Pulmonary pathogenesis in a murine model of inhaled arsenical exposure.

Arsenic trioxide (ATO), an inorganic arsenical, is a toxic environmental contaminant. It is also a widely used chemical with industrial and medicinal uses. Significant public health risk exists from its intentional or accidental exposure. The pulmonary pathology of acute high dose exposure is not well defined. We developed and characterized a murine model of a single inhaled exposure to ATO, which was evaluated 24 h post-exposure. ATO caused hypoxemia as demonstrated by arterial blood-gas measurements. ATO administration caused disruption of alveolar-capillary membrane as shown by increase in total protein and IgM in the bronchoalveolar lavage fluid (BALF) supernatant and an onset of pulmonary edema. BALF of ATO-exposed mice had increased HMGB1, a damage-associated molecular pattern (DAMP) molecule, and differential cell counts revealed increased neutrophils. BALF supernatant also showed an increase in protein levels of eotaxin/CCL-11 and MCP-3/CCL-7 and a reduction in IL-10, IL-19, IFN-γ, and IL-2. In the lung of ATO-exposed mice, increased protein levels of G-CSF, CXCL-5, and CCL-11 were noted. Increased mRNA levels of TNF-a, and CCL2 in ATO-challenged lungs further supported an inflammatory pathogenesis. Neutrophils were increased in the blood of ATO-exposed animals. Pulmonary function was also evaluated using flexiVent. Consistent with an acute lung injury phenotype, respiratory and lung elastance showed significant increase in ATO-exposed mice. PV loops showed a downward shift and a decrease in inspiratory capacity in the ATO mice. Flow-volume curves showed a decrease in FEV0.1 and FEF50. These results demonstrate that inhaled ATO leads to pulmonary damage and characteristic dysfunctions resembling ARDS in humans.

Efficacy of combined fractional carbon dioxide laser and topical tazarotene in nail psoriasis treatment: A randomized intrapatient left-to-right study.

BACKGROUND: Treatment of nail psoriasis is disappointing; due to poor penetrability of topical therapies and variable efficacy of systemic therapies. Fractional carbon dioxide laser (FCL) may enhance penetration of topical therapy for nail psoriasis. OBJECTIVE: To evaluate the efficacy and safety of FCL plus topical tazarotene versus tazarotene monotherapy in the treatment of nail psoriasis. METHODS: Twenty-seven patients with bilateral fingernail psoriasis randomly received 3 sessions of FCL at four-week interval plus once-daily tazarotene 0.1% gel for one hand, and once-daily tazarotene 0.1% gel only for 3 months on the other hand. The primary outcome was modified Nail Psoriasis Severity Index (mNAPSI) at 3 and 6 months compared to baseline, and the secondary outcomes included dermoscopic examination and patient global assessment. Adverse events were reported. RESULTS: The total, nail matrix, and nail bed mNAPSI scores were significantly improved at 3 and 6 months by both regimens, but they decreased more after FCL/tazarotene combination (p = 0.001, p = 0.023, and p = 0.001, respectively). Combination therapy showed faster improvement of nail matrix signs and greater efficacy for nail bed signs. The dermoscopic features of the nail plate were the most responsive after both treatments. The combined therapy was more effective in improving the dermoscopic nail bed features. Patient's global assessment scores were significantly higher after the combined therapy. Both treatments were well tolerated. CONCLUSION: Fractional CO2  laser is an effective and well-tolerated treatment for nail psoriasis; it improves the outcomes of topical tazarotene especially in nail bed lesions.