Biomedical subjects
Publications and source records attributed to M A Lopes.
Tuberculosis is one of the major causes of ill health and death worldwide. Nevertheless, tuberculous lesions of the oral cavity are rare and can be a diagnostic challenge, particularly in young immunocompetent patients. Most of the cases are secondary to pulmonary disease and the primary form is uncommon. In this paper, we present a case of primary oral tuberculosis, affecting the floor of mouth in a 13-year-old Brazilian male patient.
BACKGROUND: Oral avascular bone necrosis is an important adverse effect of chemotherapy and biphosphate therapy. OBJECTIVE: To report our experience in oral avascular bone necrosis in cancer patients assigned to undergo chemotherapy. PATIENTS AND METHODS: Fourteen patients presenting oral avascular bone necrosis were selected from the clinical files of five Stomatological Clinics in Brazil. Clinical data as well as treatment and prognosis information were obtained from all 14 patients. RESULTS: Twelve patients (86%) were submitted to biphosphonate therapy. The most important symptom was pain, present in all cases, and the mandible was the most common involved site. Most patients (79%) had their conditions managed by antibiotic therapy and surgical debridation; however complete response was achieved in only three cases (21%). CONCLUSION: Avascular bone necrosis is a serious oral side-effect of cancer chemotherapy, particularly in patients using biphosphonates, and antibiotic therapy and surgical debridation were not able to promote complete response in most cases.
Entubulation repair of peripheral nerve injuries has a lengthy history. Several experimental and clinical studies have explored the effectiveness of many biodegradable and non-degradable tubes with or without addition of molecules and cells. The main objective of the present study was to develop an economical and also an easy way for culturing a neural cell line which was capable of growing, differentiating and producing locally nerve growth factors that are otherwise extremely expensive, inside 90 PLA/10 PLG nerve guides. For this purpose the authors have chosen the N1E-115 cell line, a clone of cells derived from mouse neuroblastoma C-1300 with the perspective of using this differentiated cellular system to cover the inside of 90 PLA/10 PLG nerve guides placed to bridge a gap in the rat sciatic nerve experimental model. The N1E-115 cells proliferate in normal culture medium but undergo neuronal differentiation in response to DMSO. Upon induction of differentiation, proliferation of N1E-115 cells ceases, extensive neurite outgrowth is observed and the membranes become highly excitable. While it is known that Ca2+ serves as an important intracellular signal for various cellular processes, such as growth and differentiation. It is also known that can be toxic to cells and is involved in the triggering of events leading to excitotoxic cell death in neurons. The [Ca2+]i in non-differentiated N1E-115 cells and after distinct periods of differentiation, have been determined by the epifluorescence technique using the Fura-2-AM probe. The results of this quantitative assessment revealed that N1E-115 cells which undergo neuronal differentiation for 48 hours in the presence of 1.5% DMSO are best qualified to be used to cover the interior of the nerve guides since the [Ca2+]i was not found to be elevated indicating thus that the onset the cell death processes was not occurred.
The genotoxic effects of X-ray emitted during dental panoramic radiography were evaluated in exfoliated cells from oral epithelium through a differentiated protocol of the micronucleus test. Thirty-one healthy individuals agreed to participate in this study and were submitted to this procedure for diagnosis purpose after being requested by the dentist. All of them answered a questionnaire before the examination. Cells were obtained from both sides of the cheek by gentle scrapping with a cervical brush, immediately before the exposure and after 10 days. Cytological preparations were stained according to Feulgen-Rossenbeck reaction and analyzed under light and laser scanning confocal microscopies. Micronuclei, nuclear projections (buds and broken eggs) and degenerative nuclear alterations (condensed chromatin, karyolysis and karyorrhexis) were scored. The frequencies of micronuclei, karyolysis and pycnosis were similar before and after exposure (P > 0.90), whereas the condensation of the chromatin and the karyorrhexis increased significantly after exposure (P < 0.0001). In contrast, both bud and broken egg frequencies were significantly higher before the examination (P < 0.005), suggesting that these structures are associated to the normal epithelium differentiation. The results suggest that the X-ray exposure during panoramic dental radiography induces a cytotoxic effect by increasing apoptosis. We also believe that the score of other nuclear alterations in addition to the micronucleus improves the sensitivity of genotoxic effects detection.
Salivary gland tumours are uncommon with a broad heterogeneity. The most common benign tumour is the pleomorphic adenoma, whereas mucoepidermoid carcinoma and adenoid cystic carcinoma predominate among the malignancies. Most salivary gland tumours occur in the parotid, and consequently clinical and biological data are normally derived from this site. This work describes the expressions of PCNA, Ki-67 and p53 in 15 pleomorphic adenomas, 15 mucoepidermoid carcinomas and 15 adenoid cystic carcinomas of the submandibular gland. Our results showed that all pleomorphic adenomas were negative for p53 and Ki-67 with 66.6% being positive for PCNA. Conversely, p53 was positive in 53% of the mucoepidermoid carcinomas and in 20% of the adenoid cystic carcinomas. Ki-67 was expressed in 47.7% of the mucoepidermoid carcinomas and 40% of the adenoid cystic carcinomas. All malignant tumours were positive for PCNA. These results indicate that the proliferative rate analysed with PCNA and Ki-67 and the expression of p53 in pleomorphic adenoma and adenoid cystic carcinoma of the submandibular gland were similar to those described in the parotid and minor salivary glands. However, mucoepidermoid carcinomas showed higher expression of these markers than those of other salivary glands. This work is the first describing the expression of these immunohistochemical markers exclusively in submandibular salivary gland tumours.
Metastases of osteosarcoma in the mouth are rare, and only few cases have been described. We present a case of telangiectatic osteosarcoma of the femur in a 15-year-old girl, who developed metastases in the humerus, lungs and retromolar area 4 years after initial diagnosis and treatment. The girl died 2 months after the diagnosis of metastases despite treatment with chemotherapy. This report emphasizes that telangiectatic osteosarcoma has a very poor prognosis, particularly when multiple metastases develop.
Lipomas represent about 1 to 5% of all neoplasms of the oral cavity. Although relatively common, few large series of intraoral lipomas and its variants are seen in the literature. Therefore, the authors present the clinical, histological and immunohistochemical features of 46 cases of intraoral lipomas reviewed from the files of the University of Campinas Dental School from 1970 to 2001. Most of the cases affected adults, without gender predilection, and the main involved sites were the buccal mucosa (21 cases), tongue (six cases), lips (six cases) and floor of mouth (five cases). The histological analysis revealed 21 cases of lipoma, 18 fibrolipomas, four intramuscular lipomas, two minor salivary gland lipomas and one spindle cell lipoma. PCNA and ki-67 expression indexes were higher in spindle cell lipoma, intramuscular lipomas and fibrolipomas compared to common lipomas, but the differences were not statistically significant. All lesions were removed surgically and none showed recurrence, regardless of the various proliferative activities.
Central mucoepidermoid carcinomas are uncommon tumours, representing about 2 to 4% of all mucoepidermoid carcinomas. They are histologically low-grade cancers, usually affecting the mandible as uni- or multilocular radiographic lesions. The authors report four cases of central mucoepidermoid carcinomas affecting the mandible and discuss their clinical, radiographic and histological findings. Four females were affected, with a mean age of 42 years and all cases involved the posterior mandible. Treatment included surgery in three cases and surgery associated to neck dissection and radiotherapy in one case. Two patients showed no recurrence and were alive without signs of the disease after a mean follow-up of 78 months. The other two patients showed local recurrence and one was alive with disease after a follow-up of 384 months, and the other was followed-up for 324 months dying by other causes without signs of the tumour. Central mucoepidermoid carcinomas of the mandible are low-grade tumours, and effective surgical treatment involving wide local excision or en bloc resection allows patients to have a favourable prognosis after long-term follow-up.
The processing route and the final microstructural and mechanical characteristics of a novel biomaterial composite are described. This new material is composed of 70 wt% Si3N4 ceramic phase and 30 wt% bioglass, the later performing as a liquid sintering aid system and simultaneously providing bioactivity characteristics to the composite. The conditions for fabrication of an almost fully dense material (approximately 98% of relative density) were pursued. Optimised parameters were 1350 degrees C-40 min-30 MPa by hot-pressing technique. The very fast densification rate of the process avoided the crystallisation of the bioglass intergranular phase and therefore its intrinsic properties were maintained. Also, the large amount of glassy phase assured the densification by liquid phase assisted grain rearrangement without Si3N4 phase transformation. The final mechanical properties of the Si3N4 bioglass were as follows: fracture toughness, K(IC) = 4.4 MPa m(1/2); Vickers hardness, Hv = 10.3 GPa; Young's modulus, E = 197 GPa; bending strength, sigma(g) = 383 MPa; Weibull modulus, m = 8.3. These values provide an attractive set of properties among other bioactive materials, namely by upgrading the main drawback of bioceramcs and bioglasses for high-load medical applications, which is the lack of satisfactory fracture toughness.
Wettability and surface charge studies were performed on a novel Si3N4-30wt% bioglass biocomposite. Contact angle and surface tension variation with time were determined at 25 degrees C, respectively, by the sessile and pendant drop techniques, for distinct testing liquids: water, diiodomethane, simulated body fluid (SBF) and bovine serum albumin (BSA) dissolved in SBF solution. This biocomposite revealed a hydrophilic character (theta = 26.6 +/- 2.0 degrees) and a surface tension value (66.6 mJ m(-2)) comparatively higher than those of the most common bioceramics. An important characteristic is the high work of adhesion towards SBF + BSA (96.4 +/- 0.2mJ m(-2)) that was measured. The Si3N4-bioglass material is negatively surface charged above the pH(IEP) = 2.5 in aqueous SBF + BSA solution, as a result of the presence at the surface of unsaturated Si-O bonds and Si-OH groups. The very high negative zeta potential at pH approximately 7 (-58.6 +/- 5.5mV) influenced albumin adsorption and mechanisms are discussed in terms of entropy and enthalpy gains from conformational unfolding and cations coadsorption.
The in vitro osteocompatibility of a novel Si(3)N(4)-bioglass composite (70-30% weight proportion) with improved mechanical properties (fracture toughness = 4.4 M Pa m(1/2); bending strength = 383 +/- 47 MPa) is reported. Immersion of the composite samples in culture medium (30 min to 7 days) resulted in rapid protein adsorption to the surface and, also, dissolution of the intergranular phase of bioglass (time-dependent process) with the formation of different size cavities. "As-received" and pre-treated material samples presented a similar behaviour concerning the proliferation of MG63 osteoblast-like cells, evaluated during a 5-day culture period. Seeded materials showed a higher cell growth rate as compared to cultures performed on the standard plastic culture plates. To assess the osteogenic potential of the composite, "as-received" material samples were seeded with human bone marrow cells and cultured for 35 days in experimental conditions that favour the development of the osteoblastic phenotype. The cell adhesion process was similar to that observed in control cultures. Cells successfully adapted to the irregularities of the surface and were able to grow towards inside the cavities; in addition, osteogenic differentiation occurred with the formation of abundant cell-mediated mineralised deposits. Results suggest that this Si(3)N(4)-bioglass composite seems to be a promising candidate for high-stress medical applications.
The aim of this study was to determine the effect of the incorporation of silicon on the surface charge of hydroxyapatite (HA) and to assess surface structural changes of HA and Si-HA induced by dissolution in both static and dynamic systems. X-ray photoelectron spectroscopy (XPS) analysis showed that SiO(4)(4-) groups were substituted for PO(4)(3-) groups in the silicon-hydroxyapatite (Si-HA) lattice according to a previously proposed substitution mechanism without the formation of other crystalline phases, such as tricalcium phosphate or calcium oxide. The substituted silicon induced a decrease in the net surface charge and the isoelectric point of HA as determined by zeta potential (ZP) measurements. At physiological pH=7.4 the surface charge of Si-HA was significantly lowered compared to unmodified HA, i.e. -50+/-5 to -71+/-5 eV, caused by the presence of silicate groups in the HA lattice, which may account for a faster in vitro apatite formation using SBF testing. XPS results indicated that silicon seems to be preferentially leached out from Si-HA surface compared to other ionic species after dissolution studies in tris-buffer using a dynamic system.
We describe two additional cases of solitary fibrous tumour (SFT) affecting the mouth. SFT is very uncommon in the oral cavity and we found only 14 cases reported in the literature. Our two cases were well circumscribed, slow growing tumours that, after surgical removal, did not recur. Case 1 was a 3 cm nodule on the right cheek. Hypo and hypercellular adjacent areas were mainly patternless, and the stroma was formed by thin collagen fibrils. Case 2 was a 4.8 cm mass in the anterior portion of the tongue. Microscopically it was formed by spindle cells embedded in a vascularized sclerotic collagen matrix. Some areas were hypercellular with scarce collagen fibrils. The immunohistochemical findings were similar in both cases, with strong immunoreactivity for vimentin, CD34, bcl-2, focal positivity for Ki-67 and negativity for other immunomarkers. Based on these clinical, microscopical and immunohistochemical features the final diagnosis of these two cases was SFT. Diagnosis of SFT is difficult and, although uncommon, it should be considered in the differential diagnosis of oral soft tissue tumours.
Denture stomatitis (DS) is frequently associated with high levels of Candida in saliva and deficient denture hygiene. In order to analyse the incidence of DS and its pre-disposing factors, we evaluated 77 edentulous patients before and 6 months after the placement of new complete dentures. Denture stomatitis was observed in 50.6 and 18.2% of the patients at the first and second evaluation, respectively. Salivary flow, Candida counts in saliva and Candida species were similar in both evaluations. Denture stomatitis and Candida in saliva were more common in females. Our results showed that denture replacement and denture hygiene improvement were useful for DS resolution, particularly types I and II. However, oral and denture hygiene must be continuous, inasmuch as salivary Candida counts remained high and it is considered an important pre-disposing factor for DS.
The aim of this study is to report on five cases of intraoral pleomorphic adenoma (PA) in patients under 18 years of age and to review the literature. Intraoral salivary gland tumours were reviewed in two Brazilian institutions and five cases of PA in patients under 18 years of age were found. Clinical data were obtained from the medical records and paraffin-embedded tissues were sectioned for proliferating cell nuclear antigen (PCNA) and p53 immunohistochemical analysis. Four patients were female and one was male; two cases affected the palate, two the upper lip and one the tongue. All five patients were treated surgically and after long follow-up periods no recurrences were observed. Tumour cells were weakly positive for PCNA and negative for p53. PA should be considered in the differential diagnosis of submucosal nodules in young patients. In youngsters, PA seems to have similar biological characteristics as in adults, with low recurrence rates after surgical resection.
Antioxidant status of 35 endurance horses was studied during an 80 (OD80) or 160 km (OD160) race. Packed cell volume (PCV), total plasma protein (TPP), plasma ascorbic acid (VIT C), plasma alpha-tocopherol (VIT E) and erythrocyte glutathione (GSH) concentrations, erythrocyte glutathione peroxidase (GPX), plasma aspartate aminotransferase (AST) and plasma creatine kinase (CK) activities were measured at 0, 40, 80 km and 60 min of recovery (REC) at OD80, and 0, 64, 106, 142, 160 km and REC at OD160. In both races, no changes were found in plasma VIT E concentration, but VIT C and GSH concentrations decreased (P<0.05), and mean GPX, AST and CK activities increased from 0 km (P<0.05). Indices of muscle cell leakage (plasma AST and CK) were correlated (r = 0.36 to 0.67; P<0.03) with indices of antioxidant status (VIT C, GSH and GPX). Associations between increased muscle leakage and decreased antioxidant status may, in part, reflect oxidative stress and suggest the testing of antioxidant supplements in endurance horses to improve performance and welfare.
In vitro and in vivo bioactivity studies were performed to assess the biocompatibility of CaO-P2O5 glass-reinforced hydroxyapatite (GR-HA) composites. The ability to form an apatite layer by soaking in simulated body fluid (SBF) was examined and surfaces were characterized using FTIR reflection and thin-film X-ray diffraction analyses. Qualitative histology, histomorphometric measurements, and push-out testing were performed in a rabbit model for characterizing bone/implant bonding. Under the in vitro conditions using SBF, an apatite layer could not be formed on GR-HA composites within 8 weeks. Results of push-out testing showed bonding between the composites and bone, ranging from 130-145 N after 2 weeks of implantation. After the longest implantation period, 16 weeks, the GR-HA composite prepared with the higher content of CaO-P2O5 glass showed the highest bonding force, 606 +/- 45 N, compared to 459 +/- 30 N for sintered HA. Development of immature bone and modifications in the turnover of a more mature bone on the surface of GR-HA composites were similar to those on sintered HA.
Overexpression and amplification of several genes (MDM2, CDK4 and SAS) located on chromosome 12q13-15 have been noted to occur in various human sarcomas. As a result, two major growth regulation pathways may be inhibited. MDM2 may down regulate the p53-mediated growth control and CDK4 may affect pRB-mediated events. To determine the frequency of alterations in these genes and their correlation with clinicopathologic features, we analyzed the MDM2 and CDK4 protein levels by immunohistochemistry and assessed MDM2, CDK4 and SAS amplification by real-time PCR in nine osteosarcomas of the jaws. Positive staining for CDK4 and MDM2 was observed in eight cases (88.8%) and five cases (55.5%), respectively. Intense CDK4 staining was noted in four cases (two high grade, one intermediate grade and one low grade). Intense MDM2 staining was observed in the same four previous cases, as well as, one additional high-grade tumor. Individual DNA amplification for CDK4, MDM2 and SAS was observed in six cases for each gene. Co-amplification was observed in five cases that showed CDK4 and MDM2 concomitant amplification and four cases that displayed amplification for all of the genes. In addition, among the five cases that presented CDK4 and MDM2 amplification, strong overexpression of CDK4 and MDM2 was observed in three and in four cases, respectively (three high grade and one intermediate grade). These results suggest that 12q13-15 genes are involved in neoplastic disease and concurrent amplification and overexpression of these genes might help to define high-grade tumors.