Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) pathway in the protective effect of remifentanil or ischemic preconditioning (IPC) against hepatic ischemia-reperfusion (I/R) injury in rats.Methods One hundred and forty-four male SD rats,weighing 200-250 g,were randomly assigned into 6 group ( n =24 each):sham operation group (group S),I/R group,remifentanil group (group R),IPC group,SB203580 (a specific p38MAPK inhibitor) + remifentanil group (group SB + R),and SB + IPC group.The animals were anesthetized with intraperitoneal 20％ urethane 1 mg/kg.Partial liver ischemia was produced by clamping the hepatic pedicle supplying left lobe and middle lobe for 30 min,followed by 120 min reperfusion.In group R,remifentanil was infused intravenously at 2μg· kg- 1 · min- 1 starting from 30 min before ischemia until the end of reperfusion.In IPC group,the rats were subjected to 3 episodes of 5 min ischemia at 5 min intervals before I/R.SB203580 0.2 mg/kg was injected intravenously at 5 min before remifentanil infusion or IPC in groups SB + R and SB + IPC,and the equal volume of normal saline was given in the other groups.Six rats in each group were selected at 30,60,90 and 120 min of reperfusion and venous blood samples were taken from inferior vena cava for measurement of serum ALT and AST activities and concentrations of TNF-a and 1L-1β.The rats were then sacrificed and liver tissues were taken for microscopic examination and determination of phosphor-p38MAPK expression by Western blot.Results Compared with group S,serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased at each time point (P ＜ 0.05) and pathological injury was aggravated in group I/R.Compared with group I/R,serum AST and ALT activities and serum levels of TNF-a and IL-lβ were significantly decreased and phosphor-p38MAPK expression was up-regulated at 90 min of reperfusion in groups R and IPC ( P ＜ 0.05).The serum AST and ALT activities and serum levels of TNF-α and IL-1β were significantly increased,phosphor-p38MAPK expression was down-regulated at 90 min of reperfusion ( P ＜ 0.05),and pathological injury was aggravated in group SB + R compared with group R,and in group SB + IPC compared with group IPC.Conclusion Activation of p38MAPK pathway and inhibition of inflammatory response may be involved in the mechanism by which remifentanil or IPC reduces the hepatic I/R injury in rats.

Objective To investigate the protective effect of propotol against hepatic ischemiareperfusion injury in rats on mitochondrial permeability transition pore (MPTP) and the mechanism of GSK-3β.Methods Thirty SD rats were randomly assigned into five groups (n =6):sham operation group (S group),ischemia reperfusion group (I/R group),CsA pretreatment group (C group),propofol pretreatment group (P group),and propofol plus atractyloside pretreatment group (A + P group).Nauta liver ischemia-reperfusion rat model was used.Liver lobes were subjected to warm ischemia for 60min and then reperfusion for 120 min.In P group,propofol [12 mg/(kg · h)] was administered in the femoral vein for 30 min before ischemia until the end of reperfusion.In C group,CsA (2 mg/kg) was administered in the femoral vein for 20min before ischemia.In A + P group,20 μmol/kg of atractyloside was given through the femoral vein 10min before the injection of propofol.Rats were sacrificed at the end of reperfusion,and venous blood and hepatic tissue specimens from the same part of ischemia were obtained from different groups.Results Compared with S group,the AST and ALT levels were increased significantly,mitochondrial swelling were increased and mitochondrial membrane potential were decreased significantly in I/R group and A + P group.Casepase-3 were increased significantly and p-GSK3β Ser9 were decreased significantly in I/R group and A + P group.Compared with I/R group,the content of AST and ALT were decreased significantly,mitochondrial swelling were decreased and mitochondrial membrane potential were increased significantly,casepase-3 release were decreased significantly and p-GSK3β Ser9 were increased significantly in P group and C group.GSK-3β in each group displayed no significant difference.Conclusions Propofol can significantly reduce hepatic ischemia-reperfusion injury.The protective effect of propofol may be achieved via the inhibition of GSK-3β activation,increased p-GSK-3β Ser9 level,suppressing MPTP opening and decreasing hepatocytes apoptosis.

The study is to prepare taste masking and enteric-coated clarithromycin granules by melting and fluid bed coating technology. Clarithromycin and matrix materials were melted at a certain temperature, and then made into particles by fluidized bed coating. X-ray powder diffraction and scanning electron microscopy were used to identify the crystal and morphology of drug loading granules. In vitro dissolution method was used for the observation of the drug release behavior. The results showed that the drug particles size range was 0.2 - 0.6 mm; the crystal form of clarithromycin in the granule did not change; enteric-coated granules accumulated release in 0.1 mol L(-1) hydrochloric acid in 2 h was less than 10%, while in pH 6.8 phosphate buffer in 1 h was more than 80%. The taste masking and enteric-coated clarithromycin granules not only have good taste masking effect, but also have a good release behavior. It is expected to have better clinical application.

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.

PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a solvothermal reaction and characterized with transmission electron microscopy (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and photothermal destruction of cancer cells were evaluated. Then the doxorubicin loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity and combined chemotherapy/photothermal therapy (PTT) effect were investigated. Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH-dependent. The drug loading capacity in water was 21%. The results of MTT indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug loading capacity can be used for chemotherapy and photothermal therapy. The synergetic anti-tumor activity indicates the potential for the combined application of chemotherapy and photothermal therapy in cancer treatment.
Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Survival ; drug effects ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Carriers ; Ferrosoferric Oxide ; chemistry ; Humans ; Hyperthermia, Induced ; MCF-7 Cells ; Magnetite Nanoparticles ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry

Objective To investigate the protective effect of propofol pretreatment against hepatic ischemia-reperfusion injury and oxidative stress in rats and the mechanism of the role of GSK-3 β.Methods Sixty SD rats were randomly divided into four groups:sham operation group (S group),ischemia-reperfusion group (I-R group),propofol pretreatment group (P group),TDZD-8 pretreatment group (T group).The hepatic ischemia-reperfusion rat models were established by the method of Nauta.Rats were subjected to 30-min,60-min and 90-min 70％ warm ischemia of liver followed by reperfusion for 120 min,respectively.Propofol (12 mg/kg · h) was injected via femoral vein 30 min before ischemia till the end of reperfusion in P group and TDZD-8 (1 mg/kg) were injected via femoral vein 20 min before ischemia in T group.The animals were killed at 120 min after reperfusion.Blood samples and the liver tissue were obtained.The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),lactate dehydrogenase (LDH),malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed.Liver morphological changes were observed using optical microscopy.p-GSK-3β Ser9 and total GSK-3 β expression was determined by Western blot.Results Compared with S group,AST,ALT,LDH and MDA level was increased,SOD level was reduced,and p-GSK-3 β Ser9 expression was significantly reduced in I-R group.Compared with I-R group,the content of AST,ALT,LDH and MDA was reduced significantly,SOD increased significantly,and the content of p-GSK-3β Ser9 increased significantly in P group and T group.There were no significant differences between P group and T group.The hematoxylin-eosin staining of hepatic tissues revealed in I-R group had severe structural damage and periportal inflammatory cells infiltrated,hepatocyte necrosis and sinusoidal congestion.In P group and T group,liver tissues had normal structure,less cell death,edema and inflammatory cell infiltration.Conclusions Propofol can significantly reduce hepatic ischemia reperfusion injury by reducing oxidative stress and lipid hydroperoxides.This protective effect of Propofol may be associated with the inhibition of GSK-3 β by GSK-3 β Ser9 phosphorylation.

Objective To investigate the prevalence of fecal incontinence (FI) among adult women in Beijing area, and to analysis risk factors associated with FI. Methods A stratified multiple-cluster systemic method was used to recruit women ≥ 20 years old in 6 districts of Beijing. A self-administrated questionnaire was used to collect information about Fl and possible risk factors. Results There were three thousand and 58 women participated in the survey, the average age was (48 ± 16 ) years (range 20 -79 years). The prevalence of FI was 1.28% ( 39/3058 ), which was related to age. There were five factors entered the logistic regress model, which were included age ≥40 years old ( OR = 3.3, 95% CI: 1.7 -6. 8), urinary incontinence ( OR = 3.0, 95% CI: 1.5 - 6. 1 ), vaginal delivery ( OR = 2.4, 95% CI:1.2 -4. 9), household per capita income ≤2000 RMB per month ( OR = 3. 3, 95 % CI: 1.6 - 6. 5 ), and feeling fatigue ( OR = 3.0, 95% CI: 1.5 - 5.8). Conclusion Prevalence of FI is low among adult women in Beijing area, while risk factors associated with Fl are complicated and further studies are necessary to be conducted.

The study is to prepare taste masking and enteric-coated clarithromycin granules by melting and fluid bed coating technology. Clarithromycin and matrix materials were melted at a certain temperature, and then made into particles by fluidized bed coating. X-ray powder diffraction and scanning electron microscopy were used to identify the crystal and morphology of drug loading granules. In vitro dissolution method was used for the observation of the drug release behavior. The results showed that the drug particles size range was 0.2 - 0.6 mm; the crystal form of clarithromycin in the granule did not change; enteric-coated granules accumulated release in 0.1 mol L(-1) hydrochloric acid in 2 h was less than 10%, while in pH 6.8 phosphate buffer in 1 h was more than 80%. The taste masking and enteric-coated clarithromycin granules not only have good taste masking effect, but also have a good release behavior. It is expected to have better clinical application.
Clarithromycin ; administration & dosage ; chemistry ; Crystallization ; Drug Carriers ; Drug Compounding ; methods ; Excipients ; chemistry ; Microscopy, Electron, Scanning ; Particle Size ; Tablets, Enteric-Coated ; Taste ; Technology, Pharmaceutical ; methods ; X-Ray Diffraction

Objective To observe the influence of circadian rhythm disruptions on exercise capability in rats. Methods A total of 30 spontaneously hypertensive rats (SHR) and age and weight matched homologous normal blood pressure WKY rats were randomly divided into normal circadian rhythm group (control group), twelve hours cir-cadian rhythm disruption group (observation group 1), six hours circadian rhythm disruption group (observation group 2). Each group included ten SHR rats and WKY rats, changing the light/dark time to construct circadian rhythm disruption model. Exercise endurance, blood pressure and heart rate after exhaustion were measured be-fore and one, two and three months after modeling. Results The interaction of time and circadian rhythm was significant on the exhaustion time of SHR rats (F=2.409, P=0.047). After three months of modeling, the exhaustion time of the control group was more than that of the obser-vation groups 1 and 2 (F=4.290, P=0.032). The interaction of time and circadian rhythm was not significant on the exhaustion time of WKY rats (F=0.717, P=0.638), there was no significant difference in the exhaustion time among groups (P>0.05). For SHR rats, after three months of modeling, the systolic pressure, diastolic pressure and mean arterial pressure after exhaustion of the observation group 1 were higher than those of the control group and the observation group 2 (P<0.05), the heart rate of the observation groups 1 and 2 was higher than that of the control group (P<0.05). But there was no significant difference in the systolic pressure, diastolic pressure, average arterial pressure and heart rate of WKY rats among groups (P>0.05). Conclusion Circadian rhythm disruptions can reduce the exercise endurance of SHR rats, which may be related to the cardiovascular function impairment.

OBJECTIVETo assess the role of p38 mitogen-activated protein kinases (p38MAPK) in the protective effect of remifentanil preconditioning (RPC) on hepatic ischemia-reperfusion injury in rats.

METHODSNinety-six male SD rats were randomly assigned into sham-operated group, ischemia-reperfusion group (I/R group), RPC group, and SB (an inhibitor of p38 MAPK) +RPC group. The rats were sacrificed at the end of reperfusion, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured. HE staining was used to observe the hepatic histopathological changes, and Western blotting was employed to examine p38MAPK and pp38MAPK protein expression. TUNEL staining was used to examine cell apoptosis in the liver tissues.

RESULTSCompared with sham-operated group, I/R group showed significantly increased serum levels of AST, ALT, TNF-α and IL-1β with obvious histopathological changes and cell apoptosis in the liver. RPC significantly decresed the elevated serum levels of AST, ALT, TNF-α and IL-1β and lessened hepatic histopathological changes, and caused reduced p38MAPK phosphorylation and hepatic cell apoptosis index. The protective effects of RPC were abolished by SB 203580 pretreatment.

CONCLUSIONRPC attenuates the production of inflammatory factors by activating p38MAPK signal pathway to improve hepatic ischemia-reperfusion injury, and these effects can be blocked by SB203580, a p38MAPK inhibitor.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Imidazoles ; pharmacology ; Interleukin-1beta ; blood ; Ischemia ; physiopathology ; Ischemic Preconditioning ; methods ; Liver ; blood supply ; MAP Kinase Signaling System ; Male ; Piperidines ; therapeutic use ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid ; agonists ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; blood ; p38 Mitogen-Activated Protein Kinases ; metabolism