Claudin expression is dysregulated in prostate adenocarcinomas but does not correlate with main clinicopathological parameters

Aims: Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas. The aim of this study was to determine the expression of claudins 1, 2, 3, 4, 5, 7, and 11 in prostate samples from Brazilian patients and correlate it with the clinicopathological features of prostate cancer. Methods: Using a tissue microarray (TMA) of specimens of prostate adenocarcinoma and benign prostatic hyperplasia (BPH) we analysed the expression of claudins 1, 2, 3, 4, 5, 7, and 11 by immunohistochemistry. Results: Claudin 4 was down-regulated and claudins 2, 3, and 5 were overexpressed in prostate adenocarcinomas compared with BPH samples. Expression of claudins 1 and 7 was similar in tumours and BPH samples. Claudin 11 was absent from all prostate samples. Overexpression of claudin 3 was associated with perineural invasion (p = 0.014) and tended to occur in advanced stages of the disease (p = 0.064). Increased expression of claudin 5 was marginally associated with perineural invasion (p = 0.060). Conclusions: Our results suggest that alterations in claudin expression occur in prostate cancer cells, although we have not found an association with the main clinicopathological parameters.

Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases

Aims Claudins are integral transmembrane proteins of the tight junctions, critical for maintaining cell adhesion and polarity. Alterations in the expression of individual claudins have been detected in carcinomas and appear to correlate with tumour progression. Methods In this study, a panel of anti-claudin antibodies (anti-claudins 1, 2, 3, 4, 5 and 7) was employed to map claudin expression in 136 cases of oral squamous cell carcinoma (OSCC) organised in a tissue microarray. Results Claudins were expressed in a reticular pattern up to the prickle layer in normal mucosal epithelium. In OSCC, claudins were strongly present in well-differentiated tumours, they presented mild and low expression in moderately differentiated OSCC, and were negative in poorly differentiated OSCC; the absences of claudin 1 (p = 0.002) and claudin 4 (p<0.001) were associated with moderately/poorly differentiated tumours. Strong expression of claudin 4 was associated with decreased perineural infiltration (p = 0.024). Claudins 5 and 7 were mostly negative or weakly expressed in all cases studied. Expression of claudin 7 was associated with the early clinical stages of the disease, whereas loss of claudin 7 tended to be more frequent in advanced stages of OSCC (p = 0.054). Absence of claudin 7 was also associated with absent vascular infiltration (p = 0.045) and with presence of recurrence (p = 0.052). Conclusions Claudin expression patterns showed a strong correlation with histological type of OSCC; claudin expression was decreased in areas of invasion, and negative in poorly differentiated tumours. This pattern may be related to evolution and prognosis of these tumours, especially in the case of claudin 7, which seems to be associated with a poor prognosis in OSCC.

Solubility study of phytochemical cross-linking agents on dentin stiffness

Objectives: The effects of interactions between cross-linking proanthocyanidins (PA) in polar solvents and type-I collagen of demineralized dentin were investigated. Methods: Three PA-rich extracts, two from grape seed (GSEP and GSES) and one from cocoa (COE), were dissolved (water, ethanol:water and acetone:water) and analyzed for their ability to increase the modulus of elasticity of demineralized dentin. Sound dentin beams (0.5 mm x 1.7 mm x 7 mm) were fully demineralized and divided into 12 groups according to the type of cross-linking agent and solvents used. Specimens were immersed in the respective solutions and tested at baseline, 10, 30, 60, 120 and 240 min. Results: The elastic modulus (EM) of dentin was significantly increased by the PA treatment regardless of time (p < 0.05 for all times). The extracts showed different solubility in different solvents. GSEP showed the highest increase in EM when diluted in distilled water and acetone at all exposure times. Both GSEs showed superior results when diluted in distilled water and after 4 h of treatment, while COE produced strongest enhancement when dissolved in ethanol:water. Conclusions: The results indicates that herbal extraction process and other pharmacognostic parameters have an important influence on extract solubility as well as constitution and, consequently, on the PA-dentin matrix interaction. (C) 2010 Elsevier Ltd. All rights reserved.

Effect of ion exchange on strength and slow crack growth of a dental porcelain

Objectives. To determine the effect of ion exchange on slow crack growth (SCG) parameters (n, stress corrosion susceptibility coefficient, and sigma(f0), scaling parameter) and Weibull parameters (m, Weibull modulus, and sigma(0), characteristic strength) of a dental porcelain. Methods. 160 porcelain discs were fabricated according to manufacturer`s instructions, polished through 1 mu m and divided into two groups: GC (control) and GI (submitted to an ion exchange procedure using a KNO(3) paste at 470 degrees C for 15 min). SCG parameters were determined by biaxial flexural strength test in artificial saliva at 37 degrees C using five constant stress rates (n =10). 20 specimens of each group were tested at 1 MPa/s to determine Weibull parameters. The SPT diagram was constructed using the least-squares fit of the strength data versus probability of failure. Results. Mean values of m and sigma(0) (95% confidence interval), n and sigma(f0) (standard deviation) were, respectively: 13.8 (10.1-18.8) and 60.4 (58.5 - 62.2), 24.1 (2.5) and 58.1 (0.01) for GC and 7.4 (5.3 -10.0) and 136.8 (129.1-144.7), 36.7 (7.3) and 127.9 (0.01) for GI. Fracture stresses (MPa) calculated using the SPT diagram for lifetimes of 1 day, 1 year and 10 years (at a 5% failure probability) were, respectively, 31.8, 24.9 and 22.7 for GC and 71.2, 60.6 and 56.9 for GI. Significance. For the porcelain tested, the ion exchange process improved strength and resistance to SCG, however, the material`s reliability decreased. The predicted fracture stress at 5% failure probability for a lifetime of 10 years was also higher for the ion treated group. (C) 009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Inducible nitric oxide synthase-deficient mice show exacerbated inflammatory process and high production of both Th1 and Th2 cytokines during paracoccidioidomycosis

Paracoccidioidomycosis, the major systemic mycosis in Latin America, is caused by fungus Paracoccidioides brasiliensis. To analyze the influence of inducible nitric oxide synthase (iNOS) in this disease, iNOS-deficient (iNOS(-/-)) and wild-type (WT) mice were infected intravenously with P. brasiliensis 18 isolate. We found that, unlike WT mice, iNOS(-/-) mice did not control fungal proliferation, and began to succumb to infection by day 50 after inoculation of yeast cells. Typical inflammatory granulomas were found in WT mice, while, iNOS(-/-) mice presented incipient granulomas with intense inflammatory process and necrosis. Additionally, splenocytes from iNOS(-/-) mice did not produce nitric oxide, however, their proliferative response to Con-A was impaired, just like infected WT mice. Moreover, infected iNOS(-/-) mice presented a mixed pattern of immune response, releasing high levels of both Th1 (IL-12, IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines. These data suggest that the enzyme iNOS is a resistance factor during paracoccidioidomycosis by controlling fungal proliferation, by influencing cytokines production, and by appeasing the development of a high inflammatory response and consequently formation of necrosis. However, iNOS-derived nitric oxide seems not being the unique factor responsible for immunosuppression observed in infections caused by P. brasiliensis. (c) 2008 Elsevier Masson SAS. All rights reserved.

Influence of nicotine on healing process of autogenous bone block grafts in the mandible: A histomorphometric study in rats

Purpose: The aim of this study was to perform qualitative and quantitative analyses of the effect of nicotine on autogenous bone block grafts and to describe events in the initial healing phase and the differences in the repair processes between animals exposed to nicotine and controls. Materials and Methods: Forty-eight female Wistar rats were randomly divided into 2 groups, the nicotine group and the saline group. All animals received either nicotine (3 mg/kg) or saline 4 weeks before the surgical procedure and continued to receive nicotine from surgery to sacrifice at 7, 14, or 28 days. The autogenous bone block graft was harvested from the calvaria and stabilized on the external cortical area near the angle of the mandible. Results: The histologic analyses of the nicotine group depicted a delay in osteogenic activity at the bed-graft interface, as well as impairment of the organization of the granulation tissue that developed instead of blood clot. Nicotine-group specimens exhibited less bone neoformation, and the newly formed bone was poorly cellularized and vascularized. The histometric analysis revealed significantly less bone formation in the nicotine group at both 14 days (23.75% +/- 6.18% versus 51.31% +/- 8.31%) and 28 days (42.44% +/- 8.70% versus 73.00% +/- 4.99%). Conclusion: Nicotine did jeopardize the early healing process of autogenous bone block grafts in rats but did not prevent it.

Evaluation of distances between the mandibular teeth and the alveolar process in Brazilians with normal occlusion

Introduction: The aims of this study were to evaluate the distances between the mandibular permanent teeth and the alveolar process in Brazilians with normal occlusion and to compare them with normal American values. Methods: We used 59 mandibular casts from untreated subjects who had permanent dentition and the 6 keys to normal occlusion. A computer program was used to calculate the distances between the dental reference points and the alveolar process for each tooth. The mean values were then compared to the normal values by applying the Student t test at a significance level of 0.05. Results: The results showed a progressive increase of these distances from the anterior region (incisors) to the posterior region (molars), from 0.00 to 2.49 mm. All measurements had statistically significant differences from the American sample, except for the values for canines and first premolars. Conclusions: Brazilians with normal occlusion have more lingual crown positions for the incisors, second premolars, and molars compared with Americans with normal occlusion. Although these findings were statistically significant, they are unlikely to be clinically significant. (Am J Orthod Dentofacial Orthop 2010; 137: 308.e1-308.e4)

Effects of neonatal handling on central noradrenergic and nitric oxidergic systems and reproductive parameters in female rats

Early-life environmental events that disrupt the mother-pup relationship may induce profound long-lasting changes on several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces sexual behavior and induces anovulatory estrous cycles in female rats. On the afternoon of proestrus, neonatally handled females show a reduced surge of luteinizing hormone (LH) and an increased content of gonadotropin-releasing hormone in the medial preoptic area (MPOA). In order to detect the possible causes for the reduced ovulation and sexual behavior, the present study aimed to analyze the effects of neonatal handling on noradrenaline (NA) and nitric oxide (NO) levels in the MPOA on the afternoon of proestrus. Neonatal handling reduced MHPG (NA metabolite) levels and MHPG/NA ratio in the MPOA, indicating decreased NAergic activity. Additionally, neonatal handling decreased NO levels, as measured by the metabolites (NO x), nitrite and nitrate in the same period. We may conclude that the neonatal handling procedure decreased activity of the NAergic and NOergic systems in the MPOA during proestrus, which is involved in the control of LH and FSH secretion, and this may possibly explain the anovulatory estrous cycles and reduced sexual behavior of the neonatally handled female rats. Copyright (c) 2007 S. Karger AG, Basel.

Lead Deposition in Bovine Enamel during a pH-Cycling Regimen Simulating the Caries Process

Like fluoride, lead (Pb) accumulates on the enamel surface pre-eruptively, but it is not yet known whether it also deposits on enamel while dental caries is developing. This study evaluates Pb distribution in bovine enamel slabs submitted to a pH-cycling regimen simulating the caries process. The slabs were subjected to 8 cycles of de- and remineralizing conditions, and Pb (as acetate salt) was added to the de- and remineralized solutions at concentrations of 30 mu g/l (experimental group, E1) and 300 mu g/l (experimental group, E2). The control group (C) consisted of solutions to which Pb was not added. After the pH cycling, 100-mu m sections of the slabs were analyzed by polarizing microscopy, to observe the extent of caries-like lesions, and these sections were used for Pb estimation by Synchrotron radiation X-ray microfluorescence. Caries lesions were observed along all superficial enamel surfaces to an extent of 120 mu m. A Pb concentration gradient was observed in enamel, which decreased toward dentine. The highest Pb signals were observed for group E2, and the differences were statistically significant at enamel depths of 0 (C vs. E2; p = 0.029) and 50 mu m (C vs. E2 and E1 vs. E2; p = 0.029). In conclusion, this study suggests that if Pb is present in the oral environment, it may deposit in enamel during the caries process. Copyright (C) 2011 S. Karger AG, Basel

Masticatory process in individuals with maxillary and mandibular osteoporosis: electromyographic analysis

The masseter and temporal muscles of patients with maxillary and mandibular osteoporosis were submitted to electromyographic analysis and compared with a control group. In conclusion, individuals with osteoporosis did not show significantly lower masticatory cycle performance and efficiency compared to the control group during the proposal mastications. This study aimed to examine electromyographically the masseter and temporal muscles of patients with maxillary and mandibular osteoporosis and compare these patients with control patients. Sixty individuals of both genders with an average age of 53.0 +/- 5 years took part in the study, distributed in two groups with 30 individuals each: (1) individuals with osteoporosis; (2) control patients during the habitual and non-habitual mastication. The electromyographic apparel used was a Myosystem-BR1-DataHomins Technology Ltda., with five channels of acquisition and electrodes active differentials. Statistical analysis of the results was performed using SPSS version 15.0 (Chicago, IL, USA). The result of the Student`s t test indicated no significant differences (p > 0.05) between the normalized values of the ensemble average obtained in masticatory cycles in both groups. Based on the results of this study, it was concluded that individuals with osteoporosis did not show significantly lower masticatory cycle performance and efficiency compared to control subjects during the habitual and non-habitual mastications. This result is very important because it demonstrates the functionality of the complex physiological process of mastication in individuals with osteoporosis at the bones that compose the face.

High concentration of residual aluminum oxide on titanium surface inhibits extracellular matrix mineralization

In the present study we characterized titanium (Ti) surfaces submitted to different treatments and evaluated the response of osteoblasts derived from human alveolar bone to these surfaces. Five different surfaces were evaluated: ground (G), ground and chemical etched (G1-HF for 60 s), sand blasted (SB-Al2O3 particles 65 pm), sand blasted and chemical etched (SLA1-HF for 60 s and SLA2-HF for 13 s). Surface morphology was evaluated under SEM and roughness parameters by contact scanning instrument. The presence of Al2O3 was detected by EDS and the amount calculated by digital analyses. Osteoblasts, were cultured on these surfaces and it was evaluated: cell adhesion, proliferation, and viability, alkaline phosphatase activity, total protein content, and matrix mineralization formation. Physical and chemical treatments produced very different surface morphologies. Al2O3 residues were detected on SB and SLA2 surfaces. Only matrix mineralization formation was affected by different surface treatments, being increased on rough surface (SLA1) and reduced on surface with high amount of Al2O3 residues (SB). On the basis of these findings, it is possible to conclude that high concentration of residual Al2O3 negatively interfere with the process of matrix mineralization formation in contact with Ti implant surfaces. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 87A: 588-597, 2008

Ultrastructural Analysis of Radicular Dentine Surface Submitted to CO(2) Laser at Different Parameters

Background: There are no reported studies comparing different parameter settings of the CO(2) laser and irradiation direction considering their effect on the morphology of radicular dentine surface. Purpose: To evaluate the alterations of radicular dentine (cervical, middle, and apical thirds) irradiated with CO(2) laser at different potencies and irradiation directions. Study Design: Roots of 35 canines were prepared and randomly distributed according to the laser potency: GI: no laser treatment (control) (n = 5); GII, 2 W (n = 10); GIII: 4 W (n = 10); GIV: 6 W (n = 10). Each group (excepting GI) was divided in two subgroups according to the irradiation distance (n = 5): (A) parallel and (B) perpendicular to the root canal walls. The roots were splited longitudinally and analyzed by scanning electron microscopy in a qualiquatitative way. The scores were submitted to Kruskal-Wallis and Dunn`s tests. Results: No significant statistical differences were observed among root canal thirds (P > 0.05). The specimens irradiated with 2 W were statistically different (P < 0.05) from those irradiated with 4 and 6 W, which were statistically similar between themselves (P > 0.05). With 2, 4, and 6 W at in parallel irradiation and 2 W in perpendicular direction, the surface showed a fissured aspect. With 4 W in perpendicular direction and 6 W in parallel and perpendicular direction, surface was modified by laser action and exhibited fused areas. Conclusions: The intensity of the effects is dependent on the laser-irradiation dosimetries. Alterations were more intense when higher parameters were used. Microsc. Res. Tech. 72:737-743, 2009. (C) 2009 Wiley-Liss, Inc.

A sociolinguistic approach to applied epistemology: Examining technocratic values in global 'knowledge' policy

This special issue presents an excellent opportunity to study applied epistemology in public policy. This is an important task because the arena of public policy is the social domain in which macro conditions for ‘knowledge work’ and ‘knowledge industries’ are defined and created. We argue that knowledge-related public policy has become overly concerned with creating the politico-economic parameters for the commodification of knowledge. Our policy scope is broader than that of Fuller (1988), who emphasizes the need for a social epistemology of science policy. We extend our focus to a range of policy documents that include communications, science, education and innovation policy (collectively called knowledge-related public policy in acknowledgement of the fact that there is no defined policy silo called ‘knowledge policy’), all of which are central to policy concerned with the ‘knowledge economy’ (Rooney and Mandeville, 1998). However, what we will show here is that, as Fuller (1995) argues, ‘knowledge societies’ are not industrial societies permeated by knowledge, but that knowledge societies are permeated by industrial values. Our analysis is informed by an autopoietic perspective. Methodologically, we approach it from a sociolinguistic position that acknowledges the centrality of language to human societies (Graham, 2000). Here, what we call ‘knowledge’ is posited as a social and cognitive relationship between persons operating on and within multiple social and non-social (or, crudely, ‘physical’) environments. Moreover, knowing, we argue, is a sociolinguistically constituted process. Further, we emphasize that the evaluative dimension of language is most salient for analysing contemporary policy discourses about the commercialization of epistemology (Graham, in press). Finally, we provide a discourse analysis of a sample of exemplary texts drawn from a 1.3 million-word corpus of knowledge-related public policy documents that we compiled from local, state, national and supranational legislatures throughout the industrialized world. Our analysis exemplifies a propensity in policy for resorting to technocratic, instrumentalist and anti-intellectual views of knowledge in policy. We argue that what underpins these patterns is a commodity-based conceptualization of knowledge, which is underpinned by an axiology of narrowly economic imperatives at odds with the very nature of knowledge. The commodity view of knowledge, therefore, is flawed in its ignorance of the social systemic properties of ��knowing’.