Objective To study the role the pathogenesis of early acute lung injury (ALI) of rabbits induced by intravascular injection of endotoxin (ET) with the intervening method of Chloroquine. Methods Rabbits were randomly assigned to three groups: control group, ET group, and ET+ chloroquine group. Acute lung injury was induced by intravascular injection of ET (500μg/kg). The arterial gas analyses, leucocyte and platelet counts in peripheral blood, PLA2 activity both in serum and lung tissue, lipid peroxide (LPO) and superoxide dismutase (SOD) in lung tissue were measured. Electron microscope and light microscope were used to observe the pathological injuries in pulmonary tissue. The protective effects of chloroquine in early ALI were evaluated. Results Compared with saline controls, rabbits treated with ET displayed the early lung injuries, such as the decrease of PaO2 (P＜0.05), the decrease of leucocytes and platelets in peripheral blood, the leukocytes sequestration in lung tissue. The PLA2 activity significantly increased in ET group compared with control group and chloroquine group both in serum and pulmonary tissue. In ET group, concentration of LPO increased in lung tissue (P＜0.05), while concentration of SOD decreased (P＜0.05). Severe histopathological injuries were presented in ET group, including pulmonary edema, lung tissue haemorrhage, inflammatory cells infiltration, asphyxial membrand formation, partial pulmonary closure and emphysema.Ultrastructural changes showed both type Ⅰ and type Ⅱ epithelial cells injury in ET group, the edema of endothelial cells, interalveolar septum thickening. In chloroquine group, PaO2 didn't decrease, PLA2 activities in serum and pulmonary tissue were lower than ET group (P＜0.05, P＜0.05), while the concentration of LPO in lung tissue decreased (P＜0.01) and SOD increased significantly (P＜0.01). Pathological examination showed slight pulmonary edema, inflammatory cells infiltration were extenuated, ultrastructural examination proved that the injuries were alleviated by chloroquine compared with ET group. Conclusion Intravascular injection of ET could successfully induce the early ALI models in rabbits. Chloroquine could inhibit the PLA2 activation and reduce the oxidative injury in lung tissue. The experiment result demonstrated PLA2 activation and oxidative stress played important roles in the pathophysiological process of early ET-induced ALI in rabbits.

Objective To study the changes in activity of phospholipase A2 (PLA2) in the course of endotoxin (ET) induced acute lung injury (ALI) inrabbits and the antagonizing effect of fructose-1, 6-diphosphate (FDP), in order to evaluate the therapeutic effect of FDP on ET-induced ALI. Methods Flapeared white rabbits were randomly assigned to three groups: control group (group A), ET challenge group (group B) and treatment group (ET challenged followedby FDP, group C). Group A animals were injected with saline (2ml/kg) as control. Group B animals were injected with ET (500μg/kg) solution followed by saline. Total amount of liquid was 2ml/kg. Group C animals were given the same amount of ET solution followed by injection of FDP (300mg/kg) solution. Total amount of liquid was also 2 ml/kg. During the experiment, respiratory rate, heart rate, blood pressure, arterial blood gases and the plasma PLA2 activity were determined at 0h, 0. 5h, 2h, 4h and 6h respectively. The rabbits were sacrificed at 6h, pulmonary PLA2 activity was assessed, and the pathologic changes in pulmonary tissues were examined with light microscope and transmission electron microscope. Results Compared with group A,rabbits of group B manifested the typical characters of ALI after ET injection, and the PLA2 activity in both serum and pulmonary tissue was much higher than those of group A (P＜0. 01).Values of the PLA2 activity in group C were between those of the two former groups. At the rame time, obvious pathological changes indicating lung injury were observed in group B and only mild pathological changes could be discerned in group C. Conclusion Activation of PLA2 activity is an important factor in pathogenesis of ET-induced ALI. FDP can antagonize the PLA2 activity and protect rabbits from early ET induced ALI to a certain extent.

Objective To study the roles of phospholipase A 2 (PLA 2) and oxidative stress in the pathogenesis of acute lung injury(ALI) of rabbits induced by intravascular injection of endotoxin (ET), as well as the protective effects of chloroquine. Methods Rabbits were randomly assigned to three groups: control group, ET group, and ET+chloroquine group(n=8). Acute lung injury was induced by intravascular injection of ET (500?g/kg). The arterial blood gas analysis and serum PLA 2 activity were measured before and after the ET challenge. At the end of the experiment, PLA 2 activity, content of malodialdchyde (MDA), and superoxide dismutase (SOD) in lung tissue were assayed. Electron microscope and light microscope were used to observe the pathological injuries in the pulmonary tissue. Results Compared with saline controls, rabbits treated with ET manifested signs of ALI, such as the decrease of PaO 2(P

Objective To study the changes in activity of phospholipase A_2 (PLA_2) in the course of endotoxin (ET)-induced acute lung injury (ALI) in rabbits and the antagonizing effect of fructose-1,6-diphosphate (FDP), in order to evaluate the therapeutic effect of FDP on ET-induced ALI. Methods Flap-eared white rabbits were randomly assigned to three groups: control group (group A), ET challenge group (group B) and treatment group (ET challenged followed by FDP, group C). Group A animals were injected with saline (2ml/kg) as control. Group B animals were injected with ET (500?g/kg) solution followed by saline. Total amount of liquid was 2ml/kg. Group C animals were given the same amount of ET solution followed by injection of FDP (300mg/kg) solution. Total amount of liquid was also 2 ml/kg. During the experiment, respiratory rate, heart rate, blood pressure, arterial blood gases and the plasma PLA_2 activity were determined at 0h, 0.5h, 2h, 4h and 6h respectively. The rabbits were sacrificed at 6h, pulmonary PLA_2 activity was assessed, and the pathologic changes in pulmonary tissues were examined with light microscope and transmission electron microscope. Results Compared with group A, rabbits of group B manifested the typical characters of ALI after ET injection, and the PLA_2 activity in both serum and pulmonary tissue was much higher than those of group A (P

BACKGROUND: Fructose-1, 6-diphosphate (FDP) is an intermediate product in the course of cellular glycometabolism, and has many biological effects, such as improving cellular energy metabolism, stabilizing biological membrane, inhibiting inflammation intermedium release, antagonizing oxidation, and so on.OBJECTIVE: To observe the changes of oxidative stress reaction in the course of endotoxin (ET) induced acute lung injury (ALI) in flap-eared white rabbits and the antagonistic action of FDP, and to explore the therapeutic effects of FDP on ALI.DESIGN: Complete randomized group design, controlled experiment.SETTING: Department of Respiratory Medicine, General Hospital of Chinese PLA. MATERIALS: The experiment was conducted in the laboratory of Department of Respiratory Medicine, General Hospital of Chinese PLA between May and December 2003. Twenty-four cleaning male flap-eared white rabbits were selected and randomly assigned into control group, injured group and interventional group with 8 animals in each group.METHODS: ①Control group: The rabbits were injected with saline (2 mL/kg) through vein. Injured group: The rabbits were injected with ET (500 μg/kg) solution dissolved in 2 mL saline through cannulation in cervical vein once within 5 minutes, and then saline was injected once (Total amount of the solution was 2 mL/kg). Interventional group: The rabbits were injected with the same amounts of ET solution within 5 minutes as that in the injured group, but FDP (300 mg/kg) solution was injected later (Total amount of solution was also 2 ml/kg). ②Peripheral blood and arterial blood were collected at 0, 0.5, 2, 4 and 6 hours in each group. Peripheral blood cell count and arterial blood gas were measured with autoblood cell analyzer and blood gas analyzer, respectively. After rabbits were sacrificed through bloodletting at the 6th hour, content of lipid peroxide (LPO) and activity of superoxide dismutase (SOD) in the pulmonary tissues of rabbits were measured with barbituric acid colorimetry and pyrogallol auto-oxidizing suppression, respectively. In addition, some right lower lobes of pulmonary tissues were observed on pathology with transmission electron microscope (TEM). ③Data accorded with normal distribution and homogeneity of variance were compared by t-test, or by rank sum test.MAIN OUTCOME MEASURES: ① Comparison of result of arterial blood gas and blood cell count measured before experiment, after 0.5, 2, 4 and 6 hours experiment in rabbits of each group. ②Rabbits were sacrificed after 6 hours experiment, the pulmonary contents of LPO and the activities of SOD were measured, and the pathologic changes were also examined.RESULTS: ①At 0.5 hour after ET injected, arterial blood oxygen pressure and white blood cell count in peripheral blood were lower significantly in the rabbits of the injured group as compared with those of the control group (t=-4.27, P ＜ 0.01,z=2.64, P ＜ 0.01 ). Arterial blood oxygen pressure and white blood cell count in peripheral blood in the interventional group showed insignificant difference as compared with the control group (P ＞ 0.05). The arterial blood oxygen pressure in the interventional group was obviously higher than that in the injured group (t=4.32,P ＜ 0.01 ). ②At the 4th hour after experiment, the arterial blood oxygen pressure in the interventional group was distinctly higher than those of the control group and the injured group (t=4.98, 2.40, P ＜ 0.01, 0.05). The white blood cell count in the injured group was dramatically less than those of the control group (z=2.42,P ＜ 0.05). ③At the 6th hours after experiment, the arterial blood oxygen pressure in the interventional group was markedly higher than those of the control group (t=3.39,P ＜ 0.01), The white blood cell count in the injured group was remarkably less than those of the control group (z=2.16,P ＜ 0.05). Content of pulmonary LPO in the injured group was significantly higher than that in the control group (t=3.70,P ＜ 0.01)while the activity of SOD was obviously lower than that in the control group(t=-4.12,P<0.01).Markedly pathological lesion appeared in the pulmonary tissue. Six hours later, the content of pulmonary LPO and the activity of pulmonary SOD in the interventional group had no remarkable difference from those in the control group (P ＞ 0.05), and the pulmonary pathologic injury showed less obvious.CONCLUSION: The relative deficiency of oxidative stress reaction can aggravate oxidative injury, which is an important role in pathogenesis of ET-induced ALI. FDP can improve abilities of oxidative stress reaction, inhibit oxidative injury and protect rabbits from ET-induced ALI in flapeared rabbits to a certain extent.

Objective To investigate the changes in interleukin-19(IL-19)in lungs of rabbits with acute lung injury(ALI)induced by endotoxin(ET),so as to study the mechanism of injury of ET to the lung and the protective mechanism of meloxicam.Methods Twenty four male Japanese flap-eared white rabbit was randomly assigned to three groups:control group,ET-treated group and treatment with meloxicam group.Rabbit ALI model was replicated with intravascular ET injection(700?g/kg),and meloxicam was intravenously injected(2.5mg/kg)for treatment group.The content of IL-19 was measured with ELSIA method and the changes in malondialdehyde(MDA)and superoxide dismutase(SOD)were determined in every group.Results IL-19 expression in ET challenged group was significantly higher than that in control group(P

Objective To observe the pulmonary pathologic changes of endotoxin (ET)-induced acute lung injury (ALI) in rabbits and the potential protective effects of fructose-1,6-diphosphate (FDP) on the ET-induced ALI of rabbits. Methods 24 flap-eared albation rabbits were randomly assigned to 3 groups, 8 for each, as follows: control group (group A), ET-treated group (group B) and combination group (treated by ET and FDP, group C). ALI was induced by injection of ET at one time. Group A was only injected with placebo, normal saline. ET was given to the rest groups. In group C, FDP was given as an intervening measure after rabbits injured. Rabbits were sacrificed at 6h time point. The pulmonary pathologic changes were observed. Some markers of pulmonary tissues, including the content of lipid peroxide (LPO), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α(6-keto-PGF1α), interleukin-13 (IL-13) and the activity of superoxide dismutase (SOD), were observed. Results Compared with group A, the contents of LPO and TXB2 of group B showed significant increase (P＜0.05, P＜0.01), the SOD activity of group B weakened obviously (P＜0.01), the contents of 6-keto-PGF1α and IL-13 showed no statistical differences. The LPO content and the SOD activity of group C were similar to those of group A, the contents of TXB2, 6-keto-PGF1α and IL-13 of group C were much higher than those of group A (P＜0.01). Estimated by light microscope and electron microscope, the structure of lung tissue of group A is basically normal, the pathologic injuries of lung tissue of group B were much more severer and that of group C were slighter. Conclusion In the progress of ET-induced ALI, the oxidative injury, imbalance of TXB2/6-keto-PGF1α ratio and the secretion deficiency of protective cytokines play important role in inducing pathologic injuries of lung tissues. FDP can inhibit oxidative injury, ameliorate TXB2/6-keto-PGF1α balance and promote the secretion of protective cytokines, which, in turn, can protect rabbits from ET-induced ALI to some extent.

Objective To evaluate the influence of cytochrome P450 (CYP2C9 and CYP4F2) polymorphisms on anticoagulant intensity of warfarin after cardiac valve replacement.Methods A total of 136 patients tak ing warfarin after cardiac valve replacement were identified and classified into 4 groups:CYP2C9 wild type group (CYP2C9*1*1),CYP2C9 mutated type group (CYP2C9*3),CYP4F2 rs2108622 wild type group (CC) and CYP4F2 rs2108622 mutated type group (CT or TT).The patients' baseline data,initial dose of warfarin and base INR measurement resuhs were recorded and then the follow-up was conducted.The initial administration of warfarin to INR standard time for the first time,total amount of warfarin and the average daily amount were recorded.Results Patients carrying CYP2C9* 1* 1 had increased time to reach INR target value for the first time (P ＜ 0.05);and the total warfarin doses and average daily dose when INR reached target value were higher than those carrying CYP2C9*3 (P ＜ 0.05).When compared with those in two wild type groups,patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type needed the shortest time when INR reached target value for the first time,and the total warfarin doses and average daily dose when INR first reached target value was the lowest,which showed significant difference (P ＜ 0.05).And when compared with CYP2C9 mutated type group,the INR average time to reach the first target was shortened and the total warfarin dose of patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type was lower (P ＜ 0.05).Conclusion The gene polymorphisms of CYP2C9 and CYP4F2 are significant hereditary factors influencing warfarin dose.Detection of CYP2C9 and CYP4F2 genotypes prior to medication and predicating warfarin dosage may result in lower incidence of over-anticoagulation and reduce the dosage-adjusting time of warfarin.

Objective To evaluate the effectiveness of multiple spiral CT angiography in diagnosis of pulmonary embolism.Methods 16 patients clinically suspected of pulmonary embolism underwent multiple spiral CT angiography.Emboli were found in the 8 patients of all on multiple spiral CT angiography.5 of the patients were reexamined with this method 20 to 30 days after thrombolysis. Results In 8 patients with pulmonary embolism,43 vessels were involved with pulmonary embolism.The presence of pulmonary embolism on CT was seen as a total occlusion,partial filling defect,mural filling defect et al;dilated of pulmonary artery trunk;all signs with deceleration of pulmonary blood or “mosaic sign”. 5 patients were reexamined with this method.The emboli dissoved partly or entirely.Conclusion Multiple spiral CT angiography is a noninvasive and effective method for examining pulmonary embolism.

Objective To evaluate the display ability and the clinical application of multislice spiral CT virtual endoscopy (CTVE) in the diagnosis of vascular diseases. Methods Fifty-six patients were examined by CT virtual endoscopy.32 patients also had DSA for comparison.18 patients were confirmed by operation (3 patients also had DSA).9 patients with pulmonary embolism were confirmed by other examinations and treatments.Results 56 patients showed successful CT virtual endoscopy images.CT virtual endoscopy images could clearly show the inner wall and inner structures of the vessels,mural thrombus,calcification form,stenosis of the vessels,the true and false lumina of aortic dissections,the lesion of false aneurysm,and the anatomic relationship between the lesion and surrounding structures of the normal vessels.Out of the 32 patients with vessel abnormalities on DSA,24 patients (75%) showed the lesions on CTVE.17 out of 18 patients with operation showed the lesions on CTVE.All 9 patients with pulmonary embolism showed the abnormalities on CTVE.Chi-square test:? 2=5.2809,P=0.071 patients showed the vascular diseases on CTVE in 56 patients (84%).Conclusion MSCT virtual endoscopy could provide more information of the vessel by displaying the inner wall and allowing users to map the vessels in a display.It is helpful in correct diagnosis and guiding surgery.