AIMIn order to explore the mechanism of central motilin-induced feeding behavior, the effects of erythromycin, a motilin receptor agonist, on glucose responsive neurons in hypothalamus were observed.

METHODSExtracellular recordings were made from single neurons in region of lateral hypothalamic area (LHA) and ventromedial hypothalamic nucleus (VMH) in anesthetized rats. On the basis of their responsiveness to intracarotid injection of 0.58 mol/L glucose solution 0.2 ml, glucose-sensitive neurons (GSNs) in LHA and glucoreceptor neurons (GRNs) in VMH were recognized. Effects of intracerebroventricularly (i. c. v.) administration of 4 microg erythromycin on neural activities of glucose responsive neurons and non-glucose responsive neurons were examined. The mixture of EM and GM-109 1 microl were used to GSNs and GRNs which were sensitive to i. c. v. administration of EM.

RESULTSIn LHA, EM increased activity of GSNs significantly (P < 0.05 vs non-glucose-sensitive neurons group). Whereas in VMH, EM significantly decreased the activities of GRNs (P < 0.01 vs non-glucoreceptor neurons group). The mixture of EM and GM-109 had no effect on GSNs and GRNs.

CONCLUSIONEM, a motilin receptor agonist, can stimulate GSNs in LHA and suppress GRNs in VMH and this may contribute to central motilin's effect on feeding behavior.

Animals ; Erythromycin ; pharmacology ; Hypothalamus ; cytology ; Neurons ; cytology ; drug effects ; Rats ; Rats, Wistar ; Receptors, Cell Surface ; metabolism ; Receptors, Gastrointestinal Hormone ; antagonists & inhibitors ; Receptors, Neuropeptide ; antagonists & inhibitors

As an important neurotransmitter, adenosine displays its functions by acting on the adenosine receptors. Recent studies have shown that the distribution, expression and balance among subtypes of adenosine receptors are closely related with cognitive activities, and changes of adenosine receptors play key roles in neurodegenerative disorders including Alzheimer's disease. It has been pointed out that prolonged activation of adenosine receptors by high level adenosine may lead to the disturbance of balance among adenosine receptor subtypes. This imbalance mainly performed as increased expression of A2a receptor and decreased expression of A1 receptor, and enhancement of the excitatory signals mediated by A2a receptor and weakened inhibitory signals mediated by A1 receptor. Changes of these two subtypes of adenosine receptors may lead to a lot of disorders of neurological activities which developed into dysfunction of cognition to the end. These findings imply that the potential of maintaining the balance among adenosine receptors on the treatment of AD would facilitate both the revealing of the mechanism and the cure of AD.
Adenosine ; physiology ; Alzheimer Disease ; physiopathology ; Humans ; Neurotransmitter Agents ; physiology ; Receptors, Purinergic P1 ; classification ; physiology

Objective: To observe the therapeutic effect of sinew-regulating bone-setting manipulations for knee osteoarthritis (KOA) model rabbits and its impacts on the chondrocyte apoptosis rate and the levels of interleukin (IL)-1β and nitric oxide (NO). Methods: According to the random number table method, 30 New Zealand white rabbits were divided into a normal group (n=9) and a modeling group (n=21). Rabbits in the modeling group were used to establish KOA models with the modified Hulth method. At the 8th week, three rabbits were sacrificed to verify the model and the remaining 18 rabbits were randomly divided into a model group (n=9) and an intervention group (n=9). Rabbits in the normal group and model group were bred routinely without any intervention. Rabbits in the intervention group were treated with the sinew-regulating bone-setting manipulations, 10 min/time, once every other day for a total of 20 times. The Lequesne MG knee function rating was used to evaluate the behavioral differences of the rabbits in each group. The Pelletier score was used to evaluate the general changes of the rabbits. The Mankin score was used to evaluate the pathology of knee cartilages. The enzyme-linked immunosorbent assay and nitrate reductase methods were used to determine the levels of IL-1β and NO in serum and synovial fluid of each group, respectively. In situ terminal deoxynucleotidyl transferase-mediated nick and labeling method was used to determine the apoptosis of chondrocytes in each group. Results: Compared with the normal group, the scores of Lequesne MG, Pelletier and Mankin, and the levels of IL-1β and NO in the model group were increased (P<0.05), which indirectly indicated the success of the model. Compared with the model group, the scores of Lequesne MG, Pelletier and Mankin, IL-1β and NO levels, and chondrocyte apoptosis rate of the intervention group were decreased, and the differences were statistically significant (P<0.05). Conclusion: The sinew-regulating bone-setting manipulations can reduce the levels of IL-1β, NO, and chondrocyte apoptosis rate, and delay the articular cartilage degeneration, therefore, having a good therapeutic effect on KOA.

OBJECTIVETo compare the durability of quantum dots with that of green fluorescein for labeling survivin antisense oligonucleotide (ASODN) and investigate the difference in growth and apoptosis of cells transfected with the labeled survivin ASODN.

METHODSSurvivin ASODN labeled with quantum dots or green fluorescein was transfected into MCF-7 cells via Lipolifectmain(TM2000). The proliferation of MCF-7 cells was assessed with MTT assay, survivin mRNA expression determined by RT-PCR and its protein expression measured by Western blot analysis. The apoptosis rate of the transfected cells was estimated by flow cytometry, and the fluorescence distribution in the cells observed under fluorescent inverted microscope.

RESULTSThe mRNA and protein expressions of survivin were significantly decreased in the MCF-7 cells after cell transfection with survivin ASODN labeled with quantum dots or green fluorescein, and no significant difference was noted between the two labeling methods (P>0.05). Nor did survivin ASODN transfection with different labeling methods produced significant difference in cell proliferation and apoptotic rate (P>0.05). For green fiuorescein labeling, the fluorescence disappeared 4 days after transfection, whereas the fluorescence sustained for 1 week for quantum dots labeling.

CONCLUSIONSurvivin ASODNs labeled with quantum dots and green fiuorescein do not significantly differ in survivin expression or the transfected cell proliferation and apoptosis rate, but quantum dot labeling can be more stable with longer maintcnance of the labeling.

Apoptosis ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Fluorescein ; chemistry ; Gene Expression ; Humans ; Inhibitor of Apoptosis Proteins ; Microscopy, Fluorescence ; Microtubule-Associated Proteins ; genetics ; metabolism ; Oligonucleotides, Antisense ; chemistry ; genetics ; Quantum Dots ; Reverse Transcriptase Polymerase Chain Reaction ; Staining and Labeling ; methods ; Transfection

OBJECTIVETo investigate penetration characteristics of artemether and the effect of different permeation enhancer on transdermal permeation of artemether through rat skin.

METHODThe permeation experiments were performed using rat skin on modified Franz diffusion cells in vitro. The concentrations of artemether in receptor compartment at specified time points were determined by HPLC.

RESULTThe permeating ratio through human skin of artemether solution was Js (2.78 +/- 0.78) microg x cm(-2) x h(-1), the quantity of drug penetrated through and accumulated in the skin by the end of the experiment were (69.07 +/- 3.01) microg x cm(-2), (58.93 +/- 3.56) microg x cm(-2) respectively. Four different permeation enhancers can improve the transdermal permeation of artemether.

CONCLUSIONArtemether have the potential to be developed to new transdermal preparation.

Adjuvants, Pharmaceutic ; chemistry ; Animals ; Artemisinins ; administration & dosage ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; In Vitro Techniques ; Male ; Permeability ; drug effects ; Rats ; Rats, Wistar ; Skin ; drug effects ; metabolism

OBJECTIVETo evaluate the specific killing effects of combination of recombinant adenovirus mediated double suicide gene driven by KDR promoter and survivin antisense oligonucleotide(ASODN) on colorectal cancer cells and vascular endothelial cells.

METHODSThe 293 packaging cells were transfected with the plasmids of pAdEasy-CDglyTK and the recombinant adenovirus were generated. The KDR expressive cells of SW620, ECV304 were infected with adenovirus, meanwhile survivinASODN was transferred into the same cells. The infection rate of adenovirus and transfection efficiency of survivinASODN were observed and the expression of CDglyTK was detected by RT-PCR. The expression of survivin was measured by Western blot. The killing effects and bystander effects on SW620, ECV304 were examined through MTT method.

RESULTSThe cells which were infected with the adenovirus mediated double suicide gene could be transfected with the survivin ASODN and the infection rate was not affected as well as the transfection efficiency. The high expression of CDglyTK gene was found in SW620, ECV304 cells infected with recombinant adenovirus and survivin ASODN decreased the survivin protein level. The survival rate of gene therapy group was significantly lower than that of negative group. The combination of survivin ASODN and AdKDR-CDglyTK gene therapy showed significantly lower survival rate of SW620 and ECV304 cells as compared with the AdKDR-CDglyTK or survivin ASODN used alone (P<0.05). The survival rate was slightly lower in GCV 100 microg/ml, 5-FC 2000 microg/ml than that AdKDR-CDglyTK used alone (P>0.05). The combined therapy of AdKDR-CDglyTK and survivin ASODN showed synergistic killing efficacy and more significant bystander effects.

CONCLUSIONThe combined gene therapy of AdKDR-CDglyTK system and survivin ASODN has stronger specific killing effects on colorectal cancer cells and vein endothelial cells.

Adenoviridae ; genetics ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; Endothelial Cells ; metabolism ; Genes, Transgenic, Suicide ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; genetics ; Oligonucleotides, Antisense ; genetics ; Receptors, Vascular Endothelial Growth Factor ; genetics ; Transcription Initiation Site

OBJECTIVETo explore the relationship between the proliferation, differentiation of rat hepatic stem like cell line WB-F344 and cytokines in vitro.

METHODS(3)H thymidine labelling of new synthesized DNA was used to examine the mitogenic responsiveness of WB-F344 cells to cytokines, western blot was used to study the expression of cytokines receptors on hepatic stem cells, and apoptotic cells were detected by Flow cytometry.

RESULTSWB-F344 cells showed a proliferative response to the cytokines of hepatocyte growth factor (HGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), Insulin at the dose of 80 ng/ml, and the relative cpm values are 982.95, 906.32, 863.98 and 968.67 respectively, while non response to interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) at the same dose, and an inhibition or apoptosis response to transforming growth factor-beta (TGF-beta) at 80 ng/ml with a 26.89% apoptotic rate. Western blot showed that there were HGF, EGF, FGF, TGF-beta receptors expressed on WB-F344 cells. When WB-F344 cells were cultured in the differential system (DMEM, 10% Fcs, HGF 10 to approximately 50 ng/ml, EGF 20 ng/ml, Insulin 1 microg/ml, Dex 1 micromol/L), the cells could differentiated into hepatocytes. In addition, HGF could scattered WB-F344 cells.

CONCLUSIONThe proliferation and differentiation of liver stem cells are regulated by various cytokines which may play an important role when liver is damaged seriously.

Animals ; Cell Differentiation ; drug effects ; Cell Division ; drug effects ; Cytokines ; pharmacology ; Epidermal Growth Factor ; pharmacology ; Hepatocyte Growth Factor ; pharmacology ; Insulin ; pharmacology ; Liver ; cytology ; Rats ; Rats, Inbred F344 ; Stem Cells ; cytology ; drug effects ; Transforming Growth Factor beta ; pharmacology

OBJECTIVEThe wetland at Dalian Bay in the Northeast of China has been polluted by oil severely. The effect of various microbes and operation parameters on the bioremediation of oil-polluted wetlands at Dalian Bay was investigated and reported previously. In the study, other operation conditions related to the status of medium were investigated via statistical experimental design and analysis and a necessary information is involved to use micro-technology in the application.

METHODSThe method used involved the direct inoculation of selected bacteria, which were capable of degrading oil. The operation conditions were further optimized and evaluated by gravimetrical assay.

RESULTSThe optimal pH and temperature for the studied bacteria to degrade the existing oil pollutants were established as pH 8.0 and 27 degrees C. The mixed of various bacteria showed better results in terms of oil degradation than any single one. Among the selected four factors, disturbance, oxidant, nutrients, and biosurfactant, the former two contributed more impacts on the oil degradation in the early stage of process, while the latter two became the limiting factors in the late stage. Three sets of optimal conditions were obtained for each individual stage, but no one was suitable for the overall process.

CONCLUSIONThe study demonstrated the technical feasibility of using direct inoculation into the contaminated soil samples to remove oil pollutants. It suggested that the operation conditions should be monitored and adjusted during the different stages of bio-reactions in the process to achieve the best result of oil degradation.

Bacteria ; metabolism ; Biodegradation, Environmental ; China ; Ecosystem ; Hydrogen-Ion Concentration ; Oceans and Seas ; Petroleum ; metabolism ; Soil ; analysis ; Soil Pollutants ; chemistry ; metabolism ; Temperature

OBJECTIVETo evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN).

METHODS32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed.

RESULTSIgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13).

CONCLUSIONSPerioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.

Adult ; Aged ; Body Weight ; Crohn Disease ; immunology ; surgery ; therapy ; Female ; Humans ; Immunoglobulins ; blood ; Male ; Malnutrition ; etiology ; Middle Aged ; Nutritional Status ; Parenteral Nutrition ; Pneumonia ; etiology ; Postoperative Complications ; etiology

OBJECTIVETo compare the pharmacokinetics and tissue distribution of alpha-asarone in lipid emulsion and aqueous solution for injection and study the feasibility of lipid emulsion of alpha-asarone as the parenteral drug delivery system.

METHODHPLC was used to determine the drug concentration in rat plasma and mice tissues after intravenous (i.v.) administration of lipid emulsion and aqueous solution of alpha-asarone at a single dose (40 mg x kg(-1)), respectively.

RESULTThe plasma concentration-time profiles of lipid emulsion and aqueous solution of alpha-asarone after intravenous administration of them are similar and the drug concentration-time data were fitted to a two-compartment open model. The results of tissues distribution showed that distribution contents of alpha-asarone from lipid emulsion and aqueous solution in vivo are similar in lungs but lipid emulsion increased the uptake in livers and spleens, and decreased the uptake in hearts and kidneys for alpha-asarone.

CONCLUSIONThe plasma concentration-time profiles of alpha-asarone in lipid emulsion and aqueous solution are similar, but lipid emulsion significantly altered the tissue distribution of alpha-asarone, which may be beneficial to decrease its potential toxicity to heart and kidney.

Animals ; Anisoles ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Emulsions ; chemistry ; Female ; Injections, Intravenous ; Kinetics ; Lipids ; chemistry ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution