TPA对离体豚鼠心脏收缩性及对氯仿致小鼠心律失常保护作用的研究

目的 :观察TPA的强心作用及抗心律失常作用。方法 :Langendorff灌流离体豚鼠心脏 ,观察药物对心脏收缩力及心率的影响 ;用氯仿致小鼠心律失常 ,观察TPA对心脏的保护作用。结果 :1 0 3mol·L 1TPA二甲亚砜液、1 0 3mol·L 1盐酸TPA液都能非常显著地加强心脏收缩力 ,增幅分别达 1 86± 40 % (P <0 .0 1 ,n =8)、1 64± 3 1 % (P <0 .0 1 ,n =9) ,其强心作用与阳性对照 (7.0 6× 1 0 6 mol·L 1毒毛旋花甙K ,增幅 1 94± 42 % ,n =6)相比无显著性差异彩 ;TPA对心率及心跳节律影响较小。TPA有抗氯仿致小鼠室颤的作用 ,3 0mg·kg 1TPA组室颤发生率 (3 8% ,n =2 1 )与阴性对照发生率 (88% ,n =1 6)相比有非常显著的差异 (P <0 .0 1 )。结论 :TPA有较强增强心肌收缩力作用及抗心律失常作用 ,有进一步研究的价值     

蛋白激酶B在佛波酯诱导人胃癌细胞系凋亡中的作用

目的探讨佛波酯(TPA)诱导胃癌细胞系凋亡过程中蛋白激酶B(PKB)的作用。方法通过BrdU处理,流式细胞术检测以及DAPI染色,荧光显微镜观察分析TPA对胃癌BGC-823细胞的影响;免疫印迹法检测TPA对PKB蛋白表达水平、磷酸化的影响;核浆分离获得核浆蛋白,用于免疫印迹法检测TPA对胃癌细胞内PKB和其Ser 473位点磷酸化的核浆表达影响,以及激光扫描共焦显微镜观察TPA是否改变胃癌细胞内PKB的分布。结果TPA诱导BGC-823细胞凋亡;TPA下调BGC-823细胞内PKB蛋白表达,并且与TPA作用时间和TPA浓度呈正相关,与PP2A降解作用无关;TPA抑制PKB的Ser 473位点磷酸化,而对其Thr 308位点磷酸化没有明显影响;TPA下调细胞核内PKB的表达以及Ser 473位点的磷酸化;TPA并不改变PKB在胃癌细胞内的分布。结论PKB的抑制作用可能参与TPA诱导胃癌细胞凋亡过程;由TPA诱导的胃癌细胞凋亡可能部分是由于细胞核内PKB蛋白表达和Ser 473位点磷酸化下降所致。     

Anti-inflammatory activity of Chrysanthemum indicum extract in acute and chronic cutaneous inflammation

Aim of the study

Although Chrysanthemum indicum Linné (Compositae) has long been used in traditional Korean, Chinese, Japanese medicine to treat various immune-related diseases the underlying mechanism(s) by which these effects are induced remains to be defined in vivo model system. We investigated the effects of 70% ethanolic extract from Chrysanthemum indicum Linné (CIE) on skin inflammation in mice.

Materials and methods

Production of pro-inflammatory cytokines (TNF-α and IL-1β), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema.

Results

CIE inhibited topical edema in the mouse ear, following administration at 200 mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, CIE was effective at reducing inflammatory damage induced by chronic TPA exposure.

Conclusions

These results demonstrate that CIE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the extract may have therapeutic potential in a variety of immune-related cutaneous diseases.     

Local Coagulofibrinolysis in the Postsurgical Recovery of Patients with Chronic Subdural Haematoma

Summary  Postoperative recovery of patients with chronic subdural haematoma (CSH) was investigated by comparing pre- and postoperative coagulant and fibrinolytic activity in the haematoma contents of 15 patients with SCH. Patients in this study were treated draining the haematoma cavity without irrigation, a procedure dubbed the closed drainage. Haematomas were collected during, and 24 hrs after, surgery. Postoperative fibrinolytic activity was lower than that observed pre-operatively. In particular, levels of tissue plasminogen activator activity (TPA), and fibrin and fibrinogen degradation products (FDP) all decreased. In contrast, coagulant activity increased postoperatively.  This paper will discuss the role of local coagulofibrinolysis in the postoperative recovery of CSH patients.     

Precancerous lesions upon sporadic activation of beta-catenin in mice

BACKGROUND & AIMS: Inappropriate activation of beta-catenin in adult tissues is associated with a wide variety of cancers, especially in the digestive tract. Classic transgenic and knockout murine models in which beta-catenin is activated in large fields of cells have provided experimental support in favor of a role for this molecule in tumorigenesis. However, these models do not reproduce the sporadic nature of the majority of human cancers, beginning with the activation of an oncogene at random in a single cell. METHODS: We used the "hit and run" strategy to generate a mouse model in which the expression of an activated form of beta-catenin occurs sporadically in vivo. RESULTS: Sporadic, multifocal lesions were observed in the stomach of 3% of mice aged 8 months and older. These lesions were associated with loss of Sonic hedgehog (Shh), and a causal relationship between beta-catenin activation and Shh inhibition was established in gastric cells in vitro. No lesion was detected in the intestine or in the liver. In addition, one third of female mutant mice developed benign perimammary papillomas. Mutant mice were also hypersensitive to chemically induced premalignant skin lesions. CONCLUSIONS: These results challenge the view that activation of beta-catenin induces malignant cancerogenesis, because they show in mice that sporadically activated beta-catenin is sufficient for tumor initiation, yet without further malignant progression, and that it sensitizes cells to environmental hits. This model represents a powerful tool to investigate the interplay between genetic and environmental factors in tumor progression.     

胸水TPA、CEA、NSE联合检测的临床应用价值

目的　通过检测胸水组织多肽抗原(TPA)、癌胚抗原(CEA)、神经元烯醇化酶(NSE)含量,探讨TPA以及同CEA、NSE联合检测对良恶性胸水的临床诊断价值。方法　应用化学发光免疫分析法检测5 6例良性疾患组患者和72例恶性肿瘤组患者胸水及血清TPA、CEA、NSE含量,并进行比较分析。结果　良性胸水TPA、CEA、NSE含量分别为112 .3±6 5 6. 2u/L ,1. 2 3±0 .90ng/ml,8. 10±8 36ng/ml,而恶性胸水组含量分别为4 .175±2 6 .96 9u/L ,198. 7±2 37. 9ng/ml,2 8 .0 3±30 . 7ng/ml,经统计学分析,良恶性胸水之间三项肿瘤标志物具有极显著性差异(P <0 .0 0 1)。结论　胸水TPA、CEA、NSE检测有利于良恶性胸水的鉴别诊断,胸水三项肿瘤标志物检测比血清具有更重要的意义,三项标志物联合检测可以提高对肺癌诊断的灵敏度和特异性。     

Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in plasma samples

Objectives:

Platelet release of α granule-derived CXC chemokines and dense granule-derived serotonin in plasma samples was evaluated.

Methods:

Concentrations of the CXC chemokines β-TG and PF4 were assayed by an enzyme immunoassay; serotonin was measured by an HPLC method.

Results:

β-TG and PF4 were more easily released than serotonin by in vitro procedures. Use of the anti-platelet cocktail CTAD and preservation of the samples at 4°C were necessary to accurately measure β-TG and PF4, but not serotonin.

Conclusions:

Assaying serotonin may be useful for assessing platelet activation in vivo as a laboratory test because of facile preparation of plasma samples.     

Management of acute myocardial infarction 1990: a perspective

Rising costs have reached a point at which physicians must assume a major role in dealing with the cost of medicine. Little information is available regarding actual practice at the community hospital level. In order to develop some insight on this issue, a survey of cardiovascular specialists was conducted regarding management of acute myocardial infarction in 1990. The results indicate a major lack of correlation between efficacy, cost, and practice patterns in terms of current knowledge. Perhaps legal concerns have contributed to these current practice patterns. Clearly, aside from choice of thrombolytic agent and/or PTCA, early treatment of acute myocardial infarction has emerged as a most important factor in reducing mortality.     

The soft-tissue tumours induced in Syrian hamsters by herpes simplex virus type 1 and a chemical promoter

Adult male Syrian hamsters were inoculated subcutaneously with herpes simplex virus type 1 (HSV-1, 10⁶ PFU) or ultraviolet-inactivated HSV-1. One week later 12-O-tetradecanoylphorbol 13-acetate (TPA, 2×20 nmol weekly) was topically applied to the dorsal skin at the site of virus inoculation for 6 months. Control animals received HSV-1 only or topical treatment with TPA in acetone or acetone alone. Small tumour nodules developed in the HSV-1 group close to the site of virus inoculation 10–15 months after the beginning of the experiment. The neoplasms were classified as angiolipomas, chondromyxomas, a hibernoma, and an unclassified tumor resembling a Kaposi sarcoma in humans. The topical TPA treatment alone induced melanocytic hyperplasia and sebaceous gland hyperplasia. The soft-tissue tumours differed markedly from the structure of the soft-tissue sarcomas induced in Syrian hamsters by viruses of the papova and polyoma groups. Since the spontaneous incidence of benign soft-tissue tumours in our close hamster colony is extremely low, we concluded that mutagenic HSV-1 effects on hamster mesenchymal cell DNA may be involved in the process of formation of the observed benign neoplasms.Abbreviations HSV-1 herpes simplex virus type 1 - TPA 12-O-tetradecanoylphorbol 13-acetate     

Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma

The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer.Abbreviations TATI tumour-associated trypsin inhibitor - TPA tissue polypeptide antigen - TPS tissue polypeptide-specific antigen - CEA carcinoembryonic antigen - CA carbohydrate antigen