Prospective study of dentoskeletal changes in class II division malocclusion treatment with twin force bite corrector

Objective: To evaluate the dentoskeletal changes of Class II malocclusion treatment with the Twin Force Bite Corrector (TFBC). Materials and Methods: The sample comprised 86 lateral cephalograms obtained from 43 subjects with Class II division 1 malocclusion; the subjects were divided into two groups. The experimental group comprised 23 patients with a mean initial age of 12.11 years who were treated with the TFBC for a mean period of 2.19 years. The control group included 40 lateral cephalograms from 20 Class II nontreated patients, with an initial mean age of 12.55 years and a mean observation period of 2.19 years. The lateral cephalograms were evaluated before and after orthodontic treatment in group 1 and in the beginning and end of the observation period in group 2. t-Tests were used to compare the initial and final cephalometric characteristics of the groups as well as the amount of change. Results: The experimental group presented greater maxillary growth restriction and mandibular retrusion than the control group, as well as greater maxillomandibular relationship improvement and greater labial tipping of the mandibular incisors. The results also showed a greater decrease in overbite and overjet in the experimental group, and there were no statistically significant differences in the craniofacial growth pattern between groups. Conclusions: The TFBC promotes restriction of anterior maxillary displacement without significant changes in mandibular length and position and improvement of maxillomandibular relationship without changes in facial growth and significant buccal tipping of mandibular incisors. Class II correction with the TFBC occurred primarily as a result of dentoalveolar changes.

Correction of Class II malocclusion with Class II elastics: a systematic review

Introduction: The aim of this prospective clinical study was to investigate the cephalometric changes produced by bonded spurs associated with high-pull chincup therapy in children with Angle Class I malocclusion and anterior open bite. Methods: Thirty patients with an initial mean age of 8.14 years and a mean anterior open bite of 3.93 mm were treated with bonded spurs associated with chincup therapy for 12 months. An untreated control group of 30 subjects with an initial mean age of 8.36 years and a mean anterior open bite of 3.93 mm and the same malocclusion was followed for 12 months for comparison. Student t tests were used for intergroup comparisons. Results: The treated group demonstrated a significantly greater decrease of the gonial angle, and increase in overbite, palatal tipping of the maxillary incisors, and vertical dentoalveolar development of the maxillary and mandibular incisors compared with the control group. Conclusions: The association of bonded spurs with high-pull chincup therapy was efficient for the correction of the open bite in 86.7% of the patients, with a 5.23-mm (SD, 61.69) overbite increase.

Evaluation of the dental arch asymmetry in natural normal occlusion and Class II malocclusion individuals

OBJECTIVE: To verify the presence and degree of asymmetry of dental arches in Brazilian individuals with natural normal occlusion and Class II, Divisions 1 and 2 malocclusions. METHODS: The study evaluated the symmetry of the maxillary and mandibular dental arches of 180 pairs of dental casts, divided into: Group I = 60 pairs of natural normal occlusion individuals; Group II = 60 pairs of Class II, Division 1 malocclusion individuals; and Group III = 60 pairs of Class II, Division 2 malocclusion individuals. A device was used to measure dental midline deviation and the canine tip in the dental arches (in degrees). It was also verified the distance of the upper canines from the palatal suture, intercanine distance, and anteroposterior upper and lower first molar position. RESULTS: Dental arches of individuals from all groups presented asymmetry, regardless of the presence of malocclusion. Group I showed a lower asymmetry degree in relation to Groups II and III. The asymmetry in Groups II and III was similar. CONCLUSION: The dental arches of individuals with natural normal occlusion and with Class II, Division 1 and Division 2 malocclusions showed asymmetry. The asymmetry degree was higher in the mandibular dental arches than in the maxillary dental arches in all 3 evaluated groups.

Study of the number of occlusal contacts in maximum intercuspation before orthodontic treatment in subjects with Angle Class I and Class II Division 1 malocclusion

OBJECTIVE: Define and compare numbers and types of occlusal contacts in maximum intercuspation. METHODS: The study consisted of clinical and photographic analysis of occlusal contacts in maximum intercuspation. Twenty-six Caucasian Brazilian subjects were selected before orthodontic treatment, 20 males and 6 females, with ages ranging between 12 and 18 years. The subjects were diagnosed and grouped as follows: 13 with Angle Class I malocclusion and 13 with Angle Class II Division 1 malocclusion. After analysis, the occlusal contacts were classified according to the established criteria as: tripodism, bipodism, monopodism (respectively, three, two or one contact point with the slope of the fossa); cuspid to a marginal ridge; cuspid to two marginal ridges; cuspid tip to opposite inclined plane; surface to surface; and edge to edge. RESULTS: The mean number of occlusal contacts per subject in Class I malocclusion was 43.38 and for Class II Division 1 malocclusion it was 44.38, this difference was not statistically significant (p>0.05). CONCLUSIONS: There is a variety of factors that influence the number of occlusal contacts between a Class I and a Class II, Division 1 malocclusion. There is no standardization of occlusal contact type according to the studied malocclusions. A proper selection of occlusal contact types such as cuspid to fossa or cuspid to marginal ridge and its location in the teeth should be individually defined according to the demands of each case. The existence of an adequate occlusal contact leads to a correct distribution of forces, promoting periodontal health.

Cephalometric effects of the use of 10-hour Force Theory for Class II treatment

OBJECTIVE: This study aimed to evaluate the cephalometric effects promoted by the orthodontic treatment of Class II malocclusion patients with the use of the 10-Hour Force Theory, that consists in the use of fixed appliances with 8 hours a day using a cervical headgear appliance and 16 hours a day using Class II elastics, 8 hours on the first mandibular molar and 8 hours in the second mandibular molar. METHODS: Sample comprised 31 patients with mean initial age of 14.90 years, final mean age of 17.25 years and mean treatment time of 2.35 years. The lateral cephalograms in pre-treatment and post-treatment stages were evaluated. Evaluation of cephalometric changes between initial and final treatment phases was performed by paired t test. RESULTS: The cases treated with the 10-Hour Force Theory presented a slight restriction of anterior displacement of the maxilla, increase in the effective length of the mandible, significant improvement of the maxillomandibular relationship, significant increase in anterior lower face height, distal tipping of the maxillary premolar crowns, extrusion and distal tipping of the roots of maxillary molars, significant proclination and protrusion of mandibular incisors, significant extrusion and mesialization of mandibular molars, besides a significant correction of the molar relationship, overjet and overbite. CONCLUSION: The use of the 10-Hour Force Theory in treatment of Class II malocclusion provided satisfactory results.

HLA class II mismatch alleles as targets of the alloreactive CD4 T-cell response

In allogeneic hematopoietic stem cell transplantation (allo-HSCT), alloreactive T lymphocytes of donor origin mediate the beneficial graft-versus-leukemia effect but also induce graft-versus-host disease (GvHD). Since human leukocyte antigens (HLA) mismatch alleles represent major targets of alloreactive T lymphocytes, patient and donor are usually matched for the class I molecules A, B, C, and for the class II molecules DRB1 and DQB1, in order do reduce the risk of GvHD. The HLA-DPB1 locus, however, is still ignored in donor selection. Interestingly, clinical studies have demonstrated that disparities at HLA-DQB1 alleles as well as distinct HLA DPB1 mismatch constellations do not adversely affect the outcome of allo-HSCT. It has also been shown that HLA class II is predominantly expressed on hematopoietic cells under non-inflammatory conditions. Therefore, this PhD thesis focused on the application of CD4 T cells in adoptive immunotherapy of leukemias.rnIn the first part of this thesis we developed a rapid screening approach to detect T-cell reactivity of donors to single HLA class II mismatch alleles. Allo-HLA reactivity was measured in naive, memory, and entire CD4 T cells isolated from PBMC of healthy donors by flow cytometric cell sorting according to expression of the differentiation markers CD45RA, CD45RO, CD62L, and CCR7. T-cell populations were defined by a single marker to facilitate translation into a clinical-grade allo-depletion procedure. Alloreactivity to single HLA-DR/-DQ mismatch alleles was analyzed in short-term mixed lymphocyte reactions (MLR) in vitro. As standard antigen-presenting cells, we used the HLA-deficient cell line K562 upon electroporation with single HLA-DR/-DQ allele mRNA. We observed in IFN-γ ELISpot assays that allo-HLA-reactivity preferentially derived from subsets enriched for naive compared to memory T cells in healthy donors, irrespective of the HLA mismatch allele. This separation was most efficient if CD62L (P=0.008) or CD45RA (P=0.011) were used as marker. Median numbers of allo-HLA-reactive effector cells were 3.5-fold and 16.6-fold lower in CD62Lneg and CD45RAneg memory CD4 T cells than in entire CD4 T cells, respectively. In allele-specific analysis, alloreactivity to single HLA-DR alleles clearly exceeded that to HLA-DQ alleles. In terms of alloproliferation no significant difference could be observed between individual CD4 T-cell subsets. rnThe second part of this thesis dealed with the generation of allo-HLA-DQ/-DP specific CD4 T cells. Naive CD45RApos CD4 T cells isolated from healthy donor PBMC by flow cytometric cell sorting were stimulated in MLR against single allo-HLA-DQ/-DP alleles transfected into autologous mature monocyte-derived dendritic cells by mRNA electroporation. Rapidly expanding HLA-DQ/-DP mismatch reactive T cells significantly recognized and cytolysed primary acute myeloid leukemia (AML) blasts, fibroblasts (FB) and keratinocytes (KC) in IFN-γ ELISpot and 51chromium release assays if the targets carried the HLA DQ/ DP allele used for T cell priming. While AML blasts were recognized independent of pre-incubating them with IFN-γ, recognition of FB and KC required IFN-γ pre treatment. We further investigated HLA class II expression on hematopoietic and non-hematopoietic cells by flow cytometry. HLA class II was not detected on primary FB, KC, and non-malignant kidney cells, but was expressed at significant levels on primary AML blasts and B-LCL. Up-regulation of HLA class II expression was observed on all cell types after pre-incubation with IFN-γ.rnIn summary, the novel K562-HLA based MLR approach revealed that naive-depleted CD4 T-cell subsets of healthy individuals contain decreased allo-HLA reactivity in vitro. We propose the application of CD45RAneg naive-depleted CD4 T cells as memory T cell therapy, which might be beneficial for HLA-mismatched patients at high-risk of GvHD and low-risk of leukemia relapse. Memory T cells might also provide important post-transplant immune functions against infectious agents. Additionally, the screening approach could be employed as test system to detect donors which have low risks for the emergence of GvHD after allo-HSCT. In the second part of this thesis we developed a protocol for the generation of allo-HLA-DQ/-DP specific CD4 T cell lines, which could be applied in situations in which patient and donor are matched in all HLA alleles but one HLA-DQ/-DP allele with low GvHD potential. These T cells showed lytic activity to leukemia cells while presumably sparing non-hematopoietic tissues under non-inflammatory conditions. Therefore, they might be advantageous for allo-HSCT patients with advanced stage AML after reduced-intensity conditioning and T-cell depletion for the replenishment of anti-leukemic reactivity if the risk for disease relapse is high. rn

Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss?

Human narcolepsy with cataplexy is a neurological disorder, which develops due to a deficiency in hypocretin producing neurons in the hypothalamus. There is a strong association with human leucocyte antigens HLA-DR2 and HLA-DQB1*0602. The disease typically starts in adolescence. Recent developments in narcolepsy research support the hypothesis of narcolepsy being an immune-mediated disease. Narcolepsy is associated with polymorphisms of the genes encoding T cell receptor alpha chain, tumour necrosis factor alpha and tumour necrosis factor receptor II. Moreover the rate of streptococcal infection is increased at onset of narcolepsy. The hallmarks of anti-self reactions in the tissue--namely upregulation of major histocompatibility antigens and lymphocyte infiltrates--are missing in the hypothalamus. These findings are questionable because they were obtained by analyses performed many years after onset of disease. In some patients with narcolepsy autoantibodies to Tribbles homolog 2, which is expressed by hypocretin neurons, have been detected recently. Immune-mediated destruction of hypocretin producing neurons may be mediated by microglia/macrophages that become activated either by autoantigen specific CD4(+) T cells or superantigen stimulated CD8(+) T cells, or independent of T cells by activation of DQB1*0602 signalling. Activation of microglia and macrophages may lead to the release of neurotoxic molecules such as quinolinic acid, which has been shown to cause selective destruction of hypocretin neurons in the hypothalamus.

Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB1*03-DQB1*02 (P < 4 x 10(-43)) and DRB1*1301-DQB1*0603 (P < 3 x 10(-7)). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility.

Extraction of maxillary first molars improves second and third molar inclinations in Class II Division 1 malocclusion

The aim of this study was to assess the changes in inclination of the maxillary second (M2) and third (M3) molars after orthodontic treatment of Class II Division 1 malocclusion with extraction of maxillary first molars.

CTLA4-Ig Restores Rejection of MHC Class-II Mismatched Allografts by Disabling IL-2-Expanded Regulatory T Cells

Allograft acceptance and tolerance can be achieved by different approaches including inhibition of effector T cell responses through CD28-dependent costimulatory blockade and induction of peripheral regulatory T cells (Tregs). The observation that Tregs rely upon CD28-dependent signals for development and peripheral expansion, raises the intriguing possibility of a counterproductive consequence of CTLA4-Ig administration on tolerance induction. We have investigated the possible negative effect of CTLA4-Ig on Treg-mediated tolerance induction using a mouse model of single MHC class II-mismatched skin grafts in which long-term acceptance was achieved by short-term administration of IL-2/anti-IL-2 complex. CTLA4-Ig treatment was found to abolish Treg-dependent acceptance in this model, restoring skin allograft rejection and Th1 alloreactivity. CTLA4-Ig inhibited IL-2-driven Treg expansion, and prevented in particular the occurrence of ICOS(+) Tregs endowed with potent suppressive capacities. Restoring CD28 signaling was sufficient to counteract the deleterious effect of CTLA4-Ig on Treg expansion and functionality, in keeping with the hypothesis that costimulatory blockade inhibits Treg expansion and function by limiting the delivery of essential CD28-dependent signals. Inhibition of regulatory T cell function should therefore be taken into account when designing tolerance protocols based on costimulatory blockade. Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons

Detection of proximal secondary caries at cervical class II-amalgam restoration margins in vitro

To compare the performance of LFpen (DIAGNOdent pen) with two different wedge-shaped tips to conventional bitewing radiography (BW) for detecting proximal secondary caries at the cervical margin of amalgam restorations in vitro.

Curing capability of halogen and LED light curing units in deep class II cavities in extracted human molars

Class II cavities were prepared in extracted lower molars filled and cured in three 2-mm increments using a metal matrix. Three composites (Spectrum TPH A4, Ceram X mono M7 and Tetric Ceram A4) were cured with both the SmartLite PS LED LCU and the Spectrum 800 continuous cure halogen LCU using curing cycles of 10, 20 and 40 seconds. Each increment was cured before adding the next. After a seven-day incubation period, the composite specimens were removed from the teeth, embedded in self-curing resin and ground to half the orofacial width. Knoop microhardness was determined 100, 200, 500, 1000, 1500, 2500, 3500, 4500 and 5500 microm from the occlusal surface at a distance of 150 microm and 1000 microm from the metal matrix. The total degree of polymerization of a composite specimen for any given curing time and curing light was determined by calculating the area under the hardness curve. Hardness values 150 microm from the metal matrix never reached maximum values and were generally lower than those 1000 microm from the matrix. The hardest composite was usually encountered between 200 microm and 1000 microm from the occlusal surface. For every composite-curing time combination, there was an increase in microhardness at the top of each increment (measurements at 500, 2500 and 4500 microm) and a decrease towards the bottom of each increment (measurements at 1500, 3500 and 5500 microm). Longer curing times were usually combined with harder composite samples. Spectrum TPH composite was the only composite showing a satisfactory degree of polymerization for all three curing times and both LCUs. Multiple linear regression showed that only the curing time (p < 0.001) and composite material (p < 0.001) had a significant association with the degree of polymerization. The degree of polymerization achieved by the LED LCU was not significantly different from that achieved by the halogen LCU (p = 0.54).

Influence of beveling and ultrasound application on marginal adaptation of box-only Class II (slot) resin composite restorations

A laboratory study was performed to assess the influence of beveling the margins of cavities and the effects on marginal adaptation of the application of ultrasound during setting and initial light curing. After minimal access cavities had been prepared with an 80 microm diamond bur, 80 box-only Class II cavities were prepared mesially and distally in 40 extracted human molars using four different oscillating diamond coated instruments: (A) a U-shaped PCS insert as the non-beveled control (EMS), (B) Bevelshape (Intensiv), (C) SonicSys (KaVo) and (D) SuperPrep (KaVo). In groups B-D, the time taken for additional bevel finishing was measured. The cavities were filled with a hybrid composite material in three increments. Ultrasound was also applied to one cavity per tooth before and during initial light curing (10 seconds). The specimens were subjected to thermomechanical stress in a computer-controlled masticator device. Marginal quality was assessed by scanning electron microscopy and the results were compared statistically. The additional time required for finishing was B > D > C (p < or = 0.05). In all groups, thermomechanical loading resulted in a decrease in marginal quality. Beveling resulted in higher values for "continuous" margins compared with that of the unbeveled controls. The latter showed better marginal quality at the axial walls when ultrasound was used. Beveling seems essential for good marginal adaptation but requires more preparation time. The use of ultrasonic vibrations may improve the marginal quality of unbeveled fillings and warrants further investigation.

A treatment method for Class II Division 1 patients with extraction of permanent maxillary first molars

Throughout the years, various treatment modalities have been presented for the treatment of Class II Division 1 malocclusions. The goal of this paper is to present a treatment approach that involves the extraction of the maxillary first molars followed by use of fixed appliances with low-friction brackets. This treatment approach has proven to be an efficient treatment modality for Class II Division 1 malocclusions, especially with noncompliant patients.