d-Limonene is a lipid-soluble bioactive food component found in citrus peel. It has demonstrated strong chemopreventive effects in rodent mammary, gastric, skin, liver, and lung cancers and is correlated with a significantly reduced risk for human squamous cell skin carcinoma. Because d-limonene is fat-soluble, it may have enhanced chemopreventive activity in fatty tissues such as breast. No previous methodology to quantify d-limonene in the adipose had been developed which significantly limited d-limonene tissue distribution research. For this research, an assay to extract d-limonene from adipose tissue and quantify with GC/MS was developed and validated. Linear calibration curves were established over the range of 0.0-2,526 ng d-limonene. Extraction recovery was 80%. Satisfactory within day precision (RSD 6.75 to 9.56%) and accuracy (% difference of 2-4%) were achieved. This sensitive, accurate, and precise assay to quantify d-limonene in adipose can be used for future human or animal fatty tissue deposition studies.

d-Limonene is a monoterpene found in high concentration in citrus peel oil. Evidence from animal models and cell culture indicate that it has strong anti-cancer effects, particularly in mammary cancer models. Chapter 1; "D-LIMONENE: A BIOACTIVE FOOD COMPONENT FROM CITRUS AND EVIDENCE FOR A POTENTIAL ROLE IN BREAST CANCER PREVENTION AND TREATMENT" is a review paper accepted to Oncology Reviews. This review describes the evidence for <italic>d<italic>-limonene's anti-cancer mechanisms, bioavailability and safety, focusing on relevance to breast cancer prevention. Chapter 2; "ADIPOSE TISSUE ACCUMULATION OF D-LIMONENE WITH THE CONSUMPTION OF A LEMONADE PREPARATION RICH IN D-LIMONENE CONTENT" is published in Nutrition and Cancer journal and describes a phase I clinical trial in which participants consumed 40 oz of high-limonene lemonade daily. This study demonstrated that after 4 weeks of oral consumption of high-limonene lemonade, d-limonene deposits in high levels in adipose tissue. Chapter 3; "A CLINICAL BIOMARKER STUDY OF TOPICALLY APPLIED D-LIMONENE FOR BREAST CANCER PREVENTION" was submitted to Nutrition and Cancer journal. In this phase 0 clinical study, four weeks of a 10% d-limonene formulation resulted in minimal change in NAF and plasma biomarkers or d-limonene levels. Biomarkers in NAF and plasma, however, were significantly differently correlated with BMI and menopausal status, perhaps suggesting effect modifications. Chapter 4: "MOUSE MAMMARY TISSUE DISTRIBUTION OF D-LIMONENE AND PERILLIC ACID FOLLOWING ORAL AND TOPICAL D-LIMONENE ADMINISTRATION," was a study comparing d-limonene and perillic acid disposition after administration of 10% and 20% d-limonene in coconut oil in topical and oral forms to SKH-1 mice. This study demonstrated that d-limonene deposits in high levels in mouse mammary tissue after both oral and topical administration short-term, but is largely cleared after 24 hours in this model. Perillic acid deposits in high levels in adipose after oral administration, and these high concentrations remained after 24 hours. Chapter 5: "IMPLICATIONS AND FUTURE DIRECTIONS" provides a summary of the key findings from these three projects and proposals for future research. The appendices provide results from smaller d-limonene projects, as well as extensions of the body of the dissertation work.

Tender coconut water (TCW) is one of most consumed natural energy drinks. Although it is widely available in tropical countries, because of its natural health benefits it is increasingly consumed in other parts of the world. Therefore there has been an increased requirement for packaging and shipping. TCW is highly susceptible to microbial contamination during extraction and packaging, requiring pasteurization. Thermal pasteurization leads to loss of flavor and color of coconut water. The purpose of this study was to test the feasibility of a non-thermal method of pasteurization of TCW using natural antimicrobials like curcumin, eugenol, and d-limonene with curcumin. The non-thermal pasteurization method was developed in two different processes, i.e. a batch and flow-filter process. Batch cold pasteurization process was conducted by suspending liposome encapsulated antimicrobials immobilized on glassbeads in TCW at 4oC by shake flask assay. Maximum Reduction of Listeria monocytogenes and Escherichia coli W1485 in pasteurized TCW were observed to be 5 log CFU per ml of TCW within 7 days of incubation under the presence of nano-liposomes containing 50 mM of curcumin, d- limonene or eugenol. There was no change in color and aroma of TCW after 1 month of storage at 4oC. the flow filter cold pasteurization process was developed using filter medium coated with nano-liposomes encapsulated antimicrobial leading to extended release of the natural antimicrobial curcumin to the coconut water in 4oC. Listeria monocytogenes and E. coli W1485 were used as model organisms to test effectiveness of cold pasteurization. Reduction of L. monocytogenes and E. coli W1485 in pasteurized TCW was observed to be 5.2 and 4.5 log10CFU/ml of TCW respectively within 17.25 min of incubation under the presence of nano-liposomes containing 50 mM of curcumin. There was no change in color and aroma of TCW after 1 week of storage at 4oC.

Ozone (O₃) and terpenoids react to produce secondary organic aerosol (SOA). This work explored novel ways that these reactions form SOA indoors, with five investigations, in two categories: investigations of (i) the impacts of particle controls on indoor SOA formation, and (ii) two fundamental aspects of indoor SOA formation. For category (i), two investigations examined the particle control devices of ion generators, which are air purifiers that are ineffective at removing particles and emit ozone during operation. With a terpenoid source present (an air freshener), ion generators acted as steady-state SOA generators, both in a 15 m³ chamber and 27 m³ room. The final investigation in category (i) modeled how heating, ventilating, and air-conditioning (HVAC) systems influence SOA formation. Influential HVAC parameters were flow rates, particle filtration, and indoor temperature for residential and commercial models, as well as ozone removal by particle-laden filters for the commercial model. For category (ii), the first investigation measured SOA formation from ozone reactions with single terpenoids and terpenoid mixtures in a 90 L Teflon-film chamber, at low and high ozone concentrations. For low ozone, experiments with only d-limonene yielded the largest SOA number formation, relative to other mixtures, some of which had three times the effective amount of reactive terpenoids. This trend was not observed for high ozone experiments, and these results imply that ozone-limited reactions with d-limonene form byproducts with high nucleation potential. The second investigation in category (ii) explored SOA formation from ozone reactions with surface-adsorbed terpenoids. A model framework was developed to describe SOA formation due to ozone/terpenoid surface reactions, and experiments in a 283 L chamber determined the SOA yield for ozone/d-limonene surface reactions. The observed molar yields were 0.14–0.16 over a range of relative humidities, and lower relative humidity led to higher SOA number formation from surface reactions. Building materials on which ozone/d-limonene surface reactions are predicted to lead to substantial SOA formation are those with initially low surface reactivity, such as glass, sealed materials, or metals. The results from category (ii) suggest significant, previously unexplored mechanisms of SOA number formation indoors. / text

Anyžinis lofantas (Agastache foeniculum (Pursh) Kuntze) – tai vaistinis, prieskoninis daugiametis augalas. Vienas iš notrelinių šeimos dekoratyvus, daugiametis žolinis augalas, kilęs iš Šiaurės Amerikos. Lietuvoje kol kas dar mažai paplitęs. Auginamas botanikos soduose ir darželiuose, vertinamas kaip labai kvapnus, medingas ir vaistinis augalas. Anyžinis lofantas dirvai mažai reiklus, turi gerai išvystytą šaknų sistemą, todėl nebijo sausros. Geriau auga derlingesnėje žemėje, nepiktžolėtose priesmėlio arba lengvo priemolio dirvose, atviroje, saulėtoje vietoje. Žydi nuo birželio vidurio iki spalio mėnesio. Žiedai – ryškiai violetiniai arba melsvi. Agastache foeniculum paruoštas VDU Kauno Botanikos sode, 2010 metais masinio žydėjimo metu. Sausoje žaliavoje yra 1,71-2,10 % eterinio aliejaus, kurio svarbiausios dalys yra D-limonenas ir estragolis. Nupjauta žolė džiovinama paskleista plonu sluoksniu gerai vėdinamoje arba 35°C temperatūros patalpoje. Išdžiovinta žolė atskiriama nuo stambesnių stiebų ir laikoma sudėta į medžiaginius maišus. Tinkamai išdžiovinta žolė yra 12 - 14 % drėgnumo. Džiovinimas – vienas svarbiausių etapų, kuris labiausiai įtakoja galutinę vaistinės žaliavos kokybę. Šiame darbe – buvo identifikuoti Agastache foeniculum eterinių aliejų komponentai: D- limonenas, estragolis, kariofilenas. Vaistinio anyžinio lofanto eterinių aliejų ekstraktai ruošti naudojant superkritinio skysčio CO2 ekstrakciją. Jų analizė atlikta dujų chromatografu– masių spektrometrijos... [toliau žr. visą tekstą] / Blue giant hyssop (Agastache foeniculum (Pursh Kuntze) is medicinal perennial plant. This ornamental plant is native to North America. In Lithuania is not yet widely spread. It is cultivated in botanical gardens and is valuable because is a fragrant, melliferous medicinal plant. Blue giant hyssop is not strict for soil and has a well developed system of the roots, so it is resistant to drought. This plant prefers a good soil and sunny places. It blooms from the middle of June to October. The flowers are violet or royal-blue. Agastache foeniculum raw material was prepared in Kaunas botanical garden of VMU during flowering season in 2010. In dry raw material is about 1.71 – 2.10  of essential oils, the basic components are D-limonene and estragol. The grass after cutting was spread in a thin layer in well ventilated room or in the room at 35 C temperature. The dried grass was separated from stems and stored in huckaback bags. The well dried grass has about of 12-14  moisture. The drying is one of the most important periods which influence the final quality of drug raw material. In this work the components of essential oils of Agastache foeniculum have been identified. The extracts of volatile oils of Agastache foeniculum were prepared by supercritical CO2 extraction. After the analysis the relative quantities of essential oils components as well as composition have been evaluated by gas chromatography-mass spectrometry detector. Investigations have showed that the... [to full text]

Submitted by LUIS FRANCISCO MICHELI (luis.micheli@unesp.br) on 2018-10-19T18:59:13Z No. of bitstreams: 1 Versão Final r4.pdf: 3404641 bytes, checksum: 84fa67d5e2f835f7f6d2a8db1089132f (MD5) / Approved for entry into archive by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br) on 2018-10-19T19:13:56Z (GMT) No. of bitstreams: 1 micheli_lf_me_bauru.pdf: 3404641 bytes, checksum: 84fa67d5e2f835f7f6d2a8db1089132f (MD5) / Made available in DSpace on 2018-10-19T19:13:56Z (GMT). No. of bitstreams: 1 micheli_lf_me_bauru.pdf: 3404641 bytes, checksum: 84fa67d5e2f835f7f6d2a8db1089132f (MD5) Previous issue date: 2018-09-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A reação de transesterificação de óleos vegetais com álcool etílico ou metílico dá origem a ésteres metílicos ou etílicos de ácidos graxos, conhecidos como biodiesel. Este apresenta propriedades próximas do óleo diesel mineral como o número de cetano, massa específica, poder calorífico e relação ar-combustível. Porém, problemas decorrentes de sua maior viscosidade resultam em uma pulverização deficiente pelos bicos injetores levando a uma combustão de qualidade inferior, e com isso, formação de depósitos indesejáveis no interior do motor, alterações nas propriedades do óleo lubrificante e na composição dos gases de escape. Frente a essa questão se faz necessário o estudo da utilização de um aditivo capaz de tornar as características do biodiesel mais adequadas à sua utilização em motores de ignição por compressão e também o acompanhamento das alterações na composição dos gases de escape. O aditivo estudado nesse trabalho foi o d-limoneno, um hidrocarboneto obtido como subproduto da citricultura, que foi adicionado ao óleo diesel à ser utilizado como combustível do conjunto moto-gerador utilizado nos ensaios. Neste sistema foram aplicadas diferentes cargas e coletados os dados relativos à emissão do motor. Resultados relevantes como a redução de material particulados foram observados mesmo com a adição de pequenas quantidades de d-limoneno. / The transesterification of vegetable oils with methanol or ethanol results in methyl esters or ethyl esters of fatty acid, known as biodiesel. This one presents similar features of diesel oil, such as cetane number, specific weight, heat of combustion and air-fuel ratio. However, arising problems from its higher viscosity leads to a poor spraying by the fuel injectors and so to a low-grade combustion, causing formation of undesirable deposits inside the engine, changes in the properties of the lubricating oil and in the composition of the exhaust gas. Owing to this issue, it is necessary to study an additive able to make biodiesel characteristics more appropriate to be used in compression ignition engines, as well as a monitoring of changes in exhaust gas composition. The chosen additive was d-limonene, a hydrocarbon obtained as a byproduct of citriculture, which was added to diesel fuel to be used as fuel for the motor-generator set used in the tests. Different loads were applied to this system and the engine emission data were collected. Relevant results such as the reduction of particulate material were observed even with small amounts of d-limonene added. / CAPES:DS 1600969

In this study, low density polyethylene (LDPE) and polyethylene terephalate (PETE) resin beads were ground to a coarse powder and exposed to sterilization treatments applied to the food contact surface of packaging materials used in aseptically processed and packaged food. Electron paranlagnetic resonance (EPR) analyzed free radical (-CH2CHCH=CHCHz-) production on the surface of LDPE exposed to heat (107°C) and treatments of heat (107°C) + 30% hydrogen peroxide solution (H20 2). As the temperature was raised from 100° to 200°C, peak intensity of carbon radicals produced gradually increased. The sensitivity of EPR prevented detection of free radicals on LDPE, exposed to H20 2 treatment, due to residual peroxide and H20 condensation on the surface of LDPE. D-limonene was placed in 12ml sealed glass vials containing a sodium citrate buffer solution (pH=3.7), under atmospheric O₂ (21%) conditions. Oxidation of d-limonene, placed in intimate contact with untreated, HzOz treated, and ultraviolet (VV) light (650mW/cm2) treated LDPE for 15 weeks, was measured to determine the capacity of an oxidized polymer to initiate autoxidation. The oxidation of d-limonene in vials containing no polymer was also measured. Production of carvone and carveol were used as an index for oxidation. No polymer and UV treated samples showed significantly (P<0.05) higher levels of calVone and calVeol than samples containing untreated and HzOz treated LDPE. Samples containing no polymer oxidized d-limonene at the highest rate, but not significantly faster than solutions containing UV treated LDPE. Accumulation of carvone and carveol was zero order. / Ph. D.

Today, the scenario of the world and brazilian energy matrix is of great difficulty, due to increased demand for fossil fuels causing instabilities in prices and in the fuel sector, as well as serious environmental risks to the whole population. The difficult time comes driving the search for new sources of renewable and clean energy such as biogas. In this way, this work aimed to evaluate the anaerobic biodigestion from the residue of agro-industry of citrus using inoculum from swine waste water. We used 12 anaerobic batch type reactors, fed with different concentrations of residues of citrus being inoculated with the swine waste. Were testadas4 citrus residue concentrations (25%, 50%, 75% and 100%) during 60 days. It was observed that the increase in the concentration of residues of citrus caused a decrease in pH and metanogênica activity specifies fact that can be assigned inhibiting substance (D-Limonene) present in citrus peel, which when not undergo a pre-treatment can negatively affect the work of metanogênicas microorganisms. However, the proportion of 25% of citrus residue with 10% p.10536–10540 of swine waste for better production of methane when no pre-treatment of the citrus. / Nos dias atuais, o cenário da matriz energética mundial e brasileira é de grande dificuldade, devido ao aumento da demanda pelos combustíveis fosseis o que causa instabilidades nos preços e no setor dos combustíveis, além de sérios riscos ambientais a toda população. O momento difícil vem impulsionando a procura por novas fontes de energia renováveis e limpas, como o biogás. Desta forma, este trabalho teve como objetivo avaliar a biodigestão anaeróbia a partir do resíduo da agroindústria do citrus utilizando como inóculo a água residual da suinocultura. Foram utilizados 12 reatores anaeróbios tipo batelada, alimentados com diferentes concentrações de resíduos de citrus sendo inoculadas com dejetos da suinocultura. Foram testadas4 concentrações de resíduo de citrus (25%, 50%, 75% e 100%) durante 60 dias. Foi observado que o aumento da concentração de resíduos de citrus causou uma diminuição do pH e, conseqüentemente atividade metanogênica especifica fato que pode ser atribuído a substância inibidora (D-limoneno) presente na casca do citrus, que quando não passam por um pré-tratamento podem afetar negativamente os trabalhos dos microorganismos metanogênicas. Entretanto, sugere-se a proporção de 25% de resíduo de citrus com 10% de inoculo de dejetos suínos para uma melhor produção de metano quando não houver pré-tratamento do citrus.

BERTOLINI, WAGNER L. H. M. A influência do D-limoneno como promotor de absorção do ácido 5-aminolevulínico para Terapia Fotodinâmica do câncer de pele: avaliação in vitro e in vivo da permeação e retenção cutâneas. 2009 118f. Tese (Doutorado). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Preto Universidade de São Paulo, Ribeirão Preto, 2009. O câncer é a segunda doença principal do planeta, muito próximo de se tornar a mais incidente. Os tratamentos tradicionais do câncer, tais como cirurgia, radioterapia e quimioterapia apresentam severos efeitos colaterais ao paciente devido à citotoxicidade que podem causar às células normais, além das cancerosas. Objetivando minimizar estes efeitos indesejáveis pesquisadores de diversas áreas afins vislumbram novas técnicas, novos tipos e formas de tratamentos que apresentem um melhor perfil terapêutico; que possam agir de forma mais seletiva contra as células cancerosas, minorando os efeitos indesejáveis em relação às células saudáveis. Dentre as técnicas pesquisadas destaca-se a Terapia Fotodinâmica (TFD). Esta é uma técnica de tratamento nova e promissora. A técnica do tratamento consiste em aplicar, no tecido alvo, substâncias fotossensibilizantes, posteriormente ativadas com luz de comprimentos de onda específicos, com a finalidade de produzir destruição celular, por meio da ação de produtos citotóxicos fotoativados. Destaca-se a seletividade apresentada pela técnica, que deve ser reconhecida como uma das vantagens entre as técnicas empregadas no tratamento do câncer. O presente trabalho objetiva verificar a influência do D-limoneno como promotor de permeação do ácido 5-aminolevulínico (5-ALA) em aplicação tópica. Isto visa aumentar a permeação do 5-ALA quando aplicado topicamente. O 5-ALA é convertido a protoporfirina-IX (PpIX) pela via do ciclo Heme. Esta é um potente agente fotossensibilizador endógeno. O interesse no uso deste promotor foi aumentar a taxa de penetração do 5-ALA, possibilitando a permeação de maiores quantidades do fármaco em questão. Para isto foram realizados estudos de permeação in vitro do 5-ALA, em concentração de 1% (p/p) utilizando-se formulações (emulsões O/A) com diferentes concentrações do promotor D-limoneno (0, 5, 10, 20 e 30%), (p/p). Observou-se que o fluxo in vitro do 5-ALA através da pele de orelha de porco aumentou para todas as formulações empregadas quando comparado ao controle, sem D-limoneno, para um período de estudo de 12h. A retenção no estrato córneo e na [epiderme + derme] apresentou aumento significativo, evidenciando, assim, um efeito eficiente do D-limoneno como promotor. Experimentos in vivo foram conduzidos em camundongos objetivando a análise do efeito da formulação na produção e acúmulo de PpIX na pele. Observou-se que o D-limoneno aumentou significantemente a quantidade de PpIX extraída da pele. Os resultados in vitro e in vivo mostraram o potencial do D-limoneno como promotor de absorção cutânea para o 5-ALA para a TFD tópica do cancer de pele. / BERTOLINI, WAGNER L. H. M. D-limonene influence in the cutaneous penetration enhancer for 5-aminolevulinic acid in photodynamic therapy of skin cancer: in vitro and in vivo skin permeation and retention studies. 2009 118f. Thesis (Doctoral). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Preto Universidade de São Paulo, Ribeirão Preto, 2009. The topical administration of 5-ALA has been distinguished on skin cancer photodynamic therapy (PDT) because of its efficiency in the treatment of tumors and the reduced phototoxic collateral effects. However, this effectiveness is limited by its low penetration in the skin. A proposal to optimize the 5-ALA penetration in the skin is the use of cutaneous penetration enhancers, which seek to alter the cutaneous barrier for many bioactive molecules. The aim of this work was the pharmaceutical development of formulations containing D-limonene as a cutaneous penetration enhancer, seeking the increase of the cutaneous penetration of 5-ALA for skin cancer PDT. The in vitro flux of 5-ALA present in 1% (w/w) from different formulations containing D-limonene (20 e 30% w/w) was significantly increased after 12 hours of experiment, in comparison with formulations without D-limonene, mainly for the formulations containing 20% and 30% of D-limonene with 1% of 5-ALA (1,45 and 2,01 times, respectively). The stratum corneum (SC) and [epidermis + dermis] without SC retention were also significantly increased, showing an enhancer effect of the promoter. In addition, in vivo experiments were accomplished in mice, with the purpose of analyzing the formulation effect on the PpIX production and accumulation in the skin. It was observed that the penetration enhancer\'s presence significantly increased the amount of PpIX extracted from the skin. Both in vitro and in vivo results showed the potentiality of the formulations containing D-limonene as a cutaneous penetration enhancer for 5-ALA delivery on the skin cancer PDT.

Made available in DSpace on 2016-08-19T12:56:42Z (GMT). No. of bitstreams: 1 Dissertacao Gilson Vitorino.pdf: 2030180 bytes, checksum: 2cdb690e4f8dd7c201d29d466e8f25b7 (MD5) Previous issue date: 2013-09-23 / Studies are conducted to find substances of vegetable origin, such as alternative chemical control to combat the dengue vector, once there is no validated vaccine for that. In this paper, from the extraction and analytical study of the essential oil of the fresh peel of Citrus sinensis L.Osbeck was possible to analyze the larvicidal effect of the oil against third stage larvae of Aedes aegypti (Linnaeus, 1762). The oil was extracted quantitatively by steam distillation process using Clevenger type apparatus. The physico-chemical properties of essential oil were determined (density, refractive index, solubility, color and appearance). The oil was characterized analytically by infrared (FTIR) and gas chromatography-mass spectrometry (GC-MS),thus identifying its major compound. LC50 from the oil was calculated from the Reed-Muench method (1938) and Pizzi (1950), respectively. The yield of oil was 2.47% m/m.Through spectroscopic techniques used,it was possible to identify 15 compounds, justifying presence of d-limonene as a major constituent. The essential oil exhibited LC50 of 99.014 (± 2.098) μg.mL-1 and the standard d-Limonene 126.037 (± 2.092) μg.mL-1. The results indicate that the essential oil Citrus sinensis L. Osbeck comprises substances with larvicidal effect against mosquito Aedes aegypti. / Estudos são desenvolvidos no sentido de encontrar substâncias de origem vegetal, como controle químico alternativo ao combate do vetor da dengue, uma vez em que até o presente momento não há vacina validada para a mesma. No referido trabalho, a partir da extração e do estudo analítico do óleo essencial das cascas frescas de Citrus sinensis L.Osbeck , foi possível analisar o efeito larvicida do óleo contra as larvas em terceiro estágio do mosquito Aedes aegypti (Linnaeus, 1762). Extraiu-se quantitativamente o óleo pelo processo de hidrodestilação, usando aparelho do tipo Clevenger. Determinaram-se as propriedades físico-químicas do óleo essencial (densidade, índice de refração, solubilidade, cor e aparência). Caracterizou-se analiticamente o óleo por infravermelho (FTIR) e cromatografia gasosa acoplada a espectrômetro de massas (CG-EM), identificando desta forma o seu composto majoritário. Calculou-se a CL50 do óleo, a partir dos métodos de Reed-Muench (1938) e Pizzi (1950), respectivamente. O rendimento do óleo foi de 2,47% m/m. Através das técnicas espectroscópicas utilizadas, foi possível identificar 15 compostos, justificando a presença do d-Limoneno como constituinte majoritário. O óleo essencial exibiu CL50 de 99,014 (±2,098) μg.mL-1 e o padrão d-Limoneno 126,037 (±2,092) μg. mL-1. Os resultados apresentados indicam que o óleo essencial Citrus sinensis L. Osbeck, é constituído por substâncias que possuem efeito larvicida frente ao Aedes aegypti.