Dentoskeletal changes following mini-implant molar intrusion in anterior open bite patients.

OBJECTIVE: To evaluate skeletal and dental changes after intrusion of the maxillary molars in subjects with anterior open bite. MATERIALS AND METHODS: This retrospective cephalometric study evaluated skeletal and dental changes resulting from the use of maxillary orthodontic mini-implants in 31 consecutively treated patients. Radiographs were taken at the start and end of maxillary molar intrusion to evaluate the associated changes. Statistical analysis was performed using a one-sample t-test. RESULTS: The mean treatment observation time was 1.31 years (SD  =  2.03). The maxillary first molars (P  =  0.0026) and second molars (P  =  0.039) were intruded. However, the mandibular first molars (P  =  0.0004) and second molars (P  =  0.003) erupted in adolescent patients. Both the maxillary and mandibular first molars inclined distally (P  =  0.025 and P  =  0.044, respectively). The mandibular plane angle decreased (P  =  0.036), lower facial height decreased (P  =  0.002), and the occlusal plane angle increased (P  =  0.009). The overbite increased (P < .0001). The ANB angle decreased (P < .0001). Mandibular dental and skeletal changes were more apparent in adolescents, while adults tended toward maxillary changes. CONCLUSIONS: Vertical traction from orthodontic mini-implants reduces the maxillary posterior dentoalveolar height, thereby assisting orthodontic closure of anterior open bite. However, simultaneous eruption or extrusion of the mandibular molars should be controlled. Adolescent patients tend to demonstrate more favorable effects of mandibular autorotation than do adults.

Conditional expression of human ß-hexosaminidase in the neurons of Sandhoff disease rescues mice from neurodegeneration but not neuroinflammation.

This study evaluated whether GM(2) ganglioside storage is necessary for neurodegeneration and neuroinflammation by performing ß-hexosaminidase rescue experiments in neurons of HexB(-/-) mice. We developed a novel mouse model, whereby the expression of the human HEXB gene was targeted to neurons of HexB(-/-) mice by the Thy1 promoter. Despite ß-hexosaminidase restoration in neurons was sufficient in rescuing HexB(-/-) mice from GM(2) neuronal storage and neurodegeneration, brain inflammation persisted, including the presence of large numbers of reactive microglia/macrophages due to persisting GM(2) presence in this cell type. In conclusion, our results suggest that neuroinflammation is not sufficient to elicit neurodegeneration as long as neuronal function is restored.

Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice.

BACKGROUND: The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo. METHODS: We employed the inducible Col1-IL1ßXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology. RESULTS: Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aß pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1ßXAT compound transgenic mouse. CONCLUSION: This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases.

The trigeminal retrograde transfer pathway in the treatment of neurodegeneration.

The trigeminal sensory system was evaluated for the retrograde transfer of gene therapy vectors into the CNS. The feline immunodeficiency viral vector, FIV(HEXB), encoding for the human HEXB gene, was injected intra-articularly in the temporomandibular joint of 12 week-old HexB(-/-) mice displaying clinical and histopathological signs of Sandhoff disease. This treatment regiment reduced GM(2) storage and ameliorated neuroinflammation in the brain of HexB(-/-) mice, as well as attenuated behavioral deficits. In conclusion, retrograde transfer along trigeminal sensory nerves may prove to be a valuable route of gene therapy administration for the treatment of lysosomal storage disorders and other neurodegenerative diseases.

Spinal interleukin-1beta in a mouse model of arthritis and joint pain.

OBJECTIVE: Pain from arthritis has been associated with peripheral sensitization of primary sensory afferents and the development of inflammation at the dorsal horns. This study was undertaken to determine whether the role of spinal interleukin-1beta (IL-1beta) in central processing of pain is important in the development of arthritis. METHODS: Col1-IL-1betaXAT mice and GFAP-IL-1betaXAT mice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in the right and left temporomandibular joints (TMJs), or in the cisterna magna, respectively, to induce IL-1beta expression in the dorsal horns of the spinal horn. To inhibit intrathecal IL-1 receptor type I (IL-1RI) signaling, FIV(IL-1Ra) vector was injected into the cisterna magna of Col1-IL-1betaXAT mice. The effects of IL-1RI receptor inhibition in GFAP-IL-1betaXAT mice were studied in the GFAP-IL-1betaXAT-IL-1RI(-/-) compound mouse model. Neuroinflammatory, sensory, and behavioral changes were evaluated in conjunction with arthritic changes in the TMJ, assessed by histopathologic and immunohistochemical analyses. RESULTS: Induction of an osteoarthritis-like condition in the TMJ in the Col1-IL-1betaXAT mouse model resulted in up-regulation of murine IL-1beta at the dorsal horns. Moreover, intrathecal inhibition of IL-1RI in Col1-IL-1betaXAT mice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL-1beta in the recently developed GFAP-IL-1betaXAT somatic mosaic model of neuroinflammation led to development of arthritis-like pathology accompanied by increased pain-like behavior. CONCLUSION: Our results indicate that joint pathology and pain are dependent on spinal IL-1beta, and suggest the presence of a bidirectional central nervous system-peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis.

Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration.

Myeloid-derived immune cells, including microglia, macrophages and monocytes, have been previously implicated in neurodegeneration. We investigated the role of infiltrating peripheral blood mononuclear cells (PBMC) in neuroinflammation and neurodegeneration in the HexB-/- mouse model of Sandhoff disease. Ablation of the chemokine receptor CCR2 in the HexB-/- mouse resulted in significant inhibition of PBMC infiltration into the brain, decrease in TNFalpha and MHC-II mRNA abundance and retardation in clinical disease development. There was no change in the level of GM2 storage and pro-apoptotic activity or astrocyte activation in HexB-/-; Ccr2-/- double knockout mice, which eventually succumbed secondary to GM2 gangliosidosis.

A longitudinal study of normal asymmetric mandibular growth and its relationship to skeletal maturation.

INTRODUCTION: Our aims in this investigation were to assess asymmetric mandibular growth relative to skeletal maturation and to determine whether asymmetric growth occurs during a period of high growth velocity. METHODS: We evaluated lateral oblique and hand-wrist radiographs of 30 male and 30 female Class I participants in the Burlington Growth Study who were assessed at 3 time periods with the skeletal maturation index (SMI). The body, the ramus, the effective length, and the gonial angle on each side of the mandible were measured. Asymmetry between the right and left sides was analyzed with the SMI and for sex dependency. RESULTS: The left ramus was consistently longer than the right in all evaluation periods (P <.05). The right body was consistently longer than the left in all evaluation periods (P <.05). The effective length showed no asymmetry until the last maturation group, when the right side was longer (P <.05). The gonial angle had no significant differences. Tests to determine differences between the sexes showed no significance in asymmetry, but the body, the ramus, and the effective length were longer in males than in females (P <.05). CONCLUSIONS: Asymmetry does not occur or increase during any specific growth period.

Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype.

We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.

Amelioration of pain and histopathologic joint abnormalities in the Col1-IL-1beta(XAT) mouse model of arthritis by intraarticular induction of mu-opioid receptor into the temporomandibular joint.

OBJECTIVE: To evaluate opioid receptor function as a basis for novel antinociceptive therapy in arthritis. METHODS: We induced human mu-opioid receptor (HuMOR) expression in arthritic joints of mice, using the feline immunodeficiency virus (FIV) vector, which is capable of stably transducing dividing, growth-arrested, and terminally differentiated cells. Male and female Col1-IL-1beta(XAT)-transgenic mice developed on a C57BL/6J background and wild-type littermates were studied. RESULTS: A single injection of FIV(HuMOR) into the temporomandibular joints of Col1-IL-1beta(XAT)-transgenic mice 1 week prior to induction of arthritis prevented the development of orofacial pain and joint dysfunction, and reduced the degree of histopathologic abnormality in the joint. In addition, FIV(HuMOR) prevented the attendant sensitization of trigeminal sensory neurons and activation of astroglia in brainstem trigeminal sensory nuclei. These effects were mediated by the transduction of primary sensory neurons via transport of FIV vectors from peripheral nerve endings to sensory ganglia, as evidenced by HuMOR expression in neuronal cell bodies located in the trigeminal ganglia, as well as in their proximal and distal nerve branches located in the main sensory and subnucleus caudalis of the brainstem and joints, respectively. The presence of MOR ligands predominantly in the descending trigeminal nucleus suggested that the observed antinociception occurred at the subnucleus caudalis. Articular chondrocytes and meniscal tissue were also infected by FIV(HuMOR), which presumably exerted an antiinflammatory effect on cartilage. CONCLUSION: Our results indicate that prophylactic therapy with MOR overexpression in joints can successfully prevent the development of pain, dysfunction, and histopathologic abnormalities in the joints in arthritis. These findings may provide a basis for the future development of spatiotemporally controlled antinociceptive and antiinflammatory therapy for arthritis.

Validity of panoramic radiographs for measuring mandibular asymmetry.

The objective of this study is to evaluate the accuracy of panoramic radiographs for diagnosing vertical asymmetry of the posterior mandible. The first part of the study used a model to evaluate the reproducibility of this particular panoramic machine. The tube traverse did not significantly affect the linear measurements, but the side of the machine where the structure was located produced an average of 2.1% variation in the total height of the mandible. In the second part of the study, the left-right (%) differences were measured on the panoramics and the laminographs of five skulls with lead markers. These differences were compared with the percent difference measured directly on the skull and with each other and suggested that the laminograph could be used as the "gold standard" for measuring posterior vertical mandibular asymmetry. The third part of the study evaluated a patient sample (N = 42). The correlation coefficient between the two types of films was determined to be 0.92 for total height and 0.39 for condyle height. Using the 6% cutoff reported in the literature, the sensitivity of the panoramics to diagnose asymmetry for the total height was determined to be 0.62 and the specificity 1.0. This study suggests that the panoramic radiograph can be used to evaluate vertical posterior mandibular asymmetry, but there will be some underdiagnosis.

Intraarticular induction of interleukin-1beta expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain.

OBJECTIVE: To examine the effects of intraarticular induction of interleukin-1beta (IL-1beta) expression in adult mice. METHODS: We used somatic mosaic analysis in a novel transgenic mouse with an inducible IL-1beta transcription unit. Transgene activation was induced by Cre recombinase in the temporomandibular joints (TMJs) of adult transgenic mice (conditional knockin model). The effects of intraarticular IL-1beta induction were subsequently evaluated at the cellular, histopathologic, and behavioral levels. RESULTS: We developed transgenic mice capable of germline transmission of a dormant transcription unit consisting of the mature form of human IL-1beta as well as the reporter gene beta-galactosidase driven by the rat procollagen 1A1 promoter. Transgene activation by a feline immunodeficiency virus Cre vector resulted in histopathologic changes, including articular surface fibrillations, cartilage remodeling, and chondrocyte cloning. We also demonstrated up-regulation of genes implicated in arthritis (cyclooxygenase 2, IL-6, matrix metalloproteinase 9). There was a lack of inflammatory cells in these joints. Behavioral changes, including increased orofacial grooming and decreased resistance to mouth opening, were used as measures of nociception and joint dysfunction, respectively. The significant increase in expression of the pain-related neurotransmitter calcitonin gene-related peptide (CGRP) in the sensory ganglia as well as the auxiliary protein CGRP receptor component protein of the calcitonin-like receptor in the brainstem further substantiated the induction of pain. CONCLUSION: Induction of IL-1beta expression in the TMJs of adult mice led to pathologic development, dysfunction, and related pain in the joints. The somatic mosaic model presented herein may prove useful in the preclinical evaluation of existing and new treatments for the management of joint pathologic changes and pain, such as in osteoarthritis.

Technique for fabricating a cement-retained single-unit implant-supported provisional restoration in the esthetic zone.

The fabrication of provisional restorations is an important stage in implant treatment. In the esthetic zone, the potential for error without the use of provisional restorations in the selection of the abutments, framework design, appropriate vertical dimension of occlusion, occlusal profile, and the esthetic interpretation may be significant. Provisional restorations are indicated in esthetic zones, for the contouring of the gingiva, to achieve an acceptable emergence profile, to have custom-guided tissue healing, and to induce appropriate soft-tissue topography. This article describes the fabrication of a provisional restoration for a single-unit implant-supported crown.

Normal and abnormal temporomandibular joint disc and posterior attachment as depicted by magnetic resonance imaging in symptomatic and asymptomatic subjects.

PURPOSE: This investigation provides a detailed assessment of the morphologic and signal intensity changes of the temporomandibular joint disc and posterior disc attachment as depicted by magnetic resonance imaging in symptomatic versus asymptomatic subjects. PATIENTS AND METHODS: Sixty-one asymptomatic volunteers and 58 symptomatic subjects were imaged using a 1.5 tesla magnetic resonance system utilizing bilateral high-resolution surface coils with the jaw in the closed and maximal opened position. Disc shape and signal intensity characteristics were tabulated along with a detailed assessment of the various regions of the disc posterior attachment in a blinded fashion as to symptomatology. RESULTS: Deformity of the disc was noted in 34 of 116 (29.3%) of joints in patients and in 5 of 122 (4%) of joints of volunteers ( P < .0005; chi-square test). There was a large region of increased signal intensity in the posterior band of the disc on proton- or T1- weighted images in 13 of 116 (11.2%) joints in patients versus 1 of 122 (0.8%) joints in asymptomatic subjects ( P < .0005). In all joints with disc displacement with or without reduction, the temporal posterior attachment was visualized in only 43.5% in the closed jaw position ( P < .0005 versus all normal joints) and in 30.4% ( P < .0005 versus all normal joints) in the open jaw position. CONCLUSION: Magnetic resonance allows an in vivo characterization of the fine structural details of the disc and the disc posterior attachment, separating normal from internal derangement temporomandibular joints.

Mandibular asymmetry in adult patients with unilateral degenerative joint disease.

The purpose of this study was to evaluate the association between unilateral degenerative joint disease (UDJD) and lower facial asymmetry. Twenty symptomatic patients and 20 asymptomatic volunteers were studied. Posteroanterior radiographs and bilateral mandibular laminographs were used to evaluate lower face and mandibular asymmetry. The two-way analysis of variance test was used to compare the groups. The posteroanterior radiographs did not reveal vertical asymmetry for the patients. The group with the left side affected exhibited deviation of the mandibular dental midline, the menton, and the antigonion toward the affected side. The laminographs of the same group revealed decreased condylar height and increased antigonial notching in the affected side. The results suggest that subjects with UDJD may manifest lower face asymmetry. This can be of clinical value when adult patients exhibiting asymmetry are to be treated.

Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with bilateral disk displacement without reduction.

The purpose of this study was to evaluate the effect of bilateral disk displacement without reduction (BDDN) on the skeletal and dental pattern of affected individuals. There were 59 symptomatic female patients and 46 asymptomatic normal female volunteers. All study participants had bilateral high-resolution magnetic resonance imaging scans in the sagittal (closed and open) and coronal (closed) planes to evaluate the temporomandibular joints. Linear and angular cephalometric measurements were taken to evaluate the skeletal, denture base, and dental characteristics of the two groups. A smaller cranial base length (Ba-Na) was found in the symptomatic group. The facial plane angle was smaller, and the angle of convexity was larger because of the retropositioned mandible. The lower denture base was also retruded as shown by the smaller SNB angle. The BDDN group exhibited a larger overjet. The mandibular plane angle was steeper, the Y-axis was more vertical (S-Gn to FH), the posterior ramal height (Ar-Go) was shorter, and the angle between the mandibular and the palatal plane (PP to MP angle) was increased in the symptomatic group. No significant dental differences were found. This study showed that alterations in skeletal morphology might be associated with BDDN. This study suggests that subjects with BDDN may manifest altered craniofacial morphology. The clinician should be aware of that possibility, especially for the growing patients and the surgical candidates.

A comparison of the porcelain fracture resistance of screw-retained and cement-retained implant-supported metal-ceramic crowns.

STATEMENT OF PROBLEM: The presence of a screw opening on the occlusal surface of implant-supported metal-ceramic crowns may decrease the porcelain fracture resistance and shorten the longevity of the crown. PURPOSE: The purpose of this study was to compare the porcelain fracture resistance between screw-retained and cement-retained implant-supported metal-ceramic crowns and to assess whether narrowing the occlusal table or offsetting the screw-access opening affects fracture resistance. MATERIAL AND METHODS: Forty standardized maxillary premolar metal copings were fabricated with a Pd-Ga alloy (Protocol) on an implant abutment. Copings were divided into 4 groups (n=10): Group 1 (Screw-retained; occlusal surface buccolingual width=5 mm), screw access opening placed in the center of the occlusal surface; Group 2 (Screw-retained; occlusal surface buccolingual width=5 mm), screw access opening positioned 1 mm offset from the center of the occlusal surface toward the buccal cusp; Group 3 (Cement-retained; occlusal surface buccolingual width=5 mm), copings were not altered; and Group 4 (Cement-retained; occlusal surface buccolingual width=4 mm), copings designed to have a reduced occlusal surface width. All castings were finished with aluminum oxide stones and airborne-particle abraded. Two layers of opaque and dentin porcelain were applied, respectively, on all specimens, which were then glazed. The crown specimens were positioned in a custom testing apparatus and vertically loaded on the middle of the occlusal surface with a universal testing machine at a crosshead speed of 0.5 mm/min until fracture. Mean values of load at fracture (Kgf) were calculated in each group and compared with a 1-way analysis of variance and Tukey's Studentized test (alpha=.05). RESULTS: Mean values of loads required to fracture the crowns were as follow: Group 1: 95.01+/-46.6 Kgf; Group 2: 108.61+/-57.9 Kgf; Group 3: 390.94+/-151.3 Kgf; Group 4: 380.04+/-211.8 Kgf. Groups 1 and 2 required a significantly lower force to fracture the crowns compared with Groups 3 and 4 (P=.0001). Comparing Group 1 with 2 (P=.9) and Groups 3 with 4 (P=.6), no significant differences were noted. CONCLUSIONS: Screw-retained implant-supported metal-ceramic crowns demonstrated a significantly lower porcelain fracture resistance than cement-retained crowns. Placing the screw access opening 1 mm offset from the center of the occlusal surface did not result in lower fracture resistance. Cement-retained crowns with 4- or 5-mm buccolingual width of the occlusal surface showed similar porcelain fracture resistance.

Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with unilateral disk displacement with reduction.

The purpose of this study was to evaluate the effect of unilateral disk displacement with reduction (UDDR) on the skeletal and dental pattern of affected individuals. There were 18 symptomatic female patients and 46 asymptomatic normal female volunteers. All study participants had bilateral high-resolution magnetic resonance scans in the sagittal (closed and open) and coronal (closed) planes to evaluate the temporomandibular joints. Linear and angular cephalometric measurements were taken to evaluate the skeletal, denture base, and dental characteristics of the two groups. Analysis of variance was used to compare the symptomatic with the control subjects. A few skeletal differences were found. There was an overall reduction in length of the anterior (S-Na) and posterior (S-Ba) cranial base measurements in the UDDR group. The cranial base angle was also increased. Both upper and lower dentures bases were retropositioned. The posterior ramal height (Ar-Go) was shorter in the symptomatic group. This study showed that alterations in skeletal morphology may be associated with UDDR. The mechanisms that produce DD or the mechanisms that cause this skeletal alteration are yet to be clarified. This study suggests that subjects with UDDR may manifest altered craniofacial morphology. The clinician should be aware of this possibility, especially for growing patients.

Transverse craniofacial features and their genetic predisposition in families with nonsyndromic unilateral cleft lip and palate.

OBJECTIVE: The purpose of this study was to evaluate the transverse craniofacial form in families with nonsyndromic cleft lip and palate (NSCLP). It was hypothesized that affected as well as noncleft NSCLP family members are characterized by a common array of craniofacial features that differ from the general population. DESIGN: This was a prospective cross-sectional investigation that included affected children with NSCLP and their noncleft parents and siblings. PATIENTS, PARTICIPANTS: A total of 114 subjects (14 affected girls, 17 affected girls, 15 unaffected male siblings, 10 unaffected female siblings, 29 unaffected biological mothers, and 29 unaffected biological fathers) were included. Subject records comprised of posteroanterior cephalometric radiographs obtained from all 114 subjects. MAIN OUTCOME MEASURES: The width of midfacial structures, including the orbit and nose, was increased in NSCLP families, compared with published norms. Interestingly, the face was disproportionally wider in relation to total facial height. The transverse craniofacial form of children with or without clefts significantly correlated with that of their parents. Mothers displayed strong correlation with their affected and unaffected sons, whereas fathers correlated to their daughters, suggesting a possible sex-linked developmental influence. CONCLUSION: Better understanding of the genetic inheritance of craniofacial features associated with cleft lip and palate may ultimately contribute to the development of cleft risk assessment methods.