AIMTo investigate the effects of exogenous NO donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1) on automaticity of the rabbit sino-atrial node in vitro and the action mechanism.

METHODSThe intracellular microelectrode technique is used to record the action potentials of rabbit sino-atrial node and APA (amplitude of AP), V(max) (maximal rate of depolarization), VDD (velocity of diastolic depolarization), RPF (rate of pacemaker firing) are analyzed.

RESULTSSNP(10(-5) - 10(-2) mol/L) increased its RPF and VDD dose-dependently. 10(-3) mol/L SNP increased RPF (beats/min) from 163 +/- 10.8 to 195.0 +/- 13.1 increased VDD (mV/s) from 50.3 +/- 9.6 to 70.2 +/- 12.1 (P < 0.01). SIN-1(10(-3) - 10(-2) mol/L) also increased RPF and VDD (P < 0.01).10(-4) mo/L Methylene blue (MB), a blocker of GMP cyclase, prevented the positive chronotropic effect and increasement of VDD induced by 10(-3) mol/L SNP totally (P < 0.01). 2. CsCl (2 mmol/L), a blocker of I(f) prevented the increasement of RPF and VDD in part (P < 0.05). 3. NIF (0.46 micromol/L), a blocker of I(Ca-L, had no significant effects on chronotropic effect and increasement of VDD (P < 0.01).

CONCLUSIONExogenous NO can increase the automaticity of rabbit sino-atrial node in vitro. The chronotropic effect is involved in NO-cGMP pathway and results from increasement of I(f) in the sino-atrial node at least in part; I(ca-L) is unlikely to play a major role in this effect.

Action Potentials ; Animals ; Heart Rate ; Molsidomine ; analogs & derivatives ; pharmacology ; Nitric Oxide ; metabolism ; Nitroprusside ; pharmacology ; Rabbits ; Sinoatrial Node ; drug effects ; physiology

Animals ; Apoptosis ; drug effects ; Capsules ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Hepatocytes ; pathology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; pathology ; Male ; Phytotherapy ; Rats ; Rats, Wistar

AIM AND METHODSUsing double immunohistochemical method for Fos and tyrosine hydroxylase(TH) to examine the effects of intracerebroventricular (icv) administration of adrenomedullin (AM) on catecholaminergic neurons and the expression of c-fos gene in rat brain nuclei involved in cardiovascular regulation in order to define whether the effects of central administration of adrenomedullin (AM) were induced by activating the catecholaminergic neurons.

RESULTS(1) Following icy administration of AM (3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the brainstem, the hypothalamus and the forebrain. (2) Following icy administration of AM (3 nmol/kg), double-labeled neurons for Fos and TH increased significantly in the area postrema (AP), the nucleus of the solitary tract (NTS), the nucleus paragigantocellularis lateralis (PGL) and the locus coeruleus (LC). (3) Pretreatment with calcitonin gene-related peptide receptor antagonism CGRP (8-37) (30 nmol/kg) significantly reduced the action of AM (3 nmol/kg) in the brain.

CONCLUSIONAM activates the nuclei involved in cardiovascular regulation in the forebrain, the hypothalamus and the brainstem, and that the central actions of AM are induced by activating the catecholaminergic neurons of brainstem nuclei involved in cardiovascular regulation. CGRP receptor can mediate the effects of AM in brain.

Adrenomedullin ; administration & dosage ; pharmacology ; Animals ; Brain Stem ; drug effects ; Calcitonin Gene-Related Peptide ; metabolism ; Hypothalamus ; drug effects ; Male ; Neurons ; drug effects ; metabolism ; Peptide Fragments ; metabolism ; Prosencephalon ; drug effects ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase ; metabolism

OBJECTIVETo investigate the therapeutic efficiency of antiviral treatment with pegylated-interferon (Peg-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) and to explore whether liver histopathological features or other factors influence the HBeAg seroconversion treatment response.

METHODSEighty HBeAg-positive CHB patients with diagnosis confirmed by liver puncture were treated with Peg-IFN(2a or 2b)body weight dose, once weekly). At treatment week 48, the rate of HBeAg seroconversion was determined and used to analyze the influence of liver histopathological features (liver biopsy assessment of: inflammation, graded G0 to G4; fibrosis stage, graded S0 to S4), sex, age, differential levels (pre-treatment baseline vs. week 48 post-treatment) of serum alanine transferase (ALT), and HBV DNA, by binary logistic analysis.

RESULTSAt week 48, the overall rate of HBeAg seroconversion was 30.0%. The rate of HBeAg seroconversion gradually advanced with increased liver inflammation (X2 = 8.435, P = 0.015): 9.09% of the 22 patients with G1; 31.58% of the 38 patients with G2; 47.30% of the 19 patients with G3; the one patient with G4. In contrast, the rate of HBeAg seroconversion showed a much weaker association with liver fibrosis (X2 = 5.917, P = 0.116). Only baseline HBeAg level, and no other baseline index, was significantly different between the patients who achieved HBeAg seroconversion and those who did not. Liver inflammation and baseline HBeAg level were identified as influencing factors of HbeAg seroconversion in response to Peg-IFN treatment.

CONCLUSIONPeg-IFN therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive CHB patients with severe liver inflammation; histological analysis of pre-treatment liver biopsies may help to identify patients most likely to benefit from the antiviral regimen.

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; pathology ; Humans ; Interferon-alpha ; therapeutic use ; Liver ; pathology ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Serologic Tests

OBJECTIVETo explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901 cells to doxorubicin.

METHODSGastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apoptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53.

RESULTSThe level of apoptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PI3K activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression.

CONCLUSIONPI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.

Androstadienes ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Enzyme Activation ; Humans ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Phosphorylation ; Protein Kinase Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-mdm2 ; metabolism ; Signal Transduction ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo study the relation between body mass index (BMI) and percentage body fat (PBF) in Chinese adolescent, and to compare the prevalence of overweight and obesity using BMI or PBF standards.

METHODSBMI from 757 girls with an average aged of 10.1 years in the rural areas, 165 girls average aged 13.5 years in suburbs and 172 boys average aged 13.7 years in suburb of Beijing, were measured. Their body compositions were also measured by dual-energy X-ray absorptiometry (DEXA).

RESULTSBMI was found closely correlated with PBF in each age group of rural and suburb girls and suburb boys with the correlation coefficient(r) of 0.59 - 0.83. When age, height and pubertal development were controlled, r became 0.54 - 0.88. The prevalence rates of obesity in rural girls, suburb girls and suburb boys were 33.1%, 21.8% and 21.5%, when PBF cutoff values (girls: PBF >or= 35%, boys: PBF >or= 25%) were used. However, the rates became 2.4%, 3.0% and 4.0% when BMI cutoff values of International Obesity Task Force (IOTF) were used. Compared with PBF cutoff values for obesity, the IOTF recommended BMI cutoff values had relatively lower sensitivity (7.3% - 18.9%) and higher specificity (100%).

CONCLUSIONBMI correlated well with PBF in Beijing adolescent. IOTF-BMI cutoff values showed low sensitivity and high specificity to Chinese adolescent which might be suitable for identifying obesity but not for the purpose of screening.

Adolescent ; Adolescent Development ; physiology ; Age Factors ; Body Composition ; physiology ; Body Mass Index ; Child ; China ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Multivariate Analysis ; Obesity ; diagnosis ; epidemiology ; Rural Population ; statistics & numerical data ; Sex Factors ; Suburban Population ; statistics & numerical data ; Urban Population ; statistics & numerical data

Animals ; Apoptosis ; drug effects ; Cell Line ; Cell Proliferation ; Curcuma ; Extracellular Matrix ; metabolism ; Hepatic Stellate Cells ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Plant Oils ; pharmacology ; Rats

To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Coagulation ; Blood Coagulation Tests ; Child ; Female ; Fibrin Fibrinogen Degradation Products ; Hemorrhage ; pathology ; Humans ; Leukemia ; blood ; pathology ; Leukocyte Count ; Male ; Middle Aged ; Platelet Count ; Prothrombin Time ; Retrospective Studies ; Thrombin Time ; Young Adult

The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) on cell cycle and apoptosis of thymus, spleen and bone marrow cells in mice totally irradiated with sublethal dose, and to explore its mechanisms. BALB/c mice irradiated with 5.5 Gy 60Co gamma-ray were randomly divided into control group and MSC group. Mice in MSC group were infused with 0.4 ml containing 2.5x10(7)/kg of MSCs through tail vein at 1 hour after irradiation. Mice in control group were infused with 0.4 ml normal saline. The cell apoptosis and cell cycle of thymus, spleen and bone marrow cells were detected by flow cytometry at 6, 12, 24 and 72 hours after irradiation and the P53 protein expressions in thymus and bone marrow cells were assayed by immunohistochemistry at 12 hours after irradiation. The results showed that the arrest of cells in G0/G1 and G2/M phase, and decrease of cells in S phase appeared at 6 hours after irradiation, those reached peak respectively at 12 hours in thymus cells, 6 hours in spleen and 24 hours in bone marrow, then the cell counts in G0/G1 phase decreased and the cell counts in S and G2/M phases increased. At 72 hours the cell counts in G0/G1 phase were less than the normal level and the cell counts in S phase were more than the normal level. The above changes of cell cycle in thymus and spleen were more rapid in spleen and more obvious in amplitude than that in bone marrow, the change of cell cycle in MSC group was more rapid and obvious than those in control group. After irradiation the apoptosis cells increased from 6 hours, reached the highest level at 12 hours and decreased to the normal level gradually after 24 hours in two groups; the apoptosis rates in spleen and thymus cells were higher than that in bone marrow cells. In comparison with the control group, the apoptosis rate in thymus cells at 12 hours, in spleen cells at 12 and 24 hours, and in bone marrow cells at 24 hours were fewer in MSC group. The cells expressing P53 protein in control group were more than that in MSC group. It is concluded that the MSCs accelerate the running of cell cycle in these hematopoietic tissue cells of irradiated mice, reduce the cell apoptosis and promote the recovery from injuries in hematopietic and immunological organs, thus protect the irradiated mice at early stage.
Animals ; Apoptosis ; physiology ; Bone Marrow Cells ; pathology ; Cell Cycle ; Female ; Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Inbred BALB C ; Radiation Injuries, Experimental ; pathology ; therapy ; Random Allocation ; Spleen ; pathology ; Thymus Gland ; pathology ; Whole-Body Irradiation

OBJECTIVETo observe the therapeutic effect and major complications of haploidentical nonmyeloablative allogeneic peripheral blood stem cell transplantation (NST) for refractory or relapsed leukemia.

METHODSThe results of 30 patients, including 14 cases of acute myeloid leukemia (AML), 11 cases of acute lymphoblastic leukemia (ALL), 5 case of chronic myelogenous leukemia (CML) (accelerated and blastic phase) with refractory or relapsed leukemia (RF/RL) who underwent haploidentical NST from August 2000 to April 2009 were analyzed. The conditioning regimen consisted of fludarabine (flu), antithymocyte globulin (ATG), cyclophosphamide (CTX), total body irradiation (TBI) and cytarabine (Ara-C) or myleran (Bu). Graft-versus-host disease (GVHD) prevention programmes consisted of Cyclosporine (CsA), mycophenolate mofetil (MMF), CD25 monoclonal antibody combined with mesenchymal stem cells (MSC).

RESULTSTwenty six cases of patients were full donor engraftment and 4 cases mixed chimerism into full donor chimerism. The average duration of neutrophil >0.5×10⁸/L after NST was 11 (9-16) days, and platelet >20×10⁸/L 17 (12-60) days. Upon follow-up of 16 to 120 months, 12-month transplant-related mortality (TRM) was 46.7%, acute Ⅱ-Ⅳgraft-versus-host disease (aGVHD) incidence was 40.0%. The probability of 3-year disease relapse, EFS and overall survival (OS) rates were 16.7%, 46.2% and 50.0% respectively.

CONCLUSIONHaploidentical NST could improve OS and EFS of refractory or relapsed leukemia and reducce TRM to some extent.

Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult