone does not satisfactorily explain. We propose an additional and complementary underlying mechanism of glucocorticoid resistance.</p> <p>Results</p> <p>Using acanthosis nigricans (AN) and skin vasoconstrictor (SVC) response to topically applied beclomethasone dipropionate as markers of insulin and glucocorticoid resistance, respectively, we compared anthropometric, biochemical, pro-inflammatory markers and the SVC response in subjects with AN in two studies: STUDY 1 was used to compare subjects with AN (Grade 4, n = 32), with those without AN (n = 68) while STUDY 2 compared these responses among a cross-section of diabetic patients (n = 109) with varying grades of AN (grade 0, n = 30; grade 1, n = 24; grade 2, n = 18; grade 3, n = 25; grade 4, n = 12).</p> <p>Findings</p> <p>In both studies there was an inverse relationship between AN Grade 4 and the SVC response, (P < 0.001). In STUDY 1, AN Grade 4 was associated with age, waist circumference, BMI, fasting blood glucose, plasma lipids and hs-CRP (P < 0.05). SVC was an independent predictor of CRP and those with combined AN and a negative SVC response, CRP levels were highest. In Study 2 when the SVC response in subjects with type 2 diabetes mellitus with varying degrees of AN was studied, it showed that for any degree of AN, the SVC response is more likely to be negative and was independent of gender and ethnicity.</p> <p>Conclusion</p> <p>An absent SVC response represents a new biomarker for the metabolic syndrome and the exaggerated inflammatory response, which characterizes the metabolic syndrome, may be an outcome of deficient glucocorticoid action in vascular tissue.</p

Bariatric Surgery in the Caribbean: Is It Safe in a Low-Volume, Third World Setting?

Bariatric surgery is a well-recognized modality of management of obesity. In addition to obesity, it effectively controls diabetes mellitus, and hypertension. It has been recommended that bariatric surgery should be done in “designated centers” of excellence where there is a high volume of case turnover. Caribbean nations are not spared from the global spread of the obesity epidemic; however, not many patients get the benefits of bariatric surgery. This study aimed to establish that bariatric surgery could be safely and efficiently undertaken in a low-volume center outside the “designated centers” with comparable patient outcomes even in a third world setting. Though “patient numbers” generally imply better outcome, in an environment where these numbers cannot be achieved, patients should not be denied the access to surgery once good outcomes are achieved