Impact of PI and NNRTI HAART-based therapy on oral lesions of Brazilian HIV-infected patients

Background: The incidence of oral lesions related to human immunodeficiency virus (HIV) infection have been investigated after treatment with highly active antiretroviral therapy (HAART) including protease inhibitors (PI) but no data are available on the effect of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy on incidence of acquired immunodeficiency syndrome (AIDS) oral manifestations or impact of HAART on oral manifestations of HIV infection in Brazil. The aim of this study was to describe the effects of anti-HIV therapy on the incidence of oral lesions during 17 years of AIDS epidemics in a Brazilian population. Methods: From 1989 to 2006, we collected data from 1595 consecutive HIV patients at the Special Care Dentistry Center, Sao Paulo, Brazil. We compared the effect of PI- and NNRTI-based antiretroviral therapy (ARVT) on the annual incidence of Kaposi sarcoma (KS), oral candidiasis (OC) and hairy leukoplakia (HL). The chi-squared test was used to test the association between oral lesions and therapeutic regimen (P < 0.05). Results: None of patients on ARVT presented with KS. Patients who used (nucleoside reverse transcriptase inhibitors) NRTI + PI were 0.9 times as likely to present with HL as those who used NRTI + NNRTI. This finding, however, was not statistically significant (P = 0.5). The relative risk for OC was 0.8 in patients with PI-based HAART. The increased risk among those on PIs was statistically significant (P = 0.004). Conclusions: The superiority of NNRTI regimens in decreasing OC incidence is consistent with current therapeutic guidelines which recommend NNRTI-based therapy as the treatment of choice for initial ARVT.

Oral manifestations after immune reconstitution in HIV patients on HAART

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P=0.78), sex (P=0.41) or previous history of ART (P=0.55) between IR and non-IR patients. In the IR group, the most common OM was. parotid enlargement (57.14%) (P=0.619), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that > 80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8(+)PD1(+) in PBMC when compared with controls. On the other hand, increased frequency of CD4(+) and CD8(+) T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-gamma and higher levels of TGF-beta were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

Resource entitlements of indigenous minorities, their poverty and conservation of nature: Status of Australian Aborigines, comparisons with India's tribals, theory and changing policies globally

Considers the relevance of A.K. Sen’s theory of entitlements to the situation facing indigenous tribal people, its relationship to institutionalism, and to theories of property rights. Changing world views about the resource entitlements that should be given to local communities are outlined concentrating on the views expressed by the World Conservation Union (IUCN). These changing views have relevance for the resource entitlements of indigenous tribal communities and are reflected in differences in the policy approaches inherent in the Convention on International Trade in Endangered Species (CITES) and the more recent Convention on Biological Diversity. The latter embodies the view that provision of greater resource entitlements to local communities can provide economic incentives for nature conservation. There is a case for Indigenous Australians to be given greater rights to market the natural produce from their lands. Despite progress with land rights, they are not entitled to market much of the natural produce from their land. The socioeconomic status of Australian Aborigines is outlined. Their standard of living and their life expectancy are low by world standards and in comparison to other Australians. This is partly a result of historical events that have restricted their rights. These events are outlined briefly. Views differ about the appropriate development paths for Indigenous Australians and these are assessed. Concern on environmental and economic grounds is expressed about the view that the economic development of Australian Aboriginal communities would be accelerated by replacing their communal land titles by private land titles and encouraging Western-style agriculture and commercial development of their lands. Some comparisons are also made with the situation of India’s Tribals.

Prevalence of Upper Cervical Vertebrae Anomalies in Patients With Cleft Lip and/or Palate and Noncleft Patients

Objectives: To investigate the prevalence of upper cervical vertebrae anomalies in patients with isolated cleft lip, isolated cleft palate, and complete cleft lip and palate, as well as to compare the prevalence of these anomalies between groups, between genders, and with noncleft patients. Design: Retrospective cross-sectional study of randomly selected patients. Setting: Radiology Section, Hospital for Rehabilitation of Craniofacial Anomalies and Department of Orthodontics, Bauru School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil. Participants: The sample comprised 300 lateral cephalograms of cleft patients, aged 12 to 13 years, of both genders, from the files of the Hospital for Rehabilitation of Craniofacial Anomalies-University of Sao Paulo and 300 lateral cephalograms from noncleft patients of the Department of Orthodontics, Bauru School of Dentistry. Cephalograms of patients with syndromes were not included. Method: Radiographs were interpreted on a film viewer by a single examiner; the profiles of vertebrae were traced on acetate paper, and cervical vertebrae anomalies were registered and categorized into posterior arch deficiencies, fusion, and association of both. Main Outcome Measures: Statistical comparison of groups using the chi-square test. Results: In the cleft group, 38.67% of the patients had cervical vertebrae anomalies. Of those in the noncleft sample, 31% showed anomalies of the cervical spine. This difference was statistically significant. There was no statistically significant difference when the types of clefts were compared with each other or when both genders were compared in both samples. Conclusions: This study confirms the association between clefts and cervical anomalies. Additional research on this topic is necessary.

Tooth abnormalities and soft tissue alterations in patients with G/BBB syndrome

OBJECTIVE: The G/BBB syndrome is an X-linked recessive disorder characterized by eye anomalies, laryngotracheoesophageal cleft, congenital heart disease, genitourinary anomalies and gastrointestinal disorders. Patients may also present cleft lip and palate, high-arched palate and thin upper lip. This study aimed to investigate the occurrence of tooth abnormalities and soft tissue changes in patients with G/BBB syndrome. DESIGN: Cross-sectional. SUBJECTS AND METHODS: Twenty-one patients with G/BBB syndrome were analyzed as to the presence of tooth abnormalities and soft tissue alterations. MAIN OUTCOME MEASURES: The prevalence of tooth agenesis and supernumerary teeth was compared to patients without morphofunctional alterations, matched for gender and age. RESULTS: All patients had complete cleft lip and palate; 95.23% of patients presented tooth abnormalities, mainly hypoplastic alterations, with predominance of alterations of number, followed by alterations of structure, shape and position. The frequency of tooth agenesis and supernumerary teeth was significantly higher compared with the control group; 11 patients presented incisiform supernumerary teeth in the mandibular anterior region. Ankyloglossia was observed in 11 of 21 patients. CONCLUSION: The presence of mandibular anterior supernumerary teeth and ankyloglossia should be investigated in the clinical evaluation of patients with suspected diagnosis of the G/BBB syndrome. Oral Diseases (2008) 14, 747-753