ABSTRACT
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.
ABSTRACT
Abstract Background: Soybean milk by-product (SMBP) is a potential alternative feed ingredient in swine diets due to its high protein content. However, information on energy and nutritional values of SMBP used as swine feed ingredient is limited. Objective: To estimate energy values and protein digestibility of SMBP in pigs based on in vitro assays. Methods: Four SMBP samples were obtained from 3 soybean milk-producing facilities. In vitro total tract disappearance (IVTTD) and in vitro ileal disappearance (IVID) of dry matter (DM) in the SMBP samples were determined. In vitro ileal disappearance of crude protein was determined by analyzing crude protein content in undigested residues after determining IVID of DM. Digestible and metabolizable energy of SMBP were estimated using gross energy, IVTTD of DM, and prediction equations. Results: Sample 4 had greater IVTTD of DM than that of sample 3 (97.7 vs. 94.4%, p<0.05), whereas IVID of DM in sample 4 was lower compared with sample 1 (53.5 vs. 65.0%, p<0.05). In vitro ileal disappearance of crude protein in sample 2 was greater than that in sample 1 and 3 (92.6 vs. 90.6 and 90.1%; p<0.05). The estimated metabolizable energy of SMBP ranged from 4,311 to 4,619 kcal/kg as-is basis and the value of sample 3 was the least (p<0.05) among SMBP samples. Conclusion: Energy values and protein digestibility should be determined before using SMBP in swine diets.
Resumen Antecedentes: El subproducto de la leche de soja (SMBP) es un ingrediente alimenticio alternativo con uso potencial en dietas porcinas dado su alto contenido de proteína. Sin embargo, la información sobre sus valores energéticos y nutricionales para alimentación de cerdos es muy limitada. Objetivo: Estimar los valores de energía y la digestibilidad de la proteína del SMBP en cerdos con base en ensayos in vitro. Métodos: Se obtuvieron cuatro muestras de SMBP de tres empresas productoras de leche de soja. Se determinaron la desaparición de tracto total in vitro (IVTTD) y la desaparición ileal in vitro (IVID) de la materia seca (DM) en las muestras de SMBP. La desaparición ileal in vitro de proteína cruda se determinó analizando el contenido de proteína cruda en residuos no digeridos después de determinar la IVID de la DM. La energía digestible y metabolizable de SMBP se estimó utilizando la energía bruta, IVTTD de la DM y ecuaciones de predicción. Resultados: La muestra 4 tuvo una mayor IVTTD de la DM que la muestra 3 (97,7 vs. 94,4%, p<0,05), mientras que la IVID de la DM en la muestra 4 fue menor en comparación con la muestra 1 (53,5 vs. 65,0%, p<0,05). La desaparición ileal in vitro de la proteína cruda en la muestra 2 fue mayor que la de las muestras 1 y 3 (92,6 vs. 90,6 y 90,1%; p<0,05). La energía metabolizable estimada de SMBP varió de 4.311 a 4.619 kcal/kg (en base húmeda) y el valor de la muestra 3 fue el menor (p<0.05) entre las muestras de SMBP. Conclusión: Los valores de energía y la digestibilidad de la proteína deben determinarse antes de usar el SMBP en dietas porcinas.
Resumo Antecedentes: O subproduto do leite de soja (SMBP) é um potencial ingrediente alternativo na dieta de suínos, considerando seu alto teor de proteínas. No entanto, as informações sobre os valores energéticos e nutricionais do SMBP usado como ingrediente alimentar para suínos são limitadas. Objetivo: Estimar valores energéticos e digestibilidade protéica do SMBP em suínos com base em ensaios in vitro. Métodos: Foram obtidas quatro amostras de SMBP de três instalações produtores de leite de soja. Foram determinados o desaparecimento total do trato in vitro (IVTTD) e o desaparecimento ileal in vitro (IVID) da matéria seca (DM) nas amostras de SMBP. O desaparecimento ileal in vitro da proteína bruta foi determinado pela análise do conteúdo de proteína bruta em resíduos não digeridos após a determinação da IVID do DM. A energia digerível e metabolizável do SMBP foi estimada usando energia bruta, IVTTD do DM e equações de predição. Resultados: a amostra 4 apresentou maior IVTTD de DM do que a amostra 3 (97,7 vs. 94,4%, p<0,05) enquanto a IVID do DM na amostra 4 foi menor em comparação com a amostra 1 (53,5 vs. 65,0%, p<0,05). O desaparecimento ileal in vitro da proteína bruta na amostra 2 foi superior ao da amostra 1 e 3 (92,6 vs. 90,6 e 90,1%; p<0,05). A energia metabolizável estimada do SMBP variou de 4.311 a 4.619 kcal/kg no estado em que se encontra e o valor da amostra 3 foi o menor (p<0,05) entre as amostras do SMBP. Conclusão: os valores energéticos e a digestibilidade das proteínas devem ser determinados antes do uso do SMBP nas dietas suínas.
ABSTRACT
Abstract Zoonoses are major causes of morbidity and mortality worldwide. Among them, Brazilian Spotted Fever (BSF) is an important one that occurs in some regions of South America and can be transmitted by the "star tick" Amblyomma sculptum. Application of acaricides against the larval stage is important as strategy of population control. However, there is still a deficiency of studies on chemical control of A. sculptum and the present work aims to evaluate the in vitro acaricidal activity of cypermethrin, flumethrin, deltamethrin, fipronil, coumaphos and chlorpyrifos against A. sculptum larvae. Bioassays were performed using the larval immersion test method. A discriminatory analysis between the antiparasitic classes most used for tick control was carried out, which made it possible to determine the classes with higher potential for controlling A. sculptum larvae. Our results showed that A. sculptum larvae present highest sensitivity to the synthetic pyrethroid group, followed by the phenylpyrazole, organophosphate and macrocyclic lactone groups. These findings may support studies on improvement of tick control as in animals as in the environment.
Resumo As zoonoses são a maior causa de morbidade de mortalidade no mundo. A Febre Maculosa Brasileira (FMB) é uma importante zoonose que ocorre em algumas regiões da América do Sul e pode ser transmitida pelo "carrapato-estrela" Amblyomma sculptum. A aplicação de acaricidas, frente ao estágio larval, é importante como estratégia no controle da população. No entanto, ainda há uma deficiência de estudos para o controle químico de A. sculptum. Devido à necessidade de mais informações sobre o controle de A. sculptum, o presente trabalho tem como objetivo avaliar a atividade acaricida in vitro de cipermetrina, flumetrina, deltametrina, fipronil, coumafós e clorpirifós frente a larvas de A. sculptum. Os bioensaios foram realizados pelo método Teste de Imersão de Larva. Foi realizada uma análise discriminatória entre as classes antiparasitárias mais utilizadas para controle de carrapatos, possibilitando determinar classes com maior potencial para o controle de larvas de A. sculptum. Os resultados deste trabalho mostraram que as larvas de A. sculptum apresentam maior sensibilidade ao grupo dos piretroides sintéticos, seguido pelos grupos fenilpirazóis, organofosforados e lactonas macrocíclicas. Esses achados poderiam apoiar estudos visando ao controle do carrapato tanto em animais quanto no meio ambiente.
Subject(s)
Animals , Ixodidae , Acaricides/classification , Acaricides/chemistry , South America , Rocky Mountain Spotted Fever/parasitology , Rocky Mountain Spotted Fever/prevention & control , Rocky Mountain Spotted Fever/transmission , LarvaABSTRACT
Abstract Tissue engineering suggests different forms to reconstruct tissues and organs. One of the ways is through the use of polymeric biomaterials such as poly(L-lactic acid) (PLLA). PLLA is a recognized material in tissue engineering due to its characteristics as biocompatibility and bioresorbability. In this work PLLA fibrous membranes were produced by a simple technique known as rotary jet spinning. The rotary jet spinning consists of fibrous membranes production, with fibers of scale nano/micrometric, from a polymeric solution through the centrifugal force generated by the equipment. The membranes formed were subjected to preliminary in vitro assays to verify the cytotoxicity of the membranes made in contact with the cells. Direct cytotoxicity assays were performed through the MTT, AlamarBlue® and Live/Dead® tests, with fibroblastic and osteoblastic cells. The results obtained in this study showed that PLLA membranes produced by rotary jet spinning showed promising results in the 24-hours contact period of the cells with the PLLA fibrous membranes. The information presented in this preliminary study provides criteria to be taken in the future procedures that will be performed with the biomaterial produced, aiming at its improvement.
Subject(s)
Biocompatible Materials , Lactic Acid , Tissue Engineering/methods , In Vitro Techniques/instrumentationABSTRACT
Este trabalho avaliou a interferência do estresse subletal em pH ácido na sobrevivência de Lactobacillus rhamnosus GG em suco misto de juçara e manga com pH ajustado para 3,0 e 3,5 e a resistência desta bactéria ao trato gastrointestinal simulado in vitro durante 28 dias de armazenamento a 6,0 °C. O estresse ácido previamente aplicado nas células de L. rhamnosus GG não aumentou sua resistência ao trato gastrointestinal simulado in vitro e a bactéria apresentou viabilidade mínima de 3,89 Log UFC/mL após a passagem pela fase entérica II. Os tratamentos utilizados, bem como o tempo de armazenamento, não influenciaram (p>0,05) na viabilidade de L. rhamnosus GG. Portanto, o estresse ácido subletal aplicado não se mostrou eficaz no aumento da sobrevivência da bactéria até 28 dias de armazenamento, mas a mesma apresentou boa sobrevivência no suco em pH ácido, mesmo quando não submetida ao estresse prévio em pH 4,0 por 1 hora a 37 °C.
This work evaluated the interference of sublethal stress at acidic pH in the survival of Lactobacillus rhamnosus GG in mixed jussara and mango juice with pH adjusted to 3,0 and 3,5, and the resistance of this bacterium to the gastrointestinal tract simulated in vitro during 28 days of storage at 6.0 °C. The acid stress previously applied to the cells of L. rhamnosus GG did not increase its resistance to the simulated gastrointestinal tract in vitro and thebacterium had a minimum viability of 3.89 Log CFU/mL after passage through the enteric phase II. The treatments used, as well as the storage time, did not influence (p>0.05) the viability of L. rhamnosus GG. Therefore, the sublethal acid stress applied was not effective in increasing the survival of the bacteria until 28 days of storage, but it presented good survival in the juice at acid pH, even when not submitted to previous stress at pH 4.0 per 1 hour at 37 °C.
Subject(s)
In Vitro Techniques , Probiotics , Gastrointestinal Tract , Lacticaseibacillus rhamnosus , Bacteria , Whole Foods , Fruit and Vegetable Juices , Food AnalysisABSTRACT
The genus Eugenia sp. (Myrtaceae) comprises plants with reported antioxidant and antidiarrheal capability among other therapeutic potentials. The aim of this study was to evaluate the antimicrobial activity of essential oil; diuretic and hypotensive activities of aqueous extracts from leaves of Eugenia uniflora. The antimicrobial activity was evaluated . The diuretic and hypotensive activities were evaluated in normotensive Wistar rats by measuring blood pressure and urine flow after received four different concentrations of aqueous extracts (10%, 15%, 20% and 25%). Essential oil inhibited the growth of Candida parapsilosis and Candida albicans with MIC values lower than 14.41 mg/mL, equal to 57.75 mg/mL for Candida krusei. Among antibacterial effect, essential oil inhibited growth with a MIC equals to 153.93 mg/mL for all strains tested, except for Escherichia coli (MIC equals to 307.96 mg/mL. Aqueous extracts showed powerful reductions of the arterial pressure (34% and 31% lower than the control), after administration of 10% and 25% of aqueous extract, respectively. However, the animals that received the aqueous extract at the 15% and 20% concentrations presented a discrete hypotensive effect (20% and 21% lower than control group, respectively) concomitantly to powerful diuretic effect (280% and 91% higher than control group, respectively). These data confirmed the potential biological effect of this species, and represents an important step toward a depth study on the therapeutic properties of this species
O gênero Eugenia sp. (Myrtaceae) compreende plantas com capacidade antimicrobiana e antioxidante entre outros potenciais terapêuticos. O objetivo deste estudo foi avaliar a atividade antimicrobiana de óleo essencial; atividade diurética e hipotensora de extrato aquoso de folhas de Eugenia uniflora. A atividade antimicrobiana foi avaliada pela determinação da concentração inibitória mínima (MIC) e concentração mínima bactericida (MBC) de cepas bacterianas e concentração fungicida mínima (MFC) para fungos. A atividade diurética e hipotensora foi avaliada em ratos Wistar normotensos pela mensuração da pressão sanguínea e fluxo urinário após administração de quatro diferentes concentrações de extrato aquoso (10%, 15%, 20% e 25%). Óleo essencial inibiu o crescimento de Candida parapsilosis e Candida albicans com valores de MIC menores que 14,41 mg/mL, igual a 57,75 mg/mL para Candida krusei. A respeito do efeito antimicrobiano, o óleo essencial inibiu o crescimento de todas as cepas testadas, com MIC igual a 153,93 mg/mL, exceto para Escherichia coli (MIC igual a 307.96 mg/mL). O extrato aquoso mostrou redução importante da pressão arterial (34% e 31% quando comparado ao controle), após administração de 10% e 25% do extrato aquoso, respectivamente. Contudo, os animais que receberam o extrato aquoso na concentração de 15% e 20% apresentaram discreto efeito hipotensor (20% e 21% menor que o grupo controle, respectivamente) concomitantemente ao importante efeito diurético (280% e 91% maior quando comparado ao grupo controle, respectivamente). Esses achados confirmam o potencial efeito biológico dessa espécie, e representa um importante embasamento para estudos relacionados as propriedades terapêuticas da Eugenia uniflora
Subject(s)
Humans , Oils , Diuretics , Eugenia , Hyperglycemia , Anti-Infective Agents , Antifungal Agents , Antihypertensive Agents , Brazil , DNA-Directed DNA Polymerase , AntioxidantsABSTRACT
Angiogenesis, the development of new capillary vessels, has a host of clinical manifestations. The identification of agents that increase or decrease angiogenesis is of great pharmaceutical interest. Classically, in vitro angiogenesis utilizes human umbilical vein endothelial cells (HUVEC) grown in matrigel. This valid and simple method has the drawbacks that each cell population is distinct and the constraint of obtaining primary source material. Herein we utilize the established EA.hy926 endothelial cell line as our model for in vitro angiogenesis and present a novel formula to quantify endothelial cell remodeling to identify pro- and anti-angiogenic agents. Furthermore, our technique details the procedures to identify and quantify compounds that have the capacity to generate pro- or anti-angiogenic factors when given to non-endothelial cells, which we define herein as angiogenic potential. In conclusion, we propose a novel formula that we are confident accurately reflects the degree of in vitro angiogenesis allowing the quantification of prospective angiogenic compounds.
Subject(s)
Humans , Angiogenesis Inducing Agents/pharmacology , Collagen/pharmacology , Endothelial Cells/drug effects , Laminin/pharmacology , Neovascularization, Physiologic/drug effects , Proteoglycans/pharmacology , Cell Line , Drug Combinations , Drug Evaluation, Preclinical , Neovascularization, Physiologic/physiologyABSTRACT
Background and purpose:As a new and important radiotherapy technique,intensity-modulated radiation therapy(IMRT) has been widely used in the clinic,but it requires longer time to deliver for one treatment session.The purpose of this study was to investigate the radiobiological effects of CNE and A549 cell lines irradiated by IMRT model.Methods:Part Ⅰ:The radiobiological characteristics of CNE and A549 cell lines were studied with standard clonogenic assays,using standard liner-quadratic model and incomplete repair model to fit the dose-survival curves.Part Ⅱ:a total dose of 8 Gy was given in two fractions with different interfraction intervals to compare the differences of cell surviving fractions(SF).Part Ⅲ:fractionated irradiation of 2 Gy,2 Gy?2,2 Gy?3,2 Gy?4 were given with one fraction per day simulating clinical dose-time-fractionation pattern in 2,20 and 40 min per fraction,respectively.Results:The ?/? of CNE and A549 was 1.76 and 12.41 Gy,respectively;the cell surviving fractions increased when the interfraction interval was longer,The values of SF2 were 0.0237 and 0.0243 in 2 min irradiation group,0.0304 and 0.0296 in 20 min irradiation group,and increased to 0.0378 and 0.0359 in 40 min irradiation group,respectively.Conclusion:The prolonged fraction delivery time would significantly decrease theradiobiological effects,it is strongly recommended that the delivery time be kept as short as possible,or do appropriate dose compensation.
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Estrogen receptor binding assay is to assess the estrogenic activity of chemicals by determining the ability of competing with 17?-estradiol to bind with estrogen receptor.It has the strengths of simplicity,speediness with good reproducibility.This literature reviewed mainly the mechanism,the research progress,test method,influencing factors of this assay as well as its application.