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Item Ação da formulação mucoadesiva contendo Bidens pilosa L (Asteraceae) sobre a mucosite intestinal induzida por 5- fluorouracil em camundongos(Universidade Federal de Goiás, 2013-08-27) Ávila, Paulo Henrique Marcelino de; Valadares, Marize Campos; Bozinis, Marize Campos Valadares; Fuiza, Tatiana de Sousa; Mendonça , Elismauro Francisco deThe gastrointestinal mucositis is a side effect caused by anti-cancer chemotherapy. Among the drugs used in antineoplastic therapy 5-fluorouracil (5-FU) deserves special attention since the incidence of intestinal mucositis is 80% on treated patients. Despite many studies on intestinal mucositis induced by chemotherapy has been carried out, there aren't effective methods for treating intestinal mucositis, only palliative measures. Moreover, several studies reported anti-inflammatory and immunomodulatory activity of Bidens Pilosa L (BPL). Objective: To investigate the action of BPL in intestinal mucositis induced by 5-FU in mice. Methods: in this study, male Swiss mice were given doses of BPL (75, 100 and 125 mg / kg) and vehicle formulation administered orally (gavage) for 6 days, while doses of 5-FU (200 mg / kg ) were administered (intraperitoneal) from the 4th to 6th day (except in the groups treated with vehicle and formulation of BPL). On day 7, the mice were euthanized and the portion instestinal of each animal was extracted to perform the histomorformetria; expression analysis of Bax, Bcl2 p53 and Ki67 by immunohistochemistry analysis of the inflammatory process through the activity of the enzyme myeloperoxidase (MPO), and evaluation lipid peroxidation by determination of levels malondialdehyde (MDA). It is importantly to note that only the dose of BPL 100 mg/kg which showed better results in the analysis weight and histomorphometric , was chosen to make the immunohistochemistry, MDA and MPO assays.Results:The doses of BPL 75, 100 and 125 mg / kg showed reduce damage triggered by 5-FU in the intestinal mucositis. However the dose of 100 mg / kg was presented the best results in terms of reduction in body mass, as well as morphometric and histological changes induced by 5-FU. Furthermore it was found that treatment with only 3 doses of BPL (75, 100 and 125 mg / kg) caused no toxicological change. It was also found that the expression rate between Bax and Bcl2 were lower in the 100 mg / kg of BPL. Moreover, the dose of 100 mg / kg of BPL showed proliferative effect with increased expression of Ki67 and reduction of inflammatory infiltrate and lipid peroxidation intestinal tissue Conclusion: The results demonstrated that BPL reduced overall damage by 5-FU in intestinal mucositis induced in mice.Item Administração transdérmica de cloridrato de raloxifeno encapsulado em nanopartículas lipídicas: estudos de pré-formulação para seleção dos lipídeos e tensoativos(Universidade Federal de Goiás, 2017-09-26) Alves, Guilherme Liberato; Taveira, Stephânia Fleury; http://lattes.cnpq.br/0382450621383005; Taveira, Stephânia Fleury; Marreto, Ricardo Neves; Gelfuso, Guilherme MartinsIntroduction: Raloxifene hydrochloride (RLX) is a widely prescribed drug for the treatment of osteoporosis and breast cancer. However, RLX presents a low oral bioavailability (2%), being an excellent candidate for transdermal drug delivery. The aim of this work was to develop nanostructured lipid carriers (NLC) containing RLX for transdermal drug delivery. In order to choose proper excipients, a compatibility study was performed. Methodology: Compatibility study was performed with differential scanning calorimeter (DSC), thermogravimetric anaysis (TGA), derivative thermogravimetry (DTG), isothermal stress testing (IST) and solubility study. RLX quantification was performed by high performance liquid chromatography (HPLC). After choosing the excipients, CLN were obtained by the microemulsion technique. Characterization was performed for mean diameter, polidispersivity index (PdI), zeta potential, entrapment efficiency (EE%) and stability. In vitro release and permeation studies were performed in Franz diffusion cells. Results and discussion. Conclusions: Drug-excipient compatibility studies allowed the development of stable and monodisperse CLN, capable of controlling drug release and increase its permeation in the skin when compared to the non-encapsulated drug in the control formulation.Item Alternativas tecnológicas para aumentar a biodisponibilidade de anti-inflamatórios: gel mucoadesivo termorreversível e aplicação de sílica mesoporosa para amorfização(Universidade Federal de Goiás, 2020-03-20) Antonino, Rayane Santa Cruz Martins de Queiroz; Nascimento, Thais Leite; http://lattes.cnpq.br/4065607913504134; Lima, Eliana Martins; http://lattes.cnpq.br/7248774319455970; Lima, Eliana Martins; Alonso, Christian Gonçalves; Gil, Eric de Souza; Silva, Luís Antônio Dantas; Brito, Wesley de AlmeidaImproving the therapeutic response of drugs is one of the major goals of pharmaceutical technology. This large area of research and development uses multidisciplinary technologies and knowledge aimed at optimizing drug delivery systems. It seeks, for example, to reduce side effects with the application of nanoparticulate systems (Chung et al., 2019), to improve the reach of drugs in the central nervous system (CNS) through new delivery and administration systems (Qureshi et al., 2019), increase the delivery and therapeutic action of drugs by promoting longer drug contact time at the site of action, such as the development of mucoadhesive formulations for the treatment of inflamed mucous membranes (Léber et al., 2019). It also seeks to increase the bioavailability of drugs with low aqueous solubility by obtaining the amorphous form of the drug either through porous adsorbent systems, such as mesoporous silicas, but also to increase the stability of the amorphous form in relation to the storage time (Zůza et al., 2019). The search for better therapeutic efficacy of drugs was the main motivation for this research, using different technologies for the development of formulations with different therapeutic objectives and targets. The first part of this research aimed to develop a mucoadhesive in situ thermoreversible gel, capturing a corticosteroid for the treatment of mucous regions with inflammation. This first part produced three scientific publications that are organized as the first two chapters of this document and an annex. The second part of the research aimed to investigate the adsorbent role of mesoporous silica in two different drugs in terms of the tendency to crystallization, aiming beyond bioavailability to increase the physical stability of the systems and the impact of the drugs on the storage of the systems. Through the development of this study, a scientific article was produced presented in the third and last chapter of this document. In summary, the research developed during the PhD period is organized in two parts, in which: Chapter 01 - This chapter has mucoadhesion as its central theme, and constitutes a review of the literature published as a chapter in the book “Sciences applied to health products”, by the publisher of the State University of Goiás in 2019, ISBN 978-85-5582- 060-1 (annex 3). Strategies for the development of new mucoadhesive pharmaceutical forms, mucus and its function in the human body, the theories that analyze mucoadhesion, the mucoadhesive formulations already available and the techniques and assays used to quantify mucoadhesion were covered in this chapter. Chapter 02 - In this chapter we describe the development and characterization in vitro / in vivo of a mucoadhesive in situ gelling formulation using poloxamer 407 (Pluronic® F 127), a thermoreversible polymer, capturing budesonide (BUD), a potent corticosteroid used for treatment of a wide range of inflammatory diseases, including those that affect mucous membranes, such as in the gastrointestinal tract. This chapter was published in 2019 as an original article in the Journal of Controlled Release, entitled Thermoreversible mucoadhesive polymer-drug dispersion for sustained local delivery of budesonide to treat inflammatory disorders of the GI tract (appendix 4). The term with the approval by the ethics committee for the use of animals is attached (annex 1). Another publication, referring to oral pharmaceutical compositions of corticosteroids that gel in situ, was the production of a patent (annex 2). Patent filed and published at the United States Patent and Trademark Office, with international application under Patent Cooperation Treaty (PCT), WO 2018/193423 A1, 2018. This patent is the result of a partnership between the University and a pharmaceutical industry, Ferring Pharmaceuticals, established for the development of mucoadhesive pharmaceutical formulations. In turn, depending on the second part, which deals with technologies aimed at optimizing bioavailability and promoting greater stability using porous adsorbent systems, we have chapter 3. Chapter 03 - In this chapter, a method has been described to determine the monolayer loading capacity (MLC) of naproxen, a weak drug to amorphize, in mesoporous silica (MS). MS can be used as a carrier to stabilize the amorphous form of a drug. In addition, the impact of monolayer, pore filling and excess, on the physical stability of this system was studied and compared to ibuprofen, a strong drug to amorphize. Finally, we investigated the impact of drug loading on storage below and above the glass transition temperature (Tg), in particular with a focus on the amorphous (in) stability of the confined drug, for both drugs. Using Theoretical Functional Density Theory (DFT) and Molecular Dynamics ab initio (AIMD), the binding energies for the monolayer suggest that the monolayer is thermodynamically more favorable than the crystalline form, while the confined amorphous form is thermodynamically less favorable. This chapter was published as an original article in the International Journal of Pharmaceutics: X, in 2019 (Annex 5).Item Análise de deleção/ duplicação nos genes BRCA1 e BRCA2 em pacientes de Goiás-Brasil com suspeita da síndrome do câncer de mama e ovário hereditário(Universidade Federal de Goiás, 2018-03-07) Goveia, Rebeca Mota; Lacerda, Elisângela de Paula Silveira; http://lattes.cnpq.br/9390789693192751; Lacerda, Elisângela de Paula Silveira; Gamba, Bruno Faulin; Lima, Aliny Pereira de; Rocha, Rosângela Hatori; Bérgamo, Nádia AparecidaIntroduction: Breast cancer is the second most common cancer in the world, and the most common among women, only 5% to 10% are hereditary and half of them are caused by hereditary breast and ovarian cancer (HBOC) , caused by variations in the BRCA1 and BRCA2 genes. Objectives: The present study aimed to identify the prevalence of deletions and duplications in BRCA1 and BRCA2 genes in breast cancer patients in Goiás, Brazil. Materials and methods: We evaluated 46 breast cancer patients who met National Comprehensive Cancer Network (NCCN) criteria for HBOC syndrome screening. A 4 ml blood sample was collected for DNA extraction using commercial kit and the MLPA (Multiplex Ligation Dependent Probe Amplification) technique was performed using the SALSA MLPA P002 BRCA1 and SALSA MLPA P045 BRCA2 / CHECK2 kits. Results and discussion: The majority of the patients were female (97.83%) and the mean age of the patients was 37.52 years. In this group, 43.47% of the patients were younger than 35 years at the time of diagnosis and 35% of them were diagnosed with triple negative tumors. The most common molecular subtype was luminal A (46.2%) followed by triple negative tumors (28.20%). No patient was found with rearrangements in BRCA1. In the BRCA2 gene, one patient (2.12%) presented a false positive result for the heterozygous deletion of exon 27, which may have been caused by the presence of a small change in the probe binding region. Conclusion: This was the first study performed to analyze large deletions and duplications in patients from the central-western region of Brazil. We can conclude that the frequency of large deletions and duplications in the BRCA1 and BRCA2 genes in the Goian population is low.Item Análise de métodos alternativos ao uso de animais para a classificação da irritação ocular induzida por corantes têxteis(Universidade Federal de Goiás, 2015-05-29) Ducas, Rafael do Nascimento; Oliveira, Gisele Augusto Rodrigues de; http://lattes.cnpq.br/6221735418479539; Valadares, Marize Campos; http://lattes.cnpq.br/6157755243167018; Valadares, Marize Campos; Parise, Michelle Rocha; Oliveira, Gisele Augusto RodriguesThe evaluation of the toxicity of chemicals still involves the use of animals. However, due to animal welfare and ethical values, research laboratories and regulatory agencies are working together to develop scientifically valid alternative methods. Currently, the Bovine Cornea Opacity and Permeability Test (BCOP) can be used as an alternative methodology to the Draize Test in the determination of ocular irritation and corrosion. In addition, recent data from the literature show that the association between alternative methods represents a useful tool in the evaluation of these parameters. In this context, the objective of this study was to evaluate the efficacy of the BCOP test and the Short-Term Exposure Test (STE) in determining the ocular irritation of Reactive Orange 16 (RO16) and Reactive Green 19 (RG19) based on the United Nations Globally Harmonized System of Classification (UN GHS) and in accordance with the Occupational Safety and Health Administration - Hazard Communication Standard 29 CFR 1910 (OSHA HCS), as Category 2A (eye irritant), using the in vivo test from Draize. The STE test (OECD 491) was used to evaluate cytotoxicity in SIRC cells and the BCOP (OECD 437) assay for opacity, permeability and bovine cornea histopathology. According to the STE test, the RO16 dye obtained cell viability of 47% at 5% concentration and 51% of cell viability at the concentration of 0.05%. The corange RG19 presented cell viability of 41.5% in the concentration of 5% and 44% of cell viability in the concentration of 0.05%. Thus, the dyes were classified as Category 1 of the GHS. The BCOP assay, however, classified only RG19 dye as GHS Category 1 with IVIS: 112,760. The RO16 dye resulted in an IVIS: 12.027, not being classified by this method. To complement this assay, histopathological analyzes were performed, which allowed the observation of significant loss of epithelial cells, intense cytoplasmic vacuolization and damage to the epithelial structure of the corneas exposed to RG19 dye. Although not classified by the BCOP, the corneas exposed to RO16 showed surface coating losses and cytoplasmic vacuolization. Therefore, the STE test alone was not sufficient to define the categorization of the ocular irritation potential of the dyes in relation to the GHS system, but its association with the BCOP test added by the histomorphometric analysis may be an alternative for the prediction of this effect, investigation of other dyes to confirm this fact.Item Análise temporal do perfil de doações e da taxa de inaptidão sorológica de um banco de sangue público no Brasil(Universidade Federal de Goiás, 2018-03-06) Pessoni, Lívia Lara; Alcântara, Keila Correia de; http://lattes.cnpq.br/3089303305362001; Alcântara, Keila Correia de; Santos, Thalyta Renata de Araújo; Leles, Renan NunesIntroduction: Rigor in the selection process of donors led to a decrease in the number of individuals who meet the criteria of clinical and serological suitability for blood donation. In contrast, advances in medicine and the life expectancy of the population have led to an increase in the consumption of blood components. These factors created a challenge for hemotherapy services to guarantee the fulfillment of transfusion demand, combining the availability of blood products in their quality. This scenario led to the search for strategies to attract donors, such as the introduction of incentives to increase the number of donations. Objectives: Conduct a temporal analysis of the profile of blood donations performed in a public blood bank. Materials and methods: Retrospective study of donations between 2010-2016. Part of the analysis was stratified into three periods: before, during and after changing the criteria of an incentive program. Multinomial and multivariate logistic regression was used to verify the association between the explanatory variables and the positive serologies. Trends was evaluated by Prais Winsten's Regression. The Kruskal Wallis test was used to evaluate the seasonality. Results: 149,983 donations (1.08% of the local population) were performed, with a reduction of 29% (p <0.05). 49% of the donations were of the voluntary modality, 30% of campaign, 18% of replacement and 3% of other types of donation. The campaign donations had a 5.67% increase during the first study period (p <0.05), a decrease of 0.85% in the 2nd period (p> 0.05) and 6.65% in the 3rd period (p> 0.05) resulting in a total decrease of 5.02% (p <0.05). The transfusional transmissible infections rate was 3.71%, with a stationary tendency and the chance of donors having a serological disability was lower (OR = 0.8628; CI: 0.8126 - 0.9161; p < 0.0001). Seroprevalences for HBV, syphilis, HCV, HIV, Chagas disease and HTLV were 1.63%, 0.87%, 0.46%, 0.21%, 0.21% and 0.09%, espectively. The prevalence of HBV decreased (b = -0.021, p <0.001), while syphilis increased (b = 0.112; p = 0.001). Conclusion: The amount of blood donation is decreasing, which may be related to the decrease in campaign donations.Item Análise toxicológica por técnicas de triagem aplicada em amostras biológicas post-mortem de casos suspeitos de intoxicação provenientes de Instituto de Criminalítisca(Universidade Federal de Goiás, 2014-02-12) Silva, Maria Augusta Alves; Cunha, Luiz Carlos da; http://lattes.cnpq.br/6349547031976679; Cunha, Luiz Carlos da; Alcântara, Keila Correia de; Effting, CristianeThe toxicological analyzes on various samples are extremely important and can be used for multiple purposes, such as monitoring of drug addicts, forensic analysis, doping control, therapeutic monitoring, analyses of environmental contaminants, etc. The objective of this study was to analyze post - mortem blood samples of the Instituto de Criminalística de Goiás (IC) by immunochromatography and systematic toxicological analysis HPLC - PDA to check the presence or absence of toxic agents. The chromatographic conditions of the method were: mobile phase monobasic potassium phosphate buffer pH 2.3 and acetonitrile, flow rate 1 ml / min, Lichrospher RP8 column, 5μm, 250 x 4.0 mm, scanning range 200-380 nm, the calibration standards were MPPH system, caffeine, benzene and histamine. It was used the database proposed by UVTOX Pragst et al (2001). As part of the partial validation the matrix effect was evaluated by liquid-liquid extraction of whole blood samples contaminated with 8 standards in known concentration. The whole blood samples were extracted at different pH values and analyzed by HPLC -PDA. Through the areas obtained from each standard, it was calculated the standardized factor matrix which showed a coefficient of variation less than 10 %. In order to compare two screening techniques for detection of drugs of abuse, post-mortem blood samples from the IC (n = 35) were also analyzed by immunochromatography, yielding 10 samples positive for amphetamine, 3 for benzoylecgonine and 1 for Δ9THC. The ATS by HPLC – PDA analyses showed only 1 sample positive for benzoylecgonine, 2 samples for amphetamines, and 3 benzodiazepines. In the other samples, no substance toxicological interest was detected. Both immunochromatography as systematic toxicological analysis proved useful tools in screening post-mortem blood.Item Aplicação de diferentes métodos para detecção de eventos adversos a medicamentos em uma unidade de terapia intensiva brasileira(Universidade Federal de Goiás, 2016-12-06) Martins, Renato Rocha; Lopes, Flavio Marques; http://lattes.cnpq.br/5357681644138108; Lopes, Flavio Marques; Silva, Ana Elisa Bauer de Camargo; Dewulf, Nathalie de Lourdes Souza; Santos, Sílvia Helena Rabelo dos; Pereira, Edna Regina SilvaAdverse drug events are damage caused by drugs. Their detection is important to identify risks that affect health system users and to design strategies that improve quality on healthcare. This study aimed to apply different methods of adverse drug event detection in patients admitted to intensive care unit of a public tertiary hospital in the Brazilian Midwest from September 2015 to April 2016. This study was approved by Hospital Alberto Rassi Ethics Committee on Research by report number 1,177,803 and the patients were invited to join voluntarily by signing the Informed Consent Form. In order to achieve the above objectives, this research was conducted in two phases. In the first phase, an analytical, retrospective study compared the use of trigger tool and a non-targeted chart review regarding to adverse drug event detection during hospitalization. Identified events were analyzed by multiprofessional team and classified as their causality, predictability, severity and damage level. In the second phase, this is an analytic, interventional study with purpose of evaluate the impact of medication therapy management on detection of drug-related problems and prevention of adverse drug events. Results found in two phases of this study allowed to recognize that all these tested methods were suitable for the purpose. The search for adverse events performed by trigger tool and a non-targeted chart review allowed identification of similar amounts of events, type of event and related drugs. In both groups the most frequently encountered events were related to metabolic, gastrointestinal, cardiovascular and hematological systems. In this phase, trigger tool application showed to be, among the strategies evaluated, the most convenient. The similar performance to non-targeted chart review supports the use of trigger tool in intensive care units routine, since this method requires less time to retrieve information from medical records. However, the possibility of early identifying a drug-related problem, preventing it from reaching the patient, and the possibility of intervening in non-preventable events, reducing harm, confer an advantage on medication therapy management. The proposed clinical pharmaceutical service allowed the detection of 50 adverse drug events, a low frequency compared to other methodologies. Although, this method was not considered inappropriate for the purpose, since it allowed identification and intervention in 170 other drug-related problems that had potential to cause patient damage. Problems identified at this phase were more often related antibacterials use, caused by improper drug combinations, inadequate dosing, and led to interventions that were accepted by the multiprofessional team, with more than 85% of adherence and total problem solving. These proposed detection methods allowed us to recognize characteristics of adverse drug events occurring in the institution. This information can be used later in order to outline strategies for improvement on healthcare quality. Inserting a clinical pharmacist into the multiprofessional team was a protective factor for critically ill patients, since this professional set up an additional barrier in order to detect and prevent adverse drug events, improving the safety on pharmacotherapy.Item Aplicação De Fungos Filamentosos Na Β-Glicosilação Da Entacapona(Universidade Federal de Goiás, 2011-02-25) LUSTOSA, Keyla Rejane Magno Dias; OLIVEIRA, Valeria de; http://lattes.cnpq.br/6300240031300604The study of bioconversion of biologically active compounds by microorganisms, mainly filamentous fungi and their possible glycosylated derivatives have been extensively explored and have brought promising results. Microbial models of animal metabolism, based on the similarity of the hepatic metabolism and microbial enzyme, became an alternative for the elucidation of metabolic routes of both drugs as well as new drug candidates. In this context, the objective of this study was to explore the ability of filamentous fungi to promote the bioconversion of entacapone and perform the identification, purification and characterization of derivatives formed. We selected eight filamentous fungi Absidia blakesleana ATCC 26617, Aspergillus candidus ATCC 1009, Beauveria bassiana ATCC 7159, Beauveria sp, Cunninghamella echinulata ATCC 9244, Cunninghamella echinulata ATCC 9245, Cunninghamella elegans ATCC 26169 and Rhizopus arrhizuz ATCC 11145, six of them proved to be effective in the metabolism of entacapone, Cunninghamella echinulata ATCC 9245 being the most promising. Were detected 5 different functionalized derivatives, one of which the majority was characterized by Nuclear Magnetic Resonance of Carbon (13C NMR) and Hydrogen (1H NMR), High-Performance Liquid Chromatography coupled to Mass Spectrometer (HPLC-MS/MS) and Infrared Spectroscopy (IR) as a β-glycosylated derivative of entacapone (E, Z): 4 hydroxy-5-nitrophenyl-3-O-(β)-D-glucopyranose-(E)-2-cyano-N, N-diethyl-3-acrylamide.Item Aplicação de fungos filamentosos para S-oxidação do ácido 2-[4-(1,4-tiazinan-4-ilsulfonil) fenilcarbamoil] benzóico (LASSBio-596)(Universidade Federal de Goiás, 2012-06-04) Cavaion, Juliana Camila Lopes; Oliveira, Valéria de; Oliveira, Valéria de; Garrote, Clévia Ferreira Duarte; Silva, Vinícius Barreto daFilamentous fungi have cytochrome P450 enzyme system similar to mammals whose application allows catalyze phase I oxidative reactions of metabolism. Obtaining functionalized derivatives by these microorganisms was the main purpose of this dissertation. Studies in silico to predict metabolism in the programs MetaPrint2D and SMARTCyp indicated S-oxidation, aromatic hydroxylation and dealkylation reactions, as the most likely S-oxidation in thiomorpholine ring of 2-[4-(1,4-thiazinan-4-ylsulfonyl)phenylcarbamoyl]benzoic acid (LASSBio-596). The filamentous fungi Absidia blakesleana ATCC 26617, Aspergillus candidus ATCC 1009, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Cunninghamella echinulata ATCC 9245, Cunninghamella elegans ATCC 36112, Fusarium roseum ATCC 14717 and Streptomyces vendulae ATCC 8664 were used for biotransformation of LASSBio-596. In the reaction conditions applied, substrate dissolved in methanol with concentration of 0.25 mg/mL added to liquid culture medium PDSM and incubated at 27 °C with 200 rpm for 96 hours, the fungus Beauveria bassiana ATCC 7159 performed S-oxidation in the thiomorpholine ring resulting in sulfone derivative of LASSBio-596, called LaBioCon 214, yield of 5.84 %, and it was found the hydrolysis of amide reaction obtaining the compound 4-(thiomorpholinosulfonyl)aniline, LaBioCon 202, yield of 13.8 %. It was noted the solvent used affects the biotransformation process. The monitoring of the reactions and purification of the derivatives obtained were performed by high performance liquid chromatography with ultraviolet detector at 267 nm and preparative chromatography with column Microsorb 100-5 C18 (250 x 10 mm, 5 μm). Subsequently, sulfone derivative was obtained, called LaBioCon 223, by synthesis. Structural characterization was made by classical methods such as 1H NMR and mass spectrometry.Item Aplicação de métodos inovadores na avaliação do potencial alergênico de nanomateriais(Universidade Federal de Goiás, 2019-05-30) Bezerra, Soraia Ferreira; Valadares, Marize Campos; http://lattes.cnpq.br/6157755243167018; Valadares, Marize Campos; Nascimento, Thais Leite; Cunha, Luiz Carlos; Silva, Luiz Antônio DantasIntroduction: The excessive use of fullerene (C60), titanium dioxide (TiO2) and single-wall carbon nanotubes (SWCNTs) in several areas of the industry has resulted in increased human and environmental exposures, evidencing the need for the assessment of toxicological profile of these nanomaterials (NMs). Studies have shown that the interaction of these materials in different systems, including the immune system, may cause several alterations at the cellular and tissue level, demonstrating the need to assess the allergenic potential of these NMs. Nonetheless, few data are available regarding the applicability of in vitro evaluation platforms for NMs toxicity assessment. Objective: The aim of this study was to investigate the skin sensitization potential of NMs (TiO2, SWCNTs and C60) through innovative animal-free methods with regulatory and/or scientific validation. Methods: after dispersion in aqueous solvent, the samples were characterized through the Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) techniques, while the internalization assays were carried out using the dark field microscopy technique (Cytoviva). For the assessment of skin sensitization potential, validated methodologies for regulatory/scientific purposes were used. The key-event 1 of skin sensitization adverse outcome pathway (AOP) (reactivity with skin peptides) was evaluated using the micro-Direct Peptide Reactivity Assay (micro-DPRA) technique and the key event 3 (dendritic cells activation) using the U-SENSTM assay followed by cytokine quantification through the Cytometric Bead Array method by cytometer of flux. Results: NMs were well dispersed when sonicated allowing the evaluation of the allergenicity and modulation of cytokines tests. With the PDI values SWCNTs (0.148), C60 (0.105) e TiO2 (0.548). The internalization assays demonstrated that NMs were internalized by fibroblasts, achieving the intracellular compartment. The mDPRA demonstrated that the NMs interacts potentially with skin peptides, demonstrating a significant percentage of depletion, characterizing these materials as moderate positive sensitizers according to the first key-event of sensitization. Data from the U-SENSTM assay also demonstrated an increase in CD86 marker expression with Stimulation Index (SI) higher than 150 in a concentration-dependent manner, with EC150 for SWCNTs (189.48 μg/mL), C60 (91.72 μg/mL) and TiO2 (183.05 μg/mL). Additionally, cytokine quantitation assays demonstrated a significant production increase of IL-8 by U937 monocytic cell line exposed to NMs, which is a known biomarker of dendritic cell activation. Conclusion: The results demonstrated that micro-DPRA and U-SENSTM methods are applicable for skin sensitization potential assessment of nanomaterials. Furthermore, the evaluated materials presented a positive profile for skin sensitization regarding the first and the third key-event of the Adverse Outcome Pathway of allergenicity.Item Aplicação de um algoritmo para avaliação do desempenho de testes diagnósticos para dengue durante epidemia no Centro-Oeste, Brasil (2012-2013)(Universidade Federal de Goiás, 2017-04-20) Botelho, Pedro Henrique Dias; Féres, Valéria Christina de Rezende; http://lattes.cnpq.br/8089054699896454; Bara, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267; Bara, Maria Teresa Freitas; Alcântara, Keila Correia de; Argolo, Angela Ferreira Lopes de Teive e; Rocha, Benigno Alberto Moraes daIntroduction. Laboratory tests are essential for dengue diagnosis, in that sense algorithms are proposed, which proposes instructions for a more effective laboratory dengue diagnosis. Aim. To evaluate the performance of laboratory tests in the confirmation of suspected dengue cases, appling an algorithm, during a dengue epidemic in Goiânia, Central West Brazil 2012-2013. Methodology. This is a retrospective analytical observational study in a database of a prospective cohort with suspected dengue cases. The algorithm applied was based on three periods in the acute phase of disease, 0-3, 4-7 and >7 days after onset of symptoms (DOS) and in detection of immunoglobulins M and G (IgM and IgG), non-structural 1 protein antigen (NS1Ag) and viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Positivity was seen individually and in association of tests in the algorithm and per day of infection, and used to confirm cases. The tests performance was evaluated by the sensitivity, specificity and accuracy of each test when compared to the others association, also in the algorithm. The results were statistically analyzed using SPSS Statistics 17.0, R software and OPENEPI. Results. 592 patients with suspected dengue were included, 415 (70.1%) were laboratory confirmed. In the 0-3 DOS period, the best positivities were by RT-PCR (81.6%) and NS1Ag (63.3%). While, IgM obtained the best positivities in 4-7 and >7 DOS periods (85.5% and 93.3%, respectively). Individually, RT-PCR and IgM tests were the most efficient to add positivity to diagnosis at the beginning and at the end of the acute phase of infection, respectively. Sensitivity results were similar to those of positivity, whereas NS1Ag specificities were greater than 90% at all periods. Conclusion. The algorithm sowed which laboratorial test was the best for the course of disease. Until 3 DOS, molecular is most sensitive test; between 4-7 DOS, two techniques may be required to obtain an accurate diagnostic. NS1Ag test, presented less detection in secondary infection cases, however, they was more specific test and can be used in differential diagnosis of dengue. These results contributed to diagnostic decision in the epidemiological context with concomitant arbovirus circulation.Item APLICAÇÃO DO ENSAIO DE DISSOLUÇÃO NA AVALIAÇÃO DA QUALIDADE DE MEDICAMENTOS FITOTERÁPICOS À BASE DE Passiflora sp(Universidade Federal de Goiás, 2008-10-29) COSTA, Ane Rosalina Trento; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267Phytomedicines must to have as active ingredients only products derived from plants. The quality control of these medicines has not yet properly established criteria even with the growing consumption of these drugs worldwide. Among the assays to evaluate the quality there is the test of dissolution, used to examine the release of the active principle from a capsule or tablet in medium that simulates the place of their absorption. Among the nature drugs best known there is Passiflora incarnata L., whose possess sedative action. The C-flavonoid glycosides vitexin and isovitexin are the main components found in aereal parts of Passiflora sp and are used as markers of the genus in the tests of quality control. This study was conducted to apply the test of dissolution to phytotherapy containing passion flower. The method for quantifying of capsules and tablets used was the spectrophotometric assay described in British Pharmacopoeia (2007) to the powder of P. incarnata. The method has been validated for capsules and then used in the tests of dissolution, with apparatus shovel, 37 C ± 0.5 ° C, speed of 50 rpm in 500 mL of the medium of dissolution 0.1 M HCl pH 1.2, collecting 50 ml at the end of 30 minutes. We have investigated an alternative method for quantification of total flavonoids in ultraviolet spectrophotometer , in a wavelength of 269 nm or 350 nm, looking for a more simple and quick method to be used in routine testing, and because be less polluting and unhealthy. In the tests carried out to quantify the levels of total flavonoids found for the manipulated capsules were 2% for powder and 0.975 % for dry extract; for industrialized tablets the levels were 5.5% and 1.52%. The dissolution assay of the pharmaceutical forms at this study showed that the capsules containing dry extract or powder and one of the industrialized tablets showed 87%, 75% e 76%, respectively, of dissolution within 30 minutes of tests. In relation to the proposed alternative method, was selected the wavelength 350 nm for direct quantification of flavonoids presents in the phytomedicines and at the medium of dissolution. It can be noted that the results were consistent and similar to the datas of the validated method: 85% to dry extract, 80% to powder e 75% to one of the industrialized tablets. Whereas the phytomedicines represent a niche market and an opportunity for diversification of the national pharmaceutical industry, it is necessary to defined parameters of quality to ensure its therapeutic action. So, the studies of dissolution are an essential tool which helps to ensuring the quality of these medicines.Item Aplicação do fungo filamentoso Beauveria bassiana spp. na produção de derivado potencialmente vasodilatador e antiproliferativo de naringenina(Universidade Federal de Goiás, 2012-03-23) SILVEIRA, Juliana Penso da; OLIVEIRA, Valeria de; http://lattes.cnpq.br/6300240031300604Item Aplicação do modelo microbiano do metabolismo animal ao estudo da biotransformação de um potencial agente anti-hipertensivo(Universidade Federal de Goiás, 2013-05-27) Guimarães, Telma de Matos; Oliveira, Valéria de; Oliveira, Valéria de; Costa, Maísa Borges; Menegatti, RicardoThe " Microbial Models of Mammalian Metabolism" using filamentous fungi be used to study the biotransformation as an alternative to identify and product mammalian metabolites, with the goal of evaluate the profile of biotransformation of LASSBio 897, this This model was appliedto 3-thyenilidine-3,4-methylenedioxybenzoylhydrazide (LASSBio-897), a potential antihypertensive agent. The fungi Aspergillus alliaceus NRRL315, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC9244, NRRL1757 and Mortierela isabelina NRRL 1757 e Muccor plumbeus ATCC4740 were selected for the biotransformation LASSBio-897. The biotransformation was carried outin culture medium PDSM and Corn Steep at two different concentration sof the substrate.The monitoring of there action kinetics was done by methods thin layer chromatography (TLC) and high performance liquid chromatography(HPLC), separation and purification of the formed products was performed by colun chromatography (CC). Nuclear magnetic resonance (RMN) methods, mass spectrometry and spectroscopyin the region of Infrared (IR) assisted in the elucidation of the structure of the biotransformation products of LASSBio 897. We identified four metabolites in the reaction mixture and, based on information obtained by MS and NMR was proposed structure of 3-tienilidena-3,4-dihydroxybenzoilidrazine (Met. I), 1,3-benzodioxol-5-carboxamide (Met. II), 1, 3-benzodioxol acid (Met. III) and sulfoxide (Met. IV); A simultaneous study of the pharmacokinetics of LASSBio 897 in healthy Beagle dog indicated the presence of MET.I and II in dog serum confirming the importance of applying this model.to obtain metabolites mamalia.Item Aplicação do modelo microbiano do metabolismo animal ao estudo da biotransformação de um potencial agente cardioativo(Universidade Federal de Goiás, 2011-02-28) Carneiro, Emmanuel de Oliveira; Oliveira, Valéria de; http://lattes.cnpq.br/6300240031300604; Oliveira, Valéria de; Porto, André Luiz Meleiro; Andrade, Carolina HortaDrug metabolism, or biotransformation, is the enzymatically catalyzed conversion of a drug to a chemically distinct product, known generically as metabolite. The biotransformation impact on drugs biological fate makes essential to study it in the early stages of drug development. Traditionally, in vivo metabolism are conducted in animal models, whose biological fluids are examined for metabolites identification. The observation that simple microorganisms can mimic most of the phase I and some phase II reactions performed in mammals has shown they represent an alternative to produce high amounts of metabolites in vitro. The main organisms used are filamentous fungi, with particular attention to Beauveria bassiana and the genus Cunninghamella. The aim of this work is the application of B. bassiana as a microbial model to study LASSBio-294 biotransformation profile in parallel to an animal model. This substance has demonstrated significant positive inotropic and vasodilatory properties, turning it a potential cardioactive prototype. A capsule with LASSBio-294 was administered to a dog in a pilot study and analyzed by High Performance Liquid Chromatography with Ultraviolet detection (HPLCUV). B. bassiana ATCC 7159 incubation supernatant samples were taken and analyzed by HPLC- UV. At the end of the process, formed metabolites were extracted and purified. One product was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). According to the HPLC-UV analysis, B. bassiana ATCC 7159 produced a major metabolite detected in higher concentration after 24 hours of incubation. This metabolite was the same detected in dog serum samples. The biosynthesis of this metabolite resulted in a yield of 6%. The spectral data show the produced metabolite by dog and B. bassiana ATCC 7159 is a LASSBio-294 sulfoxide derivative. In vitro biosynthesis allowed to obtain, in considerable yield, the main mammalian metabolite detected in the in vivo method.Item Aproveitamento da casca e polpa de Baru (Dipteryx alata Vogel) no desenvolvimento de um protótipo de suplemento alimentar, enriquecido com selênio(Universidade Federal de Goiás, 2019-06-28) Santos, Cláudia Maria Barbosa; Santiago, Raquel de Andrade Cardoso; http://lattes.cnpq.br/0424807117498265; Conceição, Edemilson Cardoso da; http://lattes.cnpq.br/7193007113950510; Santiago, Raquel de Andrade Cardoso; Nóbrega, Andréa Bezerra da; Morais, Carla Cristina deIntroduction. Baru is a plant typical of the Cerrado Biome, whose nutritional potential is little explored, especially in the case of bark and pulp. It is known that baru has a fibrous pulp, and despite the benefits it can provide such as, reduced food consumption by increasing satiety power and consequent reduction in waist hip ratio, control of arterial hypertension and improvement of intestinal functioning , 68% of the population has less fiber intake than recommended. For this reason your supplementation may be beneficial. In addition to fiber, another important nutrient for health is selenium, given its association with changes or malfunctioning of the digestive tract. Objective. Develop a prototype food supplement in sachets, from bark and pulp of baru, that meets the daily nutritional needs of fiber and selenium. Methods. The raw material was obtained and characterized. The microbiological quality, centesimal composition, evaluation of the accelerated stability study of bark pulp powder and baru pulp and the prototype of the supplement were evaluated. Results and discussion. The raw material was adequate for the quality parameters. With the addition of excipients the prototype remained stable, with respect to the microbiological profile, humidity, fibers, selenium and other parameters. Two sachets with 30 g of supplement provides an energy value of 67.40 kcal, 1.56 g of protein, 0.82 g of lipids, 13.44 g of carbohydrates, 9.42 g of fibers, 200.32 g of selenium, 24.20 mg of calcium, 144.90 μg of copper, 0.98 mg of iron, 0.018 mg of phosphorus, 9.86 mg of magnesium, 0.283 mg of manganese, 211.468 mg of potassium, 6.591 mg of sodium and 0.225 mg of zinc. The labeling of the prototype of the supplement may be attributed as: source of fibers, source and / or selenium-rich, source of copper and low sodium content. Conclusion. The elaborated formulation was able to meet the recommendations for food supplement in relation to dietary fiber and selenium, for the population group above 19 years of age, can be used for other food purposes and also contribute to the use of parts of the fruit that are discarded.Item Atividade antitumoral e antiangiogênica de Synadenium umbellatum Pax in vitro e in vivo(Universidade Federal de Goiás, 2008-03-11) NOGUEIRA, Iara Antonia Lustosa; BOZINIS, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018Synadenium umbellatum Pax is a vegetable belonging to Euphorbiaceae, popularly known as cola-nota , milagrosa , and cancerola , is empirically used as a natural remedy for fighting cancer. In this study we assessed the antitumoral and antiangiogenic activity in vitro and in vivo of ethanolic crude extract and hexanic and chloroformic fractions of S. umbellatum. Citotoxicity assessment tests in vitro were carried out through MTT reduction and Trypan blue exclusion methods, by using Ehrlich ascitic tumor cells and K-562 lineage. Antitumoral and antiangiogenic activity in vivo essays were carried out through Ehrlich ascitic tumor experimental model in Swiss mice. Ethanolic crude extract was tested in 5, 10 and 25 mg/kg/day doses, whereas chloroformic fraction was tested in 1.2; 2.3 and 5.8 mg/kg/day doses, and hexanic fraction in 0.4; 0.8; and 1.9 mg/kg/day doses, for 10 days. The results showed concentration-dependent citotoxic activity, presenting through MTT method the inhibitory concentrations of 50% (Cl 50) 0.4, 0.1, and 0.08 mg/ml for ethanolic crude extract, chloroformic and hexanic fractions, respectively. And in the Trypan blue exclusion test, cell inhibition was 75%, 68%, and 80%, and 95%, 58%, and 64% for Ehrlich ascitic tumor cells and K-562 lineage, respectively. Ethanolic crude extract in the 25mg/kg/day dose increased the animals survival rate, parallely with the reduction of the amount of tumoral cells, beyond present activity on the tumor angiogenesis, and reduce vascular endothelial growth factor levels. Chloroformic and hexanic fractions, in in vivo essays, did not present significant outcomes. Thus, can conclude in the condition this study, that S. umbellatum shows antitumoral and antiangiogenic activityItem Atividade hepatoprotetora do extrato hidroalcólico do resíduo agroindustrial de jabuticaba (Myrciaria cauliflora O. Berg), e do extrato etanólico das folhas de fruta-pão (Artocarpus altilis (Parkinson) Fosberg), em camundongos(Universidade Federal de Goiás, 2015-04-01) Silva, Marina Alves Coelho; Cunha, Luiz Carlos da; http://lattes.cnpq.br/6349547031976679; Cunha, Luiz Carlos da; Valladão, Adryano Augusto; Parente, Leila Maria LealWas evaluated the hepatoprotective effect of hydro alcoholic extract of the agroindustrial waste of jaboticaba-paulista (HEJB (Myrciaria cauliflora O. Berg, Myrtaceae) and ethanolic extract of breadfruit leaves (EEBL) (Artocarpus altilis (Park.) Fosberg, Moraceae) in experimental model of hepatotoxicity carbon tetrachloride (CCl4). The jaboticaba tree is native to Brazil and largely grown. It has a potential antioxidant, with phenolic compounds present primarily in the peel of fruit, which is a waste from the manufacturing process jaboticaba wine. Breadfruit is originating to the Pacific Islands and is distributed throughout the world. Fruits and leaves of this plant species have compounds with pharmacological properties, such as flavonoids. Were used Swiss mice, male, divided in eight groups, with five being the control groups (I: Baseline, received no treatment; II: olive oil, 10 mL/kg, i.p.; III: Propylene glycol 50%, 10 ml/kg, v.o. IV: 0.3% CCl4 in olive oil 10 mL/kg, i.p., negative control; V: Silymarin 200 mg/kg, v.o., positive control) and four treated groups, v.o. (VI: HEJB 250 mg/kg, VII: HEJB 500 mg/kg, VIII: EEBL: 250 mg/kg). Except groups I and II, all others received 0.3% CCl4 in olive oil on the 7th day of treatment, 2 hours after administration v.o. Were monitored the weight gain and no had significant difference between groups. At the end of the treatments, blood and liver of the animals were removed for biochemical analysis, after the animals were submitted to euthanasia and macroscopic evaluation of organs and cavities. The potential hepatoprotective and antioxidant activity of plant extracts were observed through the hepatic enzyme L-alanine aminotransferase (ALT), L-aspartate aminotransferase (AST), glutathione peroxidase (GPx ), glutathione reductase (GR) and catalase (CAT) and the dosage of malondialdehyde (MDA) - which required validation analytical HPLC-PDA. The bioanalytical method has a linear, selective, accurate, precise, and without interfering with LOQ 0.5 nmol/mL and LOD of 0.25 nmol/ml, suitable for the dosage of MDA in plasma and liver. There was a decrease of MDA in liver tissue, for the two extracts, as well as decreased levels of AST / ALT and GR to post-treatment with EHJB. The agroindustrial waste of jaboticaba fruit peel and the ethanolic extract of breadfruit leaves showed antioxidant activity in vivo.Item Avaliação da atividade antileucêmica in vitro e toxicológica in vivo do composto LQFM-018(Universidade Federal de Goiás, 2011-08-31) Costa, Fabiana Bettanin; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Bozinis, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018; Blanco, Marcos Luengo; Cruz, Andrezza Furquim daCancer is a serious public health problem not only in Brazil but worldwide. Among the various types of cancer known, leukemia is a one of high incidence. In this context, our study aimed to verify the citotoxicity of the compound LQFM-018, in leukemic cells. Both the method of trypan blue exclusion as in the MTT, it was observed a concentration and time dependent response after treatment with the compound LQFM-018. The cell death mechanism was assessed by flow cytometry. The cell cycle analysis showed a decrease of cells in G1 phase with a consequent increase in S phase and G2 / M. The cell death mechanism detected by annexin-V test showed that the K-562 cells were mainly in necrosis. The increased release of LDH also corroborated with the necrotic process. In the treated cells, there was not a significant expression of tumor suppressor protein p-53. The expression of nuclear factor кB increased and decreased expression of ROS. It was also found an increased expression of TNF-R1 receptor, cytochrome-c, decreased ΔΨm and not the expression of proteins Bax and Bcl-2. Acute oral toxicity test was done in vivo. According to the results, the compound LQFM-018 was classified as category 5. The statistical analysis was done using Student t test and ANOVA followed or not by Bonferroni post-test. Was considered statistically significant p<0.05. From these results, we found that the compound LQFM-018 presents potential antitumor activity, but other tests are needed to confirm these results.