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1.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
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1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with tmax of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUCbrain, IN) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUCbrain, IV) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.  相似文献   

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To study the use of 1 % isosulfan blue dye in identifying sentinel node, sensitivity and specificity of frozen section and predictive value of sentinel node in predicting other nodal status in the cases of oral cavity and oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion as well as neck dissection as per recommended treatment protocol, were selected from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the induction of general anaesthesia. Neck dissection was performed and first node taking up the blue dye was identified, dissected, removed and was sent for frozen section. In two of the 15 cases a sentinel node was identified (sensitivity of the technique—13 %). Both the sentinel nodes were positive for presence of metastasis on final histopathology (specificity—100 %). However, five cases had nodal metastasis on final histopathological examination of the neck dissection specimen (sensitivity of sentinel lymph node biopsy—40 %). Frozen section examination had a sensitivity and specificity of 100 %. All data was analyzed using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel node is a simple and cheap technique, however, it has low sensitivity as compared to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per op gamma probe localization and using isosulfan dye for sentinel node identification. Sentinel lymph node is representative of nodal status and correlates well with the final histopathological examination of the dissected neck nodes.  相似文献   
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Archives of Pharmacal Research - Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia sappan L. possesses anti-inflammatory effects. We studied the efficacy of...  相似文献   
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