Tratamento da classe II divisão 2 com aparelho de Herbst após o pico de crescimento puberal

Patients with Class II division 2 malocclusion and mandibular retrusion have limited treatment options after the growth peak, such as surgical-orthodontic treatment or mandibular advancement devices. Among bite-jumping devices, the Herbst appliance allows greater increase of mandibular growth since it does not require patient compliance and allows continuous use. This case report presents the treatment of a Class II division 2 malocclusion in a patient after growth peak, performed in two stages. The first stage included the upper incisors proclination and overjet increase with multibracket appliance to benefit next stage. The second stage involved mandibular advancement using Herbst appliance aiming to correct the Class II molar relationship. The treatment resulted in a stable occlusion with periodontal health, normal functions and facial aesthetics improvement. Dental and skeletal changes arising from treatment could be assessed by cephalometric analysis and superimposition of pretreatment and post-treatment cephalometric tracings. Antero-posterior discrepancy was corrected by means of dental movement as well as by mandibular growth increment stimulated by the Herbst appliance.

Aparelho de Thurow modificado e aparelho ortodôntico fixo no tratamento da classe II com mordida aberta anterior

This work had aim to present two clinical cases with open bite Class II malocclusion that treated in the phase of the mixed dentition with the modified Thurow appliance and in the permanent dentition with fixed appliance. The dentoskeletal effects of these appliances were carefully analyzed with the aid of metallic implants inserted in both maxilla and mandible. The correction of the malocclusion and the improvement of the skeletal, dental and facial relationship were observed in both cases. The modified Thurow appliance followed by fixed-appliance as a two-phase treatment protocol revealed to be an effective treatment approach for the two young people that initially presented a Class II division 1 malocclusion associated to anterior open bite presented.

Avaliação das alterações dentárias e esqueléticas induzidas pelo uso do aparelho de Herbst no tratamento da classe II na dentadura mista: Revisão sistemática

Objective: evaluate the immediate dental and skeletal changes induced by the Herbst appliance on early treatment of Angle´s Class II malocclusion. Material and Method: several electronic databases such as Scopus, Pub Med, Medline, Cochrane Library, Lilacs and Scielo were searched. The abstracts that fullfilled the selection criteria were selected and those that did not provide enough information about these criteria were selected but the final decision of including them or not on the research, was taken after the complete reading of the article. The selection criteria were: clinical studies with Class II individuals, both male and female, with initial age of 7 to 10 years, treated with the Herbst appliance that analysed the dental and/or skeletal changes evaluated on lateral cephalometric radiographs; researches where the treatment performed did not involve extractions or surgical interventions; studies that included patients without syndromes or health concerns and articles published in English or Portuguese. Results and Conclusions: five articles were selected. The articles showed that significant changes happened in the mandibular sagittal lenght, on facial convexity angle, on maxillo-mandibular relationship, on retroclination of the upper incisors and on distal movement of the upper molars, on proclination of the lower incisors and on extrusion of the lower molars. The appliance exerted a limited effect on the anterior relocation of the maxillary complex and on facial heights. However, more studies about the performance of the Herbst appliance on early treatment of Class II are needed.

Lateral cephalometric diagnosis of asymmetry in Angle Class II subdivision compared to Class I and II

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Morphometric analysis of long-term dentoskeletal effects induced by treatment with Balters bionator

Objective: To evaluate the long-term effects of the standard (Class II) Balters bionator in growing patients with Class II malocclusion with mandibular retrusion by using morphometrics (thin-plate spline [TPS] analysis). Materials and Methods: Twenty-three Class II patients (8 male, 15 female) were treated consecutively with the Balters bionator (bionator group). The sample was evaluated at T0, start of treatment; T1, end of bionator therapy; and T2, long-term observation (including fixed appliances). Mean age at the start of treatment was 10 years 2 months (T0); at posttreatment, 12 years 3 months (T1); and at long-term follow-up, 18 years 2 months (T2). The control group consisted of 22 subjects (11 male, 11 female) with untreated Class II malocclusion. Lateral cephalograms were analyzed at the three time points for all groups. TPS analysis evaluated statistical differences (permutation tests) in the craniofacial shape and size between the bionator and control groups. Results: TPS analysis showed that treatment with the bionator is able to produce favorable mandibular shape changes (forward and downward displacement) that contribute significantly to the correction of the Class II dentoskeletal imbalance. These results are maintained at a long-term observation after completion of growth. The control group showed no statistically significant differences in the correction of Class II malocclusion. Conclusions: This study suggests that bionator treatment of Class II malocclusion produces favorable results over the long term with a combination of skeletal and dentoalveolar shape changes.

O momento oportuno para a abordagem ortodontica no tratamento da classe II

Because it still brings polemic among the professionals, it was mention once more, in this literature review, the theme that aims to define the appropriate timing to approach the bad occlusions of Class II, and also when it would the right opportunity to treat them, in way that would convey to the patient consistent, stable results in a long term. These are important aspects to be taken into consideration by orthodontists, either by those who defend the early treatment or by those who defend the late treatment. Therefore, the present study aims to aid the clarification of daily doubts regarding this aspect.

Estabilidade em longo prazo do tratamento da má oclusão de classe II, divisão 1, com a utilização de um aparelho funcional propulsor mandibular fixo: relato de caso

O tratamento da má oclusão de Classe II sem extrações dentárias vem ganhando popularidade na comunidade ortodôntica já há três décadas. Aparelhos funcionais fixos vêm sendo utilizados por profissionais, de maneira crescente, para promover compensações dentoalveolares e corrigir a má oclusão de Classe II. Os efeitos mais significativos são observados em pacientes com padrão de crescimento horizontal. Um caso clínico será relatado com o uso do aparelho fixo Twin Force Bite Corrector em uma paciente do sexo feminino, para a correção da Classe II. Esse dispositivo de ancoragem fixa dispensa o uso de aparelhos funcionais removíveis e não necessita da cooperação do paciente.

Stability of maxillary anterior crowding treatment

OBJECTIVE: To evaluate the stability and the relapse of maxillary anterior crowding treatment on cases with premolar extraction and evaluate the tendency of the teeth to return to their pretreatment position. METHODS: The experimental sample consisted of 70 patients of both sex with an initial Class I and Class II maloclusion and treated with first premolar extractions. The initial mean age was 13,08 years. Dental casts' measurements were obtained at three stages (pretreatment, posttreatment and posttreatment of 9 years on average) and the variables assessed were Little Irregularity Index, maxillary arch length and intercanine. Pearson correlation coefficient was used to know if some studied variable would have influence on the crowding in the three stages (LII1, LII2, LII3) and in each linear displacement of the Little irregularity index (A, B, C, D, E) in the initial and post-retention phases. RESULTS: The maxillary crowding relapse ( LII3-2) is influenced by the initial ( LII1), and the teeth tend to return to their pretreatment position. CONCLUSION: The results underline the attention that the orthodontist should be given to the maxillary anterior relapse, primarily on those teeth that are crowded before the treatment.

Influence of treatment with and without extractions on the growth pattern of dolichofacial patients

OBJECTIVE: The objective of this retrospective study was to compare, by means of lateral cephalograms, the facial growth pattern changes due to the treatment with and without extractions of four first premolars in dolichofacial individuals. METHODS: Groups 1 and 2 were constituted of 23 dolichofacial patients each, with Class II malocclusion, division 1 and initial age average of 12.36 and 12.29 years, respectively. Patients from Group 1 were treated without extractions and Group 2 was treated with extraction of the four first premolars, given that both used occipital headgear. Groups were compatibilized according to age, treatment period, gender and malocclusion severity. The t test was applied for intergroups comparison. RESULTS: Most variables (SN.PP, SN.Ocl and FMA) did not present statistically significant difference between groups. CONCLUSION: Although the treatment with extractions tend to reduce the mandibular plane angle (SN.GoGn) and the facial axis (NS.Gn), the analyzed treatment protocols did not affect in a clinically relevant way the facial growth pattern.

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

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

Interferon-γ Induces Expression of MHC Class II on Intestinal Epithelial Cells and Protects Mice from Colitis

Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD) and involve CD4(+) T cells, which are activated by major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells (APCs). However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC) affects CD4(+) T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL)-10 receptor-blocking antibodies (anti-IL10R mAb). To assess the role of interferon (IFN)-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+) T-helper type (Th)1 cells - but not group 3 innate lymphoid cells (ILCs) or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+) T cells and forkhead box P3 (FoxP3)(+) regulatory T (Treg) cells. IFN-γ produced mainly by CD4(+) T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD.

Transcriptional regulation of the invariant chain associated with MHC class II molecules

The invariant chain associated with the major histocompatibility complex (MHC) class II molecules is a non-polymorphic glycoprotein implicated in antigen processing and class II molecule intracellular transport. Class II molecules and invariant chain (In) are expressed primarily by B lymphocytes and antigen-presenting cells such as macrophages and can be induced by interferon gamma (IFN-$\gamma$) in a variety of cell types such as endothelial cells, fibroblasts, and astrocytes. In this study the cis-acting sequences involved in the constitutive, tissue-specific, and IFN-$\gamma$ induced expression of the human In gene were investigated and nuclear proteins which specifically bound these sequences were identified.^ To define promoter sequences involved in the regulation of the human In gene, 790 bp 5$\sp\prime$ to the initiation of transcription were subcloned upstream of the gene encoding chloramphenicol acetyl transferase (CAT). Transfection of this construct into In expressing and non-expressing cell lines demonstrated that this 790 bp In promoter sequence conferred tissue specificity to the CAT gene. Deletion mutants were created in the promoter to identify sequences important for transcription. Three regulatory regions were identified $-$396 to $-$241, $-$241 to $-$216, and $-$216 to $-$165 bp 5$\sp\prime$ to the cap site. Transfection into a human glioblastoma cell line, U-373 MG, and treatment with IFN-$\gamma$, demonstrated that this 5$\sp\prime$ region is responsive to IFN-$\gamma$. An IFN-$\gamma$ response element was sublocalized to the region $-$120 to $-$61 bp. This region contains homology to the interferon-stimulated response element (ISRE) identified in other IFN responsive genes. IFN-$\gamma$ induces a sequence-specific DNA binding factor which binds to an oligonucleotide corresponding to $-$107 to $-$79 bp of the In promoter. This factor also binds to an oligonucleotide corresponding to $-$91 to $-$62 of the interferon-$\beta$ gene promoter, suggesting this factor may be member of the IRF-1/ISGF2, IRF-2, ICSBP family of ISRE binding proteins. A transcriptional enhancer was identified in the first intron of the In gene. This element, located in a 2.6 kb BamHI/PstI fragment, enhances the IFN-$\gamma$ response of the promoter in U-373 MG. The majority of the In enhancer activity was sublocalized to a 550 bp region $\sim$1.6 kb downstream of the In transcriptional start site. ^

AVALIAÇÃO COMPARATIVA DA AGRADABILIDADE FACIAL DE PACIENTES COM MÁ-OCLUSÃO DE CLASSE II TRATADOS COM COMPENSAÇÃO DENTÁRIA OU CIRURGIA ORTOGNÁTICA

O objetivo deste estudo foi avaliar, por meio de fotografias em norma frontal e lateral, a agradabilidade facial obtida com o tratamento de pacientes portadores de má oclusão de classe II. Foram selecionados dois grupos de pacientes que receberam abordagens diferentes de tratamento, um submetido à cirurgia ortognática e o outro à compensação dentária. As fotografias em norma lateral e frontal obtidas ao início e final do tratamento foram distribuídas aleatoriamente e dispostas em apresentação de multimídia para serem submetidas à avaliação subjetiva de indivíduos leigos e ortodontistas, em uma escala linear crescente. Os resultados foram avaliados comparativamente entre os grupos leigos e ortodontistas, entre os estágios inicial e final do tratamento e entre os grupos tratados com a abordagem cirúrgica e compensatória, com o intuito de estabelecer qual das duas abordagens oferece maior agradabilidade facial. Concluímos que houve proximidade entre as avaliações de leigos e ortodontistas quanto à agradabilidade facial, sendo os leigos mais críticos. Tanto leigos quanto ortodontistas deram escores significativamente maiores para as fotos pós-tratamento nos casos compensatórios e cirúrgicos; os casos cirúrgicos em norma lateral obtiveram os resultados melhores.

Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene

Retinoids, synthetic and natural analogs of retinoic acid, exhibit potent growth inhibitory and cell differentiation activities that account for their beneficial effects in treating hyperproliferative diseases such as psoriasis, actinic keratosis, and certain neoplasias. Tazarotene is a synthetic retinoid that is used in the clinic for the treatment of psoriasis. To better understand the mechanism of retinoid action in the treatment of hyperproliferative diseases, we used a long-range differential display–PCR to isolate retinoid-responsive genes from primary human keratinocytes. We have identified a cDNA, tazarotene-induced gene 3 (TIG3; Retinoic Acid Receptor Responder 3) showing significant homology to the class II tumor suppressor gene, H-rev 107. Tazarotene treatment increases TIG3 expression in primary human keratinocytes and in vivo in psoriatic lesions. Increased TIG3 expression is correlated with decreased proliferation. TIG3 is expressed in a number of tissues, and expression is reduced in cancer cell lines and some primary tumors. In breast cancer cell lines, retinoid-dependent TIG3 induction is observed in lines that are growth suppressed by retinoids but not in nonresponsive lines. Transient over-expression of TIG3 in T47D or Chinese hamster ovary cells inhibits colony expansion. Finally, studies in 293 cells expressing TIG3 linked to an inducible promoter demonstrated decreased proliferation with increased TIG3 levels. These studies suggest that TIG3 may be a growth regulator that mediates some of the growth suppressive effects of retinoids.