New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

The 97(th) American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD) with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo(®)) to the development of AstraZeneca's novel dual dopamine D(2)-receptor/β(2)-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion) also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH(2)-terminal kinase and syk kinase) were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases

The heterotopic tracheal allograft as an animal model of obliterative bronchiolitis

Heterotopic tracheal allografts in small rodents have been shown to share many characteristics with the development of obliterative bronchiolitis (OB) in the clinic and therefore provide a suitable animal model for the study of OB. The model facilitates the examination of the pathogenesis of the disease and the elucidation of the cellular and molecular mechanisms involved in its development. The model provides a less technically demanding alternative to whole lung transplantation in small rodents and should lead to a speedier identification of new treatments that might prevent the development of post-transplantation OB in the clinic

Generic critical points of normal matrix ensembles

The evolution of the degenerate complex curve associated with the ensemble at a generic critical point is related to the finite time singularities of Laplacian Growth. It is shown that the scaling behavior at a critical point of singular geometry $x^3 \sim y^2$ is described by the first Painlev\'e transcendent. The regularization of the curve resulting from discretization is discussed.Comment: Based on a talk given at the conference on Random Matrices, Random Processes and Integrable Systems, CRM Montreal, June 200

Recommended reading list of early publications on atomic layer deposition-Outcome of the "Virtual Project on the History of ALD"

Atomic layer deposition (ALD), a gas-phase thin film deposition technique based on repeated, self-terminating gas-solid reactions, has become the method of choice in semiconductor manufacturing and many other technological areas for depositing thin conformal inorganic material layers for various applications. ALD has been discovered and developed independently, at least twice, under different names: atomic layer epitaxy (ALE) and molecular layering. ALE, dating back to 1974 in Finland, has been commonly known as the origin of ALD, while work done since the 1960s in the Soviet Union under the name "molecular layering" (and sometimes other names) has remained much less known. The virtual project on the history of ALD (VPHA) is a volunteer-based effort with open participation, set up to make the early days of ALD more transparent. In VPHA, started in July 2013, the target is to list, read and comment on all early ALD academic and patent literature up to 1986. VPHA has resulted in two essays and several presentations at international conferences. This paper, based on a poster presentation at the 16th International Conference on Atomic Layer Deposition in Dublin, Ireland, 2016, presents a recommended reading list of early ALD publications, created collectively by the VPHA participants through voting. The list contains 22 publications from Finland, Japan, Soviet Union, United Kingdom, and United States. Up to now, a balanced overview regarding the early history of ALD has been missing; the current list is an attempt to remedy this deficiency. (C) 2016 Author(s).Peer reviewe

TRPA1 Agonists Evoke Coughing in Guinea Pig and Human Volunteers

Rationale: Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and one meta-analysis concluded that over-the-counter remedies are ineffective. There is also increasing concern about their use in children. Environmental irritants such as air pollution and cigarette smoke are thought to evoke cough by stimulating airway sensory nerves; however, how this occurs is not fully understood

Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD

1. Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses. 2. In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat. In order to characterize the receptor involved rat vagus preparations were utilized. Quinagolide (D(2/3) agonist), ropinirole (D(2/3/4) agonist), SKF 38393 (D(1/5) agonist), AR-C68397AA (Viozan™) (dual D(2)/B(2) agonist) and dopamine inhibited hypertonic saline induced depolarization by approximately 50%. Data suggests that AR-C68397AA and quinagolide also inhibited depolarization of the human vagus. 3. The quinagolide response was blocked by sulpiride (D(2/3) antagonist) but not SCH 23390 (D(1/5) antagonist); ropinirole was partially blocked by sulpiride, totally blocked by spiperone (at a concentration that blocks all dopamine receptors) but not by SCH 23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH 23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH 23390 but not by sulpiride or spiperone whereas dopamine was blocked by spiperone. The effect of dopamine was not stimulus-specific as it inhibited capsaicin-induced depolarization of the rat vagus in a spiperone sensitive manner. 4. In conclusion, dopamine receptor ligands inhibit depolarization of the rat and human vagus. These data suggest that dopamine receptor agonists may be of therapeutic benefit in the treatment of symptoms such as cough and mucus secretion which are evident in respiratory diseases such as asthma and chronic obstructive pulmonary disease