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61.
BACKGROUND: The resistance of thrombi to fibrinolysis induced by plasminogen activators remains a major impediment to the successful treatment of thrombotic diseases. This study examines the contribution of activated factor XIII (factor XIIIa) to fibrinolytic resistance in experimental pulmonary embolism. METHODS AND RESULTS: The fibrinolytic effects of specific inhibitors of factor XIIIa-mediated fibrin-fibrin cross-linking and alpha2-antiplasmin-fibrin cross-linking were measured in anesthetized ferrets with pulmonary emboli. Five experimental groups were treated with heparin (100 U/kg) and/or tissue plasminogen activator (TPA, 1 mg/kg) and the percent (mean+/-SD) lysis of emboli was determined: (1) control, normal factor XIIIa activity (14.1+/-4. 8% lysis); (2) inhibited factor XIIIa activity (42.7+/-7.4%); (3) normal factor XIIIa activity+TPA (32.3+/-7.7%); (4) inhibited factor XIIIa activity+TPA (76.0+/-11.9%); and (5) inhibited alpha2-antiplasmin-fibrin cross-linking+TPA (54.7+/-3.9%). Inhibition of factor XIIIa activity increased endogenous lysis markedly (group 1 versus 2; P<0.0001), to a level comparable to that achieved with TPA (group 2 versus 3; P<0.05). Among groups receiving TPA, selective inhibition of factor XIII-mediated alpha2-antiplasmin-fibrin cross-linking enhanced lysis (group 3 versus 5; P<0.0005). Complete inhibition of factor XIIIa also amplified lysis (group 3 versus 4; P<0.0001) and had greater effects than inhibition of alpha2-antiplasmin cross-linking alone (group 4 versus 5; P<0.0005). No significant fibrinogen degradation occurred in any group. CONCLUSIONS: Factor XIIIa-mediated fibrin-fibrin and alpha2-antiplasmin-fibrin cross-linking both caused experimental pulmonary emboli to resist endogenous and TPA-induced fibrinolysis. This suggests that factor XIIIa may play a critical role in regulating fibrinolysis in human thrombosis. 相似文献
62.
Rita Moretti Paola Torre Rodolfo M. Antonello Giuseppe Cazzato Stefania GriggioAntonio Bava MD 《Current therapeutic research》2002,63(7):443-458
Background: Patients with vascular dementia (VaD) show cholinergic deficits that may result in characteristic clinical syndromes for different subtypes of the condition. In addition to executive function, subcortical VaD is characterized by behavioral and emotional problems, reflecting deterioration of the frontal lobe.Objective: The purpose of this study was to determine the effect of rivastigmine on the specific symptoms of subcortical VaD.Methods: Patients received rivastigmine 3 to 6 mg/d (n = 8) or low-dose aspirin (cardioaspirin) 100 mg/d (n = 8) for 22 months in an open-label study design. Rivastigmine-treated patients began therapy with the lower dosage of rivastigmine 3 mg/d, which was increased to the higher dosage of 6 mg/d after 4 weeks. Disease severity was assessed using the Clinical Insight Rating Scale. Behavior was assessed using the NeuroPsychiatric Inventory (NPI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Cornell Scale for Depression in Dementia (CSDD). The main results of this study, including executive function, NPI, and caregiver stress scores, have been presented elsewhere.Results: Sixteen patients were enrolled. Patients receiving rivastigmine showed statistically significant improvements in their BEHAVE-AD and CSDD scores (P = 0.001 and P = 0.02, respectively, versus cardioaspirin). Comparison of individual items on the BEHAVE-AD scores of the rivastigmine group with the cardioaspirin group indicated statistically significant improvements in activity disturbance, affective disturbance, aggressiveness, anxiety/phobia, hallucinations, and paranoia/delusions (P = 0.007, P = 0.035, P = 0.008, P = 0.003, P = 0.006, and P = 0.001, respectively). Similarly, comparison of the NPI scores of the 2 groups showed that the rivastigmine group experienced significantly greater improvements in anxiety, hallucinations, and wandering (P = 0.001, P = 0.005, and P = 0.014, respectively). Side effects in both groups were tolerable and there were no study withdrawals.Conclusions: In this preliminary study, rivastigmine treatment was well tolerated and effective. Improvements in the symptoms that characterize subcortical VaD were observed, suggesting that rivastigmine may have provided targeted treatment in areas of the brain that are particularly affected in this patient population. A large, double-blind, placebo-controlled study of rivastigmine in patients with VaD is warranted. 相似文献
63.
Hematopoietic growth factors not only modulate blood progenitor cell activity but also alter the function of mature phagocytes. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL for 60 min) did not stimulate luminol-enhanced chemiluminescence of polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as much as a 15-fold increase in chemiluminescence in response to f-met- leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%] and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low even after rhGM-CSF priming, but MNLs added to the PMNs (PMN- MNL) resulted in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence. The enhancing factor(s) from MNLs were inherent rather than induced by the GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN chemiluminescence equal to mixed MNLs. We could not detect cell-free "enhancing factor(s)," but cell-to-cell contact further enhanced rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%. Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune serum) decreased both fMLP-stimulated rhGM-CSF- primed PMNs and PMN-MNL chemiluminescence, suggesting that TNF on the PMN surface is enhancing GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN superoxide release (sevenfold), but PMN superoxide release was not further enhanced by the presence of MNLs. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity was observed when mixed PMN-MNL were primed with GM-CSF in a cell pellet-promoting cell-to-cell contact. This enhanced activity can be attributed, in part, to both inherent enhancing factor(s) on lymphocytes and PMN-associated TNF induced by GM-CSF. 相似文献
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65.
小鼠颅神经嵴细胞的培养和特征 总被引:6,自引:4,他引:2
目的:在体外原代培养Balb/c小鼠胚胎的颅神经嵴细胞。为颅面部各种组织细胞的发育研究提供细胞来源。方法:采用胰酶消化法分离小鼠胚胎第8.5天的颅神经管,从小鼠颅神经管中游离出来的细胞即为颅神经嵴细胞,用免疫组织化学方法鉴定细胞的来源,并测定细胞的生长曲线。结果:成功地培养出小鼠的颅神经嵴细胞,其形态类似成纤维样细胞,免疫组化检测结果表明,神经特异性烯醇化酶(NSE)抗体染色结果阳性。细胞的群体倍增时间为43.65h。结论:原代培养的小鼠颅神经嵴细胞生长稳定,来源明确,是颅面部各种细胞的发育和分化研究中一种有用的工具。 相似文献
66.
Wolff SN; Marion J; Stein RS; Flexner JM; Lazarus HM; Spitzer TR; Phillips GL; Herzig RH; Herzig GP 《Blood》1985,65(6):1407-1411
High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches. 相似文献
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