To explore the effect of ulinastatin on perioperative glycocalyx and lung function in patients undergoing mitral valve replacement surgery.
 Methods: Fourty patients, undergoing mitral valve replacement, were randomly allocated into a control group and an ulinastatin group, which were administrated 50 mL normal saline or 2×104 U/kg ulinastatin at the beginning of cardiopulmonary bypass (CPB), respectively. The radical artery blood was collected at 4 time points: After induction of anesthesia (T0), at 10 min after the start of CPB (T1), 1 h after the end of CPB (T2), and 8 h after operation. The concentration of syndecan-1 and TNF-α in blood was measured. Moreover, the blood gas analysis was preformed and the oxygen index (OI) and difference in alveolar arterial oxygen partial pressure (PA-aO2) were calculated at T0, T2, and T3.
 Results: There were no significant difference between the 2 groups in OI, PA-aO2, and the concentration of syndecan-1 and TNF-α at T0 (P>0.05). The concentration of syndecan-1 and TNF-α was significantly increased at T1 and T2 in the 2 groups, and reached peak at T2. Compared with the control group, the concentration of syndecan-1 and TNF-α was decreased in the ulinastatin group at T1, T2, and T3 (P<0.05). Compared with T0, OI was lower and PA-aO2 was higher at T2 and T3 in both groups, but the 2 indexes were improved in the ulinastatin group compared with those in the control group (P<0.05).
 Conclusion: Ulinastatin can improve the post-operative pulmonary ventilation function in patients with mitral valve replacement. The mechanism may be associated with the inhibition of TNF-α release and the reduction of glycocalyx shedding induced by ulinastatin.
Cardiopulmonary Bypass ; Glycocalyx ; drug effects ; Glycoproteins ; pharmacology ; Heart Valve Prosthesis Implantation ; Humans ; Lung ; drug effects ; Mitral Valve ; surgery ; Oxygen ; blood ; Syndecan-1 ; blood ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

This study was aimed to investigate the association of candidate gene polymorphisms and obesity or overweight in young Korean children. A total of 190 Korean preschool children (96 control, 48 overweight, and 46 obese children) were genotyped for the angiotensin converting enzyme (ACE) insertion (I)/deletion (D), angiotensin II type 2 receptor (AT2) C3123A, transforming growth factor (TGF)-β1 T869C, vascular endothelial growth factor (VEGF) T460C, and tumor necrosis factor (TNF)-α G308A polymorphisms. No differences were found among the groups with respect to age, sex, birth weight, blood pressure levels, and serum concentrations of glucose and total cholesterol. Obese children showed a higher incidence of ACE DD genotype and D allelic frequency compared to the controls (odds ratio [OR], 2.7, 95% confidence interval [CI], 1.01–7.21; OR, 2.5, 95% CI, 1.49–4.19; all P < 0.05). The frequency of TC genotype and C allele in the TGF-β1 T869C polymorphism (OR, 2.08, 95% CI, 1.01–4.27; OR, 1.93, 95% CI, 1.15–3.21) and that in the VEGF T460C polymorphism (OR, 2.5, 95% CI, 1.19–5.28; OR, 2.15, 95% CI, 1.26–3.68) was also higher in obese children than in control subjects (all P < 0.05). Overweight children exhibited a higher frequency of the A allele in the AT2 C3123A polymorphism compared to the controls (OR, 1.72, 95% CI, 1.03–2.88, P < 0.05). There were no differences in the TNF-α G308A polymorphism among the groups. The ACE I/D, AT2 C3123A, TGF-β1 T869C, and VEGF T460C polymorphisms can affect susceptibility to obesity or overweight in Korean children.
Alleles ; Angiogenic Proteins ; Birth Weight ; Blood Pressure ; Child ; Child, Preschool* ; Cholesterol ; Genetic Variation ; Genotype ; Glucose ; Humans ; Incidence ; Obesity ; Overweight ; Pediatric Obesity* ; Peptidyl-Dipeptidase A ; Receptor, Angiotensin, Type 2 ; Renin-Angiotensin System ; Transforming Growth Factors ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A

OBJECTIVETo investigate the relationship between atrial fibrillation (AF) and serum soluble CD163.

METHODSA total of 336 patients with heart valve disease were included in this study, including 167 with AF and 169 with sinus rhythm. The clinical data were compared between the two grops, and Logistic regression analysis was used to identify the risk factors associated with AF.

RESULTSThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor (TNF), interleukin-6 (IL - 6), high-sensitivity C-reactive protein (hs-CRP) and left atrial diameter (LAD) all differed significantly between the two groups (P<0.05). Serum soluble CD163 levels in AF patients were significantly higher than those in patients with sinus rhythm (P<0.05). Serum soluble CD163 was positively correlated with TNF (r=0.244, P=0.244), IL-6 (r=0.186, P=0.186), hs-CRP (r=0.183, P=0.183) and LAD (r=0.194, P=0.194) in patients with AF. Logistic regression analysis showed that LAD, IL-6, TNF, hs-CRP and CD163 were all associated with AF. ROC curve analysis showed that the area under curve of serum soluble CD163 was 0.861 in patients with AF (CI 95%: 0.820-0.901, P<0.01) with a sensitivity and a specificity of 80.8 and 76.9%, respectively.

CONCLUSIONSerum soluble CD163 level may be a risk factor for AF, and an increased soluble CD163 level may indicate active inflammation in AF patients.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Atrial Fibrillation ; blood ; C-Reactive Protein ; analysis ; Heart Atria ; pathology ; Humans ; Inflammation ; blood ; Interleukin-6 ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Receptors, Cell Surface ; blood ; Risk Factors ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVE: To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan. METHODS: A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA. RESULTS: RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0.167), but signifi cant diff erence was found between female RA patients and female controls (GG/TG/TT: 3/49/24 vs 8/28/48, P<0.001). No significant difference was found in the frequency of TNFRSF1B +676 T or G allele between RA patients and controls (P>0.05). RA patients showed a signifi cantly higher level of serum soluble tumor necrosis factor receptor II (sTNFR II) than controls [(7.83±2.61) ng/mL vs (4.32±1.67) ng/mL, P<0.001], but there was no diff erence among the three genotypes (P>0.05). No association was found between TNFRSF1B+676 gene polymorphism and RA clinical characteristics. CONCLUSION In Han Chinese population of Hunan province, TNFRSF1B+676 gene polymorphisms are not associated with the genetic risk of RA .
Alleles ; Arthritis, Rheumatoid ; ethnology ; genetics ; Asian Continental Ancestry Group ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Tumor Necrosis Factor, Type II ; blood ; genetics ; Risk Factors

Hypercoagulable state and thrombosis are major lethal causes of ulcerate colitis (UC). The aim of the present study is to explore the change and role of protein C (PC) system in UC thrombosis. 4% dextran sulfate sodium (DSS) was used to induce the UC model, and the body weight, the length of colon, and the weight of spleen were measured after intake of DSS as drinking water for 1 week. The macroscore and microscore were examined. The quantity of macrophage in colon smooth muscle was observed by immunofluorescence, and TNF-α and IL-6 levels in plasma were evaluated by ELISA. Intravital microscopy was applied to observe colonic mucosal microvascular circulation, activities of PC and protein S (PS) were determined by immunoturbidimetry, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) expressions were detected by immunohistochemistry. In vitro, TNF-α and IL-6 levels were tested in supernatant of macrophage separated from colonic tissue. After stimulation of mouse colonic mucosa microvascular endothelial cells by TNF-α and IL-6 respectively, the activities of PC, PS, activated protein C (APC) were evaluated, and the expressions of EPCR and TM were detected by Western blotting. The results revealed that compared with control, the DSS mouse showed weight loss (P < 0.05), a shortened colon (P < 0.05), and swelled spleen (P < 0.05), accompanied by higher histological score (P < 0.05), as well as infiltration of macrophages, elevated TNF-α and IL-6 levels in plasma (P < 0.01). The intravital microscopy results revealed that compared with control, DSS mice showed significantly enhanced adhesion of leukocytes and colonic mucosal microvascular endothelial cells (P < 0.01), meanwhile, decreased activity of PC and PS in plasma (P < 0.01 or P < 0.05), and down-regulated expression of EPCR (P < 0.01). The degree of inflammation was negatively correlated with the PC activity. In vitro, TNF-α and IL-6 levels were increased in the supernatant of macrophages from DSS mice colonic tissue (P < 0.05), and after incubation of TNF-α or IL-6 with colonic mucosal microvascular endothelial cells, the APC activity was decreased (P < 0.05 or P < 0.01), and expression of EPCR was down regulated (P < 0.05). These results suggest that PC system is inhibited in UC mouse. Presumably, the mechanism may be due to the secretion of cytokines from macrophages and subsequential influence on the function of endothelia cells. Furthermore, enhancement of PC system activity may serve as a new strategy for the treatment of UC.
Animals ; Blood Coagulation Factors ; metabolism ; Colitis, Ulcerative ; chemically induced ; physiopathology ; Dextran Sulfate ; Immunohistochemistry ; Inflammation ; Interleukin-6 ; blood ; Intestinal Mucosa ; pathology ; Macrophages ; cytology ; Mice ; Protein C ; metabolism ; Receptors, Cell Surface ; metabolism ; Spleen ; pathology ; Tumor Necrosis Factor-alpha ; blood

To study the protective effect of Danqi Piantan capsule ( DPC) and its antelope horn substitution (DPCAS) on the cerebral ischemia, in order to preliminary study the possibility of replacing antelope horn with artificial bezoar. In this study, the left middle cerebral artery occlusion (MCAO) was adopted. Totally 150 SD rats were randomly divided into 5 groups: the sham operation group, the model group, the Danqi Piantan capsule (DPC) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn (DPCRA) group (0.246 g x kg(-1) x d(-1)), the Danqi Piantan capsule without antelope horn and with double artificial bezoar (DPCDB) group (0.246 g x kg(-1) x d(-1)). The MCAO model was prepared 1 h later after the administration on the 5th day. At 24 h after the operation, the inner canthus blood was collected to determine the serum superoxide dismutase (SOD) activity and the endothelin (ET) content. At 72 h after the operation, the cerebral infarct size and the cerebral index were determined by TTC-staining. The fluorescent quantitative PCR method was used to detect brain Bcl-2, Caspase-3, IL-1β, P-selectin, E-selectin, ICAM-1 mRNA expressions. The mmunohistochemical method was used to detect ICAM-1, IL-1β, TNF-α, IL-6 expressions in ischemic penumbra. According to the results, compared with the model group, DPCDB and DPC groups showed almost consistent results, indicating both of the two group can significantly improved cerebral infarction index and cerebral index (P < 0.05), increase the serum SOD activity (P < 0.05), decrease the serum ET level and Caspase-3 expression, IL-1β, P-selectin, E-selectin, ICAM-1 mRNA expressions in brain tissues (P < 0.05) and expressions of ICAM-1, IL-1,6, TNF-α, IL-6 positive cells in ischemic penumbra (P < 0.05) and increase the Bcl-2 expression (P < 0.05). The DPCRA group showed much lower impacts on indexes than DPCDB and DPC groups. This suggests that DPCDB and DPC reveal similar efficacies and antelope horn in Danqi Piantan capsule can be substitutes by artificial bezoar.
Animals ; Antelopes ; Bile ; chemistry ; Biological Factors ; administration & dosage ; chemical synthesis ; chemistry ; Brain ; drug effects ; metabolism ; Caspase 3 ; genetics ; metabolism ; Drug Compounding ; Horns ; chemistry ; Humans ; Infarction, Middle Cerebral Artery ; drug therapy ; genetics ; metabolism ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Interleukin-1beta ; genetics ; metabolism ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; genetics ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo explore the effects of hydrogen-rich saline (HS) on liver of severely scalded rats with delayed resuscitation.

METHODSTwenty-four SD rats were inflicted with 40% TBSA full-thickness scald using a temperature-controlled scalding apparatus. The injured rats were divided into lactated Ringer's solution (RS) and HS groups according to the random number table, with 12 rats in each group. Rats in groups RS and HS were respectively resuscitated with an intraperitoneal injection of 4 mL × kg⁻¹ × %TBSA⁻¹ of RS or HS (self-prepared, with concentration of hydrogen 0.6 mmol/L) 6 hours after injury up to 48 hours after scald. The infusion volume of the second 24 hours after injury was a half of that of the first 24 hours. At post scald hour (PSH) 6 (before resuscitation), 12, 24, and 48, blood was collected from the heart of 3 rats in each group, and then the rats were sacrificed for harvesting liver tissue. The pathological change in liver tissue was observed with HE staining. The number of hepatic neutrophils was counted with a hematocytometer. Serum levels of AST and ALT were determined with full-automatic biochemical analyzer. Contents of TNF-α, IL-1β, IL-6, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver tissue were determined with ELISA. Absorbance value of malondialdehyde (MDA) in liver tissue was detected and quantified with spectrophotometer. Data were processed with analysis of variance of repeated measurement and LSD-t test.

RESULTSAt PSH 48, moderate infiltration of inflammatory cells and hepatic hyperemia were observed in rats of group HS as compared with group RS. At PSH 12, 24, and 48, the number of neutrophils in group HS was respectively (25.3 ± 1.8) × 10⁵, (19.6 ± 0.6) × 10⁵, and (14.1 ± 3.2) × 10⁵ cells per mililitre, and they were significantly lower than those in group RS \[(31.9 ± 2.0) × 10⁵, (30.9 ± 2.2) × 10⁵, and (23.8 ± 3.0) × 10⁵ cells per mililitre, with t values respectively 5.6, 7.6, and 8.7, P values below 0.05\]. At PSH 6 and 12, the serum levels of AST and ALT and the levels of TNF-α, IL-1β, and IL-6 in liver tissue were close between the two groups (with t values respectively 0.3-3.9 and 0.9-3.8, P values above 0.05). At PSH 24 and 48, the serum levels of AST and ALT in group HS were respectively (308 ± 24) and (210 ± 15) U/L and (93 ± 7) and (70 ± 5) U/L, which were significantly lower than those in group RS \[(541 ± 39) and (505 ± 18) U/L, with t values respectively 17.5 and 16.7, P values below 0.05; (156 ± 9) and (166 ± 21) U/L, with t values respectively 30.3 and 6.9, P values below 0.05\]. At PSH 24 and 48, the levels of TNF-α, IL-1β, and IL-6 in liver tissue in group HS were respectively (20.7 ± 1.6) and (13.7 ± 1.5) pg/mg, (7.7 ± 1.5) and (6.3 ± 1.2) pg/mg, and (8.7 ± 1.2) and (6.0 ± 2.0) pg/mg, which were significantly lower than those in group RS \[(32.7 ± 5.0) and (25.7 ± 4.0) pg/mg, with t values respectively 5.2 and 5.7, P values below 0.05; (16.3 ± 2.5) and (12.0 ± 2.7) pg/mg, with t values both as 4.7, P values below 0.05; (14.7 ± 2.1) and (13.3 ± 1.5) pg/mg, with t values respectively 10.4 and 4.4, P values below 0.05\]. The level of MDA at PSH 6 and levels of 8-OHdG at PSH 6 and 12 in liver tissue were close between the two groups (with t values respectively 0.1, 0.7, and 4.3, P values above 0.05). In group HS, the levels of MDA in liver tissue at PSH 12, 24, and 48 were respectively (15.3 ± 1.5), (8.7 ± 1.2), and (6.7 ± 1.5) mmol/mg, and the levels of hepatic 8-OHdG at PSH 24 and 48 were respectively (124 ± 12) and (79 ± 10) pg/mg, which were significantly lower than those in group RS \[(27.3 ± 4.7), (20.3 ± 1.5), and (14.0 ± 1.0) mmol/mg, with t values respectively 5.2, 5.7, and 5.1, P values below 0.05; (191 ± 10) and (136 ± 15) pg/mg, with t values respectively 8.0 and 8.1, P values below 0.05\].

CONCLUSIONSResuscitation with HS could protect liver of severely scalded rats with delayed resuscitation possibly by reducing infiltration of neutrophils, thus lowering the content of inflammatory cytokines, and effectively alleviating oxidative stress.

Animals ; Burns ; metabolism ; physiopathology ; Deoxyguanosine ; analogs & derivatives ; blood ; Hydrogen ; pharmacology ; Interleukin-6 ; Liver ; drug effects ; metabolism ; physiopathology ; Male ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Resuscitation ; Sodium Chloride ; pharmacology ; Soft Tissue Injuries ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance is a strong risk factor for type 2 diabetes mellitus. The aim of this study was to investigate the effect of myricetin on adiposity, insulin resistance, and inflammatory markers in mice with diet-induced insulin resistance. MATERIALS/METHODS: Five-week-old male C57BL/6J mice were fed a basal diet, a high-fat, high-sucrose (HFHS) diet, or the HFHS diet containing 0.06% myricetin or 0.12% myricetin for 12 weeks after a 1-week adaptation, and body weight and food intake were monitored. After sacrifice, serum lipid profiles, glucose, insulin, adipocyte-derived hormones, and proinflammatory cytokines were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. RESULTS: Myricetin given at 0.12% of the total diet significantly reduced body weight, weight gain, and epidydimal white adipose tissue weight, and improved hypertriglyceridemia and hypercholesterolemia without a significant influence on food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, decreased significantly by 0.12% myricetin supplementation in mice fed the HFHS diet. Myricetin given at 0.12% of the total diet significantly reduced serum levels of leptin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in mice fed the HFHS diet. CONCLUSIONS: These findings suggest that myricetin may have a protective effect against diet-induced obesity and insulin resistance in mice fed HFHS diet, and that alleviation of insulin resistance could partly occur by improving obesity and reducing serum proinflammatory cytokine levels.
Adipose Tissue, White ; Adiposity ; Animals ; Blood Glucose ; Body Weight ; Cytokines ; Diabetes Mellitus, Type 2 ; Diet* ; Eating ; Glucose ; Homeostasis ; Humans ; Hypercholesterolemia ; Hypertriglyceridemia ; Inflammation ; Insulin ; Insulin Resistance* ; Interleukin-6 ; Leptin ; Male ; Mice* ; Obesity ; Risk Factors ; Tumor Necrosis Factor-alpha ; Weight Gain

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Adult ; Alkaline Phosphatase/blood ; Arthritis, Rheumatoid/blood/diagnosis/*drug therapy ; Biological Markers/blood ; Bone Morphogenetic Proteins/blood ; Bone Remodeling/*drug effects ; Collagen Type I/blood ; Female ; Genetic Markers ; Homeostasis ; Humans ; Immunoglobulin G/*administration & dosage ; Immunosuppressive Agents/*administration & dosage ; Inflammation Mediators/blood ; Male ; Middle Aged ; Peptides/blood ; Receptors, Tumor Necrosis Factor/*administration & dosage ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

With excess nutrition, the burden of obesity is a growing problem worldwide. The imbalance between energy intake and expenditure leads to variable disorders as all major risk factors for cardiovascular disease. There are many hypothetical mechanisms to explain obesity-associated hypertension. Activation of the RAAS is a key contributing factor in obesity. Particularly, the RAAS in adipose tissue plays a crucial role in adipose tissue dysfunction and obesity-induced inflammation. The phenotypic changes of adipocytes occur into hypertrophy and an inflammatory response in an autocrine and paracrine manner to impair adipocyte function, including insulin signaling pathway. Adipose tissue produce and secretes several molecules such as leptin, resistin, adiponectin, and visfatin, as well as cytokines such as TNF-alpha, IL-6, MCP-1, and IL-1. These adipokines are stimulated via the intracellular signaling pathways that regulate inflammation of adipose tissue. Inflammation and oxidative stress in adipose tissue are important to interact with the microvascular endothelium in the mechanisms of obesity-associated hypertension. Increased microvascular resistance raises blood pressure. Therefore, a regulatory link between microvascular and perivascular adipose tissue inflammation and adipokine synthesis are provided to explain the mechanism of obesity-associated hypertension.
Adipocytes ; Adipokines ; Adiponectin ; Adipose Tissue ; Blood Pressure ; Cardiovascular Diseases ; Cytokines ; Endothelium ; Energy Intake ; Health Expenditures ; Hypertension* ; Hypertrophy ; Inflammation ; Insulin ; Insulin Resistance ; Interleukin-1 ; Interleukin-6 ; Leptin ; Nicotinamide Phosphoribosyltransferase ; Obesity* ; Oxidative Stress ; Resistin ; Risk Factors ; Tumor Necrosis Factor-alpha