Introduction: Histopathological analysis of the foreskin has become more common in the last two decades. Objectives: This study aims to analyze the morphology of the foreskin and determine the ...effects of topical corticosteroid therapy on this tissue. Materials and Methods: We retrospectively evaluated forty foreskin samples from children aged from 2 years to 15 years with phimosis undergoing circumcision at our institution over a 2-year period. In the foreskin samples, we analyzed the elastic fibers (Verhoeff), epidermal thickness (hematoxylin and eosin), and Annexin 1 and Langerhans cells (LCs) (immunohistochemistry).Results: In the present study, 18 (45%) patients made use of topical corticosteroids, and 22 (55%) did not, while 4 (10%) had a history of balanoposthitis as previous complication. Forty patients were divided according to the parameter analyzed: with or without previous complication and with or without previous topical corticotherapy. Annexin 1 expression was significantly higher in group with a history of complications when compared with group without complications (P = 0.024) and lower in the group of those who used corticosteroids when compared with those who did not used corticosteroids (P = 0.364). In the analysis of all samples, the density of mature LCs was significantly higher when compared with immature LCs (P < 0.0001). The density of immature LCs was significantly higher in patients without previous complications when compared with group with complications (P = 0.028). Conclusions: These findings contribute to a better understanding of the histopathological aspects of previous complications and of treatment with corticosteroids in children with phimosis.
ABSTRACT The slow darkening of grains is sought by bean breeders because the consumers consider that darker grains demand more time for cooking. The analysis currently used takes around 90 days to ...differentiate grain color among genotypes. The objective was to evaluate the color as a function of the value of L* (lightness) of carioca beans, by natural and accelerated methods to verify equivalence between methods, validation of the methodology and identification of genotypes tolerant to the darkening. The grain darkening was compared and evaluated by natural darkening method under shelf conditions, in days storage, and accelerated darkening method under ultraviolet light, in hours. The natural darkening time of 90 days was statistically equal to 24 hours of accelerated darkening, and the difference among the genotypes could be obtained in a shorter time, indicating a correspondence in the methods. The accelerated darkening method can be used to shorten the analysis time in the routine of breeding programs.
RESUMO O escurecimento lento de grãos é almejado por melhoristas de feijoeiro porque o consumidor considera que grãos mais escuros apresentarão maior tempo para cocção. A análise empregada atualmente leva ao redor de 90 dias para diferenciação da cor do grão entre os genótipos. Objetivou-se avaliar a cor em função do valor de L* (luminosidade) de feijoeiro do tipo carioca pelos métodos natural e acelerado para verificar equivalência entre os métodos, validação da metodologia e identificação de genótipos tolerantes ao escurecimento. O escurecimento de grãos foi comparado e avaliado pelo método de escurecimento natural em condições de prateleira, em dias de armazenamento, e pelo método de escurecimento acelerado, em condições de luz ultravioleta, em horas. O escurecimento natural de 90 dias foi estatisticamente igual a 24 horas de escurecimento acelerado, e a diferença entre os genótipos pôde ser obtida em menor tempo, indicando correspondência entre os métodos. O método de escurecimento acelerado pode ser utilizado para encurtar o tempo de análise na rotina dos programas de melhoramento.
Problems with the foreskin are common reasons for pediatric surgery consultations. We collected the foreskin of 40 patients for 2 years and these samples were divided into groups with and without ...previous topical corticosteroid. We carried out histochemical hematoxylin & eosin and Picrosirius analyses of the foreskin. Collagen fibers and inflammatory infiltrate was higher in samples from patients who had complications related to phimosis. Fibrosis was higher in patients who used topical corticosteroid. A histopathologic study of the foreskin may provide an additional analysis of patients undergoing circumcision and it can also improve the accuracy of surgical indication.
Abstract Galactoceles in children, either cystic or pseudotumors, are described in the literature as a rare cause of increasing breast size and can appear in males. We report a case of galactocele in ...a 15-month-old male, treated at our institution. The patient presented with a tumor in the right breast that had appeared 6 months earlier with no pain, signs of inflammation, or nipple secretion. Twelve cases found in the literature emphasize the importance of including galactocele in the differential diagnosis of benign breast masses in infancy.
A Terapia fotodinâmica (TFD) é uma conhecida opção terapêutica para diversos tipos de lesões malignas e não-malignas. A TFD age por meio de uma reação fotoquímica, formando agentes oxidativos que ...causam inúmeros danos às estruturas subcelulares e posterior morte da célula. Em grande parte dos casos são necessárias várias sessões da TFD para erradicação completa da lesão neoplásica. No entanto, vários estudos clínicos têm sido publicados mostrando recrescimento tumoral e um aumento na resistência do tumor às sessões posteriores da TFD. Neste estudo apresentamos um modelo teórico para descrever os efeitos causados por sucessivas sessões da TFD quando ocorre recrescimento tumoral. Para isso, considera-se uma distribuição de dose limiar que representa a variedade celular de um modelo teórico de tumor. A existência de uma variedade de células com diferentes doses limiares pode ser a causa de uma resposta parcial do tecido à terapia, implicando em recrescimento do tecido tumoral. Neste modelo, assume-se que esta distribuição de dose limiar é representada por uma distribuição Gaussiana modificada. Em termos de dose limiar, valores mais altos implicam em maior resistência à TFD. Se a distribuição é larga, o tratamento não é capaz de eliminar todas as células. A fração de células que sobrevivem promovem o recrescimento tumoral; no entanto, a população de células no tumor recrescido apresenta diferentes características quando comparada com a população de células do tumor original. Para avaliar a ocorrência da seleção das células mais resistentes foi realizada uma investigação sobre as alterações da resposta das células tumorais, após múltiplas sessões da terapia fotodinâmica. Para simular este tipo de procedimento foram realizadas sucessivas sessões da TFD em culturas de células de hepatocarcinoma (HepG2). Entre as sessões de TFD foi aguardado um intervalo de tempo suficiente para que as células sobreviventes se reproduzissem e formassem uma nova cultura celular. O fotossensibilizador utilizado nos experimentos foi o Photogem® e a iluminação realizada em 630 ± 10nm. Os resultados dos experimentos in vitro forneceram evidências do aumento da resistência das células neoplásicas da linhagem HepG2 após sucessivas aplicações da TFD. Este aumento é previsto pelo modelo teórico e pode estar relacionado com a variação das características da população celular, que é expressa neste modelo pela distribuição de dose limiar. No entanto, o aumento da resistência da população celular à TFD previsto pelo modelo teórico é mais acentuado do que o aumento observado no experimento com culturas celulares, portanto, mais estudos serão necessários para adequar o modelo à condição real. Com base na variabilidade das células tumorais, as simulações demonstraram que a dose de luz insuficiente pode induzir um aumento da resistência do tumor às posteriores sessões da TFD. Este modelo poderá ser utilizado para avaliar qual o tipo de distribuição de dose limiar pode-se encontrar em tumores reais e quais as conseqüências causadas pela atenuação da luz em função da profundidade do tumor. A idéia apresentada neste estudo motivará novos estudos para identificar a importância da distribuição de dose limiar em tumores submetidos à TFD.
Photodynamic therapy is a well known treatment option for many types of malignant and nonmalignant lesions. This technique causes cell damage through a photochemical reaction, generating oxidative agents responsible for tumor cell killing. In several cases, multiple PDT-sessions are needed to promote cancer eradication. However, several clinical studies have been reported an increase of tumor resistance after a PDT-session. We present a theoretical model to describe the effects caused by successive PDT sessions based on the consequences of a partial response caused by the threshold dose distribution within the hypothetical tumor. In this model, we assume that this threshold dose distribution is represented by a Modified Gaussian Distribution. In terms of threshold dose, higher values imply higher resistance to PDT. If the distribution is broad, the treatment cannot result in the killing of all tumor cells. The survival cell fraction promotes a tumor regrowth with different characteristics compared to the original cell population. We applied the model in a hypothetical tumor to exemplify the idea here presented. The qualitative analysis extracted from our theoretical model shows a behavior that is in agreement with results obtained in our results from in vitro experiments and several clinical observations. To investigate the occurrence of a selection of higher threshold dose cells, an experiment that evaluated the response of tumor cells after multiple sessions of photodynamic therapy was carried out. To simulate this procedure, successive sessions of PDT in hepatocellular carcinoma cells (HepG2) were performed. A time interval between PDT-sessions was respected to allow surviving cells division, resulting in a new cell culture. The photosensitizer used in the experiments was Photogem® and a 630 ± 10nm irradiation was performed. The result of in vitro experiments provided evidence of increasing resistance of HepG2 cells after successive PDT-sessions. This increase is predicted by the theoretical model and may be related to variations in the tumor cell population, which is expressed by the variation of the distribution of threshold dose, according to the model. However, the increased PDT resistance of the cell population provided by the theoretical model is more pronounced than the one experimentally observed. Based on tumor cell variability, the simulations demonstrated that insufficient light dose can induce an increase in tumor resistance to further PDT sessions. This model maybe used to evaluate which type of threshold dose distribution we can find in real tumors, and the consequences caused by light attenuation observed from the illuminated surface and deeper tumor regions. This proposed model shows relative agreement to clinical literature. However, further experimental observations shall improve the model here presented. The idea presented in this study shall motivate further studies to identify the importance of cell threshold distribution in tumors submitted to PDT techniques.
Um conceito central na dosimetria da terapia fotodinâmica (TFD) é o limiar de dose (Dth do inglês threshold dose). O Dth é definido como a quantidade mínima de luz que deve ser absorvida pelas ...moléculas de fotossensibilizador (FS) dentro das células malignas a serem tratadas para que ocorra a morte celular por necrose ou apoptose. Os resultados do estudo da captação de FS por células Hep G2 demonstraram que uma população celular de linhagem, cultivada em monocamada, apresenta captação de Photogem (PG) heterogênea, ou seja, algumas células têm maior capacidade de captar moléculas de PG, outras células captam o PG em menor quantidade. A captação heterogênea de PG pode ser a causa para fenômenos de seleção de células mais resistentes à TFD. É razoável supor que as subpopulações celulares de uma mesma massa de células malignas possam apresentar diferentes valores de Dth. Definiu-se uma função de distribuição das doses limiares (g()) como uma função de distribuição gaussiana, e para a sua parametrização desenvolveu-se um método para o cultivo in vitro de culturas tridimensionais (culturas 3D), mais fidedignas ao tecido neoplásico maligno que as culturas tradicionais. Utilizando-se o método de levitação magnética (MLM) e o método de impressão magnética (MIM) para a dosimetria da TFD, foi possível parametrizar a g(Dth), investigar a resistência celular à TFD. O MLM demonstrou ser facilmente manuseável na rotina experimental, e consistente para o teste in vitro de novos FS. Comparando-se as culturas MDA-MB-231e Hep G2, obtidas por MLM por mais de 185 horas de levitação, pode-se concluir que as células Hep G2 formaram uma estrutura celular mais densa e que ofereceu mais resistência ao dano causado pela TFD. É notável como as células Hep G2 retomaram o crescimento, e restabeleceram-se em cultura de modo semelhante ao grupo controle, por meio da reconstrução da matriz extracelular (MEC). Enquanto isso, no caso das células MDA-MB-231, a integridade da cultura não foi restabelecida após a aplicação da TFD, formando uma cultura fragmentada. O dano mais evidente, para ambas as culturas, foi observado nas margens dos tumores, evidenciando que os componentes importantes da reação fotodinâmica, como o fotossensibilizador, a luz e o oxigênio, estavam presentes em maiores quantidades na superfície da cultura, em comparação às outras regiões tumorais. Os resultados obtidos demonstram que para o Photogem (PG) é necessária uma fluência de luz da ordem de 40 J.cm-2, para que o efeito fotodinâmico promova morte celular nas culturas 3D obtidas pelo MLM. O resultado da combinação de dois tipos celulares, o maligno (MDA-MB-231) e o sadio (HPF), demonstrou que o efeito fotodinâmico é efetivo quando se tem controle adequado da entrega dos agentes da terapia, independentemente do tipo celular. Algumas células sobreviveram ao tratamento, e existe um forte indicativo de que a presença de fibroblastos HPF esteja relacionada a esta pequena parcela de células que receberam dose de luz inferior ao seu Dth. Os resultados demonstraram que quanto maior a fluência de luz, menor é o IC50 do PG. Para a fluência de luz de 60 J.cm-1 obteve-se um IC50 de 3,1 μg.mL-1, e para a fluência de luz de 30 J.cm-1 obteve-se um IC50 de 18,0 μg.mL-1.
Photodynamic therapy (PDT) dosimetry includes a central concept: the threshold dose (Dth), which is the minimum amount of light to be absorbed by the photosensitizer (PS) molecules to induce irreversible oxidative damage, and hence to cause cell death by necrosis or apoptosis. It is reasonable to assume that cells subpopulation in one individual tumor cell mass may present different Dth values, which implies the existence of a distribution of Dth values defined by a Gauss distribution function (g(Dth)). Developing methods for more realistic tissue emulation with in vitro cultures, such as three-dimensional (3D) cultures, have been encouraged aiming to avoid the above-mentioned dissimilarities. A 3D cell culture is preferable compared to monolayer cell cultures, because it provides cell-cell and cell-substrate interaction, and makes evaluating a culture and its volumetric dimension (which resembles the tumor morphology) possible. This study also includes the development of a 3D model, using the magnetic levitation method (MLM) and the magnetic printing method (MIM, from Portuguese método de impressão magnetic) for PDT dosimetry. The aim is to define parameters for g(Dth), to investigate cell resistance to PDT, and to achieve a fast and consistent method for new PS in vitro tests. By comparing cultures from the different cell types studied, the ones obtained by MLM for more than 185 hours were found to present a denser cellular structure, which provided improved resistance to PDT-induced damage. Hep G2 cells showed a remarkable behavior by being able to recover culture integrity; meanwhile MDA-MB-231 cells were not able to do so. The most evident damage, for both cell culture types, was observed on tumor margins, showing that the main elements to play a role in PDT reaction (PS, light and oxygen) were present in larger quantities, at culture surface, when compared with internal regions of the cell culture. Results obtained for PG show that a light fluence of about 40 J.cm-2 is required to induce cell death by photodynamic effect on 3D cells obtained by MLM. A combination of two different cell types - a tumor cell line and a healthy cell line - shows clearly that there is no difference for the photodynamic outcome if one holds enough control on the therapeutic parameters. The results presented in this thesis show that even a strain cell population, grown in a monolayer cell culture, results in a non-homogeneous PG uptake, which means that part of the cells seems to be able to collect PG molecules more efficiently than other cells. This difference in collection among cells may be the cause of a selection of cells that are more \"resistant\" to PDT. There were cells that survived treatment, and the presence of HPF fibroblasts might be the cause of these surviving cells, since their Dth might have not been achieved. The results showed that as higher is the light fluence, as lower is the IC50 of PG. The fluence of 60 and 30 J.cm-1 resulted in IC50 of 3.1 and 18.0 μg.mL-1, respectively.
The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of ...non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1β/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF β1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days.
Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.
•Fluoride altered cytokine-chemokines in the kidney.•F modified the tissular miRNAs profile related to renal inflammation.•Renal EMT and cancer pathways were induced after exposure to fluoride.
With the growing demand for food production worldwide, natural landscapes are increasingly being replaced by agricultural areas, which directly affects biodiversity and local ecosystem services. ...Agroforestry systems, which are the intentional integration of trees and shrubs into crop and animal farming systems, are a more sustainable production approach that has been increasing in several forested areas around the globe. Here, we examine the trends of agroforestry in the Brazilian Legal Amazon and estimate the associated value of ecosystem services mediated by pollinators. Using data from 2006 and 2017, we detected an increase in agroforestry activity in the Amazon, both in the number (3.27%) and in the area (23.18%) of establishments. Crop production in forested areas increased by 45.61% in the same period, and the main products cultivated in both years were native products from the Amazon, such as açaí , Brazil nut and babassu. Although the crop data are from forested areas, all the five crops with the highest production value are associated with agroforestry in the Amazon. Pollination services also increased during the same period from US$73.3 to US$156.7 million (113.76%). In 2006, the value of pollination services corresponded to 44% of the total crop production, and it jumped to 64.43% in 2017. Bees and beetles were the two main groups of pollinators quoted for the analysed crops. Our estimates show the important contribution of pollinators to crop production in the Amazon forest. However, a growing loss of Amazon forest has been observed, and this can jeopardize pollinators and have detrimental consequences on food production in the near future. Public policies are urgently needed to encourage crop production in harmony with natural areas, combining the protection of forests and pollinators with food production.
•The number and area of Amazon agroforestry systems increased from 2006 to 2017.•Palms have the highest crop production value in the Amazon forested areas.•Most of the analysed crops (73%) were had some dependence on pollinators.•Pollination services corresponded to 64.36% of the total production value in 2017.•Bees and beetles are the main crop pollinators in Amazon agroforestry systems.
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