Metal Node Control of Brønsted Acidity in Heterobimetallic Titanium-Organic Frameworks.

Compared to indirect framework modification, synthetic control of cluster composition can be used to gain direct access to catalytic activities exclusive of specific metal combinations. We demonstrate this concept by testing the aminolysis of epoxides with a family of isostructural mesoporous frameworks featuring five combinations of homometallic and heterobimetallic metal-oxo trimers (Fe3, Ti3, TiFe2, TiCo2, and TiNi2). Only TiFe2 nodes display activities comparable to benchmark catalysts based on grafting of strong acids, which here originate from the combination of Lewis Ti4+ and Brønsted Fe3+-OH acid sites. The applicability of MUV-101(Fe) to the synthesis of ß-amino alcohols is demonstrated with a scope that also includes the gram scale synthesis of propranolol, a natural ß-blocker listed as an essential medicine by the World Health Organization, with excellent yield and selectivity.

HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients.

OBJECTIVE: Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients. METHODS: Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively. RESULTS: mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC. CONCLUSION: HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression.

Splicing machinery is impaired in rheumatoid arthritis, associated with disease activity and modulated by anti-TNF therapy.

OBJECTIVES: To characterise splicing machinery (SM) alterations in leucocytes of patients with rheumatoid arthritis (RA), and to assess its influence on their clinical profile and therapeutic response. METHODS: Leucocyte subtypes from 129 patients with RA and 29 healthy donors (HD) were purified, and 45 selected SM elements (SME) were evaluated by quantitative PCR-array based on microfluidic technology (Fluidigm). Modulation by anti-tumour necrosis factor (TNF) therapy and underlying regulatory mechanisms were assessed. RESULTS: An altered expression of several SME was found in RA leucocytes. Eight elements (SNRNP70, SNRNP200, U2AF2, RNU4ATAC, RBM3, RBM17, KHDRBS1 and SRSF10) were equally altered in all leucocytes subtypes. Logistic regressions revealed that this signature might: discriminate RA and HD, and anti-citrullinated protein antibodies (ACPAs) positivity; classify high-disease activity (disease activity score-28 (DAS28) >5.1); recognise radiological involvement; and identify patients showing atheroma plaques. Furthermore, this signature was altered in RA synovial fluid and ankle joints of K/BxN-arthritic mice. An available RNA-seq data set enabled to validate data and identified distinctive splicing events and splicing variants among patients with RA expressing high and low SME levels. 3 and 6 months anti-TNF therapy reversed their expression in parallel to the reduction of the inflammatory profile. In vitro, ACPAs modulated SME, at least partially, by Fc Receptor (FcR)-dependent mechanisms. Key inflammatory cytokines further altered SME. Lastly, induced SNRNP70-overexpression and KHDRBS1-overexpression reversed inflammation in lymphocytes, NETosis in neutrophils and adhesion in RA monocytes and influenced activity of RA synovial fibroblasts. CONCLUSIONS: Overall, we have characterised for the first time a signature comprising eight dysregulated SME in RA leucocytes from both peripheral blood and synovial fluid, linked to disease pathophysiology, modulated by ACPAs and reversed by anti-TNF therapy.

Combining Wire Localization of Clipped Nodes with Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: Preliminary Results from a Prospective Study.

BACKGROUND: The ideal technique for lymph node staging for patients with pathologically confirmed node-positive breast cancer at diagnosis and neoadjuvant chemotherapy (NAC) is unclear. OBJECTIVE: The aim of this study was to analyze the feasibility of wire/clip localization and sentinel lymph node biopsy (SLNB) for the axillary staging of these patients. METHODS: We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and an SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an axillary lymph node dissection (ALND). The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. RESULTS: Forty-two patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in all patients (100%), with SLNB performed successfully in 95.3% of patients. The SLN and wire-marked node matched in 80% of patients; 73.8% of patients did not undergo ALND. DISCUSSION AND CONCLUSIONS: Several studies have evaluated the efficacy of various procedures for lymph node marking for women with prechemotherapy lymph node involvement. Most of the studies reported high identification rates (> 94.8%), with false negative rates of < 7%. Similarly, our study allows us to conclude that combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and NAC offers a high identification rate (100%) and a high correlation between the wire-marked lymph node and the SLN (80%). This procedure has enabled the suppression of ALND for a significant number of patients (73%).

All-Trans Retinoic Acid Inhibits Migration and Invasiveness of Rheumatoid Fibroblast-Like Synoviocytes.

Fibroblast-like synoviocytes (FLSs) are pivotal in inflammation and joint damage of rheumatoid arthritis (RA). They acquire an active and aggressive phenotype, displaying increased migration and invasiveness and contributing to perpetuate synovial inflammation and destruction of cartilage and bone. The main current therapies of RA are focused against inflammatory factors and immune cells; however, a significant percentage of patients do not successfully respond. Combined treatments with drugs that control inflammation and that reverse the pathogenic phenotype of FLS could improve the prognosis of these patients. An unexplored area includes the retinoic acid, the main biologic retinoid, which is a candidate drug for many diseases but has reached clinical use only for a few. Here, we explored the effect of all-trans retinoic acid (ATRA) on the aggressive phenotype of FLS from patients with RA. RA FLSs were treated with ATRA, tumor necrosis factor (TNF), or TNF+ATRA, and cell migration and invasion were analyzed. In addition, a microarray analysis of expression, followed by gene-set analysis and quantitative polymerase chain reaction validation, was performed. We showed that ATRA induced a notable decrease in FLS migration and invasion that was accompanied by complex changes in gene expression. At supraphysiological doses, many of these effects were overridden or reverted by the concomitant presence of TNF. In conclusion, these results have demonstrated the therapeutic potential of retinoic acid on RA FLS provided TNF could be counterbalanced, either with high ATRA doses or with TNF inhibitors. SIGNIFICANCE STATEMENT: All-trans retinoic acid (ATRA) reduced the rheumatoid arthritis (RA) fibroblast-like synoviocyte migration and invasiveness and down-regulated gene expression of cell motility and migration genes. At supraphysiological doses, some of these effects were reverted by tumor necrosis factor. Therefore, ATRA could be an RA drug candidate that would require high doses or combined treatment with anti-inflammatory drugs.

Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients.

OBJECTIVE: To examine the role of Tie2 signalling in macrophage activation within the context of the inflammatory synovial microenvironment present in patients with RA and PsA. METHODS: Clinical responses and macrophage function were examined in wild-type and Tie2-overexpressing (Tie2-TG) mice in the K/BxN serum transfer model of arthritis. Macrophages derived from peripheral blood monocytes from healthy donors, RA and PsA patients, and RA and PsA synovial tissue explants were stimulated with TNF (10 ng/ml), angiopoietin (Ang)-1 or Ang-2 (200 ng/ml), or incubated with an anti-Ang2 neutralizing antibody. mRNA and protein expression of inflammatory mediators was analysed by quantitative PCR, ELISA and Luminex. RESULTS: Tie2-TG mice displayed more clinically severe arthritis than wild-type mice, accompanied by enhanced joint expression of IL6, IL12B, NOS2, CCL2 and CXCL10, and activation of bone marrow-derived macrophages in response to Ang-2 stimulation. Ang-1 and Ang-2 significantly enhanced TNF-induced expression of pro-inflammatory cytokines and chemokines in macrophages from healthy donors differentiated with RA and PsA SF and peripheral blood-derived macrophages from RA and PsA patients. Both Ang-1 and Ang-2 induced the production of IL-6, IL-12p40, IL-8 and CCL-3 in synovial tissue explants of RA and PsA patients, and Ang-2 neutralization suppressed the production of IL-6 and IL-8 in the synovial tissue of RA patients. CONCLUSION: Tie2 signalling enhances TNF-dependent activation of macrophages within the context of ongoing synovial inflammation in RA and PsA, and neutralization of Tie2 ligands might be a promising therapeutic target in the treatment of these diseases.

Evaluation of a clinical pharmacogenetics model to predict methotrexate response in patients with rheumatoid arthritis.

Variability of response to treatment hinders successful management of rheumatoid arthritis (RA). Consequently, a clinical pharmacogenetics model for predicting response to methotrexate (CP-MTX) has been previously proposed that includes four clinical variables (disease activity, sex, the presence of rheumatoid factor and smoking status) and four SNPs (rs2236225, rs17602729, rs1127354, and rs2372536) in genes of the folate pathway. It showed good performance, but failed to attract attention, likely, in relation with lack of clear clinical benefit. Here, we have revised the value of the CP-MTX model directly addressing its clinical benefit by focusing on the expected benefit-cost of the predictions. In addition, our study included a much larger number of RA patients (n = 720) in MTX monotherapy than previous studies. Benefit of CP-MTX prediction was defined as the patients that would have received combination therapy as first treatment because they were correctly predicted as non-responders to MTX monotherapy. In contrast, cost of CP-MTX prediction was defined as the responder patients that were wrongly predicted as non-responders. Application of CP-MTX predictions to our patients showed a good benefit-cost relationship, with half of the 66.7% non-responders to MTX monotherapy rightly directed to alternative treatments (a benefit of 33.3%) at the cost of 8.5% wrongly predicted non-responders. These benefits-costs were consistent with reanalysis of the previously published studies. Therefore, predictions of CP-MTX showed a good benefit-cost relationship for informing MTX prescription.

Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice.

Pharmacological inhibition of signaling through lysophosphatidic acid (LPA) receptors reduces bone erosions in an experimental model of arthritis by mechanisms involving reduced osteoclast differentiation and bone resorption and increased differentiation of osteoblasts and bone mineralization. These results led us to hypothesize that LPA receptor inhibition would be beneficial in osteoporosis. Our aim was to test this hypothesis with the LPA receptor antagonist, Ki16425, in ovariectomized mice, a model of postmenopausal osteoporosis. Ovariectomized mice treated with Ki16425 showed bone loss similar to that observed in the controls. Osteoblast markers, Alpl, Bglap and Col1a1, were increased at the mRNA level but no changes were detected in serum. No additional difference was observed in the Ki16425-treated mice relative to the ovariectomized controls with regard to osteoclast function markers or assays of matrix mineralization or osteoclast differentiation. Thus, pharmacological inhibition of LPA receptor was not beneficial for preventing bone loss in ovariectomized mice, indicating that its favorable effect on bone remodeling is less general than hypothesized.

The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

Lysophosphatidic acid receptor inhibition as a new multipronged treatment for rheumatoid arthritis.

OBJECTIVE: To investigate the effect of lysophosphatidic acid (LPA) receptor inhibition in a mouse model of autoantibody-mediated arthritis. METHODS: Arthritis was induced in C57BL/6 mice by K/BxN serum transfer. Arthritic mice were treated with the LPA receptor antagonist, Ki16425 and arthritis severity was assessed clinically and histologically. Expression of inflammatory mediators in joints was identified by a mouse cytokine array and validated by western blot and real-time PCR assays. Effects of treatment with LPA receptor antagonist or with small interfering RNA on bone metabolism were assessed by in vitro assays of osteoclastogenesis, bone resorption, osteoblasts differentiation and bone mineralisation. RESULTS: Mice treated with the LPA receptor antagonist Ki16425 showed attenuated arthritis characterised by reduction of synovial inflammation, cartilage damage and, more markedly, bone erosion. We detected increased apoptosis, reduction of inflammatory mediators and of bone remodelling proteins in arthritic joints from mice treated with Ki16425. In addition, we demonstrated that inhibition or suppression of LPA1 receptor reduces osteoclast differentiation and bone resorption and, on the contrary, it promotes differentiation of osteoblasts and bone mineralisation. CONCLUSIONS: Pharmacological inhibition of LPA1 receptor in the K/BxN serum-transfer arthritis model led to reduction of severity of arthritis involving multiple mechanisms, increased apoptosis, reduced inflammatory mediators and proteins involved in bone remodelling, that show LPA1 as a very promising target in rheumatoid arthritis treatment.

Corrigendum: Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis.

[This corrects the article DOI: 10.3389/fimmu.2022.943293.].

Time-resolved control of nanoparticle integration in titanium-organic frameworks for enhanced catalytic performance.

Among the multiple applications of metal-organic frameworks (MOFs), their use as a porous platform for the support of metallic nanoparticles stands out for the possibility of integrating a good anchorage, that improves the stability of the catalyst, with the presence of a porous network that allows the diffusion of substrates and products. Here we introduce an alternative way to control the injection of Au nanoparticles at variable stages of nucleation of a titanium(iv) MOF crystal (MUV-10). This allows the analysis of the different modes of nanoparticle integration into the porous matrix as a function of the crystal formation stage and their correlation with the catalytic performance of the resulting composite. Our results reveal a direct effect of the stage at which the Au nanoparticles are integrated into MUV-10 crystals not only on their catalytic activity for the cyclotrimerization of propargyl esters and the hydrochlorination of alkynes, but also on the selectivity and recyclability of the final solid catalyst, which are far superior than those reported for the same reactions with TiO2 supports.

Male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study.

BACKGROUND: Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test. METHODS: We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire. RESULTS: We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18-76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11-21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0-2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0-3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2-5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3-7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0-2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5-3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3-3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0-3.1). Clinical signs tended to cluster. CONCLUSIONS: Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis.

Lysophosphatidic acid receptor 1 suppression sensitizes rheumatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis.

OBJECTIVE: To investigate the role of lysophosphatidic acid (LPA) receptors in the proliferation and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Expression of LPA receptors 1-3 was analyzed by real-time polymerase chain reaction (PCR). LPAR1 and LPAR2 were suppressed in RA FLS by small interfering RNA (siRNA) transfection. Proliferation of RA FLS after tumor necrosis factor (TNF) and LPA stimulation was determined with a luminescent cell viability assay. Apoptosis was analyzed by quantification of nucleosome release and measurement of activated caspase 3/7. Genes involved in the apoptotic response were identified with a human apoptosis PCR array and validated with Western blot assays. The requirement of these genes for apoptosis sensitization was assessed by siRNA transfection. Secretion of mediators of inflammation was analyzed by enzyme-linked immunosorbent assay. RESULTS: Only LPAR1 and LPAR2 were expressed by RA FLS, and their levels were higher than those in osteoarthritis (OA) FLS. Suppression of LPAR1 abrogated TNF-induced proliferation and sensitized the RA FLS, but not the OA FLS, to TNF-induced apoptosis. These changes occurred despite an increased early inflammatory response to TNF. Sensitization to apoptosis was associated with changes in expression of multiple apoptosis-related genes. Three of the up-regulated proapoptotic genes were further studied to confirm their involvement. In contrast, suppression of LPAR2 showed no effect in any of these analyses. CONCLUSION: LPA(1) is an important receptor in RA FLS. Its suppression is accompanied by a global increase in the response to TNF that is ultimately dominated by sensitization to apoptosis.

Lymph node staging after primary systemic therapy in women with breast cancer and lymph node involvement at diagnosis.

OBJECTIVE: The main objective of this study is to analyze the efficacy of combined axillary marking (lymph node clipping and sentinel lymph node biopsy (SLNB)) for axillary staging in patients with primary systemic treatment (PST) and pathologically confirmed node-positive breast cancer at diagnosis. The secondary objective is to determine the impact of lymph node marking in the suppression of axillary lymph node dissection (ALND) in the study group. METHODS: We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and a SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an ALND. The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. RESULTS: Eighty one patients met the inclusion criteria. We identified and extirpated the clip/ wire-marked node in 80 of 81 patients (98.8%), with SLNB performed successfully in 88,9% of patients. The SLN and wire-marked node matched in 78.9% of patients; 76.2% of patients did not undergo ALND. CONCLUSIONS: The combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and PST offers a high identification rate (98.8%) and a high correlation between the wire-marked lymph node and the SLN (78.9%). This procedure has enabled the suppression of ALND in 76.2% of patients.

Assessment of anti-malondialdehyde-acetaldehyde antibody frequencies in rheumatoid arthritis with new data from two independent cohorts, meta-analysis, and meta-regression.

BACKGROUND: Autoantibodies are critical elements in RA pathogenesis and clinical assessment. The anti-malondialdehyde-acetaldehyde (anti-MAA) antibodies are potentially useful because of their claimed high sensitivity for all RA patients, including those lacking RF and anti-CCP antibodies. Therefore, we aimed to replicate these findings. METHODS: We independently attempted replication in Santiago and Barcelona using sera from 517 and 178 RA patients and 272 and 120 healthy controls, respectively. ELISA protocols for anti-MAA antibodies included five antigens (human serum albumin in three formulations, fibrinogen, and a synthetic peptide) and assays for the IgG, IgM, and IgA isotypes. We integrated our results with information found by searching the Web of Science for reports of anti-MAA antibodies in RA. The available patients (4989 in 11 sets) were included in a meta-analysis aimed at heterogeneity between studies. Factors accounting for heterogeneity were assessed with meta-regression. RESULTS: The sensitivity of anti-MAA antibodies in our RA patients was low, even in seropositive patients, with the percentage of positives below 23% for all ELISA conditions. Our results and bibliographic research showed IgG anti-MAA positive patients ranging from 6 to 92%. The extreme between-studies heterogeneity could be explained (up to 43%) in univariate analysis by sex, African ethnicity, the site of study, or recruitment from the military. The best model, including African ancestry and smoking, explained a high heterogeneity fraction (74%). CONCLUSION: Anti-MAA antibody sensitivity is extremely variable between RA patient collections. A substantial fraction of this variability cannot be attributed to ELISA protocols. On the contrary, heterogeneity is determined by complex factors that include African ethnicity, smoking, and sex.

Semaphorin3B promotes an anti-inflammatory and pro-resolving phenotype in macrophages from rheumatoid arthritis patients in a MerTK-dependent manner.

Previous works from our group show that Semaphorin3B (Sema3B) is reduced in RA and plays a protective role in a mouse arthritis model. In turn, MerTK plays a protective function in murine arthritis models, is expressed by synovial tissue macrophages and is linked to remission in patients with RA. In this study, we examined the role of Sema3B in the phenotypic characteristics of RA macrophages and the implication of MerTK. Peripheral blood monocytes from RA patients were differentiated into IFN-γ (RA MØIFN-γ) or M-CSF (RA MØM-CSF) macrophages and stimulated with LPS, Sema3B or their combination. Alternatively, RA fibroblast like synoviocytes (FLS) were stimulated with RA MØIFN-γ and RA MØM-CSF supernatants. Gene expression was determined by qPCR and protein expression and activation by flow cytometry, ELISA and western blot. Sema3B down-regulated the expression of pro-inflammatory mediators, in both RA MØIFN-γ and RA MØM-CSF. We observed a similar reduction in RA FLS stimulated with the supernatant of Sema3B-treated RA MØIFN-γ and RA MØM-CSF. Sema3B also modulated cell surface markers in macrophages towards an anti-inflammatory phenotype. Besides, MerTK expression and activation was up-regulated by Sema3B, just as GAS6 expression, Resolvin D1 secretion and the phagocytic activity of macrophages. Importantly, the inhibition of MerTK and neuropilins 1 and 2 abrogated the anti-inflammatory effect of Sema3B. Our data demonstrate that Sema3B modulates the macrophage characteristics in RA, inducing a skewing towards an anti-inflammatory/pro-resolving phenotype in a MerTK-dependant manner. Therefore, here we identify a new mechanism supporting the protective role of Sema3B in RA pathogenesis.

Cranial base and maxillary changes in patients treated with Frankel' s functional regulator (1b).

OBJECTIVES: The purpose of this study was to assess cranial base and maxillary growth in patients with Class II-type I malocclusions when treated with Frankel' s functional regulator (FR-1b). STUDY DESIGN: The treatment group was made up of 43 patients that were divided into two groups: prepubescent (n: 28), and pubescent (n: 15). The control group included 40 patients who did not receive any kind of treatment and were likewise divided into a prepubescent group (n: 19), and a pubescent group (n: 21). A computerized cephalometric study was carried out and superimpositions were done in order to assess the antero-posterior, vertical and rotational movement of the maxilla. RESULTS: The results indicate that anterior cranial length is not affected by the regulator but the cranial deflection of the treatment group was diminished. Although a slight counterclockwise rotation effect on the upper jaw was observed due to treatment, no growth restriction of the maxilla in a vertical or antero-posterior direction was observed compared to other non-treated Class II-type I malocclusion patients. CONCLUSION: The functional regulator does not have any effect on anterior cranial length, but it does affect the angulation of the cranial base. According to our results, the appliance has demonstrated a flattening effect of the cranial base (p<0.05) in the treated sample. The functional regulator induces counterclockwise rotation rather than vertical or sagittal changes in the maxilla.

Effects on the maxilla and cranial base caused by cervical headgear: a longitudinal study.

OBJECTIVES: The aim of this study is to test the possible orthopedic effects of cervical headgear on the cranial base and maxilla. STUDY DESIGN: a sample consisting of 79 subjects with skeletal class II malocclusion was divided into two groups. The experimental group was made up of 41 patients all treated with cervical headgear. The control group included a total of 38 non-treated patients. Each one of these groups was then subdivided according to age into one of three groups: prepubescent, pubescent or post-pubescent. Cephalometric parameters were compared in both groups in order to measure the cranial base angle and the vertical and sagittal position of the maxilla. Additionally, cephalometric superimpositions taken at the beginning and end of the study were compared. RESULTS: results revealed significant differences in the cranial base angle and in the SNA angle (p<0.05). However, no differences were observed in the variables that measure the maxillomandibular relationship. While no changes were noted in the palatal plane slope, a flattening of the cranial base was found caused by the cervical headgear, in addition to a retrusion of point A that does not mean there was a reduction in the maxillomandibular relationship. CONCLUSIONS: cervical headgear treatment induces cephalometric flattening of the cranial base and a decrease of the SNA angle.

Study of mandibular growth in patients treated with Fränkel's functional regulator (1b).

OBJECTIVES: The purpose of this study was to assess mandibular growth in patients with Class II division 1 malocclusions when treated with Fränkel's functional regulator 1b. STUDY DESIGN: The treatment group was made up of 43 patients that were divided into two groups: prepubescent (n:28), and pubescent (n:15). The control group included 40 patients who did not receive any kind of treatment and were likewise divided into a prepubescent group (n:19), and a pubescent group (n:21). A computerized cephalometric study was carried out and superimpositions were done in order to assess the antero-posterior, vertical and rotational movements of the mandible. A two-way ANOVA with interaction was done to compare the changes between the control group and the treatment group, while the Student t for independent samples was used to compare each age group. RESULTS: The Gnathion and Gonion points showed significant differences in the whole sample (p<0.001) as well as in the prepubescent (p<0.001) and pubescent groups (p<0.05). Rotational changes of the mandible measured using the facial axis and mandibular plane showed no statistical differences between both groups (p>0.05). CONCLUSION: The results show that the FR produces vertical orthopedic growth in the mandible but not horizontal growth compared to non-treated Class II-type I malocclusion patients. No rotational changes were found in the mandible, but we did record mandibular growth along the inclination of the facial axis.