Aplasia cutis congénita con encefalocele: a propósito de un caso clínico

La aplasia cutis es una rara alteración congénita caracterizada por la ausencia de piel, pudiendo llegar a estructuras más profundas: músculo, hueso y duramadre, como en el presente caso. Se localiza más frecuentemente en el cuero cabelludo, donde se asocia a un defecto óseo en el 20% de los casos. Recién nacido de sexo femenino, término, adecuado para la edad gestacional, vigoroso. Con diagnóstico prenatal a las 36 semanas de edad gestacional de encefalocele. Constatándose al nacimiento microcefalia, hipoplasia ósea y cutánea, encefalocele en línea media de cráneo. Se realizó manejo por equipo multidisciplinario, se practicaron varias intervenciones quirúrgicas, con buena evolución.

Summary: Aplasia Cutis is a rare congenital condition, defined by the absence of skin in a particular body region, it can also compromise muscle, bone and dura mater as shown in this case. It is mostly located on the scalp, where it is associated with a bone defect in 20% of cases. We will discuss the case of a female newborn, term gestation, vigorous at birth, with prenatal diagnosis of encephalocele at 36 weeks of gestational age. We observed microcephaly, bone and skin hypoplasia, encephalocele in the midline of the skull at birth. Several surgical interventions were carried out and the follow-up was made by a multidisciplinary team, with good evolution.

A Aplasia Cútis é uma alteração congênita rara, caracterizada pela ausência de pele, podendo atingir estruturas mais profundas: muscular, óssea e dura-máter, como neste caso. Localiza-se mais frequentemente no couro cabeludo, onde está associada a um defeito ósseo em 20% dos casos. É apresentado caso de recém-nascida do sexo feminino, a termo, adequada para idade gestacional, vigorosa. Com diagnóstico pré-natal às 36 semanas de idade gestacional de Encefalocele. Microcefalia, hipoplasia óssea e cutânea e encefalocele na linha média do crânio foram confirmadas ao nascimento. O manejo foi realizado por equipe multidisciplinar, diversas intervenções cirúrgicas, com boa evolução.

Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis.

BACKGROUND: Cancer is a complex, multifactorial disease, and a major public health problem, as it is a leading cause of morbidity and mortality worldwide. Although treatments have significantly improved, still more effective drugs are searched. One source for these drugs is natural products (NPs). One NP that has shown anticancer activity is Limonene. However, the mechanisms of limonene's antiproliferative, anticancer and antineoplastic activity are not fully understood. OBJECTIVE: The objective of this study is to undertake a systematic review and meta-analysis of the literature on this subject. METHODS: A comprehensive literature search was performed using the Scopus, MEDLINE-PubMed, Web of Science, and Science Direct databases using the keywords: "limonene", "cancer", "neoplasm", and "tumor". The inclusion criteria were: in vivo and in vitro studies on the use of limonene in cancer published in English, Portuguese and Spanish until December 2019. Review articles, meta-analyses, abstracts, conference papers, editorials/ letters and case reports were excluded. RESULTS: The search identified 3568 articles, of which, 126 were selected for full reading, with 11 papers meeting the review criteria. Six more papers were added from the references of the initial 11 texts, giving a total of 17 papers. There was a high level of agreement in inclusion/exclusion (Kappa index > 80%). The risk of bias in the texts was shown to be high. CONCLUSION: The meta-analysis suggests that limonene acts mainly on tumor regression induced apoptosis and is a promising natural product for use in the treatment of several types of cancer.

Terpenes with Antitumor Activity: A Patent Review.

BACKGROUND: Cancer is a major public health concern, and is one of the leading causes of death globally. Surgical removal, chemotherapy or hormonal therapy, radiation therapy, or a combination of them are treatment for cancer, many of which are ineffective or have serious side effects. In view of this, there is a search for new, more effective alternatives for cancer prevention and treatment. One possible source of compounds are natural products; among them, terpenes, a large class of organic compounds, have shown promise due to their anti-inflammatory, anti-tumorigenic, and hypolipidemic properties, among others recorded in the literature. OBJECTIVE: The study aims to use a patent review to evaluate the development and use of terpenes, or formulations containing terpenes, in new therapeutic options for the treatment of various types of cancer. METHODS: This patent review was carried out using the specialized patent databases of WIPO and Espacenet. The selection of patents was based on the following inclusion criteria which included pre-clinical and/or clinical trials, and demonstrated anti-tumor effects. RESULTS: Eight patents were identified, six from China, and two from Japan. In this review, all patents confirmed having good antitumor activity for many types of cancer cells. In addition, the inventors indicate more studies pre-clinical and clinical trials giving greater clarity and accurate reflection of the activity of the products studied. CONCLUSION: Natural products are an important source of compounds for use in the fight against cancer that can act synergistically, and help in the treatment of cancer.

Ethanolic extract of Croton blanchetianus Ball induces mitochondrial defects in Leishmania amazonensis promastigotes.

Leishmaniasis is a neglected disease caused by Leishmania. Chemotherapy remains the mainstay for leishmaniasis control; however, available drugs fail to provide a parasitological cure, and are associated with high toxicity. Natural products are promising leads for the development of novel chemotherapeutics against leishmaniasis. This work investigated the leishmanicidal properties of ethanolic extract of Croton blanchetianus (EECb) on Leishmania infantum and Leishmania amazonensis, and found that EECb, rich in terpenic compounds, was active against promastigote and amastigote forms of both Leishmania species. Leishmania infantum promastigotes and amastigotes presented IC50 values of 208.6 and 8.8 µg/mL, respectively, whereas Leishmania amazonensis promastigotes and amastigotes presented IC50 values of 73.6 and 3.1 µg/mL, respectively. Promastigotes exposed to EECb (100 µg/mL) had their body cellular volume reduced and altered to a round shape, and the flagellum was duplicated, suggesting that EECb may interfere with the process of cytokinesis, which could be the cause of the decline in the parasite multiplication rate. Regarding possible EECb targets, a marked depolarization of the mitochondrial membrane potential was observed. No cytotoxic effects of EECb were observed in murine macrophages at concentrations below 60 µg/mL, and the CC50 obtained was 83.8 µg/mL. Thus, the present results indicated that EECb had effective and selective effects against Leishmania infantum and Leishmania amazonensis, and that these effects appeared to be mediated by mitochondrial dysfunction.

The Patenting and Technological Trends in Candidiasis Treatment: A Systematic Review (2014-2018).

BACKGROUND: In the last few decades, mycoses caused by opportunistic fungi namely Candida species has gained significant attention. Such infections are very common and present high mortality rates, especially in immunocompromised patients. Currently, a limited number of antifungal drugs are available for the treatment of these infections and are also often related to severe adverse side effects. Therefore, new drugs and innovative technologies for the treatment of this infection are necessary. OBJECTIVE: The aim of this study was to evaluate the development of new drugs, formulations, as well as patents for the treatment of infections caused by Candida spp. METHODS: The present patent review was carried out through a specialized search database Espacenet. The patent selection was based on the following inclusion criteria: Recent patents published in English or Spanish containing candidiasis as the keyword in the title, abstract or full text. This survey was conducted in October and November 2018. RESULTS: As a result of that, 22 patents were selected to the final selection, the most common routes of application were oral (n = 6), vaginal (n = 6), topical (n = 5) and others (n = 5). This fact is related to the clinical manifestations of candidiasis. CONCLUSION: Through this review, it was possible to identify significant improvements and advances in the area of antifungal therapeutic innovation research. In addition, we demonstrated the growing interest of academic and industrial groups in pharmaceutical development and novel formulations for the treatment of candidiasis. New therapeutic options can contribute to improve the quality of patient's life, prevent infections and promote the search for an innovative and effective treatment of Candida infections.

Report from the BfR expert hearing on practicability of hormonal measurements: recommendations for experimental design of toxicological studies with integrated hormonal end points.

This publication summarizes discussions that were held during an international expert hearing organized by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany, in October 2017. The expert hearing was dedicated to providing practical guidance for the measurement of circulating hormones in regulatory toxicology studies. Adequate measurements of circulating hormones have become more important given the regulatory requirement to assess the potential for endocrine disrupting properties for all substances covered by the plant protection products and biocidal products regulations in the European Union (EU). The main focus was the hypothalamus-pituitary-thyroid axis (HPT) and the hypothalamus-pituitary-gonadal axis (HPG). Insulin, insulin-like growth factor 1 (IGF-1), parathyroid hormone (PTH) and vitamins A and D were also discussed. During the hearing, the experts agreed on specific recommendations for design, conduct and evaluation of acceptability of studies measuring thyroid hormones, thyroid stimulating hormone and reproductive hormones as well as provided some recommendations for insulin and IGF-1. Experts concluded that hormonal measurements as part of the test guidelines (TGs) of the Organisation for Economic Co-operation and Development (OECD) were necessary on the condition that quality criteria to guarantee reliability and reproducibility of measurements are adhered to. Inclusion of the female reproductive hormones in OECD TGs was not recommended unless the design of the study was modified to appropriately measure hormone concentrations. The current report aims at promoting standardization of the experimental designs of hormonal assays to allow their integration in OECD TGs and highlights research needs for better identification of endocrine disruptors using hormone measurements.

Prevalence of HIV and associated factors among visceral leishmaniasis cases in an endemic area of Northeast Brazil.

INTRODUCTION: Cases of visceral leishmaniasis (VL) and HIV co-infection have increased worldwide. We investigated the prevalence of HIV and associated factors among VL patients in Sergipe state, Brazil. METHODS: We conducted a population-based study of all cases of VL and HIV reported in Sergipe from 1999 to 2015. RESULTS: We studied a total of 917 patients; 41 (4.5%) co-infection cases were detected. VL-HIV co-infected patients were more likely to have weight loss, cough, treatment failure or loss to follow-up and death. CONCLUSIONS: The prevalence of VL-HIV co-infection was high and co-infected patients were more likely to have adverse outcomes.

Prevalence of HIV and associated factors among visceral leishmaniasis cases in an endemic area of Northeast Brazil

Abstract INTRODUCTION Cases of visceral leishmaniasis (VL) and HIV co-infection have increased worldwide. We investigated the prevalence of HIV and associated factors among VL patients in Sergipe state, Brazil. METHODS We conducted a population-based study of all cases of VL and HIV reported in Sergipe from 1999 to 2015. RESULTS We studied a total of 917 patients; 41 (4.5%) co-infection cases were detected. VL-HIV co-infected patients were more likely to have weight loss, cough, treatment failure or loss to follow-up and death. CONCLUSIONS The prevalence of VL-HIV co-infection was high and co-infected patients were more likely to have adverse outcomes.

New therapeutic patents used for the treatment of leprosy: a review.

Leprosy is a granulomatous disease, infectious and transmissible, which affects the skin and peripheral nerves, having Mycobacterium leprae as causative agent. The manifestation of this disease causes cutaneous lesions, peripheral neuropathies and, in more extreme cases, may generate deformities and disabilities in affected individuals. Patents were identified using the descriptor 'leprosy' and code A61K of the international patent classification, which indicates only products that meet human needs. The analysis was made using the WIPO, ESPACENET and USPTO databases, until the month of September 2016. Through this review, we found a variety of in vitro, pre-clinical and clinical studies relating to the treatment of leprosy with different types of compounds and forms of administration. New treatment proposals should include pain reduction capabilities, prevention or limitation of the appearance of cutaneous lesions, as well as prevention of the progression of the disease to more severe stages that may lead to loss of function or potentiate the individual's immune response to the M. leprae bacillus in order to prevent bacterial spread. We concluded that any patents developed with natural products were not found in the treatment of leprosy. All the deposited products were synthetic origin, mostly tested in humans and of varied forms of administration.

Partial characterization of a novel amphibian hemoglobin as a model for graduate student investigation on peptide chemistry, mass spectrometry, and atomic force microscopy.

Graduate students in chemistry, and in biological and biomedical fields must learn the fundamentals and practices of peptide and protein chemistry as early as possible. A project-oriented approach was conducted by first-year M.Sc and Ph.D students in biological sciences. A blind glass slide containing a cellular smear and an aqueous cellular extract were offered to the students. Qualitative and quantitative cell morphological parameters were analyzed by atomic force microscopy. The fractionation of the aqueous extract was conducted by reversed-phase chromatography followed by analysis of the isolated and partially purified proteins and peptides by mass spectrometry (MS). The proteins were treated by peptidases and the obtained peptide fragments were sequenced by de novo MS/MS, together with peptides already present in the extract. The most abundant protein fractions were identified as the alpha and beta chains of hemoglobin from an amphibian of the Leptodactylus genera. Two of the peptides sequenced by the students were synthesized by the solid-phase methodology, one of those being obtained by the split-and-pool library synthesis method. Thus, the students were able to learn some advanced principles and practices of protein chemistry and bionanotechnology in a 6-weeks project-oriented approach.

The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a beta2 integrin-dependent pathway.

Magnetic nanoparticles surface-functionalized with meso-2,3-dimercaptosuccinic acid (MNPs-DMSA) constitute an innovative and promising approach for tissue- and cell-targeted delivery of therapeutic drugs in the lung. Transendothelial migration of leukocytes in the lung is a side effect of endovenous administration of MNPs-DMSA. Using cytologic and phenotypic analysis of murine bronchoalveolar lavage cells, we identified monocytes/macrophages as the main subpopulation of leukocytes involved in this process. Moreover, ultrastructural analysis revealed the presence of nanoparticles inside of numerous macrophages from bronchoalveolar lavage. MNPs-DMSA at concentrations as high as 1 x 10(15) nanoparticles/mL had no toxic effects on macrophages, as evidenced by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Notably, MNPs-DMSA up-regulated the mRNA expression of E-, L- and P-selectin and macrophage-1 antigen in the murine lung. Upregulation of these cell adhesion molecules was associated with an increased concentration of tumor necrosis factor-alpha in lung. Finally, the critical relevance of the beta(2) integrin-dependent pathway in leukocyte transmigration elicited by MNPs-DMSA was demonstrated by use of knockout mice. Our results characterize mechanisms of the pro-inflammatory effects of MNPs-DMSA in the lung, and identify beta(2) integrin-targeted interventions as promising strategies to reduce pulmonary side effects of MNPs-DMSA during biomedical applications.

Mutirões habitacionais: intervenção e pesquisa em um processo de construção de moradias populares / Building Co-operative Housing : intervention and research within the process of building affordable housin

Este trabalho tem como objetivo compreender o funcionamento de três associações comunitárias ligadas ao Movimento dos Sem Terra Leste I na construção de moradias populares em regime de mutirão e autogestão. O campo de forças que contribui para a configuração deste espaço coletivo passa pelo discurso do movimento, do qual as associações fazem parte, e sua estrutura interna, pelas formas como os técnicos do poder público vêem os mutirões e se relacionam com as associações, pelo funcionamento de outros movimentos, já que essas práticas também vão moldando a resposta estatal. Assim, buscamos compor o cenário em que se dão esses processos retomando o histórico dos movimentos sociais e dos programas de mutirões dentro da problemática estrutural da sociedade brasileira, os discursos que produziram e produzem estas práticas e os efeitos possíveis em sua dimensão micropolítica. O cotidiano de trabalho das famílias mutirantes, como se organizavam e discutiam as questões referentes à obra foram nossos principais interesses. Como resultado, apresentamos algumas discussões referentes à dinâmica das associações, à função das assembléias e das regras e o modo das tomadas de decisão tentando problematizar e apontar seus possíveis efeitos na produção de novas formas de organização. Como a pesquisa se deu intrinsecamente ligada ao trabalho como profissional, junto às associações de construção, o processo de pesquisa foi um transformar para conhecer e as descrições e problematizações que estão presentes nesta dissertação também são a sistematização do movimento constante de reflexão e atuação naquele processo de construção(AU)

This work has the objective of understanding the functioning of three community associations linked to the Movimento dos Sem Terra Leste I [East I Landelss Moviment] in the construction of cooperative housing under the regime of self-building cooperative. The field of forces that contributes to the configuration of this collective space occurs upon the movements discourse of which the associations take part and their internal structure, upon the way in which public technicians see the self-building cooperatives and their relationship with the associations, and upon the functioning of other movements, once these practices also shape governmental response. Therefore, we intend to compose the scenario in which these processes occur, revisiting the history of social movements and self-building cooperative programs within the Brazilian cultural structure, as well as the discourses which those practices produced and continue to produce, and their possible effects in their micro-politics dimension. The daily works of cooperative families, the way they organized themselves and discussed the issues regarding the building process were our main interest. As a result we present some discussion over the dynamics of community associations, the functioning of community meetings and their rules, and decision making process, whilst questioning and pointing out their possible effects on the production of new forms of organization. Since the research had been undertaken while within the professional work among self-building cooperatives, the process of researching was a transforming-to-knowing experience. The description and questioning presented in this thesis are also a systematization of the constant movement of reflection and acting upon the process of building(AU)