Whereas high-dose ultraviolet B (UVB) is detrimental to the epidermal permeability barrier, suberythemal doses of UVB are used to treat atopic dermatitis (AD), which is characterized by defective permeability barrier and antimicrobial function. As epidermal permeability barrier and antimicrobial peptide (AMP) expression are coregulated and interdependent functions, we hypothesized that suberythemal doses of UVB exposure could regulate AMP expression in parallel with permeability barrier function. Hairless mice were exposed to 40 mJ cm(-2) UVB (about 1/2 minimal erythema dose) daily for 1 or 3 days. Twenty-four hours after the last exposure, epidermal barrier function was assessed and skin specimens were taken for western blotting, immunohistochemistry, and quantitative reverse transcription-PCR for mouse beta-defensin (mBD)-2, mBD3 and cathelin-related antimicrobial peptide (CRAMP). mRNA levels of the vitamin D receptor (VDR), 1alpha-hydroxylase and key epidermal lipid synthetic enzymes were also quantified. After 3 days of UVB exposure, acceleration of barrier recovery and augmentation in expression of epidermal differentiation markers (for example, involucrin and filaggrin) occurred in parallel with increased mBD2, mBD3, and CRAMP expression at both the mRNA and protein level. VDR, 1alpha-hydroxylase, and the major epidermal lipid synthetic enzymes were also upregulated. When an inhibitor of 1alpha, 25 dihydroxyvitamin D(3) formation, ketoconazole, was applied immediately after UVB exposure, the cutaneous vitamin D system was inhibited, which in turn blocked epidermal lipid synthesis, AMP expression, and permeability barrier homeostasis, suggesting that the beneficial effect of low-dose UVB depends, at least in part, on activation of the cutaneous vitamin D system. Our results provide new insights into the mechanisms whereby low-dose UVB comprises effective therapy for AD.

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.

Background and Purpose-Subarachnoid hemorrhage (SAH) may appear on computerized tomography scans after mechanical thrombectomy for acute ischemic stroke. The incidence and prognosis of this observation remain unknown. We investigated the frequency and clinical consequences of SAH after treating acute ischemic stroke with a multimodal approach heavily weighted toward mechanical thrombectomy with Solitaire stent. Methods-Seventy-four consecutive patients with acute ischemic stroke underwent mechanical thrombectomy with a Solitaire stent as a first-line treatment. Nonenhanced computerized tomography scans were performed before, immediately after, and 24 hours after treatment to detect SAH. Clinical outcome was assessed after treatment, on day 1, at discharge, and at 3 months. Clinical and radiological data were compared between patients with and without SAH. Results-Twelve patients (16.2%) exhibited SAH associated with pure SAH (n=4) or mixed SAH and contrast extravasation (n=8). The SAH was located in the ipsilateral Sylvian fissure (n=11) or bilateral parietooccipital sulci (n=1). Patients with SAH had no periprocedural vessel perforations or arterial dissections and no postprocedural neurological deteriorations.Rescue angioplasty was performed more frequently in SAH group than in control group (33.3% vs 9.7%; P=0.05).Patients with SAH and those without had similar recanalization rates and clinical outcomes. Conclusions-SAH on post-therapeutic computerized tomography scans were not uncommon after primary mechanical thrombectomy with a Solitaire stent, but they seemed to be benign. Rescue angioplasty and unidentified, small vessel ruptures due to mechanical stretch during stent retrieval might give rise to these lesions. (Stroke. 2013;44:414-419.)

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One strain of Lactobacillus salivarius, two strains of Lactobacillus reuteri and Lactobacillus amylovorus, and two strains of Bifidobacterium thermacidophilum with antagonistic effect against Clostridium perfringens were isolated from porcine gastrointestinal tract. Isolates were assayed for their ability to survive in synthetic gastric juice at pH 2.5 and were examined for their ability to grow on agar plate containing porcine bile extract. There was a large variation in the survival of the isolates in gastric juice and growth in the medium containing 0.3% (w/v) bile. L. salivarius G11 and L. amylovorus S6 adhered to the HT-29 epithelial cell line. Cell-free supernatant of L. amylovorus S6 showed higher antagonistic activity as effective as the antibiotics such as neomycin, chlortetracycline, and oxytetracycline against bacterial pathogens including C. perfringens, Salmonella typhimurium, Staphylococcus aureus, Vibrio cholerae, Edwardsiella tarda, and Aeromonas salmonicida subsp. salmonicida.