Health as a Planning Problem: Combatting Diseases of Poverty

Diseases of Poverty (DOP), a group of parasitic and bacterial diseases characterized by their high prevalence and debilitating effects on poor communities, affect almost 12 million Americans per year. With over 20 variations, including hookworm and Chagas, DOP can have profoundly detrimental impacts on the individuals and communities affected. We can understand the issue of DOP within the United States as a result of two main factors: the lack of private and public knowledge of DOP and failing infrastructures across the South. Because many determinants of DOP are outside the direct control of the health sector and are laden with social, economic, and environmental influences, an effective policy solution should focus on improving disease-promoting environments and the failing water and waste infrastructure systems in which at-risk individuals live. Policies focused on water and waste infrastructure can play a proactive role in preventing the spread of DOP through ensuring safer and cleaner living spaces, aiding in the prevention – not just treatment – of DOP. More specifically, a multi-level infrastructure policy that targets funds and resources to rural, low-income communities through cooperation between all levels of government is essential to address DOP. I propose a DOP infrastructure program specifically for rural, low-income communities in which the federal government provides block grants to state governments and sets guidelines for spending while localities are responsible for the collection, use, and application of state-appropriated funds.https://deepblue.lib.umich.edu/bitstream/2027.42/154843/1/Kiningham_HealthasaPlanningProblem.pd

Density and Distribution of White-tailed Deer (\u3cem\u3eOdocoileus virginianus\u3c/em\u3e) in Cades Cove, Great Smoky Mountains National Park, Tennessee

Three census techniques were used from June 1978 to August 1979 to estimate population densities of white-tailed deer (Odocoileus virginianus) in Cades Cove, Great Smoky Mountains National Park, Tennessee. Roadside counts were conducted 3 times a week; once at dawn, dusk, and dark. Drive counts were made every 3 months and a 3-week sampling interval was used to make pellet counts. Seasonal density estimates ranged from: 0.29 to 0.58 deer/ha (dark counts) , 0.29 to 0.76 deer/ha (drive counts) , and 0.18 to 0.47 deer/ha (pellet counts). Adult sex ratios obtained from dawn and dark counts made during August (44.6 bucks:100 does) and November (22.0 bucks:100 does) indicated that there were more does than bucks in the population. These uneven adult sex ratios might be due to the dispersal of bucks out of Cades Cove during rut. Fawn:doe ratios made during the summer and fall roadside counts were 27.9 fawns:100 does in 1978 and 8.4 fawns: 100 does in 1979. The difference between these ratios could be the result of a delay in fawning in 1979 compared to 1978 and not an actual decrease in fawn recruitment. The similar density estimates obtained for the summer of 1978 (0.41 deer/ha) and 1979 (0.43 deer/ha) appeared to indicate that fawn recruitment in 1978 was equal to mortality and emigration among older deer in the cove. Of the 3 census techniques used, roadside counts were determined to be the best to estimate densities of deer in the Cove. Drive counts had 2 major disadvantages compared to roadside counts: (1) they required large amounts of manpower, and (2) they generated small sample sixes in both areas sampled and deer counted. Pellet counts were difficult to conduct during periods of leaf fall and snow cover. High rates of deterioration and/or disappearance of pellet groups in open fields made pellet counts in those areas unreliable. Pellet counts should be reserved for areas where techniques utilizing direct counts are impractical. The deer population in Cades Cove has increased since a die-off in 1971. At the present time the population might be stabilizing but, at a high density, ranging from 0.29 deer/ha to 0.58 deer/ha. As a result, disease and continued habitat degradation are probable. Three alternatives to the present management practices of the Cove were considered: (1) the removal of deer, (2) stopping cattle grazing and hay mowing to allow for the resumption of plant succession, and (3) developing the educational and research potentials of the Cove. Adoption of the latter alternative was recommended

Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin

Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O2•−), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O2•− was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O2•− was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O2•− abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O2•− with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O2•− production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans

Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

<p>Abstract</p> <p>Background</p> <p>Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours.</p> <p>Methods</p> <p>In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-κB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts.</p> <p>Results</p> <p>We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: <it>KLK7 </it>(<it>kallikrein 7</it>), <it>SOD2 </it>(<it>superoxide dismutase 2</it>), <it>100P </it>(<it>S100 calcium binding protein P</it>), <it>PI3 </it>(<it>protease inhibitor 3, skin-derived</it>), <it>CSTA </it>(<it>cystatin A</it>), <it>RARRES1 </it>(<it>retinoic acid receptor responder 1</it>), and <it>LXN </it>(<it>latexin</it>). The differential expression of the <it>KLK7 </it>and <it>SOD2 </it>transcripts was confirmed by Northern blot. Moreover, we observed that <it>SOD2 </it>expression correlates with the differential NF-κB activation exhibited by TNF-sensitive and TNF-resistant cells.</p> <p>Conclusion</p> <p>This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.</p

The effects of baicalein and baicalin on mitochondrial function and dynamics: A review

Mitochondria play an essential role in cell survival by providing energy, calcium buffering, and regulating apoptosis. A growing body of evidence shows that mitochondrial dysfunction and its consequences, including impairment of the mitochondrial respiratory chain, excessive generation of reactive oxygen species, and excitotoxicity, play a pivotal role in the pathogenesis of different diseases such as neurodegenerative diseases, neuropsychiatric disorders, and cancer. The therapeutical role of flavonoids on these diseases is gaining increasing acceptance. Numerous studies on experimental models have revealed the favorable role of flavonoids on mitochondrial function and structure. This review highlights the promising role of baicalin and its aglycone form, baicalein, on mitochondrial function and structure with a focus on its therapeutic effects. We also discuss their chemistry, sources and bioavailability

Manganese Superoxide Dismutase: Guardian of the Powerhouse

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production