The influence of the place of residence, smoking and alcohol consumption on bone mineral content in the facial skeleton.

BACKGROUND: Environmental factors exert their influence on the living organism throughout ontogeny. More and more often, researchers find correlations between specific environmental factors and the so-called diseases of affluence. Deficits and excess of essential elements also leave their mark on the skeleton. AIM: To investigate the influence of alcohol consumption, tobacco smoking and place of residence, according to sex and calendar age, on the concentrations of micro-, macro- and toxic elements in human facial bones. MATERIAL & METHODS: Patients undergoing surgical treatment were examined for the mineral content in the collected bone material. The bone contents of the following elements were determined: Ca, K, Mg, Na, P, Fe, Zn, Mo, Ba, Mn, Li, Be, Co, B, Sr, Cr, Pb, Cd, Ni, and Al, depending on the type of facial bone, sex, calendar age, alcohol consumption, tobacco smoking and place of residence. RESULTS: Sex and alcohol consumption showed the highest degree of correlation with the content of the minerals included in the study. Alcohol drinking was found to exert the strongest influence on women's bodies, the highest number of statistically significant correlations was demonstrated between the content of minerals in the examined bones and alcohol drinking in women. Other factors included in the analysis had a different impact on men and women, the concentrations of elements included in the study differed depending on age, tobacco smoking and place of residence. CONCLUSIONS: The observed differences in the element mineral composition of the human facial skeleton may be explained by developmental specifics and functional adaptation. However, general biological characteristics (sex, age), environmental factors (place of residence), as well as smoking and alcohol use may exert significant influence on the concentrations of micro-, macro- and toxic elements in particular regions of the human skeleton. The impact of environmental factors is a very complex phenomenon, which may be stronger or more subtle, leaving its mark on the bone structure. The environmental factors included in the analysis had a different influence on men than women.

Chondromyxoid Fibroma Arising in Craniofacial Sites: A Clinicopathologic Analysis of 25 Cases.

Chondromyxoid fibroma (CMF) is a rare benign tumor, usually arising in the metaphysis of long bones in young adults. Occurrence in craniofacial bones presents a particular diagnostic challenge given its unusual location and resemblance to malignant mimics. We describe the clinicopathologic features of 25 cases of craniofacial CMF identified between 1999 and 2017. Patients were 14 men and 11 women, with median age of 44 years (range, 5 to 83 y). Sites of involvement were sphenoid (7), ethmoid (5), maxilla (3), occipital (2), nasal septum (2), palatine (2), temporal (2), orbit (1), and undisclosed skull (1). Tumor size ranged from 0.8 to 6.0 cm (median, 2.0 cm). Of the 21 tumors with available radiology, 15 arose on the bone surface with expansion into adjacent sinuses; 6 were intraosseous. Bony erosion/destruction was present in most (13/16) cases, and 7/12 showed calcification on imaging. Microscopically, most tumors showed a lobulated growth pattern with hypocellular central chondromyxoid areas and peripheral hypercellularity, though many samples were fragmented. Tumor cells had ovoid to tapered nuclei and abundant palely eosinophilic cytoplasm, frequently with stellate cell processes. Mitoses ranged from 0 to 2 per 10 high-power fields (median count, 0). None showed necrosis. Significant atypia was present in 2 cases, 1 of which was a previously radiated recurrence. Bone infiltration was present in 6 cases. Thirteen tumors had focal calcification, and 2 had foci of hyaline cartilage. All tumors were negative for keratin and GFAP (0/24), with frequent positivity for SMA (7/7) and occasional staining for EMA (5/24) and S-100 (2/24). Most patients underwent piecemeal excision or curettage (5/5 positive margins when reported). Follow-up data were available for 15 patients, and 5 suffered local recurrence. Craniofacial CMF poses diagnostic pitfalls including frequent aggressive radiologic features and lack of a specific immunophenotype. Tumors may recur, largely due to the difficulty of obtaining clear surgical margins in this anatomic region. Furthermore, propensity for local destruction and invasion can create significant morbidity.

Cell morphologic changes and PCNA expression within craniofacial sutures during monkey Class III treatment.

OBJECTIVES: To evaluate and compare the cellular morphologic changes and proliferating cell nuclear antigen (PCNA) expression within craniofacial sutures in growing Rhesus monkeys treated with a Class III functional appliance. MATERIALS AND METHODS: Six Rhesus monkeys in the mixed dentition stage were divided into three groups: a 45-day experimental group, a 90-day experimental group, and a control group. Monkeys in the experimental groups were fitted with a Class III magnetic twin-block appliance. Cellular changes in six craniofacial sutures-the zygomaticomaxillary, zygomaticotemporal, transverse palatine, pterygopalatine, zygomaticofrontal, and frontomaxillary sutures were qualitatively and quantitatively evaluated by means of histomorphologic analysis, TEM, and immunohistochemical test of PCNA. RESULTS: Obvious and altered bone remodeling combined with bone deposition and resorption was present in craniofacial sutures in the experimental groups. Increased activity of enlarged fibroblasts with abundant organelles was revealed. PCNA expression increased in the 45-day group compared with the control group, followed by the 90-day group. The highest percentage of PCNA-positive cells was found in the pterygopalatine suture in the 45-day group and the zygomaticomaxillary suture in the 90-day group. CONCLUSIONS: The pterygopalatine and zygomaticomaxillary sutures are more active among the craniofacial sutures in the craniofacial complex remodeling during Class III treatment. The magnetic twin-block appliance effectively promoted suture remodeling by enhancing the activity and proliferation of osteoblasts, osteoclasts, and fibroblasts, especially in the early phase.

A rapid, flexible method for incorporating controlled antibiotic release into porous polymethylmethacrylate space maintainers for craniofacial reconstruction.

Severe injuries in the craniofacial complex, resulting from trauma or pathology, present several challenges to functional and aesthetic reconstruction. The anatomy and position of the craniofacial region make it vulnerable to injury and subsequent local infection due to external bacteria as well as those from neighbouring structures like the sinuses, nasal passages, and mouth. Porous polymethylmethacrylate (PMMA) "space maintainers" have proven useful in staged craniofacial reconstruction by promoting healing of overlying soft tissue prior to reconstruction of craniofacial bones. We describe herein a method by which the porosity of a prefabricated porous PMMA space maintainer, generated by porogen leaching, can be loaded with a thermogelling copolymer-based drug delivery system. Porogen leaching, space maintainer prewetting, and thermogel loading all significantly affected the loading of a model antibiotic, colistin. Weeks-long release of antibiotic at clinically relevant levels was achieved with several formulations. In vitro assays confirmed that the released colistin maintained its antibiotic activity against several bacterial targets. Our results suggest that this method is a valuable tool in the development of novel therapeutic approaches for the treatment of severe complex, infected craniofacial injuries.

A deep penetrating facial congenital melanocytic tumor with bone involvement and ipsilateral eye blindness.

Bone involvement has been described in tumors with melanocytic differentiation such as melanotic neuroectodermal tumor of infancy, and very rarely in cellular blue nevi and neurocristic cutaneous hamartoma. We present an unusual case of facial congenital melanocytic tumor that involved the underlying bones and maxillary sinus and led to unilateral blindness. A newborn with a large red bluish patch with peripheral brown and black macules overlying marked swelling on the left side of his face was presented. The tumor was shown by magnetic resonance imaging, scintigraphy, and histopathology to invade the underlying bones and maxillary sinus and to compress the left eyeball resulting in blindness. Histopathology, immunohistochemistry, morphometric computerized microscopy, molecular genetic mutation analysis, and fluorescent in situ hybridization studies were more congruent with a melanocytic nevus. An 8.5-year follow-up was uneventful, with spontaneous partial shrinkage of the tumor.

The study of barium concentration in deciduous teeth, impacted teeth, and facial bones of Polish residents.

The study determines the concentration of Ba in mineralized tissues of deciduous teeth, permanent impacted teeth, and facial bones. The study covers the population of children and adults (aged 6-78) living in an industrial area of Poland. Teeth were analyzed in whole, with no division into dentine and enamel. Facial bones and teeth were subjected to the following preparation: washing, drying, grinding in a porcelain mortar, sample weighing (about 0.2 g), and microwave mineralization with spectrally pure nitric acid. The aim of the study was to determinate the concentration of Ba in deciduous teeth, impacted permanent teeth, and facial bones. The concentration of barium in samples was determined over the ICP OES method. The Ba concentration in the tested bone tissues amounted to 2.2-15.5 µg/g (6.6 µg/g ± 3.9). The highest concentration of Ba was present in deciduous teeth (10.5 µg/g), followed by facial bones (5.2 µg/g), and impacted teeth (4.3 µg/g) (ANOVA Kruskal-Wallis rank test, p = 0.0002). In bone tissue and impacted teeth, Ba concentration increased with age. In deciduous teeth, the level of Ba decreased with children's age.

Unusual multifocal intraosseous papillary intralymphatic angioendothelioma (Dabska tumor) of facial bones: a case report and review of literature.

Papillary intralymphatic angioendothelioma (PILA) or Dabska tumor is extremely rare, and often affects the skin and subcutaneous tissues of children. Since its first description by Dabska, only a few intraosseous cases have been described in the literature and none of them presents with multifocal osteolytic lesion of bones. We present a case of unusual multifocal intraosseous PILA in facial bones occurring in a 1 year 3 month old male child. Computed tomography (CT) scan revealed multifocal osteolytic lesions were located at the left zygoma, left orbital bone and right maxillary. Histologically, the lesions were ill-defined and composed of multiple delicate interconnecting vascular channels with papillae formation which projected into the lumen lined by atypical plumped endothelial cells. The vascular channels were also lined by plump cuboidal endothelial cells with focal hobnailed or "match-head" appearance. In some areas, endothelial cells formed solid-appearing aggregates with vessel lumens. By immunohistochemistry, the tumor cells were positive for CD31, CD34 and D2-40 at varying intensity. A final diagnosis of intraosseous PILA was made. To the best of our knowledge, this case is the first case of primary multifocal osseous PILA. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1919488629100787.

Bisphosphonate-related osteonecrosis of jaw (BRONJ): an anti-angiogenic side-effect?

Bisphosphonates are recommended in the treatment of osteoporosis and some cancers, in which case they prevent the appearance of bone metastasis. The patients taking bisphosphonates are at increased risk of developing bisphosphonate-related osteonecrosis of jaw (BRONJ) which is characterised by the presence of an un-healing wound after dental surgery. BRONJ might represent an anti-angiogenic side effect. However, the real number of patients with BRONJ might be higher than currently recorded. Considering the differential diagnosis which includes various primary and secondary cancers, a correct histopathological diagnosis is very important. The morphological criteria for diagnosis of BRONJ are highlighted in this material.

A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue.

The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.

Residual monomers released from glass-fibre-reinforced composite photopolymerised in contact with bone and blood.

PURPOSE: The aim of this study was to determine the quantity of residual monomers of glass fibre-reinforced composite released into water from the composite that had been photopolymerized in contact with bone and blood. MATERIALS AND METHODS: E-glass fibre reinforced composite (FRC) made of E-glass fibre veil and the bis-GMA-TEGDMA-PMMA resin system was used in the study. In the first group, pieces of non-polymerised FRC were photopolymerised (40 s) in air which influenced the oxygen inhibited resin layer (positive control). In the second group, the FRC was polymerized between two glass plates allowing both surfaces to be well polymerized (negative control). In the test groups, the FRC was polymerized in contact with bone or in contact with blood. FRC specimens from all four groups were incubated in three milliliters of deionised water at 37 degrees C for three days. At the end of the incubation period, the residual monomers were extracted from the water with dichloromethane, and the residual monomers of TEGDMA and bis-GMA quantitatively analysed by HPLC. The degree of monomer conversion was measured by FTIR from the surface of the test specimen. Differences between the groups were analysed using one-way ANOVA (p < 0.05). RESULTS: The total quantity of residual monomers released from FRC polymerized in contact with bone was lower (0.55 wt%) than in the positive control group (0.97 wt%) (p = 0.021), and only slightly exceeded that of the negative control group (0.42 wt%) (p = 0.717). The total quantity of monomers released from FRC polymerized in contact with blood was at the level of the negative control group. The main residual monomer released was TEGDMA. The surfaces of the positive and negative controls showed a clear difference between the degree of monomer conversion, 34.0 and 62.8%, respectively, when analysed with FTIR (p < 0.001). CONCLUSION: The surface of the bone or contact with blood did not significantly inhibit the photoinitiated free radical polymerisation of the dimethacrylate monomer system of the FRC.

From genotype to phenotype: the differential expression of FGF, FGFR, and TGFbeta genes characterizes human cranioskeletal development and reflects clinical presentation in FGFR syndromes.

Mutations in the fibroblast growth factor receptor (FGFR) genes 1, 2, and 3 are causal in a number of craniofacial dysostosis syndromes featuring craniosynostosis with basicranial and midfacial deformity. Great clinical variability is displayed in the pathologic phenotypes encountered. To investigate the influence of developmental genetics on clinical diversity in these syndromes, the expression of several genes implicated in their pathology was studied at sequential stages of normal human embryo-fetal cranial base and facial ossification (n = 6). At 8 weeks of gestation, FGFR1, FGFR2, and FGFR3 are equally expressed throughout the predifferentiated mesenchyme of the cranium, the endochondral skull base, and midfacial mesenchyme. Both clinically significant isoforms of FGFR2, IgIIIa/c and IgIIIa/b, are coexpressed in maxillary and basicranial ossification. By 10 to 13 weeks, FGFR1 and FGFR2 are broadly expressed in epithelia, osteogenic, and chondrogenic cell lineages. FGFR3, however, is maximally expressed in dental epithelia and proliferating chondrocytes of the skull base, but poorly expressed in the osteogenic tissues of the midface. FGF2 and FGF4, but not FGF7, and TGFbeta1 and TGFbeta3 are expressed throughout both osteogenic and chondrogenic tissues in early human craniofacial skeletogenesis. Maximal FGFR expression in the skull base proposes a pivotal role for syndromic growth dysplasia at this site. Paucity of FGFR3 expression in human midfacial development correlates with the relatively benign human mutant FGFR3 midfacial phenotypes. The regulation of FGFR expression in human craniofacial skeletogenesis against background excess ligand and selected cofactors may therefore play a profound role in the pathologic craniofacial development of children bearing FGFR mutations.

The role of transforming growth factor alpha in rat craniofacial development and chondrogenesis.

To explore the possible role of transforming growth factor alpha (TGF-alpha) in craniofacial development, its expression in the craniofacial region of rat embryos from embryonic day (d) 9 to d 20 was examined by in situ hybridisation and immunostaining. The TGF-alpha transcripts were first detected in the neural fold of embryonic d 9 and 10 embryos. In the craniofacial region, the TGF-alpha transcripts were not detected until embryonic d 16 in mesenchyme surrounding the olfactory bulb, within the olfactory bulb, the nasal capsule, vomeronasal organ, and vibrissal follicle. In addition, TGF-alpha message was detected in mesenchyme in the vicinity of Meckel's cartilage, and in the dental epithelium and lamina. This expression pattern of TGF-alpha transcripts persisted until embryonic d 17 but disappeared by d 18. The presence of TGF-alpha protein largely coincided with TGF-alpha message although, unlike the message, it persisted throughout later embryogenesis in the craniofacial region. The possible function of TGF-alpha in chondrogenesis was explored by employing the micromass culture technique. Cartilage nodule formation in mesenchymal cells cultured from rat mandibles in the presence of TGF-alpha was significantly inhibited. This inhibitory effect of TGF-alpha on chondrogenesis was reversed by addition of antibody against the EGF receptor, which crossreacts with the TGF-alpha receptor. The inhibitory effect of TGF-alpha on chondrogenesis in vitro was further confirmed by micromass culture using mesenchymal cells from rat embryonic limb bud. Taken together, these results demonstrate the involvement of TGF-alpha in chondrogenesis during embryonic development, possibly by way of a specific inhibition of cartilage formation from mesenchymal precursor cells.

Expression of bone morphogenetic protein-4 (BMP-4), bone morphogenetic protein-7 (BMP-7), fibroblast growth factor-8 (FGF-8) and sonic hedgehog (SHH) during branchial arch development in the chick.

Expression of Fgf-8, Bmp-4, Bmp-7, and shh in the branchial arches of the chick embryo is examined by in situ hybridization. Fgf-8 expression is initially broad and diffuse, becoming more tightly restricted, particularly in the epithelium of the posterior ectodermal margin (PEM) of the 2nd branchial arch. Bmp-7 transcripts, first seen at stage 12 in discrete regions corresponding to the developing branchial clefts, are later detected in both clefts and arches, including the PEM of the 2nd arch while Bmp-4 transcripts are detected at stage 18 in the distal tips of the arches. Shh expression remains localized, overlapping with both Bmp-7 and Fgf-8 in the PEM of the 2nd arch at stages 16 and 18. Based on these data, a model is proposed for the role of these signalling molecules in branchial arch development.