In controlled release applications a drug is molecularly dispersed in a polymer phase. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of the drug release can be controlled by interfering with the swelling rate of the beads or by influencing diffusion through the viscosity of the polymer. Beads that contain chitosan were prepared through the ionotropic gelation method where tripolyphosphate (TPP) was used as the crosslinking agent. Beads that consisted of 3% w/v isoniazid (lNH) and 5% w/v chitosan were prepared in a 5% w/v TPP solution (pH 8.7) as the primary beads. To improve the drug loading of chitosan isoniazid beads (ClB) the TPP concentration, pH of the TPP solution and the INH concentrations were altered for maximum drug loading. To increase the porosity of the beads of chitosan beads Explotab® (EXPL), Ac-Di-Sol® (ADS) and Vitamin C (VC) were added individually to chitosan solutions at concentrations of 0.1, 0.25 and 0.5% w/v before adding the mixture to the TPP solution. Morphology, swelling and drug loading studies were used to evaluate the different formulations. After these excipients were added individually they were also added in combinations of two excipients respectively and characterised. From the results of the drug loading studies the beads that contained only chitosan and isoniazid showed a percentage drug loading of (43.92%) which is the best of all the beads that were analyzed. The multi excipient combination of Ac-Di-Sol® and Explotab® showed the best swelling capability at both pH levels. Dissolution studies were conducted on all the formu lations over a period of 6 hours (360 minutes) at pH 5.6 and pH 7.4. From the dissolution results it were clear that no chitosan dissolved at both pH values. The dissolution of single pharmaceutical excipient (SPE) and multi pharmaceutical excipient (MPE) formulations can be arranged in the following order: VC/ADS < VC < ADS/EXPL < ADS < VC/EXPL < CIB < EXPL. Explotab® is a potential excipient for enhanced drug release over a wide pH range. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Zugl.: Hamburg, Univ., Diss., 2009

Thesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007. / Bibliography: leaves 295-322.

Universiẗat, Diss., 2004--München.

Dissertation (Ph.D.)--Helsingin yliopisto, 2006. / Includes bibliographical references. Available in PDF format via the World Wide Web.

Thesis (M.S.)--Universidad de Puerto Rico, Recinto Universitario de Mayagüez, 2005. / Tables. Printout. Includes bibliographical references (leaves 68-73)

Thesis (MSc (Plant Biotechnology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Vitamin C (ascorbate or AsA) is a secondary metabolite produced in many eukaryotes including yeasts, plants and animals. It plays essential roles as an anti-oxidant and enzyme cofactor, functions as an electron donor and -acceptor and is involved in various developmental processes. This study was initiated with the aim of increasing vitamin C production in tomato. Three genes, namely GDP-mannose pyrophosphorylase (GMPase) from Saccharomyces cerevisiae, arabinono-1,4-lactone oxidase (ALO) from Saccharomyces cerevisiae and myo-inositol oxygenase 2 (MIOX2) from Arabidopsis thaliana were ectopically expressed in the tomato cultivar Money Maker. GMPase converts D-mannose-6-P to GDP-D-mannose. This reaction forms part of the well characterized, “Smirnoff-Wheeler” pathway. ALO catalyzes the terminal step in erythroascorbate synthesis in yeast. In situ it also metabolizes the plant and animal substrates for ascorbate manufacture. Myo-inositol (MI) is converted into D-glucuronate by the activity of MIOX. D-Glucuronate is a precursor to L-guluno-1,4-lactone synthesis which is the precursor to AsA in animals and thought to be present in plants. The genes were independently introduced with the aid of Agrobacterium tumefaciens mediated transformation and expressed under the control of the CaMV 35S promoter. Plants with increased GMPase activity consistently showed increased L-ascorbate levels in leaves and fruit of between 20- and 70% compared to the wild-type. Plants transcribing the ALO gene exhibited small increases in L-ascorbate in green fruit (p < 0.1). Leaf tissue from MIOX plants displayed significant activity increases (p < 0.05), and substantial decreases in MI. In green fruit two MIOX lines had increases in activity, cell wall uronic acids and AsA levels. Marginal increases in L-ascorbate would not warrant industrial application, but follow-up research with over-expression of other enzymes of the “Smirnoff-Wheeler” pathway should be explored. / AFRIKAANSE OPSOMMING: Vitamien C (askorbiensuur of AsA) is ʼn sekondêre metaboliet wat in baie eukariote, insluitend gis, plante en diere geproduseer word. Dit speel ʼn noodsaaklike rol as ʼn anti-oksidant en ensiem kofaktor, funktioneer as ʼn elekronskenker en aanvaarder en is betrokke in verskillende ontwikkelings prosesse. Hierdie studie was geїnisieer met die doel om vitamien C produksie in tamatie te vermeerder. Drie gene, naamlik GDP-mannose pirofosforilase (GMPase) van Saccharomyces cerevisiae, arabinono-1,4-laktoon oksidase (ALO) van Saccharomyces cerevisiae en mio-inositol oksigenase 2 (MIOX2) van Arabidopsis thaliana was ektopies uitgedruk in the tamatie kultivar, Money Maker. GMPase skakel D-mannose-6-P om na GDP-D-mannose. Hierdie reaksie is deel van die goed gekenmerkde “Smirnoff Wheeler” baan. ALO kataliseer the terminale stap in eritroaskorbiensuur sintese in gis. In situ metaboliseer dit ook die plant en dier substrate om askorbiensuur te vervaardig. Mio-inositol (MI) is omgeskakel na D-glukuronsuur deur die aktiwiteit van MIOX. D-glukuronsuur is ʼn voorloper in L-guluno-1,4-laktoon sintese wat dan ʼn voorloper is van AsA in diere en word ook verdink om in plante teenwoordig te wees. Die gene was onafhanklik ingestel met die hulp van Agrobakterium tumefaciens gemedїeerde transformasie en uitgedruk onder die beheer van die CaMV 35S promotor. Plante met verhoogde GMPase aktiwiteit het in blare en vrugte konsekwente toename in L-askorbiensuur vlakke met tussen 20 – 70% gewys in vergelyking met wilde-tipe. Plante wat ALO getranskribeer het, het klein stygings in L-askorbiensuur in groen vrugte gewys (p < 0.1). Blaarweefsel van MIOX plante wat verhoogde aktiwiteit vertoon het, (p < 0.05), het ook aansienlike dalings in MI gehad. In groen vrugte van MIOX het twee lyne verhoogte aktiwiteit, selwand uronsuur en AsA vlakke gehad. Klein toename in L-askorbiensuur is nie gepas vir industriële toepassing nie, maar opvolg navorsing moet ondersoek word met die oor-uitdrukking van ander “Smirnoff-Wheeler” baan ensieme.

Made available in DSpace on 2014-06-11T19:23:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-11Bitstream added on 2014-06-13T19:50:30Z : No. of bitstreams: 1 manjate_da_me_arafcf.pdf: 904109 bytes, checksum: 93344d2596a14d27effae840c502b0f8 (MD5) / Ministério da Ciência, Tecnologia e Inovação (Mcti) / Universidade Estadual Paulista (UNESP) / O vírus da hepatite C é um agente infeccioso responsável pela inflamação do fígado e cuja progressão leva a hepatite C podendo produzir complicações como a cirrose, insuficiência hepática e hepatocarcinoma. A infecção pelo VHC progride com inflamação, provocando danos no parênquima hepático, no metabolismo de nutrientes neste órgão, aumento de espécies reativas de oxigênio e à diminuição das concentrações plasmáticas de antioxidantes. Este processo favorece a persistência da replicação viral e a cronicidade podendo levar à ineficiência da resposta imune e agravamento do quadro clínico do paciente. A vitamina C plasmática atua na primeira linha de defesa do organismo inativando as espécies reativas de oxigênio e protegendo os constituintes celulares contra possíveis danos, pois estimula a produção do interferon e citocinas antiinflamatórias, proliferação dos linfócitos T, aumento da atividade anti-apoptótica, entre outras. Uma das principais fontes de vitamina C na dieta humana são as frutas cítricas, em especial o suco de laranja. O objetivo deste estudo foi avaliar o estado nutricional, bioquímico e oxidativo de pacientes com hepatite C crônica. Os pacientes ingeriram 500 mL/dia de suco de laranja durante 8 semanas. No início e final do protocolo proposto foram realizadas avaliações dietéticas, antropométricas, bioquímicas e do estresse oxidativo. Os resultados mostraram que a ingestão regular de suco de laranja não alterou as variáveis antropométricas mas reduziu algumas variáveis bioquímicas, sendo o colesterol total, LDL-c, insulina, destacando-se a redução da proteína C reativa, que houve aumento da capacidade antioxidante e redução da peroxidação lipídica no soro dos pacientes. Pelos resultados observa- se que a ingestão do suco de laranja pode contribuir positivamente para redução do processo inflamatório e do... / Hepatitis C virus is an agent responsible for liver inflammation and the progression can leads to hepatitis C and complications such as cirrhosis, liver failure and hepatocellular carcinoma.VHC infection progresses to inflammation, causing damage in the liver parenchyma, metabolism of nutrients, increase reactive oxygen species and decrease plasma concentration of antioxidants. This process favors the persistence of viral replication and chronic liver disease and lead to inefficiency of the immune response and aggravation of the clinical status of the patients. The plasma vitamin c acts as the first line of defense by inactivation reactive oxygen species and protecting cellular components potential damage and stimulates the production of interferon and anti-inflammatory cytokines, proliferation of T linphocytes increase of anti-apoptotic among others. The greatest sources of vitamin C in the human diet are citrus fruits, especially orange juice. This study is aimed to evaluate the nutritional, biochemical and oxidative status of patients with chronic hepatitis C infection. The patients ingested 500 mL/Day of orange juice for eight weeks. At the beginning and end of the study were avaluated dietary, anthropometric, biochemical and marcs of oxidative stress. The study showed that regular intake of orange juice did not change the nutritional status, reduced some biochemical variables, and increased the antioxidant capacity and decrease lipid peroxidation in the serum of the patients. This study summarizes that the ingestion of orange juice can contribute positively to reduce inflammation oxidative stress have effect to hypocholesterolemic effect to chronic hepatitis C patients

Resumo: O vírus da hepatite C é um agente infeccioso responsável pela inflamação do fígado e cuja progressão leva a hepatite C podendo produzir complicações como a cirrose, insuficiência hepática e hepatocarcinoma. A infecção pelo VHC progride com inflamação, provocando danos no parênquima hepático, no metabolismo de nutrientes neste órgão, aumento de espécies reativas de oxigênio e à diminuição das concentrações plasmáticas de antioxidantes. Este processo favorece a persistência da replicação viral e a cronicidade podendo levar à ineficiência da resposta imune e agravamento do quadro clínico do paciente. A vitamina C plasmática atua na primeira linha de defesa do organismo inativando as espécies reativas de oxigênio e protegendo os constituintes celulares contra possíveis danos, pois estimula a produção do interferon e citocinas antiinflamatórias, proliferação dos linfócitos T, aumento da atividade anti-apoptótica, entre outras. Uma das principais fontes de vitamina C na dieta humana são as frutas cítricas, em especial o suco de laranja. O objetivo deste estudo foi avaliar o estado nutricional, bioquímico e oxidativo de pacientes com hepatite C crônica. Os pacientes ingeriram 500 mL/dia de suco de laranja durante 8 semanas. No início e final do protocolo proposto foram realizadas avaliações dietéticas, antropométricas, bioquímicas e do estresse oxidativo. Os resultados mostraram que a ingestão regular de suco de laranja não alterou as variáveis antropométricas mas reduziu algumas variáveis bioquímicas, sendo o colesterol total, LDL-c, insulina, destacando-se a redução da proteína C reativa, que houve aumento da capacidade antioxidante e redução da peroxidação lipídica no soro dos pacientes. Pelos resultados observa- se que a ingestão do suco de laranja pode contribuir positivamente para redução do processo inflamatório e do ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hepatitis C virus is an agent responsible for liver inflammation and the progression can leads to hepatitis C and complications such as cirrhosis, liver failure and hepatocellular carcinoma.VHC infection progresses to inflammation, causing damage in the liver parenchyma, metabolism of nutrients, increase reactive oxygen species and decrease plasma concentration of antioxidants. This process favors the persistence of viral replication and chronic liver disease and lead to inefficiency of the immune response and aggravation of the clinical status of the patients. The plasma vitamin c acts as the first line of defense by inactivation reactive oxygen species and protecting cellular components potential damage and stimulates the production of interferon and anti-inflammatory cytokines, proliferation of T linphocytes increase of anti-apoptotic among others. The greatest sources of vitamin C in the human diet are citrus fruits, especially orange juice. This study is aimed to evaluate the nutritional, biochemical and oxidative status of patients with chronic hepatitis C infection. The patients ingested 500 mL/Day of orange juice for eight weeks. At the beginning and end of the study were avaluated dietary, anthropometric, biochemical and marcs of oxidative stress. The study showed that regular intake of orange juice did not change the nutritional status, reduced some biochemical variables, and increased the antioxidant capacity and decrease lipid peroxidation in the serum of the patients. This study summarizes that the ingestion of orange juice can contribute positively to reduce inflammation oxidative stress have effect to hypocholesterolemic effect to chronic hepatitis C patients / Orientador: Thais Borges César / Coorientador: João Bosco Faria / Banca: Paulo Inácio da Costa / Banca: Ellen Cristini Freitas / Mestre

abstract: The antioxidant, antihistamine, and chemotactic properties of vitamin C provide the theoretical basis linking vitamin C supplementation to combating the common cold; yet, the clinical evidence is mixed. To date, vitamin C intervention trials have not systematically recorded cold symptoms daily or looked at fluctuations in plasma histamine over an extended period. Also, trials have not been conducted in individuals with marginal vitamin C status. This study examined the impact of vitamin C supplementation during cold season on specific cold symptoms in a population with low plasma vitamin C concentrations. Healthy young males who were not regular smokers or training for competitive sports between the ages of 18 and 35 with below average plasma vitamin C concentrations were stratified by age, body mass index, and vitamin C status into two groups: VTC (500 mg vitamin C capsule ingested twice daily) or CON (placebo capsule ingested twice daily). Participants were instructed to fill out the validated Wisconsin Upper Respiratory Symptom Survey-21 daily for 8 weeks. Blood was sampled at trial weeks 0, 4, and 8. Plasma vitamin C concentrations were significantly different by groups at study week 4 and 8. Plasma histamine decreased 4.2% in the VTC group and increased 17.4% in the CON group between study weeks 0 and 8, but these differences were not statistically significant (p>0.05). Total cold symptom scores averaged 43±15 for the VTC group compared to 148±36 for the CON group, a 244% increase in symptoms for CON participants versus VTC participants (p=0.014). Additionally, recorded symptom severity and functional impairment scores were lower in the VCT group than the CON group (p=0.031 and 0.058, respectively). Global perception of sickness was 65% lower in the VTC group compared to the CON group (p=0.022). These results suggest that 1000 mg of vitamin C in a divided dose daily may lower common cold symptoms, cold symptom severity, and the perception of sickness. More research is needed to corroborate these findings. / Dissertation/Thesis / M.S. Nutrition 2012