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.

Conjoined twins with mirror-image cleft lip and palate: Case report in Brazil

The observation of mirror-image clefts in conjoined twins may suggest an influence from environmental factors (e.g., poor blood supply) on the appearance of clefts. The present paper reports on a pair of male thoracopagus twins born to a 20-year-old woman. The twins were stillborn. Both twins exhibited complete unilateral cleft lip and palate with mirror-image configuration, affecting the left side for twin A and the right side for twin B. The twins also shared some organs. The case is discussed with similar information in the literature, with reference to possible related etiologic factors. Reporting on such occurrences throughout the world is important to shed light on important aspects underlying the formation of clefts.

Sialolithiasis of the Submandibular Gland

Sialolithiasis of the salivary gland is a benign pathology that occurs most frequently in the submandibular gland because of its anatomic features. Depending on the sialolith size and calcification degree, it can be visible in radiographic examinations. Commonly, patients may experience pain and/or edema, when the ducts are obstructed. The authors report the case of sialolithiasis of the submandibular gland in a 42-year-old, female, white-skinned patient, noticed during routine dental examination. Following diagnosis confirmed by clinical and radiographic examinations, the treatment plan consisted of surgery for removal of the calcified mass. The prognosis is often good, and generally there is no recurrence.

Saethre-Chotzen Syndrome, Pro136His TWIST Mutation, Hearing Loss, and External and Middle Ear Structural Anomalies: Report on a Brazilian Family

Objective: To describe the clinical, speech, hearing, and imaging findings in three members of a Brazilian family with Saethre-Chotzen syndrome (SCS) who presented some unusual characteristics within the spectrum of the syndrome. Design: Clinical evaluation was performed by a multidisciplinary team. Direct sequencing of the polymerase chain reaction amplified coding region of the TWIST1 gene, routine and electrophysiological hearing evaluation, speech evaluation, and imaging studies through computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed. Results: TWIST1 gene analysis revealed a Pro136His mutation in all patients. Hearing evaluation showed peripherial and mixed hearing loss in two of the patients, one of them with severe unilateral microtia. Computed tomography scan showed structural middle ear anomalies, and MRI showed distortion of the skull contour as well as some of the brain structures. Conclusions: We report a previously undescribed TWIST1 gene mutation in patients with SCS. There is evidence that indicates hearing loss (conductive and mixed) can be related both with middle ear (microtia, high jugular bulb, and enlarged vestibules) as well as with brain stem anomalies. Here we discuss the relationship between the gene mutation and the clinical, imaging, speech, and hearing findings.

Influence of Orthognathic Surgery on Voice Fundamental Frequency

Considering that orthognathic surgery promotes changes in orofacial structures constituting the resonating system, functional changes secondary to surgery are expected to affect speech, leading to the need for further speech and voice adjustments. Thus, understanding the possible relationships of these structures with voice production is important. Therefore, this Study aimed to describe the changes in voice fundamental frequency of a patient submitted to orthognathic surgery and observe if there is a relationship with hyoid bone positioning at the different treatment periods. The results revealed that voice fundamental frequency increased after surgery, returning to values close to the preoperative condition, which corresponded to vertical movement of the hyoid bone.

The anti-MMP activity of benzalkonium chloride

Objective: This study evaluated the ability of benzalkonium chloride (BAC) to bind to dentine and to inhibit soluble recombinant MMPs and bound dentine matrix metalloproteinases (MMPs). Methods: Dentine powder was prepared from extracted human molars. Half was left mineralized; the other half was completely demineralized. The binding of BAG to dentine powder was followed by measuring changes in the supernatant concentration using UV spectrometry. The inhibitory effects of BAC on rhMMP-2, -8 and -9 were followed using a commercially available in vitro proteolytic assay. Matrix-bound endogenous MMP-activity was evaluated in completely demineralized beams. Each beam was either dipped into BAG and then dropped into 1 mL of a complete medium (CM) or they were placed in 1 mL of CM containing BAG for 30 days. After 30 days, changes in the dry mass of the beams or in the hydroxyproline (HYP) content of hydrolysates of the media were quantitated as indirect measures of matrix collagen hydrolysis by MMPs. Results: Demineralized dentine powder took up 10-times more BAG than did mineralized powder. Water rinsing removed about 50% of the bound BAC, whilst rinsing with 0.5 M NaCl removed more than 90% of the bound BAG. BAG concentrations 0.5 wt% produced 100% inhibition of soluble recombinant MMP-2, -8 or -9, and inhibited matrix-bound MMPs between 55 and 66% when measured as mass loss or 76-81% when measured as solubilization of collagen peptide fragments. Conclusions: BAC is effective at inhibiting both soluble recombinant MMPs and matrix-bound dentine MMPs in the absence of resins. (C) 2010 Elsevier Ltd. All rights reserved.

State of the art etch-and-rinse adhesives

Objectives: The aim of this study was to explore the therapeutic opportunities of each step of 3-step etch-and-rinse adhesives. Methods: Etch-and-rinse adhesive systems are the oldest of the multi-generation evolution of resin bonding systems. In the 3-step version, they involve acid-etching, priming and application of a separate adhesive. Each step can accomplish multiple goals. Acid-etching, using 32-37% phosphoric acid (pH 0.1-0.4) not only simultaneously etches enamel and dentin, but the low pH kills many residual bacteria. Results: Some etchants include anti-microbial compounds such as benzalkonium chloride that also inhibits matrix metalloproteinases (MMPs) in dentin. Primers are usually water and HEMA-rich solutions that ensure complete expansion of the collagen fibril meshwork and wet the collagen with hydrophilic monomers. However, water alone can re-expand dried dentin and can also serve as a vehicle for protease inhibitors or protein cross-linking agents that may increase the durability of resin-dentin bonds. In the future, ethanol or other water-free solvents may serve as dehydrating primers that may also contain antibacterial quaternary ammonium methacrylates to inhibit dentin MMPs and increase the durability of resin-dentin bonds. The complete evaporation of solvents is nearly impossible. Significance: Manufacturers may need to optimize solvent concentrations. Solvent-free adhesives can seal resin-dentin interfaces with hydrophobic resins that may also contain fluoride and antimicrobial compounds. Etch-and-rinse adhesives produce higher resin-dentin bonds that are more durable than most 1 and 2-step adhesives. Incorporation of protease inhibitors in etchants and/or cross-linking agents in primers may increase the durability of resin-dentin bonds. The therapeutic potential of etch-and-rinse adhesives has yet to be fully exploited. (C) 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Esthetic Analysis of Gingival Components of Smile and Degree of Satisfaction in Individuals With Cleft Lip and Palate

Objective: To evaluate soft tissue characteristics in individuals with cleft lip and palate and the degree of satisfaction of these individuals after rehabilitation. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, Brazil. Patients: Forty-five individuals with repaired complete unilateral cleft lip and palate, aged 15 to 30 years. Interventions: One hundred thirty-five frontal facial photographs were obtained at rest and in natural and forced smile. Specialists in periodontics evaluated the soft tissue characteristics. Both patients and specialists evaluated the smiles and scored them as esthetically unpleasant, acceptable, or pleasant. Main Outcome Measures: Comparison of the cleft area with the contralateral region was performed for evaluation of soft tissue. The results of the degree of satisfaction with smile were expressed as percentages and means. The findings between patients and periodontists experienced or inexperienced with cleft care were compared. Results: Statistically significant differences were observed for alveolar process deficiency and absence of papilla in the esthetic area between groups (p < .05). Results show 84.4% of individuals considered their smile as esthetically pleasant. Specialists in periodontics of both groups scored the natural smile and forced smile as esthetically acceptable. There was a statistically significant difference in the mean of patients compared with both groups of specialists in periodontics (p < .05). Conclusions: Evaluation and knowledge of the soft tissue characteristics is extremely important for successful rehabilitation. The esthetic values and degree of patient satisfaction are essential for treatment success, since smile reconstruction should be esthetically pleasant to the patient.

Are Teeth Close to the Cleft More Susceptible to Periodontal Disease?

Objective: To evaluate whether teeth close to the cleft area present higher prevalence and severity of periodontal disease than teeth in other regions. Design: Cross-sectional. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo. Patients: There were 400 Individuals with complete unilateral or bilateral cleft lip and palate, aged 15 to 49 years, without any previous periodontal treatment. Main Outcome Measures: All clinical parameters were evaluated in six sites for each tooth. The arithmetic means were calculated for each sextant. Results: Of the sextants, 86.75% presented means of probing depth smaller than or equal to 3 mm. No sextant exhibited means of probing depth greater than or equal to 6 mm. There was a statistically significant difference (p < .001) in probing depth according to age, types of cleft, and sextant; 95.87% of sextants presented mean attachment levels smaller than or equal to 3 mm, The sextant with cleft did not present higher means of probing depth, clinical attachment level, plaque index, and gingival index. There was gingival bleeding in 99.08% of the sample and plaque In 97.40%. The type of cleft was not an Important factor Influencing the prevalence of periodontal disease. Age seems to be an Important factor influencing the prevalence and severity of periodontal disease for all aspects Investigated. Conclusions: Periodontal disease In individuals with clefts occurred in a similar manner as observed in other populations. The presence of the cleft does not seem to Increase the prevalence of the disease.

Evaluation of the presence or absence of papilla between tooth and implant

Objective: The purpose of this study was to evaluate the papilla level adjacent to single-tooth implants in the maxillary anterior region in individuals with cleft lip, alveolus, and palate to verify whether there is correlation among the vertical distance, horizontal distance, dental/prosthetic crown shape, and periodontal/peri-implant biotype with the presence of interproximal papilla. Design: Cross-sectional. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo (HRAC/USP). Patients: 77 papillae in 40 patients. Interventions: The periodontal/peri-implant biotype was clinically evaluated and characterized as thin or thick. Intraoral photographs were used to evaluate the presence or absence of papilla. Main Outcome Measures: Classification in scores (0 to 3) and determination of length (CL) and width (CW) of crowns adjacent to papillae. The CW/CL ratio was calculated for each crown in order to characterize it as square-shaped or triangular-shaped. The vertical and horizontal distances were obtained by radiographic evaluation. Results: The correlations between vertical distance and papilla score and horizontal distance and papilla score were statistically significant (p= .02 and p = .01). There was no significant difference between crown shape and periodontal/peri-implant biotype in distinct correlations with the papilla score (p = .41 and p = .07). Conclusion: The results suggest that the vertical and horizontal distances may have independent or combined relationship with the existence of interproximal papilla; the periodontal/peri-implant biotype (phenotype) was not correlated with the presence or absence of papilla, as well as the shape of the dental/prosthetic crown.

Survival of Dental Implants in the Cleft Area-A Retrospective Study

Objective To evaluate the survival rate of dental implants placed in the cleft area Design Retrospective study Setting Hospital for Rehabilitation of Craniofacial Anomalies, Brazil Institutional Tertiary Healthcare Center Patients 120 patients who received dental implants in the grafted cleft area in the years 1999 to 2005 Interventions Clinical data were evaluated from the records of 120 patients according to the following criteria placement grafted, cleft area, and age at surgery, age at placement of dental implants, site and dimension of implants, interval between placement of implants and the last clinical follow-up, and interval between placement and removal or indication for removal of implants Main Outcome Measures Percentage of survival rate of implants Results Mean age at placement of the bone graft was 17 6 years and 21 years at placement of implants A total of 123 cleft areas received secondary bone graft and bone graft to install implants (regraft) The mean survival rate was 34 months since placement of the implant to the last clinical follow-up and 26 months since placement of the prosthesis Seven dental implants were removed The survival rate since placement to the last clinical follow-up was 94 3% Conclusion Rehabilitation of the cleft area with dental implants is a viable and secure alternative, with good prognosis

Cleft Palate Obturation With Branemark Protocol Implant-Supported Fixed Denture and Removable Obturator

A 41-year-old man with cleft palate presented with a wide dehiscence and missing teeth. Six implants had been placed for fabrication of an overdenture, which was unsatisfactory. A bar was waxed and cast for connection to the implants; precision attachments were placed laterally for retention. A fixed partial denture was fabricated, and milled crowns were fabricated at the molar region to provide a guiding plane for insertion of a removable palatal obturator. Good swallowing and speech outcomes were achieved. This technique provided functional and esthetic benefits, enhanced oral hygiene, and improved the psychological condition of the patient.

Effects of Orthopedic Rapid Maxillary Expansion on Internal Nasal Dimensions in Children With Cleft Lip and Palate Assessed by Acoustic Rhinometry

The objective of the current study was to characterize the internal nasal dimensions of children with repaired cleft lip and palate and transverse maxillary deficiency, using acoustic rhinometry and analyze the changes caused by rapid maxillary expansion (RME). A convenience sampling of 19 cleft lip and palate individuals, aged 14 to 18 years, of both sexes, previously submitted to primary surgeries and referred for RME were analyzed prospectively at the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, Bauru, Sao Paulo, Brazil. All patients underwent acoustic rhinometry before installation of the expansor and at 30 and 180 days after the active expansion phase. Nasal cross-sectional areas and volumes corresponding to the nasal valve (CSA(1) and V(1)) and the turbinates (CSA(2), CSA(3), and V(2)) regions were determined before and after nasal decongestion. Rapid maxillary expansion led to a statistically significant increase (P < 0.05) in mean CSA(1), CSA(2), V(1), and V(2) (without nasal decongestion) and in CSA(1) and V(1) (with decongestion) in the group as a whole. Individual data analysis showed that 58% of the patients responded positively to RME, with an average increase in CSA(1) of 26% (with decongestion), whereas 37% of the patients had no significant change. Only 1 patient (5%) showed a decrease. The findings contribute toward the characterization of nasal deformities determined by the cleft and demonstrate the positive effect RME had on nasal morphophysiology in a significant number of the patients who underwent this procedure.

MMP-9 and CD68(+) cells are required for tissue remodeling in response to natural hydroxyapatite

Large bone defects represent major clinical problems in the practice of reconstructive orthopedic and craniofacial surgery. The aim of this study was to examine, through immunohistochemistry approach, the involvement of MMP-9 and CD68(+) cells during tissue remodeling in response to natural hydroxyapatite (HA) implanted in rat subcutaneous tissue. Before experimentation, forty animals were randomly distributed into two experimental groups: Group-I (Gen-Ox (TM) micro-granules) and Group-II (Gen-Ox (TM) macro-granules). Afterwards, the biopsies were collected after 10, 20, 30, and 60 days post-implantation. Our results showed that at 10 days, a low-renewal foreign body type granuloma formation was observed in most of the cases. Macrophage- and fibroblast-like cells were the predominant type of cells positively stained for MMP-9 in both groups. Once macrophage-like cells seemed to be the major source of MMP9, antibody against pan-CD68 epitope was used to correlate these findings. In agreement, MMP-9 and CD68(+) cells were distributed at the periphery and the central region of the granuloma in all experimental periods, however no staining was observed in cell contacting to material. Besides macrophages, the lysosomal glycoprotein epitope recognized by CD68 antibodies can be expressed by mast cell granules and sometimes by fibroblasts. Taken together, our results suggest that xenogenic HA promotes extracellular matrix remodeling through induction of MMP-9 activity and presence of CD68(+) cells.

Surgical planning for resection of an ameloblastoma and reconstruction of the mandible using a selective laser sintering 3D biomodel

Ameloblastoma is a benign locally aggressive infiltrative odontogenic lesion. It is characterized by slow growth and painless swelling. The treatment for ameloblastoma varies from curettage to en bloc resection, and the reported recurrence rates after treatment are high; the safety margin of resection is important to avoid recurrence. Advances in technology brought about great benefits in dentistry; a new generation of computed tomography scanners and 3-dimensional images enhance the surgical planning and management of maxillofacial tumors. The development of new prototyping systems provides accurate 3D biomodels on which surgery can be simulated, especially in cases of ameloblastoma, in which the safety margin is important for treatment success. A case of mandibular follicular ameloblastoma is reported where a 3D biomodel was used before and during surgery.