Papers by Larissa Pereira Brumano

Prescriptions for anorectic psychotropic drugs in the municipality of Juiz de Fora, Minas Gerais,... more Prescriptions for anorectic psychotropic drugs in the municipality of Juiz de Fora, Minas Gerais, Brazil Resumo A obesidade é um grave problema de saúde pública, com prevalência crescente em níveis epidêmicos. Tratamento farmacológico é uma das abordagens terapêuticas, mas deve ser precedido de mudança de hábitos alimentares e prática regular de atividades físicas. Há preocupação com o uso não racional de medicamentos anorexígenos, independente da condição de doença. O estudo avaliou as dispensações destes psicotrópicos realizadas em 2009, Juiz de Fora, MG. Realizou-se a pesquisa em boletins de consumo, enviados mensalmente à VISA municipal, e em registros obtidos no SNGPC. De 7.759 notificações pesquisadas, 93,3% foram dispensadas por farmácias magistrais e 6,7% por drogarias. Daquele total, 55,4% foram de anfepramona, 33,1% de femproporex e 11,5% de mazindol. Com base em relatório da Anvisa, as três substâncias apresentaram consumo maior no município (DDD/mil hab/ano) do que no país como um todo, para o mesmo período. O profissional com maior número de receitas aviadas teve 3.535 dispensações. Todas foram dispensadas em farmácias, sendo 99,5% em um único estabelecimento. O cenário mostra a dispensação de anorexígenos como problema relevante de saúde coletiva e indica a necessidade de reavaliação dos critérios de monitoramento de sua prescrição, dispensação e consumo. Palavras-chave Dispensação, Anorexígenos, Obesidade, Uso racional de medicamentos

The production of second generation (2G) ethanol remains an interesting proposition for the imple... more The production of second generation (2G) ethanol remains an interesting proposition for the implementation of sustainable and net carbon-neutral energy systems. 2G makes use of renewable lignocellulosic feedstocks, generating fermentable sugars that are converted to ethanol or other bio-based products. To be economically viable, 2G biore neries must make use of all processing streams, including the less desirable C5 sugar stream. In this work, a strategy of sequential acid and alkaline pretreatment of the lignocellulosic feedstock switchgrass for improvement of fermentable sugar yield, and the subsequent utilization of wild yeasts for co-fermentation of its C5-C6 sugar streams are presented. Hemicellulose-enriched hydrolysates, obtained by dilute acid pretreatment of switchgrass, were fermented by a newly-isolated wild Scheffersomyces parashehatae strain-UFMG-HM-60.1b; corresponding ethanol yield (Y PS) and volumetric productivity (Q P) were 0.19 g/g and 0.16 g/L h, respectively. Afterwards, the remaining switchgrass cellulignin fraction was subjected to optimized alkaline deligni cation at 152 ºC for 30 min. The deligni ed solid fraction was subjected to contiguous enzymatic sacchari cation and fermentation, releasing a C6 sugar stream in which Saccharomyces cerevisiae 174 strain displayed a productivity of 0.46 g/g (Y PS) and 0.70 g/L h (Q P), whereas the S. parashehatae UFMG-HM-60.1b presented Y PS and Q P of 0.29 g/g and 0.38 g/L h, respectively. Upon combining the conversion of hemicellulose (37%) and cellulose-derived sugars (57%), the S. parashehatae strain provided higher yield (94%) than the generic S. cerevisiae (90%). Henceforth, our integrated pretreatment and co-fermentation process provides a pathway for maximum utilization of the switchgrass carbohydrates for 2G ethanol production.

Journal of Chemical Education, 2020
Protein PEGylation refers to the covalent binding of polyethylene glycol (PEG) moieties to a prot... more Protein PEGylation refers to the covalent binding of polyethylene glycol (PEG) moieties to a protein and has been increasingly applied, mainly in the biopharmaceutical industry. This technique may increase bioavailability and stability by decreasing immunogenicity and proteolytic attack. Given the industrial interest and the relevance of this technique, an example of a common PEGylation reaction is herein proposed, using lysozyme as a model protein. This class is divided into three parts: the first one is composed by the PEGylation reaction per se, the second one aims at the analytical quantification of the PEGylation yield, and the third aims to understand the effects of PEGylation on protein activity. Students should gain skills in comprehending this type of chemical reaction, calculating reaction yields, and realizing the benefits of protein PEGylation. This experimental class comprises two lab classes with the expected duration of 2 h each and is intended for students in the third and fourth years of courses such as pharmaceutical sciences, biochemistry, chemistry, biotechnology, and correlated areas.
Fermentation, Aug 17, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Biossurfactantes são moléculas anfifílicas produzidas por micro-organismos que possuem grande pot... more Biossurfactantes são moléculas anfifílicas produzidas por micro-organismos que possuem grande potencial na substituição de surfactantes químicos, pois apresentam maior biodegradabilidade e estabilidade. A busca por novos micro-organismos, matérias-primas e estratégias de produção é essencial para a viabilização da sua produção. Assim, a fermentação em estado sólido (FES) apresenta-se como uma tecnologia alternativa de produção, com a vantagem de evitar a formação de espuma, e a utilização de leveduras para o processo é vantajosa, pois muitas não apresentam risco de patogenicidade. O objetivo deste trabalho foi selecionar uma levedura capaz de produzir biossurfactante por FES, determinar as condições do processo, comparar com a fermentação submersa (FS), caracterizar bioquimicamente o biossurfactante e testar sua aplicação para biorremediação. Para tanto, 37 leveduras foram avaliadas quanto à produção de biossurfactante em caldo Kitamoto, por meio de testes das atividades tensoativa ...

Sugarcane Biofuels, 2019
The development of sustainable and clean energy sources has gained great importance worldwide due... more The development of sustainable and clean energy sources has gained great importance worldwide due to realization of the urgent need to curb greenhouse gases’ emissions in order to mitigate the effects of climate change. Sugarcane biofuels are important alternative to fossil fuels as they offer environmental and socioeconomic advantages. Brazil leads the world for ethanol production from cane juice, an abundant renewable source in the country. In this context, the status of sugarcane crop in Brazil, capacity of its sugar and ethanol industry, and the current standing of its lignocellulosic biorefineries are presented in this chapter. Additionally, the impact of biofuels economy of Brazil, as well as the acceptance and adaptability at the user’s end are discussed. Moreover, new possibilities of 2G biofuel production after prospective technological improvements to make them even feasible are presented.

Bioresource Technology, 2020
Advanced biorefineries, which aim at valorizing biomass (from agriculture, forestry, aquaculture,... more Advanced biorefineries, which aim at valorizing biomass (from agriculture, forestry, aquaculture, among others) into a wide spectrum of products and bioenergy, are seen today as key to implement a sustainable biobased economy. Although different concepts of biorefinery are currently under development, further research and improvement are still required to obtain environmentally friendly and economically feasible commercial scale biorefineries. Valorization of all biomass components and integration of different disciplines are some of the strategies that have been considered to improve the economic and environmental performance. This paper summarizes and discusses the most recent innovations and strategic orientations for the development of advanced biorefineries. Focus is given on the valorization of non-carbohydrate components of biomass (protein, acetic acid and lignin), on-site and tailor-made production of enzymes, big data analytics, and interdisciplinary efforts. The idea is to provide new insights and directions to support the development and large-scale implementation of biorefineries.

Preparative Biochemistry and Biotechnology, 2019
L-asparaginase is an important enzyme used in the pharmaceutical and food industry, which can be ... more L-asparaginase is an important enzyme used in the pharmaceutical and food industry, which can be produced by different microorganisms using low cost feedstocks. In this work, sugarcane bagasse (SCB) was used as support for enzyme production in solid-state fermentation (SSF) by A. terreus. Initially, the influence of the variables carbon and nitrogen sources on the enzyme production was studied following an experimental design carried out in Erlenmeyer flasks. Statistical analysis indicated the use of 0.54% of starch, 0% of maltose, 0.44% of asparagine, and 1.14% of glutamine in the medium, resulting in enzyme activity per volume of produced extract of 120.723 U/L. Then, these conditions were applied in a horizontal column reactor filled with SCB, producing 105.3 U/L of enzyme activity. Therefore, the potential of extracellular L-asparaginase enzyme production in the column reactor using sugarcane bagasse as support was demonstrated and it represents a system that can favor large scale production.

Biomass Conversion and Biorefinery, 2021
The Antarctic continent is a reservoir of new genetic resources to the bioprospection of microorg... more The Antarctic continent is a reservoir of new genetic resources to the bioprospection of microorganisms adapted to the polar conditions and capable to produce molecules with differentiated properties. Biosurfactants are a promising alternative to replace synthetic surfactants due to their eco-friendly characteristics and the possibility of being produced from raw materials, such as lignocellulosic biomass. The aim of the current study was to evaluate the biosurfactants produced by Antarctic yeast strains using detoxified sugarcane straw hemicellulosic hydrolysate (DSSHH). Therefore, the biosurfactant production, using xylose as the carbon source, was first evaluated in semi-defined medium and subsequently in DSSHH. The Naganishia adellienses L95 showed the highest emulsification index (52%) and total xylose consumption (40 g.L−1) in DSSHH. The biosurfactant produced by the yeast strain L95 was partially characterized, and its emulsion remained stable under low-temperature conditions (0 and 4 °C), at high salt concentration (10%), and alkaline condition. The screening of yeasts for the attainment of natural products that have potential biotechnological applications is of great importance. The results showed the potential of L95 to produce biosurfactants in DSSHH.
BioEnergy Research, 2021
The ratios R τ /P ≡ Γ(τ → P ντ [γ])/Γ(P → µνµ[γ]) (P = π, K) provide sensitive tests of lepton un... more The ratios R τ /P ≡ Γ(τ → P ντ [γ])/Γ(P → µνµ[γ]) (P = π, K) provide sensitive tests of lepton universality |gτ /gµ| = 1 and are a useful tool for new physics searches. The radiative corrections to R τ /P are computed following a large-NC expansion to deal with hadronic effects: Chiral Perturbation Theory is enlarged by including the lightest multiplets of spin-one heavy states such that the relevant Green functions are well-behaved at high energies. We find δR τ /π = (0.18 ± 0.57)% and δR τ /K = (0.97 ± 0.58)%, which imply |gτ /gµ| π = 0.9964 ± 0.0038 and |gτ /gµ| K = 0.9857 ± 0.0078, compatible with and at 1.8σ of lepton universality, respectively. We test unitarity and bind nonstandard effective interactions with the τ → P ντ [γ] decays.
Pharmaceutical Biotechnology, 2021

Pharmaceutics, 2020
Since 1961, L-asparaginase has been used to treat patients with acute lymphocytic leukemia. It ra... more Since 1961, L-asparaginase has been used to treat patients with acute lymphocytic leukemia. It rapidly depletes the plasma asparagine and deprives the blood cells of this circulating amino acid, essential for the metabolic cycles of cells. In the search for viable alternatives to produce L-asparaginase, this work aimed to produce this enzyme from Escherichia coli in a shaker and in a 3 L bioreactor. Three culture media were tested: defined, semi-defined and complex medium. L-asparaginase activity was quantified using the β-hydroxamate aspartic acid method. The defined medium provided the highest L-asparaginase activity. In induction studies, two inducers, lactose and its analog IPTG, were compared. Lactose was chosen as an inducer for the experiments conducted in the bioreactor due to its natural source, lower cost and lower toxicity. Batch and fed-batch cultures were carried out to reach high cell density and then start the induction. Batch cultivation provided a final cell concent...
New and Future Developments in Microbial Biotechnology and Bioengineering, 2020
Abstract The present chapter continues the description of the pharmaceutical applications of biom... more Abstract The present chapter continues the description of the pharmaceutical applications of biomolecules that was started in the previous one. However, here we shift our focus onto production and design strategies. We begin by presenting different biopharmaceutical processing technologies, highlighting the role of continuous manufacturing and molecular biology tools in improving production yield and quality. Finally, prompted by the recent advances of the pharmaceutical sector, we provide the reader with a road map for implementing “Quality-by-Design” in the development of biopharmaceuticals.

Xylitol is a polyol of interest to food, dental and pharmaceutical industries because of its favo... more Xylitol is a polyol of interest to food, dental and pharmaceutical industries because of its favorable characteristics such as sweetening capacity, insulin-independent metabolism effects and its lack of carcinogenic properties. It is usually produced by chemical processes that are expensive due to their high energy consumption and many purification steps. Biotechnological routes are promising because they can be carried out using mild conditions and have the possibility of using hydrolysates from renewable sources as raw materials without the need of extensive purification of xylose before the fermentation step. Different lignocellulosic materials have been studied as alternative raw materials in the fermentative process for xylitol production. However, the structure of lignocellulose is recalcitrant and a pretreatment step is necessary to release monomeric sugars that does not form compounds toxic to microorganisms. Another challenge for xylitol production by fermentation is the id...

Industrial Crops and Products, 2018
Abstract In second-generation bioethanol production, pretreatment and saccharification have been ... more Abstract In second-generation bioethanol production, pretreatment and saccharification have been considered one of the most expensive steps. Thus, we present an approach to improve bioethanol yield by using surfactant concomitantly with corncob pretreatment and saccharification. A response surface methodology (RSM) evaluated the Tween 80 (0%, 5.0%, and 10.0% w/w), in both corncob pretreatment and saccharification, and the enzyme dosage (CellicCTec2: 5.0, 17.5, and 30.0 FPU/gdry matter) on enzymatic digestibility of the acid pretreated biomass. According to the results, higher glucose yields (∼80-85%) could be obtained by reducing the highest enzyme dosage to 41.67% concomitantly by reducing the Tween 80 to 34.2% or 63% by adding it (10% w/w) into only the pretreatment or saccharification, respectively. The RSM suggested applying enzyme dosage between 17.5 and 25.5 FPU/gdry matter associated with the highest Tween 80 amount to improve glucose yield. For statistical validation model, the maximum glucose (80.54%) and xylose (70.66%) yields were obtained for 10.0% of surfactant in both pretreatment and saccharification (25.50 FPU/gdry matter). The hydrolysate was supplemented and fermented by Scheffersomyces stipitis CBS 6054. This yeast fermented the sugars glucose (98.95%), xylose (64.90%), and cellobiose (60.12%) efficiently into ethanol with high yield (0.37 g/g) and volumetric productivity (1.02 gethanol/L.h).

Agradeço a Deus, pelas oportunidades e pessoas especiais que colocou em meu caminho, também por t... more Agradeço a Deus, pelas oportunidades e pessoas especiais que colocou em meu caminho, também por todo amparo e força nas dificuldades, que foram essenciais para que eu chegasse até aqui. Ao prof. Dr. Silvio Silvério da Silva, por ter acreditado em mim e me apoiado desde o início. Por todo ensinamento e orientação que levarei para a vida. Agradeço as oportunidades e tudo aquilo que acrescentou ainda mais a minha formação. Meu sincero muito obrigada! À profa. Dr. Miriam Aparecida de Oliveira Pinto, que me guiou desde os meus primeiros passos na vida científica e por me abrir as portas para este desafio. Obrigada pelo exemplo, confiança e por sua amizade incondicional. Aos professores do Departamento de Biotecnologia, em especial Dr. Júlio César dos Santos, Dra. Maria das Graças de Ameida Felipe, Dra. Inês Roberto e Dr. Arnaldo Prata pelos ensinamentos, dedicação, amizade e apoio. Ao Dr. Joachim Venus, Roland e Mary por me receberem tão bem e confiarem no meu trabalho. Às alunas de iniciação científica e amigas Taciana, Maki e Sara, indispensáveis na realização do trabalho. Obrigada por toda a dedicação e por fazerem tudo mais fácil e divertido. Aos colegas do laboratório Rafael, Sabrina, Itzcóatl, Matheus, Adriana, Kelly, Paulo, Leyanis, Guilherme, Ruly, Michelle, Juliana, Veridiana, Letícia e Júlia pela convivência no dia-a-dia, em especial aos amigos Felipe, Javier e Gilda pelos bons momentos, companheirismo e apoio constante. Aos funcionários Nadir, Walkíria, Paulinho, Isnaldi e demais servidores do departamento, pela disponibilidade, sorrisos e boa vontade em ajudar sempre. Aos amigos da pós-graduação pelos momentos de descontração, por trazerem alegrias no dia-a-dia e nas festas, em especial às minhas amigas e companheiras de república Isabele, Isabela, Fernanda, Luísa e Daiana pelos momentos dentro e fora da faculdade, pela amizade, carinho e conselhos que foram tão importantes para mim. À minha família, meus pais Daniel e Cleuza, e irmãos Danielle e Bruno, pilares essenciais na minha formação, fonte inesgotável de amor, aprendizado, força e confiança de que mesmo com problemas tudo pode ter seu lado alegre. Meus avós amados que mesmo distantes fisicamente sempre estiveram perto e torceram pelo meu sucesso. Aos meus tios e primos queridos que sempre acreditaram em mim. Ao Caio, meu amor, por todo carinho, paciência e apoio nas horas difíceis. Obrigada por me trazer tantas alegrias e acrescentar tanto à minha vida, me tornando uma pessoa melhor. Por fim, agradeço aos professores da banca examinadora, pela atenção na leitura e sugestões desta tese e à CAPES, FAPESP, e CNPq, órgãos cujo apoio financeiro viabilizou este trabalho. " Nada na vida deve ser temido, somente compreendido. Agora é a hora de compreender mais para temer menos. " (Marie Curie) RESUMO BRUMANO, L. P. Produção de biossurfactante por levedura utilizando fermentação em estado sólido em bagaço de cana-de-açúcar. 2017. 162 p. Tese (Doutorado

Frontiers in Bioengineering and Biotechnology, 2019
L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic l... more L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventing metastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity. Consequently, in accordance with Quality-by-Design (QbD) principles, ingenious new products tailored to minimize adverse reactions while increasing patient survival have been devised. In the following pages, the reader is invited for a brief discussion on the most recent developments in this field. Firstly, the review presents an outline of the recent improvements on the manufacturing and formulation processes, which can severely influence important aspects of the product quality profile, such as contamination, aggregation and enzymatic activity. Following, the most recent advances in protein engineering applied to the development of biobetter ASNases (i.e., with reduced glutaminase activity, proteolysis resistant and less immunogenic) using techniques such as site-directed mutagenesis, molecular dynamics, PEGylation, PASylation and bioconjugation are discussed. Afterwards, the attention is shifted toward nanomedicine including technologies such as encapsulation and immobilization, which aim at improving ASNase pharmacokinetics. Besides discussing the results of the most innovative and representative academic research, the review provides an overview of the products already available on the market or in the latest stages of development. With this, the review is intended to provide a solid background for the current product development and underpin the discussions on the target quality profile of future ASNase-based pharmaceuticals.

Renewable Energy, 2017
Due to forthcoming scarcity of fossil fuels and serious environmental concerns, concerted efforts... more Due to forthcoming scarcity of fossil fuels and serious environmental concerns, concerted efforts are required to develop the intensified and robust ethanol production from renewable sources. Currently, lignocellulosic materials are among the main available renewable carbon source in the world. Within this context, we present a novel proposal of intensification of the process for second generation (2G) ethanol production from sugarcane bagasse (SCB) employing fluidized bed reactor. Successive steps of SCB i.e. alkaline pre-treatment, saccharification and fermentation to ethanol were carried out in a same column reactor without opening it during the entire process. In the alkaline pretreatment process, a 22 full factorial design of experiments was designed and executed to evaluate the effect of NaOH concentration (from 0.1 to 0.5 M) and time (from 1 to 4 h) on the enzymatic digestibility of pretreated biomass. Enzymatic hydrolysis yielded glucose and xylose of around 87% and 43%, were achieved, respectively, in saccharification step, when used alkaline pre-treated biomass conducted in process by using variables in high level. Thus, Simultaneous saccharification and co-fermentation (SSCF) were performed by using the wild xylose and glucose fermenting yeast Scheffersomyces shehatae UFMG-HM 52.2, verifying ethanol yield and productivity of 0.34 g/g and 0.18 g L/h, respectively. Results showed the potential of using fluidized bed reactor for ethanol production under different process conditions, reducing equipments and process costs with mass transference.

Bioresource technology, Jan 19, 2017
Surfactants are amphiphilic molecules with large industrial applications produced currently by ch... more Surfactants are amphiphilic molecules with large industrial applications produced currently by chemical routes mainly derived from oil industry. However, biotechnological process, aimed to develop new sustainable process configurations by using favorable microorganisms, already requires investigations in more details. Thus, we present a novel approach for biosurfactant production using the promising yeast Aureobasidium pullulans LB 83, in stirred tank reactor. A central composite face-centered design was carried out to evaluate the effect of the aeration rate (0.1-1.1min(-1)) and sucrose concentration (20-80g.L(-1)) in the biosurfactant maximum tensoactivity and productivity. Statistical analysis showed that the use of variables at high levels enhanced tensoactivity, showing 8.05cm in the oil spread test and productivity of 0.0838cm.h(-1). Also, unprecedented investigation of aeration rate and sucrose concentration relevance in biosurfactant production by A. pullulans in stirred tan...
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Papers by Larissa Pereira Brumano