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O diabetes mellitus tipo 1 é a segunda doença crônica e distúrbio endócrino-metabólico mais frequente na infância. Tem sido cada vez mais diagnosticado nas crianças, devido ao amplo espectro de rastreamento. Estima-se uma prevalência entre 1,1 a 1,4/ 1000 crianças menores de 15 anos. Tal situação pode afetar a qualidade de vida das crianças, familiares. Os fatores ambientais podem influenciar nesse fator. A idade, sexo, tipo de seguro a saúde têm associação estatisticamente significativa com a melhor qualidade de vida. A educação materna, estado civil materno, o regime de insulina e realização de controle glicêmico modificam a qualidade de vida materno- infantil. A idade média de início da doença é de 8,8 anos, estreando com cetoacidose diabética. A hemoglobina glicosilada (HbA1c) é o outro ponto de alteração. Altos níveis são obtidos tanto na adesão quanto na qualidade de vida. A qualidade de vida está associada ao uso de um sistema de monitoramento contínuo de glicose, para se evitar hipoglicemias menos graves e complicações renais. Diante de tal situação, objetiva-se a realizar uma revisão de literatura sobre o tema para avaliar o impacto da DM1 e suas repercussões na vida da criança. Assim, percebe-se que tem impactado de forma direta na vida tanto da família, quanto da criança, principalmente na aceitação do novo estilo de vida. Logo, estudos são fundamentais para análise dos benefícios de se melhorar a qualidade de vida com apoio da equipe multiprofissional. Type 1 diabetes mellitus is the second most common chronic disease and endocrine-metabolic disorder in childhood. It has been increasingly diagnosed in children, due to the broad spectrum of screening. It is estimated a prevalence between 1.1 to 1.4/1000 children under 15 years of age. Such a situation can affect the quality of life of children and family members. Environmental factors can influence this factor. Age, sex, type of health insurance have a statistically significant association with better quality of life. Maternal education, maternal marital status, insulin regimen and glycemic control modify maternal-infant quality of life. The mean age of onset of the disease is 8.8 years, debuting with diabetic ketoacidosis. Glycosylated hemoglobin (HbA1c) is the other point of change. High levels are obtained in both adherence and quality of life. Quality of life is associated with the use of a continuous glucose monitoring system to avoid less severe hypoglycemia and renal complications. Faced with such a situation, the objective is to carry out a literature review on the subject to assess the impact of DM1 and its repercussions on the child's life. Thus, it can be seen that it has had a direct impact on the lives of both the family and the child, especially in the acceptance of the new lifestyle. Therefore, studies are essential to analyze the benefits of improving the quality of life with the support of the multidisciplinary team. La diabetes mellitus tipo 1 es la segunda enfermedad crónica y trastorno endocrino-metabólico más frecuente en la infancia. Se ha diagnosticado cada vez más en niños, debido al amplio espectro de detección. Se estima una prevalencia entre 1,1 a 1,4/1000 menores de 15 años. Tal situación puede afectar la calidad de vida de los niños y miembros de la familia. Los factores ambientales pueden influir en este factor. La edad, el sexo, el tipo de seguro de salud tienen una asociación estadísticamente significativa con una mejor calidad de vida. La educación materna, el estado civil materno, el régimen de insulina y el control glucémico modifican la calidad de vida materno-infantil. La edad media de aparición de la enfermedad es de 8,8 años, debutando con cetoacidosis diabética. La hemoglobina glicosilada (HbA1c) es el otro punto de cambio. Se obtienen altos niveles tanto en adherencia como en calidad de vida. La calidad de vida se asocia al uso de un sistema de monitorización continua de glucosa para evitar hipoglucemias menos graves y complicaciones renales. Ante tal situación, el objetivo es realizar una revisión bibliográfica sobre el tema para evaluar el impacto de la DM1 y sus repercusiones en la vida del niño. Así, se puede apreciar que ha tenido un impacto directo en la vida tanto de la familia como del niño, especialmente en la aceptación del nuevo estilo de vida. Por lo tanto, los estudios son esenciales para analizar los beneficios de mejorar la calidad de vida con el apoyo del equipo multidisciplinario.

DNA-damaging agents are widely used in cancer therapy; however, their use is limited by dose-related toxicities, as well as the development of drug resistance. Drug discovery is essential to overcome these limitations and offer novel therapeutic options. In a previous study by our research group, pradimicin-IRD—a new polycyclic antibiotic produced by the actinobacteria Amycolatopsis sp.—displayed antimicrobial and potential anticancer activities. In the present study, cytotoxic activity was further confirmed in a panel of five colon cancer, including those with mutation in TP53 and KRAS , the most common ones observed in cancer colon patients. While all tested colon cancer cells were sensitive to pradimicin-IRD treatment with IC 50 in micromolar range, non-tumor fibroblasts were significantly less sensitive (p 1 and G 0 /G 1 phases of the cell cycle. Additionally, mass spectrometry analysis indicated that pradimicin-IRD interacted with the DNA double strand. In summary, pradimicin-IRD exhibits multiple antineoplastic activities—including DNA damage, cell cycle arrest, reduction of clonal growth and apoptosis—in the HCT 116 cell line. Furthermore, pradimicin-IRD displays a TP53-independent regulation of p21 expression in HCT 116 TP53 −/− , HT-29, SW480, and Caco-2 cells. This exploratory study identified novel targets for pradimicin-IRD and provided insights for its potential anticancer activity as a DNA-damaging agent.

Twelve chlorogenic acid derivatives and two flavones were isolated from Moquiniastrum floribundum (Asteraceae, other name: Gochnatia floribunda). Compounds were evaluated in relation to their cytotoxicity and antiradical properties. Cytotoxicity was not observed for compounds, however, chlorogenic acid derivatives showed antiradical activity and were more active than the Trolox standard. Quinic acid esterified with caffeoyl group at C-4 position showed higher antiradical activity compared to acylation at C-3 or C-5 positions. Additional caffeoyl groups esterified in quinic acid increase the antiradical activity observed for 4-caffeoylquinic acid. Excepted to 3,4-dicaffeoylquinic acid methyl ester, methyl ester derivatives show higher capacity of trapping radicals than their respective acids. Consequently, the presence of caffeoyl group at C-4 position of quinic acid is suggested as fundamental to obtain the highest antiradical activity.

We proposed a new residual to be used in linear and nonlinear beta regressions. Unlike the residuals that had already been proposed, the derivation of the new residual takes into account not only information relative to the estimation of the mean submodel but also takes into account information obtained from the precision submodel. This is an advantage of the residual we introduced. Additionally, the new residual is computationally less intensive than the weighted residual. Recall that the computation of the latter involves an n×n matrix, where n is the sample size. Obviously, that can be a problem when the sample size is very large. In contrast, our residual does not suffer from that. It can be easily computed even in large samples. Finally, our residual proved to be able to identify atypical observations as well as the weighted residual. We also propose new thresholds for residual plots and a scheme for the choice of starting values to be used in maximum likelihood point estimation in the class of nonlinear beta regression models. We report Monte Carlo simulation results on the behavior of different residuals. We also present and discuss two empirical applications; one uses the proportion of killed grasshoppers in an assay on the grasshopper Melanopus sanguinipes with the insecticide carbofuran and the synergist piperonyl butoxide, which enhances the toxicity of the insecticide, and the other uses simulated data. The results favor the new methodology we introduce.

Amphidinolides are cytotoxic macrolides produced by symbiotic unicellular microalgae of the genus Amphidinium. Here we describe the identification of four related molecules belonging to this macrolide family isolated from the invertebrate Stragulum bicolor. The new molecules, named amphidinolide PX1-PX3 and stragulin A (1&ndash, 4), show an unprecedented carbon skeleton whose complete stereochemistry has been determined by spectroscopic and computational methods. Differences in the structures of these molecules modulate their biological activity in a panel of tumor cell lines, but the opened derivative stragulin (4) shows a very potent and specific cytotoxic activity (IC50 0.18 &micro, M) against the aggressive human melanoma cell A2058.

Three new plakortides, 7,8-dihydroplakortide E (1), 2, and 10, along with known natural products 3, 4, spongosoritin A (5), 6-8, and plakortide P (9), were isolated from Brazilian specimens of Plakortis angulospiculatus. Compounds 2, 3, 5, and 7-9 displayed cytotoxic activities with IC50 values ranging from 0.2 to 10 μM. Compounds that contained a dihydrofuran ring were generally less active and displayed time dependence in their activity. The activities of compounds 2 and 7-9, carboxylic acids bearing a common six-membered endoperoxide, were higher overall than for compounds 3 and 5. The modes underlying the cytotoxic actions of plakortides 2, 3, 5, 7, and 9 were further investigated using HCT-116 cells. While dihydrofurans 3 and 5 induce a G0/G1 arrest, six-membered peroxides 2, 7, and 9 delivered a G2/M arrest and an accumulation of mitotic figures, indicating a distinctly different antimitotic response. Confocal analysis indicated that microtubules were not altered after treatment with 2, 7, or 9, therein suggesting that the mitotic arrest may be unrelated to cytoskeletal targets. Overall, we find that two related classes of natural products obtained from the same extract offer cytostatic activity, yet they do so through discrete pathways.

Natural products discovered by using agnostic approaches, unlike rationally designed leads or those obtained through high-throughput screening, offer the ability to reveal new biological pathways and, hence, serve as an important vehicle to unveil new avenues in drug discovery. The ritterazine-cephalostatin family of natural products displays robust and potent antitumor activities, with sub-nanomolar growth inhibition against multiple cell lines and potent activity in xenograft models. Herein, we used comparative cellular and molecular biological methods to uncover the ritterazine-cephalostatin cytotoxic mode of action (MOA) in human tumor cells. Our findings indicated that, whereas ritterostatin GN 1N , a cephalostatin-ritterazine hybrid, binds to multiple HSP70s, its cellular trafficking confines activity to the endoplasmic reticulum (ER)-based HSP70 isoform, GRP78. This targeting results in activation of the unfolding protein response (UPR) and subsequent apoptotic cell death.

Benthic cnidarians are colonial marine animals that host a rich population of associated and symbiotic microorganisms. In a recent paper we described for the first time the isolation of amphidinolide P (1) from the Brazilian octocoral Stragulum bicolor. Amphidinolides and similar compounds had been previously reported only from dinoflagellates of the genus Amphidinium; thus the presence of 1 in the invertebrate opens intriguing questions on the role and occurrence of these molecules in marine ecosystems. Here we report the identification of four further amphidinolides from the same soft coral, including the known amphidinolide T1 (2) and the new analogues here named amphidinolides C4 (3), B8 (4), and B9 (5). The chemical structures have been elucidated mainly by extensive study of spectroscopic data. Cytotoxic activities of 3 and 4 were evaluated against the colon adenocarcinoma cell line HCT-116.

We proposed a new residual to be used in linear and nonlinear beta regressions. Unlike the residuals that had already been proposed, the derivation of the new residual takes into account not only information relative to the estimation of the mean submodel but also takes into account information obtained from the precision submodel. This is an advantage of the residual we introduced. Additionally, the new residual is computationally less intensive than the weighted residual. Recall that the computation of the latter involves an n×n matrix, where n is the sample size. Obviously, that can be a problem when the sample size is very large. In contrast, our residual does not suffer from that. It can be easily computed even in large samples. Finally, our residual proved to be able to identify atypical observations as well as the weighted residual. We also propose new thresholds for residual plots and a scheme for the choice of starting values to be used in maximum likelihood point estimation in the class of nonlinear beta regression models. We report Monte Carlo simulation results on the behavior of different residuals. We also present and discuss two empirical applications; one uses the proportion of killed grasshoppers in an assay on the grasshopper Melanopus sanguinipes with the insecticide carbofuran and the synergist piperonyl butoxide, which enhances the toxicity of the insecticide, and the other uses simulated data. The results favor the new methodology we introduce.

Dinoflagellates are an important source of unique bioactive secondary metabolites. Symbiotic species, commonly named zooxanthellae, transfer most of their photosynthetically fixed carbon to their host. The mutualistic relationship provides the organic metabolites used for energy production but there are very few reports of the role of the dinoflagellates in the production of secondary metabolites in the symbiotic association. Corals and other related cnidarians are the most well-known animals containing symbiotic dinoflagellates. In the present paper we describe the isolation of amphidinolide P (1) from the octocoral Stragulum bicolor and its prey, the nudibranch Marionia limceana, collected off the coasts of Fortaleza (CearA, Brazil). The coral extracts also contained 3-O-methyl derivative (2) of amphidinolide P, together with minor compounds still under investigation. Amphidinolides have been so far reported only in laboratory cultures of Amphidinium sp., thus compounds 1 and 2 represents the first identification of these polyketides in invertebrates. The finding proves the possibility to isolate amphidinolides from a natural symbiosis, enabling further biological and biotechnological studies. (C) 2015 Sociedade Brasileira de Earmacognosia. Published by Elsevier Editora Ltda. All rights reserved.

Lippia microphylla Cham. (Verbanaceae) is an endemic underexploited Brazilian vegetal. This work reviewed the biological potentialities of Lippia microphylla, emphasizing the properties of essential oils (EOs) and analyzed scientific indicators about genus Lippia and L. microphylla. Databases from 1948 to the present were searched and a software (Vantage Point 7.1) associated with Derwent Innovation Index was used to identify the indicators of the genus Lippia, and biological activities and compounds in the L. macrophylla species. Ethnopharmacological records report use of L. microphylla leaves to treat gastrointestinal disorders, influenza, bronchitis, cough, nasal congestion and sinusitis during vaporization, whose aromatic volatile oils are rich in monoterpenes, especially cineole, terpineol and thymol. Other EOs have larvicidal activity on Aedes aegypti larvae, and antifungal, antibacterial and cytotoxic and antitumor action on human and murine cancer cells. Brazil is the country with more articles about Lippia species, but it deposited only 9 patents since 1993. Most of the publications about L. microphylla are concentrated in food and chemical sciences. This bioprospection helps to choice areas of interest for capital investment and to give support for Brazilian Institutions to establish cooperation and improve technological impact at the point of view of creation and innovation. [J Intercult Ethnopharmacol 2015; 4(3.000): 256-263]

A synthetic method to obtain α- and β-pyran naphthoquinones 10 and 11 with a hydroxyl substituent on the aromatic ring was developed. Two series of α- and β-pyran naphthoquinones were obtained from the 8-hydroxy-lawsone, and their anticancer properties were evaluated against four tumor cell lines. In general, the new compounds displayed good activity, possibly indicating that these compounds have increased pro-oxidant capacity. The 9-hydroxy-α-lapachone and 7-hydroxy-β-lapachone analogues of the natural products α-lapachone and β-lapachone were successfully produced by this methodology.