Eosinophils may predict occult lymph node metastasis in early oral cancer

Objective The aim of this study was to investigate whether tumor-associated tissue eosinophilia (TATE) in early oral squamous cell carcinoma (OSCC) would aid in predicting occult lymph node metastasis. Patients and methods Seventy-one patients undergoing elective neck dissection for T1 and T2 OSCC were evaluated for clinical features, prognosis, and TATE. The degree of TATE in OSCC was statistically analyzed in relation to the clinicopathological features, tumor invasion, occult lymph node metastasis, and survival using chi (2) test and Kaplan-Meier method. Results Statistical analysis revealed that intense TATE was a significant feature (p = 0.004) to predict occult lymph node metastasis in patients with early OSCC. All regional recurrences of the OSCC occurred in patients showing intense TATE. Conclusions These results suggest that intense TATE can be clinically used as a predictive factor for occult lymph node metastasis. Clinical relevance The presence of intense TATE is an adjunctive histopathological marker to reinforce the indication of elective neck dissection of the patients with early OSCC.

Accuracy of Screening for Potentially Malignant Disorders of the Oral Mucosa by Dentists in Primary Care

Purpose: To examine the accuracy of a screening programme for potentially malignant disorders of the oral mucosa by visual inspection in primary health care. Materials and Methods: The study was based on secondary data from the Primary Care Information System maintained by seven units of family health in Sao Paulo City managed by a non-governmental agency. The reference population was composed of 15,072 residents 50 years old or more of both genders. The study population comprised 2,980 individuals. During screening in community settings, the oral mucosa was examined by trained dentists and distributed into two categories: (a) screen negative (b) screen positive. All participants underwent comprehensive clinical exams by a general dental practitioner supervised by a specialist. Individual records were grouped in a working dataset. Point and 95% confidence interval estimates were calculated regarding measures of sensitivity (Se), specificity (Sp) and positive and negative predictive values (PPV and NPV, respectively). Results: 18.0% of the population was considered screen positive. A total of 133 lesions (4.5%) were identified and 8 cases of oral cancer were confirmed, which corresponded to a prevalence rate of 27 cases in 10,000 people, a much higher rate than expected. The measures found were Se: 91.7% (85.3-95.6), Sp: 85.4% (84.1-86.7), PPV: 22.7% (19.3-26.5), NPV: 99.5% (99.2-99.8). The visual screen presented high accuracy. Conclusion: The test presented high sensibility and specificity values. From a public health point of view, the high accuracy levels showed the importance of oral health teams on family health strategy for more comprehensive primary care. Targeting risk groups and delegating the screening to community health agents may improve PPV and coverage.

Paper-Based Analytical Device for Electrochemical Flow-Injection Analysis of Glucose in Urine

This article describes a new design for a paper-based electrochemical system for flow injection analysis. Capillary wicking facilitates a gravity-driven flow of buffer solution continuously through paper and nitrocellulose, from a buffer reservoir at one end of the device to a sink at the other. A difference in height between the reservoir and the sink leads to a continuous and constant flow. The nitrocellulose lies horizontally on a working electrode, which consists of a thin platinum layer deposited on a solid support. The counter and reference electrodes are strategically positioned upstream in the buffer reservoir. A simple pipetting device was developed for reliable application of (sub)microliter volumes of sample without the need of commercial micropipets; this device did not damage the nitrocellulose membrane. Demonstration of the system for the determination of the concentration of glucose in urine resulted in a noninvasive, quantitative assay that could be used for diagnosis and monitoring of diabetes. This method does not require disposable test strips, with enzyme and electrodes, that are thrown away after each measurement Because of its low cost, this system could be used in medical environments that are resource-limited.

Effects of eating disorders on oral fungal diversity

Background. The eating disorders anorexia and bulimia nervosa can cause several systemic and oral alterations related to poor nutrition and induced vomiting; however, the oral microflora of these patients is poorly studied. Objective. The aim of this study was to evaluate fungal microflora in the oral cavity of these patients by culture-dependent and culture-independent methods. Study Design. Oral rinse samples were cultured to assess the prevalence of Candida species, and the isolates were identified by API system. Microorganism counts were compared by the Mann-Whitney test (5%). Ribotyping, a type of molecular analysis, was performed by sequencing the D1/D2 regions of 28S rRNA. Results. Our results demonstrated that the eating disorder group showed higher oral Candida spp. prevalence with culture-dependent methods and higher species diversity with culture-independent methods. Conclusions. Eating disorders can lead to an increased oral Candida carriage. Culture-independent identification found greater fungal diversity than culture-dependent methods. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:512-517)

Changes in the surface of four calcium silicate-containing endodontic materials and an epoxy resin-based sealer after a solubility test

Aim To compare the changes in the surface structure and elemental distribution, as well as the percentage of ion release, of four calcium silicate-containing endodontic materials with a well-established epoxy resin-based sealer, submitted to a solubility test. Methodology Solubility of AH Plus, iRoot SP, MTA Fillapex, Sealapex and MTA-Angelus (MTA-A) was tested according to ANSI/ADA Specification 57. The deionized water used in the solubility test was submitted to atomic absorption spectrophotometry to determine and quantify Ca2+, Na+, K+, Zn2+, Ni2+ and Pb2+ ions release. In addition, the outer and inner surfaces of nonsubmitted and submitted samples of each material to the solubility test were analysed by means of scanning electron microscopy and energy-dispersive spectroscopy (SEM/EDX). Statistical analysis was performed by using one-way anova and Tukeys post hoc tests (a = 0.05). Results Solubility results, in percentage, sorted in an increasing order were -1.24 +/- 0.19 (MTA-A), 0.28 +/- 0.08 (AH Plus), 5.65 +/- 0.80 (Sealapex), 14.89 +/- 0.73 (MTA Fillapex) and 20.64 +/- 1.42 (iRoot SP). AH Plus and MTA-A were statistically similar (P > 0.05), but different from the other materials (P < 0.05). High levels of Ca2+ ion release were observed in all groups except AH Plus sealer. MTA-A also had the highest release of Na2+ and K+ ions. Zn+2 ion release was observed only with AH Plus and Sealapex sealers. After the solubility test, all surfaces had morphological changes. The loss of matrix was evident and the filler particles were more distinguishable. EDX analysis displayed high levels of calcium and carbon at the surface of Sealapex, MTA Fillapex and iRoot SP. Conclusions AH Plus and MTA-A were in accordance with ANSI/ADAs requirements regarding solubility whilst iRoot SP, MTA Fillapex and Sealapex did not fulfil ANSI/ADAs protocols. High levels of Ca2+ ion release were observed in all materials except AH Plus. SEM/EDX analysis revealed that all samples had morphological changes in both outer and inner surfaces after the solubility test. High levels of calcium and carbon were also observed at the surface of all materials except AH Plus and MTA-A.

Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism

Background: Combined oral contraceptives used in an extended regimen have been studied because of their potential benefits; however, there have been few publications on extended regimens of contraceptive vaginal rings. The aim of this study was to assess the effects of these two extended regimens on the lipid metabolism of women using these contraceptive methods during 1 year. Study Design: This prospective study enrolled 150 women: 75 used a vaginal contraceptive ring (11.7 mg etonogestrel and 2.7 mg ethinyl estradiol), and 75 used oral contraceptives (30 mcg ethinyl estradiol and 150 mg desogestrel). Both groups used their respective method for 84 days followed by a 7-day pause during I year. At baseline and every 3 months during the study period, blood was collected to assess total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and apolipoprotein (apo) A-I and B. The analysis of variance test was used to analyze differences in the results of these exams over time. Results: A total of 62 vaginal ring and 61 oral contraceptive users completed the study. There were no significant differences in the discontinuation rate, mean total cholesterol and fraction levels, apo B concentration or apo A-I/apo B ratio. Vaginal ring users had significantly higher apo A-I levels than oral contraceptive users. Conclusion: Despite the vaginal route of administration, the steroids released by the ring had the same effects on the lipid metabolism and lipoprotein levels typically seen with ethinyl estradiol given either by oral or parenteral routes. (C) 2012 Elsevier Inc. All rights reserved.

Biowaiver monographs for immediate-release solid oral dosage forms: Stavudine

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing stavudine (d4T) are reviewed. According to Biopharmaceutics Classification System (BCS), d4T can be assigned to BCS class I. No problems with BE of IR d4T formulations containing different excipients and produced by different manufacturing methods have been reported and, hence, the risk of bioinequivalence caused by these factors appears to be low. Furthermore, d4T has a wide therapeutic index. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing d4T as the single active pharmaceutical ingredient (API) provided that (a) the test product contains only excipients present in the IR d4T drug products that have been approved in a number of countries for the same dosage form, and (b) both test product and its comparator are either very rapidly dissolving or rapidly dissolving with similarity of dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1016, 2012

Ventilatory threshold is related to walking tolerance in patients with intermittent claudication

Background: This study assessed the relationship between lower limb hemodynamics and metabolic parameters with walking tolerance in patients with intermittent claudication (IC). Patients and methods: Resting ankle-brachial index (ABI), baseline blood flow (BF), BF response to reactive hyperemia (BFRH), oxygen uptake (VO2), initial claudication distance (ICD) and total walking distance (TWD) were measured in 28 IC patients. Pearson and Spearman correlations were calculated. Results: ABI, baseline BF and BF response to RH did not correlate with ICD or TWD. VO2 at first ventilatory threshold and VO(2)peak were significantly and positively correlated with ICD (r = 0.41 and 0.54, respectively) and TWD (r = 0.65 and 0.71, respectively). Conclusions: VO(2)peak and VO2 at first ventilatory threshold, but not ABI, baseline BF and BFHR were associated with walking tolerance in IC patients. These results suggest that VO2 at first ventilatory threshold may be useful to evaluate walking tolerance and improvements in IC patients.

Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes

The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

Urinary copper excretion before and after oral intake of D-penicillamine in parents of patients with Wilson's disease

Background: Urinary copper excretion higher than 100 mu g/24 h is useful for diagnosing Wilson's disease. D-Penicillamine challenge test may produce higher levels than 1400 mu g/24 h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering D-penicillamine to the parents of Wilson's disease patients. Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1 g D-penicillamine. Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8 x 27.8 mg%; 71.4 x 88.0 mu g%; p <= 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2 x 18.7 mu g/24 h, p = 0.01), but did not differ between the genders after D-penicillamine (521.7 x 525.3, range 31.6-1085.1 mu g/24 h, p = 0.8). Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after D-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after D-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Effects of 3 weeks GMP oral administration on glutamatergic parameters in mice neocortex

Overstimulation of the glutamatergic system (excitotoxicity) is involved in various acute and chronic brain diseases. Several studies support the hypothesis that guanosine-5'-monophosphate (GMP) can modulate glutamatergic neurotransmission. The aim of this study was to evaluate the effects of chronically administered GMP on brain cortical glutamatergic parameters in mice. Additionally, we investigated the neuroprotective potential of the GMP treatment submitting cortical brain slices to oxygen and glucose deprivation (OGD). Moreover, measurements of the cerebrospinal fluid (CSF) purine levels were performed after the treatment. Mice received an oral administration of saline or GMP during 3 weeks. GMP significantly decreases the cortical brain glutamate binding and uptake. Accordingly, GMP reduced the immunocontent of the glutamate receptors subunits, NR2A/B and GluR1 (NMDA and AMPA receptors, respectively) and glutamate transporters EAAC1 and GLT1. GMP treatment significantly reduced the immunocontent of PSD-95 while did not affect the content of Snap 25, GLAST and GFAP. Moreover, GMP treatment increased the resistance of neocortex to OGD insult. The chronic GMP administration increased the CSF levels of GMP and its metabolites. Altogether, these findings suggest a potential modulatory role of GMP on neocortex glutamatergic system by promoting functional and plastic changes associated to more resistance of mice neocortex against an in vitro excitotoxicity event.

Oral health and access to dental care services in relation to the Health Necessities Index. Sao Paulo, Brazil, 2008

The Health Department of Sao Paulo, Brazil, has developed a Health Necessities Index (HNI) to identify priority areas for providing health assistance. In 2008, a survey of the status of oral health was conducted. The objective of this ecological study was to analyze the status of oral health in relation to the HNI. The variables, stratified by the age of 5, 12 and 15 years old were: percentage of individuals with difficulty of access to dental care services; DMFT and DMFS; prevalence of the need for tooth extraction and treatment of dental caries. Data were analyzed for the 25 Health Technical Supervision Units (HTS). The Statistical Covariance Test was used as well as the Pearson correlation coefficient and linear regression model. A positive correlation was observed between high scores of the HNI and difficulty of access to services. In the HTS with high scores of HNI a higher incidence of dental caries was observed, a greater need for tooth extractions and low caries-free incidence. In order to improve health conditions of the population it is mandatory to prioritize actions in areas of social deprivation.

Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats

Objective: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to similar to 0.15 mg% resveratrol RS), or RS in low (L, 0.15 mg%) or high (H, 400 mg%) doses in chow. Background: Both RW and RS exhibit cardioprotection. RS extends lifespan in obese rats. It is unclear whether RW consumption or low-dose RS delay vascular aging and prolong life span in the absence of overt risk factors. Methods: Endpoints were aerobic performance, exercise capacity, aging biomarkers (p53,p16,p21, telomere length and telomerase activity in aortic homogenates), vascular reactivity. Data were compared with controls (C) given regular chow. Results: Expressions of p53 decreased similar to 50% similar to with RW and LRS (p < 0.05 vs. C), p16 by similar to 29% with RW (p < 0.05 vs. C) and p21 was unaltered. RW and LRS increased telomere length >6.5-fold vs. C, and telomerase activity increased with LRS and HRS. All treatments increased aerobic capacity (C 32.5 +/- 1.2, RW 38.7 + 1.7, LRS 38.5 + 1.6, HRS 38.3 + 1.8 mlO2 min(-1) kg(-1)), and RW or LRS also improved time of exercise tolerance vs. C (p < 0.05). Endothelium-dependent relaxation improved with all treatments vs. C. Life span, however, was unaltered with each treatment vs. C = 673 +/- 30 days, p = NS. Conclusions: RW and LRS can preserve vascular function indexes in normal rats, although not extending life span. These effects were translated into better aerobic performance and exercise capacity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Six minute walk test Z score: Correlations with cystic fibrosis severity markers

Background: The six-minute-walk-test (6MWT) has been increasingly used in cystic fibrosis (CF) patients. However, few studies in children have correlated 6MWT with current parameters used to evaluate CF severity. Moreover, no study transformed the values of distance walked from meters into Z scores to avoid bias like age and gender, which are sources of 6MWT variability. Methods: A cross-sectional descriptive study was performed to analyze the correlations (Spearman) among forced expiratory volume in one second (FEV1), body mass index (BMI), chest radiography (CXR), chest tomography (CT), and 6MWT Z score (Z-6MWT). Clinically stable CF patients, aged 6-21 years, were included. Results: 34 patients, 14F/20M, mean age 12.1 +/- 4.0 years were studied. The mean Z-6MWT was -1.1 +/- 1.106. The following correlations versus Z-6MWT were found: FEV1 (r=0.59, r(2)=0.32, p=0.0002), BMI Z score (r=0.42, r(2)=0.17, p=0.013), CXR (r=0.34, r(2)=0.15, p=0.0472) and CT (r=-0.45, r(2)=0.23, p=0.0073). Conclusions: In conclusion there was a significant, but poor, correlation between the six minute walk test Z score and the cystic fibrosis severity markers currently in use. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Association of AXIN2 with Non-syndromic Oral Clefts in Multiple Populations

We have previously shown the association of AXIN2 with oral clefts in a US population. Here, we expanded our study to explore the association of 11 AXIN2 markers in 682 cleft families from multiple populations. Alleles for each AXIN2 marker were tested for transmission distortion with clefts by means of the Family-based Association Test. We observed an association with SNP rs7224837 and all clefts in the combined populations (p = 0.001), and with SNP rs3923086 and cleft lip and palate in Asian populations (p = 0.004). We confirmed our association findings in an additional 528 cleft families from the United States (p < 0.009). We tested for gene-gene interaction between AXIN2 and additional cleft susceptibility loci. We assessed and detected Axin2 mRNA and protein expression during murine palatogenesis. In addition, we also observed co-localization of Axin2 with Irf6 proteins, particularly in the epithelium. Our results continue to support a role for AXIN2 in the etiology of human clefting. Additional studies should be performed to improve our understanding of the biological mechanisms linking AXIN2 to oral clefts.