Дисертації з теми "Sesamolin"

Дисертація на здобуття наукового ступеня кандидата технічних наук за спеціальністю 05.18.06 – технологія жирів, ефірних масел і парфумерно-косметичних продуктів. – Національний технічний університет «Харківський політехнічний інститут» Міністерства освіти і науки України, Харків, 2019 р. Дисертація присвячена науковому обґрунтуванню та розробці технології білково-жирових сумішей підвищеної харчової цінності спеціального призначення. Сформульовано робочу гіпотезу щодо використання в складі білково-жирової суміші насіння олійних культур соняшника, льону та кунжуту як джерел незамінних амінокислот, ессенціальних жирних кислот, вітамінів, мікроелементів, рослинних антиоксидантів. Науково обґрунтовано склад білково-жирової суміші підвищеної харчової цінності спеціального призначення (насіння льону; насіння кунжуту; насіння соняшника; рафінована кукурудзяна олія). Визначено органолептичні, фізико-хімічні, мікробіологічні та технологічні показники якості білково-жирової суміші. Розраховано залежність періоду індукції окиснення ліпідів білково-жирової суміші в закритій тарі від температури зберігання. Розроблено технологічне рішення щодо зниження активності інгібіторів протеолітичних ферментів білково-жирової суміші для максимально можливого збільшення її харчової цінності, яке полягає в її зволоженні та обробці надвисокочастотним випромінюванням. Запропоновано технологічну схему виробництва білково-жирової суміші підвищеної харчової цінності на основі олійної сировини, розроблено та узгоджено проект технічних умов на білково-жирові суміші з олійного насіння. Науково обґрунтовано рецептури жировмісних кондитерських виробів – кремової цукеркової маси для виробництва цукерок типу «трюфель» і шоколадної пасти з додаванням білково-жирової суміші підвищеної харчової цінності. Оцінено фізико-хімічні показники розроблених кондитерських виробів, вони відповідають нормам.
The dissertation for obtaining the scientific Degree of Candidate of Technical Sciences in the specialty 05.18.06 – technology of fats, essential oils and perfumery and cosmetic products. – National Technical University «Kharkov Polytechnic Institute», Ministry of Education and Science of Ukraine, Kharkiv, 2019. The thesis is devoted to the scientific substantiation and development of technology of protein-fat mixtures with increased nutritional value for nutrition of athletes. A working hypothesis on the use of sunflower, flax and sesame oilseeds as sources of essential amino acids, essential fatty acids, vitamins, microelements, and plant antioxidants in the composition of the protein-fat mixture has been formulated. The composition of protein-fat mixture of increased nutritional value of a special purpose (flax seeds; sesame seeds; sunflower seeds; refined corn oil) has been scientifically substantiated. Organoleptic, physico-chemical and technological quality control parameters of the protein-fat mixture were determined. The dependence of the induction period of lipid oxidation of the protein-fat mixture in a closed container on the storage temperature was calculated. A technological solution to reduce the proteolytic enzymes inhibitors activity of the protein-fat mixture for maximize its nutritional value, which consists in its wetting and processing by microwave radiation, has been developed. The technological scheme for the production of a protein-fat mixture of increased nutritional value based on oilseeds was proposed, a draft technical specification for protein-oil mixtures from oilseeds was developed and agreed upon. Recipes of fat-containing confectionery products – cream candy mass for the production of "truffle" cream candies and chocolate paste with the addition of protein-fat mixture of high nutritional value were scientifically based. Physical and chemical quality control parameters of the developed confectionery were evaluated, they corresponded to the norms.

Дисертація на здобуття наукового ступеня кандидата технічних наук (доктора філософії) за спеціальністю 05.18.06 «Технологія жирів, ефірних масел і парфумерно-косметичних продуктів» (18 – Виробництво та технології). – Національний технічний університет «Харківський політехнічний інститут», Міністерства освіти і науки України, Харків, 2019. Дисертацію присвячено науковому обґрунтуванню та розробці технології білково-жирових сумішей підвищеної харчової цінності. Актуальність теми дослідження пов’язана з тим, що дотепер практично немає вітчизняних спеціалізованих продуктів, зокрема для харчування спортсменів. Відомо, що найбільш важливими нутрієнтами для відновлення організму спортсмена є білки з певним співвідношенням амінокислот, поліненасичені жирні кислоти (ПНЖК) -3 групи, вітаміни та мінеральні речовини, які в недостатній кількості присутні в традиційних харчових продуктах. Тому часто спортсмени змушені вживати різноманітні біологічно активні добавки, що позиціонуються як спортивне харчування, нормативна база яких в Україні відсутня. Створення новітніх білково-жирових продуктів на науково обґрунтованій основі збагатить раціон харчування спортсменів, що, в свою чергу, позитивно вплине на повноцінне тренування та покращення спортивних результатів. Перспективною сировинною базою для означених продуктів, які є концентрованим джерелом поживних речовин, зокрема, незамінних нутрієнтів, є олійне насіння. Розробка науково обґрунтованої технології білково-жирових сумішей підвищеної харчової цінності для харчування спортсменів є актуальним науковим завданням, яке вирішується в дисертаційній роботі. Актуальність теми та вагомість результатів дисертаційної роботи підтверджується тим, що вона виконувалась згідно плану проведення науково-дослідних робіт Українського науково-дослідного інституту олій та жирів (м. Харків) у рамках держбюджетних науково-дослідних робіт НААН України: «Розробка білково-жирової основи для раціонального харчування спортсменів» (ДР № 0117U002374) та «Розробка способу інактивації інгібіторів протеїназ в білково-жировій основі для раціонального харчування» (ДР № 0116U000178), де здобувач був відповідальним виконавцем окремих етапів роботи. Практичне значення роботи для олійножирової промисловості полягає в обґрунтуванні раціонального співвідношення компонентів білково-жирової суміші (насіння льону, кунжуту, соняшника та кукурудзяної олії) для харчування спортсменів, яке є ефективним за вмістом незамінних амінокислот з розгалуженим ланцюгом (лейцином, ізолейцином, валіном) та триптофаном, максимально збагачене ПНЖК ω-3 групи та рослинними антиоксидантами; визначенні технологічних умов її обробки надвисокочастотним випромінюванням для збільшення харчової цінності; обґрунтуванні рецептур кремових цукерок типу «трюфель» і шоколадної пасти, збагачених білково-жировою сумішшю. Розроблено та узгоджено проект технічних умов: ТУ У 10.86.1 – 02071180.001:2018 «Білково-жирові суміші з олійного насіння». Проведено апробацію виробництва білково-жирової суміші з насіння льону, кунжуту, соняшника та рафінованої дезодорованої кукурудзяної олії, а також шоколадної пасти, збагаченої білково-жировою сумішшю, в промислових умовах ТОВ «Вегетус» (м. Харків). Результати дисертаційних досліджень впроваджено в навчальний процес кафедри органічного синтезу і нанотехнологій НТУ «ХПІ» під час викладання дисциплін «Хімічні технології харчових добавок та косметичних засобів», «Розробка комплексних харчових добавок» та «Застосування харчових добавок», в курсовому та дипломному проектуванні, а також у науково-дослідній роботі студентів. У дисертаційній роботі вперше одержано нові наукові дані щодо особливостей складу жирних кислот, стеринової фракції, комплексу антиоксидантів, амінокислот білків та сортових особливостей до накопичення ксенобіотиків насіння досліджених олійних культур, адаптованих до вирощування в Україні; науково обґрунтовано склад білково-жирової суміші (насіння льону, кунжуту, соняшника та кукурудзяної олії) спеціального призначення, яка є ефективною за вмістом ессенціальних жирних кислот, незамінних амінокислот та рослинних антиоксидантів; експериментально визначено у вигляді апроксимаційних моделей залежність періоду індукції окиснення ліпідів білково-жирової суміші від вмісту сезамолу, сезамоліну, α-ліноленової жирної кислоти та масової частки вологи. У дисертаційній роботі набуло подальшого розвитку експериментальне обґрунтування високої харчової цінності насіння олійних культур – соняшника, льону та кунжуту не тільки як джерела есенціальних жирних кислот, але й незамінних амінокислот – лейцину, ізолейцину і валіну; застосування надвисокочастотного випромінювання та зволоження олійної сировини для зниження активності інгібіторів протеолітичних ферментів і збільшення засвоюваності компонентів білково-жирової суміші. Компонентами білково-жирової суміші обрано підсушене насіння льону, кунжуту та соняшника. Вибір обґрунтовано тим, що насіння цих олійних культур поки ще не містить модифікованих генів і може стати джерелом білків рослинного походження, ессенціальних ПНЖК, мікроелементів, а також низки цінних сполук, які потрібні для здоров’я спортсменів. Досліджено загальний хімічний склад, жирнокислотний склад, склад стеринової і токоферольної фракцій, амінокислотний, вітамінний та мінеральний склад насіння льону (сорти Південна ніч, Ківіка, Симпатік), кунжуту (сорти Ілона, Кадет, Боярин) та соняшника (кондитерські сорти Лакомка, Алмаз, Запорізький кондитерський), адаптованих до вирощування в Україні. Насіння льону характеризується найбільшим вмістом α-ліноленової кислоти. Кунжутне насіння містить антиоксиданти сезамол і токофероли. Сезамол здатен посилювати антиокиснювальну дію токоферолів в оліях, а тому такий комплекс можна пропонувати для використання як антиоксиданту в жирових продуктах для спортсменів. В свою чергу, соняшникове насіння містить значну кількість токоферолів. Обране олійне насіння також містить фітостерини, які мають низку лікувально-профілактичних властивостей, зокрема знижують рівень загального холестерину в організмі. Сировина багата на амінокислоти лейцин, ізолейцин, валін, які є незамінним матеріалом для побудови м’язової тканини та приймають участь у процесах її анаболізму й відновлення. Саме ці амінокислоти в плазмі крові людини конкурують з амінокислотою триптофан, що визначає швидкість проникнення триптофану в мозок і зниження моторної активності та працездатності, тобто виникнення втоми. Насіння олійних культур обраних сортів містить значну кількість вітамінів групи В та вітаміну Е. Проаналізовано здатність олійного насіння обраних сортів щодо накопичення токсичних речовин, а саме важких металів та нітратів. Результати досліджень свідчать про те, що кількість солей важких металів – міді, цинку, свинцю та кадмію, а також і нітратів в усіх сортах значно менша за ГДК. В результаті аналізу отриманих даних як сировину для виробництва білково-жирової суміші обрано наступні сорти олійного насіння: Південна ніч (льон), Ілона (кунжут), Лакомка (соняшник). Науково обґрунтовано склад білково-жирової суміші підвищеної харчової цінності спеціального призначення: насіння льону – 51,00 ± 2,55 %; насіння кунжуту – 21,25 ± 1,06 %; насіння соняшника – 12,75 ± 0,63 %, рафінована дезодорована кукурудзяна олія – 15,00 ± 0,75 %. Вміст жиру в суміші становить 55,92 ± 2,80 %, вміст білку – 17,50 ± 0,88 %. Співвідношення лінолевої та -ліноленової жирних кислот у суміші становить близько 1,2 : 1,0; а незамінні амінокислоти з розгалуженим ланцюгом знаходяться в співвідношенні лейцин : ізолейцин : валін, яке дорівнює близько 2,0 : 1,2 : 1,4. Визначено органолептичні, фізико-хімічні та технологічні показники якості білково-жирової суміші. Розраховано залежність періоду індукції окиснення ліпідів білково-жирової суміші в закритій тарі від температури зберігання. Встановлено, що період індукції окиснення ліпідів білково-жирової суміші за 85±2 °С при запропонованому співвідношенні компонентів знаходиться в інтервалі 175 – 195 хв., що перевищує приблизно в 2,7 – 3,0 рази – період індукції окиснення лляного насіння як найбільш термолабільного компоненту та приблизно в 1,3–1,4 рази період індукції соняшникового насіння. Окисну стабільність білково-жирової суміші гарантує те, що при виготовленні її використано компоненти, що не піддавалися тривалій температурній обробці. Але присутність в складі олійного насіння інгібіторів протеолітичних ферментів знижують засвоєння білка організмом та істотно обмежують його застосування в харчовій промисловості. У зв’язку з цим розроблено технологічне рішення щодо зниження активності інгібіторів протеолітичних ферментів олійної сировини білково-жирової суміші для максимально можливого збільшення її харчової цінності, яке полягає в її зволоженні та обробці надвисокочастотним випромінюванням ( = 2450 МГц). Експериментально встановлено раціональні умови обробки олійної сировини: зволоження до вмісту вологи 11 – 13 % і час обробки надвисокочастотним випромінюванням 210 – 260 с, що дозволить підвищити біологічну цінність суміші, а саме збільшити ступінь розщеплення і засвоюваності білків у шлунково-кишковому тракті. Запропоновано технологічну схему виробництва білково-жирової суміші підвищеної харчової цінності на основі олійної сировини, розроблено та узгоджено проект технічних умов ТУ. У. 10.86.1 – 02071180.001:2018 на білково-жирові суміші з олійного насіння. Науково обґрунтовано рецептури жировмісних кондитерських виробів – кремової цукеркової маси для виробництва цукерок типу «трюфель» і шоколадної пасти з додаванням 15 % білково-жирової суміші підвищеної харчової цінності. Експериментально доведено, що періоди індукції цукеркової маси і шоколадної пасти запропонованого складу перевищують контрольні показники на 44 і 55 % відповідно. Для визначення впливу білково-жирової суміші на споживчі властивості кондитерських виробів проведено органолептичну оцінку дослідних зразків, на базі якої виявлено, що використання білково-жирової суміші в складі кремових цукеркових мас і шоколадної пасти впливає на такі органолептичні показники як смак і аромат, які у дослідних зразків вище, ніж у контрольних. Зокрема, в дослідних зразках кондитерських виробів проявляється характерний пікантний горіховий аромат і смак; довше зберігається відчуття «наповненості» у роті («mouth-feeling»). Подальше збільшення вмісту суміші – понад 15 % – приводить до появи борошнистого присмаку і характерного аромату лляного насіння. Виходячи з результатів органолептичної оцінки, обрано ефективну концентрацію білково-жирової суміші в кондитерських виробах на рівні 15 %. Результати визначення фізико-хімічних показників якості кондитерських виробів свідчать, що при додаванні в кремову конфетну масу і шоколадну пасту 15 % білково-жирової суміші зміна масової частки вологи та масової частки жиру відбувається в рамках нормованих величин. Зниження вмісту загального цукру не впливає на органолептичні властивості кондитерських виробів, але знижує собівартість продукції. Розроблені продукти порівняно з контролем мають вищій вміст незамінних амінокислот, змінюється їх ліпідний склад – значною мірою зростає вміст ПНЖК ω-3 групи. У складі розроблених кондитерських виробів також присутня значна кількість харчових волокон – нутрієнту, який прискорює відчуття насичення, а також є фактором формування нормальної кишкової мікрофлори і попередження ожиріння.
The dissertation for obtaining the scientific degree of candidate of technical sciences (PhD.) in the specialty 05.18.06 – technology of fats, essential oils and perfumery and cosmetic products. – National Technical University «Kharkov Polytechnic Institute», Ministry of Education and Science of Ukraine, Kharkiv, 2019. The dissertation is devoted to scientific substantiation and development of the technology of protein-fat mixtures of increased nutritional value. The relevance of the research topic is related to the fact that up to now there are practically no domestic specialized products in particular for nutrition of sportsmen. It is known that the most important nutrients for the recovery of the athlete's organism are proteins with a certain ratio of amino acids, polyunsaturated fatty acids (PUFA) -3 groups, vitamins and minerals that are present in insufficient amounts in traditional foods. Therefore, athletes are often forced to take various dietary supplements, which are positioned as sports nutrition, and there is no regulatory framework for these products in Ukraine. Creating the newest protein-fat products on a scientifically based basis will enrich the diet of athletes, which, in turn, will positively affect the full-fledged training and improved athletic performance. Oilseeds are a promising raw material base for these products, which are a concentrated source of nutrients, in particular, essential nutrients. The development of scientifically based technology of protein-fat mixtures of increased nutritional value for sportsmen is a relevant scientific task, which is solved in the dissertation. Relevancy of a subject and significance of dissertation is confirmed by the fact that it has been carried out according to the plan of researches of the Ukrainian research institute of oils and fats (Kharkiv) within the state budgetary research of NAAS of Ukraine: «Development of a protein-fat base for rational nutrition of athletes» (RW № 0117U002374) and «Development of a method for inactivating proteinase inhibitors in a protein-fat base for a balanced nutrition» (RW № 0116U000178), where the applicant was an executive of separate stages of work.. Practical value of work for the oil and fat industry consists in justify the rational ratio of the components of the protein-fat mixture (flax, sesame, sunflower and corn oil) for nutrition of athletes, which is effective for essential amino acids with branched chain (leucine, isoleucine, valine) and tryptophan, the most enriched with PUFA ω-3 groups and plant antioxidants; in determining the technological conditions of its processing by microwave radiation to increase the nutritional value; in substantiation of the recipes of «truffle» cream candies and chocolate paste enriched with protein-fat mixture. The draft technical specification TU U 10.86.1 – 02071180.001:2018 «Protein-fat mixtures from oilseeds» was developed and agreed. Approbation of the production of protein-fat mixture from flax seeds, sesame, sunflower and refined deodorized corn oil, as well as chocolate paste, enriched with protein-fat mixture, was conducted in industrial conditions of Vegetus LLC (Kharkiv). Results of dissertation researches were introduced in educational process of organic synthesis and nanotechnologies department of NTU «КPI» when teaching disciplines «Chemical technologies of food additives and cosmetics», «Development of complex food additives» and «Use of food additives», in course and degree design, as well as in a students research work. For the first time, new scientific data on the composition of fatty acids, sterol fraction, antioxidant complex, amino acid composition and varietal characteristics to the accumulation xenobiotics in oilseeds adapted for cultivation in Ukraine has been obtained; scientifically based composition of protein-fat mixture for special purposes (flax seeds, sesame, sunflower and corn oil), which is effective relative to the content of essential fatty acids, essential amino acids and plant antioxidants; the dependence of the induction period of lipid oxidation of the protein-fat mixture on the content of sesamol, sesamolin, α-linolenic fatty acid and the mass fraction of moisture in the form of approximation models was experimentally determined. The experimental substantiation of the high nutritional value of oilseeds – sunflower, flax, and sesame, – not only as sources of essential fatty acids, but also essential amino acids – leucine, isoleucine, and valine, – received further development; the use of microwave radiation and wetting oilseeds to reduce the activity of inhibitors of proteolytic enzymes and increase the digestibility of the components of the protein-fat mixture were received further development in the thesis. The dried flax, sesame and sunflower seeds were selected as components of the protein-fat mixture. The choice is justified by the fact that the seeds of these oilseeds still do not contain modified genes and can become a source of plant-derived proteins, essential PUFAs, trace elements, as well as a number of valuable compounds necessary for the health of athletes. The overall chemical composition, fatty acid composition, composition of sterol and tocopherol fractions, amino acid, vitamin and mineral composition of flax seeds (Southern Night, Civica, Sympatik), sesame (Ilona, Cadet, Boyarin) and sunflower varieties (confectionery varieties Lakomka, Almaz, Zaporizkyi kondyterskyi), adapted to growing in Ukraine, were investigated Flax seeds are characterized by the highest content of α-linolenic acid. Sesame seed contains antioxidants sesamol and tocopherols. Sesamol is able to enhance the antioxidant effect of tocopherols in oils, so this complex can be offered for use as an antioxidant in fatty products for athletes. In turn, sunflower seeds contain significant amounts of tocopherols. Selected oilseeds also contain phytosterols, which have a number of therapeutic and prophylactic properties, in particular, reduce the level of total cholesterol in the body. Raw materials are rich in amino acids (leucine, isoleucine, valine), which are indispensable materials for building muscle tissue and are involved in the processes of its anabolism and recovery. It is these amino acids in human blood plasma that compete with tryptophan amino acid, which determines the rate of tryptophan penetration into the brain and the decrease in physical activity and efficiency, that is, the occurrence of fatigue. Seeds of oilseeds of selected varieties contain significant amounts of B vitamins and E vitamin. The ability of oilseeds of selected varieties of accumulation of toxic substances, namely heavy metals and nitrates was analyzed. Research results indicate that the amount of salts of heavy metals – copper, zinc, lead and cadmium, – as well as nitrates in all grades is much less than the MPC. As a result of the analysis of the obtained data the following varieties of oilseeds were selected as raw materials for the production of protein-fat mixture: Southern night (flax), Ilona (sesame), Lakomka (sunflower). The composition of protein-fat mixture of increased nutritional value of special purpose was scientifically substantiated: flax seeds – 51.00 ± 2.55 %; sesame seeds – 21.25 ± 1.06 %; sunflower seeds – 12.75 ± 0.63 %, refined deodorized corn oil – 15.00 ± 0.75 %. The fat content in the mixture is 55.92 ± 2.80 %, the protein content was 17.50 ± 0.88 %. The ratio of linoleic and -linolenic fatty acids in the mixture was about 1.2: 1.0; and the essential branched-chain amino acids (leucine: isoleucine: valine) were in the 2.0 : 1.2 : 1.4 ratio. Organoleptic, physico-chemical and technological quality control parameters of the protein-fat mixture were determined. The dependence of the induction period of lipid oxidation of protein-fat mixture in a closed container from storage temperature was calculated. It was established that the induction period of lipid oxidation of protein-fat mixture with the proposed ratio of components was in the range of 175–195 minutes at 85 ± 2 °C, which was about 2.7–3.0 times longer than the induction period of flaxseed component and about 1.3–1.4 times – the induction period of sunflower seeds. The oxidative stability of the protein-fat mixture was ensured by the fact that components, which were used in its manufacture, had not been subjected to prolonged heat treatment. But the presence of proteolytic enzymes inhibitors in the composition of oil seeds reduces the digestion of protein by the body and significantly limits its use in the food industry. In this regard, a technological solution to reduce the activity of proteolytic enzymes inhibitors of oilseeds of protein-fat mixture to maximize its nutritional value has been developed. This solution consists in its wetting and processing by microwave radiation ( = 2450 MHz). Rational conditions of oilseeds processing (hydration to 11–13 % moisture content and 210–260 s microwave radiation processing time) were experimentally established. These conditions will increase the biological value of the mixture, namely, increase the degree of cleavage and digestibility of proteins in the gastrointestinal tract. The technological scheme for the production of a protein-fat mixture of increased nutritional value based on oilseeds was proposed, a draft technical specification TU U 10.86.1 – 02071180.001:2018 for protein-oil mixtures from oilseeds was developed and agreed upon. Recipes of fat-containing confectionery – cream candy mass for the production of truffle-type sweets and chocolate paste with the addition of 15 % protein-fat mixture of high nutritional value were scientifically substantiated. It was experimentally proved that the induction periods of the candy mass and chocolate paste of the proposed composition exceed the control values by 44 and 55 %, respectively. The organoleptic evaluation of test samples was carried out to determine the effect of protein-fat mixture on consumer properties of confectionery products. Based on its results it was determined that the use of protein-fat mixture in cream candy masses and chocolate paste influenced on such organoleptic indicators like taste and aroma that were higher than in control samples. In particular, there were a characteristic savory nutty aroma and taste, longer remains «mouth-feeling»in the prototypes of confectionery products. A further increase in the content of the mixture – more than 15 % – leaded to the appearance of a mealy taste and characteristic aroma of flaxseed. The effective concentration of the protein-fat mixture in the confectionery products was chosen at the level of 15 % based on the results of the organoleptic assessment The results of determining the physico-chemical quality control parameters of confectionery indicated that when 15% of the protein-fat mixture was added to a creamy candy mass and chocolate paste, the change in the mass fraction of moisture and the mass fraction of fat occurred within the framework of normalized values. Reducing the total sugar content did not affect the organoleptic properties of confectionery, but reduced the cost of production. The developed products have a higher content of essential amino acids compared to the control, their lipid composition changes – the content of PUFAs of the ω-3 group increases significantly. As part of the developed confectionery products, there is also a significant amount of dietary fiber – a nutrient that accelerates the feeling of fullness, as well as a factor in the formation of normal intestinal microflora and the obesity prevention.

Microbiological oil solutions of provitamin A (β-carotene) as a dietary supplement are not widely used due to their low oxidation stability. The aim of research is determination of the effect of sesame antioxidants on the oxidative stability of provitamin A in oil solutions. The peroxide number of vegeTable oils is determined by the standard method by the titrimetric method. The value of the period of induction of oil oxidation is determined graphically from the growth curves of peroxide numbers. The content of tocopherols in oils is determined by spectrophotometric method. The content of sesamol and sesamoline in oils is determined by the colorimetric method. The oxidative stability of oils is determined using the accelerated "active oxygen" method. To plan the experiment and process the data, mathematical methods are applied using the software Microsoft Office Excel 2003. The oxidation stability of blended oils (a mixture of sesame, high oleic, sunflower and corn refined oils) and its components is investigated. Blended oil has a lower oxidative stability than sesame oil, but higher than corn and high oleic sunflower. The oxidative stability of the blend is enhanced by the antioxidant content of sesamol and sesamoline. The content of the above antioxidants, as well as the amount of tocopherols, is studied in blended oils. The oxidation stability of the obtained solution of provitamin A in blended oils is investigated. The period of induction of oxidation of blended oils with the addition of 0.2 % β-carotene increases by 1.3 times compared with the period of induction of the original blended oil. Blended long-life oil is recommended to be used to stabilize fat-soluble biologically active compounds.

Made available in DSpace on 2014-06-11T19:27:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-02-27Bitstream added on 2014-06-13T18:31:53Z : No. of bitstreams: 1 romerolafuente_je_me_arafo.pdf: 647496 bytes, checksum: a962eecc305aefe482abd482be57f8c5 (MD5)
Neste trabalho propusemo-nos a avaliar a efetividade da radiografia digital direta, quando empregada na técnica simplificada de análise de maturação óssea. Foram selecionadas 30 crianças de ambos os sexos, com faixa etária entre 9 e 14 anos para o sexo feminino e, entre 11 e 16 anos para o sexo masculino. De cada criança foram obtidas duas radiografias, uma pela técnica convencional e outra digital direta para a posterior análise comparativa das imagens. O filme e o sensor foram posicionados e centralizados na região da articulação metacarpofalangeana do polegar esquerdo, de forma que o centro do sensor ou filme coincidisse com a posição da articulação metacarpofalangeana. As radiografias convencionais e digitais diretas foram analisadas por uma Odontopediatra, procurando identificar no osso sesamóide: ausência (A), calcificação inicial (CI) e calcificação presente (CP). Na falange proximal do polegar esquerdo, foram identificados os estágios de capeamento epifisário a= epífise menor que a largura da diáfise, b= epífise igual à largura da diáfise, c= estágio de capeamento, d= fusão da epífise com a diáfise. As observações foram submetidas a análise estatística chegando-se as seguintes conclusões: 1 - A ossificação do osso sesamóide mostrou a melhor correlação entre os dois tipos de radiografias analisadas 2 - O observador apresentou melhor índice de coincidência nos fatores analisados na radiografia digital, sendo sua maior dificuldade o reconhecimento do estágio do início da calcificação do osso sesamóide na radiografia convencional.
The aim of this study was to evaluate the analysis of bone maturation in the simplified radiographic technique thirty children, age from 9 to 14 years old for female and from 11 to 16 for male took part of this study. From each child were obtained two radiographies, using conventional and digital techniques. The film and the sensor were positioned centralized in the area of the metacarpophalangeal joint of the left Thumb. The images were analyzed by a Pediatric Dentist. Calibrated to identify in the sesamoid bone: absence (A), initial calcification (CI) and present calcification (CP). In the proximal phalange of the left thumb were identified the epiphyseal changes: a - Ephiphysis equal in width to diaphysis, b= Appearance of sesamoid of the thumb, c= Capping of epiphysis, d= Fusion of epiphysis. The results shouled that the sesamoid bone avaliation had the best correlation in both radiographies : Conventional and Digital. The observer was more reliable when analysed digital X rays.

Orientador: Lourdes Aparecida Martins dos Santos Pinto.
Banca: Rita de Cássia Loiola Cordeiro
Banca: Maria Cristina Borsatto
Resumo: Neste trabalho propusemo-nos a avaliar a efetividade da radiografia digital direta, quando empregada na técnica simplificada de análise de maturação óssea. Foram selecionadas 30 crianças de ambos os sexos, com faixa etária entre 9 e 14 anos para o sexo feminino e, entre 11 e 16 anos para o sexo masculino. De cada criança foram obtidas duas radiografias, uma pela técnica convencional e outra digital direta para a posterior análise comparativa das imagens. O filme e o sensor foram posicionados e centralizados na região da articulação metacarpofalangeana do polegar esquerdo, de forma que o centro do sensor ou filme coincidisse com a posição da articulação metacarpofalangeana. As radiografias convencionais e digitais diretas foram analisadas por uma Odontopediatra, procurando identificar no osso sesamóide: ausência (A), calcificação inicial (CI) e calcificação presente (CP). Na falange proximal do polegar esquerdo, foram identificados os estágios de capeamento epifisário a= epífise menor que a largura da diáfise, b= epífise igual à largura da diáfise, c= estágio de capeamento, d= fusão da epífise com a diáfise. As observações foram submetidas a análise estatística chegando-se as seguintes conclusões: 1 - A ossificação do osso sesamóide mostrou a melhor correlação entre os dois tipos de radiografias analisadas 2 - O observador apresentou melhor índice de coincidência nos fatores analisados na radiografia digital, sendo sua maior dificuldade o reconhecimento do estágio do início da calcificação do osso sesamóide na radiografia convencional.
Abstract: The aim of this study was to evaluate the analysis of bone maturation in the simplified radiographic technique thirty children, age from 9 to 14 years old for female and from 11 to 16 for male took part of this study. From each child were obtained two radiographies, using conventional and digital techniques. The film and the sensor were positioned centralized in the area of the metacarpophalangeal joint of the left Thumb. The images were analyzed by a Pediatric Dentist. Calibrated to identify in the sesamoid bone: absence (A), initial calcification (CI) and present calcification (CP). In the proximal phalange of the left thumb were identified the epiphyseal changes: a - Ephiphysis equal in width to diaphysis, b= Appearance of sesamoid of the thumb, c= Capping of epiphysis, d= Fusion of epiphysis. The results shouled that the sesamoid bone avaliation had the best correlation in both radiographies : Conventional and Digital. The observer was more reliable when analysed digital X rays.
Mestre

Thesis (Ph. D.)--West Virginia University, 2009.
Title from document title page. Document formatted into pages; contains xi, 165 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 131-163).

Dillapiol is a naturally occurring methylenedioxyphenyl (MDP) compound that acts as an insecticide synergist comparable in activity to the widely used piperonyl butoxide (PBO). More than thirty synthetic analogs of dillapiol and sesamol were prepared and evaluated for their inhibitory activity in a cloned human Cytochrome P450 3A4 (CYP 3A4) enzyme in order to assess their use as pesticide synergists and to determine the next generation of compounds. These compounds represent a second generation of analogs based on the knowledge gained from compounds prepared and evaluated by a former member of our group. The choice of new structures was also influenced by the surprising and important observations by Dr. Suqi Liu that compound 21 inhibited not only CYP 3A4 but also glutathione-S- transferase (GST). A set of compounds related to 21 were sent to BASF (Durham NC) for evaluation of their synergistic activity, toxicity and persistence in soil studies. In a number of instances these analogs outperformed PBO as synergists even when given at 1:1 synergist: pesticide ratio compared to PBO at 5:1 when tested against a variety of resistant insects in BASF laboratories in the USA, Holland, India and Indonesia. All of the compounds were shown to be non-toxic to animal life. Their half-life in soils was typically less than 10 days. The results obtained form the basis of two BASF - University of Ottawa patent applications. The most potent CYP3A4 inhibitors synthesized as part of this project are the sulfones 15and 15a. These compounds are 107 and 71 times more potent than dillapiol, respectively which has an IC50 of 8.9 ±0.3 µM. The ortho- chlorobenzyl ether 48 was shown to be 74 times more potent than dillapiol. The synthesis of Z02 analogs in which the NH and C (O) substituents of the B unit are in the ortho-, meta- and para-orientation compared to the meta-orientation of Z02 is reported. The bioactivities of these compounds were compared with previously synthesized meta- substituted analogs to determine which of the three orientations, ortho-, meta-, or para-, resulted in the most potent compounds. In vitro bioassay results obtained by the Brown group allow us to draw conclusions on the effects of the structural characteristics necessary for optimization of activity. Results acquired thus far have suggested that both the ortho- or para- substituted analogs have reduced activity relative to the meta- substituted analogs. Replacement of the oxygen in the CD unit by a sulfoxide and sulfone gave compounds with slightly improved inhibition of SOX9 but with still lower activity relative to Z02. The SAR performed in this project did not result in compounds superior to Z02. Nevertheless, the results described in this thesis give guidance for future SAR studies. It is recommended that future synthetic efforts be concentrated on the metaoriented analogs.

Made available in DSpace on 2016-08-03T16:31:04Z (GMT). No. of bitstreams: 1 Glauber Fabre Carinhena1.pdf: 160083 bytes, checksum: 9ff28bf9a976e1529fd0641542f508ea (MD5) Previous issue date: 2006-03-23
Este estudo foi realizado com o propósito de testar a reprodutibilidade, a confiabilidade e a concordância existente entre os métodos de Martins e Sakima (1977) para a radiografia de mão e punho, e Hassel e Farman (1995) e Baccetti et al. (2002) para as vértebras cervicais, quando comparados 2 a 2, e entre todos, conjuntamente. A amostra constou de 72 radiografias, sendo 36 telerradiografias em norma lateral da cabeça e 36 radiografias de mão e punho do lado esquerdo, de 36 indivíduos com Síndrome de Down (SD), sendo 13 do sexo feminino e 23 do masculino na faixa etária entre oito anos e seis meses até 18 anos e sete meses, com média de 13 anos e dez meses. De acordo com os resultados obtidos concluímos que, os índices de maturação avaliados por meio das vértebras cervicais e os centros de ossificação observados nas radiografias de mão e punho foram estatisticamente significativos, obtendo um excelente grau de concordância entre eles, considerados reprodutíveis e confiáveis. Quando comparados onjuntamente, todos os métodos se mostraram estatisticamente significantes com grau de concordância de razoável a boa, sendo considerados confiáveis na aplicação clínica.

碩士
義守大學
生物技術與化學工程研究所碩士班
98
SMB (simulated moving bed) is a continuous chromatographic separation technology. Compared with batch-type preparative chromatography, the advantages of SMB include high yield, high purity, and high efficiency per unit weight of the adsorbent. In addition, SMB can be readily scaled-up for higher volume purification and can be conducted relatively quickly to meet the demand of tightened schedule in new product development. This work report the separations of sesamin and sesamolin, respectively, by two SMBs. The two SMBs have different piping design and configuration. The 1st SMB has four sections and 2nd SMB has three sections. Both sections has two subsections so the 1st SMB is marked as 2-2-2-2 and the 2nd is 2-2-2-0. Effect of ingredient of desorbent, flow rate of desorbent, temperature, concentration of mixture, and impurities are reviewed by the triangle theory to explain the periodical change of concentration of effluents.

碩士
國立臺灣大學
食品科技研究所
93
Sesamol (benzo[1,3]dioxol-5-ol) has been generally regarded as the main antioxidative component in sesame oil. It was produced from sesamolin during the bleaching process of sesame oil with acid clay or upon roasting of sesame seed. The purpose of this study was to investigate the oral bioavailability and pharmacokinetic characteristics of sesamol in rats, both microdialysis and traditional blood sampling methods were employed. We developed a rapid and sensitive high performance liquid chromatographic method coupled with microdialysis system to measure the unbound sesamol from various biological fluids. Multiple microdialysis probes were concurrently inserted into the jugular vein, bile duct, brain striatum and the median lobe of liver of each anesthetized rat for sampling after sesamol administration (30 mg/kg) through the femoral vein. Separation of the unbound sesamol from various biological fluids was performed by a reversed phase C18 column (4.6 mm i.d. × 250 mm, 4 μm particle size). The mobile phase consisted of acetonitrile-10 mM sodium dihydrogen phosphate buffer (35:65, v/v) (adjusted to pH 4.0 with phosphoric acid) at a flow rate of 1 ml/min. The UV detector wavelength was set at 294 nm. The results showed that the maximum concentration of sesamol in blood, bile, brain and liver were 8.36 ± 1.47, 2.65 ± 0.63, 3.33 ± 0.55 and 1.17 ± 0.14 μg/ml; the half-lives were 7.51 ± 1.01, 10.3 ± 4.0, 6.49 ± 2.18 and 6.49 ± 1.14 min; the area under the concentration versus time curves (AUCs) were 75.3 ± 18.2, 44.1 ± 8.3, 44.0 ± 7.0 and 11.4 ± 7.6 min μg/ml, respectively. The extent of systemic unbound sesamol distributed to bile, brain and liver, calculated as AUCbile/AUCblood, AUCbrain/AUCblood and AUCliver/AUCblood were 0.602 ± 0.126, 0.603 ± 0.120 and 0.140 ± 0.074. In addition, the results indicated that sesamol penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion. The oral bioavailability is defined as the fraction of the dose which reaches the systemic circulation as intact drug. Blood samples were collected at various time intervals after sesamol administration and then assayed by a validated HPLC system. The separation of sesamol in rat plasma was performed under the similar HPLC condition as in the microdialysis samples except the mobile phase was adjusted to pH 4.15. After sesamol administration (30, 100 and 300 mg/kg, p.o. and 30 mg/kg, i.v.), the maximum concentration of sesamol were 11.2 ± 6.2, 22.2 ± 7.3, 60.5 ± 14.0 and 38.8 ± 16.8 μg/ml; the half-lives were 9.43 ± 4.33, 13.2 ± 4.9, 11.1 ± 2.4 and 15.3 ± 5.8 min; AUCs were 110 ± 70, 443 ± 150, 1140 ± 360 and 343 ± 96 min μg/ml, respectively. The results showed that the concentrations of sesamol declined rapidly and the elimination half-lives did not relate to the dosage ranges. AUCs presented dose dependent manner. These results suggested that sesamol appears a linear pharmacokinetic phenomenon. The oral bioavailability of sesamol was 34.8% in rats. The protein binding ratio of sesamol was 82.8% in rat plasma.

博士
臺北醫學大學
臨床醫學研究所
100
Sesamol is a potent phenolic antioxidant which possesses antimutagenic, antihepatotoxic, and antiaging properties. Platelet activation is relevant to a variety of acute thrombotic events and coronary heart diseases. There have been few studies on the effect of sesamol on platelets. Therefore, the aim of this study was to systematically examine the detailed mechanisms of sesamol in preventing platelet activation in vitro and in vivo. Sesamol (2.5-5 microM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists. Sesamol inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TXA2) formation, and phospholipase C (PLC)gamma 2, protein kinase C (PKC), and mitogen-activated protein kinase (MAPK) phosphorylation in washed platelets. Sesamol markedly increased cAMP and cGMP levels, endothelial nitric oxide synthase (eNOS) expression, and NO release as well as vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the sesamol-mediated inhibitory effects on platelet aggregation and p38 MAPK phosphorylation, and sesamol-mediated stimulatory effects on VASP and eNOS phosphorylation, and NO release. Sesamol also reduced hydroxyl radical (OH˙) formation in platelets. In an in vivo study, sesamol (5 mg/kg) significantly prolonged platelet plug formation of mice. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function. NF-κB signaling events, including IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 μg/ml) in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 μM). Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 μM)-mediated inhibitory effects of IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA) inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLC)γ2 phosphorylation, protein kinase C (PKC) activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization. The most important findings of this study demonstrate for the first time that sesamol possesses potent antiplatelet activity, which may involve activation of the cAMP-eNOS/NO-cGMP pathway, resulting in inhibition of the PLCγ2 -PKC-p38 MAPK-TXA2 cascade, and finally inhibition of platelet aggregation. Sesamol treatment may represent a novel approach to lowering the risk of or improving function in thromboembolism-related disorders. In addition, we further found could sesamol activate cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data also demonstrating that inhibition of NF-κB interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cardiovascular disease, cancer and various inflammatory diseases.

碩士
朝陽科技大學
應用化學系碩士班
91
This research is focused on the study of Sesamol, which is the main chemical intermediate used in the manufacture of the antidepressant drug called Paroxetine. The main objectives of this study are: 1) The identification of Sesamol’s impurities, including their physical and chemical properties. That information would be helpful for the drug manufacturer to reduce the production cost. 2) Comparison of the impurities analysis results using two different analysis methods (Gas chromatography and High Performance Liquid Chromatography) and select the one which can be more suitable for the monitoring of the In-Process chemical reaction control. The source of the Sesamol sample was the industrial grade reagent made by Sinon company (Taiwan). The procedure of this research starts with the GC-MS analysis of the Sesamol sample. Based on the GC-MS analysis, the main ingredient, along with the four detectable impurities were shown on the mass spectra (I, II, III, IV). However, the mass spectra library failed to identify the two names (II, III) out of the four impurities. To find out the names of those two chemicals, we synthesized the impurity (II, III) and purified the Sinon company‘s sesamol for standard. Then, the remaining two impurities (I, IV) were bought from TCI Co. and other companies from PROC. To separate the impurities from each other, HPLC and PLC (Preparative Liquid Chromatography) were applied to find out the best separation condition for the impurities and collect them one by one (collected by PLC). Once the purified impurities were obtained, the exact chemical structures of each impurity were determined by using a combination of NMR, FTIR, GC-MS and HPLC. Finally, all the Sesamol’s impurities were analyzed using both GC and HPLC for analytical comparison. The names of the four Sesamol derived impurities are: 1,3-Benzodioxole (C7H6O2), 1,3-Benzodioxole-formate ester (C8H6O4), Sesamol acetate (C9H8O4), 1,3-Benzodioxole-5-carboxaldehyde (C8H6O3). Based on the GC analysis results of Sesamol and It’s impurities, it was understood that the linearity constant ( r ) was good (over 0.980) and the LOD plus LOQ were 5~7×10-3ng (except for 1,3-Benzodioxole-formate ester which has LOD of 0.240ng) and 1.8~80.1×10-2ng respectively. On the other hand, the analysis results from HPLC were even better with ( r ) value over 0.999 plus the LOD and LOQ values of 6~23×10-2ng and 21~75×10-2ng respectively. Conclusion: Due to the low volatility of 1,3-Benzodioxole-formate ester, high polarity which, tends to remain in GC’s column plus its high CV% value, it would be more suitable to use HPLC as the tool for drug manufacturer’s monitoring of the In-Process chemical reaction control. Even though the GC can detect all four impurities in Sesamol, It would be more preferable to measure the Sesamol using HPLC.

碩士
國立成功大學
臨床藥學研究所
97
Introduction. Natural phenolic compound is abundant in daily foods. Studies in recent years have reported that this class of compounds contains numerous beneficial health effects. Sesamol is one of the phenolic compounds in sesame. It was produced from sesamolin during the bleaching process of sesame oil with acid clay or upon roasting of sesame seed. Several effects of sesamol, including free radical scavenging, antioxidation, preventing cardiovascular diseases, and chemoprevention have been reported by previous in vitro studies. Sesamol undergoes rapid and extensive phase II conjugation metabolism and converts to sesamol glucuronide and sesamol sulfate. Glucuronidation is mediated by uridine diphosphateglucuronosyl transferases (UGTs) and is a common metabolic pathway for various drugs. Therefore, it is of great importance to examine the pharmacokinetic interactions between sesamol and drugs that are UGTs substrates. Purpose. The aim of this study was to investigate the pharmacokinetics and drug interactions of sesamol in SD rats. A sensitive HPLC method for simultaneous determination of sesamol and its conjugate metabolites in rat plasma was also developed for the purpose. Method. Rats received several dose levels of sesamol intravenously and orally in the control groups. In the experiment groups, rats received sesamol after the treatment with valproic acid. Concentrations of sesamol, its metabolites and valproic acid were followed at scheduled intervals after drug administration to characterize their kinetic profiles in rats. Result. A sensitive HPLC method for the analysis of sesamol and its major metabolites in biological fluid was developed. The method was applied successfully to pharmacokinetic studies of sesamol in rats. Following bolus injection of 5-30 mg/kg to rats, the disposition of sesamol in plasma was linear. However, nonlinear disposition was evident after oral administration of 15-50 mg/kg of sesamol with the bioavailability of 10.3-35.2%. After co-administration with valproic acid intravenously, the plasma levels of valproic acid，sesamol and its conjugate metabolites were rapidly decreased. In the oral experiment group, the plasma levels of valproic acid and sesamol were increased and the major metabolites of sesamol were decreased one hour later. Conclusion. Sesamol undergoes rapid and extensive conjugation metabolism and converts to sesamol glucuronide and sesamol sulfate. Saturation of sulfation might be an explanation for the nonlinear pharmacokinetics of sesamol in the oral control groups. Co-administration of the UGTs substrates sesamol and valproic acid by oral route in rats resulted in a two-fold increase of the maximum concentration of valproic acid with plasma level higher than the therapeutic range. These drug interactions may produce adverse reactions, and even the toxic effects. In the bolus injection group, the interactions caused the rapid decrease of plasma valproic acid concentration to sub-therapeutic levels and may resulte in the development of epileptic seizures.

Many pathologic lesions and several types of fractures in the equine forelimbs involved the bony elements of the metacarpophalangeal joints (fetlock joints) especially the third metacarpal bones and the proximal sesamoid bones. Although the bones of the fetlock joint have been described in a general manner, the variations between equine breeds are still insufficient and differences within the breeds are not completely covered. Therefore, the aim of the current study was to identify the morphometrical variations of these bones between and within some different equine breeds.
Right and left metacarpal, proximal phalangeal and proximal sesamoid bones were collected from 23 horses (10 Thoroughbreds, 5 Standardbreds and 8 Ponies) euthanized for non-orthopaedic reasons. The bones were boiled between 95°C and 99°C for 30 hours, then cleaned and left for 24 hours at room temperature for air drying. Finally, the bones were dried in the drying cabinet at 49.5°C for 8 hours. A number of dimensional parameters were measured using a custom-built apparatus, calliper and plastic tape. These measurements included proximodistal height, lateromedial width, and dorsopalmar depth. All the statistical data were analysed using the ANOVA test and SPSS statistic software except the repeatability data which were analysed by calculating the repeatability coefficient.
This study showed that there were significant variations between the medial and lateral sides of all bones in all breeds. The length to the lateral condyle of Mc3 was greater than the length to the medial condyle of Mc3 in all breeds. The width and depth of the medial condyle was greater than the lateral condyle in all breeds. The lengths of the lateral sides of the P1 bones were greater than the lengths of the medial sides in the right forelimbs of Thoroughbreds and Standardbreds. The width of the medial articular cavity of P1 was greater than the width of the lateral articular cavity except in the left limb of Ponies. The depth of the medial articular cavity of P1 was greater than the depth of the lateral articular cavity except in the left limb of Standardbreds. The lateral sesamoid bones in both limbs of Thoroughbreds and Ponies were significantly longer or tended to be longer than the medial sesamoid bones. The lateral sesamoid bones were wider than the medial sesamoid bones in both limbs of Ponies. The depths of the lateral sesamoid bones were the significantly greater or tended to be greater than those of the medial sesamoid bones in both limbs of Thoroughbreds and Standardbreds.
There were many morphometrical variations in the bony elements of the equine fetlock joints of Thoroughbreds, Standardbreds and Ponies. Further studies are needed to identify the reasons and mechanical effects of these differences.

碩士
國立成功大學
環境醫學研究所
94
Acute respiratory distress syndrome (ARDS) is an inflammatory process caused by a variety of direct and indirect injuries to the lungs. Clinical studies indicate that nitric oxide (NO) and pro-inflammatory cytokines are involved in the pathogenesis of ARDS. Sesamol, one of the lignans in sesame oil, has been reported to reduce nitric oxide production and inducible NO synthase (iNOS) expression, and attenuate multiple organ failure during endotoxemia. However, the effect of sesamol on LPS-induced acute pulmonary injury has never been investigated. The aim of this study was to examine the effects of sesamol on LPS-induced acute pulmonary inflammation in rats. Acute pulmonary inflammation was induced by LPS (5 mg/kg, intraperitoneally) in Wistar rats. Sesamol (10 mg/kg, subcutaneously) was given just after LPS administration. Pulmonary edema, myeloperoxidase (MPO) activity, NO production, and iNOS expression were assessed 12 h after sesamol. Sesamol decreased pulmonary edema, MPO activity, NO production, and iNOS expression. Further, sesamol dose-dependently inhibited LPS (100 ng/kg)-stimulated NO production, iNOS expression, and pro-inflammatory cytokine generation in primary alveolar macrophages. It is suggested that the inhibitions of iNOS expression and pro-inflammatory cytokine production might be associated with sesamol-exerted anti-inflammation in LPS-induced acute pulmonary inflammation, at least partially.

碩士
國立成功大學
環境醫學研究所
93
Iron overload causes oxidative stress resulted in organ injury. Sesame oil and its lignan sesamol are potent antioxidants, both of which can reduce reactive oxygen species and lipid preoxidation; and attenuate multiple organ failure during oxidative stress. The aim of this study was to investigate the effects of sesame oil and sesamol on iron-induced oxidative stress and multiple organ injury in mice. Mice were given sesame oil (4 ml/kg, s.c.) or sesamol (30 mg/kg, s.c.) just after ferric-nitrilotriacetate (Fe-NTA) (2 mg/kg, i.p.) and parameters were determined 3 hours after Fe-NTA administration. Superoxide anion, serum Fe2+ concentration, serum nitric oxide production, blood hydroxyl radical, and lipid peroxidation were examined. He¬patic and renal functions were assessed by biochemical and histological examinations. Sesame oil or sesamol significantly reduced superoxide anion, Fe2+ concentration, hydroxyl radical, and lipid peroxidation; and attenuated hepatic and renal injuries in Fe-NTA-treated mice. Sesame oil and sesamol ameliorated hepatic and renal function after the onset of iron poisoning. In summary, sesame oil and sesamol attenuated hepatic and renal injuries preventively and therapeutically, which may result from the amelioration of oxidative stress in acute iron poisoning in mice.

碩士
國立成功大學
環境醫學研究所
93
Lipopolysaccharide (LPS), a main component of Gram-negative bacterial cell wall, is a potent inducer of inflammatory response and organ injury in animals and mammalians. Sesamol, a lignan of sesame oil, has an inhibitory effect on LPS-induced nitric oxide production in glia cell line; however, whether sesamol could protect against LPS-initiated inflammation and organ injury have never been investigated. The aim of this study was to investigate the effect and the possible mechanism of sesamol on inflammation-associated organ injury induced by LPS in mice. Sesamol significantly attenuated LPS-induced hepatic and renal injuries in mice. Sesamol decreased LPS-enhanced nitric oxide production in serum in mice and in RAW264.7 murine macrophage cell line. Sesamol reduced inducible nitric oxide synthase protein expression in LPS-treated leukocytes and RAW264.7 cells. Sesamol markedly increased interleukin-10 generation but failed to affect tumor necrosis factor-alpha and interleukin-1betta levels after LPS challenge in mice. In addition, sesamol significantly decreased the phosphorylation of I-kappaB and blockaded NF-kappaB translocation by avoiding p65 to enter into nucleus in RAW264.7 cells. In summary, sesamol attenuated LPS-induced inflammation and hepatic and renal injuries by inhibiting nitric oxide production, which might be a result of the enhancement of IL-10 production and the inhibition of NF-kappaB translocation, in mice.

碩士
國立成功大學
環境醫學研究所
94
Overstimulation of noradrenergic neurons, nicotinic acetylcholine receptors (nAChR), γ-aminobutyric acid (GABA), or N-methyl-D-aspartate (NMDA) receptor in the brain results in seizures. The aim of this study was to investigate the roles of multiple receptors in sesamol-initiated seizures in mice. Our pilot data showed that sesamol induced seizures in a dose-dependent manner in mice. In this study, seizures were induced by sesamol (300 mg/kg, ip) administration, and then seizures score and duration of convulsion were recorded in male BALB/c mice. Agonists and antagonists of various receptors were administrated 30 min before sesamol-induced seizures. Noradrenergic (α1, α2, β1 and β2), nAChR, GABAA, GABAB, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor were associ-ated with sesamol-induced seizures. Prazosin (noradrenergic α1 antagonist), clonidine (noradrenergic α2 agonist), yohimbine (noradrenergic β2 antago-nist), mecamylamine (nAChR antagonist), muscimol (GABAA agonist), ba-clofen (GABAB agonist), NBQX (AMPA antagonist) and MK-801 (NMDA antagonist) augmented sesamol-initiated seizures. It was suggested that noradrenergic receptors, nAChR, GABA, AMPA and NMDA receptors are involved in sesamol-induced seizures in mice.

Parkinson’s disease is an age-related neurodegenerative disorder. The major symptoms of Parkinson’s disease are closely linked to the pathology of the disease. The main pathology of Parkinson’s disease consists of the degeneration of neurons of the substantia nigra pars compacta (SNpc), which leads to reduced amounts of dopamine in the brain. One of the treatment strategies in Parkinson’s disease is to conserve dopamine by inhibiting the enzymes responsible for its catabolism. The monoamine oxidase (MAO) B isoform catalyses the oxidation of dopamine in the central nervous system and is therefore an important target for Parkinson’s disease treatment. Inhibition of MAO-B provides symptomatic relief for Parkinson’s disease patients by increasing endogenous dopamine levels as well as enhancing the levels of dopamine after administration of levodopa (L-dopa), the metabolic precursor of dopamine. Recent studies have shown that phthalide can be used as a scaffold for the design of reversible MAO inhibitors. Although phthalide is a weak MAO-B inhibitor, substitution on the C5 position of phthalide yields highly potent reversible MAO-B inhibitors. In the present study, sesamol and benzodioxane were used as scaffolds for the design of MAO inhibitors. The structures of sesamol and benzodioxane closely resemble that of phthalide, which suggests that these moieties may be useful for the design of MAO inhibitors. This study may be viewed as an exploratory study to discover new scaffolds for MAO inhibition. Since substitution at C5 of phthalide with a benzyloxy side chain yielded particularly potent MAO inhibitors, the sesamol and benzodioxane derivatives possessed the benzyloxy substituent in the analogous positions to C5 of phthalide. These were the C5 and C6 positions of sesamol and benzodioxane, respectively. The sesamol and benzodioxane derivatives were synthesised by reacting sesamol and 6- hydroxy-1,4-benzodioxane, respectively, with an appropriate alkyl bromide in the presence of potassium carbonate (K2CO3) in N,N-dimethylformamide (DMF). 6-Hydroxy-1,4- benzodioxane, in turn, was synthesised from 1,4-benzodioxan-6-carboxaldehyde. The structures of the compounds were verified with nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses, while the purities were estimated by high-pressure liquid chromatography (HPLC). Sixteen sesamol and benzodioxane derivatives were synthesised. To determine the inhibition potencies of the synthesised compounds the recombinant human MAO-A and MAO-B enzymes were used. The inhibition potencies were expressed as the corresponding IC50 values. The results showed that the sesamol and benzodioxane derivatives are highly potent and selective inhibitors of MAO-B and to a lesser extent MAOA. The most potent MAO-B inhibitor was 6-(3-bromobenzyloxy)-1,4-benzodioxane with an IC50 value of 0.045 μM. All compounds examined displayed selectivity for the MAO-B isoform over MAO-A. Generally the benzodioxane derivatives were found to be more potent inhibitors of human MAO-A and MAO-B than the sesamol derivatives. The reversibility and mode of MAO-B inhibition of a representative derivative, 6-(3- bromobenzyloxy)-1,4-benzodioxane, was examined by measuring the degree to which the enzyme activity recovers after dialysis of enzyme-inhibitor complexes, while Lineweaver- Burk plots were constructed to determine whether the mode of inhibition is competitive. Since MAO-B activity is completely recovered after dialysis of enzyme-inhibitor mixtures, it was concluded that 6-(3-bromobenzyloxy)-1,4-benzodioxane binds reversibly to the MAO-B enzyme. The Lineweaver-Burk plots constructed were linear and intersected on the y-axis. Therefore it may be concluded that 6-(3-bromobenzyloxy)-1,4-benzodioxane is a competitive MAO-B inhibitor. To conclude, the C6-substituted benzodioxane derivatives are potent, selective, reversible and competitive inhibitors of human MAO-B. These compounds are therefore promising leads for the future development of therapy for Parkinson’s disease.
MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2015

博士
國立成功大學
基礎醫學研究所
93
Sepsis, mainly caused by bacterial infection, is one of the major causes of death in clinical patients. More than 200,000 patients die of sepsis every year in the United States, and is the top 13 cause of death in Taiwan. However, no effective interventions in treating sepsis have been reported during past two decades. Sesame oil is regarded as a health food. Sesame oil-supplemented diet decreases pro-inflammatory cytokines and mortality in septic mice. The aim of the present study was to examine the effects and the possible mechanisms of sesamol (3,4-methylenedioxyphenol), a lignan in sesame oil, against sepsis. Two common septic models were used, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Data showed that a single dose of ses-ame oil can attenuate multiple organ failure and decrease mortality by reducing oxida-tive stress when given before and after the onset of sepsis in rats; however, both min-eral oil and corn oil did not show the similar effects. Sesamol decreased serum lipid peroxidation, nitric oxide, and IL-1beta production, and attenuated CLP-induced multi-ple organ injury. Furthernire, sesamol showed the proventive and therapeutic effects on mortality induced by CLP in rats. Sesamol significantly attenuated LPS-induced oxidative stress and multiple organ failure, reduced the generation of hydroxyl radical, peroxynitrite, and superoxide anion. Sesamol also inhibited nitric oxide production and inducible nitric oxide synthase expression, and the production of tumor necrosis factor-alpha and interleukin-1beta. Sesamol decreased the LPS-induced expression of CD14 and Toll-like receptor 4 in RAW264.7 cells. Sesamol potently decreased the binding between LPS and LPS-binding protein (LBP). We concluded that sesame oil attenu-ated multiple organ failure and decreased mortality in septic rats. Sesamol might be an important component of sesame oil for treating sepsis by inhibiting the binding be-tween LPS and LBP. However, more investigations are needed before application of sesamol in treating septic patients.

碩士
國立成功大學
環境醫學研究所
99
Patients with stress-related mucosal disease have higher morbidity and mortality than the others at intensive care unit. 3,4-Methylenedioxyphenol (sesamol) has potent antioxidative and anti-inflammatory effects. The aim of this study is to investigate the effect of sesamol on water immersion restraint (WIR)-induced stress-related mucosal disease in rats. Rat gastric ulcer and hemorrhage were induced by WIR. The validation of WIR was tested first. For protective effect of sesamol, rats were pretreated orally with various doses of sesamol (0.1, 0.3, or 1 mg/kg) 30 min before WIR. Restrained on restraint board at 25℃ for 4 h induced severe ulcer and hemorrhage. Social support effect did not affect the induction of stress ulcer. WIR increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-?, interleukin (IL)-1?, and IL-6 levels, compared with non-WIR group, but failed to affect mucosal lipid peroxidation and mucus secretion. Sesamol significantly decreased gastric ulceration and hemorrhage, decreased mucosal tumor necrosis factor ? (TNF-??, interleukin 1???IL-1??, and interleukin 6 (IL-6) productions, and increased interleukin 10 (IL-10), compared with WIR control group. Sesamol inhibited nuclear factor-?B (NF-?B) activity in sesamol-treated groups compared with WIR control group. In addition, increased myeloperoxidase (neutrophil marker) and CD68 (macrophage marker) levels in gastric mucosa were found in WIR-treated rats. Sesamol significantly decreased CD68 levels but not myeloperoxidase in mucosa compared to WIR-control groups. We hypothesize that sesamol protects against stress-related mucosal disease by inhibiting gastric mucosal proinflammatory cytokines production in rats.

碩士
國立中興大學
食品科學系
92
Abstract Prostaglandin endoperoxide H synthase (PGHS) consists of cyclooxygenase and peroxidase. Based on the difference of expression site and functions, PGHS is divided into two forms: COX-1 and COX-2. During inflammation, COX-2 is up-regulated by pro-inflammatory agents such as cytokines and lipopolysaccharide (LPS) leading to synthesis of PGE2. Aspirin (ASA) is one of the non-steroidal anti-inflammatory drugs (NSAIDs) and it can either inhibit COX-2 activity by acetylating the COX-2 active site or down-regulating COX-2 gene expression. ASA is associated with perforation of gastrointestinal ulcer because of inhibition of COX-1. Some studies show that vitamin E can inhibit COX-2 activity and can synergistically inhibit the enzyme when combined with ASA. Sesamol is an antioxidant and anti-inflammatory substance. Animal studies suggest that sesamol can inhibit COX-2 activity. The purpose of this study was to evaluate the effect of sesamol on COX-2 activity and its possible synergism with ASA. We pre-incubated RAW 264.7 cells with 30 M and 100 M sesamol with or without 300 M ASA for 3 hr followed by incubation with LPS for 6 hr. The results showed that sesamol itself did not inhibit COX-2 expression but synergistically inhibited COX-2 expression when combined with ASA. Another purpose of this study was to investigate whether sesamol affects COX-1. The result showed that sesamol alone or in combination with ASA did not affect COX-1 expression. Regarding COX-2 activity (assayed as PGE2 concentration), we found that, although ASA or sesamol alone reduced PGE2 contents slightly, the combination of sesmaol and ASA did not enhance the inhibition of the PGE2 level. In summary, under the experimental conditions that cell viability is not affected, we demonstrate that sesamol itself only slightly inhibits COX-2 activity and does not affect the expression of COX-2 and COX-1 proteins, but the combination of sesamol with ASA synergistically inhibit COX-2 but not COX-1 protein expression. However, sesamol in combination with ASA exhibits no additive inhibition of PGE2 synthesis.

碩士
國立成功大學
環境醫學研究所
95
Sepsis, mainly caused by bacteria-induced systemic inflammation, is the top 13 cause of death in Taiwan. Lipopolysaccharide (LPS), a component of Gram-negative bac-terial cell wall, has been reported to play an important role in the pathogenesis of sep-sis. Sesamol attenuates inflammation and increases the survival rate in LPS-challanged rats; however, the exact mechanism is obscured. The aim of this study was to investi-gate the mechanism underlying the anti-inflammatory effect of sesamol in LPS-stimulated primary macrophages. Sesamol (a) inhibited tumour necrosis factor-a, in-terleukin-1b, and nitrite production in LPS-treated macrophages; (b) decreased the protein and mRNA expressions of inducible nitric oxide synthase; (c) reduced tran-scription factor nuclear factor-kB translocation and DNA binding activity, and (d) increased inhibitor kB expression; and (e) decreased nitrite production induced by interleukin-1b or peptidoglycan, but not tumor necrosis factor-a. In conclusion, sesamol might reduce LPS-stimulated pro-inflammatory mediators release by interfer-ing toll/interleukin-1 receptor signaling pathway in primary peritoneal macrophages.

碩士
國立成功大學
醫學檢驗生物技術學系
94
Acinetobacter baumannii is a gram negative coco-bacillus, which is ubiquitous present in fresh water and soil. A. baumannii is also a well recognized pathogen causing nosocomial pneumonia, predominantly in patients with endotracheal intubation, prolonged mechanical ventilation, and underlying lung diseases. Because almost all commercially available antibiotics are ineffective against A. baumannii, it is necessary to develop a new strategy to treat infections caused by A. baumannii. Lactoferrin (LF) is an iron-binding glycoprotein with a molecular mass of 80 KDa. Lactoferrin is present in milk, saliva, mucous secretion, and other biological fluids of mammals. LF has both anti microbial and immune modulating/enhancing ac-tivities. Sesamol (SM) is a main component of sesame oil (SO) and it has po-tent anti-inflammatory and antioxidant activities. In this study, the effects of LF, SO, and SM on a mouse infection model of A. baumannii were investigated. It was found that treatment with LF, SO, and SM could protect mice from A. baumannii-induced lethality. The results revealed higher survival rate, lower liver and kidney damage and decreased serum TNF-a production in mice treated with LF, SO, or SM than the control mice. Furthermore, the growth of A. baumannii was inhibited in the presence of LF in vitro, but in vitro inhibition is not seen in the presence of SM. Therefore, LF, SO, and SM may have protective effects against A. baumannii infection through different mechanisms.

碩士
嘉南藥理科技大學
生物科技系暨研究所
100
Osteoporosis is a skeletal disorder characterized by an imbalance between bone resorption and bone formation results in loss of bone mass. To search for safer treatment approaches and drug is an important objective. Sesamol, which is derived from sesame lignans, was reported as an antioxidant, neuroprotective, and anti-inflammatory chemical. In this study, sesamol assess the impact of human osteosarcoma cell line MG-63 and murine macrophage cell line RAW 264.7. In the osteoblasts, XTT assay show lower than 50 μM sesamol will not affect the MG-63 cell proliferation, and 20 μM sesamol significantly increased the activity of alkaline phosphatase (ALP), an early-stage marker of osteoblast differentiation. In addition, the mineralized bone nodule formation increased in response to 20 μM sesamol stimulate the MG-63 cells. The effect of sesamol on the osteoblast marker gene or protein expression using RT-PCR or western blotting analysis, the results showed that Runx2 and OPG gene and protein expression did not increase with the dose-dependent manner, but can promote the protein level of RANKL. Further analysis of sesamol on the signal pathways of osteoblastic differentiation. The observation that enhance BMP2 protein expression, and at the level of Smad1/5/8 in the BMP pathway and p38 in the MAPK pathway phosphorylations. On the other hand, our study was to explore the effect of sesamol in the osteoclasts. The data show lower than 10 μM sesamol will not affect the RAW 264.7 cell proliferation. The data obtained from tartrate-resistant acid phosphatase (TRAP) staining, RT-PCR and western blotting analyses indicated that RAW 264.7 cells after sesamol pretreatment can inhibit RANKL-induced osteoclast differentiation; and suppress the expression of osteoclast differentiation-related genes such as TRAP, CTSK and MMP9 and NFATc1; and sesamol attenuated the RANKL-induced p44/42 MAPK and NF-κB p52 activation. Therefore, sesamol may have the potential treatment of osteoporosis therapy.

碩士
東吳大學
微生物學系
98
The thread of lung cancer increases day by day. Smoking elevates the risk to lung cancers and in some of them acetylcholine receptors (AChR) are related. In this study, we evidenced the anti-apoptosis caused from the effects on nicotinic AChR (nAChR). This claim draws from the data that epibatidine reverses the Campothecine (CPT)-induced cytotoxicity in human lung squmous adenocarcinoma A549. By the using this model, we investigated possible chemicals to suppress the anti-apoptosis effects of nAChR. Moreover, methacholine, another mAChR agonist, enhanced human lung carcinoma cell H520 proliferation which was suppressed by atropine, mAChR antagonist. Using this model, we also investigated those chemicals to suppress the anti-proliferation effects of mAChR. Sesame seeds (Sesamum indicum), which has been shown to exhibit a variety of benefits, are well known as healthy food. Sesamin and sesamol, derived from sesame seed, possess　multiple functions such as anti-oxidation, antihypertensive, cholesterol -lowering, lipid-lowering and anticancer activities. In past, most studies of them were focused on its anti-oxidation ability. The studies shifted to their anti-cancer activities in this decade. Previous studies in our lab, we found that sesamin inhibited nAChR-coupled calcium signaling. But, the effects of the components derived from sesame seeds on calcium signaling coupled with the proliferation and the anti-apoptosis in non-small cell lung cancer are not well investigated till now. Thus, the purpose of this thesis is to clarify the effects. In neuroblastoma cell SH-SY5Y, we used fura-2 measurement for [Ca2+]i measurement to select anti- cholinergic substances from sesame seed constituents. RT-PCR and western-blotting were used for checking the existence of AChR. Fura-2 measurements were used for checking the function of AChR on A549 cells and H520 cells. MTT assay and subG1 were used for nAChR coupled proliferation. MTT assay were used for mAChR coupled anti-apoptosis. In this study, we found novel biological effects of sesamin and sesamol, that is their inhibition functions on nAChR and the anti-apoptosis functions induced by epibatidine treatment. We also found several compounds in sesame seed extracts exhibited the inhibition functions on mAChR, in the proliferation induced by methacholine and the anti-apoptosis induced by epibatidine. We estimate sesamin and other ligin compounds in sesame seeds possess potentials on the clinical therapy of non-small cell lung cancer in the future.

碩士
國立臺灣大學
食品科技研究所
99
Alzheimer’s disease is the most common form of dementia. It is a neurodegenerative disorder characterized by impairment in cognitive functions and changing in mood and behavior. The hallmarks of this disease are the presence of extracellular beta-amyloid deposition and intracellular hyperphosphorylated tau protein. Senescence-accelerated mouse prone-8 (SAMP8) is an age-accelerated mice model rather than gene-mutated mice model. In addition, SAMP8 mice also show the cognitive impairment and beta amyloid deposition. The objectives of this study were to investigate the potentials of sesamol and Z-ligustilide to ameliorate learning / memory impairment and Alzheimer’s disease pathophysiology in SAMP8 mice. Our results demonstrated that a 12-week oral administration of Z-ligustilide or sesamol could consolidate the fear-conditioning memory of SAMP8 mice and also slightly improved the spatial learning and memory. Using immunohistochemical (IHC) staining for certain brain sections of mice, we found that there was a decreasing trend in the deposition of beta amyloid after administration of sesamol and Z-ligustilide. Using ELISA to detect beta amyloid, the results were similar to IHC staining; however the treatment groups were not significantly different from the control group. To evaluate the oxidative stress status of the mice, liver TBARS were determined. We found that treatment groups had lower TBARS level. To correlate the results of behavior tests, beta amyloid content, and oxidative stress status, we concluded that there was neither strong correlation between cognitive impairment and beta amyloid, nor oxidative stress and beta amyloid. These results suggested that beta amyloid and oxidative stress may not be the crucial factors to influence cognitive ability in SAMP8 mice.