脑缺血再灌注损伤的炎症反应机理研究进展

脑缺血再灌注损伤过程包含一系列复杂的病理生理变化,各因素之间又相互影响.本文就近年来备受关注的炎症反应机理做一综述.     

Platelet proteins as autoantibody targets in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP), caused by autoantibodies directed against certain platelet antigens, is the most common entity of the immune thrombocytopenias. ITP is an acquired disorder and can affect both children and adults. However, the clinical syndromes of ITP are distinct between children and adults. Childhood (acute) ITP characteristically is acute in onset, occurs within 1-2 weeks of an infection, usually of viral origin, resolves spontaneously within 6 months. Adult (chronic) ITP has an insidious onset and rarely resolves spontaneously. Over the last decade considerable new information has accumulated as to the pathophysiological mechanisms of immune thrombocytopenias. In addition, most of the knowledge on this disorder has been obtained from studies of adult patients with chronic ITP. The present work gives an updated overview of the platelet autoantigens and the molecular immunological reactions in ITP.     

Axonopathy, tau abnormalities, and dyskinesia, but no neurofibrillary tangles in p25-transgenic mice

Neurofibrillary tangles, one of the pathologic hallmarks of Alzheimer's disease (AD), are composed of abnormally polymerized tau protein. The hyperphosphorylation of tau alters its normal cellular function and is thought to promote the formation of neurofibrillary tangles. Growing evidence suggests that cyclin-dependent kinase 5 (cdk5) plays a role in tau phosphorylation, but the function of the enzyme in tangle formation remains uncertain. In AD, cdk5 is constitutively activated by p25, a highly stable, 25kD protein thought to be increased in the AD brain. To test the hypothesis that p25/cdk5 interactions promote neurofibrillary pathology, we created transgenic mouse lines that overexpress the human p25 protein specifically in neurons. Mice with high transgenic p25 expression have augmented cdk5 activity and develop severe hindlimb semiparalysis and mild forelimb dyskinesia beginning at approximately 3 months of age. Immunohistochemical and ultrastructural analyses showed widespread axonal degeneration with focal accumulation of tau in various regions of the brain and, to a lesser extent, the spinal cord. However, there was no evidence of neurofibrillary tangles in neuronal somata or axons, nor were paired helical filaments evident ultrastructurally. These studies confirm that p25 overexpression can lead to tau abnormalities and axonal degeneration in vivo but do not support the hypothesis that p25-related induction of cdk5 is a primary event in the genesis of neurofibrillary tangles.     

Necrotizing Enterocolitis: A Review of Pathogenetic Mechanisms and Implications for Prevention

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature neonates that accounts for 3000 to 4000 deaths each year in the United States. The pathogenesis is not well understood, however theories suggest that prematurity, enteral feeding, bacterial colonization, and intestinal ischemia contribute to the intestinal injury. Furthermore, recent studies have shown that platelet activating factor and perhaps other inflammatory mediators mediate bowel necrosis in animals and possibly in humans. Although no specific intervention for NEC treatment exists, preventive therapy using either enteral IgA supplementation, breast milk feeding, antibiotic prophylaxis, or exogenous steroid administration have reduced the incidence of this overwhelming disease in small randomized trials. These modalities and perhaps PAF antagonists or other inflammatory mediator inhibitors may reduce the incidence or severity of NEC in the next several years.     

The effects of platelet apheresis in total hip replacement surgery on platelet activation

BACKGROUND: Autologous platelet rich plasma (PRP) harvest with autotransfusion devices has been used for 10 years in cardiac surgery and recently in orthopedics as a blood saving method. The quality of the harvested platelets has not been adequately examined, in part because of methodological difficulties in studying platelet function during surgery. METHODS: Twenty patients undergoing primary total hip replacement (THR) were studied. Ten patients underwent an immediate preoperative platelet apheresis to obtain concentrated platelet rich plasma (c-PRP). The other 10 patients not undergoing apheresis were allocated to a control group. Platelet activation was evaluated as the population expressing P-selectin on the surface of platelets in the c-PRP and in blood samples collected pre-, per- and postoperatively. The method used was flow cytometry. RESULTS AND CONCLUSIONS: A minor population of activated platelets was found to be circulating in the patients' blood, with a highly significant difference between patients (P = 0.005), and with a range of 1-23% in peroperative activation. PRP harvest did not significantly alter platelet activity. The platelet apheresis procedure did not inhibit platelet function in the c-PRP, as judged by a high proportion of platelets that could be activated in ADP stimulation experiments (mean value +/- SD 86% +/- 7.5%).     

Elevated platelet count in patients with endometrial carcinoma: correlation with selected prognostic factors and with survival

Platelets may play a role in the metastatic process and, among gynecologic malignancies, thrombocytosis has been reported in cervical and ovarian malignancy. The present study was conducted in order to assess the prevalence of thrombocytosis in endometrial carcinoma and to correlate platelet count with prognostic factors and with survival. The prevalence of preoperative thrombocytosis was assessed in 66 endometrial carcinoma patients and their platelet count was correlated with selected prognostic factors and with projected survival. The prevalence of thrombocytosis ( 400 000 µL⁻¹) was low (one of 66 patients) compared with that in cervical and ovarian carcinoma. Nevertheless, a significant ( P = 0.032) correlation was found between an elevated ( 300 000 µL⁻¹) platelet count and unfavorable grade of differentiation. Patients with an elevated count also had a poorer survival rate and a higher prevalence of older age, high stage and deep myometrial invasion, but this trend did not reach statistical significance. The combination of unfavorable grade and an elevated platelet count had a higher specificity and positive predictive value for deep myometrial invasion than unfavorable grade alone. The prevalence of thrombocytosis in endometrial carcinoma is low. An elevated platelet count may have some prognostic significance, but its ultimate role in endometrial carcinoma remains to be elucidated.     

Effect of the water extract of Galega officinalis L. on human platelet aggregation in vitro

Galega officinalis L. is a traditional medicinal plant from Bulgaria. It was found that the aqueous extract of Herba Galegae suppressed platelet aggregation in vitro induced by adenosine diphosphate, epinephrine, thrombin and collagen. The compounds with antiaggregating action have not as yet been isolated from Galega officinalis.     

Percutaneous umbilical blood sampling

In the present day, fetal blood is sampled from the umbilical vein via a needle guided by dynamic ultrasound from the maternal abdomen (percutaneous umbilical blood sampling, PUBS). PUBS has become important in the fields of fetal physiology, diagnosis and therapy. Indications for PUBS are fetal karyotyping, prenatal diagnosis of blood disorders and congenital infection, and evaluation of fetal hypoxemia. Although risk of fetal loss following PUBS depends on the indication for the procedure and the experience of the operator, the rate of fetal loss after PUBS is assumed to be around 1%. Recent advances in molecular and cytogenetic techniques have restricted the number of reasons for using PUBS. However, since this technique offers a considerable advantage in enabling access directly to the fetal circulation, PUBS is likely to be used more frequently for fetal therapy than for prenatal diagnosis in the future.     

肾上腺素诱导兔血小板聚集的实践与理论探讨

目的创建以Ａｄｒ诱导兔血小板聚集的方法，并对受体分子特性作初步探讨。方法以高Ｋ＋缓冲液等取代兔ＰＲＰ中血浆，以Ａｄｒ诱导聚集，以Ａｐｙｒ证实结果。结果兔血小板悬浮于高Ｋ＋缓冲液时Ａｄｒ能单独诱导真正的聚集。结论由此推测血小板膜上α２肾上腺素受体分子可能为由两种亚单位组成：促聚亚单位和辅助亚单位。人辅助亚单位当Ａｄｒ浓度高达聚集阈值以上时可被激活，与促聚亚单位结合为活性的二聚体，与Ａｄｒ进一步结合发生聚集作用。兔辅助亚单位则还需要高Ｋ＋方能被激活     

Modulation of Tissue-type Plasminogen Activator Expression by Platelet Activating Factor in Human Glioma Cells

Purpose. For tumor growth, proteolytic remodeling of the extracellular matrix (ECM) is a key factor. To determine proteolytic activity in human glioma cells, fibrinolytic activity, mRNA expression of fibrinolytic factors, and fibrinolytic inhibitors were studied in human glioma cell lines. The effect of platelet activating factor (PAF), a potent mediator of inflammatory and immune responses, on this fibrinolytic activity was also examined. Methods. The fibrinolytic activities of conditioned medium and cell lysates from human glioma cell lines, A172, T98G, U87 and TM1 were studied by fibrin plate zymography. mRNA expression of tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors (PAI-1, PAI-2) was measured by Northern blot analysis. PAF was added to the medium, and its effects on cell proliferation, fibrinolytic activity, mRNA expression of plasminogens and inhibitors were studied. Results. mRNA expression of plasminogens and inhibitors differed between individual cell lines. Only the medium and cell lysates from A172 cells revealed fibrinolytic activity. A172 cells showed mRNA expression of tPA. PAF at low concentrations, such as 1 nM, stimulated A172 cell proliferation, and high concentrations of PAF inhibited proliferation. PAF stimulated tPA release into the conditioned medium. mRNA expression of tPA was stimulated by low concentrations of PAF and inhibited by high concentrations. Conclusion. The variability of mRNA expression of plasminogen activators (PAs) between different glioma cell lines may indicate that plasminogens and their inhibitors do not directly correlate with brain tumor growth. PAF may be an important factor in the local control of fibrinolytic activity in glioma and its proliferation.