A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Stented esophageal transfixion injury

Esophageal perforation is a rare, but life-threatening condition with a mortality rate ranging between 10% and 40%. It can happen at the level of the cervical, intrathoracic, or intra-abdominal segment. It usually occurs as a result of iatrogenic injury after endoscopic procedures or as a spontaneous rupture. It is seen less frequently in trauma after gunshot or stab wounds. Stenting of the esophagus after iatrogenic perforation is well documented in the literature, but yet it is to be published for management of penetrating injury. We report a case of esophageal perforation with a wooden fence post treated successfully with a covered esophageal stent.     

Endoscopic ultrasound in esophageal carcinoma: comparison with multislice computed tomography and importance in the clinical decision making process

AIM: As resective surgery for oesophageal carcinoma is only appropriate for a selected cohort of patients, preoperative staging plays an important role in the management of these patients. This study assessed the accuracy of endoscopic ultrasound (EUS) staging in comparison with computerised tomography (CT) staging and the impact of EUS in management of patients with oesophageal carcinoma undergoing gastro-esophagectomy. METHODS: Ninety-six consecutive patients with oesophageal carcinoma underwent preoperative staging with multislice CT and EUS. Of these, 50 patients underwent gastro-esophagectomy, allowing preoperative staging data from these imaging modalities to be compared to postoperative histopathological staging, classified according to the TNM system. Management plans for these patients made without use of EUS were then compared to those following EUS staging. RESULTS: The overall accuracy rate of EUS for T staging was 64%, showing good agreement with postoperative histopathological staging of the resected specimen (weighted k=0.42, 95%CI= 0.32-0.52). In terms of clinical decision making, the T stage accuracy rose to 90% when differentiating T1 from T2/3 lesions. In terms of N staging, the overall accuracy was 72% (weighted k=0.44, 95% CI=0.34-0.54). In comparison, N staging by CT was significantly less accurate (62% vs 72%, P<0.01, chi squared) and showed poor agreement with postoperative histopathological nodal staging (weighted k=0.24, 95%CI =0.11-0.37). Importantly, in 56% of patients, staging information obtained from EUS instigated change in management compared to that configured without EUS. CONCLUSION: EUS enhances preoperative staging of oesophageal cancer and is important in preoperative clinical decision making process, especially with increasing use of neoadjuvant chemotherapy.     

Electron microscope and biochemical observations of the surface active phospholipids on the articular surfaces and in the synovial fluid of the temporomandibular joint: a preliminary investigation.

PURPOSE: The goal of this article is to investigate the surface-active phospholipids located on the articular surfaces and in the temporomandibular joint (TMJ) synovial fluid (SF) by means of electron microscopy and biochemical analysis. MATERIALS AND METHODS: Synovial fluids and articular cartilage samples taken from 6 normally functioning TMJs were studied. The osmiophilic lining of human TMJ articular surfaces has been studied by using special nondestructive fixation procedures. To study the SF, negative staining technique has been used. In addition, thin-layer chromatography has been used to identify the phospholipids extracted from synovial fluid of human TMJs. RESULTS: In the SF, granular bodies were identified with diameter of between 170 and 280 nm. Their diameter decreased dramatically when exposed to phospholipase-A(2). The amorphous and highly osmophilic material on the articular surface include membrane-bound vesicles (270 nm in diameter) with lamellated pattern surrounding the amorphous-dense core. Biochemical extraction revealed phosphatidylcholine as the major component of the polar lipids. CONCLUSIONS: This preliminary study presents findings that suggest that phospholipids present in the TMJ may provide an efficient boundary lubrication that enables the disc to slide down the slope of the eminence on joint function.     

d-生物素的立体专一性全合成研究

对confaione的d-生物素(1)全合成进行了改进,从半胱氨酸计算,总收率3.7%。5与4-溴代三苯膦丁酸甲酯进行Wittig-Schlosser缩合反应可立体专一性地转化成反式-烯(6)。以叠氮三甲基硅烷代替叠氮化锂亲核进攻9分子中C3-溴原子,可显著地提高顺式-叠氮内酰胺10的收率。     

锌酞菁脂质体光动力作用引起小鼠肿瘤的细胞程序性死亡

电镜观察了锌酞菁脂质体光动力作用引起小鼠ＭＳ－２纤维肉瘤的形态学变化。发现其作用很强，并对肿瘤细胞有明显的直接影响。肿瘤细胞的结构表现出明显的程序性细胞死亡（ａｐｏｐｔｏｓｉｓ，ｐｒｏｇｒａｍｍｅｄｃｅｌｄｅａｔｈ）的特点：胞核染色质凝聚边集、核固缩、核破裂、染色质凝块流失、胞质内吞噬现象、胞膜表面肿胀粗钝的胞突形成、细胞碎裂等。加深了对锌酞菁脂质体光敏作用机理的认识，但其详细的发生机制和调节途径有待阐明。     

Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance to Streptococcus pneumoniae in chinchillas infected with influenza A virus

Patients infected with influenza A virus (IAV) are at increased risk for bacterial superinfections, and this occurs in association with depressed polymorphonuclear leukocyte (PMNL) function. Recently, we reported that in vitro exposure of human PMNL to granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses IAV-induced cell dysfunction. The present study used an established animal model of IAV infection to examine whether G-CSF and/or GM-CSF can overcome IAV- induced PMNL dysfunction and thereby prevent secondary infections. Preliminary studies determined a dosing schedule of these cytokines that caused significant priming of chinchilla PMNL. In subsequent studies, animals were inoculated intranasally with IAV (day 1) followed 3 days later by Streptococcus pneumoniae, and administered daily intraperitoneal injections with a cytokine or placebo on days 3 through 9. Animals had blood obtained on multiple occasions for PMNL studies, and were followed-up for evidence of pneumococcal disease. Both cytokines caused significant priming of the PMNL chemiluminescence response and this was associated with reversal of the IAV-induced PMNL dysfunction. However, neither cytokine decreased the incidence of pneumococcal disease.