A partial agonist of PPARγ prevents paclitaxel-induced peripheral neuropathy in mice, by inhibiting neuroinflammation.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of paclitaxel, affecting 30-50% of patients. Increased survival and concern with patients' quality of life have encouraged the search for new tools to prevent paclitaxel-induced neuropathy. This study presents the glitazone 4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-N-phenylbenzene-sulfonamide (TZD-A1) as a partial agonist of peroxisome proliferator-activated receptor γ (PPARγ), its toxicological profile and effects on paclitaxel-induced CIPN in mice. EXPERIMENTAL APPROACH: Interactions of TZD-A1 with PPARγ were analysed using in silico docking and in vitro reporter gene assays. Pharmacokinetics and toxicity were evaluated using in silico, in vitro and in vivo (C57Bl/6 mice) analyses. Effects of TZD-A1 on CIPN were investigated in paclitaxel-injected mice. Axonal and dorsal root ganglion damage, mitochondrial complex activity and cytokine levels, brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ, were also measured. KEY RESULTS: Docking analysis predicted TZD-A1 interactions with PPARγ compatible with partial agonism, which were corroborated by in vitro reporter gene assays. Good oral bioavailability and safety profile of TZD-A1 were shown in silico, in vitro and in vivo. Paclitaxel-injected mice, concomitantly treated with TZD-A1 by i.p. or oral administration, exhibited decreased mechanical and thermal hypersensitivity, effects apparently mediated by inhibition of neuroinflammation and mitochondrial damage, through increasing Nrf2 and PPARγ levels, and up-regulating BDNF. CONCLUSION AND IMPLICATIONS: TZD-A1, a partial agonist of PPARγ, provided neuroprotection and reduced hypersensitivity induced by paclitaxel. Allied to its safety profile and good bioavailability, TZD-A1 is a promising drug candidate to prevent and treat CIPN in cancer patients.

Pôster como estratégia de aprendizado na disciplina de humanidades: contribuições para a formação do médico / Use of posters as a learning strategy in the humanities discipline: contributions to the training of medical professionals

RESUMO Introdução: Com a implementação do Sistema Único de Saúde (SUS) no Brasil, houve a reformulação do currículo médico sob uma perspectiva biopsicossocial. Para atender a essa demanda no âmbito acadêmico, o componente de humanidades médicas (HM) foi delineado para estimular reflexões interdisciplinares de cunho ético-humanista. A proposta é potencializada com o desenvolvimento de estratégias educacionais capazes de garantir a execução da disciplina no contexto das metodologias ativas. Nessa perspectiva, no ano de 2020, devido à pandemia da Covid-19, o formato tradicional de aulas presenciais necessitou de adaptação para o ensino remoto, o que suscitou a concepção e proposta de adoção de pôster criativo como recurso metodológico. Objetivo: Este estudo teve como objetivo analisar as possíveis contribuições da produção do pôster criativo para o aprendizado e processo de formação do médico, no contexto da disciplina de HM. Método: Trata-se de um estudo de abordagem qualitativa de viés exploratório-descritivo. A coleta foi realizada mediante entrevista individual semiestruturada, por meio virtual, no período de agosto a novembro de 2022. Após a transcrição, utilizou-se a análise de conteúdo temática desenvolvida por Bardin para auxiliar na análise dos relatos transcritos e na elaboração de unidades temáticas. A interpretação seguiu referenciais teóricos interdisciplinares do campo da saúde e componentes da disciplina de HM. Resultado: No total, 20 acadêmicos de uma universidade pública do estado do Pará compuseram a amostra deste estudo. A partir da organização e leitura das transcrições, emergiram as seguintes categorias: experiência no ensino presencial; experiência no ensino remoto; processo de elaboração do pôster; arte e humanidades médicas; contribuições da disciplina e do pôster. Conclusão: O uso da ferramenta pôster destaca o papel dos acadêmicos como protagonistas do seu aprendizado no recorte de HM. A maioria referiu o uso do pôster como elemento potencializador para a reflexão proposta pela disciplina, favorecido pela mediação da arte, em diversas modalidades de expressão. Houve a oportunidade de os acadêmicos exporem seus sentimentos e compreensões acerca de temáticas sensíveis à formação médica.

ABSTRACT Introduction: The implementation of the Unified Health System in Brazil led to a need to reformulate the medical curriculum from a biopsychosocial perspective. In the academic field, the Medical Humanities (MH) component has stimulated interdisciplinary reflections of an ethical-humanist nature. This exercise is streamlined with the development of educational strategies capable of guaranteeing the execution of the discipline in the context of active methodologies. From this perspective, in 2020, due to the COVID 19 pandemic, the traditional format of face-to-face classes was forced to be adapted for remote teaching, which led to the conception and proposal for adoption of posters as a methodological resource. Objective: To analyze the possible contributions of creative poster production to the physician's learning and training process, in the context of the medical humanities discipline. Method: A qualitative exploratory-descriptive approach. The data was collected through virtual, semi-structured, individual interviews, from August to November 2022. Following transcription of the interviews, thematic content analysis developed by Bardin (2011) was used to assist in the analysis of the transcribed reports and the development of thematic units. The interpretation followed interdisciplinary theoretical references in the field of health and components of the medical humanities discipline. Result: The study sample was composed of 20 academics from a public university in the state of Pará. From the organization and reading of the transcripts, the following thematic units emerged: experience in face-to-face teaching; experience in remote teaching; poster creation process; art and medical humanities; contributions from the discipline and the poster. Conclusion: The use of posters as a tool highlights the role of academics as protagonists of their own learning in the medical humanities field. The majority referred to the use of the poster as an element that enhanced the reflection proposed by the discipline, favored by the mediation of art, in different forms of expression. It offered an opportunity for academics to express their feelings and understandings about topics sensitive to medical training.

Association between sleep pattern and pharmacological treatment in children with attention deficit disorder with hyperactivity: a systematic review / Associação entre padrão de sono e tratamento farmacológico em crianças com transtorno do déficit de atenção com hiperatividade: uma revisão sistemática

Abstract Objective: The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD). Data source: A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide. Data synthesis: The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency. Conclusions: The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.

RESUMO Objetivo: Analisar a interferência do tratamento farmacológico no padrão de sono das crianças com transtorno do déficit de atenção com hiperatividade (TDAH). Fontes de dados: Busca eletrônica de alta sensibilidade nas bases de dados Cochrane Library, Medical Literature Analysis and Retrieval System Online (MEDLINE) via United States National Library of Medicine (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) via Biblioteca Virtual em Saúde (BVS), Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Web of Science, de acordo com o preconizado pelo Cochrane Handbook, de artigos que passaram pela revisão por pares segundo o Guia PRESS. Síntese dos dados: Os estudos que contemplaram o uso das drogas atomoxetina (ATX), guanfacina, metilfenidato (MPH), dasotralina, L-teanina e lisdexanfetamina mostraram eficiência na redução dos sintomas do TDAH, embora todos os medicamentos, exceto a atomoxetina, tenham afetado a qualidade do sono — reduzindo REM total, fase não REM, tempo de sono de ondas lentas e maior latência de início do sono. Conclusões: Os fármacos utilizados no tratamento do TDAH costumam cursar com repercussões negativas sobre a qualidade do sono de crianças, e o fármaco atomoxetina demonstrou menores efeitos sobre essa variável.

Xanthones and Cancer: from Natural Sources to Mechanisms of Action.

Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.

Biological and Toxicological Evaluation of N-(4methyl-phenyl)-4-methylphthalimide on Bone Cancer in Mice.

BACKGROUND: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. METHODS: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. RESULTS: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. CONCLUSION: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.

All that glitters is not gold: Panning cytotoxic natural products and derivatives with a fused tricyclic backbone by the estimation of their leadlikeness for cancer treatment.

Tricyclic compounds call the attention because of their pharmacological properties, and are considered a preferred platform for the development of drugs. Especially, in cancer treatment, these planar compounds are known for their ability to stack with DNA base pairs, acting as intercalators. In this sense, natural products (NPs) are a prodigal source of polycyclic compounds, comprising classes, such as carbolines, anthraquinones and xanthones. However, most of these compounds lack suitable physico-chemical properties, compatible to oral bioaviability. In this perspective, this paper aims to overview the role of tricyclic cores in the development of cytotoxic compounds, focusing on the leadlikeness estimation of the most prominent NP classes and their synthetic derivatives.

Synthetic chalcones as potential tool for acute- and chronic-pain control.

The purpose of this study was to validate the potential anti-hypersensitive activity of two chalcones, (2E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (ANCh) and N-{4-[(2E)-3-(4-nitrophenyl)prop-2-enoil]phenyl}acetamide (AcANCh), by different models of acute and persistent pain in mice, besides in silico analysis. Molecules computational investigation for prediction of Lipinki's and Veber's rules to determine solubility, % absorption, drug likeness and toxicity liabilities was performed. Male and female C57BL/6 mice (20-30 g, n = 6) were used. Firstly, mice were pre-treated with the compounds ANCh or AcANCh and then submitted to the models of acute hypersensitivity by the intraplantar injection of different phlogistic agents. The mechanical sensitivity was assessed using von Frey hairs (0.6 g). The obtained data shows that both compounds presented important inhibitory effects on mechanical hypersensitivity induced by carrageenan (with oral bioavailability). The anti-hypersensitive effect was also accompanied by the interference in leukocyte migration, interleukin-1ß (IL-1ß) and tumour necrosis factor (TNF) levels reduction and by the absence of unspecific effects. Added to the in vivo results, the in silico analysis presented none violation in Lipinski's or Veber's rules, good probability to cell membrane permeability and oral bioavailability, positive values of drug likeness and few risk of computational toxicity. ANCh partially reduced the hypersensitivity induced by IL-1ß and TNF, epinephrine and prostaglandin E2 (PGE2). AcANCh had similar effect, except for the absent of inhibition in PGE2-injected mice. Both compounds were capable of reducing the mechanical hypersensitivity presented in all persistent models of hypersensitivity (inflammatory pain, chronic nerve constriction and cancer pain), with emphasis for ANCh. These results suggest that both chalcones could represent good strategies for the control of acute and chronic pain, without important side effects. ANCh seems to involve cell migration and cytokines production as the main mechanism, together with interference in PGE2 neuronal sensitization pathway. In vivo and in silico analyses reinforce the potential characteristics of the compounds to become future drugs.

Anti-hypersensitivity effects of the phthalimide derivative N-(4methyl-phenyl)-4-methylphthalimide in different pain models in mice.

The treatment of chronic pain remains a challenge for clinicians worldwide, independent of its pathogenesis. It motivates several studies attempting to discover strategies to treat the disease. The in silico analysis using molecular docking approach demonstrated that the phthalimide N-(4methyl-phenyl)-4-methylphthalimide (MPMPH-1) presented high affinity to adenylyl-cyclase enzyme (AC). It also prominently reduced the mechanical hypersensitivity of mice challenged by Forskolin, an AC activator. This effect lasted for up to 48h after Forskolin injection, presenting activity longer than MDL-12330A (AC inhibitor). MPMPH-1 was also effective in reducing the hypersensitivity induced by IL-1ß, bradykinin, prostaglandin E2 or epinephrine, chemical mediators that have, among others, AC as pivotal protein in their signalling cascade to induce mechanical-pain behaviour. The compound presented marked inhibition in inflammatory-pain models induced by carrageenan, lipopolysaccharide or complete Freund's adjuvant, including neutrophil migration inhibition. Furthermore, it also seems to act in both peripheral and pain central-control pathways, being also effective in reducing the persistent cancer-pain behaviour induced by melanoma cells in mice. MPMPH-1 could represent a promising pharmacological tool to treat acute and chronic painful diseases, with good bioavailability, local activity, and lack of locomotor-activity interference. Further studies are necessary to determine the exact mechanism of action but it seems to involve AC enzyme as possible target.

Osteogenic potential of different chalcones in an in vivo model: a preliminary study

Aim. To evaluate the osteogenic potential of chalcones using the rat critical size calvarial defect. Methods. The chalcones were synthesized from acetophenone following the Claisen-Schmidt aldol condensation method by varying the substituted benzaldehydes (3,4-Cl; 4-Cl; 4-CH3; 4-OCH3, H). The five chalcone molecules were evaluated in three concentrations (1 percent, 5 percent and 10 percent) in comparison to control and vehicle (Vaseline) groups. The results of the remaining wound areas were calculated statistically by the ANOVA method followed by the Student-Newman-Keuls test and the histological sections were analyzed qualitatively by light microscopy. Results. All molecules at 10 percent concentration showed significant bone closure compared to the control, vehicle and chalcone groups at 1 percent concentration (p<0.01). Active osteoblasts were observed on the repair surfaces in all groups treated with chalcones. Treatment with the C5 molecule at concentration of a 10 percent resulted in greater bone neoformation compared to the other molecules, with features of secondary bone observed. Conclusion. The chalcones evidenced a dose-dependent osteogenic potential and C5 was more effective in bone repair

Effects of 1,3,5-triphenyl-4,5-dihydro-1H-pyrazole derivatives on cell-cycle and apoptosis in human acute leukemia cell lines.

Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V - fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski's "rule of five" for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent.

Antiproliferative effect of synthetic cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against human cancer cell lines.

This work describes the antiproliferative potential of 14 cyclic imides (methylphtalimides, carboxylic acid phtalimides and itaconimides) against several human cancer cell lines. The antiproliferative effect was evaluated using the sulforhodamine B assay. Although some compounds from methylphtalimide and carboxylic acid phtalimide classes exhibited a selective antiproliferative activity, the itaconimides (11-14) exhibited the best results, especially compound 14, which presented a TGI (concentration that produces total growth inhibition) value of 0.0043 µM against glioma (U251), being inactive against the non-tumor cell line (HaCat). Absorption, distribution, metabolism and excretion in silico evaluations suggest that these compounds are promising candidates.

In vitro antiproliferative activity of uncommon xanthones from branches of Garcinia achachairu.

Context Garcinia achachairu Rusby (Clusiaceae) popularly known as 'achachairu' is used in folk medicine to treat rheumatism, inflammation, pain and gastric disorder. Objective The present study investigated the chemical profile and antiproliferative effects of the methanolic extract, fractions and two xanthones, against some carcinoma cell lines in vitro. Materials and methods The compounds were isolated and identified by chromatographic and spectroscopic methods. The extract, fractions and compounds were tested human tumour cell lines of U-251 (glioma), MCF-7 (breast), NCI/ADR-RES (ovary expressing multi-drug resistance phenotype), 786-0 (kidney), NCI-H460 (lung, non-small cells), PC-3 (prostate) and HT-29 (colon), non-tumour cell line HaCat (human keratinocytes) in doses of 0.25-250 µg mL (-) (1) for 48 h. The antiproliferative activity was determined by spectrophotometric quantification (at 540 nm) of the cellular protein content using sulphorhodamine B assay. The prediction of parameters involved in the molecular bioavailability was executed directly by ChemDoodle (version 5.0.1) software (iChemLabs, LLC, Somerset, NJ). Results 3-Demethyl-2-geranyl-4-prenylbellidypholine (1) and 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrane (2,3:3,2)-4-(3-methylbut-2-enyl) xanthone (2), gartanin (3) and stigmasterol (4) were identified on the basis of spectroscopic techniques. Compounds 1 and 2 exhibited cytocidal activity, especially against breast, prostate and kidney cell lines, with TGI values of 15.8, 4.9, 9.1 and 39.4, 44.7, 40.9 µg/mL, respectively. Discussion and conclusion The presence of two sets of hydrophobic and hydrophilic groups in separate domains in each molecule might play a role in the mediation of tumour-specific action. Our data show that G. achachairu have potent antiproliferative action and should be considered an important source of potent anticancer compounds.

Associações e dissociações no campo da educação física: para onde vai o trabalho dos grupos de trabalho? / Associations and dissociations in the field of physical education: to where is it going the work of the working groups? / Asociaciones y disociaciones en el campo de la educación física: ¿a dónde va el trabajo de los grupos de trabajo?

Resumo Reflexão apoiada na produção científica relacionada à educação física e inclusão escolar publicada na Revista Brasileira de Ciências do Esporte de 2000 a 2010. Efetuou-se levantamento e avaliação dos trabalhos revisados a partir de suas palavras-chave, objetivos, metodologias, resultados e conclusões. O tema inclusão escolar no campo da educação física foi pouco abordado na produção científica veiculada na Revista, a despeito de ser assunto gerador de inquietações acadêmico-profissionais. Esse fato pode contribuir para fragilizar a compreensão dos profissionais da área sobre a relação entre educação física e inclusão escolar e remete a reflexões de interesse sobre a função de associações científicas no diálogo com questões presentes no cotidiano da intervenção profissional.

Abstract Review of the scientific literature related to Physical Education and School Inclusion published in the Revista Brasileira de Ciências do Esporte from 2000 to 2010 by survey and evaluation of the revised papers based on key words, objectives, methodologies, results and conclusions. The School Inclusion in the field of Physical Education was rarely addressed in the scientific production published in the Revista, despite being a subject which generates academic and professional concern. This may contribute to undermining the understanding of professionals about the relationship between Physical Education and School Inclusion, and refers to reflections on the role of scientific associations in the dialogue with issues from the daily routine of the professional intervention.

Resumen Análisis de la producción científica relacionada con la educación física y la inclusión escolar en la Revista Brasileira de Ciências do Esporte de 2000 a 2010 tras el estudio y la evaluación de los trabajos revisados a partir de palabras clave, objetivos, metodologías, resultados y conclusiones. El tema de la educación física y la inclusión escolar se ha abordado poco en la producción científica publicada en la Revista a pesar de tratarse de un asunto que genera inquietudes académicas y profesionales. Este hecho puede contribuir a menoscabar la comprensión de los profesionales sobre la relación entre educación física e inclusión escolar, y remite a reflexiones de interés sobre la función de asociaciones científicas en el diálogo con cuestiones cotidianas de la intervención profesional.

Evaluation of direct pulp capping with a synthetic chalcone: a preliminary histological study / Evaluación del recubrimiento pulpar directo con una chalcona sintética: estudio histológico preliminar

The aim of this study is to evaluate the action of the synthetic chalcone 1-phenyl-3-(4-chlorophenyl)-2-propen-1-one to induce pulp healing in rats. Material and Methods: Sixty lower first molars of male Wistar rats were divided into 3 groups (n=20): control (no treatment); calcium hydroxide and chalcone. After relative isolation, the cavities were prepared using a sterile low-speed » round dental bur. After controlling the hemorrhaging, all the pulp exposures were capped with the capping material, by groups. The cavities were sealed with glass ionomer cement and the repair process was assessed at 21 days of procedure. The data were statistically analyzed using the Fisher exact test (p<0.05). Results: Moderate inflammation was observed in all the experimental groups and significant (p<0.05) reparative dentin (tertiary) formation in the calcium hydroxide and chalcone groups. The chalcone group showed dentinal tubules and a low number of cellular inclusions (p<0.05). Conclusion: The chalcone used in this study indicates potential as an inducer of reparative dentine (tertiary) in a rat model...

El objetivo de este estudio es evaluar la acción de la chalcona sintética 1-fenil-3- (4-clorofenil) -2-propen-1-ona para inducir la reparación de la pulpa dentaria en ratas. Materiales y métodos: Sesenta primeros molares inferiores de ratas Wistar machos se dividieron en 3 grupos (n = 20): control (sin tratamiento); hidróxido de calcio y chalcona. Después del aislamiento relativo, las cavidades se prepararon usando una fresa dental redonda de » estéril a baja velocidad. Después de controlar la hemorragia, todas las exposiciones pulpares se taparon con el material de recubrimiento de acuerdo con los grupos del experimiento. Las cavidades fueron selladas con cemento de ionómero de vidrio y el proceso de reparación se evaluó a los 21 días del procedimiento. Los datos fueron analizados estadísticamente mediante la prueba exacta de Fisher (p<0,05). Resultados: Se observó inflamación moderada en todos los grupos experimentales y significativa (p <0,05) formación de dentina reparadora (terciaria) en los grupos de hidróxido de cálcio y chalcona. El grupo de chalcona mostró túbulos dentinarios y un bajo número de inclusiones celulares (p <0,05). Conclusión: La chalcona utilizada en este estudio indica potencial como un inductor de la dentina reparadora (terciaria) en ratas...

A magnetic nanogel based on O-carboxymethylchitosan for antitumor drug delivery: synthesis, characterization and in vitro drug release.

This paper studied the synthesis, characterization and use of the magnetic chitosan nanogel for carrying meleimidic compounds. The hydrogel polymer was prepared using O-carboxymethylchitosan, which was crosslinked with epichlorohydrin for subsequent incorporation of iron oxide magnetic nanoparticles. The characterization revealed that the magnetic material comprises about 10% of the hydrogel. This material is comprised of magnetite and maghemite and exhibits ferro-ferrimagnetic behavior. The average particle size is 4.2 nm. There was high incorporation efficiency of maleimides in the magnetic nanogel. The release was of sustained character and there was a greater release when an external magnetic field was applied. The mathematical model that best explained the process of drug release by the magnetic hydrogel was that of Peppas-Sahlin. The magnetic nanogel proved to be an excellent candidate for use in drug-delivery systems.

Osteogenic potential of a chalcone in a critical-size defect in rat calvaria bone.

BACKGROUND: This study describes the bone formation stimulated by the application of a type of chalcone to critical-size defects in rat calvarial bone. MATERIAL AND METHODS: Sixty female Wistar rats were divided into 6 groups of 10 animals per group: control (no treatment), vehicle (vaseline) and the chalcone (1-phenyl-3-(4-chlorophenyl)-2-propen-1-one) suspended in vaseline at 10%. A critical-size defect of 5 mm was prepared using a trephine in the calvarial bone, after which the treatment was applied, in a single dose, according to the experimental group. The samples were evaluated macroscopically using ImageJ software, and histologically 30 and 45 days after surgery. RESULTS: At 30 days after surgery, there was significant bone formation (p < 0.05) in the groups treated with chalcone, compared with the other groups. Many active osteoblasts were observed adjacent to the borders of the newly formed bone tissue. 45 days after surgery in the chalcone group, the surgical defects showed complete bone closure. CONCLUSION: The results of this study suggest that chalcone has significant potential to induce the formation of new bone.

Synthesis and biological evaluation of N-antipyrine-4-substituted amino-3-chloromaleimide derivatives.

This paper describes the synthesis of new cyclic imides obtained by reaction with N-antipyrine-3,4-dichloromaleimides and different aromatic amines. The analgesic activity of the synthesized compounds was initially investigated against the writhing test in mice, followed by analysis of the most promising compounds in this model and in the formalin-induced model. The results indicate that the compounds containing the electron-withdrawing substituents in the para position of the substitute ring exerted more potent analgesic activity in mice, being much more potent than the prototype N-antipyrine-3,4-dichloromaleimide and some reference drugs. Some compounds exhibited activity against human opportunistic and pathogenic fungi, with MIC values of between 40 and 100 µg/mL (91.74 and 236.96 µM), and it was verified that only a few compounds presented potential for cytotoxic activity.

Antiproliferative effects of a series of cyclic imides on primary endothelial cells and a leukemia cell line.

The present study describes the cytotoxic properties of a series of 15 cyclic imides observed against different endothelial cells and K562 leukemic cells. Initially, eight structurally unrelated compounds were evaluated against cultured bone marrow endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC). Only two imides showed cytotoxic activity at 10 microM. In continuation of our screening, eight compounds, structurally related to the compound with the higher cytotoxic activity, were assayed against endothelial cells and the K562 leukemic cell line. All of these new compounds except two exhibited cytotoxic and antiproliferative activities at concentrations below 10 microM against BMEC and HUVEC, respectively. The K562 leukemia cell line was only affected by concentrations of 100 microM. Preliminary SAR analysis indicated that the cytotoxic activity of these compounds was related to the presence of a planar imide ring directly bound to an aromatic ring.

Rhizobacteria able to produce phytotoxic metabolites

To contribute for the development of environmental friendly methods for weed control, a selection of rhizobacteria able to produce phytotoxic substances was carried out. Initially, 35 strains previously isolated from plants in the south of Minas Gerais State (Brazil) were grown in tryptic soy broth. After removal of bacterial cells, the resulting liquids were freeze-dried and extracted with methanol/ethyl acetate (1:1). The extracts were concentrated under vacuum and dissolved in water to be submitted to a lettuce (Lactuca sativa L.) seed assay. Metabolites produced by five strains reduced the number of normal seedlings to values statistically bellow the one observed for the negative control, being the most expressive results obtained with Bacillus cereus Frankland and Frankland, isolated from Ricinus communis L., which was able to cause rotted rootlets to 82.4 percent of seedlings. The bacterium metabolites also avoided germination of 52 percent Brachiaria decumbens Stapf seeds and the remaining 48 percent resulted in abnormal seedlings. Metabolites from B. cereus were submitted to a purification process guided by the lettuce seed assay. As a consequence, one substance causing rotted rootlets to all lettuce seedlings during the seed assay at 0.057 g/L was isolated and will be identified in future studies.

Com vistas a contribuir para o desenvolvimento de métodos não agressivos ao meio ambiente, para o controle de plantas invasoras, buscou-se selecionar rizobactérias produtoras de substâncias fitotóxicas. Inicialmente, 35 culturas previamente isoladas de plantas da região sul do Estado de Minas Gerais (Brasil) foram cultivadas em caldo soja tripticaseína. Após remoção das células bacterianas, os líquidos resultantes foram liofilizados e extraídos com metanol/acetato de etila (1:1). Os extratos foram concentrados sob vácuo e submetidos a testes com sementes de alface (Lactuca sativa L.). Os metabólitos produzidos por cinco isolados bacterianos reduziram o número de plântulas normais para valores estatisticamente inferiores aos observados para o controle negativo, sendo os mais expressivos resultados obtidos com Bacillus cereus Frankland and Frankland, isolado de Ricinus communis L., que causou necroses nas radículas de 82,4 por cento das plântulas. Os metabólitos dessa bactéria também impediram a germinação de 52 por cento das sementes de Brachiaria decumbens Stapf e fizeram com que as 48 por cento restantes dessem origem a plântulas anormais. Os metabólitos de B. cereus foram submetidos a processos de purificação direcionados por testes com sementes de alface. Em decorrência, isolou-se uma substância, que será identificada em estudos futuros. Na concentração de 0,057 g/L, causou necrose nas radículas de todas as plântulas de alface provenientes do teste com sementes.

Silicon and acibenzolar-S-methyl as resistance inducers in cucumber, against the whitefly Bemisia tabaci ( Gennadius ) ( Hemiptera: Aleyrodidae ) biotype B

O objetivo deste trabalho foi avaliar o efeito de silicato de cálcio (CaSiO3) e do ativador acibenzolar-S-methyl (BTH) na indução de resistência em pepino à mosca-branca Bemisia tabaci (Gennadius) biótipo B. Testes de preferência com e sem chance de escolha e de antibiose foram realizados em casa-de-vegetação e no laboratório do Departamento de Entomologia da Universidade Federal de Lavras/UFLA, MG. O delineamento foi o inteiramente ao acaso com os seguintes tratamentos: 1) testemunha, 2) aplicação de 3 g de silicato de cálcio.kg-1 de substrato, 3) duas aplicações de 200 ml de solução a 1% de silicato de cálcio/vaso, 4) duas aplicações de 100 ml de solução a 0,005% de BTH/vaso e 5) aplicação de silicato de cálcio e BTH na mesma dose dos tratamentos 3 e 4. Para eliminar o efeito isolado do cálcio, foi aplicado 1g de carbonato de cálcio.kg-1 de substrato no tratamento 1 (testemunha). O silicato de cálcio e BTH causaram efeitos negativos na população da mosca-branca pela redução da oviposição, aumento do ciclo biológico e da mortalidade na fase de ninfa. Apresentaram-se, assim, como produtos alternativos a serem utilizados no manejo integrado de mosca-branca na cultura de pepino.