OBJECTIVETo observe the changes of bone histomorphometry parameters in condyle of rabbits during mandibular forward positioning.

METHODSForty rabbits with eight weeks of age were simple randomly divided into the experimental group (n = 24) and control group (n = 16).Mandibles of rabbits in the experimental groups were induced to forward position by a functional appliance.The experimental group and control group were sacrificed after 2 and 4, 8, 12 weeks.The specimens from right tempromandibular joints were processed for undemineralised sections.These sections were used for fluorescent microscopy observation and the measurement of bone histomorphometry.

RESULTSAt 8 week bone-volume fraction [(75.83 ± 1.10)%], trabecular thickness [(103.28 ± 2.89) µm], trabecular number [(2.86 ± 0.06) mm(-1)], mineral apposition rate [(2.32 ± 0.02) µm/d] and index of osteoblast [(30.20 ± 0.47) N/mm(2)] in subchondral region of the cartilage in the experimental group were significantly increased compared with the age-matched controls [respectively (64.00 ± 1.54)%, (87.00 ± 1.13) µm, (1.84 ± 0.08) mm(-1), (1.69 ± 0.02) µm/d and (21.07 ± 0.59) N/mm(2)] (P < 0.05). However, trabecular separation [(170.00 ± 2.25) µm] was lower than those in the controls [(241.50 ± 1.57) µm] with significant difference(P < 0.05). There was no significant difference in the bone histomorphometry parameters of the central region between the experimental group and the age-matched control group (P > 0.05).

CONCLUSIONSThe pattern of bone histomorphometry parameters expression in subchondral region has a high correlation with the adaptive remodeling of the condyle after functional appliance.

Animals ; Cartilage ; anatomy & histology ; growth & development ; Female ; Male ; Mandibular Advancement ; Mandibular Condyle ; anatomy & histology ; growth & development ; Orthodontic Appliances, Functional ; Rabbits ; Random Allocation

OBJECTIVETo study c-fos and substance P expression in the central nervous system following mechanical and chemical nociceptive stimulation to the masseters in rats with occlusal interference.

METHODSOcclusal interference was made by bonding a 2 mm long dentin screw in the pulp cavity of the first maxillary molar in the left side. Seven days after occlusal interference, the rats in occlusal interference and mechanical stimulus group and mechanical stimulus control group were light anesthetized and nociceptive mechanical stimulus were applied to the ipsilateral masseter. Pain response was recorded and all the animals were killed 2 hours later. The rats in the other two groups were deep anesthetized and 100 microL 5% formalin was injected into the ipsilateral masseter, killed 2 hours later. The brainstem and cervical spinal cord were processed c-fos and substance P immunoreactivity and data were quantitatively analyzed.

RESULTSBoth mechanical and chemical stimulus to the ipsilateral masseter induced increasing neuronal c-fos expression in the trigeminal nucleus and in the cervical spinal dorsal horn in occlusal interference and mechanical stimulus group and occlusal interference and chemical stimulus group (P < 0.05). Following mechanical stimulation to the ipsilateral masseter, substance P expression in the trigeminal nucleus transition zone was increased in occlusal interference and mechanical stimulus group (P < 0.05).

CONCLUSIONThe central neuronal sensitization in the brainstem may play an important role in the masticatory muscle pain induced by occlusal interference.

Animals ; Masseter Muscle ; Masticatory Muscles ; Pain ; Proto-Oncogene Proteins c-fos ; Rats ; Rats, Sprague-Dawley

ObjectiveTo investigate the regulatory effects of traditional Chinese medicine (TCM) Shufengxuanfeijiedu formula on Janus kinase signal transducer and activators of transcription (JAK-STAT) of lung tissues in mice with influenza viral pneumonia.Methods According to random number table, 60 mice were randomly divided into six groups with 10 mice in each group: normal group (N), model group (M), Tamiflu control group (C) and low (SL), medium (SM), high dose (SH) Shufengxuanfeijiedu formula groups. The mouse model of influenza virus pneumonia was reproduced by dropping of 0.05 mL 4LD50 inflluenza virus FM1 strain which can be adapted to lung tissue into the nose; while the N received nose instillation of 0.05 mL normal saline. After successful modeling for 2 hours, distilled water was given orally (by lavage) to N and M; Duffy (oseltamivir) 2.5 g·mL-1·d-1 was administrated to C; the TCM SL, SM, SH were intragastrically administered with different doses of shufengxuanfeijiedu decoction into the corresponding groups respectively (the ingredients of prescription: chrysanthemum, mulberry leaf, almond, platycodon root, forsythia, bupleurum etc. forming granules), according to the suitable dose of granules used for human body surface, the dose used for mouse surface area was calculated, the high dose means the dose used in the medium dose group doubled, the low dose means 1/2 dose used in medium group, once a day, once 0.2 mL for consecutive 4 days. Afterwards, the lung tissues were collected, the mouse differential gene expressions related to JAK-STAT pathway were detected by gene chip technology, the standards for screening of differential gene expression were as follows: up-regulated gene was P < 0.05, and the log2ratio > 1; down-regulation gene wasP < 0.05, and log2ratio < -1. The levels in lung tissue kinase (JAK) andγinterferon (IFN-γ) mRNA expressions were determined by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results Compared with those in N, the differential expression gene transcription activator, STAT5 [log2 (N/M) = 2.32], interleukin 4 receptor alpha subunit [IL4RA, log2 (N/M) = 4.77], interleukin 12 receptor [IL12R, log2 (N/M) = 1.58], JAK [log2 (N/M) = 2.41] were all obviously up-regulated, and IFN was significantly down-regulated [log2 (N/M) = -1.45] in M. Compared with those in M, C group IFN [log2 (C/M) = 1.51], various TCM dose groups [log2 (SL/M) = 1.46, log2 (SM/M) = 1.72, log2 (SH/M) = 1.40] differential expression gene IFN was significantly up-regulated, STAT5 [log2 (C/M) = -2.06, log2 (SL/M) = -1.41, log2 (SM/M) = -2.10, log2 (SH/M) = -1.89], IL4RA [log2 (C/M) = -2.52, log2 (SL/M) = -1.85, log2 (SM/M) = -2.74, log2 (SH/M) = -1.39), IL12R [log2 (C/M) = -1.48, log2 (SL/M) = -0.10, log2 (SM/M) = -1.58, log2 (SH/M) = -0.53], JAK [log2 (C/M) = -1.44, log2 (SL/M) = -0.88, log2 (SM/M) = -1.74, log2 (SH/M) = -0.53] were significantly down-regulated. In M, the JAK mRNA expression was obviously elevated (2-ΔΔCt: 3.17±0.94 vs. 1.01±0.13,P < 0.05), while the IFN-γ mRNA expression was decreased (2-ΔΔCt: 0.15±0.48 vs. 1.01±0.12,P < 0.05); compared with M, the JAK mRNA expressions in C, SM and SH groups were all obviously decreased (2-ΔΔCt: 2.02±0.63, 1.19±0.30, 1.59±0.67 vs. 3.17±0.94, allP < 0.05); while the IFN-γmRNA expressions in C, SL, SM and SH groups were elevated (2-ΔΔCt: 0.61±0.12, 0.41±0.13, 0.85±0.14, 0.78±0.20 vs. 0.15±0.48, allP < 0.05).Conclusions Shufengxuanfeijiedu formula can ameliorate the mice immune pathological injury of lung tissues induced by influenza virus by regulating JAK-STAT signal pathway and balancing Th1/2 via up-regulating the expression of IFN-γ.

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

Objective To investigate the relationship between methyle-netetrahydrofolate reductase ( MTHFR ) genetic polymorphisms and ad-verse drug reactions of methotrexate ( MTX) chemotherapy for acute lym-phoblastic leukemia ( ALL ) in China.Methods The relevant data bases were searched and reviewed.Meta -analysis was performed by software of RevMan 5.3.Results Ten studies were included , and half of them only involved MTHFR C 677 T, and the others involved both.The meta-analysis showed thatcompared with 677 CT/TT, 677 CC had a low-er risk of erythra ( P<0.05 );there were no significant differences in the total adverse drug reactions and other types of adverse drug reaction;age had no effect on the relationship between MTHFR genetic polymorphisms and adverse reactions of MTX.There were no significant differences in the total adverse reactions and different types of adverse reaction between 1298 AA and 1298 AC/CC; 1298 AA had a lower risk of mucositis than 1298 AC/CC in pediatric ALL ( P<0.05 ).Conclusion MTHFR C677 T and A1298 C polymorphisms do not seem to be good markers of MTX -re-lated total adverse drug reactions , but may affect part types such as eryth-ra and mucositis in Chinese ALL.

Objective To study the influences of mental disorders on female systemic lupus erythematosus(SLE)and analyze the factors. Methods We used symptom check list -90 (SCL-90) as a basis for judging mental disorders disease activity. Disease activity, social support and depreciation - discrimination were used as possible influencing factors. Social support and discomfort – discrimination were possible influencing factors. Multivariate unconditional logistic regression model was used to analyze the influencing factors of mental disorders. Results The total score of SCL-90 of patients with female SLE was significantly higher than that of norm models ［(136.39±48.66) vs (129.96±38.76)］ (P<0.05), in 289 SLE patients, the number of patients with mental disorders was 128 (44.3%). High monthly income(OR=0.770, 95% CI:0.604-0.981, P=0.034) was a protective factor for mental disorders. High disease activity (OR=1.792, 95% CI:1.023-3.138, P=0.042)and high discomfort–discrimination (OR=1.100, 95% CI:1.035-1.169, P=0.002)were risk factors for mental disorders. Conclusions Female SLE patients have a higher risk of mental disorders than the general population. And eliminating self-depreciation, reducing social discrimination, active employment, increasing monthly income, standardizing treatment and reducing disease activity may effectively alleviate mental disorders in SLE patients.

BACKGROUNDCytosine deaminase (CD) converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic beta-alanine without uracil phosphoribosyltransferase (UPRT). UPRT catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate, which directly kills CD::UPRT-expressing cells and surrounding cells via the bystander effect. But the pharmacokinetics and the bystander effect of CD::UPRT/5-FC has not been verified in vivo and in vitro. Before the CD::UPRT/5-FC bi-gene therapy system is used in clinical trial, it is essential to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using (19)F-magnetic resonance spectroscopy ((19)F-MRS) and optical imaging to measure non-invasive CD and UPRT expression and its bystander effect.

METHODSC6 and C6-CD::UPRT cells were cultured with 5-FC. The medium, cells and their mixture were analyzed by (19)F-MRS. Rats with intracranial xenografted encephalic C6-CD::UPRT glioma were injected intraperitoneally with 5-FC and their (19)F-MRS spectra recorded. Then the pharmacokinetics of 5-FC was proved. Mixtures of C6 and C6-CD::UPRT cells at different ratios were cultured with 5-FC and the cytotoxic efficacy and survival rate of cells recorded. To determine the mechanism of the bystander effect, the culture media from cell comprising 25% and 75% C6-CD::UPRT cells were examined by (19)F-MRS. A comparative study of mean was performed using analysis of variance (ANOVA).

RESULTS(19)F-MRS on samples from C6-CD::UPRT cells cultured with 5-FC showed three broad resonance signals corresponding to 5-FC, 5-FU and fluorinated nucleotides (F-Nuctd). For the C6 mixture, only the 5-FC peak was detected. In vivo serial (19)F-MRS spectra showed a strong 5-FC peak and a weak 5-FU peak at 20 minutes after 5-FC injection. The 5-FU concentration reached a maximum at about 50 minutes. The F-Nuctd signal appeared after about 1 hour, reached a maximum at around 160 minutes, and was detectable for several hours. At a 10% ratio of C6-CD::UPRT cells, the survival rate was (79.55 +/- 0.88)% (P < 0.01). As the C6-CD::UPRT ratio increased, the survival rate of the cells decreased. (19)F-MRS showed that the signals for 5-FU and F-Nuctd in the culture medium increased as the ratio of C6-CD::UPRT in the mixture increased.

CONCLUSIONS(19)F-MRS studies indicated that C6-CD::UPRT cells could effectively express CD and UPRT enzymes. The CD::UPRT/5-FC system showed an obvious bystander effect. This study demonstrated that CD::UPRT/5-FC gene therapy is suitable for 5-FC to F-Nuctd metabolism; and (19)F-MRS can monitor transferred CD::UPRT gene expression and catalysis of substrates noninvasively, dynamically and quantitatively.

Animals ; Antimetabolites ; pharmacokinetics ; therapeutic use ; Cell Line ; Cytosine Deaminase ; genetics ; physiology ; Flucytosine ; pharmacokinetics ; therapeutic use ; Genetic Therapy ; methods ; Glioma ; drug therapy ; therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Pentosyltransferases ; genetics ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect of Al2O3 particles sandblasting on the surface roughness, element composition and resin bond durability of zirconia ceramic.

METHODSSixty 2.5 mm thick computer aided design and computer aided manufacture (CAD/CAM) zirconia ceramic (Vita Inceram YZ) plates were fired, polished and cleaned. Half of polished ceramic plates was sandblasted with 50 µm alumina particles at 0.3 MPa for 20 s. The surface roughness of polished and sandblasted ceramic surface were measured by 3D-laser scanning microscope, and the surface element weight and atom ratio of the ceramic surface were measured by energy disperse spectroscopy (EDS). Then polished and sandblasted ceramic plates were randomized into six groups. In Group 1 and 2 the polished and sandblasted ceramic plates were bonded irrespectively with conventional resin cement (DUOLINK). In Group 3 and 4 the ceramic plates were bonded with resin cement containing MDP (Panavia F), In Group 5 and 6 the specimens were pretreated with silane coupler acitivated by MDP (Clearfil Ceramic Primer), then bond with Panavia F. The specimens of each test group were then divided into two subgroups, and to received shear test after 0 and 10 000 time thermal cycle. The data was analyzed by one-way ANOVA and independent t test.

RESULTSComparing with polishing, sandblasting reduced the oxygen atom and weight ratio of zirconia ceramic surface (P < 0.001), and increased the zirconium atom and weight ratio (P < 0.001), meanwhile increased the surface roughness (P < 0.001). The bond strength between ceramic plates and resin cement in all test groups decreased after thermocycling (P < 0.001). All specimen in test group 1 and 2 lost bond, and the bond strength of test group 3 and 5 [(0.59 ± 0.17), (0.89 ± 0.84) MPa] were significantly lower than that of test group 4 and 6 [(14.63 ± 3.03), (16.64 ± 1.90) MPa], and the bond strength of test group 6 were significanlty higher than that of test group 4.

CONCLUSIONSSandblasting improves durability of bond between zirconia ceramic and resin cement containing MDP, not only by increasing the roughness and area of ceramic surface, but also by changing its surface element composition to obtain more chemical bond.

Aluminum Oxide ; chemistry ; Ceramics ; chemistry ; Dental Bonding ; Dental Stress Analysis ; Materials Testing ; Microscopy, Electron, Scanning ; Resin Cements ; chemistry ; Shear Strength ; Surface Properties ; Zirconium ; chemistry

BACKGROUNDThe urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling.

METHODSDisc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques.

RESULTSThe expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks.

CONCLUSIONSThe expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

Animals ; Cartilage, Articular ; metabolism ; Female ; Joint Dislocations ; metabolism ; pathology ; Male ; Mandibular Condyle ; metabolism ; pathology ; Plasminogen Activator Inhibitor 1 ; genetics ; RNA, Messenger ; analysis ; Rabbits ; Temporomandibular Joint ; metabolism ; Temporomandibular Joint Disc ; Urokinase-Type Plasminogen Activator ; genetics

OBJECTIVETo investigate the effect of anterior disc displacement on the expression of urokinase plasminogen activator and its inhibitor-1 (uPA/PAI-1) in synovial tissues.

METHODSForty Japanese white rabbits were used in this study. The animals were killed at 4 days, 1, 2, 4, 8 and 12 weeks postoperatively, respectively. In situ hybridization technology was applied to detect the expression of uPA/PAI-1 mRNA in synovial membrane.

RESULTSIn normal synovial tissues, synovial lining cells and a few fibrosblasts with mild positive staining were occasionally seen. More synovial lining cells and fibrosblasts with moderate postive signals were found 1 week after operation. Since then, the degree of staining for uPA/PAI-1 increased gradually. By the end of 12 weeks postoperatively, strong signals of uPA/PAI-1 mRNA were detected.

CONCLUSIONThere is a harmonized uPA/PAI-1 system existing in synovial tissues. The high expression of uPA and PAI-1 mRNA in synovial tissues indicates that the uPA/PAI-1 system may play an important role in the process of synovitis resulted from anterior disc displacement.

Animals ; In Situ Hybridization ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; RNA, Messenger ; Rabbits ; Synovial Membrane ; Urokinase-Type Plasminogen Activator