卵巢切除与血清肿瘤坏死因子-α、转化生长因子-β1浓度的关系

目的探讨卵巢摘除与血清肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)浓度的关系. 方法 30只SD大鼠随机分为模型Ⅰ(OVXⅠ)组、模型Ⅱ(OVXⅡ)组和假手术组,OVXⅠ、OVXⅡ组大鼠卵巢切除,术后12和24周运用酶联免疫法检测大鼠血清中TNF-α、TGF-β1浓度的变化. 结果大鼠去卵巢后当雌二醇(E2)水平下降时,血清TNF-α浓度[(53.88±16.35)ng/L]升高,而TGF-β1含量[(6.78±0.75)μg/L]下降,与假手术组比差异有显著性(P＜0.05或P＜0.01);相关性分析显示,E2与TNF-α呈负相关(r=-0.384,P=0.05),而与TGF-β1正相关(r=0.750,P=0.001),两细胞因子之间亦呈负相关(r=-0.465,P=0.05). 结论 E2对TNF-α有抑制作用,但却能促进TGF-β1的分泌,TNF-α含量的增加和TGF-β1水平的降低,均能刺激骨的吸收活动,导致骨质疏松症的发生.     

润肺口服液对慢性支气管炎大鼠支气管TNF-α、ICAM-1蛋白及IL-8表达的影响

目的研究中药复方润肺口服液对慢性支气管炎（CB，CB）支气管肿瘤坏死因子（TNF-α）、细胞间黏附分子-1（ICAM-1）及白介素-8（IL-8）表达的影响，探讨其治疗CB的疗效机制。方法雄性Wistar大鼠随机分为假手术组、慢性支气管炎组、慢性支气管炎氢化可的松治疗组及慢性支气管炎润肺口服液治疗组，每组8只。大鼠慢性支气管炎模型通过熏香烟加气管内注入低剂量脂多糖制成，利用免疫组织化学观察各组大鼠支气管TNF-α、ICAM-1蛋白及IL-8的表达情况。结果熏香烟加气管内低剂量脂多糖注射可复制出较理想的慢性支气管炎模型，假手术组支气管上皮内可见TNF-α、ICAM-1蛋白及IL-8弱阳性表达；慢性支气管炎组支气管TNF-α、ICAM-1蛋白及IL-8在支气管上皮细胞、支气管周围的淋巴滤泡炎性细胞和肺泡间质细胞中可见强阳性表达；半定量图像分析显示，慢性支气管炎组TNF-α、ICAM-1蛋白及IL-8的表达明显强于假手术组（P〈0．05），慢性支气管炎润肺口服液治疗组的表达则明显弱于支气管炎组（P〈0．05）。结论润肺口服液通过下调支气管上皮细胞中TNF-α、ICAM-1蛋白及IL-8的表达，从而减轻气道炎症反应是其治疗慢性支气管炎的机制之一。     

Femoral artery catheterization complications: A study of 503 consecutive patients

This report describes a prospective randomized trial of 503 patients who underwent a cardiac catheterization or interventional procedure at a single institution. In an effort to study femoral complications postprocedure, we evaluated three methods of femoral artery hemostasis as well as 38 variables that were felt to potentially relate to local complications. Only a marginally significant relationship between the hemostasis method and complication rate was found. The factors that contributed to femoral artery complications were: restarting heparin postsheath removal, number of procedures done during one hospitalization, noncompliance of the patient with bedrest after the procedure, number of arterial punctures to initiate the procedure, and preprocedure treatment with corticosteroids.     

Influence of minoxidil on myocardial hemodynamics,regional blood flow,and morphology in beagle dogs

Summary Studies were made of the effects of two doses of minoxidil (3 mg/kg), given 24 hours apart, on cardiovascular hemodynamics, regional myocardial blood flow, and cardiac morphology in beagle dogs. Minoxidil caused increases in mean right atrial and left ventricular end-diastolic pressure. Systemic and pulmonary vascular resistance were reduced; cardiac output was increased. Left ventricular stroke work and the systolic pressure time index were unchanged by monoxidil administration. The diastolic pressure time index and ratio of diastolic/systolic pressure time index were decreased by minoxidil. Regional myocardial blood flow, measured with radioactive microspheres, increased in all regions of the heart except to the left ventricular papillary muscles. Minoxidil increased blood flow to left ventricular subendocardial tissue; however, this increase was significantly less than that observed in corresponding areas of subepicardial tissue, thus reducing the subendocardial/subepicardial tissue blood flow ratio. These results suggest that minoxidil is an effective peripheral vasodilator but may result in inadequate subendocardial perfusion. Morphologic studies disclosed two types of minoxidil-induced cardiac lesions: left ventricular papillary muscle necroses, and hemorrhagic lesions which were most prominent in right atrium and were associated with inflammation, intramural hemorrhage, and fibrinoid necrosis of small arteries. The papillary muscle necroses were attributed to hypoxia. The atrial lesions were not of ischemic or hypoxic origin, because minoxidil did not decrease blood flow to atrial tissue. It is suggested that the atrial lesions are related to excessive vasodilatation.     

Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer

BackgroundRecently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer.MethodsWe retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan–Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed.ResultsIn multivariable analysis preoperative high NLR (≧2.7) and high CA19-9 (≧230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan–Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9.ConclusionPreoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer.     

Recent Insights into the Role of Tumor Necrosis Factor in the Failing Heart

Recent studies have identified the importance of biologically active molecules such as neurohormones in disease progression in heart failure. More recently it has become apparent that in addition to neurohormones, another portfolio of biologically active molecules termed cytokines, are also expressed in the setting of heart failure. This article will review recent clinical and experimental material which suggests that tumor necrosis factor (TNF), a pro-inflammatory cytokine, may contribute to disease progression in heart failure by virtue of the direct toxic effects that this molecule exerts on the heart and circulation.     

Genetic polymorphisms in the tumour necrosis factor locus in childhood acute lymphoblastic leukaemia

Genetic polymorphisms in the tumour necrosis factor (TNF) locus influence the outcome of non-Hodgkin's lymphoma (NHL). We investigated whether these polymorphisms might contribute to the clinical course of childhood acute lymphoblastic leukaemia (ALL). Genomic DNA from 214 childhood ALL patients was analysed. Patients with a high-risk haplotype were older than patients with low-risk haplotype (P = 0.024). No statistically significant associations were found between TNF haplotype and sex, WBC counts, central nervous system involvement, immunophenotype, response to chemotherapy, and event-free survival. These data suggest that genetic polymorphisms in the TNF locus have a limited effect on the outcome of childhood ALL.     

Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition

BACKGROUND AND AIMS: The extent and severity of mucosal injury in inflammatory bowel diseases are determined by the disequilibrium between 2 opposing processes: reparative and cytoprotective mechanisms vs. inflammation-induced injury. Probiotics may provide clinical benefit by ameliorating colitis; however, their mechanisms of action remain largely unknown. Our objective was to investigate microbial-epithelial interactions that could explain the beneficial therapeutic effects of probiotics. METHODS: The effect of VSL#3-conditioned media on the nuclear factor-kappaB pathway in young adult mouse colonic epithelial cells was assessed by using monocyte chemoattractant protein-1 enzyme-linked immunosorbent assays; IkappaBalpha, IkappaBbeta, and p105 immunoblot analysis; and nuclear factor-kappaB luciferase reporter gene and proteasome assays. Effects on heat shock proteins were determined by electrophoretic mobility shift assay and immunoblot for heat shock proteins 25 and 72 in young adult mouse colonic cells. Cytoprotection against oxidant injury was determined by chromium 51 release and filamentous and globular actin assays. RESULTS: VSL#3 produces soluble factors that inhibit the chymotrypsin-like activity of the proteasome in gut epithelial cells. Proteasome inhibition is an early event that begins almost immediately after exposure of the epithelial cells to the probiotic-conditioned media. In addition, these bacteria inhibit the proinflammatory nuclear factor-kappaB pathway through a mechanism different from the type III secretory mechanisms described for other nonpathogenic enteric flora. They also induce the expression of cytoprotective heat shock proteins in intestinal epithelial cells. CONCLUSIONS: The resulting inhibition of nuclear factor-kappaB and increased expression of heat shock proteins may account for the anti-inflammatory and cytoprotective effects reported for probiotics and may be a novel mechanism of microbial-epithelial interaction. These effects seem to be mediated through the common unifying mechanism of proteasome inhibition.     

Does hyaluronan affect inflammatory cytokines in knee osteoarthritis?

Our aim was to investigate the effects of hyaluronan on inflammatory cytokines in the synovial fluid of patients with knee osteoarthritis. The study was single blind, placebo-controlled, and randomized. We administered hyaluronan to 22 patients in the study group and placebo to 19 in the control group. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines. Both HA and placebo caused a significant decrease in interleukin (IL)-6 levels (P=0.0001 and P=0.04, respectively). But it was more significant in the study group. However, IL-8 and tumor necrosis factor alpha (TNF-) levels did not change in either group (P>0.05). The amount of effusion decreased significantly in the study group (P=0.001) but not in the control group (P=0.133). It can be concluded that hyaluronan considerably decreased IL-6 levels, which correlated with clinical improvement, but had no effect on IL-8 and TNF- levels in synovial fluid. However, larger studies with longer follow-up periods are needed to explain the effect of hyaluronan on cytokines.     

Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines

Purpose

Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade^®) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).

Methods

Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.

Results

Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P ≤ 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).

Conclusions

Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.