Desenvolvimento e caracterização de nanopartículas lipídicas sólidas para administração cutânea de trans-resveratrol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Assessment of ALA-induced PpIX production in porcine skin pretreated with microneedles

Photodynamic therapy (PDT) is used for skin treatments of premalignant and cancer lesions and recognized as a non-invasive technique that combines tissue photosensitization and subsequent exposure to light to induce cell death. However, it is limited to the treatment of superficial lesions, mainly due to the low cream penetration. Therefore, the improvement of transdermal distribution of aminolevulinic acid (ALA) is needed. In this study, the kinetics and homogeneity of production of ALA-induced PpIX after the skin pre-treatment with microneedles rollers of 0.5, 1.0 and 1.5 mm length were investigated. An improvement in homogeneity and production of PpIX was shown in a porcine model. Widefield fluorescence imaging three hours after the topical application of ALA-cream in the combined treatment with microeedles rollers.

Anuran skin and basking behavior: the case of the treefrog Bokermannohyla alvarengai (Bokermann, 1956)

We investigated the morphology of the skin and the biochemistry of the lipids in the skin secretion of Bokermannohyla alvarengai, a montane treefrog that is known to bask regularly, motionless in full sunlight for extended periods of time. Our primary goal was to identify structural and biochemical modifications that might assist this frog species to accommodate the conflicting demands for heat exchange and water balance while basking. The modulation of heat exchange in basking B. alvarengai involves changes in skin coloration. We found that this response was supported by a prominent monolayer of large iridophores, whose light reflectance property is adjusted by the response of intervening melanophores. Mucosubstances and lipid compounds, mainly consisted of saturated fatty acids and presumably secreted from granular glands, were detected on the skin of B. alvarengai. These compounds formed an extra-epidermal layer over the animal's dorsal surface that might assist in the prevention of excessive water loss through evaporation. Additionally, we found well-developed skin folds at the ventral region of the frogs that lead to an increment of surface area. This feature combined with the extensive hypervascularization, also noticed for the skin of B. alvarengai, may play an important role in water reabsorption. The suite of structural and biochemical modifications identified for the integument of B. alvarengai seems to conjugate aspects relevant to both, heat exchange and water balance, allowing for this species to explore basking as an efficient thermoregulatory strategy. J. Morphol. 276:1172-1182, 2015. © 2015 Wiley Periodicals, Inc.

Tobacco in adolescence: importance to knowledge the health hazards and preventive measures

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

CHALLENGES TO THE ORGANIZATION OF A CERVICAL CANCER SCREENING PROGRAM IN MANAUS-AM

The purpose was to investigate sociodemographic characteristics of women who underwent a Pap smear test in Manaus, Amazonas, Brazil, and identify the reasons why the women had the test. This exploratory study was performed with 281 women who had taken the Pap smear test within the last five years in Manaus. Most participants were between 18 to 34 years old (54%), had 5 to 11 years of education (54.4%), had a monthly income of less than three minimum wage salaries (84.3%) and were in a stable relationship (72.2%), with an onset of sexual activity between the ages of 15 to 19 years (69.4%). The reasons for their taking the Pap test were personal choice (66.2%), recommendation by a physician (23.5%) and gynecological symptoms (10.3%). Women who received information about the Pap test from health professionals had a greater chance of being tested within the last three years (p=0.008). Women choosing to have the exam (personal choice) are prevalent, and the opportunistic service is provided to younger women, thus not reaching the group at greater risk for cancer. It is necessary to implement active recruitment strategies to reach women in situations of socioeconomic disadvantage.

Dose-dependent effect of Resveratrol on bladder cancer cells: Chemoprevention and oxidative stress

Background: Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells. Objectives: Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition. Methods: For this purpose. ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress. Results: Resveratrol induced cell death at high concentrations (>20 mu M), but not at low ones (0.1-20 mu M). Pretreatment with 2.5 mu M protected the cells from oxidative damage, whereas 50 mu M intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells. Conclusions: Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies. Published by Elsevier Ireland Ltd.

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

The impact of atmospheric particulate matter on cancer incidence and mortality in the city of Sao Paulo, Brazil

This study aimed to verify the impact of inhalable particulate matter (PM10) on cancer incidence and mortality in the city of Sao Paulo, Brazil. Statistical techniques were used to investigate the relationship between PM10 on cancer incidence and mortality in selected districts. For some types of cancer (skin, lung, thyroid, larynx, and bladder) and some periods, the correlation coefficients ranged from 0.60 to 0.80 for incidence. Lung cancer mortality showed more correlations during the overall period. Spatial analysis showed that districts distant from the city center showed higher than expected relative risk, depending on the type of cancer According to the study, urban PM10 can contribute to increased incidence of some cancers and may also contribute to increased cancer mortality. The results highlight the need to adopt measures to reduce atmospheric PM10 levels and the importance of their continuous monitoring.

Antimicrobial activity of two techniques for arm skin disinfection of blood donors in Brazil

Objective: Evaluation of the antimicrobial effect of skin disinfection techniques is essential to avoid the transmission of infectious agents during blood transfusion. The aim of this study was to examine the effectiveness of two methods of arm skin disinfection used in blood donors at a Hemotherapy Center in Brazil that represents an important centre for distributing haemocomponents to many cities in the country. Methods: Two skin disinfection techniques in 50 blood donors were evaluated. For the first arm, 10% povidone-iodine/two-stage technique was used. On the opposite arm, 0.5% chlorhexidine digluconate alcohol solution/one-stage technique was used. The swabs were seeded on three culture media: blood agar, mannitol salt agar and Mac Conkey agar. Automated bacterial classification based on biochemical tests/specific substrates was performed. Donor characteristics were collected using the computerised system of the Hemotherapy Center. Results: We found that microbial reduction was significantly higher for 10% povidone-iodine technique (98.57-98.87%) when compared with 0.5% chlorhexidine technique (94.38-95.06%). The species Leuconostoc mesenteroides and Staphylococcus hominis showed resistance to both disinfection techniques. We did not find statistically significant relationships between donor characteristics and microbial reduction. Conclusions: Arm skin disinfection with 10% povidone-iodine produced better antimicrobial activity. We must acknowledge that 10% povidone-iodine technique has the limitation of being a two-stage method. However, prevention of adverse events due to bacterial contamination and transfusion reactions should be prioritised. Production of hypoallergenic and stronger antiseptics that allowed a safe one-stage disinfection technique should be encouraged in health systems, not only in Brazil but also around the world.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

Evaluation of frozen-section analysis of surgical margins in the treatment of breast cancer

Objective: To evaluate surgical margins in cases of ductal carcinoma through a histopathological exam using frozen sections. Materials and Methods: Retrospective study encompassing 242 conservative surgeries, 179 of which included intraoperative frozensection histopathology and 63 intraoperative nonfreezing techniques (macroscopy/gross examination and cytology). The results of such analyses were compared with those of the histology processing following paraffin embedment and hematoxylin and eosin (H & E) staining. A margin was deemed free when the distance between the tumor and the surgical border was equal to or greater than two millimeters. The factors given consideration for possibly affecting the results were: age, surgical aspects (skin removal and widening of surgical margins), histopathological findings (size, affected lymph nodes, and angiolymphatic invasion), and extensive intraductal and immunohistochemical components (estrogen, progesterone, Ki-67, and HER-2 receptors). In the statistical analyses, the chi-square test was used and negative predictive values were calculated. Results: The negative predictive values were 87.1% and 79.3% for frozen and nonfrozen sections, respectively. There was no significant difference between the two groups (p = 0.14). The factors under consideration had no influence on the results of the intraoperative exam of the margins. Conclusion: The present study allowed to conclude that the intraoperative exam of the surgical margins by frozen section is not superior to a macroscopy and / or cytology exam.

Effect of topical clay application on the synthesis of collagen in skin: an experimental study

Background. Clay is often used in cosmetic treatments, although little is known about its action. Aim. To evaluate the effect of topical clay application on the histoarchitecture of collagen fibres in rat skin. Methods. Animals received a daily application of clay and retinoic acid (RA) 0.025% to the dorsal skin over 7 and 14 days, under vaporization at 37 degrees C for 40 min. Control skin was not vaporized. Samples from each region were excised, and stained with picrosirius red for collagen evaluation. Results. Seven days after clay treatment, an increase in the number of collagen fibres was observed in treated skin compared with control skin (51.74 +/- 1.28 vs. 43.39 +/- 1.79%, respectively, P < 0.01), whereas RA did not alter the collagen level (45.66 +/- 1.10%). Clay application over 14 days did not induce a further increase in skin collagen, whereas treatment with RA did (58.07 +/- 1.59%; P = 0.001 vs. control). Conclusion. Clay application promotes an increase in the number of collagen fibres, which may account for its beneficial effects.

A clinical experience of the supraclavicular flap used to reconstruct head and neck defects in late-stage cancer patients

The supraclavicular island flap has been widely used in head and neck reconstruction, providing an alternative to the traditional techniques like regional or free flaps, mainly because of its thin skin island tissue and reliable vascularity. Head and neck patients who require large reconstructions usually present poor clinical and healing conditions. An early experience using this flap for late-stage head and neck tumour treatment is reported. Forty-seven supraclavicular artery flaps were used to treat head and neck oncologic defects after cutaneous, intraoral and pharyngeal tumour resections. Dissection time, complications, donor and reconstructed area outcomes were assessed. The mean time for harvesting the flaps was 50 min by the senior author. All donor sites were closed primarily. Three cases of laryngopharyngectomy reconstruction developed a small controlled (salivary) leak that was resolved with conservative measures. Small or no strictures were detected on radiologic swallowing examinations and all patients regained normal swallowing function. Five patients developed donor site dehiscence. These wounds were treated with regular dressing until healing was complete. There were four distal flap necroses in this series. These necroses were debrided and closed primarily. The supraclavicular flap is pliable for head and neck oncologic reconstruction in late-stage patients. High-risk patients and modified radical neck dissection are not contraindications for its use. The absence of the need to isolate the pedicle offers quick and reliable harvesting. The arc of rotation on the base of the neck provides adequate length for pharyngeal, oral lining and to reconstruct the middle and superior third of the face. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The impact of atmospheric particulate matter on cancer incidence and mortality in the city of São Paulo, Brazil

This study aimed to verify the impact of inhalable particulate matter (PM10) on cancer incidence and mortality in the city of São Paulo, Brazil. Statistical techniques were used to investigate the relationship between PM10 on cancer incidence and mortality in selected districts. For some types of cancer (skin, lung, thyroid, larynx, and bladder) and some periods, the correlation coefficients ranged from 0.60 to 0.80 for incidence. Lung cancer mortality showed more correlations during the overall period. Spatial analysis showed that districts distant from the city center showed higher than expected relative risk, depending on the type of cancer. According to the study, urban PM10 can contribute to increased incidence of some cancers and may also contribute to increased cancer mortality. The results highlight the need to adopt measures to reduce atmospheric PM10 levels and the importance of their continuous monitoring.

Reorganization of secondary and tertiary health care levels: impact on the outcomes of oral cancer screening in the São Paulo State, Brazil

This study presents the strategies for prevention and early detection of oral cancer by means of screening in the elderly population of São Paulo, the richest and the most populous state of Brazil. This research was a retrospective longitudinal study based on the analysis of secondary data. The variables - number of participating cities, coverage of screening, and number of suspicious and confirmed cases of oral cancer - were divided into two periods: 2001-2004 and 2005-2008. Data were analyzed statistically by the chi-square test at 5% significance level. The implementation of a nationwide public oral health policy in 2004 and the reorganization of the secondary and tertiary health care were evaluated as mediator factors able to interfere in the achieved outcomes. From 2001 to 2008, 2,229,273 oral examinations were performed. There was an addition of 205 participating cities by the end of the studied period (p<0.0001). The coverage of oral cancer screening increased from 4.1% to 16% (p<0.0001). There was a decrease in the number of suspicious lesions (from 9% in 2005 to 5% in 2008) (p<0.0001) and in the rate of confirmed oral cancer cases per 100,000 examinations (from 20.89 in 2001 to 10.40 in 2008) (p<0.0001). After 8 years of screening, there was a decrease in the number of suspicious lesions and confirmed cases of oral cancer in the population. The reorganization of secondary and tertiary health care levels of oral care seems to have contributed to modify these numbers, having a positive impact on the outcomes of oral cancer screening in the São Paulo State.