Objective To evaluate the effects of calcitonin and 1, 25 vitamin D on the bone loss in experimental periodontitis in rats. Methods A total of 125 male Wistar rats were randomly allocated to five groups according to the treatments during 8 weeks: normal control (group A, n=25), periodontitis(group B, n=25), calcitonin (group C, prepared in sterile saline at 2 mg/L, and 2μg/kg was administered daily, s.c. , n=25), 1,25 vitamin D (group D, prepared in corn oil daily at a concentration of 2 mg/L, and 2μg/kg was administered daily, p.o. , n=25), 1,25 vitamin D plus calcitonin (group E, n=25). The experimental model of periodontitis was induced by ligating floss around mandibular first molars with orthodontic wires in B,C,D and E groups. Five rats from each group were sacrificed, and the specimens were prepared at 2, 4, 6 and 8-week. The probing depth (PD) and alveolar bone level were observed. The serum bone-specific alkaline phosphatase (BALP) and osteocalcin (OC) were measured by enzyme-linked immunosorbent assay (ELISA) at 8-week in each group. Results The values of PD were significantly lower after 4, 6 and 8 weeks in E group than those of B, C and D groups (P＜0.05). The alveolar bone loss was significantly lower after 6 and 8 weeks in group E compared with that of B, C and D groups (P＜0.05). The serum levels of BALP and OC were significantly higher after 8 weeks in E group than those of B, C and D groups (P＜0.05). Conclusion The present study suggests that 1, 25 vitamin D and calcitonin can partially inhibit the alveolar bone loss induced by periodontitis. Especially, the application of both is more effective than either drug treatment alone.

Objective To evaluate the effects of root canal cleanliness on the fracture resistance of roots filled with AH-Plus. Methods Eighty single canal premolars were instrumented using step-back technique, then were randomly di-vided into four groups (n=20 for each group). Group A was washed with distilled water for 10 min, group B1 was washed with 5%EDTA for 1 min, group B2 was washed with 5%EDTA for 5 min and group B3 was washed with 5%EDTA for 10 min. Ten samples of each group were observed by scanning electron microscope at the coronal, middle and apical thirds to exam-ine smear layer removal. The remaining samples of each group were fixed into a electronic universal testing machine and ver-tically loaded until fracture. Results The difference of coronal and middle thirds was significant between group B3 and group B2 (P<0.05). At the middle third, there was significantly improved efficiency in smear layer removal in group B2 than that of group B1(P<0.05). The mean fracture resistance was significantly higher in group B3 (391.91±12.82)N than that of group B2 (335.54±16.14)N, group B1(296.47±17.82) N and group A (264.77±16.64)N (P<0.05). Group B2 showed a signifi-cantly better fracture resistance than that of group B1 and group A (P<0.05). Conclusion The complete removal of root ca-nal smear layer can significantly improve the fracture resistances of roots filled with AH-Plus.

OBJECTIVETo study the effect and mechanism of arsenic trioxide (As2O3) on apoptosis of pulmonary eosinophiles (PE) in asthmatic guinea-pigs.

METHODSThirty guinea-pigs were divided into 3 groups at random, the control group, the asthmatic group and the As2O3 group. The dosage of As2O3 used was 2 mg/kg. The apoptotic PE were labelled by TdT-mediated dUTP nick end labelling technique, and the PE infiltration and apoptosis were detected quantitatively using computerized image analysis technique.

RESULTSIn the control group, the amount of infiltrating PE was 4.4 +/- 2.5 cells/HP and the PE apoptotic index (AI) was 0.42 +/- 0.08%. In the asthmatic group, the amount increased (P < 0.01) and AI decreased significantly (P < 0.01). After the asthmatic animals had been treated with As2O3, the two parameters changed reversedly significantly (P < 0.01), and there was a significantly negative correlation between them (r = -0.949, P < 0.01).

CONCLUSIONThe PE apoptosis abnormality is one of the important mechanisms that cause bronchial asthma, As2O3 could alleviate the airway inflammation through promoting PE apoptosis and lower PE infiltration. Low dose of As2O3 is proved to be effective with relative safety, it also has potential value in treating asthma.

Animals ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Asthma ; chemically induced ; pathology ; Eosinophils ; pathology ; Guinea Pigs ; Image Processing, Computer-Assisted ; Lung ; pathology ; Male ; Ovalbumin ; Oxides ; pharmacology ; Random Allocation

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane-bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5％sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. RESULTS: The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P<0.01, P<0.05). The expression levels of TREM-1, IL-1β and TNF-α mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P<0.01, P<0.05). The expression level of TREM-1mRNA was positively correlated with IL-1β and TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-α mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS: The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-l might play an important role in the development of intestinal barrier dysfunction in rats with SAP.

0.05), but the level of albumin dropped significantly(P

Adaptor Proteins, Signal Transducing ; Animals ; Antigens, Differentiation ; physiology ; Asthma ; etiology ; Humans ; Immune Tolerance ; Immunity, Innate ; Membrane Glycoproteins ; physiology ; Myeloid Differentiation Factor 88 ; Proteins ; physiology ; Receptors, Cell Surface ; physiology ; Receptors, Immunologic ; physiology ; Signal Transduction ; Toll-Like Receptors

AIMTo study the effects of sodium salicylate on the expression of GABAalpha NR1 and hearing response properties of inferior colliculus neurons in mice.

METHODSThirty-six kunming mice were divided into three groups (A, B, C,). The expression of GABAalpha NR1 were measured by using RT-PCR. The intensity-rates functions, intensity-latency functions and frequency-turning curves were recorded by extracellular electrophysiological recording techniques.

RESULTS(1) The expression of GABAalpha mRNA of B group was decreased remarkably than the control group (A group, P < 0.05), there weren't noticeable differences between A group and C group (P > 0.05). The expression of NR1 mRNA of B group was increased remarkably than the control group (A group, P < 0.01), there were noticeable differences between A group and C group P < 0.05). (2) The intensity-rates functions, intensity-latency functions were monotonic while the frequency-turning curves were more broad when sodium salicylate was given. (3) The intensity-rates functions, intensity-latency functions were non-monotonic while the frequency-turning curves were sharpened after lidocaine was given.

CONCLUSIONS(1) The results suggested that administration of sodium salicylate decreased the expression of GABAalpha while increased the expression of NR1mRNA. (2) The intensity-rates functions, intensity-latency functions were monotonic, the frequency-turning curves were more broad when salicylate was given and the changes above could be reversed by given lidocaine.

Acoustic Stimulation ; Animals ; Inferior Colliculi ; drug effects ; metabolism ; physiology ; Mice ; Mice, Inbred Strains ; Neurons ; drug effects ; metabolism ; physiology ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Sodium Salicylate ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

BACKGROUNDTyrosine kinase signaling cascades play a critical role in the pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib could suppress the progression of airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling in a murine model of chronic asthma.

METHODSOvalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were intragastrically administered with sunitinib (40 mg/kg) daily during the period of OVA challenge. Twelve hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodeling. The levels of total serum immunoglobulin E (IgE) and Th2 cytokines (interleukin (IL)-4 and IL-13) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The expression of phosphorylated c-kit protein in the lungs was detected by immunoprecipitation/Western blotting (IP/WB) analysis.

RESULTSSunitinib significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling in chronic experimental asthma. It reduced levels of total serum IgE and BALF Th2 cytokines and also lowered the expression of phosphorylated c-kit protein in remodelled airways.

CONCLUSIONSSunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Asthma ; chemically induced ; drug therapy ; immunology ; Blotting, Western ; Bronchial Hyperreactivity ; chemically induced ; immunology ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Immunoglobulin E ; blood ; Immunohistochemistry ; Immunoprecipitation ; In Vitro Techniques ; Indoles ; pharmacology ; Inflammation ; chemically induced ; immunology ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Lung ; drug effects ; immunology ; metabolism ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; pharmacology ; Proto-Oncogene Proteins c-kit ; metabolism ; Pyrroles ; pharmacology

BACKGROUNDContinuous positive airway pressure (CPAP) treatment has been proven to be effective in improving the symptoms of coexisting coronary heart disease (CHD) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). However, it is still unclear whether such improvements are linked to changes in vascular endothelial function. This research was carried out to investigate the effects of CPAP treatment on vascular endothelial function in patients with OSAHS and CHD.

METHODSThirty-six patients with moderate or severe OSAHS and CHD undergoing three months of CPAP treatment were recruited for this study. The changes in their morning plasma nitric oxide (NO) and endothelin (ET) levels, NO/ET ratio, total ischemic burden (TIB) of the myocardium, apnea hypopnea index (AHI), and minimal and mean pulse oxygen saturation (SpO2) were compared and analyzed before and during CPAP treatment.

RESULTSCompared with the plasma levels of ET [(51.39 +/- 11.69) ng/L] and NO [(36.67 +/- 11.86) micromol/L], NO/ET (0.71 +/- 0.14), AHI (32.4 +/- 7.9), minimal SpO2 [(68.9 +/- 11.4)%], and myocardial TIB [(66.29 +/- 16.37) mm.min] before treatment, there were significant decreases in ET [(33.41 +/- 10.03) ng/L] (P < 0.05), increases in NO [(59.89 +/- 10.26) micromol/L] and NO/ET (1.79 +/- 0.38) (P < 0.01), decreases in AHI (1.9 +/- 0.5), and increases in minimal SpO2 [(90.6 +/- 1.8)%] (all P < 0.01) and myocardial TIB [(36.42 +/- 10.87) mm.min] (P < 0.05) after three months of CPAP treatment.

CONCLUSIONCPAP treatment may play an important role in the improvement and protection of vascular endothelial dysfunction and myocardial ischemia in OSAHS patients with CHD.

Adult ; Continuous Positive Airway Pressure ; Coronary Artery Disease ; complications ; therapy ; Endothelium, Vascular ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; physiopathology ; therapy

OBJECTIVETo investigate the transduction efficiency of serotype 1, 2, 5, 6, 7, 8, 9, 10 recombinant adeno-associated viruses (rAAV) in human lung cancer cell line A549 cells and compare the transduction efficiency of conventional AAV vectors with that of self-complementary AAV (scAAV) vectors. Furthermore, the capacity of A549 cells expressing transgenic CD40L to stimulate dendritic cells (DCs) was evaluated.

METHODSLung cancer A549 cells were infected with 1 x 10(4) particules per cell of AAV encoding the green fluorescent protein (GFP) or human CD40L driven by CMV promotor, and transgene expression was analyzed by flow cytometry and fluorescence microscopy. Stimulation of isolated human dendritic cells by CD40L-expressing tumor cells was quantified by measuring secreted interleukin-12 with immunoassay.

RESULTSSerotype AAV2/5 transduced A549 cells much more efficiently than serotypes AAV2/1, AAV2/2, AAV2/6, AAV2/7, AAV2/8, AAV2/9 and AAV2/10. The transduction efficiency of scAAV2/5 was significantly higher than that of conventional AAV2/5. Furthermore, pre-treatment with carboplatin substantially increased AAV-mediated transgene expression. The scAAV2/5 vectors encoding human CD40L was used to generate CD40L. A549 cells transduce by these vectors were co-cultured with immature human DCs. As a consequence, interleukin-12 was released and measured in the culture supernatant. Specificity of immunostimulatory effect of CD40L was confirmed by blocking with a monoclonal antibody binding to human CD40L.

CONCLUSIONscAAV2/5 transduce lung adenocarcinoma A549 cell efficiently, and co-administration of chemotherapeutic agent carboplatin further enhances its transduction efficiency. It is confirmed that lung cancer cells infected with a CD40L-encoding scAAV2/5 construct can activate human DCs to secrete interleukin-12. Our findings provided a basis for future immunotherapeutic approaches including intratumoral transfer of stimulating factors.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; CD40 Ligand ; genetics ; metabolism ; physiology ; Carboplatin ; pharmacology ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; Dendritic Cells ; cytology ; secretion ; Dependovirus ; classification ; genetics ; Flow Cytometry ; Gene Expression ; drug effects ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Immunoassay ; methods ; Interleukin-12 ; secretion ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Microscopy, Fluorescence ; Recombinant Fusion Proteins ; genetics ; metabolism ; Serotyping ; Transfection