Adult male Kunming mice were divided into normal control group,propylthiouracil(PTU) treated group and PTU+T_4 treated group.Neurogranin(Ng)protein expression in the hippocampus after 8 weeks was assayed by Western blotting and immunohistochemical method.Results showed that Ng protein was decreased in the hippocampus of male mice with adult-onset hypothyroidism,suggesting that decreased Ng,which is correctable by T_4,is involved in cognitive dysfunction in adult-onset hypothyroid male mice.

OBJECTIVETo discuss the effect of Taohong Siwu Decoction (TSD) in regulating functions of endothelial cells and treating arteriosclerosis obliterans (ASO).

METHODSThe ASO model was prepared by using high-fat diet plus intimal injury. They were randomly divided into the model group (n = 10), the normal control group (n = 9), the low dose TSD group (group A, n = 12), the middle dose TSD group (group B, n = 10), and the high dose TSD group (group C, n = 9). Eight weeks after modeling, the limb blood perfusion was observed using laser Doppler flowmetry. The arterial morphology was observed using light microscope and transmission electron microscope. The number of circulating endothelial cells (CECs) was determined using Percoll density gradient centrifugation method. Serum levels of TNF-alpha, IL-1, ET-1, and NO were detected using double antibody sandwich assay of enzyme linked immunosorbent assay (ELISA).

RESULTSThe ASO rat model was successfully established. Blood lipids levels significantly increased, the blood perfusion of left hind limbs significantly decreased, the number of CECs in the peripheral blood significantly increased, the arterial lumen was irregularly narrowed, the ultra-structure of vessel walls was damaged, serum levels of TNF-alpha, IL-1, and ET-1 significantly increased, and the serum level of NO significantly decreased in the model group, showing statistical difference when compared with the normal control group (P < 0.01). Compared with the model group, significant improvement in the aforesaid indices was shown in group B and C (P < 0.05, P < 0.01).

CONCLUSIONSThe injury and abnormal functions of endothelial cells is an important pathological process of ASO. As an effective recipe for treating ASO, TSD could protect vascular endothelial cells and improve the secretion function of vascular endothelial cells.

Animals ; Arteriosclerosis Obliterans ; blood ; drug therapy ; Diet, High-Fat ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; metabolism ; Endothelin-1 ; blood ; Endothelium, Vascular ; cytology ; Interleukin-1 ; blood ; Male ; Nitric Oxide ; blood ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo explore the mechanism of the eye-acupuncture for treatment of acute cerebral ischemia-reperfusion injury.

METHODSThirty-two healthy SD rats were randomly divided into a normal group, a sham operation group, a model group and an eye-acupuncture group, 8 rats in each group. The rat model of cerebral ischemia-reperfusion was established with thread occlusion method in the model group and the eye-acupuncture group. The eye-acupuncture group was treated by eye-acupuncture at "liver region", "upper energizer area", "lower energizer area" and "kidney region" for 20 min immediately after reperfusion and at 30 min before sampling. No treatment was done in the normal group and the sham operation group, and no thread occlusion was performed in the sham operation group. The Neurologic impairment was scored and the methods of immunohistochemistry staining, western-blotting and real-time fluorescent quantitation polymerase chain reaction (RQ-PCR) were taken to detect the expression of the aquaporin protein 4 (AQP4) and its mRNA in cerebral cortex after reperfusion for 3 hours.

RESULTSThe neurologic impairment score of 1.50 +/- 0.54 in the eye-acupuncture group was significant lower than 2.63 +/- 0.92 in the model group (P < 0.01). The expression of the AQP4 protein by immunohistochemistry and western-blot respectively were 116.33 +/- 10.24 and 0.53 +/- 0.04 in the normal group, 118.97 +/- 12.72 and 0.55 +/- 0.07 in the sham operation group, and 129.30 +/- 18.36 and 0.67 +/- 0.08 in the eye-acupuncture group, with statistical significance compared to 150.88 +/- 15.82 and 0.94 +/- 0.04 in the model group (all P < 0.01), and there were significant differences between the eye-acupuncture group and the normal group (both P < 0.01). The tendency in the expression of AQP4 protein and its mRNA in all the group were almost the same.

CONCLUSIONThe eye-acupuncture therapy can relieve the cerebral ischemia-reperfusion injury and the protective mechanism is related to the downregulation of the cerebral AQP4 expression.

Acupuncture Therapy ; Animals ; Aquaporin 4 ; genetics ; metabolism ; Brain ; metabolism ; Brain Ischemia ; complications ; genetics ; metabolism ; surgery ; Disease Models, Animal ; Eye ; anatomy & histology ; Female ; Gene Expression ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; genetics ; metabolism ; therapy

OBJECTIVETo investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism.

METHODSRat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR.

RESULTS20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05).

CONCLUSIONThe Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene

Acetaldehyde ; pharmacology ; Animals ; Cells, Cultured ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinases ; metabolism ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Hepatocytes ; drug effects ; Proto-Oncogene Proteins ; Rats

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.
Animals ; Body Weight ; drug effects ; Dose-Response Relationship, Drug ; Dyslipidemias ; metabolism ; Energy Metabolism ; drug effects ; Fatty Liver ; chemically induced ; complications ; Female ; Fibroblast Growth Factors ; administration & dosage ; pharmacology ; therapeutic use ; Insulin Resistance ; Lipolysis ; drug effects ; Liver ; metabolism ; pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Sodium Glutamate

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Caco-2 Cells ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Up-Regulation ; drug effects

OBJECTIVETo evaluate the virological response of managing chronic hepatitis C (CHC) with peg-interferon alpha-2b (PEG-IFN alpha-2b) and ribavirin.

METHODSWe retrospectively analyzed the virological response of 40 patients with different genotypes of hepatitis C virus (HCV) infection after anti-HCV management. Patients were given different dosages of PEG-IFN alpha-2b and ribavirin based on their weights. The duration of treatment was 48 weeks for patients infected by HCV genotype 1, and was 24 weeks for the others. HCV RNA was tested before treatment, 12 weeks post management, end of treatment, and 24 weeks after treatment stopped.

RESULTSData from 40 patients were collected. Among them, 24 cases experienced HCV genotype 1 infection, and 16 cases were infected with other genotypes. Between these two groups, the early virological responses were 75.0% (18/24) and 87.5% (14/16), the end-of-treatment virological responses were 80.0% (16/20) and 85.7% (12/14), and the sustained virological responses were 56.2% (9/16) and 78.5% (11/14), respectively.

CONCLUSIONBody weight-based customized PEG-IFN alpha-2b in combination with ribavirin can effectively treat patients with different genotypes of CHC.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Middle Aged ; Polyethylene Glycols ; RNA, Viral ; blood ; Recombinant Proteins ; Retrospective Studies ; Ribavirin ; administration & dosage ; Treatment Outcome

Objective To evaluate the incidence of postoperative hemorrahage in children undergoing adenoidectomy , and to discuss its possible causes. Methods Included in this study were children who underwent adenoid and/or tonsil surgery at Shenzhen Chilidren's Hospital between January 2004 and November 2009. The change of hemoglobin ( Hb) and hematocrit ( Hct) were retrospectively analysed. The blood loss was estimated by the change of Hct. Results There were 2078 cases that accomplished the inclusion criteria in the period of study. Ten children bled 0. 5 - 4. 0 hours after surgery,without superfluous hemorrahage during the operation and post-tonsillectomy. This represented an incidence of 0.48% of immediate postoperative haemorrhage among the 2078 procedures analyzed. Statistical differences were found between boys (0.21%) and girls (1.10%, x2 =5.597, P<0.05). The change of Hb and Hct was positively correlated (r = 0. 95 , P < 0. 01) , the blood loss was positively correlated with the bleeding time ( r = 0. 66, P < 0. 05 ) . The causes of postoperative hemorrhage were coagulation system deficits, chronic nasopharyngitis, deficient hemostasis and immoderate ravage. To control the postoperative hemorrhage, 2 postnasal packing under topical anaesthesia and 8 electrocautery under general anaesthesia were applied. Conclusions Poor operative technique and deficient hemostasis are the major causes of primary hemorrahage. Prompt operation to control the postoperative bleeding should be done 2 hours after bleeding under general anesthesia in order to avoid severe complications.

BACKGROUNDImiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. This study investigated whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3.

METHODSThirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of T-bet and GATA-3 were measured by Western blot.

RESULTSIt was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines and increased Th1 type cytokines mRNA and protein levels; 4) modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production.

CONCLUSIONImiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Th1 phenotype.

Administration, Inhalation ; Aminoquinolines ; administration & dosage ; therapeutic use ; Animals ; Asthma ; drug therapy ; metabolism ; Bronchi ; pathology ; Bronchial Hyperreactivity ; drug therapy ; metabolism ; Cytokines ; biosynthesis ; Eosinophils ; physiology ; GATA3 Transcription Factor ; genetics ; Gene Expression Regulation ; drug effects ; Lung ; pathology ; Male ; Ovalbumin ; immunology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; T-Box Domain Proteins ; Transcription Factors ; genetics

BACKGROUNDIt is unclear whether a history of paroxysmal atrial fibrillation (PAF) would impact the effect of catheter ablation on persistent atrial fibrillation (AF). This study aimed to compare the effect of catheter ablation on persistent AF with and without a history of PAF.

METHODSOne hundred and eighty-three patients underwent catheter ablation of persistent AF lasting for > 1 month and were reviewed. Patients were divided into two groups according to whether they had a history of PAF or not. Group I consisted of persistent AF patients with a history of PAF, and group II consisted of persistent AF patients without such a history. All patients received catheter ablation focused on pulmonary vein isolation and were observed for arrhythmia recurrences, which were defined as documented episodes of AF or atrial tachycardia after a blanking period of 3 months.

RESULTSOne hundred and three patients (60.9%) in group I and sixty-six patients (39.1%) in group II were successfully followed and included in analysis. There were no significant differences in clinical and echocardiographic characteristics between both groups except for a younger age and more male patients in group II. After (15.5 ± 10.7) months of follow-up, 59 (57.3%) patients in group I and 49 (74.2%) patients in group II maintained sinus rhythm free of anti-arrhythmia drugs (P = 0.025). Multivariate analyses found left atrial anteroposterior diameter (P = 0.006) and persistent AF with a history of PAF (OR 1.792, 95%CI 1.019 - 3.152; P = 0.043) as the only independent statistical predictors of arrhythmia recurrences.

CONCLUSIONThe arrhythmia recurrence rate of catheter ablation based on pulmonary vein isolation in persistent AF with a history of PAF was higher than those without a history of PAF.

Adult ; Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; Female ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Pulmonary Veins ; surgery ; Recurrence