Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

Evapotranspiration of Residential Lawns Across the United States

Despite interest in the contribution of evapotranspiration (ET) of residential turfgrass lawns to household and municipal water budgets across the United States, the spatial and temporal variability of residential lawn ET across large scales is highly uncertain. We measured instantaneous ET (ETinst) of lawns in 79 residential yards in six metropolitan areas: Baltimore, Boston, Miami, Minneapolis-St. Paul (mesic climates), Los Angeles and Phoenix (arid climates). Each yard had one of four landscape types and management practices: traditional lawn-dominated yards with high or low fertilizer input, yards with water-conserving features, and yards with wildlife-friendly features. We measured ETinst in situ during the growing season using portable chambers and identified environmental and anthropogenic factors controlling ET in residential lawns. For each household, we used ETinst to estimate daily ET of the lawn (ETdaily) and multiplied ETdaily by the lawn area to estimate the total volume of water lost through ET of the lawn (ETvol). ETdaily varied from 0.9 ± 0.4 mm d1 in mesic cities to 2.9 ± 0.7 mm d−1 in arid cities. Neither ETinst nor ETdaily was significantly influenced by yard landscape types and ETinst patterns indicated that lawns may be largely decoupled from regional rain-driven climate patterns. ETvol ranged from ∼0 L d−1 to over 2,000 L d−1, proportionally increasing with lawn area. Current irrigation and lawn management practices did not necessarily result in different ETinst or ETdaily among traditional, water-conserving, or wildlife-friendly yards, but smaller lawn areas in water-conserving and wildlife-friendly yards resulted in lower ETvol

Shaping the Development of Prejudice: Latent Growth Modeling of the Influence of Social Dominance Orientation on Outgroup Affect in Youth

Social dominance orientation (SDO) has been theorized as a stable, early-emerging trait influencing outgroup evaluations, a view supported by evidence from cross-sectional and two-wave longitudinal research. Yet, the limitations of identifying causal paths with cross-sectional and two-wave designs are increasingly being acknowledged. This article presents the first use of multi-wave data to test the over-time relationship between SDO and outgroup affect among young people. We use cross-lagged and latent growth modeling (LGM) of a three-wave data set employing Norwegian adolescents (over 2 years, N = 453) and a five-wave data set with American university students (over 4 years, N = 748). Overall, SDO exhibits high temporal rank-order stability and predicts changes in outgroup affect. This research represents the strongest test to date of SDO’s role as a stable trait that influences the development of prejudice, while highlighting LGM as a valuable tool for social and political psychology

Factors associated with testicular self-examination among unaffected men from multiple-case testicular cancer families

<p>Abstract</p> <p>Background</p> <p>The lifetime testicular cancer (TC) risk in the general population is relatively low (~1 in 250), but men with a family history of TC are at 4 to 9 times greater risk than those without. Some health and professional organizations recommend consideration of testicular self-examination (TSE) for certain high-risk groups (e.g. men with a family history of TC). Yet little is known about factors associated with TSE behaviors in this at-risk group.</p> <p>Methods</p> <p>We collected information on this subject during an on-going NCI multidisciplinary, etiologically-focused, cross-sectional Familial Testicular Cancer (FTC) study. We present the first report specifically targeting TSE behaviors among first- and second-degree relatives (n = 99) of affected men from families with ≥ 2 TC cases. Demographic, medical, knowledge, health belief, and psychological factors consistent with the Health Belief Model (HBM) were evaluated as variables related to TSE behavior, using chi-square tests of association for categorical variables, and t-tests for continuous variables.</p> <p>Results</p> <p>For men in our sample, 46% (n = 46) reported performing TSE regularly and 51% (n = 50) reported not regularly performing TSE. Factors associated (p < .05) with regularly performing TSE in multivariate analysis were physician recommendation and testicular cancer worry. This is the first study to examine TSE in unaffected men from FTC families.</p> <p>Conclusion</p> <p>The findings suggest that, even in this high-risk setting, TSE practices are sub-optimal. Our data provide a basis for further exploring psychosocial issues that are specific to men with a family history of TC, and formulating intervention strategies aimed at improving adherence to TSE guidelines.</p

Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma.

Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential toxicity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics

Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma.

Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential toxicity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics

Benralizumab: a unique IL-5 inhibitor for severe asthma.

The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%-10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%-60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy