Influence of growth hormone on the mandibular condylar cartilage of rats

Growth hormone (GH) stimulates mandibular growth but its effect on the mandibular condylar cartilage is not well. understood. Objective: This study was designed to understand the influence of GH on mitotic activity and on chondrocytes maturation. The effect of GH on cartilage thickness was also determined. Design: An animal model witt differences in GH status was determined by comparing mutant Lewis dwarf rats with reduced pituitary GH synthesis (dwarf), with normal rats and dwarf animals treated with GH. Six dwarf rats were injected with GH for 6 days, while other six normal rats and six dwarf rats composed other two groups. Mandibular condylar tissues were processed and stained for Herovici's stain and immunohistochemistry, for proliferating cell nuclear antigen (PCNA) and alkaline phosphatase (ALP). Measurements of cartilage thickness as well as the numbers of immunopositive cells for each antibody were analysed by one-way analysis of variance. Results: Cartilage thickness was significantly reduced in the dwarf animals treated with GH. PCNA expression was significant lower in the dwarf rats, but significantly increased when these animals were treated with GH. ALP expression was significant higher in the dwarf animals, while it was significantly reduced in the dwarf animals treated with GH. Conclusions: The results from this study showed that GH stimulates mitotic activity and delays cartilage cells maturation in the mandibular condyte. This effect at the cellular Level may produce changes in the cartilage thickness. (C) 2004 Elsevier Ltd. All rights reserved.

Unraveling the molecular underpinnings of Philadelphia-negative myeloproliferative neoplasms: implications for future therapeutic strategies

The present thesis encompasses the two researches projects I conducted during my PhD program in Molecular Biology and Pathology. The common thread is represented by the analysis of the signaling pathways implicated in the pathophysiology of the two most aggressive Philadelphia-negative myeloproliferative neoplasms, namely, atypical chronic myeloid leukemia (aCML) and primary myelofibrosis (PMF). In the last decade, since the description of the JAK2V617F mutation in 2005, the field of the molecular characterization of Philadelphia-negative myeloproliferative neoplasms has experienced an astonishing implementation that led to the discovery of 16 new mutations involving signal transduction, epigenetic modifiers, cell cycle regulators. Nevertheless, their pathogenetic relevance and whether they could represent good “druggable” candidates have to be proved yet. In the first section I provide the first report of the signaling cascade down-stream the rare cytogenetic lesion t(8;9)(p22;p24)/PCM1-JAK2 associated with aCML, finding that it selectively activates the ERK1/2 signaling without affecting JAK/STAT phosphorylation. In the second part, I investigated the implication of the ε isoform of novel Protein kinase Cs (PKCs) in the pathophysiology of the aberrant megakaryocytopoiesis in PMF, concluding that the over-expression of PKCε detains a crucial relevance in the aberrant behavior of PMF megakaryocytes and its inhibition is capable to restore their normal differentiation and abrogate the anti-apoptotic signaling. Both results are discussed in the view of their therapeutic implications. In case PCM1/JAK2-related hematologic neoplasms, ERK-inhibitors rather than JAK-inhibitors (i.e. ruxolitinib) should be considered as a “tailored” drugs. In case of PMF, PKCε-inhibitors (i.e. εV1-2 peptide) configure as an appealing strategy to re-direct the megakaryocytic neoplastic clone.

AVALIAÇÃO DO PADRÃO ESQUELÉTICO VERTICAL DA FACE NA OCLUSÃO NORMAL NATURAL E NAS MALOCLUSÕES DE ANGLE, E SUA CORRELAÇÃO COM A SÍNFISE MANDIBULAR

O propósito deste estudo foi avaliar cefalometricamente, o padrão esquelético vertical da face em indivíduos com oclusão normal natural e nas diferentes maloclusões e sua correlação com a sínfise mandibular, além de avaliar a presença de dimorfismo sexual. A amostra foi composta de 200 telerradiografias cefalométricas, divididas quanto ao tipo de oclusão, em cinco grupos: grupo A, com pacientes portadores de oclusão normal natural e grupos B, C, D e E, com pacientes portadores de maloclusões, sendo cada grupo, dividido igualmente quanto ao sexo e apresentando idade média entre 13 e 16 anos. A amostra foi classificada em 3 padrões morfológicos verticais da face, de acordo com o índice da altura facial (FHR), proposto por SIRIWAT & JARABAK ou Quociente de Jarabak, em: Hiperdivergente, Neutro e Hipodivergente. Foi utilizada a variável GoMe.VT, da análise de VIGORITO, para avaliar a inclinação da sínfise e sua correlação com os padrões verticais faciais. Após a coleta de dados e da avaliação dos testes estatísticos; qui-quadrado, teste t de Student e da correlação de Pearson, concluiu-se que, o padrão Hipodivergente em todos os pacientes estudados foi o mais frequente, com 70%, sendo que a maior frequência deste padrão foi encontrado na maloclusão Classe II, divisão 2, com 87.5%, existindo outras prevalências de alguns padrões em diferentes classes de oclusões. Foi encontrada uma correlação positiva entre a inclinação da sínfise mandibular e o quociente de Jarabak apenas para a maloclusão Classe I e maloclusão Classe III. Não houve diferença estatisticamente significante entre os sexos e a classificação da morfologia quando comparados os cinco grupos, porém, quando os grupos foram analisados separadamente, foram encontradas diferenças significantes entre os sexos.

Does a mandibular RDP and new maxillary CD improve masticatory efficiency and quality of life in patients with a mandibular Kennedy class I arch?

Objectives To evaluate the change in masticatory efficiency and quality of life of patients treated with mandibular Kennedy class I removable partial dentures (RPDs) and maxillary complete dentures at the Department of Dentistry of the Federal University of Rio Grande do Norte. Materials and methods A total of 33 Kennedy class I patients were rehabilitated with maxillary complete dentures, and mandibular RPDs were selected for this non-randomized prospective intervention study. The patients had a mean age of 59.1 years. Masticatory efficiency was evaluated by colorimetric assay using fuchsin capsules. The measurements were conducted at baseline and 2 and 6 months after prosthesis insertion. Quality of life was evaluated using the Oral Health Impact Profile (OHIP-14) at baseline and 6 months after denture insertion. The Kolmogorov-Smirnov normality test was applied. Masticatory efficiency was evaluated by repeated measures ANOVA. Oral health-related quality of life was compared using the paired t test. Results There was no statistically significant difference in masticatory efficiency after denture insertion (p = 0.101). Significant differences were found (p = 0.010) for oral health-related quality of life. A significant improvement in psychological discomfort (p < 0.01) and psychological disability (p < 0.01) was observed. Mean difference value (95 % confidence interval) was 6.8 (3.8 to 9.7) points, reflecting a low impact of oral health on quality of life, considering the 0–56 range of variation of the OHIP-14 and a Cohen’s d of 1.13. Conclusion According to the results of the present study, rehabilitation with Kennedy class I RPDs and complete dentures did not influence masticatory efficiency but improved oral health-related quality of life. Clinical relevance The association between the patient’s quality of life and the masticatory efficiency is important for treatment predictability.

The influence of mandibular ridge anatomy on treatment outcome with conventional complete denture.

Visto que indicadores de prognóstico são uma ferramenta importante para a seleção de pacientes a serem tratados com prótese total, este estudo investigou a influência da forma e da resiliência do rebordo alveolar mandibular sobre a retenção e estabilidade de próteses totais convencionais. Noventa e três pacientes desdentados portadores de próteses totais superior e inferior compuseram a amostra. Os dados foram coletados quanto a forma e resiliência do rebordo mandibular. As próteses foram avaliadas para a retenção e estabilidade utilizando-se uma ferramenta objetiva e reproduzível. As associações entre as características clínicas do rebordo alveolar mandibular e retenção e estabilidade das próteses foram analisados por meio dos testes qui-quadrado e exato de Fisher (α = 0.05). Observou-se associação significativa entre a forma do rebordo e a estabilidade da prótese (p <0,05), enquanto que a resiliência foi associada significativamente com a retenção (p <0,001). Baseando-se nos resultados, a resiliência e forma do rebordo mandibular influenciaram, respectivamente, a retenção e estabilidade de próteses totais convencionais.

Morfometria dos forames mandibular, mentual e infraorbital de Lobo-guará Chrysocyon brachyurus, Illiger, 1815 aplicada a bloqueios anestésicos

CHAPTER II - The Chrysocyon brachyurus is the biggest South American canid which has a high frequency of dental injuries, both in wild and captivity. Thus, veterinary procedures are necessary to preserve the feeding capacity of hundreds of captive specimens worldwide. The aim of this study was to study the mandibular morphometry of maned wolf with emphasis on the establishment of anatomic references to the anesthetic blockage of the inferior alveolar and mental nerves. Therefore, 15 measurements in 22 hemimandibles of C. brachyurus adults were taken. For extra-oral technique of blockage of the inferior alveolar nerve at the level of the mandibular foramen, it is stated that the needle should be advanced, close to the medial surface of the mandibular ramus, by 11.4 mm perpendiculary from the palpable concavity. Alternatively, the needle can be introduced for 30.4 mm from the angular process at 20-25 degrees angle with the ventral margin. For blocking only the mentual nerve, it is recommended the introduction of needle for 10 mm, close to the lateral aspect of the mandibular body, at the level of the lower first premolar. The mandibular foramen showed similars position, size and symmetry in the maned wolfs specimens examined. The comparison of the data with those available for other carnivores reflects the necessity for determining these anatomical references specifically for each species.

Mandibular Torus : A Synthesis of New and Previously Reported Data and a Discusssion of its Cause

Using original data on 1,5000 mandibles, but mainly previously published data, I present a overview of the distribution characteristics of mandibular torus and a hypothesis concerning its cause. Pedigree studies have established that genetic factors influence torus development. Extrinsic factors are strongly implicated by other evidence: prevalence among Arctic peoples, effect of dietary change, age regression, preponderance in males and on the right side, effect of cranial deformation, concurrence with palatine torus and maxillary alveolar exostoses, and clinical evidence. I propose that the primary factor is masticatory stress. According to a mechanism suggested by orthodontic research, the horizontal component of bite force tips the lower canine, premolars and first molar so that their root apices exert pressure on the periodontal membrane, causing formation of new bone on the lingual cortical plate of the alveolar process. Thus formed, the hyperostosis is vulnerable to trauma and its periosteal covering becomes bruised causing additional deposition of bone. Genes influence torus indirectly through their effect on occlusion. A patern of increased expressivity with incidence suggests that a quasicontinuous model may provide a better fit to pedigree data than single locus models previously tested.

The Calreticulin gene and myeloproliferative neoplasms

The Philadelphia negative myeloproliferative neoplasms include polycythaemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Patients with these conditions were mainly thought to harbour JAK2V617F mutations or an Myeloproliferative leukaemia (MPL) substitution. In 2013, two revolutionary studies identified recurrent mutations in a gene that encodes the protein calreticulin (CALR). This mutation was detected in patients with PMF and ET with non-mutated JAK2 or MPL but was absent in patients with PV. The CALR gene encodes the calreticulin protein, which is a multifactorial protein, mainly located in the endoplasmic reticulum in chromosome 19 and regulates calcium homeostasis, chaperones and has also been implicated in multiple cellular processes including cell signalling, regulation of gene expression, cell adhesion, autoimmunity and apoptosis. Somatic 52 bp deletions and recurrent 52 bp insertion mutations in CALR were detected and all resulted in frameshift and clusters in exon 9 of the gene. This review will summarise the current knowledge on the CALR gene and mutation of the gene in pathological conditions and patient phenotypes.

Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56- phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.

Crecimiento tumoral agresivo coincidente con el uso de distracción osteogénica mandibular: presentación de un caso

Propósito: Comunicar un caso inusual de crecimiento tumoral agresivo en relación con el uso de distracción mandibular. La situación clínica presentada sugiere que los factores bioquímicos liberados durante la distracción ósea pueden interferir el desarrollo de los tumores malignos activos, provocando una rápida progresión. Material y métodos: Presentamos el caso de una paciente con antecedentes de carcinoma basocelular esclerosante recurrente en el área labiomentoniana izquierda. A pesar de los múltiples intentos de extirpar completamente el tumor y el estrecho seguimiento realizado, 18 años después de realizar el diagnóstico inicial las biopsias tomadas mostraron infiltración tumoral de la mandíbula. Con el fin de minimizar la cantidad de hueso y partes blandas necesarias para la reconstrucción, se decidió realizar una distracción mandibular bilateral antes de realizar la resección mandibular, aprovechando así el crecimiento muy lento que tenía el tumor. Al cabo de 5 semanas de iniciar la distracción se objetivó una gran masa tumoral de nueva aparición al nivel del suelo de la boca anterior, que posteriormente se confirmó que tenía el mismo diagnóstico histopatológico que el tumor inicial. Resultados: Debido a la inesperada ocurrencia de la complicación presentada tuvimos que abandonar la distracción, y decidimos realizar una resección de espesor total del tercio facial inferior y la reconstrucción del defecto con un injerto libre vascularizado de peroné y un colgajo miocutáneo pectoral. Conclusión: La distracción osteogénica puede complicar el curso de un proceso neoplásico local y su uso debe ser valorado como posible contraindicación en pacientes con procesos tumorales activos.

Tercer molar mandibular ectópico en región subcondilar: caso clínico y revisión de la literatura

La impactación de terceros molares en la región condilar es muy inusual. Este artículo describe el caso de cordal incluido en región subcondilar en una mujer que refirió dolor inespecífico hemifacial y varios episodios de tumefacción. Se describe el manejo quirúrgico de estas inclusiones y se realiza una revisión bibliográfica.