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Indianapolis, IN, United States

Beyer V.,Indiana University | Beyer V.,Medical University of South Carolina | Wolverton S.E.,Indianapolis
Archives of Dermatology | Year: 2010

Objectives: To analyze the current total cost of systemic therapy for psoriasis and to compare annual trends in the cost of both generic and brand-name therapies with trends in the Consumer Price Index-Urban since 2000. Design: A cost model was developed that includes costs for prescription drugs, office visits, and suggested laboratory tests and monitoring procedures. Annual trends in psoriasis drug costs from 2000 through 2008 were analyzed by calculating the percentage change in the average wholesale price from the previous year; these values were compared with changes in the yearly Consumer Price Index-Urban values. Setting: The United States. Main Outcome Measures: Total annual costs for systemic psoriasis therapies and trends in cost compared with the trends in Consumer Price Index-Urban values (equivalent to inflation). Results: Current total annual costs for systemic psoriasis therapies ranged from $1197 (methotrexate) to $27 577 (alefacept, two 12-week courses). Trends in the average wholesale price of brand-name psoriasis therapies from 2000 through 2008 demonstrate an average increase of 66% (range, -24% to +316%); thus, costs of several brand-name psoriasis drugs greatly outpaced the rates of inflation for all items and all prescription drugs. Conclusions: Despite the higher monitoring costs associated with traditional systemic therapies, annual costs of biologics exceed those of other available therapies. Current trends demonstrate that systemic psoriasis therapy costs are increasing at a much higher rate compared with general inflation. ©2010 American Medical Association. All rights reserved.

Konrad C.,Biochemistry and Molecular Biology | Wek R.C.,Indianapolis | Sullivan Jr. W.J.,Biochemistry and Molecular Biology | Sullivan Jr. W.J.,Indiana University
Eukaryotic Cell | Year: 2011

Toxoplasmosis is a significant opportunistic infection caused by the protozoan parasite Toxoplasma gondii, an obligate intracellular pathogen that relies on host cell nutrients for parasite proliferation. Toxoplasma parasites divide until they rupture the host cell, at which point the extracellular parasites must survive until they find a new host cell. Recent studies have indicated that phosphorylation of Toxoplasma eukaryotic translation initiation factor 2-alpha (TgIF2α) plays a key role in promoting parasite viability during times of extracellular stress. Here we report the cloning and characterization of a TgIF2 α kinase designated TgIF2K-D that is related to GCN2, a eukaryotic initiation factor 2 α (eIF2 α) kinase known to respond to nutrient starvation in other organisms. TgIF2K-D is present in the cytosol of both intra- and extracellular Toxoplasma parasites and facilitates translational control through TgIF2 α phosphorylation in extracellular parasites. We generated a TgIF2K-D knockout parasite and demonstrated that loss of this eIF2 α kinase leads to a significant fitness defect that stems from an inability of the parasite to adequately adapt to the environment outside host cells. This phenotype is consistent with that reported for our nonphosphorylatable TgIF2 α mutant (S71A substitution), establishing that TgIF2K-D is the primary eIF2α kinase responsible for promoting extracellular viability of Toxoplasma. These studies suggest that eIF2α phosphorylation and translational control are an important mechanism by which vulnerable extracellular parasites protect themselves while searching for a new host cell. Additionally, TgIF2α is phosphorylated when intracellular parasites are deprived of nutrients, but this can occur independently of TgIF2K-D, indicating that this activity can be mediated by a different TgIF2K. © 2011, American Society for Microbiology. All Rights Reserved.

Agarwal R.,Indianapolis | Agarwal R.,Richard udebush Va Medical Center
Current Opinion in Nephrology and Hypertension | Year: 2010

Purpose of review: Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP. Recent findings: The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity. Summary: The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rattermann M.J.,Indianapolis
Advances in School Mental Health Promotion | Year: 2014

This research presents data linking the impact of substance disorder to academic achievement, using data gathered at a recovery high school. Recovery schools provide recovery supports and a high-quality education to students with substance use disorders. The Global Appraisal of Individual Needs - Short Screener and the Northwest Evaluation Association Measures of Academic Progress were administered, and paired observations (Testing 1 (T1) vs. Testing 2 (T2)) were categorized based on information from the Global Appraisal of Individual Needs - Short Screen, as increased, decreased, or no change in substance disorder. Results confirm the impact of substance disorder on academic growth, with T1-T2 pairings in which substance disorder increased resulting in a decrease in academic growth, and T1-T2 pairings in which substance disorder decreased resulting in an increase in academic growth. The impact of no change in substance disorder from T1 to T2 varied by the time frame of the substance use, either in the past month or in the past year.

Molitoris B.A.,Indianapolis
Transactions of the American Clinical and Climatological Association | Year: 2014

Intravital 2-photon microscopy, along with the development of fluorescent probes and innovative software, has rapidly advanced the study of intracellular and intercellular processes at the organ level. Researchers can quantify the distribution, behavior, and dynamic interactions of up to four labeled chemical probes and proteins simultaneously and repeatedly in four dimensions (3D + time) with subcellular resolution in real time. Transgenic fluorescently labeled proteins, delivery of plasmids, and photo-activatable probes enhance these possibilities. Thus, multi-photon microscopy has greatly extended our ability to understand cell biology intra-vitally at cellular and subcellular levels. For example, evaluation of rat surface glomeruli and accompanying proximal tubules has shown the long held paradigm regarding limited albumin filtration under physiologic conditions is to be questioned. Furthermore, the role of proximal tubules in determining albuminuria under physiologic and disease conditions was supported by direct visualization and quantitative analysis.

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