LPS-Induced NF-kappaB activation and TNF-alpha release in human monocytes are protein tyrosine kinase dependent and protein kinase C independent

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an important mediator of septic shock. Endotoxin (LPS) signal transduction in human monocytes leads to activation of nuclear factor-kappa B (NF-kappaB) and TNF-alpha release. Previous studies have implicated activation of both protein kinase C (PKC) and protein tyrosine kinases (PTK) in LPS-induced NF-kappaB activation and TNF-alpha production. We hypothesized that inhibition of either PKC or PTK would decrease LPS-induced NF-kappaB DNA binding and TNF-alpha release in human monocytes. MATERIALS AND METHODS: Human monocytes were stimulated with PMA (50 ng/ml) alone or LPS (100 ng/ml) with and without a nonspecific serine/threonine protein kinase inhibitor staurosporine (Stauro), a specific pan-PKC inhibitor bisindolylmaleimide (Bis), or an inhibitor of PTK genistein (Gen). TNF-alpha release in culture supernatants was measured by an ELISA. NF-kappaB DNA binding was evaluated by electrophoretic mobility shift assay. RESULTS: LPS increased NF-kappaB DNA binding and TNF-alpha release in human monocytes. Nonspecific protein kinase inhibition inhibited NF-kappaB activation and TNF-alpha release, while specific PKC inhibition with Bis had no effect on LPS-induced NF-kappaB DNA binding or TNF-alpha release. PTK inhibition with Gen attenuated both LPS-induced NF-kappaB DNA binding and TNF-alpha production in human monocytes. Direct activation of PKC with PMA induced both NF-kappaB activation and TNF-alpha production by human monocytes. CONCLUSIONS: These results suggest that LPS-induced NF-kappaB activation and TNF-alpha release in human monocytes are independent of PKC activity. Furthermore, our results provide evidence that PTK plays a role in LPS-induced NF-kappaB activation and TNF-alpha release in human monocytes and thus could be a potential therapeutic target in inflammatory states.     

Hypozincaemia in febrile convulsion

To understand further the role of trace elements in the pathogenesis of febrile convulsions, serum zinc (Zn), copper (Cu), magnesium (Mg) and CSF Zn, Cu, Mg and protein levels were measured by spectrometry in patients with febrile convulsion (n=19), bacterial meningitis (n=9), viral CNS infection (n=16) and in the control groupn=10) which consisted of children with signs of meningeal irritation due to upper respiratory tract infection but normal CSF findings. Samples were obtained within 6 h after admission to hospital. Mean serum and CSF Zn levels in the febrile convulsion group were significantly lower than in the other groups (for serum Zn: 0.66±0.03 mg/l vs 0.98±0.07 mg/l, 1.06±0.08 mg/l, 1.05±0.09 mg/lP<0.05; for CSF Zn: 22.96±1.62 g/l vs 75.47 ±6.9 g/l, 50.32±5.235 g/l, 39.85 ±2.81 g/lP<0.05). A linear relationship was established between serum Zn and CSF Zn levels (P<0.001). Mean CSF Zn, Cu and protein levels in the bacterial meningitis group were significantly higher than in the other groups (for CSF Cu 63.94±6.33 g/l vs 38.77±2.70 g/l, 35.84±3.48 g/l, 33.86±2.88 g/lP<0.05; for CSF protein 0.80 ± 0.12 g/l vs 0.22±0.02 g/l, 0.53±0.08 g/l, 0.19±0.01 g/lP<0.05). In children with meningitis, the elevation of the mean CSF Zn and Cu levels may result from the breakdown of the blood-brain barrier and subsequent leakage of trace elements and protein from serum to CSF. There was no significant difference between the four groups in terms of mean serum Mg and mean CSF Mg levels.Conclusion Serum and CSF Zn levels are decreased in children with febrile seizures. Zinc deprivation may play a role in the pathogenesis of febrile seizures.     

针灸按摩治疗慢性疲劳综合征研究进展

目的：通过综述近15年来针灸按摩治疗慢性疲劳综合征的文献，为临床治疗该病提供相应的参考资料。方法：共综合了盟篇相关文献的内容，从辨证分型、治疗方法、疗程、疗效4个方面进行了归纳总结。结论：针灸按摩治疗慢性疲劳综合征具有疗效肯定、无副作用、经济安全的特点。     

Hematospermia as the presenting symptom of metastatic malignant melanoma of unknown primary origin

The presence of blood in the ejaculate is alarming to patients and may arise from many sources in the genitourinary tract. Fortunately, hematospermia is rarely due to underlying malignancy and only necessitates further evaluation with continued symptoms. We report a case of persistent hematospermia in a man with human immunodeficiency virus caused by metastatic malignant melanoma to both seminal vesicles. The evaluation included pelvic magnetic resonance imaging and transrectal ultrasound-guided biopsy. Metastases to the brain were subsequently discovered, but a primary source for the melanoma could not be identified. This is the first reported case of isolated involvement of the seminal vesicles with malignant melanoma and underscores the potential for serious disease presenting as hematospermia.     

一种新的细胞凋亡相关基因——高同型半胱氨酸诱导基因HCY-2的功能初探

目的　探讨高同型半胱氨酸 (HCY)血症引起心血管病和出生性缺陷的作用机制。方法　采用诱导筛选方法克隆高同型半胱氨酸诱导基因 HCY- 2 ,以 Northern印迹分析检测 HCY- 2基因在大鼠不同组织中的表达 ,以免疫组化方法验证 HCY- 2蛋白在大鼠不同组织中的表达。结果　以诱导筛选方法从大鼠血管平滑肌细胞内克隆到一个新的全长 c DNA,即高同型半胱氨酸诱导基因 HCY- 2 ,它编码 142个氨基酸。Northern印迹分析和免疫组化检测表明 ,HCY- 2基因可在大鼠心、肾、脑、肝、肺等组织中广泛表达。在体外 ,将重组 HCY- 2基因转移至内皮细胞中 ,能够引起细胞凋亡和 DNA损伤 ;在体内 ,将 HCY- 2基因转移至鸡胚内 ,则诱发鸡胚细胞凋亡 ,并引起畸形。结论　 HCY- 2基因可能是一种新的凋亡基因 ,高同型半胱氨酸血症可能通过 HCY- 2基因诱发心血管病和出生性畸形。     

液相色谱-质谱测定鸦胆子油脂肪乳注射液在癌症患者体内的血药浓度

目的 建立液相色谱-质谱(LC-MS)法测定癌症患者单剂量滴注鸦胆 子油脂肪乳后体内油酸浓度。方法 用自身对照试验设计,7名癌症患者,第3 天不给药,抽取不同时间点空白血浆样品;第5天,单剂量滴注鸦胆子油脂肪乳 注射液100 mL,滴注开始后,抽取不同时间点血浆样品,60 min滴完,用LC- MS法测定血药浓度。结果 线性范围为2．44-156 mg·L-1;日内、日间变异 系数均<14％;7名癌症患者单剂量滴注鸦胆子油脂肪乳注射液100 mL后,主 要药代动力学参数:tmax=(1．08±0．19)h,Cmax(95．20±29．10)mg·L-1, AUC0-7h=(265．67±59．32)mg·h·L-1,t1／2=(12．14±6．42)h。结论 本法 适用临床测定血浆中油酸浓度。     

眼灌注压对人视乳头微循环的影响

目的 了解眼外负压吸引诱导的眼灌注压改变的条件下，正常人、原发性开角性青光眼(POAG)患者和正常眼压性青光眼患者(NTG)的视乳头微循环的变化，探讨视乳头局部自身调节的幅度。方法正常人8例，POAG患者10例和NTG患者7例，采用眼外负压杯吸引诱导眼压升高，负压增加的幅度为30s50mmHg，同时测量眼压。采用HRF测量视乳头处血流量。将基础状态下视乳头血流值作为基础值，当眼压升高到30mmHg和40mmHg时，分别测量这两点视乳头微循环的血流值，在40mmHg后解除负压吸引，测量负压吸引解除后1min、5min时视乳头微循环的血流值。结果 三组视乳头的基础血流量无明显差异。当眼压升高到30mmHg时，正常组的血流量仍维持稳定，但POAG组和NTG组明显下降，POAG组下降幅度超过25％，NTG组下降幅度超过45％。当眼压升高到40mmHg，正常组视乳头血流量也出现明显下降，其中0NHF下降约30％，POAG组和NTG组下降更明显，POAG组下降幅度超过50％，NTG组下降幅度超过65％。在解除负压吸引后1min，正常组血流量增加的幅度约为31％，POAG组增加约19％，NTG组无明显增加。在负压解除后5min，三组视乳头血流基本恢复到基础状态。结论 正常组视乳头微循环有一定范围的自身调节幅度，可以耐受眼灌注压一定程度的改变，POAG组和NTG组自身调节能力均有不同程度的损害。     

胆酸钠对人卵巢癌细胞系作用的研究

目的 探讨胆酸钠单独应用及联合全反式维甲酸对2株卵巢癌细胞系(COC2、CAOV3)的体外抑制作用。方法 2003年5～8月对经不同浓度的胆酸钠及胆酸钠联合全反式维甲酸作用后的两株细胞采用MTT比色法测定细胞生长抑制率，流式细胞仪测定细胞周期变化，并行培养细胞的光镜、电镜观察。结果胆酸钠对两株细胞的抗增殖活性在50～150mg／L范围内呈现剂量依赖效应，并且在两药合用时此作用更明显；单用胆酸钠及两药联合应用均能随用药浓度而明显增加G0／G1期细胞比例，降低S、G2／M期比例，并以两药合用更为明显；光镜、电镜结果显示：胆酸钠100mg／L组与全反式维甲酸10μmol／L组细胞形态变化相似，但两者合用时细胞凋亡明显。结论 在两株卵巢癌细胞中胆酸钠不但具有单独而且有协同全反式维甲酸抑制肿瘤的作用，胆酸钠能明显降低全反式维甲酸的用量从而减少其副反应，并且不降低其抗肿瘤作用。     

The value of pulse wave velocity in the diagnosis of coronary heart disease

Objective: Using receiver operating characteristics (ROC) curve to evaluate the value of pulse wave velocity (PWV) in the diagnosis of coronary heart disease (CHD). Methods: By using coronary angiography as golden diagnostic standard of CHD, 218 patients were divided into both CHD group (n=121) and non-CHD group (n = 97). All these patients received PWV test. The efficacy of PWV of each artery segments in the diagnosis of CHD was evaluated by ROC curve. The sensitivity and specificity were calculated with the golden diagnostic standard of CHD. Results:The PWV of right carotid to femoral artery (Rc-f), left carotid to femoral artery (Lc-f), right radial to carotid artery (Rc-r), left radial to carotid artery (Lc-r) in CHD group were significantly higher than that of non-CHD group (9. 31±1. 75 vs 7.60±1.59, P<0. 01; 9. 02±1.71 vs 7. 52±1.50, P<0. 01; 8. 69±1. 37 vs 8. 00±1. 27, P<0. 01; 8.52±1. 03 vs 8. 03±1. 2, P<0. 01 respectively). However, the PWV of both right and left femoral to ankle artery (Rf-a and Lf-a) had no significant differences between the two groups. We then compared the area under curve (AUC) of each ROC(AUCROC) of PWV of Rc-f, Lc-f Rc-r and Lc-r to evaluate their diagnostic efficacy for CHD. We found that AUCROC of Rc-f PWV was the biggest (AUCROC = 0. 818), at the peak point of its ROC curve, the PWV was 8. 32 m/s. PWV>8. 32 m/s of Rc-f could predict the presence of CHD with a sensitivity of 79% and specificity of 77%. Conclusion: The PWV of Rc-f, Lc-f, Rc-r, Lc-r are significantly higher in CHD group than that in non-CHD group, and PWV of Rc-f is the most accurate in the detection of CHD. The PWV>8. 32 m/s of RC-F is a valuable predictor of CHD.