Despite the common usage of high-dose vitamin C among breast cancer patients, the published medical literature is not in agreement as to how mega-dose vitamin C may interact with conventional therapy to affect clinical outcomes. The purpose of this study was to investigate the interaction of mega-dose vitamin C with radiation therapy and with doxorubicin in the treatment of breast cancer. Cultures of EMT6 mouse mammary tumor cells were treated concurrently with varying dose of vitamin C and either radiation or doxorubicin. A clonogenic assay was then performed to determine the surviving fraction of the cells. The surviving fractions of cells in cultures receiving different doses of vitamin C were compared among themselves as well as with controls and dose response curves were generated. Results show that ascorbic acid administered in concentrations of 1 mM or 10 mM 4 hours before x-irradiation protected the cells from radiation-induced cytotoxicity. The dose-modifying factors for 1 mM and 10 mM ascorbic acid as compared to controls were 1.23 and 1.37 respectively. These results support the hypothesis that mega dose vitamin C, when taken concurrently with radiation therapy, protects cancer cells from the cytotoxic effects of ionizing radiation. No evidence was found to suggest that mega-dose vitamin C alters the antineoplastic effects of doxorubicin.

Šiame darbe naudojamas Epsilon potenciastato modelis, sujungtas su Epsilon EC-2000-XP(Ver. 1.40.67_NT) programa ir kompiuteriu. Tyrimo metu naudojama trijų elektrodų celė. Darbiniu ir pagalbiniu elektrodais naudojami platinos elektrodas. Palyginamuoju naudojamas Ag/AgCl/KClsot elektrodas. Visos potencialų vertės nurodomos palyginamojo elektrodo atžvilgiu. POT sluoksnis nusodintas potenciostatiniu ir potenciodinaminiu būdu ant platinos elektrodo, keičiant eksperimento sąlygas. Potenciodinaminiai dengimo matavimai atlikti keičiant elektrodo potencialą nuo -0,1V iki 1,0V ir nuo -0,1V iki 1,2V. Dengiant Pt elektrodą buvo atliekama 10 arba 20 ciklų. Potencialo skleidimo greitis – 10, 20, 50 ir 100 mV/s. Potenciostatiniai dengimo matavimai atlikti esant pastoviam potencialui Econst 0,9V, 1,0V ir 1,2V ir dengimo laikui (tdeng) 1, 3 arba 5 minutės. Poli(o-metilanilinu) modifikuoti elektrodai gali būti naudojami askorbo rūgšties analizei tirpaluose, kurių pH 5,5. Askorbo rūgšties koncentracijų intervale nuo 0,1mM iki 1mM gaunama tiesinė oksidacijos ribinių srovių priklausomybė nuo koncentracijos, jei askorbo rūgšties matavimai atliekami potenciostatinėmis sąlygomis. Žemiausia askorbo rūgšties nustatymo riba – 0,1mM. / The Epsilon potentiometer model combined with a PC running Epsilon EC-2000-XP (Ver. 1.40.67_NT) software was used in these theses. During the research, a three-electrode cell was used. A platinum electrode was utilised as the working and auxiliary electrode. An Ag/AgCl/KClsot electrode was used as reference electrode. All values of the potentials refer to this electrode. An POT layer was deposited under potentiostatic or potentiodynamic conditions on platinum electrode by varying parameters of the experiment. Potentiodynamic polymer formation measurements were performed by alternating the electrode potential from 0.1V to 1.0V and from 0.1V to 1.2V. When modifying Pt electrode, 10 or 20 potential cycles were performed. The potential scan rate was 10, 20, 50, and 100 mV/s. Potentiostatic polymer formation measurements were performed under the constant potential Econst 0.9V, 1.0V, and 1.2V, and the time of coating (tcoating) was 1, 3 or 5 minutes. Poly (o-methylaniline) modified electrodes can be used for the analysis of ascorbic acid in solutions with pH values 5,5. Within the concentration interval of ascorbic acid between 0,1mM and 1mM, a linear dependence between oxidation limit currents and concentration was observed when ascorbic acid measurements were carried out potentiostatic conditions. The lowest sensing limit of ascorbic acid was 0,1mM.

Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations the drug is often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Katecholamine (Dopamin, Adrenalin, Noradrenalin) und Serotonin sind wichtige Monoamin-Neurotransmitter im menschlichen zentralen Nervensystem, deren quantitative Bestimmung von großem medizinischen Interesse ist, weil damit Aussagen zum Verlauf von Nervenkrankheiten und zur Tumorgefährdung des sympathoadrenalen bzw. neuroendokrinen Systems möglich sind. Ascorbinsäure und Harnsäure finden sich in vielen Körperflüssigkeiten. Ihre Bestimmung ist klinisch ebenfalls bedeutend, da deren Konzentration als Indikatoren bekannter Krankheitsbilder dienen. Etablierte Standardmethoden, wie die Hochleistungsflüssigkeitschromatographie (HPLC) und immunologische Nachweisverfahren (ELISA) werden im klinischen Bereich zur Bestimmung der Neurotransmitter genutzt. Diese sind kostenintensiv und zeitaufwändig und daher für die Anwendung in den Arztpraxen, vor allem in Entwicklungsländern nicht geeignet. Elektrochemische Verfahren, insbesondere voltammetrische Messmethode haben den Vorteil, solche Bestimmungen in einfacher Weise zu ermöglichen. In der Literatur finden sich Angaben zu eingesetzten Elektroden auf Kohlenstoffbasis mit hoher Sensitivität für die Katecholamine. Allerdings wurden diese Elektroden meist einzeln hergestellt. Der kommerzielle Durchbruch ist deshalb bisher, hauptsächlich infolge der mangelnden Reproduzierbarkeit der Elektrodeneigenschaften und der Verfügbarkeit einfacher elektronischer Geräte ausgeblieben. Es war daher Ziel dieser Arbeit, durch industrienahe Herstellungsverfahren Graphitelektroden mit reproduzierbaren Eigenschaften zu entwickeln und diese auf ihre Eignung für den quantitativen Nachweis bioaktiver Stoffe zu erproben. Dazu waren Verfahrensschritte zu optimieren, die es erlauben, diese siebgedruckten Graphitelektroden reproduzierbar und kostengünstig zu fertigen und sie auf verschiedene Weise, z.B. durch halbleitende Polymere und nanoskalige Metalle zu modifizieren. Neben den Neurotransmittern enthalten Körperflüssigkeiten unter anderem Ascorbinsäure und Harnsäure in hohen Konzentrationen. Daher waren zunächst Modellanalyten unter Verwendung dieser Stoffe herzustellen. Die voltammetrischen Methoden, wie die zyklische Voltammetrie (CV), die Differentielle Puls-Voltammetrie (DPV) und die Square-Wave-Voltammetrie (SWV) sollten auf ihre Eignung zum Nachweis der bioaktiven Substanzen erprobt werden. Schließlich waren die Elektroden in realen Analyten zu testen. Insgesamt konnte in der vorliegenden Arbeit gezeigt werden, dass ausgewählte Neurotransmitter, Ascorbinsäure und Harnsäure sich mit differentiellen voltammetrischen Verfahren an industrienah hergestellten modifizierten Dickschichtelektroden bestimmen lassen. Es ist erstmalig gelungen, eine modifizierte Dickschichtelektrode zu entwickeln, mit der es möglich ist, Katecholamine unabhängig von Ascorbinsäure (3 mM) und Harnsäure (2 mM) quantitativ nachzuweisen. Damit eröffnen sich neue Wege für den Einsatz von elektrochemischen Sensoren für die einfache Bestimmung der Neurotransmitter vor Ort. Die beschriebenen modifizierten Dickschichtelektroden sind ohne Verlust an elektrochemischer Aktivität an der Luft oder im Grundelektrolyten monatelang lagerfähig. Die Elektroden lassen sich im Gegensatz zu den in der Literatur beschriebenen Elektroden mit Einzelfertigung kostengünstig in großer Stückzahl mit hoher Reproduzierbarkeit herstellen.

Diss. (sammanfattning) Alnarp : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

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

abstract: Vitamin C is a micronutrient with many important physiological roles. It can function as a reducing agent, a free radical scavenger, and an enzyme cofactor. Much research has examined the potential of vitamin C supplements to enhance exercise capacity in trained athletes; however, little is known regarding the effects of vitamin C supplements on the promotion of leisure-time physical activity in the general population. This area deserves attention since 1/3 of Americans have below adequate vitamin C status, and since aversion to exercise, fatigue, and altered mood states are the earliest signs of poor vitamin C status. This study analyzed the effect of supplementing 500 mg twice daily of vitamin C on self-reported leisure-time activity levels and mood states in young men. Twenty-nine healthy, young men, aged 18-35 years, were stratified by age, BMI, smoking status, and plasma vitamin C concentrations and assigned to either a control (CON) or experimental group (VTC) for the 8-week randomized, double-blinded, parallel arm trial. Subjects were instructed to keep track of their leisure-time physical activity by filling out the validated Godin Leisure-Time Exercise Questionnaire weekly for the entire study. In addition, subjects took the self-administered Profile of Mood States (POMS) at baseline, week 4, and week 8 to observe mood states. Plasma vitamin C concentrations were analyzed at the initial screening, week 4, and week 8 of the study. Plasma vitamin C concentrations significantly differed by group at week 4 and week 8. Furthermore, vitamin C supplementation significantly increased self-reported mild, moderate, and strenuous activity levels during the 8-week trial. Overall, total physical activity scores increased nearly 50% in the VTC group as compared to 18% in the CON group (p=0.001). However, mood states were not significantly impacted by vitamin C supplementation during the trial. This study provides the first experimental evidence that supplementing 500 mg of vitamin C twice daily can be effective in increasing leisure-time physical activity in healthy young men. This study, however, was unable to link improvements in physical activity rates to improved mood states. Since sedentary behaviors have been implicated in the rise of obesity in the U.S., further research should be conducted to substantiate the finding that vitamin C supplementation increases physical activity. / Dissertation/Thesis / M.S. Nutrition 2012

Neste estudo apresenta-se a síntese de duas amostras de nanopartículas de ferrita de níquel, denominadas C-NiFe2O4 e NiFe2O4, através de um método simples, de baixo custo e ambientalmente amigável. Estudos morfológicos, estruturais, eletrônicos, ópticos e magnéticos foram realizados com o intuito de caracterizar as propriedades desses materiais para que possibilitassem, além de maior grau de conhecimento, sua aplicação como sensores colorimétricos para detecção de ácido ascórbico e peróxido de hidrogênio. Mediante a análise térmica dos precursores, foi possível determinar os intervalos de temperatura de decomposição, assim como a temperatura ótima de formação das nanopartículas. A amostra NiFe2O4 é ferromagnética e corresponde a uma fase cúbica de espinélio inverso. Os dados de difração de raios X, espectroscopia Mössbauer e o modelo iônico sugerem a presença de um certo grau de substituição, possuindo em sua estrutura um cátion divalente como agente dopante. As nanopartículas de C-NiFe2O4 foram utilizadas como catalisador na oxidação do 3,3',5,5'-tetrametilbenzidina (TMB) em meio ácido para formar uma solução azul sem adição de outro reagente. Como resultado foi utilizado como sensor colorimétrico para detecção de ácido ascórbico, visto que este reduz o complexo de transferência de carga, TMBOX, novamente para TMB. A calibração analítica apresentou uma faixa linear entre 1-20 μM para a concentração de ácido ascórbico, com limite de detecção (3/m) de 0,93 μM. A determinação em suplementos de vitamina C através do método de adição de padrão mostrou a eficiência do sensor para detectar ácido ascórbico em amostras reais. Já a amostra de NiFe2O4 demonstrou atividade catalítica semelhante as peroxidases naturais, oxidando o TMB na presença de H2O2 para formar TMBOX, que dá coloração azul a solução. Dessa forma, NiFe2O4 foi utilizado em um sensor colorimétrico para detecção de H2O2 e a calibração analítica revelou duas faixas lineares, uma entre 2,28 - 28,60 μM e a outra entre 28,60 μM - 114,20 μM. O limite de detecção (3/m) foi de 1,94 μM. Ambos os métodos apresentaram boa repetibilidade, com coeficiente de variação de 3,5% e 4% respectivamente. / This study presents the synthesis of two samples of nickel ferrite nanoparticles, termed C-NiFe2O4 and NiFe2O4, through a simple, low cost and environmentally friendly method. Morphological, structural, electronic, optical and magnetic studies were carried out with the aim of characterizing the properties of these materials, which allowed the application of colorimetric sensors for the detection of ascorbic acid and hydrogen peroxide. Through the thermal analysis of the precursors, it was possible to determine the decomposition temperature ranges, as well as the optimum temperature of formation of the nanoparticles. The sample NiFe2O4 is ferromagnetic and corresponds to a cubic phase of inverse spinel. The X-ray diffraction data, Mössbauer spectroscopy and the ionic model suggest the presence of a certain degree of substitution, having in its structure a divalent cation as a doping agent. The C-NiFe2O4 nanoparticles were used as catalysts in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in acidic medium to form a blue solution without addition of another reagent. As a result, it was used as a colorimetric sensor for the detection of ascorbic acid, as it reduces the charge transfer complex, TMBOX, again to TMB. The analytical calibration showed a linear range between 1-20 μM for the concentration of ascorbic acid, with a detection limit (3 /m) of 0.93 μM. The determination of vitamin C supplements using the standard addition method showed the efficiency of the sensor to detect ascorbic acid in actual samples. Already NiFe2O4 sample demonstrated catalytic activity similar to natural peroxidases, oxidizing the TMB in the presence of H2O2 to form TMBOX, which gives blue coloration to the solution. Thus, NiFe2O4 was used in a colorimetric sensor to detect H2O2, and the analytical calibration revealed two linear ranges, one between 2.28 - 28.60 μM and the other between 28.60 μM - 114.20 μM. The detection limit (3 /m) was 1.94 μM. Both methods presented good repeatability, with a coefficient of variation of 3.5% and 4% respectively.

Neste estudo apresenta-se a síntese de duas amostras de nanopartículas de ferrita de níquel, denominadas C-NiFe2O4 e NiFe2O4, através de um método simples, de baixo custo e ambientalmente amigável. Estudos morfológicos, estruturais, eletrônicos, ópticos e magnéticos foram realizados com o intuito de caracterizar as propriedades desses materiais para que possibilitassem, além de maior grau de conhecimento, sua aplicação como sensores colorimétricos para detecção de ácido ascórbico e peróxido de hidrogênio. Mediante a análise térmica dos precursores, foi possível determinar os intervalos de temperatura de decomposição, assim como a temperatura ótima de formação das nanopartículas. A amostra NiFe2O4 é ferromagnética e corresponde a uma fase cúbica de espinélio inverso. Os dados de difração de raios X, espectroscopia Mössbauer e o modelo iônico sugerem a presença de um certo grau de substituição, possuindo em sua estrutura um cátion divalente como agente dopante. As nanopartículas de C-NiFe2O4 foram utilizadas como catalisador na oxidação do 3,3',5,5'-tetrametilbenzidina (TMB) em meio ácido para formar uma solução azul sem adição de outro reagente. Como resultado foi utilizado como sensor colorimétrico para detecção de ácido ascórbico, visto que este reduz o complexo de transferência de carga, TMBOX, novamente para TMB. A calibração analítica apresentou uma faixa linear entre 1-20 μM para a concentração de ácido ascórbico, com limite de detecção (3/m) de 0,93 μM. A determinação em suplementos de vitamina C através do método de adição de padrão mostrou a eficiência do sensor para detectar ácido ascórbico em amostras reais. Já a amostra de NiFe2O4 demonstrou atividade catalítica semelhante as peroxidases naturais, oxidando o TMB na presença de H2O2 para formar TMBOX, que dá coloração azul a solução. Dessa forma, NiFe2O4 foi utilizado em um sensor colorimétrico para detecção de H2O2 e a calibração analítica revelou duas faixas lineares, uma entre 2,28 - 28,60 μM e a outra entre 28,60 μM - 114,20 μM. O limite de detecção (3/m) foi de 1,94 μM. Ambos os métodos apresentaram boa repetibilidade, com coeficiente de variação de 3,5% e 4% respectivamente. / This study presents the synthesis of two samples of nickel ferrite nanoparticles, termed C-NiFe2O4 and NiFe2O4, through a simple, low cost and environmentally friendly method. Morphological, structural, electronic, optical and magnetic studies were carried out with the aim of characterizing the properties of these materials, which allowed the application of colorimetric sensors for the detection of ascorbic acid and hydrogen peroxide. Through the thermal analysis of the precursors, it was possible to determine the decomposition temperature ranges, as well as the optimum temperature of formation of the nanoparticles. The sample NiFe2O4 is ferromagnetic and corresponds to a cubic phase of inverse spinel. The X-ray diffraction data, Mössbauer spectroscopy and the ionic model suggest the presence of a certain degree of substitution, having in its structure a divalent cation as a doping agent. The C-NiFe2O4 nanoparticles were used as catalysts in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in acidic medium to form a blue solution without addition of another reagent. As a result, it was used as a colorimetric sensor for the detection of ascorbic acid, as it reduces the charge transfer complex, TMBOX, again to TMB. The analytical calibration showed a linear range between 1-20 μM for the concentration of ascorbic acid, with a detection limit (3 /m) of 0.93 μM. The determination of vitamin C supplements using the standard addition method showed the efficiency of the sensor to detect ascorbic acid in actual samples. Already NiFe2O4 sample demonstrated catalytic activity similar to natural peroxidases, oxidizing the TMB in the presence of H2O2 to form TMBOX, which gives blue coloration to the solution. Thus, NiFe2O4 was used in a colorimetric sensor to detect H2O2, and the analytical calibration revealed two linear ranges, one between 2.28 - 28.60 μM and the other between 28.60 μM - 114.20 μM. The detection limit (3 /m) was 1.94 μM. Both methods presented good repeatability, with a coefficient of variation of 3.5% and 4% respectively.

A obstrução de cateter venoso central totalmente implantado (CV-TI) é uma das complicações relacionadas ao seu uso. A recuperação da permeabilidade do CVC-TI é a maneira mais adequada de lidar com esta complicação por se tratar de uma intervenção mais rápida e de menor custo quando comparado com o reposicionamento ou a troca do dispositivo. O ácido ascórbico (AA) vem sendo utilizado em alguns hospitais brasileiros e resultados satisfatórios têm sido obtidos. Estudos in vitro relataram que o AA atua no processo fibrinolítico e pode contribuir para a desobstrução de cateter venoso central de longa permanência. O presente estudo tem por finalidade determinar a dose de segurança do ácido ascórbico para o tratamento da obstrução de cateter venoso central totalmente implantado. Trata-se de ensaio clínico fase II, randomizado em três grupos de tratamento (50mg, 100mg e 200mg de ácido ascórbico), não controlado, conduzido em quatro hospitais brasileiros. Para isso, foram incluídos 21 sujeitos com idade média de 53 anos, a maioria com diagnóstico de câncer de mama. Seis sujeitos obtiveram sucesso com o tratamento proposto, apresentando a desobstrução do cateter. Dentre eles, quatro receberam a dose de 50 miligramas e apresentaram desobstrução completa ou parcial. Em relação ao tempo de desobstrução, três cateteres foram desobstruídos em menos de 60 minutos e três em 60 minutos; entre eles, dois que haviam recebido dose de 50 miligramas. Observou-se, também, que houve relação entre a presença de obstrução anterior e a falha no tratamento com AA. Além disso, aqueles que não tiveram o cateter desobstruído apresentaram intervalo de tempo maior entre o diagnóstico da obstrução e o tratamento da mesma, onde foram identificados 355 dias contra 112 dias naqueles que tiveram o cateter desobstruído. A variável de segurança analisada demonstrou que o ácido ascórbico não induziu reações de hipersensibilidade nesses sujeitos. Conclui-se, portanto, que o tamanho de amostra obtido é insuficiente para afirmar que o ácido ascórbico não seja eficaz na desobstrução de cateter venoso central totalmente implantado. Os resultados encontrados neste estudo nos levam a sugerir, por ora, que a dose de 50mg pode ser testada em um ensaio clínico de fase III, com amostra maior, a fim de validar o uso do ácido ascórbico como um possível agente eficaz no tratamento da obstrução de cateter totalmente implantado. / The occlusion of totally implanted central venous catheter (TI-CVC) is one of the catheterrelated complications. The recovery of the permeability of the TI-CVC is the most appropriate way of dealing with this complication, once it is a faster and less costly intervention than the reposition or change of the device. Ascorbic acid (AA) has been used in some Brazilian hospitals and satisfactory results have been obtained. In vitro studies have reported that AA acts on the fibrinolytic process and can contribute to restore the patency of indwelling central venous catheters. This study aimed to determine the safe dosage of ascorbic acid for the treatment of occluded totally implanted central venous catheter. It is a phase II clinical trial, randomized into three treatment groups (50mg, 100mg and 200mg of ascorbic acid), not controlled, carried out in four Brazilian hospitals. In total, 21 subjects with average age of 53 years were included, most of them diagnosed with breast cancer. Six subjects had success in the proposed treatment, presenting the patency of the catheter. Among them, four were given a dose of 50 milligrams and presented complete or partial patency. Concerning the time of patency, three catheters were cleared in less than 60 minutes and three in 60 minutes, including two that had received a dose of 50 milligrams. Association between the presence of previous obstruction and failure in treatment with AA was also observed. Moreover, those who did not have the catheter cleared presented higher time interval between diagnosis of obstruction and treatment of it, being the intervals 355 days opposed to 112 days for those who had the catheter cleared. The safety variable analyzed showed that ascorbic acid did not induce hypersensitivity reactions in these subjects. It is concluded that the sample size obtained is insufficient to state that ascorbic acid is not effective in clearing totally implanted central venous catheter. Results from this study suggest, for now, that the 50mg dose can be tested in a phase III clinical trial, with larger sample, as to validate the use of ascorbic acid as an agent in the treatment of occluded totally implanted catheter.