Magister Scientiae - MSc (Biotechnology) / Breast cancer is regarded as the most common form of cancer in women and it comprises of approximately 23 % of female cancers, while affecting women at any age range. For oestrogen receptor positive patients, tamoxifen is used as a prescribed medication for breast cancer therapy. However, tamoxifen in its natural form is not active to achieve the required treatment and prevention of breast cells proliferation. Since tamoxifen is a prodrug, it need to be converted into its active form, endoxifen, for which it is achieved by the action of the cytochrome P450 enzymes. Cytochrome P450 2D6 (CYP2D6) is a member of cytochrome P450 enzymes for which are superfamily of heme enzymes characterised by their ability to catalyse the oxidative reactions of compounds, including the pathway of tamoxifen metabolism. However, due to polymorphism that lead to inactive phenotypes of CYP2D6 in this gene, there is a challenge of diagnosing if a patient can metabolise tamoxifen or not. The current diagnostic tool, Amplichip CYP450, for CYP2D6 is based on genotypes, and it lead to uncertainness as to whether the presence of functionalCYP2D6 alleles of CYP2D6 may lead to coding of active protein, thus leading to wrong treatment measures and overdose of tamoxifen. Electrochemical techniques have provided reliable, simple, quick, and sensitive methods for the determination of drug metabolism by enzymes. Therefore, it is important to develop a CYP2D6 phenotype-based sensor to detect and tell whether a particular individual can metabolise the drug or not.

Orientadora: Márcia Justino Rossini Mutton / Banca: Francisco Vicente Gaiotto Cleto / Banca: Flávia Cecílio Ribeiro Gregagnoli / Resumo: Atualmente o Brasil é o maior produtor mundial de cana-de-açúcar (Saccharum spp), sendo a região sudeste a maior responsável por esta produção. O estado de São Paulo encontra-se como o maior produtor, com aproximadamente 58,55% da produção total. Uma das maiores preocupações do setor sucroalcooleiro tem sido a qualidade da matéria-prima, a contaminação bacteriana dos processos fermentativos e a qualidade final do etanol. O setor utiliza antimicrobianos sintéticos e naturais na fermentação visando um produto final de qualidade. Objetivou-se nesse trabalho analisar a composição e a qualidade do destilado final, sob antibiótico natural própolis, comparado com o de uso convencional (o antibiótico sintético ampicilina) da fermentação proveniente de duas estirpes diferentes de levedura. Utilizou-se um esquema fatorial 3X2X6, com 3 tratamentos principais (mosto testemunha, mosto com adição de extrato etanólico de própolis e mosto com adição de ampicilina); 2 tratamentos secundários (estirpes selecionadas CAT 1 e PE 2) e 6 ciclos fermentativos, com três repetições. Foram realizadas análises tecnológicas e microbiológicas no mosto e nos destilados. Os resultados obtidos nesse trabalho mostraram que o uso de antibiótico natural própolis não afetou a microbiota das leveduras fermentativa e a composição e a qualidade do destilado. As estirpes de leveduras apresentaram o mesmo rendimento alcoólico. / Abstract: Brazil is highlighted as a big sugar cane producer, being the São Paulo State the biggest producer, having around 58.55% of the total Brazilian production. Among the sugar and alcohol sector's preoccupations, the raw material, quality, the fermentative process contamination and the ethanol final quality are the most important issues. This work aimed evaluates the composition and the distillate final quality when a natural antibiotic deviated from propolis compared to the ampicillin was used, using the CAT 1 and PE 2 strains. The factorial scheme 3x2x6 was used, being 3 main treatments (control, must + propolis ethanolic extract, and must + ampicillin); 2 secondary treatments (strains selected CAT1 and PE2), and 6 fermentative cycles, with 3 replications. Technologic and microbiologic analyses were done. Results showed that the propolis as natural biocide doesn't affected the fermentative microbiota and composition and quality of distillate. Yeasts strains CAT 1 e PE 2 didn't show differences to alcoholic yield. / Mestre

Made available in DSpace on 2014-06-11T19:27:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-19Bitstream added on 2014-06-13T18:56:03Z : No. of bitstreams: 1 halabi_af_me_jabo.pdf: 1665101 bytes, checksum: 498a750134c20b146fbf692994a022e0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Atualmente o Brasil é o maior produtor mundial de cana-de-açúcar (Saccharum spp), sendo a região sudeste a maior responsável por esta produção. O estado de São Paulo encontra-se como o maior produtor, com aproximadamente 58,55% da produção total. Uma das maiores preocupações do setor sucroalcooleiro tem sido a qualidade da matéria-prima, a contaminação bacteriana dos processos fermentativos e a qualidade final do etanol. O setor utiliza antimicrobianos sintéticos e naturais na fermentação visando um produto final de qualidade. Objetivou-se nesse trabalho analisar a composição e a qualidade do destilado final, sob antibiótico natural própolis, comparado com o de uso convencional (o antibiótico sintético ampicilina) da fermentação proveniente de duas estirpes diferentes de levedura. Utilizou-se um esquema fatorial 3X2X6, com 3 tratamentos principais (mosto testemunha, mosto com adição de extrato etanólico de própolis e mosto com adição de ampicilina); 2 tratamentos secundários (estirpes selecionadas CAT 1 e PE 2) e 6 ciclos fermentativos, com três repetições. Foram realizadas análises tecnológicas e microbiológicas no mosto e nos destilados. Os resultados obtidos nesse trabalho mostraram que o uso de antibiótico natural própolis não afetou a microbiota das leveduras fermentativa e a composição e a qualidade do destilado. As estirpes de leveduras apresentaram o mesmo rendimento alcoólico. / Brazil is highlighted as a big sugar cane producer, being the São Paulo State the biggest producer, having around 58.55% of the total Brazilian production. Among the sugar and alcohol sector’s preoccupations, the raw material, quality, the fermentative process contamination and the ethanol final quality are the most important issues. This work aimed evaluates the composition and the distillate final quality when a natural antibiotic deviated from propolis compared to the ampicillin was used, using the CAT 1 and PE 2 strains. The factorial scheme 3x2x6 was used, being 3 main treatments (control, must + propolis ethanolic extract, and must + ampicillin); 2 secondary treatments (strains selected CAT1 and PE2), and 6 fermentative cycles, with 3 replications. Technologic and microbiologic analyses were done. Results showed that the propolis as natural biocide doesn’t affected the fermentative microbiota and composition and quality of distillate. Yeasts strains CAT 1 e PE 2 didn´t show differences to alcoholic yield.

Made available in DSpace on 2014-06-11T19:27:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-13Bitstream added on 2014-06-13T18:31:27Z : No. of bitstreams: 1 oliveirafilho_jh_me_jabo.pdf: 697900 bytes, checksum: 8506e7c314e6d9e7dc607082ecfa14a5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Na produção de cachaça, a microbiota contaminante afeta diretamente o processo fermentativo, originando fermentações indesejáveis, contribuindo para menores rendimentos em álcool e um desbalanceamento na formação dos compostos secundários que caracterizam a bebida. Portanto, são necessárias práticas para minimizar e controlar essas contaminações, sendo a aplicação de antimicrobianos uma alternativa eficaz para tal controle. Dentro desse enfoque, o objetivo deste trabalho foi avaliar a eficiência de antimicrobianos naturais e sua interação com antibióticos convencionais no controle da contaminação bacteriana na produção cachaça. Para as análises tecnológicas e microbiológicas do vinho e pé-de-cuba, utilizou-se o delineamento inteiramente casualizado em parcelas sub-subdivididas, em esquema fatorial 5x2x10 com três repetições, sendo quatro biocidas (extrato de própolis marrom, extrato de própolis verde, ampicilina e interação própolis/ampicilina (P/A)) e controle (sem adição de antimicrobiano), combinando-se os tratamentos em início e final de safra por 10 ciclos fermentativos. Para as análises tecnológicas do mosto, utilizou-se o delineamento inteiramente casualizado em parcelas subdivididas, em esquema fatorial 2x10 com três repetições, sendo duas épocas da safra (inicio e final) por 10 ciclos fermentativos. Foi observado um comportamento distinto entre épocas, com maiores valores de contaminantes e acidez em mosto no final da safra. Dentre os tratamentos, o extrato de própolis marrom, própolis verde, ampicilina e interação (P/A) mantiveram os índices de viabilidade celulares a níveis elevados e superiores a 90%, com menores índices observados para o tratamento controle. As concentrações de bactérias no pé-de-cuba foram significativamente menores com o emprego dos biocidas. No tratamento controle a acidez total do vinho foi superior... / During the cachaça production, the contaminant microbiota affects directly the fermentative process, originating undesirable fermentations, minimizing the alcohol production as well an unbalancing in the secondary compounds formation that characterizes the beverage. Therefore, practices that minimize those contaminations are necessary and the antimicrobial use is one of the efficient alternatives the control. This work aimed to evaluate the natural antimicrobials efficiency as well its interaction with conventional antibiotics to control the bacterial contamination in the cachaça production. A completely randomized design in sub-divided parcels in a factorial 5x2x10 scheme with 3 replications was used, being four biocides (brown propolis extract, green propolis extract, ampicillin and propolis/ampicillin interaction – P/A) and control, combining them in the beginning and final of harvest by 10 fermentative cycles. A different behavior between treatments was observed, being the higher contamination and acidity found in the end of the harvest. Among treatments, the brown propolis extract, green propolis extract, ampicillin and P/A kept cellular viability indexes higher than 90%, and the control treatment was lower. The bacterial concentration in the inoculums was significantly smaller when biocides were used. In the control treatment the residual reducing sugars. The propolis extract and its combination with synthetic antimicrobials were efficient to control contaminant bacteria during the fermentative process

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21958号 / 医博第4500号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中川 一路, 教授 松原 和夫, 教授 西渕 光昭 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Kieferosteonekrosen stellen ein relevantes und therapiebedürftiges Krankheitsbild mit steigender Inzidenz dar. Ätiologisch unterscheidet man dabei Osteoradionekrose, Medikamenten-induzierte Osteonekrose und Osteomyelitis. Die jeweiligen pathophysiologischen Entstehungsmechanismen sind noch weitgehend ungeklärt. Sowohl im klinischen Erscheinungsbild, histologisch als auch therapeutisch bestehend starke Gemeinsamkeiten. Eine antibiotische Behandlung spielt bei allen Formen der Kieferosteonekrosen sowohl prophylaktisch, als auch therapeutisch eine entscheidende Rolle. Es ist bisher nicht bekannt, ob bei Patienten/-innen mit Kieferostenekrose nach intravenöser Applikation von Ampicillin/Sulbactam relevante Antibiotikakonzentrationen im Kieferknochen erreicht werden können. Im Zeitraum Dezember 2020 bis November 2021 wurden für diese Studie insgesamt 31 Patienten/-innen an der Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie des Universitätsklinikums Würzburg rekrutiert. Es wurden dabei die Gewebekonzentrationen von Ampicillin und Sulbactam jeweils in manifest nekrotischen Knochen und angrenzenden klinisch vitalen Bereichen bestimmt. Die Ergebnisse zeigen keine signifikanten Unterschiede in den Konzentrationen zwischen manifest nekrotischem und klinisch vitalem Kieferknochengewebe. Insgesamt können nach intravenöser Applikation von Ampicillin und Sulbactam sowohl in klinisch vitalen, als auch manifest nekrotischen Kieferknochenarealen relevante Wirkstoffkonzentrationen erreicht werden. Im Rahmen einer explorativen Datenanalyse zeigte sich eine inverse Korrelation zwischen Zeitpunkt der letzten Antibiose und den erreichten Konzentrationen Ampicillin/Sulbactam im vitalen Knochengewebe. Auch wenn sich bei Kieferosteonekrosen der Einsatz von Antibiotika in Studien und der klinischen Praxis bewährt hat, bestehen noch große Wissenslücken. Ein besseres Verständnis der pathophysiologischen Mechanismen und der spezifischen Rolle daran beteiligter Mikroorganismen könnte dabei helfen zukünftig den Einsatz von Antibiotika deutlich zielgerichteter und effizienter gestalten. / Osteonecrosis of the jaw is a relevant disease pattern that requires therapy and is increasing in incidence. Etiologically, a distinction is made between osteoradionecrosis, medication related osteonecrosis and osteomyelitis. The respective pathophysiological development mechanisms are still largely unexplained. Both in the clinical appearance, histologically and therapeutically, there are several similarities. Antibiotic treatment plays a decisive role in all forms of osteonecrosis of the jaw, both prophylactically and therapeutically. It is not yet known whether relevant antibiotic concentrations can be reached in the jawbone of patients with osteonecrosis of the jaw after intravenous application of ampicillin/sulbactam. In the period December 2020 to November 2021, a total of 31 patients were recruited for this study at the Clinic for Oral and Maxillofacial Surgery at the University Hospital Würzburg. The tissue concentrations of ampicillin and sulbactam were determined in manifestly necrotic bones and adjacent clinically vital areas. The results show no significant differences in the concentrations between manifestly necrotic and clinically vital jawbone tissue. Overall, after intravenous administration of ampicillin and sulbactam, relevant drug concentrations can be achieved in both clinically vital and manifestly necrotic areas of the jawbone. An exploratory data analysis showed an inverse correlation between the time of the last antibiotic treatment and the ampicillin/sulbactam concentrations achieved in the vital bone tissue. Even if the use of antibiotics in studies and clinical practice has proven itself in osteonecrosis of the jaw, there are still large gaps in knowledge. A better understanding of the pathophysiological mechanisms and the specific role of the microorganisms involved could help to make the use of antibiotics much more targeted and efficient in the future.

Treatment of enterococcal endocarditis requires up to 6 weeks of intravenous (IV) antimicrobial therapy. When susceptible, an ampicillin-based regimen is preferred. Studies evaluating ampicillin stability utilizing high-pressure liquid chromatography have indicated enhanced stability (greater than 24 hours at room temperature), supporting outpatient administration. Thus, we report the successful treatment of a 30-year-old male with tricuspid valve enterococcal endocarditis in an outpatient setting using continuous infusion ampicillin via an ambulatory infusion pump. The patient received daily gentamicin at an outpatient infusion center with the ampicillin dose to be infused over the next 24 hours. Outpatient ambulatory infusion pumps allow for delivery of ampicillin via continuous infusion or pump-programmed pulse dosing. Preparation and administration in an outpatient infusion center may be a viable option to circumvent stability and delivery issues. Furthermore, 81% (34/42) of treatment days were completed outpatient, supporting that this approach may increase access to treatment and help reduce the economic burden to health care.

In the first chapter, we discuss various techniques and strategies used to synthesize lignin-derived functional materials. The transformation of lignin during pyrolysis and hydrothermal carbonization is also reported. Furthermore, current applications and surface properties of lignin-based carbonaceous materials in the fields of catalysis, bio-absorption removal of pollutants, and supercapacitors are summarized. The second chapter focuses on using electromembrane extraction with high performance liquid chromatography (HPLC) for preconcentration and determination of ampicillin residues in cow milk. In the third chapter, step growth polymerization or polycondensation has been used as an efficient pathway to synthesize polymers with high thermal stability. The resulting materials have different industrial applications. For instance, they can be used as coatings or films in industries, where the materials should be stable in very high temperature (above 500 °C).

No description available.

O gênero Acinetobacter tem sido implicado em grande variedade de infecções hospitalares, principalmente em Unidades de Terapia Intensiva. O tratamento de infecções por Acinetobacter spp. é geralmente realizado com imipenem embora não haja ensaios clínicos randomizados que embasem esta recomendação. No caso de resistência a esta classe, situação cada vez mais freqüente, as opções mais estudadas são as polimixinas e ampicilinasulbactam. Diante da escassez de dados sobre o assunto, estudos que avaliem o tratamento de infecções por Acinetobacter spp resistente a carbapenem são necessários. Realizou-se um estudo de coorte retrospectivo de pacientes com infecção causada por Acinetobacter spp. resistente a carbapenem, internados no Instituto Central do Hospital das Clínicas (HC-FMUSP) e no Hospital do Servidor Público Estadual (HSPE) no período de 1996 a 2004. Foram considerados como casos os pacientes com diagnóstico de infecção hospitalar baseado em critérios estabelecido pelo Centers for Disease Control and Prevention (CDC) somado ao isolamento de Acinetobacter spp. resistente a carbapenem obtidos de materiais estéreis ou lavado bronco-alveolar.Não foram incluídos casos de infecção do trato urinário. Foi realizada a análise dos prontuários dos pacientes e foram coletadas informações clínico-demográficas, tratamento utilizado, sinais, sintomas e exames auxiliares no diagnóstico da infecção e no decorrer do tratamento. Foram avaliados três desfechos: mortalidade até o final do tratamento, mortalidade até o final da internação e evolução clínica. Oitenta e dois pacientes (30%) receberam polimixina B ou E, oitenta e cinco (31%) foram tratados com ampicilina-sulbactam, 99 (36%) não receberam tratamento específico. As características clínico-demográficas dos grupos foram semelhantes. A mortalidade durante a internação foi de 78% e boa resposta clínica foi observada em 50% dos pacientes tratados. Na análise multivariada de fatores associados à má evolução clínica, início do tratamento após 72 horas do isolamento e piora da função renal durante o tratamento foram estatisticamente significativos. Pontuação de Apache II >= 15, início do tratamento após 72 horas do isolamento; piora da função renal durante o tratamento; presença de choque séptico e uso de polimixina foram variáveis associadas com óbito até o final do tratamento. As variáveis independentemente associadas com óbito durante a internação foram: idade >= 58 anos, presença de choque séptico no dia do início do tratamento e pontuação de Apache II >=15. Concluiu-se que para o tratamento de infecções causadas por Acinetobacter spp. resistente a carbapenem, ampicilinasulbactam foi superior a polimixinas considerando mortalidade durante o tratamento. / Acinetobacter spp. is a cause of a number of infections, mainly in the ICU setting. Antimicrobials drugs frequently reported as active against Acinetobacter spp include carbapenems, colistin, ampicillin/sulbactam, amikacin, rifampin and tetracyclines and currently carbapenens are considered the main antimicrobial treatment. Unfortunately, over the past years there has been a worldwide increase in infections caused by carbapenem-resistant Acinetobacter. This poses a therapeutic challenge as few treatment options are avaible. We performed a retrospective review of the case records of patients from 1996 to 2004 who had nosocomial infections caused by carbapenem-resistant Acinetobacter spp. from 2 large teaching hospitals. Diagnosis of infection was based on CDC criteria plus the isolation of Acinetobacter from a usually sterile site or from broncoalvelolar lavage. Urinary tract infections were not included. We collected data on demographic and clinical features, treatment, signs and symptoms from medical records. We evaluate 3 outcomes: mortality until the end of treatment, in-hospital mortality and clinical outcome. Eighty two patients received polymyxins (30%), 85 were treated with ampicilin-sulbactam (31%) and 99 (36%) did not receive any of these antibiotics. The demographic and clinical characteristics of the groups were similar. Multivariate analysis showed that treatment with polymyxins, Apache II score >= 15; septic shock; treatment delay and renal failure were independent predictors of mortality. On multivariate analysis, age >= 58 years, presence of septic shock and Apache II score >=15 were prognosis factors for mortality during hospitalization. Multiple logistic regression analysis revealed that Apache II >=15 and renal failure during treatment were associated with treatment failure. In conclusion, ampicillin-sulbactam was superior to polymyxin considering mortality during treatment.