Suppression of nuclear factor-kappa B and mitogen-activated protein kinase signalling pathways by goshonoside-F5 extracted from Rubi Fructus.

Rubi Fructus, a traditional Chinese medicine, was considered as an anti-inflammatory agent in folk medicine. In the present study, we investigated the signalling pathways involved in the anti-inflammatory effects of goshonoside-F5 (GF5), isolated from Rubi Fructus, in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. GF5 decreased NO and PGE2 production in LPS-stimulated macrophages (IC50=3.84 and 3.16µM). This effect involved the suppression of NOS-2 and COX-2 gene expression at the transcriptional level. Examination of the effects of GF5 on NF-κB signalling demonstrated that it inhibits the phosphorylation of IκB-α and IκB-ß, blocking their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signalling was also observed, and phosphorylation of p38 and JNK was suppressed in the presence of GF5. Inflammatory cytokines, including IL-6 and TNF-α, were down-regulated by this compound after activation with LPS (IC50=17.04 and 4.09µM). Additionally, GF5 (30 and 90mg/kg, i.p.) significantly reduced the circulating cytokine levels (IL-6 and TNF-α) and increased survival in a mouse model of endotoxemia. These results show that GF5 significantly inhibits the pro-inflammatory response induced by LPS, both in vitro and in vivo. Our results provide a strong pharmacological basis for further understanding the potential therapeutic role of GF5 in inflammatory disease and shed new light on the bioactivity of ent-labdane diterpene glucoside.

[Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result].

OBJECTIVES: To analyze the long-term results of fibrin glue embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), and to assess the feasibility and durability of this technique. METHODS: From August 2002 to June 2010, among the 953 EVAR patients, 51 (5.4%) patients underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. A retrospective study was conducted, and characteristics of the patients, intra-sac pressure, hospital course, and long-term outcomes were recorded. RESULTS: Among the 51 patients, 19 (37.3%) patients had proximal necks long < 10 mm, and 6 (11.8%) patients had proximal neck angulation > 60°; 22 patients (3 additional iliac extension, 14 cuffs, and/or 8 stents) had been placed with additional devices. After fibrin glue injection, 50 (98.0%) of the 51 endoleaks were successfully resolved, and intra-sac pressure (including systolic, diastolic, mean pressures, pulse pressure, and the mean pressure indexes) decreased significantly in these cases. The patient who failed embolotherapy was converted to open surgery (2.0%); he died 2 months later from multiorgan failure. And other two (4.8%) patients died in the peri-operative period from myocardial infarction. The median of follow-up of 48 patients was 45 months (range 4 - 106 months). The mean maximal aneurysm diameter fell from the baseline (61.5 ± 15.2) mm to (48.8 ± 10.1) mm (P = 0.000). Three (6.2%) patients died in the follow-up duration (1 aneurysm-related, died of renal failure which was caused by the compromised renal artery). Cumulative survival was 97.9% at 1 year, 94.5% at 3 years, and 90.8% at 4 years. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSIONS: Fibrin glue embolization to eliminate type I endoleak after EVAR has yielded promising results in this study, and it can effectively and durable resolve the type I endoleaks. Balloon occlusion of the inflow of the endoleak must be done during glue injection, to enhance the safety and facilitate formation of a structured fibrin clot.

Takayasu's arteritis: clinical features and outcomes of 125 patients in China.

Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. The clinical features of TA vary in different ethnic populations. The objective of this study is to characterize the clinical features, angiographic findings, and response to treatment of patients with TA in Changhai Hospital, Shanghai, China. The hospital records of 125 patients diagnosed with TA were retrospectively evaluated. Eighty patients were followed for a median duration of 36 months. Females (86.4%) were most frequently affected. The mean age at onset was 26.9 years. Constitutional symptoms were present in only 38.4% of patients. The most common clinical finding was pulse deficit. Histological findings from 12 clinically inactive patients showed active lesions in 58.3%. Angiographic classification showed that type I was the most common, followed by type V and IV. Type I was more common in adult patients than in pediatric patients. Although immunosuppressive treatment induced remission in most patients, over 90% of those who achieved later remission relapsed. Both bypass procedures and angioplasty showed high rates of initial success, but restenosis occurred in 34.7% of bypass procedures and 77.3% of angioplasty procedures. Eight patients died during the follow-up period with the main cause of death being congestive heart failure. Constitutional symptoms were not frequent in our study. Correlation between the clinical assessment of disease activity and histologic findings is often poor in TA. Angiographic findings showed that type I was the most common in our study. Over the longer term, the outcomes of revascularization were superior to angioplasty.

[Effect of the size of abdominal aortic aneurysm on endovascular exclusion and its results].

OBJECTIVE: To evaluate the effect of the diameter of abdominal aortic aneurysm (AAA) on endovascular exclusion (EVE) and its results. METHODS: From March 1997 to June 2007, 429 AAA patients were treated with endovascular stent-graft exclusion. According to the maximal diameter of abdominal aortic aneurysm, the patients were divided into two groups: group A (diameter < 55 mm, n = 274) and group B (diameter > or = 55 mm, n = 155). The diameter of AAA, involvement of iliac artery, length, diameter and distortion of aneurismal neck in the two groups were recorded and compared retrospectively. RESULTS: Patients in group B were significantly older than group A (73.7 vs 71.1 years, P < 0.05). More patients in group B was complicated with coronary artery disease than those in group A (P < 0.05). The mean diameter of AAA in group A was (46.6 +/- 6.8) mm, and (66.8 +/- 11.2) mm in group B (P < 0.05). Proximal aneurysmal necks were shorter, wider and more tortuous in group B than those in group A (P < 0.05). Extraperitoneal approach, embolism of inner iliac artery and reconstruction of another inner iliac artery and stretch technique were more applied in group B. There were more endoleak during operation in group B and more stent-grafts were used. There was significant difference in morbidity rate between the two groups, while no statistic difference in mortality. And in group B, there were a high rate of endoleak and secondary intervention post operation. CONCLUSIONS: The diameter of AAA affects EVE and its results. In small aneurysms, EVE carries better outcome than in big aneurysms.

Simultaneous multi-tear exclusion: an optimal strategy for type B thoracic aortic dissection initially proved by a single center's 8 years experience.

BACKGROUND: Endovascular stent-grafting is widely used to treat thoracic aortic dissection. However, little information is available regarding outcome following simultaneous exclusion of multiple tears. This report details eight years of experience using simultaneous multi-tear exclusion for treatment of Stanford type B thoracic aortic dissection resulting in successful aortic remodeling without adverse events. METHODS: From September 1998 to January 2006, 29 type B thoracic aortic dissection patients (24 men, 5 women; 27 chronic, 2 acute; mean age 58 years, range 45 - 77 years) were treated by simultaneous multi-tear exclusion in our center. Magnetic resonance angiography was used as the preoperative evaluation method. Different kinds of stent-grafts were used. The patients were followed up with contrast-enhanced spiral computed tomography at 6 months postoperatively and yearly thereafter. RESULTS: Twenty-nine surgeries were completed successfully using at least 2 stent-grafts per patient (range: 2 - 6, mean: 2.7). No major procedure-related complications, such as rupture, paraplegia, aortic branch ischemia or cerebral infarction, were observed. During follow-up, favorable remodeling of the aorta was observed. CONCLUSIONS: The mid-term result of thoracic aortic dissection with simultaneous multi-tear exclusion was satisfactory. With the improvement of stent-grafts, simultaneous multi-tear exclusion should find wider application and become an optimal strategy for thoracic aortic dissection.

[Endovascular exclusion of juxtarenal abdominal aortic aneurysm with one-piece customized fenestrated endovascular stent-graft].

OBJECTIVE: To evaluate the technical feasibility of juxtarenal abdominal aortic aneurysm (AAA) repair with fenestrated endovascular stent-graft METHODS: A 64-year-old male was diagnosed with juxtarenal AAA with severe coronary artery stenosis, fenestrations was customized according to precise helical CT data to accommodate visceral and renal arteries. Under general anesthesia and dynamic supervision of digital subtraction angiography (DSA), juxtarenal AAA was excluded with the customized fenestrated stent-graft and balloon expandable mini stent-grafts were deployed into bilateral renal arteries respectively. RESULTS: After operation, DSA showed the patency of the super mesenteric artery, bilateral renal arteries and left hypogastric artery, no endoleak was found. The serum creatinine decreased slightly after operation. CT angiography revealed favorable morphology of the stent-graft without tortuosity, migration, disjoint and endoleak 10 days after the operation and patency of super mesenteric artery, bilateral renal arteries and left hypogastric artery. CONCLUSIONS: The placement of customized fenestrated endovascular stent-graft is a feasible option for juxtarenal AAA.