Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients.

NVA237 is a novel once-daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and bronchodilator efficacy of two doses of NVA237 (100 and 200 microg), versus placebo, in patients with moderate-to-severe COPD (forced expiratory volume in 1s [FEV(1)]>or=30% and <80% predicted and FEV(1)/forced vital capacity [FVC]<0.7, 30 min after inhalation of 80 microg ipratropium bromide). After appropriate washout periods, patients were randomized to treatment with NVA237 100 microg (n=92), NVA237 200 microg (n=98) or placebo (n=91) for 28 days. The primary objective was evaluation of safety, with efficacy measures included as secondary objectives. NVA237 was generally well tolerated and associated with a frequency and distribution of adverse events similar to placebo. Serious adverse events were uncommon and there was no evidence of adverse cardiovascular effects or unexpected events. Trough FEV(1) was significantly higher in those receiving NVA237 compared with placebo. For NVA237 100 microg the differences were 131 and 161 mL on Days 1 and 28, respectively (p<0.05), and for NVA237 200 microg the differences were 146 and 151 mL on Days 1 and 28, respectively (p<0.05). Peak FEV(1), FEV(1) at all timepoints up to 24h after dosing, and FEV(1) area under the curve during 5 min-5 h post-dosing were also significantly higher in both NVA237 groups, compared with placebo. Patients receiving NVA237 required fewer daily puffs of rescue medication and had a higher percentage of days on which rescue medication was not required. Overall, the present study provides further evidence of the safety, tolerability and bronchodilator efficacy of once-daily treatment with NVA237 100 and 200 microg in patients with moderate-to-severe COPD.

The treatment of facial atopic dermatitis in children who are intolerant of, or dependent on, topical corticosteroids: a randomized, controlled clinical trial.

BACKGROUND: Atopic dermatitis (AD) is most prevalent in areas of reduced skin barrier reserve, like face and neck, especially in children. Treatment with topical corticosteroids (TCS) is limited due to heightened risk of treatment-associated side-effects, thus necessitating alternative AD therapies. OBJECTIVES: The primary study objective was to determine the efficacy of pimecrolimus cream 1% in children with mild-moderate facial AD dependent on/intolerant of TCS. Secondary objectives included effects on overall Eczema Area and Severity Index (EASI), head/neck EASI, pruritus severity and time to clearance of facial AD. METHODS: A multicentre, double-blind (DB) study of < or = 6 weeks, followed by a 6-week, open-label (OL) phase was conducted. Two hundred patients (aged 2-11 years) were randomized 1:1 to pimecrolimus cream 1% (n = 99) or vehicle (n = 101) twice daily until clearance of facial AD or for a maximum of 6 weeks (DB phase). Sixteen patients receiving vehicle were allowed to switch to the OL phase at day 22. RESULTS: Significantly more pimecrolimus-treated vs. vehicle-treated patients were cleared/almost cleared of facial AD (Investigators' Global Assessment 0/1): 74.5% vs. 51.0%, P < 0.001 (day 43) [57.1% vs. 36.0%, P = 0.004 (day 22)]. Median time to clearance was 22.0 vs. 43.0 days (pimecrolimus vs. vehicle, respectively). Statistically significant differences for pimecrolimus vs. vehicle were also seen on head/neck EASI, overall EASI, and head/neck pruritus scores. Adverse events were mainly mild-moderate, occurring with similar frequency in both treatment groups. CONCLUSIONS: In children with facial dermatitis intolerant of/dependent on TCS, pimecrolimus cream 1% effectively controls eczema and pruritus and is well tolerated.

Distinction between some saccharides in scattered optical sum frequency intensity images.

Using an optical sum frequency (SF) microscope with visible and infrared light pulses for excitation, we have attempted to distinguish among four saccharide species. The saccharides we studied were d-glucose, amylopectin, beta-cyclodextrin, and amylose. The wavelength of the infrared light was resonant to CH vibration. Amylose showed very weak sum frequency scattering for CH vibration among the four saccharides. As for the other three saccharides, we found a big difference in the sum frequency spectra of their CH stretching vibration near 2900 cm-1, when the incident visible and infrared light pulses were p- and s-polarized, respectively. Based on these facts, we have demonstrated a distinction between these three saccharides in the scattered SF intensity images.

Raman scattering study of water clusters around polyrotaxane and pseudopolyrotaxane supramolecular assemblies.

We have measured Raman spectra of collective O-H stretching vibration of water clusters in polyrotaxane and pseudopolyrotaxane aqueous solutions and the aqueous solutions of their constituent molecules. The intensities of the collective bands of water clusters in the polyrotaxane and pseudopolyrotaxane solutions were approximately equal to that of their solvents. On the other hand, those in the solutions of linear polymeric chains and cyclic molecules were smaller. These results indicate that the water molecules in the solvents cannot approach to interact with the hydrophobic parts of the constituent molecules sterically when the constituent molecules form the inclusion complexes. Thus, the polyrotaxane and pseudopolyrotaxane molecules are observed as inert in terms of molecular interaction with water, although the constituent molecules have hydrophobic parts in their structure.

Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinoma of rat submandibular gland.

Fibroblast growth factor-2 (FGF-2) is a member of the heparin-binding growth factor family and has mitogenic activity. Immunohistochemical expression of FGF-2 and its receptor (FGFR) was evaluated in experimentally induced squamous cell carcinoma as well as transforming cells of rat submandibular gland (SMG) induced by 9,10-dimethyl-1,2-benzanthracene (DMBA)/sponge implantation. Proliferating cells detected by proliferating cell nuclear antigen (PCNA) staining during carcinogenesis were also compared with FGF-2 and FGFR stainings. In the normal SMG, FGF-2 and FGFR were present in the excretory, striated and intercalated duct cells. Pillar and transition cells of granular convoluted tubule (GCT) showed FGF-2 staining, PCNA-labeled cells in normal SMG were rarely observed. In 2-3 weeks after carcinogen implantation, the reactions of FGF-2 and FGFR were expressed in epithelial islands, duct-like structures and affected ductal segments. PCNA-positive cells were developed in these epithelial structures. In 4-8 weeks after carcinogen implantation squamous epithelium appeared surrounding DMBA/sponge and gradually transforming with high PCNA labeling in the based cells and strong staining of FGF-2 and FGFR. Squamous cell carcinoma arose within about 12 weeks of the experiment. In squamous cell carcinoma, there was an intense immunohistochemical expression of FGF-2 and FGFR. Basal and parabasal layers of the squamous cell carcinoma showed high PCNA labeling. FGF-2-positive cells were found in the connective tissue stroma and in inflammatory cells around the proliferating duct-like structure. Coexpression of FGF-2 and FGFR was indicated in transforming cells during carcinogenic processes and in experimental squamous cell carcinoma of rat SMG. These findings suggested that FGF may play an important role for squamous metaplasia and carcinogenesis in rat SMG as an autocrine factor and FGF-positive stromal cells may also act to stimulate epithelial proliferation.