Effect of PTK/ZK on the Angiogenic Switch in Head and Neck Tumors

Transformation of small avascular masses of tumor cells into rapidly progressive cancers is triggered by the angiogenic switch, a process that involves vascular endothelial growth factor (VEGF) signaling. We have shown that VEGF enhances the survival and angiogenic potential of endothelial cells by activating the Bcl-2-CXCL8 signaling axis. The purpose of this study was to evaluate the effect of a small-molecule inhibitor of VEGF receptors (PTK/ZK) on the initial stages of head and neck tumor angiogenesis. In vitro, PTK/ZK blocked head and neck tumor cell (OSCC3 or UM-SCC-17B)-induced Bcl-2 and CXCL8 expression in endothelial cells. Oral administration of PTK/ZK decreased xenograft head and neck tumor microvessel density, and inhibited Bcl-2 and CXCL8 expression in tumor-associated endothelial cells. Analysis of these data demonstrates that PTK/ZK blocks downstream targets of VEGF signaling in endothelial cells, and suggests that PTK/ZK may inhibit the angiogenic switch in head and neck tumors. Abbreviations: HDMEC, human dermal microvascular endothelial cells; VEGF, vascular endothelial growth factor; CXCL8, CXC ligand-8; PTK/ZK, PTK787/ZK222584.

The Effect of Framework Design on Fracture Resistance of Metal-Ceramic Implant-Supported Single Crowns

This study evaluated the effect of framework design on the fracture resistance of metal-ceramic implant-supported crowns. Screw-retained molar crowns with a screw access hole composed of metal or porcelain were compared to a cement-retained crown (control). For each group (n = 10), five crowns were subjected to dynamic loading (1,200,000 x 100 N x 2 Hz at 37 degrees C). Afterward, all specimens were loaded to failure using a universal testing machine. Significant differences could be established between the cement-and screw-retained groups (P <= .05), but no difference was found between the screw-retained groups and the specimens subjected to dynamic loading. Occlusal discontinuity of screw-retained crowns affects their resistance, and the metallic support on the screw access hole did not reinforce the crowns. Int J Prosthodont 2010;23:350-352.

Fracture resistance of endodontically treated teeth with different heights of crown ferrule restored with prefabricated carbon fiber post and composite resin core by intermittent loading

This study evaluated the fracture resistance of endodontically treated teeth restored with prefabricated carbon fiber posts and varying quantities of coronal dentin. Sixty freshly extracted upper canines were randomly divided into groups of 10 teeth each. The specimens were exposed to 250,000 cycles in a controlled chewing simulator. All intact specimens were subjected to a static load (N) in a universal testing machine at 45 degrees to the long axis. Data were analyzed by 1-way analysis of variance and Tukey test (alpha = .05). Significant differences (P < .001) were found among the mean fracture forces of the test groups (positive control, 0 mm, 1 mm, 2 mm, 3 mm, and negative control groups: 1022.82 N, 1008.22 N, 1292.52 N, 1289.19 N, 1255.38 N, and 1582.11, respectively). These results suggested that the amount of coronal dentin did not significantly increase the fracture resistance of endodontically treated teeth restored with prefabricated carbon fiber post and composite resin core. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:e52-e57)

The influence of storage condition and duration on the resistance to fracture of different fiber post systems

Purpose: To evaluate the effects of storage condition and duration on the resistance to fracture of different fiber post systems (and to morphologically assess the post structure before and after storage. Methods: Three types of fiber posts (DT Light Post, GC Post, FRC Postect Plus) were divided in different groups (n=12) according to the storage condition (dry at 37 degrees C; saline water at 37 degrees C; mineral oil at 37 degrees C and storage inside the roots of extracted human teeth immersed in saline water at 37 degrees C and duration (6, 12 months). A universal testing machine loading at a 90 degrees angle was employed for the three-point bending test. The test was carried out until fracture of the post. A 3-way ANOVA and Tukey`s test (alpha= 0.05) were used to compare the effect of the experimental factors on the fracture strength. Two posts of each group were observed before and after the storage using a scanning electron microscope. Results: Storage condition and post type had a significant effect on post fracture strength (P< 0.05). The interaction between these factors was significant (P< 0.05). Water storage significantly decreased the fracture strength, regardless of the post type and the storage duration. Storage inside roots, in oil, and at dry conditions did not significantly affect post fracture strength. SEM micrographs revealed voids between fibers and resin matrix for posts stored in water. Posts stored under the other conditions showed a compact matrix without porosities. (Am J Dent 2009;22:366-370).

IN VITRO FRACTURE RESISTANCE OF GLASS-FIBER AND CAST METAL POSTS WITH DIFFERENT LENGTHS

Statement of problem. Dental fractures can occur in endodontically treated teeth restored with posts. Purpose. The purpose of this study was to evaluate the in vitro fracture resistance of roots with glass-fiber and metal posts of different lengths. Material and methods. Sixty endodontically treated maxillary canines were embedded in acrylic resin, except for 4 mm of the cervical area, after removing the clinical crowns. The post spaces were opened with a cylindrical bur at low speed attached to a surveyor, resulting in preparations with lengths of 6 mm (group 6 mm), 8 mm (group 8 mm), or 10 mm (group 10 mm). Each group was divided into 2 subgroups according to the post material: cast post and core or glass-fiber post (n=30). The posts were luted with dual-polymerizing resin cement (Panavia F). Cast posts and cores of Co-Cr (Resilient Plus) crowns were made and cemented with zinc phosphate. Specimens were subjected to increasing compressive load (N) until fracture. Data were analyzed with 2-way ANOVA and the Tukey-Kramer test (alpha=.05). Results. The ANOVA analysis indicated significant differences (P<.05) among the groups, and the Tukey test revealed no significant difference among the metal posts of 6-mm length (26.5 N +/- 13.4), 8-mm length (25.2 N +/- 13.9), and 10-mm length (17.1 N +/- 5.2). Also, in the glass-fiber post group, there was no significant difference when posts of 8-mm length (13.4 N +/- 11.0) were compared with the 6-mm (6.9 N +/- 4.6) and 10-mm (31.7 N +/- 13.1) groups. The 10-mm-long post displayed superior fracture resistance, and the 6-mm-long post showed significantly lower mean values (P<.001). Conclusions. Within the limitations of this study, it was concluded that the glass-fiber post represents a viable alternative to the cast metal post, increasing the resistance to fracture of endodontically treated canines. (J Prosthet Dent 2009;101:183-188)

Coronal resistance to fracture of endodontically treated teeth submitted to light-activated bleaching

Objectives: The aim of this study was to assess the fracture resistance of endodontically treated teeth submitted to bleaching with 38% hydrogen peroxide activated by light-emitting diode (LED)-laser system. Methods: Fifty maxillary incisors were endodontically treated, received a zinc phosphate barrier and were embedded in acrylic resin until cemento-enamel junction. The specimens were distributed into five groups (n = 10) according to the number of bleaching sessions: GI, no treatment (control); GII, one session; GIII, two sessions; GIV, three sessions and GV, four sessions. The whitening gel was applied to the buccal surface of the tooth and inside the pulp chamber for three times in each session, followed by LED-laser activation. Specimens were submitted to the fracture resistance test (kN) and data were submitted to the Tukey-Kramer multiple comparisons test. Results: No significant difference (p > 0.05) was found between GI (0.71 +/- 0.30) and GII (0.65 +/- 0.13), which presented the highest strength values to fracture. Groups III (0.35 +/- 0.17), IV (0.23 +/- 0.13) and V (0.38 +/- 0.15) showed lower resistance to fracture (p < 0.01) when compared to GI and GII. Conclusions: The fracture resistance of endodontically treated teeth decreased after two sessions of bleaching with 38% hydrogen peroxide activated by LED-laser system. (c) 2008 Elsevier Ltd. All rights reserved.

Influence of different endodontic filling materials on root fracture susceptibility

Objective: To evaluate the influence of different endodontic materials on root fracture susceptibility. Methods: Seventy-two mandibular incisors were sectioned 1 mm below the cementoenamel junction to obtain roots of 12 mm length. Roots were submitted to chemomechanical preparation with the rotary instruments of Profile system. The obturation of root canals were performed with the following filling materials (n = 12): GI, unfilled teeth (control); GII, Endofill + gutta-percha; GIII, Sealer 26 + gutta-percha; GIV, AH Plus + gutta-percha; GV, Epiphany + gutta-percha; GVI, Epiphany + Resilon. After the sealers setting time, each root was embedded in acrylic resin. The specimens were then submitted to fracture resistance test using an Instron testing machine at 1 mm/min. Results: The ANOVA test showed no significant statistical difference (p > .05) among GI (162.16 +/- 41.4N), GII (168.46 +/- 37.5N), GIII (164.83 +/- 35.7N), GIV (168.29 +/- 38.7N), GV (172.36 +/- 20.6N) and GVI (193.11 +/- 42.8N). Conclusion: The core materials (gutta-percha or Resilon) combined with the tested endodontic sealers are not able to increase the root fracture resistance in canals submitted to chemomechanical preparation. (c) 2007 Elsevier Ltd. All rights reserved.

A for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study

Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P = 0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P = 0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P = 0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P < 0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P < 0.05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT), The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally, The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry, The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02), This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone. (C) 2001 by Elsevier Science Inc. All rights reserved.

Skeletal effects of low-intensity pulsed ultrasound on the ovariectomized rodent

Growing evidence supports low-intensity pulsed ultrasound (US) as an osteogenic mechanical stimulus. Its effects on isolated bone cells and on fractured bone are established. However, its effects on osteoporosis are not clear. This study examined US effects on ovariectomy (OVX) induced bone changes within the rodent hindlimb (distal femur and proximal tibia), and on normal bone in animals following sham-OVX. Animals were exposed to daily unilateral active-US and contralateral inactive-US for 12 weeks. Bone status was assessed using dual energy X-ray absorptiometry and histomorphometry. Ovariectomy resulted in significant bone changes. Low-intensity pulsed US did not influence these changes. These results suggest that the US dose introduced may not be a beneficial treatment for osteoporosis, and that intact bone may be less sensitive to US than fractured bone and isolated bone cells. This may relate to the biophysical mechanisms of action of US, US-bone interactions and tissue level processes taking place.

An inverse design of an open, head/neck RF coil for MRI

Radio-frequency (RF) coils are a necessary component of magnetic resonance imaging (MRI) systems. When used in transmit operation, they act to generate a homogeneous RF magnetic field within a volume of interest and when in receive operation, they act to receive the nuclear magnetic resonance signal from the RF-excited specimen. This paper outlines a procedure for the design of open RF coils using the time-harmonic inverse method. This method entails the calculation of an ideal current density on a multipaned planar surface that would generate a specified magnetic field within the volume of interest. Because of the averaging effect of the regularization technique in the matrix solution, the specified magnetic field is shaped within an iterative procedure until the generated magnetic field matches the desired magnetic field. The stream-function technique is used to ascertain conductor positions and a method of moments package is then used to finalize the design. An open head/neck coil was designed to operate in a clinical 2T MRI system and the presented results prove the efficacy of this design methodology.