Simulação da Química da Atmosfera Poluída por Automóveis Movidos a Álcool

Numerical modeling studies of urban atmospheres were performed with a photochemical box submodel which incorporates primary emission rates, temperature and solar irradiance rate coefficients. Actinic flux calculations were made for an appropriate latitude for Rio de Janeiro and initial concentrations and emission rates were taken from experimental data. The relative importance of individual reactions is discussed as well as the effect of enhanced aldehyde emissions from vehicles using ethanol and ethanol-containing fuel.

Laparoscopy in uterine cervical cancer. Current state and literature review

Cervical cancer remains the most frequent gynecological tumor in Brazil and other developing countries. Minimally invasive techniques, especially laparoscopy, have been increasingly employed in such tumors. This article aims to describe the main applications of laparoscopy in the treatment and staging of cervical cancer. In the early stages, it is possible to provide a fertility-preserving surgery in the form of radical trachelectomy and, in a study protocol, the function-preserving surgery, avoiding parametrectomy and the associated morbidity. A fully laparoscopic radical hysterectomy is fairly standard in the literature and has the tendency to become the standard of care in early cases, for patients who want to bear no more children. In advanced stages, minimally invasive surgery can offer ovarian transposition, with intent to prevent actinic castration, without upsetting the time for the start of radiotherapy and chemotherapy. Staging laparoscopic surgery, including pelvic and para-aortic lymphadenectomy, has been the subject of studies, since it has the potential to modify the extension of radiotherapy depending on the extent of lymph node spread.

Complement system in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) consists 20% of keratinocytederived non-melanoma skin cancers (NMSC), the incidence of which is increasing globally. cSCC is the most common metastatic skin cancer and it causes approximately 20% of skin cancer-related deaths. At present, there are no molecular markers for predicting which cSCC lesions are aggressive or metastasize rapidly. UV radiation is the most important risk factor for cSCC. During the development of cSCC, normal epidermal keratinocytes are transformed and form actinic keratosis (AK), which progresses to cSCC in situ (cSCCIS, Bowen’s disease) and finally to invasive and metastatic cSCC. Inflammatory factors and cells are a part of cancer microenvironment and cSCC can develop in the chronically irritated skin or in the context of chronic inflammation. The complement system is a central part of innate immunity and it regulates normal immunological and inflammatory processes. In this study, the role of complement system components and inhibitors were studied in the progression of cSCC in culture and in vivo. Elevated expression of complement factor H (CFH), complement factor I (CFI), complement component C3 and complement factor B (CFB) was noted in cSCC cells in culture. The analysis with immunohistochemistry (IHC) revealed that the expression of CFH, CFI, C3 and CFB was specifically noted in tumor cells in vivo. The staining intensity of CFH, CFI, C3 and CFB was also stronger in invasive cSCC than in AK or cSCCIS samples. The knockdown of CFH, CFI and CFB with specific siRNAs decreased cSCC cell viability and migration, whereas the knockdown of C3 reduced only cSCC cell migration. Moreover, the knockdown of CFI, C3 and CFB inhibited growth of cSCC xenograft tumors established in SCID mice in vivo. In these tumors, CFI, C3 and CFB knockdown decreased the number of proliferating cells. Moreover, the knockdown of CFI increased local inflammation and complement activation. This study provides evidence for the roles of CFH, CFI, C3 and CFB in the tumor progression indicating these as molecular biomarkers and putative therapeutic targets of cSCC.

Roles of novel biomarkers in progression of cutaneous squamous cell carcinoma

Roles of novel biomarkers was studied in progression of cutaneous squamous cell carcinoma (cSCC) as the most common metastatic skin cancer. The incidence of cSCC is increasing worldwide due to lifestyle changes such as recreational exposure to sunlight and the aging of the population. Because of an emerging need for molecular markers for the progression of cSCC, we set our goal to characterize three distinct novel markers overexpressed in cSCC cells. Our results identified overexpression of serpin peptidase inhibitor clade A member 1 (SerpinA1), EphB2 and absent in melanoma 2 (AIM2) in cSCC cell lines compared with normal human epidermal keratinocytes (NHEKs). Immunohistochemical analysis of SerpinA1, EphB2 and AIM2 revealed abundant tumor cell-specific expression of cytoplasmic SerpinA1 and AIM2 and cytoplasmic and membranous EphB2 in cSCC tumors in vivo. The staining intensity of SerpinA1, EphB2 and AIM2 was significantly stronger in cSCC as compared with carcinoma in situ (cSCCIS) and actinic keratosis (AK). Tumor cell-associated SerpinA1 and EphB2 was noted in chemically induced mouse skin SCC, and the staining intensity was stronger in mouse cSCCs than in untreated skin. AIM2 staining intensity was significantly more abundant in cSCC of organ transplant recipients (OTR) than in sporadic cSCC in vivo. EphB2 knockdown resulted in inhibition of migration in cSCC cells. In addition, knockdown of EphB2 and AIM2 was found to inhibit the proliferation and invasion of cSCC cells and to delay the growth and vascularization of cSCC xenografts in vivo. Altogether, these findings identify SerpinA1 as a novel biomarker for cSCC. In addition, characterization of the roles of EphB2 and AIM2 in the progression of cSCC was implicated them as possible therapeutic targets for the treatment of cSCC particularly in unresectable and metastatic tumors.

"Whole-Exome Sequencing Enables Rapid Determination of Xeroderma Pigmentosum Molecular Etiology"

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder haracterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (XPA through XPG and XPV). The XP-V (variant) subtype of the disease results from mutations in a gene (XPV, also named POLH) which encodes for Polg, a member of the Y-DNA polymerase family. Although the presence and severity of skin and neurological dysfunctions differ between XP subtypes, there are overlapping clinical features among subtypes such that the sub-type cannot be deduced from the clinical features. In this study, in order to overcome this drawback, we undertook whole-exome sequencing in two XP sibs and their father. We identified a novel homozygous nonsense mutation (c.897T.G, p.Y299X) in POLH which causes the disease. Our results demonstrate that next generation sequencing is a powerful approach to rapid determination of XP genetic etiology.

Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Production of bioactive diterpenoids in the Euphorbiaceae depends on evolutionarily conserved gene clusters

The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways.

Reliable and fast sensor for in vitro evaluation of solar protection factor based on the photobleaching kinetics of a nanocrystalline TiO(2)/dye UV-dosimeter

A reliable and fast sensor for in vitro evaluation of solar protection factors (SPFs) of cosmetic products, based on the photobleaching kinetics of a nanocrystalline TiO(2)/dye UV-dosimeter, has been devised. The accuracy, robustness and suitability of the new device was demonstrated by the excellent matching of the predicted and the in vivo results up to SPF 70, for four standard samples analyzed in blind. These results strongly suggest that our device can be useful for routine SPF evaluation in laboratories devoted to the development or production of cosmetic formulations, since the conventional in vitro methods tend to exhibit unacceptably high errors above SPF similar to 30 and the conventional in vivo methods tend to be expensive and exceedingly time consuming. (C) 2011 Elsevier B.V. All rights reserved.

Lesões orais com potencial de malignização: análise clínica e morfológica de 205 casos

Silveira , E. J. D. et al. Lesões orais com potencial de malignização: análise clínica e morfológica de 205 casos. J. Bras. Patol. Med. Lab., v. 45, n. 3, p. 233-238, jun 2009. ISBN 1676-2444.

Prevalência e fatores associados a lesões labiais e periorais decorrentes da exposição solar em trabalhadores de praia

This study aimed to verify the prevalence of lip and perioral lesions in worker who were under sunshine on the beaches of Natal/RN and to investigate possible associations of these with sociodemographic, occupational and general health variables. For this, 362 individuals who had one of the urban beaches (Ponta Negra / Environment / Redinha) in the city of Natal/RN as a working environment in the study. We excluded people under 18 years old. Data collection was done through epidemiological analysis and extra-oral validated questionnaire with questions that characterize socioeconomic and demographic factors, occupational exposure and general health. The male subjects (72.6%) were the majority in the sample. The people who worked directly exposed to high peaks of ultraviolet radiation, as well as informal workers predominated. Considering the total sample of individuals, ephelides in the perioral region (33.7%) and labial region (24.0%), solar lentigo perioral (15.2%) and actinic cheilitis (13.8%) stood out as the most prevalent lesions. Indoor workers and those who had a habit occurrence of injuries by 19% and 21% respectively higher when compared to outdoor workers and people without habits. The variable use of cap / hat was associated with the presence of cold sores (Qui2 = 1,328, p = 0,058). On the threshold of significance, the type of work was also associated with lesions in lip occurrence (p = 0,042). Men showed a lower incidence of perioral lesions when compared to female workers (PR=0,716, p valor = 0,002). The present study showed high prevalence of lip and perioral lesions. The premalignant lesions were the most identified, both as in lip skin. It is important therefore to be encouraged to adopt protective measures against excessive sun exposure, fairly and consistently

Análise comparativa da imunoexpressão das proteínas hmlh1 e hmsh2 em carcinomas epidermóides de lábio inferior e queilites actínicas com graus variados de displasia

Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 μm were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip

Prevalência de lesões cutâneas actínicas em pacientes com carcinoma basocelular do segmento cefálico: um estudo caso-controle

OBJETIVO: Avaliar a prevalência de lesões cutâneas actínicas em portadores de carcinoma basocelular do segmento cefálico. MÉTODOS: Foi conduzido estudo tipo caso-controle. Os casos, constituídos por pacientes com carcinoma basocelular sólido, primário, menor que dois centímetros, no segmento cefálico; e controles, por pacientes com outras dermatoses. Foram analisadas variáveis constitucionais, comportamentais e lesões actínicas. RESULTADOS: Avaliaram-se 120 casos e 360 controles. Mílio facial (OR = 2,3), leucodermia puntacta de membros superiores (OR = 2,9) e cutis romboidalis nuchae (OR = 1,8) associaram-se à neoplasia independentemente das demais variáveis, sugerindo um fenótipo de risco. Houve ainda associação com fenótipos claros, genética familiar e exposição solar cumulativa. Queimadura solar, tabagismo e alcoolismo não foram identificados como fatores de risco. O uso de fotoprotetores não evidenciou proteção; porém, o grupo controle era composto por pacientes dermatológicos, aos quais são indicados fotoprotetores regularmente. CONCLUSÃO: Lesões actínicas foram mais prevalentes em portadores de carcinoma basocelular sólido do segmento cefálico que em controles, especialmente mílio, cutis romboidalis nuchae e leucodermia puntacta, independentemente dos demais fatores de risco conhecidos.

Inflamação de queratoses seborreicas múltiplas induzida por quimioterapia com gencitabina

São diversos e comuns os efeitos mucocutâneos dos quimioterápicos, alguns por ação citotóxica, outros por hipersensibilidade ao fármaco. Os autores relatam a ocorrência de inflamação em múltiplas queratoses seborreicas pré-existentes, após terapia citorredutora com gencitabina, em paciente sob tratamento para neoplasia de pâncreas. Discutem, ainda, a benignidade do evento e alertam para a necessidade de adequada identificação dos efeitos cutâneos decorrentes da quimioterapia sistêmica.

Potentially malignant epithelial oral lesions: Discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL). PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis. RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%. CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesions. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.

Como desenhar e escrever um protocolo de pesquisa clínica em Cosmiatria

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. © 2013 by Anais Brasileiros de Dermatologia.