Cancer is one of the major causes of death worldwide, and breast cancer is the most prevalent and deadly type among women. Despite the side effects and the phenomena of chemoresistance associated with the drugs involved, chemotherapy remains the main therapeutic strategy to combat and control breast cancer. Therefore, several new classes of compounds against breast cancer have been explored, in an effort to identify new drug candidates with alternative mechanisms of action. The principal results of such exploration, focusing on caged xanthones, thiosemicarbazones and photosensitizers, are presented in this review, along with the main aspects of the drug discovery process against breast cancer. More specifically, the design, structure-activity relationship investigations and anti-breast cancer properties of these three classes are described and discussed in this work. worldwide women involved Therefore explored action exploration xanthones photosensitizers review specifically design structureactivity structure activity antibreast anti work

ABSTRACT: The aim of this study was to evaluate the influence of overtorque on integrity, strength and stress on external hexagonal implants (EH), with two different grades (N=10): conventional (C), grade 4; and modified (M), grade 4 with thermal treatment. The dimensions of EH were 3.75 x 13 mm; the specimens were fixed and submitted to SEM analysis and image acquisition. The abutment was then retained with 70 N/cm, re-analyzed by SEM, and a second image was obtained. The images were analyzed by Image J software (1.44o- NIH, USA) for dimensional variations measurement on surface of the hexagonal area. The finite element method was applied with a similar compliance to calculate the resultant stress (MPa) during the torque. Results were statistically analyzed with t-student test (5 %). The dimensional accuracy of M (0.22 mm2) was statistically significant (p<0.05). Minimum principal stress and von-Mises stress of C (-19.95 MPa, -19.94 MPa), were lower than M values (-55.83 MPa, -55.96 MPa), respectively. However, the M group showed lower deformation than C group. Therefore, more rigid titanium alloy is a promising alternative to avoid plastic deformation of prosthetic connec tions even concentrating higher stress magnitude on its structure.

RESUMEN: El objetivo de este estudio fue evaluar la influencia del sobrepar en la integridad, la fuerza y la tensión en los implantes hexagonales externos (EH), con dos grados diferentes (N = 10): convencional (C), grado 4; y modificado (M), grado 4 con tratamiento térmico. Las dimensiones de EH eran 3,75 de diámetro x 13 mm de longitud; las muestras se fijaron y se sometieron a análisis SEM y adquisición de imágenes. A continuación, el pilar se retuvo con 70 N / cm, se volvió a analizar por SEM y se obtuvo una segunda imagen. Las imágenes se analizaron con el software Image J (1.44o-NIH, EE. UU.) Para medir las variaciones dimensionales en la superficie superior del área hexagonal, que fue causada por un par excesivo. El método de los elementos finitos se aplicó con un cumplimiento similar para calcular la tensión resultante (MPa) durante el par. Los resultados se analizaron estadísticamente con la prueba t-student (5 %). La precisión dimensional de M (0,22 mm2) fue estadísticamente significativa (p <0,05). La tensión principal mínima y la tensión de von-Mises de C (-19,95 MPa, -19,94 MPa), fueron inferiores a los valores de M (-55,83 MPa, -55,96 MPa), respectivamente. Sin embargo, el hexágono del grupo M mostró menor deformación que el grupo C. Por lo tanto, la aleación de titanio más rígida es una alternativa prometedora para evitar la deformación plástica de las conexiones protésicas incluso concentrando una mayor magnitud de tensión en su estructura.

In this work, a search for antimicrobial agents against multi-drug resistant (MDR) bacteria was undertaken. It involved two natural diterpenes of different basic skeletons, named ent-kaurenoic acid and ent-pimaradienoic acid, that were used as precursors to access 28 semi-synthetic derivatives that were also submitted to biological assays. All 30 substances were assayed against a set of seven clinically isolated MDR bacteria, including three Staphylococcus aureus strains. Results classified both natural compounds as promising bactericidal antimicrobial agents against these MDR bacteria, especially for their performance in time-kill curve assay, improving on the positive control vancomycin. Moreover, di-hydro ent-pimaradienoic acid, obtained as one of the derivatives, also displayed promising minimum inhibitory concentration (MIC) values against the microorganism set, proving optimum activity against S. aureus strains. Thereby, this work also yielded a promising semi-synthetic bacteriostatic antimicrobial agent against MDR S. aureus. Furthermore, the study was carried out with 30 structures in order to verify the veracity and scope of Urzúa’s hypothesis about the structure-activity relationship between diterpenes and antimicrobial action. Our results are 93% in agreement with this hypothesis.

Sixteen 1,4-diaryl-1,2,3-triazole compounds derived from the natural products veraguensin, grandisin and machilin G were synthesized, with yields of 78-92%. Biological activity tests against Leishmania amazonensis promastigotes showed that three of these compounds were the most active, with maximum inhibitory concentration (IC50) values of 1.1, 3.71 and 7.23 µM. One compound was highly active against Leishmania infantum, with an IC50 value of 5.2 µM, and one derivative showed an IC50 value of 28.6 µM against Trypanosoma cruzi trypomastigotes. Regarding structure-activity relationship (SAR), hybrid 1,2,3-triazolic compounds containing a methylenedioxy group, showed the best antileishmanial and antitrypanosomal activities.

Abstract Piper angustifolium Lam., Piperaceae, popularly known as "matito", "pimenta-de-macaco", "pimenta-longa" or "jagurandi" in Brazil, has been commonly used in the treatment of cutaneous leishmaniasis-associated lesions, but there are few studies on the activity against visceral leishmaniasis-associated species. This study demonstrates the first in vitro antileishmanial activity of the P. angustifolium essential oil, of which the phytochemical profile showed the presence of sesquiterpenes and monoterpenes. The main compounds were spathulenol (23.8%) and caryophyllene oxide (13.1%). P. angustifolium essential oil was highly active [the half maximum inhibitory concentration = 1.43 μg/ml] against intracellular amastigotes of Leishmania infantum, the etiological agent of visceral leishmaniasis in the New and Old World. Activity was obtained 24 h after addition of the oil (6.25–50 μg/ml), with a reduction of 100% in the infection index at concentrations of 25 and 50 μg/ml. P. angustifolium essential oil showed low cytotoxicity for mammalian fibroblasts and macrophages (the half maximum inhibitory concentration values of 31.67 and 48.22 μg/ml, respectively), and it was 33 and 22 times more toxic to amastigotes than to mammalian cells, as indicated by selectivity indexes. The results demonstrated that P. angustifolium essential oil is a promising alternative for the study of potential drugs for visceral leishmaniasis.

O amplo espectro de ação dos endectocidas e a praticidade de aplicação das suas formulações pour-on são fatores que têm estimulado uma maior frequência de utilização destes produtos na criação de bovinos. Neste estudo, avaliou-se a eficácia anti-helmíntica da ivermectina, administrada via pour-on, 500mcgkg-1, contra nematódeos de bovinos provenientes de diferentes rebanhos. Foram adquiridos 12 bezerros de cada um dos quatro rebanhos selecionados. Todos os 48 bezerros utilizados apresentavam médias de ovos por grama de fezes (OPG) maiores que 500, considerando-se três contagens consecutivas. Na sequencia, os animais de cada rebanho foram divididos em dois grupos de seis bovinos cada, sendo um tratado com ivermectina 500mcgkg-1 via pour-on e outro mantido como controle. Quatorze dias depois do tratamento, os bovinos foram submetidos à eutanásia para contagem de endoparasitas. A ivermectina demonstrou resultados nulos de eficácia contra H. placei nos quatro rebanhos. Contra C. punctata, tal formulação teve eficácia nula nos rebanhos provenientes de Jaboticabal,SP, e de Formiga,MG, e eficácias de 75,8% e 58,4% nos rebanhos provenientes de São José do Rio Pardo,SP, e de São Sebastião do Paraíso,MG, respectivamente. Valores de eficácia de 94,2% (Jaboticabal), 0,0% (São José do Rio Pardo), 94,2% (Formiga) e 39,2% (São Sebastião do Paraíso) foram detectados contra O. radiatum. Com base nos resultados encontrados, pode-se concluir que as quatro populações de Haemonchus placei e de Cooperia punctata avaliadas foram resistentes à ivermectina, administrada via pour-on, 500mcgkg-1. Foram observadas cepas de Oesophagostomum radiatum resistentes à ivermectina em dois dos quatro rebanhos testados.

The broad spectrum of endectocides and the easy use mode of their pour-on formulations are factors that have stimulated a higher frequency of use these drugs in cattle. In this study was evaluated the efficacy of ivermectin pour-on using the dose of 500mcgkg-1, against nematodes in naturally infected cattle from different herds. Twelve calves were brought from each of the four farms selected. All the 48 calves used showed mean of eggs per gram of feces (EPG) greater than 500 considering three consecutive counts. Subsequently, animals from each herd were divided into two groups of six animals each, one treated pour-on with ivermectin 500mcgkg-1 and other kept as untreated control. Calves were euthanized 14 days after treatment for counting the endoparasites. Ivermectin showed null effect against H. placei in all the herds evaluated. The drug was also ineffective against C. punctata in the herds from Jaboticabal,SP and Formiga,MG, and reached efficacy of 75.8% and 58.4% in herds from São José do Rio Pardo,SP and São Sebastião do Paraíso,MG, respectively. Efficacies of 94.2% (Jaboticabal), 0.0% (São José do Rio Pardo), 94.2% (Formiga) and 39.2% (São Sebastião do Paraíso) were detectedagainst O. radiatum. Based on these results obtained on the present study, the four populations of Haemonchus placei and Cooperia punctata evaluated were resistant to ivermectin pour-on using a dose of 500mcgkg-1. Ivermectin-resistant strains of Oesophagostomum radiatum were found in two of the four herds evaluated.

This work shows the influence of several reactional parameters for obtaining graphene through successive steps of oxidation and exfoliation of bulk graphite (resulting in graphene oxide), followed by chemical reduction. The results showed that changes in temperature, reaction time, reducing agent and source of primary graphite lead to different surface compositions and stability in dispersion of graphene oxide. Also, the use of different reducing agents promoted different degrees of restoration of C=C bonds in the bidimensional structure of graphene.

O uso cada vez mais freqüente de métodos diagnósticos simples e efetivos tem contribuído significativamente para um aumento no diagnóstico de câncer da tiróide nos últimos anos. Entretanto, existem importantes evidências de que muitos dos microcarcinomas papilíferos têm um comportamento indolente e podem nunca evoluir para cânceres clínicos. Existe, portanto, uma necessidade urgente de desenvolver novas ferramentas capazes de predizer quais os tumores tiroidianos que permanecerão silenciosos e quais desenvolverão comportamento agressivo. Há uma série de marcadores clínicos de evolução bem estabelecidos e alguns estudos recentes sugerem que dados laboratoriais e métodos de imagem podem ser úteis. Marcadores moleculares também vêm sendo ativamente investigados e alguns, como BRAF, os genes GST e polimorfismos de p53, parecem promissores. Além disso, marcadores imunocitoquímicos e a medida da natureza fractal da cromatina podem aumentar a especificidade do diagnóstico anatomopatológico e ajudar a predizer o prognóstico. Existe uma necessidade imperiosa de elaborarmos diretrizes destinadas a selecionar os nódulos que merecem prosseguimento em sua avaliação, assim como novos métodos capazes de identificar lesões mais agressivas entre os geralmente indolentes tumores tiroidianos.

The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patient’s laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.

OBJETIVOS: Avaliar retrospectivamente as características clínicas/radiológicas dos pacientes admitidos com refluxo vésico-ureteral primário (RVU) entre 1969-1999. MÉTODOS: Pacientes com RVU primário foram submetidos a um protocolo de avaliação clínica, laboratorial e radiológica e acompanhados longitudinalmente. Na admissão, após controle da bacteriúria e do início da quimioprofilaxia, foram realizados avaliação laboratorial e estudo de imagens do trato urinário. Esta consistiu de uretrocistografia miccional, urografia excretora, cintilografia renal (DMSA) e ultra-sonografia. Para o presente estudo foram utilizados os dados obtidos na admissão. RESULTADOS: Foram admitidos nesse período 483 pacientes. Houve predomínio do sexo feminino (70%) e da cor branca (70%). A média de idade ao diagnóstico foi de 26 meses, sendo que 92,5% das crianças já haviam apresentado infecção urinária. Um grupo de 710 unidades renais foi analisado. A distribuição do grau de refluxo foi a seguinte: grau I (49; 7%); II (254; 36%); III (190; 26%); IV (161; 23%) e V (56; 8%). Um total de 249 unidades renais apresentaram dano renal à admissão. A distribuição quanto à intensidade da lesão foi a seguinte: leve (36%), moderada (34%) e grave (30%). Houve um risco significativo maior de lesão renal grave no sexo masculino (OR = 1,74, IC 95% = 1,2 - 2,5, p = 0,002). CONCLUSÃO: O RVU predominou no sexo feminino e em sua maioria apresentou-se em graus leves a moderados. Contudo, houve um alto percentual de dano renal à admissão e uma tendência de maior morbidade para o sexo masculino.

OBJECTIVES: To evaluate the clinical/radiological features of patients with primary vesicoureteral reflux (VUR) admitted to a single institution from 1969 to 1999. METHODS: At admission, after the institution of chemoprophylaxis, patients were investigated by CUM, DMSA, and US. The children were managed with periodical clinical and laboratory evaluations. Analyses were performed with the data obtained at admission. RESULTS: A total of 483 patients were enrolled in the protocol. There was a predominance of females (70%) and caucasian race (70%). Mean age at VUR diagnosis was 26 months and 92.5% of the patients had urinary infection before admission. A total of 710 refluxing units were analyzed. The distribution of reflux grade was: grade I (49; 7%); II (254; 36%); III (190; 26%); IV (161; 23%) e V (56; 8%). Approximately one half of the units analyzed were from patients presenting renal damage at admission. The distribution of the severity of renal damage was as follows: mild (36%), moderate (34%), and severe (30%). There was a significant risk of severe renal damage for the males (OR = 1.74, 95% CI = 1.2 - 2.5, p = 0.002). CONCLUSION: There was a predominance of VUR among females and most presented a mild or moderate degree. However, there was a high percentage of renal damage at admission and a tendency to greater morbidity for the males.