Ebselen and cytokine-induced nitric oxide synthase expression in insulin-producing cells

Interleukin-1 (IL-1) may be a mediator of β-cell damage in insulin-dependent diabetes mellitus (IDDM). The IL-1 mechanism of action on insulin-producing cells probably includes activation of the transcription nuclear factor κB (NF-κB), increased transcription of the inducible form of nitric oxide synthase (iNOS) and the subsequent production of nitric oxide (NO). Reactive oxygen intermediates, particularly H2O2, have been proposed as second messengers for NF-κB activation. In the present study, we tested whether ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a glutathione peroxidase mimicking compound, could counteract the effects of IL-1β, H2O2 and alloxan in rat pancreatic islets and in the rat insulinoma cell line RINm5F (RIN cells). Some of these experiments were also reproduced in human pancreatic islets. Ebselen (20 μM) prevented the increase in nitrite production by rat islets exposed to IL-1β for 6 hr and induced significant protection against the acute inhibitory effects of alloxan or H2O2 exposure, as judged by the preserved glucose oxidation rates. However, ebselen failed to prevent the increase in nitrite production and the decrease in glucose oxidation and insulin release by rat islets exposed to IL-1β for 24 hr. Ebselen prevented the increase in nitrite production by human islets exposed for 14 hr to a combination of cytokines (IL-1β, tumor necrosis factor-α and interferon-γ). In RIN cells, ebselen counteracted both the expression of iNOS mRNA and the increase in nitrite production induced by 6 hr exposure to IL-β but failed to block IL-1β-induced iNOS expression following 24 hr exposure to the cytokine. Moreover, ebselen did not prevent IL-1β-induced NF-κB activation. As a whole, these data indicate that ebselen partially counteracts cytokine-induced NOS activation in pancreatic β-cells, an effect not associated with inhibition of NF-κB activation.

Carcinoma basaloide - Escamoseo de cebeça: relato de 4 casos

Basaloid squamous carcinoma is an aggressive subtype of squamous carcinoma of superior aerodigestive tract. This tumor has been recently described and it seems to have higher incidence in tongue, hypopharynx and supraglottis. It has more agressive biological behavior than pure type of squamous cell carcinoma. We report 4 cases of this tumor and we present a review of the literature.

Conjunctival keratoacanthoma

Keratoacanthoma is a rapidly growing skin neoplasia that may stabilize or regress spontaneously. We describe here a case of conjunctival keratoacanthoma and comment about the clinical signs and symptoms and pathological findings.

Investigacao clinica da disfagia orofaringea

The accurate investigation of the oropharyngeal dysphagia demands a systematic sequence of physical examinations. The aim of the present work is to propose a practical rule to facilitate the clinical investigation and the management of dysphagic patients. After a detailed anamnesis, an endoscopic examination is carried out and several manouvers to observe the oral, pharyngeal and laryngeal functions are performed by the patient. Following, a second endoscopy is performed during swallows of several consistencies of food, to verify the impairment of the laryngeal and or pharyngeal activities. The elevation of the laryngeal cartilage is also evaluated.

Cigarette smoking and high-risk HPV DNA as predisposing factors for high-grade cervical intraepithelial neoplasia (CIN) in young Brazilian women

Background. This cross-sectional study was designed to evaluate the role of cigarette smoking and high-risk HPV types as risk factors of CIN 2 and 3 in young, sexually active Brazilian women. Materials and method. A series of 100 consecutive women with abnormal Pap smears were recruited, subjected to colposcopy, punch biopsy, and questionnaire for their social, sexual and reproductive factors. Of these, 77 women between 20 and 35 years of age (median 26.5 years) with biopsy-confirmed CIN 1 or CIN 2 and 3, were enrolled in this study. Representative samples from the exocervix and endocervix were obtained for HPV testing with the Hybrid Capture HPV-DNA assay, including the probes for the oncogenic HPV types (16, 18, 31, 33, 35, 45, 51, 52 and 56). Results. The overall rate of CIN 2 and 3 was 23/77 (29.8%). The women with CIN 1, 2 and 3 did not differ from each other with regard to their age, race, schooling, marital status, life-time number of sexual partners, age at first intercourse, use of oral contraceptives, or parity. However, current cigarette smoking was strongly associated with CIN 2 and 3 (p < 0,001), and among smokers, the risk of high-grade CIN increased in parallel with the time of exposure (years of smoking) p = 0.07), HPV-DNA of the oncogenic types was detected in 43 (56%) women, the risk of being HPV DNA-positive was significantly higher in CIN 2 and 3 as compared with CIN 1 (p = 0.037). Importantly, the prevalence of high-risk HPV types was significantly higher in cigarette smokers than in non-smokers (p = 0.046). Conclusions. The results indicate that the severity of CIN lesions was clearly related to two fundamental risk factors: 1) high-risk HPV types, and 2) current cigarette smoking. These two risk factors were closely interrelated in that the high-risk HPV types were significantly more frequent in current smokers than in non-smokers, suggesting the possibility of a synergistic action between these two risk factors in cervical carcinogenesis.

Clonal chromosome abnormalities found in three non-neoplastic proliferative brain lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Kras oncogene analysis of non-melanoma skin tumors in Southeastern Brazil

Skin cancers are the most common human malignant neoplasia and their incidence is growing, chiefly in tropical countries. There is evidence that ultraviolet (UV) radiation present in sunlight is important for genetic damage. Mutations due to such damage could be responsible for alterations in oncogenes and tumor suppressor genes. Recent studies have reported remarkable differences in mutation frequency of the RAS proto-oncogene in non-melanoma skin cancers. These findings may reflect differences in the molecular epidemiology of cutaneous tumors found in geographical areas with diverse sun exposure and ethnical origins of their populations. Our study proposed to perform molecular analyses of skin tumors on patients living in southeastern Brazil, in areas with high levels of sun exposure. DNA from eight solar keratose (SK), 26 basal cell carcinomas (BCC) and 19 squamous cell carcinomas (SCC) was submitted to PCR-SSCP analysis for codons 12, 13 and 61. Contradicting other authors, we found no mutations in codons 12,13 but detected two BCCs and one SCC with a mutation in codon 61. These findings suggest that the activation of KRAS oncogene may contribute to the pathogenicity of cutaneous lesions in southeastern Brazil.

Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of salivary glands

Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities. © 2001 Elsevier Science Ltd.

Distinct regions of loss of heterozygosity on 22q at different sites of head and neck squamous cell carcinomas

Background: Frequent loss of heterozygosity (LOH) has been reported in many types of cancer, including head and neck carcinomas. Somatic deletions involving specific chromosomal regions are strongly associated with inactivation of the allele of a tumor suppressor gene located within the deleted region. In most studies concerning LOH in head and neck squamous cell carcinomas (HNSCC) the different anatomical sites are not distinguished. The behavior of tumors arising at various sites differs significantly, however, suggesting different intrinsic tumor properties. In this study we compared the LOH on 22q and its relationship to clinicopathological parameters at the three major sites of HNSCC: oral cavity, larynx and pharynx. Material/Methods: LOH and microsatellite instability (MSI) were studied using seven polymorphic microsatellite markers mapped to the 22q11-q13.3 region in 37 oral, 32 laryngeal, and 31 pharyngeal carcinomas. Results: Two separate regions of LOH were identified in the laryngeal (22q11.2-12.1) and oral cavity (22q13.1-13.31) tumors. When the different anatomical sites were compared, a statistically significant difference was found between the presence of LOH at D22S421 (p<0.001), D22S315 (p=0.014) and D22S929 (p=0.026) in the laryngeal tumors. Conclusions: These data suggest that distinct regions on 22q are involved in LOH in oral cavity and laryngeal tumorigenesis but do not support a similar association between the development of pharyngeal tumors and genes located on 22q. These findings implicate the presence of different tumor suppressor genes mapping to distinct regions on chromosome 22q in oral and laryngeal carcinomas.

Papilomavírus humano (HPV) em lesões benignas e malignas de mucosa oral pelos métodos de imuno-histoquímica e hibridização in situ

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cytokeratins in epithelia of odontogenic neoplasms

Neoplasms and tumours related to the odontogenic apparatus may be composed only of epithelial tissue or epithelial tissue associated with odontogenic ectomesenchyme. The immunohistochemical detection of different cytokeratins (CKs) polypeptides and vimentin has made it easier to explain the histogenesis of many epithelial diseases. The present study aimed to describe the immunohistochemical expression of cytokeratins 7, 8, 10, 13, 14, 18, 19 and vimentin in the epithelial components of the dental germ and of five types of odontogenic tumours. The results were compared and histogenesis discussed. All cells of the dental germ were positive for CK14, except for the preameloblasts and secreting ameloblasts, in which CK14 was gradually replaced by CK19. CK7 was especially expressed in the cells of the Hertwig root sheath and the stellate reticulum. The dental lamina was the only structure to express CK13. The reduced epithelium of the enamel organ contained CK14 and occasionally CK13. Cells similar to the stellate reticulum, present in the ameloblastoma and in the ameloblastic fibroma, were positive for CK13, which indicates a nature other than that of the stellate reticulum of the normal dental germ. The expression of CK14 and the ultrastructural aspects of the adenomatoid odontogenic tumour probably indicated its origin in the reduced dental epithelium. Calcifying odontogenic epithelial tumour is thought to be composed of primordial cells due to the expression of vimentin. Odontomas exhibited an immunohistochemical profile similar to that of the dental germ. In conclusion, the typical IF of odontogenic epithelium was CK14, while CK8, 10 and 18 were absent. Cytokeratins 13 and 19 labelled squamous differentiation or epithelial cells near the surface epithelium, and CK7 had variable expression.

Malignant transformation of pleomorphic xanthoastrocytoma: Case report

We report a case of a pleomorphic xantoastrocytoma which manifested itself as a cystic isodense lesion in the right fronto-temporal lobe in a 26 year-old woman. It appeared as a soft yellow tumor with cystic cavities on surgery. Five months after this surgery, the patient was submitted to a new operation, which revealed a friable tumor, easily differentiated from the normal parenchyma, with cystic components. The histopathological examination demonstrated pleomorphic xanthoastrocytoma with malignant transformation. Histologically, the tumor at first procedure was composed of pleomorphic astrocytes with multinucleated and foamy cells. A rare case of malignant transformation in pleomorphic xanthoastrocytoma is presented, discussed and illustrated in this paper.