Aaron Gibson - Academia.edu (original) (raw)

Papers by Aaron Gibson

International Clinical Psychopharmacology, 2007

The objective of this study was to evaluate the effectiveness and tolerability of aripiprazole us... more The objective of this study was to evaluate the effectiveness and tolerability of aripiprazole use in child and adolescent psychiatric inpatients. This was a naturalistic, retrospective evaluation of the discharged patients treated with aripiprazole on the child and adolescent unit at the Austin State Hospital. To be included, patients had to be &amp;amp;amp;amp;amp;amp;amp;lt;18 years of age and treated with aripiprazole for at least two consecutive weeks during their hospital stay. We used a chart extracted Clinical Global Impression of Improvement, and a chart extracted Clinical Global Impression of Severity of Illness score to determine their effectiveness. Adverse events and side effects recorded in the physician or nursing notes were collected to establish tolerability. Forty-five patients met the criteria and were included in this analysis. Average clinical global impression of severity of illness scores at baseline and endpoint were 5.04+/-0.91 and 3.33+/-1.24 respectively. This difference was statistically significant (Wilcoxon&amp;amp;amp;amp;amp;amp;amp;#39;s signed-rank test: Z=-5.179, P&amp;amp;amp;amp;amp;amp;amp;lt;0.001). Fifty-one percent of the youth had a clinical global impression of severity of illness score that was much improved or very much improved (clinical global impression of improvement score of 1 or 2). Significant reduction in clinical global impression of severity of illness scores suggests a decline in the symptom severity for patients treated with aripiprazole. On the basis of the reported adverse events and side effects, aripiprazole was generally well tolerated. Randomized controlled trials of aripiprazole in childhood mental disorders are warranted.

Annals of Pharmacotherapy, 2006

To identify, review, and analyze studies comparing atomoxetine with psychostimulants with the int... more To identify, review, and analyze studies comparing atomoxetine with psychostimulants with the intent of determining the role of atomoxetine in the pharmacologic management of attention deficit/hyperactivity disorder (ADHD). Primary, review, and meta-analysis articles were identified by a MEDLINE search (1966-December 2005). MeSH headings used in the search include: attention deficit/hyperactivity disorder, ADHD, atomoxetine, stimulants, psychostimulants, methylphenidate, and amphetamine salts. Relevant data presented at professional meetings that we attended were also identified. All clinical studies comparing atomoxetine with psychostimulants, regardless of study design, were evaluated. Relevant efficacy and safety data from these studies were included in the discussion. At time of writing, 5 head-to-head trials had compared psychostimulants and atomoxetine in the treatment of ADHD. No significant difference between atomoxetine and methylphenidate immediate-release were found on the ADHD Rating Scale total score. Osmotic oral release system (OROS) methylphenidate showed significantly greater improvement at weeks 1 and 2, and significantly more patients treated with OROS methylphenidate were classified as responders. Patients on both atomoxetine and mixed amphetamine salts extended-release (MAS XR) showed significant improvements at endpoint over baseline; however, Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scores were significantly better with MAS XR. Tolerability was similar between atomoxetine and stimulant medications. Based on available evidence, psychostimulants are regarded as first-line pharmacologic treatment for children and adolescents with ADHD, as the efficacy and safety of these agents have been well established based on clinical trials and extensive naturalistic use. Adverse effects in some patients and abuse potential have led to the search for new treatments. Atomoxetine represents an alternative treatment for ADHD and is unlikely to be associated with abuse; however, long-term safety data are needed to further establish its place in therapy.

PloS one, 2014

Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, a... more Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR). ADMA levels in bronchoalveolar lavage fluid (BALF) and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM). Airway inflammation was assessed by bronchoalveolar lavage (BAL) total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH...

The Journal of investigative dermatology, 2015

Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression an... more Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However, their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on transepidermal water loss (TEWL), sensitization, and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, supporting a r...

PLoS ONE, 2011

Background: Asthma is a chronic inflammatory disease with a strong genetic predisposition. A majo... more Background: Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.

PLoS ONE, 2012

Rationale and Objective: Autophagy is a cellular process directed at eliminating or recycling cel... more Rationale and Objective: Autophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.

Journal of Allergy and Clinical Immunology, 2013

Background: It is well accepted that mold exposure is a major contributor to the development of a... more Background: It is well accepted that mold exposure is a major contributor to the development of asthma, and beta-glucans are often used as a surrogate for mold exposure in the environment. Beta-glucans are an important component of mold spores and are recognized by the immune system by their receptor, Dectin-1. Cladosporium cladosporioides spores have a high betaglucan content, but the beta-glucans are not available on the surface of live spores. Objective: We sought to determine whether altering the exposure of beta-glucans in C cladosporioides through heat killing could alter the immune response through binding to Dectin-1. Methods: In a murine model of mold-induced asthma, mice were repeatedly exposed to either live or heat-killed C cladosporioides and the phenotype was determined by the measurement of airway hyperresponsiveness, airway inflammation, and cytokine production. Pro-inflammatory cytokines from dendritic cells were measured by using quantitative PCR and ELISA. Results: Live C cladosporioides induced robust airway hyperresponsiveness, eosinophilia, and a predominately T H 2 response, while heat-killed C cladosporioides induced a strong T H 17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing of C cladosporioides spores effectively exposed beta-glucans on the surface of the spores and increased binding to Dectin-1. In the absence of Dectin-1, heat-killed spores induced a predominantly T H 2 response analogous to live spores. Furthermore, the production of T H 17-skewing IL-6, IL-23, and TNF-a by dendritic cells in response to heat-killed C cladosporioides was dependent on Dectin-1. Conclusions: The host immune response to C cladosporioides is dependent on the surface availability of beta-glucans rather than the total beta-glucan content. (J Allergy Clin Immunol 2013;132:159-69.)

Journal of Allergy and Clinical Immunology, 2007

Background: Allergic sensitization affects half of western populations and often precedes the dev... more Background: Allergic sensitization affects half of western populations and often precedes the development of allergic disorders including asthma. Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 receptor a2 (IL-13Ra2) is a decoy receptor for IL-13. Objective: Although the existence of soluble IL-13Ra2 has been documented, the mechanisms underlying its generation are unknown. Many allergens possess protease activity; we investigated whether IL-13Ra2 is solubilized in response to allergen treatment. Methods: We evaluated the ability of allergens to solubilize IL-13Ra2 in vitro and in vivo and examined the effect on IL-13 signaling and responses. Results: We determined that treatment of cells with house dust mite (HDM) allergen or purified Dermatophagoides pteronyssinus or Dermatophagoides farinae, but not other allergens, resulted in release of soluble IL-13Ra2 that was biologically active and inhibited IL-13 signaling. Prolonged exposure to HDM or treatment with mold allergens resulted in IL-13Ra2 degradation. This was associated with increased IL-13 signaling. A single treatment of HDM in vivo resulted in release of IL-13Ra2 into the bronchoalveolar lavage (BAL) fluid. BAL fluid from humans also contained IL-13Ra2; BAL fluid from individuals with asthma contained less IL-13Ra2 than that from controls. Conclusion: Allergen exposure can directly affect the level of soluble IL-13Ra2 in a way that affects IL-13 signaling and responses. Clinical implications: Soluble IL-13Ra2 may be an important biomarker of environmental allergen exposure and asthma. (J Allergy Clin Immunol 2007;119:375-83.)

Journal of Allergy and Clinical Immunology, 2008

IL-13 receptor alpha2 (IL-13R alpha 2) is a high-affinity receptor for IL-13, a central mediator ... more IL-13 receptor alpha2 (IL-13R alpha 2) is a high-affinity receptor for IL-13, a central mediator of allergic asthma. It acts predominantly as a decoy receptor but can also contribute to IL-13 responses under certain conditions. IL-13R alpha 2 exists in soluble and membrane forms, which can both bind IL-13 and modulate its activity. Yet the proteolytic processes that contribute to the generation of soluble IL-13R alpha 2 are largely unknown. We sought to investigate the role of matrix metalloproteinases (MMPs) in the generation of soluble IL-13R alpha 2. Acellular cleavage assays by MMPs were performed by using glutathione-S-transferase fusion proteins of murine or human IL-13R alpha 2. IL-13R alpha 2 stable-transfected cells were used for analysis of surface expression and release of soluble IL-13R alpha 2. Wild-type and MMP-8-deficient mice were used for analysis of allergen-induced airway hyperresponsiveness and solubilization of IL-13R alpha 2. Among several MMPs tested, only MMP-8 cleaved IL-13R alpha 2. Treatment of transfected human or murine cells expressing high levels of surface IL-13R alpha 2 with MMP-8 resulted in release of soluble IL-13R alpha 2 into the supernatants, with a concomitant decrease in surface IL-13R alpha 2 levels. The IL-13R alpha 2 solubilized by MMP-8 retained IL-13 binding activity. In an asthma model MMP-8-deficient mice displayed increased airway hyperresponsiveness and decreased soluble IL-13R alpha 2 protein levels in bronchoalveolar lavage fluid compared with those seen in wild-type mice after house dust mite challenge. MMP-8 cleaves IL-13R alpha 2 in vitro and contributes to the solubilization of IL-13R alpha 2 in vivo.