TAILIEUCHUNG - Báo cáo y học: " Pharmacological characterisation of antiinflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Pharmacological characterisation of antiinflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation. | Wan et al. Respiratory Research 2010 11 126 http content 11 1 126 RESPIRATORY RESEARCH RESEARCH Open Access Pharmacological characterisation of antiinflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation 1 1 1 111 Wing-Yan Heidi Wan Abigail Morris Gillian Kinnear William Pearce Joanie Mok Daniel Wyss Christopher S Stevenson1 2 3 Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models however in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in more clinically relevant chronic systems. Methods To do this we started by examining the type of inflammatory cell infiltrate which occurred after acute 3 days or chronic 12 weeks cigarette smoke exposure CSE using female C57BL 6 mice n 7-10 . To compare the effects of anti-inflammatory compounds in these models mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide 1 mg kg-1 . . roflumilast 3 mg kg-1 . . and fluvastatin 2 mg kg-1 . . were dosed 1 h before and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start we confirmed that the inflammatory phenotypes were different after acute 3 days versus chronic 12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic while in the more chronic CSE systems BALF neutrophils PMNs macrophage and lymphocyte .

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