Chronic Toxicity of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous...     

Melatonin reduces acute lung injury in endotoxemic rats

Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia. Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups： vehicle ＋ saline group, melatonin ＋ saline group, vehicle ＋ lipopolysaccharide group, melatonin ＋ lipopolysaccharide group. The rats were treated with melatonin （10 mg/kg, intraperitoneal injection （i.p.）） or vehicle （1% ethanol saline）, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, intravenous injection）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios （W/D）, myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B （NF-κB） p65 was evaluated by Western blotting. Results PaO2 in the vehicle ＋ lipopolysaccharide group decreased compared with that in the vehicle ＋ saline group. This decrease was significantly reduced in the melatonin ＋ lipopolysaccharide group. The lung tissues from the saline ＋ lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin ＋ lipopolysaccharide group. The W/D ratio increased significantly in the vehicle ＋ lipopolysaccharide group （6.1±0.18） as compared with that in the vehicle ＋ saline group （3.61±0.3） （P 〈0.01）, which was significantly reduced in the melatonin ＋ lipopolysaccharide group （4.8±0.25） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle ＋ lipopolysaccharide group compared with that in the vehicle ＋ saline group, which was reduced in the melatonin ＋ lipopolysaccharide group. The TNF-a level of pulmonary tissue increased significantly in the vehicle ＋ lipopolysaccharide group （（8.7±0.91） pg/mg protein） compared with that in the vehicle ＋ saline group （（4.3±0.62） pg/mg protein, P 〈0.01）. However, the increase of TNF-a level of pulmonary tissue was significantly reduced in the melatonin ＋ lipopolysaccharide group （（5.9±0.56） pg/mg protein, P 〈0.01）. Pulmonary IL-10 levels were elevated markedly in the vehicle ＋ lipopolysaccharide group in contrast to that in the vehicle ＋ saline group, whereas the elevation was augmented in the melatonin ＋ lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle ＋ lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin ＋ lipopolysaccharide group. Conclusion Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-κB activation.     

Effects of the TREM-1 pathway modulation during empyema in rats

Background The activation of triggering receptor expressed on myeloid cells-1 （TREM-1） in the presence of microbial components amplifies the inflammatory response. The aim of the present study was to investigate the effect of the modulation of the TREM-1 pathway during empyema in rats. Methods Adult male Wistar rats were subjected to empyema induced by intrapleural injection of Pseudomonas aeruginosa and Staphylococcus aureus. The animals were treated with LP17 （a synthetic TREM-1 inhibitor）, a control peptide, or a vehicle （normal saline）. Differential cell count, flow cytometry and histological examination were performed to evaluate local inflammatory alterations. Concentrations of tumor necrosis factor-a, interleukin-1B, and interleukin-6 in both pleural effusion and serum were measured by enzyme-linked immunosorbent assay. Results Although differential counts of each type of leukocytes in pleural effusion were not affected by LP17, a marked reduction in neutrophil numbers was seen in LP17 treated rats due to the reduction of both pleural effusion volume and total cell numbers. LP17 administration impaired concentration elevation in tumor necrosis factor-（], interleukin-1B, and interleukin-6 in both pleural effusion and serum. It was found that survival rate in LP17 treated rats was much higher than that in control rats. Conclusion The modulation of the TREM-1 pathway by the use of LP17 appears to be beneficial during empyema in rats in attenuating pleural and systemic inflammatory responses.     

Attenuation of Collagen Induced Arthritis by Centella asiatica Methanol Fraction via Modulation of Cytokines and Oxidative Stress

Objective To investigate the anti-inflammatory, antioxidant and anti-arthritic effects of Centella asiatica methanolfraction(CaM E) on collagen-induced arthritis(CIA), an animal model of rheumatoid arthritis. Methods Arthritis was induced in female wistar rats by immunization with porcine type II collagen. The CIA rats were treated orally with CaM E(50, 150, and 250 mg/kg/day) for 15 d(beginning on day 21 of the experimental period). The clinical, histological, biochemical, and immunological parameters were assessed. Results CaM E treatment(150 and 250 mg/kg) significantly attenuated the severity of CIA and reduced the synovial inflammation, cartilage erosion, and bone erosion as evident from both histological and radiographic data. The escalated plasma levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-12 alongwith nitric oxide in CIA rats decreased significantly on CaM E treatment. The serum levels of type-II collagen antibody were significantly lower in rats of CaM E(150 and 250 mg/kg) treated group than those in the arthritic group. Furthermore, by inhibiting the above mediators, CaM E also contributed towards the reversal of the disturbed antioxidant levels and peroxidative damage. Conclusion Our results clearly indicate that oral administration of CaM E suppresses joint inflammation, cytokine expression as well as antioxidant imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats.     

Matrix metalloproteinase-8 inhibitors mitigate sepsis-induced myocardial injury in rats

Background Sepsis-induced myocardial injury （SIMI） is caused by a variety of mechanisms. The aim of the study is to investigate the effects of metalloproteinase-8 （MMP-8） on SIMI and its mechanisms in rats. Methods Forty male Sprague Dawley rats were randomly divided into four groups： MMP-8 inhibitor （M81）, dexamethasone （DEX）, sepsis, and sham groups. The sepsis model was established by cecal ligation and puncture （CLP）. Rats in the M81 group immediately received an intraperitoneal injection of M81 （0.1 mg/kg） after CLP. Rats in the DEX group immediately received an intraperitoneal （IP） injection of DEX （2 mg/kg）. Rats in the sepsis and sham groups received intraperitoneal injections of normal saline. Rats were sacrificed 12 hours after CLP. Paraffin sections were stained with hematoxylin and eosin to observe the myocardium. The myocardial ultrastructure was observed with transmission electron microscopy. MMP-8, tumor necrosis factor-Q （TNF-a）, and interleukin-113 （IL-113） were detected by immunohistochemistry. The expression of MMP-8 was measured by Western blotting. TNF-a and IL-113 levels in serum and myocardial tissue were determined by enzyme-linked immunosorbent assay. Results Compared with the sham group, the myocardium in the sepsis group was seriously injured. MMP-8, TNF-α and IL-1β expression was higher in the sepsis group than in the sham group, Treatment with M81 or DEX, however, attenuated sepsis induced histopathological changes in the heart, and was associated with significant reductions in serum and myocardial levels of TNF-a and IL-113 （P 〈0.05）. M81 significantly inhibited MMP-8 expression in myocardial tissue （P 〈0.05）. In addition, treatment with DEX was not associated with a change in myocardial levels of MMP-8 （P 〉0.05）. Conclusion MMP-8 inhibitor attenuated myocardial injury in septic rats, which might be related to reduced expression of TNF-α and IL-1β.     

Reduction of pulmonary inflammatory response by erythropoietin in a rat model of endotoxaemia

Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.
Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.
Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.
Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.     

Endothelin receptor antagonist combined with a calcium channel blocker attenuate s renal injury in spontaneous hypertensive rats with diabetes

Objective To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long- acting calcium channel blocker, amlodipine, compared to the angiotensin- converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes.Methods Diabetic hypertensive rats (SHR- DM) were induced by streptozotozin injected in male SHR (7- week- old), and divided into an untreated and three treated groups: ① cilazapril treated group; ② bosentan+amlodipine treated group; and ③ amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin Ⅱ levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)- β1 were determined at the end of the 4th week.Results Mean arterial blood pressure significantly increased in SHR and SHR- DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotensin Ⅱ levels were found in the untreated SHR- DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR- DM abolished the overexpression of renal TGF- β1 by Western blot analysis and reduced the accumulation of collagen type Ⅳ, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. Conclusion Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF- β1 in diabetes with a hypertensive state.     

Protective effects of emodin and astragalus polysaccharides on chronic hepatic injury in rats

Background Chinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides （APS） in a rat model of chronic hepatic injury.
Methods Chronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachlodde （CCI4） twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin （40 mg·kg^-1·d^-1）, APS （200 mg·kg^-1·d^-1）, combination drug （emodin 40 mg·kg^-1·d^-1 combined with APS 200 mg·kg^-1·d^-1） and colchicine （0.1 mg·kg^-1·d^-1） in parallel by oral gavage （once a day for 12 weeks）. At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin （TBIL）, alanine transaminase （ALT）, aspartate transaminose （AST）, and albumin （ALB）. Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase （SOD） and malondialdehyde （MDA）. Histopathological changes were studied using optical microscopy.
Results Splenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury.
Conclusions Co-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may amelio     

Protective effect and mechanism of sodium tanshinone II A sulfonate on microcirculatory disturbance of small intestine in rats with sepsis

To explore the protective effect of sodium tanshinone ⅡA sulfonate(STS) on microcirculatory disturbance of small intestine in rats with sepsis,and the possible mechanism,a rat model of sepsis was induced by cecal ligation and puncture(CLP).Rats were randomly divided into 3 groups:sham operated group(S),sepsis group(CLP) and STS treatment group(STS).STS(1 mg/kg) was slowly injected through the right external jugular vein after CLP.The histopathologic changes in the intestinal tissue and changes of mesenteric microcirculation were observed.The levels of tumor necrosis factor-α(TNF-α) in the intestinal tissue were determined by using enzyme-linked immunoabsorbent assay(ELISA).The expression of intercellular adhesion molecule-1(ICAM-1) in the intestinal tissue was detected by using immunohistochemisty and Western blot,that of nuclear factor κB(NF-κB) and tissue factor(TF) by using Western blot,and the levels of NF-κB mRNA expression by using RT-PCR respectively.The microcirculatory disturbance of the intestine was aggravated after CLP.The injury of the intestinal tissues was obviously aggravated in CLP group as compared with S group.The expression levels of NF-κB p65,ICAM-1,TF and TNF-α were upregulaed after CLP(P<0.01).STS post-treatment could ameliorate the microcirculatory disturbance,attenuate the injury of the intestinal tissues induced by CLP,and decrease the levels of NF-κB,ICAM-1,TF and TNF-α(P<0.01).It is suggested that STS can ameliorate the microcirculatory disturbance of the small intestine in rats with sepsis,and the mechanism may be associated with the inhibition of inflammatory responses and amelioration of coagulation abnormality.     

Severity of sepsisis is correlated with the elevation of serum high-mobility group box 1 in rats

Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine,high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats.Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed.Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin Ⅰ, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney.Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.     

Effect of chronic intermittent hypoxia on theophylline metabolism in mouse liver

Background Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver,which is the most important organ for drug metabolism.This study aimed to investigate the effect of CIH...     

Proteomic analysis for detecting serum biomarkers related to smoking in humans

Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.

Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.

Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.

Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.

     

Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene

Background  Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.

Methods  We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.

Results  The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P <0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.

Conclusion  MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

     

Does vitamin D affect disease severity in patients with ankylosing spondylitis?

Background Vitamin D has been found to have a role in the function of the immune system. There have been a lot of studies investigating a relation between vitamin D and disease activity in ankylosing spondylitis (AS). However, there have not been any studies arranging AS in groups according to vitamin D levels and determining any differences among these patients in terms of disease activity, functional status, quality of life, and other clinical parameters. The aim of this study is to compare 25-hydroxy-vitamin D3 (25(OH)D3) levels in AS patients with those in normal healthy subjects and to determine the relationship between 25(OH)D3 levels and AS disease activity, functional status, and quality of life.

 

Methods  Ninety-nine consecutive patients and 42 healthy volunteers were included in this study. After a comparison between the patient group and the control group, the patient group was divided into normal, insufficient and deficient subgroups according to the plasma 25(OH)D3 levels for another comparison.

 

Results  The differences in the 25(OH)D3 level between the patient and the control groups were statistically insignificant. The number of AS patients whose 25(OH)D3 levels were classified as normal, insufficient, and deficient were 34, 29, and 36, respectively. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath AS Disease Activity Index (BASDAI) scores were higher in the low (including insufficient and deficient) 25(OH)D3 level subgroups (P <0.05). The Bath AS Functional Index (BASFI) and AS Quality of Life (ASQoL) scores were significantly different between the normal and the deficient subgroups (P <0.05).  Pain, BASDAI, ESR, and CRP were inversely correlated to the 25(OH)D3 levels (P <0.05).

 

Conclusions  The plasma 25(OH)D3 levels may decrease in AS patients and this may negatively affect disease activity, functional status and quality of life.

     

Cigarette smoking increases levels of retinol-binding protein-4 in healthy men with normal glucose tolerance

Background  Smoking is related with insulin resistance and type 2 diabetes mellitus. Retinol-binding protein-4 is a new adipocytokine associated with insulin resistance. We investigated the serum levels of a series of adipocytokines including retinol-binding protein-4 in smokers and non-smokers to explore the possible roles of adipocytokines on smoking induced insulin resistance.

Methods  A total of 136 healthy male subjects (92 smokers and 44 non-smokers) with normal glucose tolerance were enrolled in the study. Adipocytokines including retinol-binding protein-4, visfatin, leptin, resistin, adiponectin were measured for the comparison between the two groups. Serum lipid profile, glucose, true insulin and proinsulin levels were measured as well in both groups. Food intake spectrum was also investigated.

Results  Both groups had similar profile of food consumption; visfatin, leptin, resistin and adiponectin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, as well as blood pressure and body mass index, were similar in both groups. Triglycerides, retinol-binding protein-4 and homeostatic model assessment index for insulin resistance were higher in smoker group ((2.58±2.53) vs. (1.60±0.94) mmol/L, (26.05±8.50) vs. (21.83±8.40) µg/ml, and 2.25±2.08 vs. 1.58±1.15, respectively).

Conclusion  Smoking may have effect on insulin sensitivity, which is correlated with retinol-binding protein-4.

     

Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

Background  Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

Methods  Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n=6) pretreated with normal saline and the LPD group (n=6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

Results  All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6) mmHg vs. (284.3±11.3) mmHg at 6 hours after ALI, P <0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg∙ml^-1∙g^-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg∙ml^-1∙g^-1 protein).

Conclusion  These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

     

Immature CD4+ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats

Background  Allogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell (DC) is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4⁺ DCs on renal allografts in the rat model.

Methods  In this study, we induced CD4⁺ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4⁺ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo.

Results  Immature CD4⁺ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo.

Conclusions  Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4⁺ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.

     

创伤骨科患者创伤严重程度和血浆D二聚体水平的相关分析

Background  The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies. The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.

Methods  Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured. Plasma D-dimer levels in patients of these two groups were compared. The relationship between the plasma D-dimer level and the severity of the trauma was also studied.

Results  There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group. The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01). In the acute trauma group, the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).

Conclusions  Elevated plasma D-dimer is common in trauma patients. The D-dimer level and the number of fractures in the trauma patients are closely correlated. D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus, but also an indicator of the severity of trauma in acute trauma patients.