Timing of force application affects the rate of tooth movement into surgical alveolar defects with grafts in beagles.

INTRODUCTION: The purpose of this study was to investigate the influence of the timing of orthodontic force application on the rates of orthodontic tooth movement into surgical alveolar defects with bone grafts in beagle dogs. METHODS: Twelve beagles were randomly divided into 2 groups according to the surgical procedure: alveolar osteotomy alone (control) or osteotomy with bone graft (experimental group). The maxillary second premolars were protracted for 6 weeks into the surgical sites: immediately, at 2 weeks, and at 12 weeks after surgery. The orthodontic tooth movement rates and alveolar remodeling concomitant with surgical defect healing were evaluated by model measurements and histomorphometry as well as microcomputed tomography and histology. One-way analysis of variance and the Scheffé post hoc comparison were performed for investigating the rates of orthodontic tooth movement and mineralized bone formation. RESULTS: Both the orthodontic tooth movement rate and the mean appositional length of mineralized bone in the tension side of teeth were significantly accelerated when force was applied at 2 weeks in the control group and immediately in the experimental group (P <0.001). The 2-week control group showed a dramatic increase in apposition rate during 4 to 6 weeks after force application, whereas the immediate protraction experimental group did within the first 3 weeks (P <0.001). Decreased orthodontic tooth movement rates and reduced bone remodeling activities were apparent in the 12-weeks groups, especially in nongrafted defects. CONCLUSIONS: A bone graft into the surgical defect can not only allow immediate force application for accelerating orthodontic tooth movement with favorable periodontal regeneration, but also decrease the risk of inhibited orthodontic tooth movement in case of delayed force application after surgery.

Understanding viscoelastic behavior of hybrid nanocellulose film based on rheological and electrostatic observation in blended suspension.

The effects of TEMPO-mediated oxidized cellulose nanofibril (TOCN) on the viscoelastic behavior and phase of cellulose nanocrystal (CNC) in suspension and film were investigated using polarized optical microscopy, rotational rheometry, and dynamic mechanical analysis. The sodium cation from TOCN changed the electrostatic state of CNC by screening the CNC surface charge. The volume inflation of TOCN locally increased the CNC concentration in the suspension. In turn, the CNC-CNC interactions increased the viscosity and the yield stress. Based on the experimental observation, the changing mechanisms of electrostatic state and particular interaction in the TOCN/CNC suspensions were suggested. In the hybrid film, the time dependency of complex moduli was changed owing to the different networking between CNCs and TOCNs. The CNC-CNC contacts easily collapsed by strain, while the TOCN-TOCN entanglements were slowly altered. This study provides a fundamental understanding of CNC behavior for optimizing processes and composite properties.

A novel glucagon analog with an extended half-life, HM15136, normalizes glucose levels in rodent models of congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs. < 5 min) and increased bioavailability (90%) compared to native glucagon in mice. Further, HM15136 could effectively reverse acute hypoglycemia induced by insulin challenge, and multiple doses of HM15136 could sustain increased blood glucose levels in CHI rats. In conclusion, our findings indicate that HM15136 promotes sustained elevation of blood glucose, demonstrating the potential for development as a once-weekly therapy for CHI.

Biosynthesis of polylactic acid and its copolymers using evolved propionate CoA transferase and PHA synthase.

For the synthesis of polylactic acid (PLA) and its copolymers by one-step fermentation process, heterologous pathways involving Clostridium propionicum propionate CoA transferase (Pct(Cp)) and Pseudomonas sp. MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1(Ps6-19)) were introduced into Escherichia coli for the generation of lactyl-CoA endogenously and incorporation of lactyl-CoA into the polymer, respectively. Since the wild-type PhaC1(Ps6-19) did not efficiently accept lactyl-CoA as a substrate, site directed mutagenesis as well as saturation mutagenesis were performed to improve the enzyme. The wild-type Pct(Cp) was not able to efficiently convert lactate to lactyl-CoA and was found to exert inhibitory effect on cell growth, random mutagenesis by error-prone PCR was carried out. By employing engineered PhaC1(Ps6-19) and Pct(Cp), poly(3-hydroxybutyrate-co-lactate), P(3HB-co-LA), containing 20-49 mol% lactate could be produced up to 62 wt% from glucose and 3HB. By controlling the 3HB concentration in the medium, PLA homopolymer and P(3HB-co-LA) containing lactate as a major monomer unit could be synthesized. Also, P(3HB-co-LA) copolymers containing various lactate fractions could be produced from glucose alone by introducing the Cupriavidus necator beta-ketothiolase and acetoacetyl-CoA reductase genes. Fed-batch cultures were performed to produce P(3HB-co-LA) copolymers having 9-64 mol% of lactate, and their molecular weights, thermal properties, and melt flow properties were determined.

Quantitative analysis of effects of the grid specifications on the quality of digital radiography images.

A grid is one of the key components of a digital radiography (DR) system because it removes scattered radiation, which arises when X-rays penetrate an object and improves diagnostic accuracy by enhancing image quality. With the widespread use of DR systems, demand for grids with high precision has simultaneously increased. Because unsuitable grids may decrease image quality and lead to misdiagnosis, using optimised grids for DR systems is critical. In this study, we aimed to analyse the quality of X-ray images acquired using grids with different specifications and proposed standardised criteria for grid use on the basis of our results. We measured modulation transfer function (MTF), normalised noise power spectrum (NNPS) and detective quantum efficiency (DQE) using grids with different ratios (10:1, 12:1 and 15:1) with or without implementing poly methyl methacrylate (PMMA) phantoms (0-20 cm). Pixel pitch of the detector used in this experiment was 143 µm. Based on this, a grid with a line frequency of 85 line pairs/cm was selected to prevent distortion caused by implementing unoptimised grids. As a result, the NNPS was found to increase when using the grid, and the difference in MTF and DQE was only measured when the scattered X-ray was generated by stacking the PMMA phantom. However, grids showed a positive effect MTF and DQE when the PMMA phantom was implemented. Specifically, MTF and DQE improved with increase in grid ratio. Thus, it is desirable to use a high-ratio grid to improve image quality.

Heparin-cellulose-charcoal composites for drug detoxification prepared using room temperature ionic liquids.

We report novel heparin-cellulose-charcoal composites prepared using room temperature ionic liquids (RTILs) to enhance the biocompatibility and blood compatibility of activated charcoal beads while decreasing the size of their active pores.

Combined effect of photobiomodulation with a matrix metalloproteinase inhibitor on the rate of relapse in rats.

OBJECTIVE: To investigate combined effect of photobiomodulation with a matrix metalloproteinase (MMP) inhibitor on the relapse rate in relation to MMP expression in rats. MATERIALS AND METHODS: Fifty-two rats were divided into four groups according to the treatment modality: control group, irradiation group, doxycycline group, and irradiation with doxycycline group. During a relapse period of 5 days after orthodontic movement, maxillary central incisors were treated by low-level laser therapy (LLLT) as a photobiomodulation and/or doxycycline as a synthetic MMP inhibitor. Relapse rate was evaluated in association with MMP expression at the gene and protein levels. RESULTS: Relapse rates were increased by LLLT (1.57-fold) and decreased by doxycycline (0.83-fold) compared with the control, showing positive correlation with the levels of expression for all MMPs in the periodontal ligament (PDL). LLLT concomitant with doxycycline administration resulted in no significant differences of relapse rate and MMP expression from the control. CONCLUSIONS: The combined effect of photobiomodulation with an MMP inhibitor around the relapsing teeth proved to be antagonistic to PDL remodeling activity during relapse. This study suggests a basis for developing a novel biologic procedure targeting the MMP-dependent PDL remodeling to control the relapse rate.

Competitive extraction of multi-component contaminants in water by Carboxen-polydimethylsiloxane fiber during solid-phase microextraction.

A headspace analysis for groundwater contaminated with BTEX (benzene, toluene, ethylbenzene, and xylenes) was employed to investigate the feasibility and limitations of Carboxen-PDMS (polydimethylsiloxane) fiber during SPME (solid-phase microextraction). Although the response of the Carboxen-PDMS fiber was much higher than that of conventional PDMS fiber, a reduction of the extracted amount was also observed under multi-component conditions due to competitive replacement. The general affinity of analytes to the fiber was high in the order xylene>ethylbenzene>toluene> benzene. The behavior of the Carboxen-PDMS fiber was examined more precisely at constant compositional ratio, because the analysis of contaminants using Carboxen-PDMS fiber was reported to be possible at known composition. The relative affinity of each component was shown to differ according to the total amount of analytes. Furthermore, the extracted amounts of benzene and toluene did not show a consistent tendency as the concentration of each component increased. These results indicate that caution should be exercised if Carboxen-PDMS fibers are used for the analysis of BTEX in groundwater samples.

A method for mandibular dental arch superimposition using 3D cone beam CT and orthodontic 3D digital model.

OBJECTIVE: The purpose of this study was to develop superimposition method on the lower arch using 3-dimensional (3D) cone beam computed tomography (CBCT) images and orthodontic 3D digital modeling. METHODS: Integrated 3D CBCT images were acquired by substituting the dental portion of 3D CBCT images with precise dental images of an orthodontic 3D digital model. Images were acquired before and after treatment. For the superimposition, 2 superimposition methods were designed. Surface superimposition was based on the basal bone structure of the mandible by surface-to-surface matching (best-fit method). Plane superimposition was based on anatomical structures (mental and lingual foramen). For the evaluation, 10 landmarks including teeth and anatomic structures were assigned, and 30 times of superimpositions and measurements were performed to determine the more reproducible and reliable method. RESULTS: All landmarks demonstrated that the surface superimposition method produced relatively more consistent coordinate values. The mean distances of measured landmarks values from the means were statistically significantly lower with the surface superimpositions method. CONCLUSIONS: Between the 2 superimposition methods designed for the evaluation of 3D changes in the lower arch, surface superimposition was the simpler, more reproducible, reliable method.

Combined delivery of dexamethasone and plasmid DNA in an animal model of LPS-induced acute lung injury.

Dexamethasone was conjugated to low molecular weight polyethylenimine (2kDa, PEI2k). Dexamethasone conjugated PEI2k (PEI2k-Dexa) was evaluated as a combined delivery carrier of dexamethasone and plasmid DNA (pDNA) in an animal model of lipopolysaccharide (LPS) induced acute lung injury (ALI). In vitro transfection of L2 lung epithelial cells, PEI2k-Dexa exhibited higher transfection efficiency than PEI2k or a simple mixture of PEI2k and dexamethasone. In addition, the PEI2k-Dexa/pß-Luc complexes reduced the levels of pro-inflammatory cytokines in LPS activated Raw 264.7 macrophage cells. The anti-inflammatory effect of PEI2k-Dexa was higher than that of controls. The PEI2k-Dexa/pß-Luc complexes were administered to mice via intratracheal injection. PEI2k-Dexa had higher pDNA delivery efficiency than PEI2k in the lung and decreased TNF-α and IL-6 in the lung homogenates and bronchoalveolar lavage (BAL) fluid compared with the controls. Furthermore, total protein and immunoglobulin M (IgM) concentrations in BAL fluid were reduced by the PEI2k-Dexa/pß-Luc complexes. The intratracheal injection of the PEI2k-Dexa/pcDNA-EGFP complexes in the ALI model showed higher EGFP expression compared with PEI2k. Hematoxylin and eosin (H&E) staining showed that PEI2k-Dexa reduced inflammatory reaction in the lung. Therefore, PEI2k-Dexa may be useful for combination gene and drug therapy for ALI.

The effect of biodegradable gelatin microspheres on the neuroprotective effects of high mobility group box 1 A box in the postischemic brain.

High mobility group box 1 (HMGB1) is a family of endogenous molecules that is released by necrotic cells and causes neuronal damages by triggering inflammatory processes. In the cerebral ischemic brain, sustained and regulated suppression of HMGB1 has been emerged as a therapeutic means to grant neuroprotection. HMGB1 consists of two HMG boxes (A and B) and an acidic C-terminal tail, and the A box peptide antagonistically competes with HMGB1 for its receptors. In the middle cerebral artery occlusion (MCAO) in rats, a murine model of transient cerebral ischemia, administration of HMGB1 A box intraparenchymally, after encapsulated in biodegradable gelatin microspheres (GMS), which enhances the stability of peptide inside and allows its sustained delivery, at 1 h, 3 h, or 6 h after MCAO, reduced mean infarct volumes by, respectively, 81.3%, 42.6% and 30.7% of the untreated MCAO-brain, along with remarkable improvement of neurological deficits. Furthermore, the administration of HMGB1 A box/GMS suppressed proinflammatory cytokine inductions more strongly than the injection of non-encapsulated HMGB1 A box. Given that insulted brains-like ischemia have enhanced gelatinase activity than the normal brain, our results suggest that GMS-mediated delivery of therapeutic peptides is a promising means to provide efficient neuroprotection in the postischemic brain.

Enhanced protection of Ins-1 beta cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4.

In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 beta cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of pbeta-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the pbeta-SP-Ex-4 transfected cells, compared with the pbeta-Ex-4 transfected cells. To identify the beta-cell protection effect of pbeta-SP-Ex-4 delivery, the Ins-1 beta cells were transfected with pbeta-SP-Ex-4 or pbeta-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the pbeta-SP-Ex-4 transfected cells had higher beta-cell viability than the pbeta-Ex-4 transfected cells under hypoxia. In addition, the pbeta-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the pbeta-Ex-4 transfected cells. Therefore, PEI25k/pbeta-SP-Ex-4 complex may be useful to protect isolated beta cells from apoptosis during transplantation.

Synovial chondromatosis of the temporomandibular joint with condylar extension.

Synovial chondromatosis is a benign disease that rarely affects the temporomandibular joint (TMJ). It can be seen commonly in the superior joint space and presents with various signs and symptoms according to the stage of progression. Sometimes it presents as a large swelling in the preauricular area with or without cranial extension, and the clinical and radiographic findings may be misdiagnosed as other benign or malignant diseases of TMJ. Therefore, we report an uncommon case of synovial chondromatosis presenting as a large preauricular mass arising from the inferior joint space of the TMJ with bony resorption of the mandibular condyle, which mimicked osteochondroma.