ABSTRACT
Allergic rhinitis (AR) is a common, non-infectious, chronic nasal mucosal disease primarily mediated by immunoglobulin E (IgE) following allergen exposure. Currently, studies on AR mainly focus on cytokines, IgE and its receptors, basophils, eosinophils, mast cells, and related genes. Among these, an imbalance between T helper (Th) 1 and Th2 cells is considered an important mechanism underlying AR pathogenesis. The most important cytokines in AR are interleukin (Il)-4 and interferon gamma (IFN-γ) which are secreted by Th2 and Th1 cells, respectively. Il-4 and IFN-γ are antagonistic to each other in regulating IgE synthesis. In this study, the expression of extracellular signal-regulated protein kinase (ERK) 1/2 and its phosphorylation from p-ERK1/2, were significantly increased in a cluster of differentiation of 4+ T cells of AR mice, suggesting that the ERK signaling pathway in these cells is involved in the occurrence and development of AR. This result also implies an enhanced expression of deoxyribonucleic acid methyltransferases (DNMTs). To verify the relationship between ERK signaling and DNMT expression, AR mice were treated with PD98059, a specific inhibitor of the ERK1/2 signaling pathway. The results revealed that perturbations in ERK signaling were significantly positively correlated with the downregulation of DNMT1 expression. Pharmacological intervention is key to treating AR. This study demonstrated that Xingbi gel intervention affected both serum IgE levels and AR behavior scores in mice. Based on its effects on IFN-γ gene expression, the regulation of Th1/Th2 balance, and the ERK signaling pathway, research on the effects of Xingbi gel on AR may provide new avenues in its prevention and treatment.
ABSTRACT
BACKGROUND: Pulmonary edema is an important cause of complications and death in severe drowning. Continuous veno-venous hemofiltration (CVVH) may reduce pulmonary edema and thus may be a treatment modality for severe sea water drowning resuscitation. METHOS: 20 dogs were anesthetized and tracheally intubated. 10 ml/kg of sea water was infused into trachea in a minute. All animals developed signs of respiratory distress and severe hypoxia (PaO2 < 40 mmHg) within 15 minutes after infusion. They were then mechanical ventilated and randomized to receive either CVVH (n = 10) or no additional treatment (control, n = 10) and followed over 4 hours. Arterial gas, hemodynamic parameters, and the levels of circulating inflammatory cytokines including interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor α (TNFα) were determined. Additionally, blood endothelin and the levels of oxidative stress in lung were measured at sacrifice. RESULTS: 5 animals in the control group (50%) died within 4 hours after sea water aspiration, while 10 animals received CVVH all survived (p < 0.05). Importantly, CVVH significantly improved blood gas exchange as evidenced by higher PaO2, normal oxygen saturation, and no carbon dioxide retention after 3 hour of CVVH, while also correcting against acidosis. Levels of circulating IL-6, IL-8, and TNFα were elevated in control but not in CVVH group (p < 0.01). CVVH also reduced plasma endothelin and alleviated oxidative stress. Histology examination further revealed reductions in pulmonary alveolar injury, blood congestion, and inflammation by CVVH. DISCUSSION AND CONCLUSIONS: CVVH decreased mortality and pulmonary injury and largely maintained hemodynamic and acid-base balance in animals with severe sea water drowning and thus, may be added as a new measure to aid in resuscitation from severe sea water drowning. TRIAL REGISTRATION: Animal protocol number: FZG0001859 http://www.fzzyy.com.
