ObjectiveTo determine whether the inhibition of caveolin-1 tyrosine residues 14 (Cav-1-Y14) phosphorylation with protein tyrosine kinase inhibitors (PP2) will upregulate heme oxygenase-1 (HO-1) activity to protect against ventilation induced lung injury in vivo of an animal model.Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into nine groups (eachn = 6). Group A served as normal control group, in which rats did not receive ventilation but tracheotomy. Groups B1 and B2 received lung protective ventilation respectively for 1 hour or 2 hours. Groups C1 and C2 received high tidal volume (40 mL/kg) ventilation for 1 hour or 2 hours, respectively. The group D1 or D2 also received high tidal volume ventilation for 1 hour or 2 hour respectively, but they were given PP2 1 hour before high tidal volume ventilation. The groups E1 and E2 also received high tidal volume ventilation respectively for 1 hour or 2 hours, but tyrosine kinase inhibitor PP2 and HO-1 inhibitor zinc protoporphyrinⅨ(ZnPPⅨ) were given to animals 18 hours before high tidal volume ventilation. All the animals were sacrificed after ventilation, and the specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Then the changes in pathology of lung tissue was observed, and diffuse alveolar damage scores (DAD) were calculated, myeloperoxidase (MPO) activity was measured by colorimetric analysis, lung wet/dry ratio (W/D) was estimated. The expressions of phosphorylated caveolin-1 (P-Cav-1-Y14), caveolin-1 (Cav-1) and HO-1 were determined by Western Blot. The expressions of high mobility group B1 (HMGB1) and advanced glycation end product receptor (RAGE) in lung tissues were assayed with immunohistochemistry staining. The levels of tumor necrosis factor-α(TNF-α) in BALF were measured by enzyme linked immunosorbent assay (ELISA).Results There was no significant difference in all the parameters between group A and groups B. Compared with group B1, DAD score, W/D ratio, the activity of MPO and the concentration of TNF-α in BALF in group C1 were significantly increased [DAD score:7.97±0.59 vs. 0.55±0.13, W/D ratio: 5.70±1.61 vs. 5.04±0.63, MPO (U/g): 1.82±0.14 vs. 0.77±0.26, TNF-α(ng/L): 370.10±29.61 vs. 54.38±8.18, allP< 0.05], and the injury in ventilation 2 hours group was more serious than that in ventilation 1 hour group. Compared with groups C, all the parameters in groups D were significantly decreased. The parameters in groups E were significantly higher than those in groups A, B, and D, but no significant difference was found as compared with groups C. Compared with groups B, the protein expressions of Cav-1 and P-Cav-1-Y14 (gray value) in groups C were significantly increased (1 hour: 1.49±0.02 vs. 1.26±0.13, 1.34±0.02 vs. 0.87±0.04;2 hours: 1.58±0.02 vs. 1.27±0.27, 1.31±0.01 vs. 0.95±0.02, allP< 0.05), and the expression of HO-1 protein (gray value) was significantly decreased (1 hour: 0.59±0.02 vs. 1.10±0.01, 2 hours: 0.49±0.01 vs. 1.20±0.02, both P< 0.05). No significant difference in Cav-1 protein expression between groups D as well as groups E and groups C. The protein expression of P-Cav-1-Y14 in groups D and E was significantly lower than that in groups C. The protein expression of HO-1 in groups D was significantly higher than that in groups C, but the phenomenon was not found in groups E as compared with groups C. Compared with group A, the positive expression of HMGB1 and RAGE in lung tissue in groups C and E was significantly increased, but no significant difference was found between groups B as well as groups D and group A.Conclusion Cav-1-Y14 phosphorylation is the key factor for ventilator induced lung injury, which can not only lead to a decrease in vascular barrier function, but also inhibit the activity of HO-1 enzyme, thus further aggravates inflammatory injury of the lung as induced by mechanical ventilation.

Objective To investigate whether the inhibition of caveolin-1 (Cav-1) phosphorylation will regulate effectively nuclear factor-erythroid 2-related factor (Nrf2) signal pathway and downstream effector molecules and protest against ventilation induced lung injury (VILI) in an animal model in vivo. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n = 10): sham group in which rats did not receive ventilation but received tracheotomy; lung protective ventilation (PV) for 1 hour or 2 hours group; mechanical ventilation (MV) at high volume tidal (VT, 40 mL/kg) for 1 hour or 2 hours group; protein tyrosine kinase inhibitor PP2 or rosiglitazone (Rsg) pretreatment + high VT ventilation for 1 hour or 2 hours groups. The two pretreatment groups were given intraperitoneal injection PP2 15 mg/kg or intragastric administration of Rsg 5 mg/kg 1 hour before ventilation respectively. The rats were sacrificed after model reproduction, and bronchoalveolar lavage fluid (BALF) was collected. Pulmonary vascular permeability was measured by Evans blue (EB). The levels of tumor necrosis factor-α (TNF-α), activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) in BALF were determined by enzyme linked immunosorbent assay (ELISA). Then the lung tissues were collected, the lung wet/dry ratio (W/D) was calculated, the changes in pathology was observed with light microscope, and myeloperoxidase (MPO) activity was determined by colorimetric analysis. Nrf2 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of Cav-1 tyrosine residues 14 phosphorylation (pCav-1-Y14), Cav-1, peroxisome proliferators-activated receptor γ (PPARγ) and claudin-5 as well as Nrf2 in cytoplasm and nucleus were determined by Western Blot. The positive expressions of PPARγ and claudin-5 in lung tissues were assayed with immunohistochemistry staining. Results There were no obvious pathological changes in the lung tissue in sham group and PV groups, and there were no significant differences in all the parameters between the two groups either. However, the injury in lung tissue was severe in the high VT groups in which W/D ratio, EB contents, MPO activity, and TNF-α, AP-1, IL-8, NF-κB levels in BALF as well as the protein expressions of Cav-1 and pCav-1-Y14 were significantly higher than those of sham group and PV groups, and the protein expressions of PPARγ and claudin-5 were significant lower than those of sham group and PV groups with a dose-dependent manner; but Nrf2 expressions in cytoplasm and nucleus did not show a statistical increase. After pretreatment of PP2 or Rsg, W/D ratio, MPO activity, EB contents, TNF-α, AP-1, IL-8, and NF-κB in BALF were significantly decreased as compared with those of high VT group, and RT-PCR showed significant up-regulation of Nrf2 mRNA in lung tissues too. Moreover, there was a statistically significant increase in expressed Nrf2 proteins in nucleus in PP2 or Rsg groups as compared with those of high VT groups [Nrf2 in nucleus (gray value): 0.61±0.06, 0.56±0.06 vs. 0.31±0.02 at 1 hour, 0.38±0.06, 0.43±0.07 vs. 0.22±0.03 at 2 hours; all P < 0.05], but no significant difference was found in the expression of Nrf2 protein in the cytoplasm among all groups. The protein expressions of pCav-1-Y14 in PP2 pretreatment groups were significantly lower than those of high VT groups (gray value: 0.89±0.04 vs. 1.48±0.02 at 1 hour, 0.86±0.02 vs. 1.31±0.01 at 2 hours; both P < 0.05); but expressed PPARγ proteins and expressed claudin-5 proteins in PP2 or Rsg pretreatment groups were significantly higher than those of high VT groups [PPARγ (gray value): 0.34±0.07, 0.42±0.13 vs. 0.17±0.07 at 1 hour, 0.38±0.09, 0.33±0.07 vs. 0.16±0.03 at 2 hours; claudin-5 (gray value): 0.33±0.05, 0.38±0.07 vs. 0.14±0.03 at 1 hour; 0.30±0.06, 0.31±0.04 vs. 0.17±0.04 at 2 hours; all P < 0.05]. Conclusions The inhibition of Cav-1-Y14 phosphorylation can increase the expression of Nrf2 in the nucleus, then result in an increase in the protein expressions of PPARγ and claudin-5 of its effector molecules. This effect can reduce the inflammation and capillary permeability of lung tissue in the model of VILI.

OBJECTIVETo analyze the efficacy of adefovir dipivoxil combined with bicyclol in treatment of HBeAg-positive chronic viral hepatitis B (CHB).

METHODSA total of 91 patients with CHB were randomized into experimental group and control group to be treated. The patients in experimental group (46 samples) received adefovir dipivoxil orally 10 mg daily and bicyclol orally 150 mg daily for 48 weeks and those in control group (45 samples) received adefovir dipivoxil orally 10 mg daily alone for 48 weeks. The serum aminotransferace (ALT/ AST), HBV-DNA, HBeAg/antiHBe were observed before and after treatment.

RESULTSCompared with pretreatment, the serum aminotransferace were all decreased obviously in two groups, the experimental group is better (P < 0.05). HBVDNA negative conversion rate was significantly higher in experimental group than in the control group (47.8% vs. 31.1%, P < 0.05). There were nostatistically differrence between the two groups in the portion of HBeAg loss rate and HBeAg seroconversion rate. There were no obvious adverse reaction in the study.

CONCLUSIONAdefovir dipivoxil combined with bicyclol is efective in the treatment of chronic hepatitis B.

Adenine ; administration & dosage ; analogs & derivatives ; Adolescent ; Adult ; Aged ; Biphenyl Compounds ; administration & dosage ; Drug Therapy, Combination ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; Treatment Outcome ; Young Adult

Objective To observe the efficacy and safety of in-center nocturnal hemodialysis (INHD) in uremic patients. Methods Thirty-two maintenence hemodialysis (MHD) patients received INHD (3 times per week and 7.5 hours each session) for 6 months.Before and 1, 3 and 6 months after entering INHD, blood routine, hepatic and renal function,serum electrolyte, lipids, parathyroid hormone and β2-microglobulin(β2-MG) were assayed, Kt/V and URR were calculated. Blood pressure of each dialysis session 2 months before and 6 months after INHD was recorded. Cardiac ultrasound and SF-36 questionnaire before and after INHD were performed. Use of drugs was recorded. Results Compared with 2 months before INHD, predialysis BP decreased [(130.3/86.0) vs (139.3/88.6) mm Hg, P＜0.01], while post-dialysis BP raised significantly [(121.1/80.5) vs (115.0/77.8) mm Hg, P＜0.01] 6 months after INHD.Intradialysis hypertension (9.8%vs 24.0%) and hypotension (7.3% vs 14.9%) both reduced (all P＜0.01). Serum phosphorus [(1.37±0.27) vs (2.08±0.49) mmol/L, P＜0.01] and iPTH [(355.4±139.6) vs (632.3±750.0) ng/L, P＜0.01] decreased, while calcium increased [(2.64±0.25) vs (2.28±0.37) mmol/L, P＜0.01], HDL[(1.27±0.29) vs (0.75±0.08) mmol/L] increased, LDL [(2.04±0.52) vs (2.75±0.75) mmol/L] decreased (all P＜0.05). URR [(79.7±0.1)% vs (64.7±4.7)%] and Kt/V (1.40±0.44 vs 0.89±0.25, P＜0.01) increased. Serum β2-MG decreased [(17.3±3.9) vs (24.6±5.9) mg/L, P＜0.01]. LVMI decreased [(99.8±29.0) vs (114.8±72.7), P＜0.05]. Physical functioning, role-physical and role-emotional of SF-36 increased (all P＜0.01). The types of antihypertension drug, dosage of EPO, Vitamin D3 and phosphorus binder decreased (all P＜0.01).Patients of drug withdrawal increased (P＜0.05). Conclusion The hypertension, anemia,calcium-phosphorus metabolism, lipid disorder, cardiac malfunction and the quality of life are improved in INHD patients.

Humans ; Liver Cirrhosis ; diagnosis ; mortality ; physiopathology ; Logistic Models ; Prognosis

Objective To analyze the left ventricular (LV) diastolic function parameters of patients with sick sinus syndrome (SSS) and DDD pacemaker implantation during atrioventricular conduction (AVC) and right ventricular apex pacing(RVAP)mode.Methods Forty-six consecutive patients with SSS who had undergone DDD pacemaker implantation were studied.Fifty volunteers were selected as control group.Changing from AVC to RVAP mode,the acute effect on echocardiographic left ventricular diastolic function parameters,including mitral inflow PW parameters,mitral annulus tissue Doppler imaging parameters,left atrial volume index,and LV∕apical∕basal untwist parameters were measured.And all subjects were classified into normal diastolic function or three degrees of LV diastolic dysfunction.Results Compared with control group,both AVC and RVAP mode of patients with DDD pacemaker implantation resulted in the worsening of LV diastolic function as shown by(1) prolonged deceleration time of E wave, decreased descending slope of E wave,as well as decreased early diastolic velocity at the septal mitral annulus,(2) the decrease of LV∕basal∕apical untwist velocity,(3) the increase in the degree of diastolic dysfunction.Conclusions In patients with DDD pacemaker implantation,both AVC and RVAP mode are associated with the deterioration of LV diastolic function,which is particularly obvious in RVAP mode.

OBJECTIVETo optimize the formulation of immediate release tablet.

METHODThe immediate release tablet was prepared by using dry granules. The preparation was optimized by using orthogonal design which took the flow property of granules, the hardness, the disintegrating time and the dissolution rate of the tablet as indices.

RESULTThe optimized formulation contained 40% microcrystalline cellulose, 10% sodium carboxymethyl starch and 15% dextrin. The hardness disintegrating time and T50 of the tablet were 4.5 kg, 3 min, 5 min respectively.

CONCLUSIONIt is successful to prepare on immediate release tablet using the optimized formula above.

Cellulose ; Dextrins ; Drug Combinations ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry ; Solubility ; Tablets

Objective To compare the left ventricular function parameters of patients with sick sinus syndrome ( SSS ) and DDD pacemaker implantation during atrioventricular conduction ( AVC ) and right ventricular apex pacing ( RVAP ) mode . Methods Forty‐six consecutive patients with SSS who had undergone DDD pacemaker implantation were studied . Fifty volunteers were included as control group . Changing from AVC to RVAP mode ,the acute effect on echocardiographic parameters ,including LVEF , parameters of aortic/pulmonary artery pulse wave Doppler ,and parameters of left ventricular twist by speckle tracking imaging were measured respectively . Pacemaker implantation duration and cumulative ventricular pacing proportion ( Cum% VP) were recorded . The relationships of pacemaker parameter and above left ventricular function parameters were analyzed . Results Compared with control group ,values of peak rotation in LV apex and LV twist were significantly lower during AVC and RVAP mode . The value of peak rotation in LV base showed no significant difference between three groups .Apical‐basal rotation delay during RVAP was significantly longer than those during AVC and in control group respectively ( P <0 .05) . LVEF during RVAP decreased statistically ( P< 0 .05 ) ,but showed no difference during AVC , compared with the control group . The peak LV twist related positively with LVEF ,and negatively with Cum% VP . Conclusions RVA pacing decreases left ventricular function , which is independent of asynchrony contraction patterns caused by pacing . LVEF ,apical rotation and LV twist are more sensitive to demonstrate the LV dysfunction in patients with pacemaker implantation . LV twist related negatively with Cum% VP .

OBJECTIVETo study the suitable oxygen concentration in hypoxic preconditioning.

METHODSShort-term and long-term intermittent hypoxia modes were designed and the effects of various oxygen concentrations on body weight, blood oxygen saturation, swimming capability were analyzed.

RESULTSThe rate of body weight gain in rat model decreased gradually when exposed to hypoxia environment for long time. When the concentration of oxygen changed from 15% to 8%, accompanied with the decreasing of oxygen concentration, a platform was observed in blood oxygen saturation of rat model after hypoxic preconditioning training. Rat swimming capability improved significantly. After trained in 10% hypoxia environment, the swimming capability of kunming mice improved obviously.

CONCLUSIONProper level of hypoxic preconditioning training could improve hypoxia tolerance and enhance the rat sport capability significantly. 15%-10% oxygen concentration range could be regarded as a helpful effective area for hypoxic preconditioning, 10% oxygen concentration might be the eligible concentration for hypoxic preconditioning training.

Adaptation, Physiological ; physiology ; Animals ; Body Weight ; Hypoxia ; physiopathology ; Ischemic Preconditioning ; Male ; Oxygen ; analysis ; metabolism ; Physical Endurance ; physiology ; Rats ; Rats, Wistar

OBJECTIVETo observe the differences in the cytokine levels in the serum and ascites caused by Gram-positive or Gram-negative bacterial infection in patients with multiple organ dysfunction syndrome (MODS).

METHODSThe cytokines in the serum and ascites of the patients were examined by enzyme-linked immunosorbent assay in 27 patients with MODS due to Gram-positive (n=13) or Gram-negative (n=14) bacterial infection at day 1.

RESULTSThe levels of LPS and TNF-a were higher in the patients with Gram-negative bacterial infection than in patients with Gram-positive infection (P<0.05), but the levels of IL-6, IL-8 and IL-10 remained comparable between the two groups (P>0.05).

CONCLUSIONTesting of LPS and TNF-a in the serum and ascites of patients with MODS caused by Gram-positive or -negative bacterial infection may help to identify the pathogens for peritonitis resulting in MODS.

Ascites ; metabolism ; Gram-Negative Bacterial Infections ; blood ; metabolism ; Gram-Positive Bacterial Infections ; blood ; metabolism ; Humans ; Interleukin-10 ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Interleukin-8 ; blood ; metabolism ; Multiple Organ Failure ; blood ; metabolism ; microbiology ; Serum ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; metabolism