Role of sulfur dioxide in acute lung injury induced by ischemia-reperfusion of hind limbs in rats

AIM：To explore the role of endogenous and exogenous sulfur dioxide(SO2) in acute lung injury(ALI) induced by ischemia-reperfusion(IR) of limbs in rats. METHODS：The rat model of ALI was induced by ischemia and reperfusion of the hind limbs using a tourniquet. The rats(n=96) were randomly divided into 6 groups: sham, IR, sham+SO2, sham+hydroxamate(HDX), IR+SO2 and IR+HDX. The morphological changes of the lung tissues were observed under light microscope. Meanwhile, polymorphonuclear neutrophils(PMN) in alveolar septum, lung coefficient, lung levels of malondialdehyde(MDA) and intercellular adhesion molecule(ICAM)-1, serum tumor necrosis factor(TNF)-α and interleukin(IL)-1, the content of SO2 and the activity of aspartate aminotransferase(AST) in the lung tissues, and 24 h survival rate of the rats were measured. RESULTS：IR of the rat limbs resulted in the damage of the lung tissues, and the increases in PMN in alveolar septum, lung coefficient, the lung levels of MDA and ICAM-1 and the serum levels of TNF-α and IL-1 were also observed with the reductions of SO2 content and AST activity. Pretreatment with SO2 donor Na2SO3/NaHSO3 alleviated the changes of the indicators above. HDX, an inhibitor of SO2-producing enzymes, aggravated the changes above. CONCLUSION：Down-regulation of AST/SO2 pathway is involved in the pathogenesis of limb IR-induced ALI. Administration of exogenous SO2 might attenuate lung injury through anti-inflammation and anti-oxidation.     

p38 MAPK specific inhibitor SB203580 down-regulates acute pulmonary thromboembolism-induced pulmonary artery hypertension and monocyte chemoattractant protein-1 in rats

AIM：To explore the hypothesis that initiation of pulmonary hypertension involves the up-regulation of monocyte chemoattractant protein-1 (MCP-1) in acute pulmonary thromboembolism (PTE), and to evaluate the role of p38 mitogen-activated protein kinase (MAPK) in this process. METHODS：One hundred and fifty male SD rats were randomly divided into five groups (n=30): normal control group, solvent control group, acute PTE group, acute PTE plus SB203580 (a p38 MAPK specific inhibitor) pretreatment group and acute PTE plus C1142 (a rodent chimeric monoclonal antibody neutralizing rat MCP-1) pretreatment group. Thirty rats in each group were further divided into 1, 4 and 8 h subgroups (n=10). A rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. SB203580 or C1142, dissolved in 1% dimethyl sulfoxide (DMSO), was administered to the animals through caudal vein 1 h prior to the beginning of acute PTE modeling. Rats in normal control group and solvent control group were injected with normal saline and 1% DMSO, respectively. The mean pulmonary artery pressure (MPAP) and the mRNA and protein expression of MCP-1 were measured at each time point. RESULTS：Acute PTE elicited significant increase in MPAP, and up-regulated the expression of MCP-1. Pretreatment with SB203580 or C1142 significantly reduced MPAP, and down-regulated the expression of MCP-1. CONCLUSION：These findings suggest that MCP-1 is involved in the formation of acute PTE-induced pulmonary hypertension, and SB203580 down-regulates the expression of MCP-1 via p38 MAPK signaling pathway, thus attenuating pulmonary hypertension.     

喹禾灵对映体对斑马鱼毒性的手性选择性研究

为了研究喹禾灵对映体对水生生物的手性选择性毒性,对喹禾灵对映体进行了斑马鱼急性毒性试验,并研究了亚致死水平上对斑马鱼体内ATP酶活性的影响。研究发现,精喹禾灵和喹禾灵对斑马鱼的急性毒性分别为高毒和低毒;二者在诱导时间和诱导强度上对斑马鱼体内Na+,K+-ATP酶和Ca2+-ATP酶活性均表现出不同的作用方式。喹禾灵对斑马鱼Ca2+-ATP酶活性的影响在72 h时,250μg.L 1、1 000μg.L 12个处理组表现出明显诱导效应(P<0.05),在96 h各处理组均表现出诱导作用。精喹禾灵除在24 h时,5μg.L 1、10μg.L 1处理组外,其他各处理组对斑马鱼体内Ca2+-ATP酶表现出较强的诱导作用;72 h后,25μg.L 1、100μg.L 1处理组酶活性有下降趋势,其他2个处理组酶活性则继续增加。喹禾灵对斑马鱼Na+,K+-ATP酶活性的影响在48 h时,250μg.L 1、1 000μg.L 12个处理组有明显诱导效应(P<0.05),72 h时只有1 000μg.L 1处理组有明显诱导作用。精喹禾灵25μg.L 1、100μg.L 1处理组在24 h时对Na+,K+-ATP酶活性即表现出很强的诱导效果,48 h后各处理组酶活性都开始明显增加;72 h时各浓度处理组酶活性有下降趋势,96 h后基本与对照组无显著性差异。试验结果表明喹禾灵对映体对斑马鱼毒性有显著的手性选择性。     

Effect of experimental endotoxemia on thrombelastography parameters, secondary and tertiary hemostasis in dogs

Background: Thrombelastography (TEG) and indicators of secondary and tertiary hemostasis might be altered in dogs with endotoxemia. Hypothesis: Endotoxemia influences measures of coagulation in dogs. Animals: Ten healthy cross‐bred dogs. Material and Methods: Prospective laboratory study between controls (n = 5) receiving 0.9% saline IV and the study group (n = 5) treated with low‐dose lipopolysaccharide (0.02 mg/kg IV). Physical examination and sampling for measurement of leukocytes, platelets, and coagulation variables were performed at time points 0, 1, 4, and 24 hours. Coagulation variables included kaolin‐activated TEG, 1‐stage prothrombin time (OSPT), activated partial thromboplastin time (aPTT), fibrinogen, factor VIII, antithrombin, protein C, protein S, activated protein C (APC)‐ratio calculated from aPTT with and without presence of APC), and D‐Dimers. Results: Endotoxemia‐induced clinical signs included lethargy (n = 5/5), diarrhea (n = 4/5), emesis (n = 4/5), and abdominal pain (2/5). After 1 hour there was severe leukopenia (2.5 ± 0.7 × 10⁹/L; mean ± SD, P < .0001) and a 2.2‐fold increase in D‐Dimers (0.81 ± 0.64 mg/L, P < .0001). After 4 hours there was hyperthermia (40.3 ± 0.4°C, P < .0001) and increases in OSPT (10.5 ± 2.7 seconds, P < .0001), aPTT (16.7±5.2 seconds, P= 0.002). A significant decrease in fibrinogen (1.5±1.0 g/L, P= 0.001), protein C (31 ± 33%, P <.0001), protein S (63 ± 47%, P < .0001), TEG α (58 ± 19, P= .007), and TEG maximal amplitude (50 ± 19 mm, P= .003) was seen compared with the controls. APC‐ratio rose significantly (2.5 ± 0.2, P < .0001) without exceeding the reference interval (n = 4/5). Conclusion and Clinical Importance: D‐Dimers are the earliest indicator for endotoxemia‐associated coagulation abnormalities followed by decreased protein C concentration. APC‐ratio and TEG were not good screening variables.     

Evaluation of a point-of-care test for canine C-reactive protein

Background: In veterinary medicine, there is increasing interest in measuring C‐reactive protein (CRP) as a tool for diagnosis and monitoring of inflammatory diseases. Reported CRP concentrations for healthy dogs have ranged from 0 to 8.9 mg/L. Objectives: The aims of this study were to evaluate a canine‐specific point‐of‐care (POC) lateral flow immunoassay for qualitative CRP measurement in healthy and diseased dogs and to compare results with those obtained by a quantitative ELISA. Methods: Blood samples from 73 client‐owned dogs were available for testing: 16 healthy dogs and 57 dogs with a variety of infectious, inflammatory, or neoplastic diseases. CRP was measured in heparinized whole blood samples and serum with the TECOmedical Dog CRP‐visual POC test. A red line develops in the POC device if CRP is ≥5 mg/L, and results are scored as negative or positive. An ELISA validated previously for canine serum was used as the reference method. Results: For all dogs, serum CRP concentrations measured by the ELISA ranged from 0.1 to ≥350 mg/L (median=38 mg/L). Percentages of the CRP POC test results that agreed with the ELISA results were 98.6% for whole blood and 97.3% for serum samples. For serum samples, sensitivity of the POC test was 96.4% and specificity was 81.3%. For whole blood, sensitivity was 94.7% and specificity was 93.8%. Conclusions: The POC test had very good agreement with the ELISA test and had high sensitivity and specificity; therefore, it can be used as a qualitative test to screen for increases in CRP concentrations.     

Inflammatory Response of Healthy Horses Subjected to Small Colon Enterotomy and Treated or Not With Heparin

The acute phase response is a response to injury and depends on the severity of the trauma. Heparin is routinely used for postsurgical treatment of horses to prevent abdominal adhesions; however, its effect on inflammation is unknown. This study aimed to assess systemic inflammatory response of horses subjected to small colon enterotomy and to evaluate heparin effects on postsurgical inflammation. Ten adult horses were subjected to small colon enterotomy and were assigned to a control or a treatment group. Both groups received prophylactic antibiotics and flunixin, and the treatment group received 150 IU/kg heparin subcutaneously after surgery and every 12 hours for five days. WBC counts, peritoneal fluid evaluation, determination of serum and peritoneal haptoglobin (Hp), and serum amyloid A (SAA) were performed before, 12 hours, and 1, 2, 4, 6, 10, and 14 days after enterotomy. Forty-eight hours after surgery, a significant increase in serum Hp was observed in the control group, and SAA concentrations increased significantly in the both groups between 24 hours, 48 hours, and 4 days after surgery. The SAA and serum Hp concentrations produced no significant differences between the groups. Peritoneal Hp increased significantly in the control group 4 days after surgery and was significantly higher in the control group than in the treated group 14 days after surgery. Serum Hp and SAA identified the acute phase response changes faster, however, were not able to identify differences between groups. Peritoneal Hp concentrations identified inflammatory differences between the groups 14 days after surgery; the difference suggests that heparin may act decreasing inflammation.     

毒菌净对实验动物的急性及亚慢性毒性研究

应用毒菌净对实验动物的急性及亚慢性毒性研究，按寇氏法测得昆明种小白鼠灌服毒菌净的LD50为32025．8mg／kg，95％可信限为30421．1～37916．2mg／kg．亚慢性毒性试验以每天分别用640．5，3202．66405．2mg／kg体重的剂量加入饲料中，供大白鼠自由采食，分别于50d、120d检查动物，包括全身状态、称量体重、血液检验、肝、肾功能检验和病理剖检与组织切片观察等项．结果表明，对大白鼠的生理活动、组织器官无不良影响，并有促进体重增加和速效生血作用，证明毒菌净无毒性，与急性毒性试验所得的结果相符．