[Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

[Effect of the proteasome inhibitor MG-132 on hyperoxic lung injury and its mechanism in rats].

OBJECTIVE: To observe the effects of proteasome inhibitor MG-132 on hyperoxic lung injury in rats and explore the mechanism. METHODS: Thirty SD rats were randomly divided into 3 groups, namely the normoxic group, hyperoxic group, and hyperoxic with MG-132 treatment group, and rat models of hyperoxic exposure-induced lung injury were established in the latter two groups. After pathological grading of the lung injury under optical microscope and determination of the wet/dry weight ratio of the lung tissue, the expressions of ubiquitin protein and nuclear factor-kappaB (NF-kappaB) p56 and the activity of proteasome 20S and myeloperoxidase (MPO) were detected. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions in the lung tissue were also detected. RESULTS: The rats with hyperoxic exposure showed obvious pulmonary edema and increased wet/dry weight ratio of the lung tissue (P<0.01), which were significantly alleviated with MG-132 treatment (P<0.01). Compared with the normoxic group, hyperoxic exposure resulted in significant lung pathologies (P<0.01), which was reduced after MG-132 treatment. Immunohistochemistry and Western blotting demonstrated increased expression of ubiquitin protein in the lung tissue after hyperoxic exposure (P<0.01), which was lowered by MG-132 treatment (P<0.01). Proteasome 20S activity was obviously enhanced in the hyperoxic group (P<0.01) but lowered by MG-132 treatment (P<0.01). Hyperoxic exposure also caused obviously enhanced MPO activity and expressions of NF-kappaB, TNF-alpha, and IL-6 (P<0.01), which were all reduced by MG-132 treatment (P<0.05). CONCLUSION: MG-132 alleviates hyperoxic lung injury probably by inhibiting the NF-kappaB/inflammatory factor pathways.

Effect of L-arginine liposome on nitric oxide content and nitric oxide synthase gene expression in rats chronically exposed to hypoxia and hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of L-arginine liposome on nitric oxide(NO) and nitric oxide synthase gene (NOS mRNA) in rats chronically exposed to hypoxia-hypercapnia.</p><p><b>METHODS</b>Fourty male SD rats were randomly divided into four groups (n=10): normal control group(NC), hypoxia-hypercapnia group (HH), hypoxia-hypercapnia + L-arginine group(HL) and hypoxia-hypercapnia + L-arginine liposome group (HP). Contents of NO in plasma were measured using colorimetric analysis. Expression of nitric oxide synthase gene were measured with situ hybridization.</p><p><b>RESULTS</b>(1) The mean pulmonary artery pressure(mPAP) and weight ratio of right ventricle to left ventricle and septum(RV/LV + S) of HP group were obviously lower than those of HH group and HL group. (2) The NO contents in plasma of HP group were obviously higher than those of HH group and HL group (P < 0.01). (3) Situ hybridization showed the average value of integral light density(LD) of ecNOS mRNA in pulmonary arterioles was significantly higher in rats of HP group than that of HH group and HL group (P < 0.01). (4) Light microscopy showed WA/TA (vessel wall area/total area) and PAMT (media thickness ratio of pulmonary arterioles) were significantly lower in rats of HP group than those of HH group (P < 0.01).</p><p><b>CONCLUSION</b>L-arginine liposome could lower the mPAP and lighten the remodeling of pulmonary arterioles of the rats chronically exposed to hypoxia-hypercapnia than L-arginine does. It suggests that L-arginine liposome significantly promotes the membrane transportin of L-arginine.</p>