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.

Environmental and Individual Factors Associated with Nail Fluoride Concentration

Nails have been suggested as suitable biomarkers of exposure to F, with the advantage of being easily obtained. The effect of water F concentration, age, gender, nail growth rate and geographical area on the F concentration in the fingernail and toenail clippings were evaluated. Volunteers (n = 300) aged 3-7, 14-20, 30-40 and 50-60 years from five Brazilian communities (A-E) participated. Drinking water and nail samples were collected and F concentration was analyzed with the electrode. A reference mark was made on each nail and growth rates were calculated. Data were analyzed by ANOVA and linear regression (alpha = 0.05). Mean water F concentrations (8 SE, mg/l) were 0.09 +/- 0.01, 0.15 +/- 0.01, 0.66 +/- 0.01, 0.72 +/- 0.02, and 1.68 +/- 0.08 for A-E, respectively. Mean F concentrations (+/- SE, mg/kg) ranged between 1.38 +/- 0.14 (A, 50-60 years) and 10.20 +/- 2.35 (D, 50-60 years) for fingernails, and between 0.92 +/- 0.08 (A, 14-20 years) and 7.35 +/- 0.80 (E, 50-60 years) for toenails. Among the tested factors, geographical area and water F concentration exerted the most influence on finger- and toenail F concentrations. Subjects of older age groups (30-40 and 50-60 years) from D and E showed higher nail F concentrations than the others. Females presented higher nail F concentration than males. Water F concentration, age, gender and geographical area influenced the F concentration of finger- and toenails, and hence should be taken into account when using this biomarker of exposure to predict risk for dental fluorosis. Copyright (C) 2009 S. Karger AG, Basel

Polysaccharide fraction of Agaricus brasiliensis avoids tumor-induced IL-10 production and changes the microenvironment of subcutaneous Ehrlich adenocarcinoma

Subcutaneous Ehrlich tumor-bearing mice were treated with in situ inoculation of a P-glucan-rich extract of Agaricus brasiliensis (ATF), which reduced tumor growth. Histopathological analysis showed that the tumor masses of control mice (Ehr) presented giant tumor cells and many mitotic figures whereas the tumor tissue obtained from ATF-treated animals (Ehr-ATF) presented a lower frequency of both mitotic and giant cells, associated with a higher frequency of apoptotic cells than Ehr. Analysis of the lymphoproliferative activity of spleen cells showed that the treatment had a suppressive rather than a stimulatory effect. Spleen cells of the Ehr group produced higher in vitro levels of IL-10 than normal controls and this occurrence was partially avoided by treatment with ATF. Analysis of cytokine production by tumor-infiltrating cells (ELISpot) showed that ATF induced a higher number of IFN-gamma-producing cells at 7 and 14 days as well as reduction of IL-10-secreting cells at the latter time. Confocal microscopy analysis showed higher intensity of labeling of CD4+ and Mac-3+ cells in ATF-treated mice. Analysis of in situ expression of angiogenic growth factors showed a slight decrease of FGF-2 mRNA in Ehr-ATF animals (7th day) but not of VEGF-A or TGF-beta expression. This fraction could not directly lyse either lymphocytes or tumor cells and we speculate that antitumor effect of ATF could be due to induction of a selective migration of immunocompetent cells from the spleen to the tumor site and to the switch of cytokine production. (C) 2009 Elsevier Inc. All rights reserved.

Cariogenic Microorganisms and Oral Conditions in Asthmatic Children

This study evaluated the caries risk of asthmatic patients on the basis of mutans streptococci (MS) and lactobacilli levels in saliva samples as well as the index of oral hygiene and dental caries (DMFT index). The study population was composed of 80 asthmatic children, aged 3-15 years, who use specific medication, and 80 matched, healthy control children. The parents were interviewed about oral health-related factors. The World Health Organization criteria were used for dental examinations. The Kohler and Bratthal methodology was used to detect salivary MS levels and dilutions of saliva were done for lactobacilli counting. No differences between asthma and control groups were observed for caries prevalence in children aged 3-6 and 7-10 years, except in severe cases in the younger group. However, higher caries prevalence for permanent dentition was observed in 11- to 15-year-old asthmatic children. An increased dental biofilm was observed in the asthma group, as well as salivary levels of MS. No differences were observed in levels of lactobacilli. No statistical correlations were found between medication, frequency of treatment, method of consumption and caries experience, dental biofilm and salivary levels of MS or lactobacilli. However, there was a correlation between MS levels and treatment duration. The logistic regression revealed that MS level is an important risk factor for increased caries experience. Asthma should be evaluated as a risk factor for caries experience because it can increase the levels of MS and the dental biofilm. Copyright (C) 2011 S. Karger AG, Basel

Influence of Orthognathic Surgery on Voice Fundamental Frequency

Considering that orthognathic surgery promotes changes in orofacial structures constituting the resonating system, functional changes secondary to surgery are expected to affect speech, leading to the need for further speech and voice adjustments. Thus, understanding the possible relationships of these structures with voice production is important. Therefore, this Study aimed to describe the changes in voice fundamental frequency of a patient submitted to orthognathic surgery and observe if there is a relationship with hyoid bone positioning at the different treatment periods. The results revealed that voice fundamental frequency increased after surgery, returning to values close to the preoperative condition, which corresponded to vertical movement of the hyoid bone.

Factors influencing fluoride ingestion from dentifrice by children

Objective: This study assessed the percentage of the amount of dentifrice loaded onto the toothbrush that is ingested by children, taking into account age, the amount of dentifrice used during toothbrushing, and the dentifrice flavor. Methods: The sample consisted of 155 children of both genders attending public kindergartens and schools in Bauru, Brazil, divided into 5 groups (n = 30-32) of children aged 2, 3, 4, 5 and 6 years old. The dentifrices used were Sorriso(TM) (1219 ppm F, peppermint-flavored) and Tandy(TM) (959 ppm F, tutti-frutti-flavored). The assessment of fluoride intake from dentifrices was carried out six times for each child, using 0.3, 0.6, and 1.2 g of each dentifrice, following a random, crossover distribution. Brushing was performed by the children or their parents/caregivers according to the home habits and under the observation of the examiner. Fluoride present in the expectorant and on toothbrush was analyzed with an ion-specific electrode after HMDS-facilitated diffusion. Fluoride ingestion was indirectly derived. Results were analyzed by 3-way repeated-measures anova and Tukey`s tests (P < 0.05) using the percent dentifrice ingested as response variable. Results: Age and percent dentifrice ingested for both dentifrices, and the three amounts used were inversely related (P < 0.0001). Percent dentifrice ingested was significantly higher after the use of Tandy(TM) under all conditions of the study when compared with Sorriso(TM) (P < 0.0001). Significant differences were observed when brushing with 0.3 g when compared with 1.2 g, for both dentifrices tested (P < 0.05). Conclusions: The results indicate that all variables tested must be considered in preventive measures aiming to reduce the amount of fluoride ingested by young children.

Dental caries in adolescents from public schools in Maputo, Mozambique

Aim: To assess dental caries prevalence in adolescents at urban and sub-urban areas of Maputo-City, Mozambique and to identify its relationship with dental fluorosis, dental plaque, nutritional status, frequency of sugar consumption and the concentration of fluoride in public water supply. Methods: Subjects (n=601) were randomly selected from five urban schools and five sub-urban schools. Clinical examinations were performed under standardised conditions by a trained examiner using DMFT index, SiC index, fluorosis index, PHP, BMI, a sugar consumption questionnaire and water supply analysis. The bivariate analysis and Pearson correlation was used (p<0.05). Results: The mean (DMFT) was 0.9 (+/- 1.65 SD). Children in urban schools showed less dental caries (0.8 +/- 1.49SD) than children in sub-urban schools (1.1 +/- 1.80SD, p=0.03). Only 8.15% had very mild to moderate fluorosis but most presented poor oral hygiene. Cases of malnutrition were found in more sub-urban schools (n = 109; 36.22%) than in urban schools (n = 66; 22.00%) (p=0.03). The frequency of sugar consumption was higher among urban children compared to suburban schools (p<0.00). The level of fluoride in water consumption in urban schools was 0.4 ppmF, above the level of fluoride in sub-urban schools, 0.2 ppmF. Conclusion: Dental caries should not be considered a major oral health problem in Maputo at the moment. However the data suggest the implementation of a population strategy to reduce dental caries rates, in children of both urban and sub-urban areas, in Maputo.

Growth factors and cytokines modulate gene expression of cell-surface proteoglycans in human periodontal ligament cells

Cell-surface proteoglycans have been known to be involved in many functions including interactions with components of the extracellular microenvironment, and act as co-receptors which bind and modify the action of various growth factors and cytokines. The purpose of this study was to determine the regulation by growth factors and cytokines on cell-surface proteoglycan gene expression in cultured human periodontal ligament (PDL) cells. Subconfluent, quiescent PDL cells were treated with various concentrations of serum, bFGF, PDGF-BB, TGF-beta1, IL-1 beta, and IFN-gamma. RT-PCR technique was used, complemented with Northern blot for syndecan-1, to examine the effects of these agents on the mRNA expression of five cell-surface proteoglycans (syndecan-1, syndecan-2, syndecan-4, glypican and betaglycan). Syndecan-1 mRNA levels increased in response to serum, bFGF and PDGF-BB, but decreased in response to TGF-beta1, IL-1 beta and IFN-gamma. In contrast, syndecan-2 mRNA levels were upregulated by TCF-beta1 and IL-1 beta stimulation, but remained unchanged with the other agents. Betaglycan gene expression decreased in response to serum, but was upregulated by TCF-beta1 and unchanged by the other stimulants. Additionally, syndecan-4 and glypican were not significantly altered in response to the regulator molecules studied, with the exception that glypican is decreased in response to IFN-gamma. These data demonstrate that the gene expression of the five cell-surface proteoglycans studied is differentially regulated in PDL cells lending support to the nation of distinct functions for these cell-surface proteoglycans. (C) 2001 Wiley-Liss, inc.

Effect of laser phototherapy on the release of fibroblast growth factors by human gingival fibroblasts

The effects of laser phototherapy on the release of growth factors by human gingival fibroblasts were studied in vitro. Cells from a primary culture were irradiated twice (6 h interval), with continuous diode laser [gallium-aluminum-arsenium (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP),_660 nm] in punctual and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). Positive [10% fetal bovine serum (FBS)] and negative (1%FBS) controls were not irradiated. Production of keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF) was quantified by enzyme-linked immunosorbent assay (ELISA). The data were statistically compared by analysis of variance (ANOVA) followed by Tukey`s test (P a parts per thousand currency signaEuro parts per thousand 0.05). The characterization of the cell line indicated a mesenchymal nature. KGF release was similar in all groups, while that of bFGF was significantly greater (1.49-times) in groups treated with infra-red laser. It was concluded that increased production of bFGF could be one of the mechanisms by which infra-red laser stimulates wound healing.

Factors that prevent or assist the integration of assistive technology into the workplace for people with spinal cord injuries: Perspectives of the users and their employers and co-workers

Examined the barriers faced by people with Spinal Cord Injuries (SCI) when integrating their Assistive Technology (AT) into the workplace, as well as factors that contribute to successful integration. In-depth interviews were taken with 5 men (aged 37-50 yrs) with SCI, 3 of their employers and 2 co-workers. Results indicate that in addition to the barriers previously outlined in the literature related to funding the technology, time delays, information availability, training and maintenance, other issues were highlighted. Implications for service providers are considered in relation to these barriers and the factors that prompted successful integration. The author discusses limitations of the study and makes recommendations for future research. (PsycINFO Database Record (c) 2007 APA, all rights reserved)

High frequency of low-level microsatellite instability in early colorectal cancer

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Effects of a mixture of growth factors and proteins on the development of the osteogenic phenotype in human alveolar bone cell cultures

Strategies to promote bone repair have included exposure of cells to growth factor (GF) preparations from blood that generally include proteins as part of a complex mixture. This study aimed to evaluate the effects of such a mixture on different parameters of the development of the osteogenic phenotype in vitro. Osteoblastic cells were obtained by enzymatic digestion of human alveolar bone and cultured under standard osteogenic conditions until subconfluence. They were subcultured on Thermanox coverslips up to 14 days. Treated cultures were exposed during the first 7 days to osteogenic medium supplemented with a GFs + proteins mixture containing the major components found in platelet extracts [plate I et-derived growth factor-BB, transforming growth factor (TGF)-beta 1, TGF-beta 2, albumin, fibronectin, and thrombospondin] and to osteogenic medium alone thereafter. Control cultures were exposed only to the osteogenic medium. Treated cultures exhibited a significantly higher number of adherent cells from day 4 onward and of cycling cells at days 1 and 4, weak alkaline phosphatase (ALP) labeling, and significantly decreased levels of ALP activity and mRNA expression. At day 14, no Alizarin red-stained nodular areas were detected in cultures treated with GFs + proteins. Results were confirmed in the rat calvaria-derived osteogenic cell culture model. The addition of bone morphogenetic protein 7 or growth and differentiation factor 5 to treated cultures upregulated Runx2 and ALP mRNA expression, but surprisingly, ALP activity was not restored. These results showed that a mixture of GFs + proteins affects the development of the osteogenic phenotype both in human and rat cultures, leading to an increase in the number of cells, but expressed a less differentiated state.

Patch dynamics and metapopulation theory: the case of successional species

We present a mathematical framework that combines extinction-colonization dynamics with the dynamics of patch succession. We draw an analogy between the epidemiological categorization of individuals (infected, susceptible, latent and resistant) and the patch structure of a spatially heterogeneous landscape (occupied-suitable, empty-suitable, occupied-unsuitable and empty-unsuitable). This approach allows one to consider life-history attributes that influence persistence in patchy environments (e.g., longevity, colonization ability) in concert with extrinsic processes (e.g., disturbances, succession) that lead to spatial heterogeneity in patch suitability. It also allows the incorporation of seed banks and other dormant life forms, thus broadening patch occupancy dynamics to include sink habitats. We use the model to investigate how equilibrium patch occupancy is influenced by four critical parameters: colonization rate? extinction rate, disturbance frequency and the rate of habitat succession. This analysis leads to general predictions about how the temporal scaling of patch succession and extinction-colonization dynamics influences long-term persistence. We apply the model to herbaceous, early-successional species that inhabit open patches created by periodic disturbances. We predict the minimum disturbance frequency required far viable management of such species in the Florida scrub ecosystem. (C) 2001 Academic Press.

Reproduction-related risk factors for mucinous and nonmucinous epithelial ovarian cancer

The proposition that mucinous ovarian cancer has an etiology distinct from that of other histologic types has been evaluated using data from a population-based case-control study of epithelial ovarian cancer conducted in 1990-1993 among Australian women aged 18-79 years. The protective effects of parity and oral contraceptive use were greater in nonmucinous than in mucinous ovarian tumors. However, these differences appeared to be driven largely by the effect of ovulatory life, which was positively associated with nonmucinous tumors only. An association with family history of breast and/or ovarian cancer also appeared to be restricted to nonmucinous cancers. These results lend support to the hypothesis that mucinous and nonmucinous ovarian tumors develop via different causal mechanisms.