Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-018-0685-1">https://link.springer.com/article/10.1007/s12325-018-0685-1</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br

Effect of microinjection of CB1 receptor antagonist (AM 251) into the NTS prior to intravenous infusion of WIN 55,212-2.

<p>Microinjection of AM251 blocked the enhancement of the onset latency to the first swallow (A) or the intervals between swallows (B) in the swallowing reflex by WIN 55,212-2 intravenous infusion. Note that the facilitatory effect of WIN 55,212-2 on electrically stimulated swallows was persisted after the microinjection of vehicle in NTS. The photomicrograph of the microinjection site of drugs in the NTS (C). WIN: WIN 55,212-2, CB1 ant.: CB1 receptor antagonist (AM 251).</p

Effect of different doses of cannabinoid receptor agonist on the onset latency to the first swallow and intervals between swallows.

<p>Graphs demonstrating the effect of WIN 55,212-2 on the onset latency to the first (A) and intervals between electrically stimulated swallows (B). Dose-dependent facilitation of the electrically stimulated swallows by WIN 55,212-2 was observed. Data are presented as percentage of pre-infusion data and n = 5 for each group.</p

Co-localization of CB1 receptors + GAD67 and CB1 receptors + glutamate immunoreactivity.

<p>Quantification of the co-localization of CB1 receptor immunoreactivity with GAD67 and glutamate immunoreactivity in the rostrocaudal direction of the NTS (A). CB1 receptor immunoreactivity was observed to be co-localized with significantly more GAD67-ir cells than glutamate-ir cells throughout the rostrocaudal axis. The number of cells in which CB1 receptor immunoreactivity co-localized with both GAD67 and glutamate immunoreactivity was greater in the lateral portion than the medial portion of the NTS (B).</p

Effect of different doses of cannabinoid receptor antagonists on the onset latency to the first swallow and intervals between swallows.

<p>Graphs demonstrating the effect of combination of WIN 55,212-2 and cannabinoid (CB1 or CB2) receptor antagonists, and different doses of cannabinoid receptor antagonists on the onset latency to the first (A) and intervals between (B) electrically stimulated swallows. Pretreatment with a CB1 receptor antagonist blocked the effect of WIN 55,212-2, whereas pretreatment with a CB2 receptor antagonist did not. The CB1 antagonist alone and the vehicle had no significant effect on the swallowing reflex. Data are presented as percentage of pre-infusion data and n = 5 for each group. CB1 ant: CB1 receptor antagonist (AM 251), CB2 ant.: CB2 receptor antagonist (AM 630).</p

Schematic illustration of the present experimental protocol.

<p>The experimental procedure to investigate relationships between the intensity of electrical stimulation and the swallowing reflex (A). The time-course of recording points for the swallowing reflexes before and after intravenous infusion (B and C) of drugs or vehicle and microinjection of drugs into the NTS (D). R: recording 3swallows evoked by the SLN stimulation, WIN: WIN 55,212-2, CB1 ant: AM 251, CB2 ant.: AM 630, i.v.: intravenous infusion.</p

Example of facilitation of the electrically-stimulated swallowing reflex by the cannabinoid agonist, WIN 55,212-2.

<p>The onset latency to the first swallow (A) and intervals between swallows (B) induced by different intensities of electrical stimulation of the SLN of naïve rats (n = 5). The ellipses indicate the characteristics of the swallowing reflex by the electrical stimulation at 4–5 µA. The typical example that the swallowing reflex by the SLN stimulation before (C), and two hours after (D), infusion of WIN 55,212-2. Note that WIN 55,212-2 decreases the onset latency to the first swallow and the intervals between swallows.</p

Photomicrographs of immunoreactivity for CB1, GAD67 and glutamate in the NTS.

<p>The illustrations show the intermediate area (the mosaic and beige colored part) divided into four rostrocaudal levels in the NTS (A and B). Photomicrographs of immunoreactivity for CB1 receptors (Ca and Da), GAD67 (Cb), glutamate (Db), CB1 receptors + GAD67 (Cc) and CB1 receptors + glutamate (Dc) in the NTS. The left and right area surrounded by the broken line in Ca, Cb, Cc and Da, Db, Dc indicates the lateral and medial portion of the NTS, respectively. The small square boxes in Cc and Dc shows the area of the high magnified images that in Cc1 and Dc1. High magnified images demonstrating co-localization of CB1 receptors + GAD67 and CB1 receptors + glutamate are shown in Cc1 and Dc1, respectively. ap: area postrema, ts: tractus solitaries, cc: central canal.</p

Ruthenium Complexes Containing Bis(diarylamido)/Thioether Ligands: Synthesis and Their Catalysis for the Hydrogenation of Benzonitrile

Treatment of the thioethers (RNH-o-C6H4)2S (H2[R2NSN]; R = Xy, Xyf; Xy = 3,5-Me2C6H3, Xyf = 3,5-(CF3)2C6H3) with 2 equiv of n-BuLi followed by addition of 0.5 equiv of [(η6-C6H6)RuCl2]2 in THF gave the bis(diarylamido)/thioether complexes [(η6-C6H6)Ru[R2NSN]] (R = Xy (1a), R = Xyf (1b)) in moderate yields. In the presence of 1a (1 mol %) and PCy3 (2 mol %; Cy = cyclohexyl), benzonitrile was catalytically hydrogenated to give benzylamine (72%) and benzylidenebenzylamine (27%) at 80 °C and 30 atm, while the hydrogenation with 1b as a catalyst precursor resulted in the formation of benzylamine (37%) and benzylidenebenzylamine (51%) under the same reaction conditions. The yield of benzylamine was improved up to 92% by using a catalyst mixture of 1a (1 mol %)/PCy3 (2 mol %)/t-BuONa (10 mol %). On the other hand, the reaction of 1a with excess PMe3 afforded the tris(trimethylphosphine) derivative [(PMe3)3Ru[Xy2NSN]] (2). Treatment of 2 with excess PhCN, MeCN, or N2H4·H2O resulted in the replacement of a PMe3 ligand by these substrates to give [(PMe3)2LRu[Xy2NSN]] (3, L = PhCN; 4, L = MeCN; 5, L = N2H4), while the reaction of 2 with benzoylhydrazine gave the κ2-benzoylhydrazido complex [(PMe3)2Ru(κ2-(O,N)-PhC(O)NNH2)(H[Xy2NSN])] (6). Structures of 1a, 1b, 2, 5, and 6 have been determined by X-ray crystallography

Ruthenium Complexes Containing Bis(diarylamido)/Thioether Ligands: Synthesis and Their Catalysis for the Hydrogenation of Benzonitrile

Treatment of the thioethers (RNH-o-C6H4)2S (H2[R2NSN]; R = Xy, Xyf; Xy = 3,5-Me2C6H3, Xyf = 3,5-(CF3)2C6H3) with 2 equiv of n-BuLi followed by addition of 0.5 equiv of [(η6-C6H6)RuCl2]2 in THF gave the bis(diarylamido)/thioether complexes [(η6-C6H6)Ru[R2NSN]] (R = Xy (1a), R = Xyf (1b)) in moderate yields. In the presence of 1a (1 mol %) and PCy3 (2 mol %; Cy = cyclohexyl), benzonitrile was catalytically hydrogenated to give benzylamine (72%) and benzylidenebenzylamine (27%) at 80 °C and 30 atm, while the hydrogenation with 1b as a catalyst precursor resulted in the formation of benzylamine (37%) and benzylidenebenzylamine (51%) under the same reaction conditions. The yield of benzylamine was improved up to 92% by using a catalyst mixture of 1a (1 mol %)/PCy3 (2 mol %)/t-BuONa (10 mol %). On the other hand, the reaction of 1a with excess PMe3 afforded the tris(trimethylphosphine) derivative [(PMe3)3Ru[Xy2NSN]] (2). Treatment of 2 with excess PhCN, MeCN, or N2H4·H2O resulted in the replacement of a PMe3 ligand by these substrates to give [(PMe3)2LRu[Xy2NSN]] (3, L = PhCN; 4, L = MeCN; 5, L = N2H4), while the reaction of 2 with benzoylhydrazine gave the κ2-benzoylhydrazido complex [(PMe3)2Ru(κ2-(O,N)-PhC(O)NNH2)(H[Xy2NSN])] (6). Structures of 1a, 1b, 2, 5, and 6 have been determined by X-ray crystallography