Flávio Juliano Pimenta

Oral myiasis by screwworm Cochliomyia hominivorax.

We report a rare case of periodontal myiasis by New World screwworm Cochliomyia hominivorax, an obligatory larval parasite, in a 66-year-old woman. The myiasis occurred in the anterior upper jaw associated with a pre-existent generalised periodontitis. About 40 larvae were removed from the lesion. One week later the periodontal tissues were healing normally and the patient was referred to a periodontist. As all of the larvae were in the last stage, they were probably deposited 5-7 days before.

Characterization of the tumor suppressor gene WWOX in primary human oral squamous cell carcinomas

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity, representing ˜90% of all oral carcinomas and accounting for 3–5% of all malignancies. The WWOX gene (WW‐domain containing oxidoreductase) is a candidate tumor suppressor gene located at 16q23.3–24.1, spanning the second most common fragile site, FRA16D. In this report, the role of the WWOX gene was investigated in 20 tumors and 10 normal oral mucosas, and we demonstrated an altered WWOX gene in 50% (10/20) of OSCCs. Using nested RT‐PCR, mRNA transcription was altered in 35% of the tumors, with the complete absence of transcripts in 2 samples as well as absence of exons 6–8 (2 tumors), exon 7 (1 tumor), exon 7 and exon 6–8 (1 tumor) and partial loss of exons 8 and 9 (1 tumor). To determine if the aberrant transcripts were translated, Western blots were performed in all samples; however, only the normal protein was detected. By immunohistochemistry, a reduction in Wwox protein expression was observed, affecting 40% of the tumors when compared with normal mucosa. In addition, a novel somatic mutation (S329F) was found. The presence of alterations in mRNA transcription correlated with the reduced expression of Wwox protein in the tumors. These results show that the WWOX gene is frequently altered in OSCC and may contribute to the carcinogenesis processes in oral cancer.

Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations

Background Familial forms of hyperparathyroidism are responsible for approximately 10% of the cases of primary hyperparathyroidism, and their management is different from the sporadic forms. Our objective was to study the gene sequence and expression of HRPT2 and clinical outcome regarding recurrence or persistence rates in three Brazilian kindreds with familial hyperparathyroidism after up to 30 years of follow-up. Methods Clinical and biochemical data, direct sequencing of germline DNA of the HRPT2 gene, and analysis of parafibromin expression (HRPT2 gene product) using RT-PCR and immunohistochemistry of resected parathyroid neoplasms were performed. Results Affected members of kindred A were found to carry a novel, germline, nonsense mutation in exon 1 (c.96G>A; W32X) of HRPT2. Six of seven patients who have undergone less than total parathyroidectomy recurred after up to 30 years of follow-up. An unrelated affected patient from kindred B had a germline mutation in exon 7 (c.686delGAGT), and the disease recurred with several pulmonary metastases after 5 years follow-up. The affected member of kindred C also had a previously described mutation in exon 7 (c.679delAG) and the disease recurred after 10 years of follow-up. All parathyroid neoplasms from these families had diffuse loss of expression by immunohistochemistry. Conclusions An unacceptable recurrence/persistence rate (80%) associated with increasingly difficult re-operations and risk of parathyroid carcinoma in the setting of germline mutations of HRPT2 gene with familial hyperparathyroidism suggest that a more aggressive operative approach should be undertaken in these patients. Parafibromin immunohistochemistry may serve as a cost-effective screen for HRPT2-related aggressive parathyroid disease.

Immunolocalization of interleukin 4, interleukin 6, and lymphotoxin α in dental granulomas

Abstract Objective The purpose of this study was to determine the immunolocalization of the interleukin (IL) 4, IL-6, and lymphotoxin (LT) α in dental granulomas and correlate their expression with the intensity of the inflammatory infiltrate. Study design Fifteen paraffin specimens of dental granulomas were selected, and the streptavidin-biotin complex stain was used to detect IL-4, IL-6, and LT-α. Results Our results revealed a significant statistical correlation between the intensity of inflammatory infiltrate and the percentage of mononuclear cells positive for IL-4. Moreover, we observed a statistically significant correlation between the frequency of cells expressing IL-6 and LT-α. Conclusion These data suggest that the predominance of a helper T cell subtype 2 response in dental granulomas is correlated with the exacerbation of the inflammatory reaction and its evolution. Moreover, a correlation between the frequency of IL-6–positive and LT-α–positive cells suggests that the synergistic activities of these 2 cytokines may be involved in the pathogenesis of this inflammatory condition.

Molecular and immunohistochemical investigation of protein kinase a regulatory subunit type 1A (PRKAR1A) in odontogenic myxomas.

Odontogenic myxomas are rare benign neoplasms affecting the jaw. Myxomas of bones and other sites occur as part of Carney complex (CNC), a multiple neoplasia syndrome caused by mutations in the PRKAR1A gene, which codes for the regulatory subunit of protein kinase A (PKA). In the present study, 17 odontogenic myxomas from patients without CNC were screened for PRKAR1A mutations and PRKAR1A protein expression by immunohistochemistry (IHC). Mutations of the coding region of the PRKAR1A gene were identified in 2 tumors; both these lesions showed no or significantly decreased immunostaining of PRKAR1A in the tumor compared to that in the surrounding normal tissue. One mutation (c.725C>A) led to a nonconservative amino acid substitution in a highly conserved area of the gene (A213D); the other was a single base‐pair deletion that led to a frameshift (del774C) and a stop codon 11 amino acids downstream of the mutation site; both tumors were heterozygous for the respective mutations. Of the remaining tumors, 7 of the 15 without mutations showed almost no PRKAR1A in the tumor cells, whereas IHC showed that the protein was abundant in nontumorous cells. We concluded that PRKAR1A may be involved by its down‐regulation in the pathogenesis of odontogenic myxomas caused by mutations and/or other genetic mechanisms. Of the sporadic, nonfamilial tumors associated with PRKAR1A mutations, the odontogenic type was the first myxomatous lesion found to harbor somatic PRKAR1A sequence changes. Published 2005 Wiley‐Liss, Inc.

Is DARPP-32 a potential therapeutic target?

Signaling pathways play important roles in the coordination and integration of a myriad cellular functions. Because of widespread interest in the dopaminergic pathways, the protein dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein with molecular weight of 32 kDa, known by the acronym DARPP-32, occupies a central role in the biology of dopaminoceptive neurons in the central and peripheral nervous system (PNS). Its involvement has been demonstrated in many neural phenomena, including physiologic and pathologic neuroplasticity to drug effects and cognition. However, DARPP-32 has also been identified in non-neuronal tissues and its level of expression has been associated with the malignant level of some types of cancer, via modulation of cell survival and differentiation. This review considers some of these apparently compartmentalized functions of DARPP-32 and its potential as a therapeutic target.

Effect of light intensity and irradiation time on the polymerization process of a dental composite resin

Polymerization shrinkage is a critical factor affecting the longevity and acceptability of dental composite resins. The aim of this work was to evaluate the effect of light intensity and irradiation time on the polymerization process of a photo cured dental composite resin by measuring the Vickers hardness number (VHN) and the volumetric polymerization shrinkage. Samples were prepared using a dental manual light-curing unit. The samples were submitted to irradiation times of 5, 10, 20 and 40 s, using 200 and 400 mW.cm-2 light intensities. Vickers hardness number was obtained at four different moments after photoactivation (immediate, 1 h, 24 h and 168 h). After this, volumetric polymerization shrinkage values were obtained through a specific density method. The values were analyzed by ANOVA and Duncans (p = 0.05). Results showed increase in hardness values from the immediate reading to 1 h and 24 h readings. After 24 h no changes were observed regardless the light intensities or activation times. The hardness values were always smaller for the 200 mW.cm-2 light intensity, except for the 40 s irradiation time. No significant differences were detected in volumetric polymerization shrinkage considering the light intensity (p = 0.539) and the activation time (p = 0.637) factors. In conclusion the polymerization of the material does not terminate immediately after photoactivation and the increase of irradiation time can compensate a lower light intensity. Different combinations between light intensity and irradiation time, i.e., different amounts of energy given to the system, have not affected the polymerization shrinkage.

Intraoral sebaceous carcinoma

Intraoral sebaceous carcinoma (SC) is a rare tumour in the oral cavity thought to arise from malignant transformation of oral sebaceous glands. To our knowledge, only six cases of intraoral SC have been reported in the English language literature. The purpose of the present article is to report an additional case and review the literature.

Evidence of molecular alterations in the tumour suppressor gene WWOX in benign and malignant bone related lesions of the jaws.

WWOX is a tumour suppressor gene altered in various human neoplasms. Deletion of WWOX is associated with bone metabolic defects and development of osteosarcoma in mice. We hypothesized that alterations of this gene are associated with the development of benign and malignant mesenchymal bone related lesions of the jaws. We investigated WWOX mRNA by nested reverse transcription-PCR and direct sequencing and quantitative real-time PCR in two osteosarcoma, two fibrosarcoma, eight ossifying fibroma and two fibrous dysplasia fresh samples. Malignancy was associated with a decreased WWOX mRNA expression. Aberrant transcription pattern was found in five samples; however, the relative quantification (RQ) of the WWOX mRNA in such lesions was not different from those carrying only the wild-type. We provide new evidence of WWOX alterations in osteosarcomas and demonstrate for the first time alterations of this gene in fibrosarcomas as well as in ossifying fibromas of the jaws.