Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T10:28:13Z (GMT). No. of bitstreams: 1 Silva_AmandaFalcaoda_D.pdf: 1562450 bytes, checksum: f94a4f323b0604892bc95caf3aec4e5a (MD5) Previous issue date: 2014 / Resumo: Há clara evidência da importância da água fluoretada como um meio coletivo de uso de fluoreto (F), responsável pelo decréscimo na incidência de cárie dental. Entretanto, ainda se discute a respeito de seu mecanismo de ação, quer seja relacionado ao aumento da concentração de F na saliva pelo contato com a água fluoretada, quer seja pelo retorno do íon à cavidade bucal, após sua absorção, pela secreção salivar. Além disso, não apenas a ingestão de água fluoretada, mas também de alimentos com ela preparados, tem potencial anticárie, porém desconhece-se se há diferença entre ambas as formas de utilização na capacidade de elevar a concentração salivar de F. Assim, o objetivo deste trabalho foi avaliar a biodisponibilidade de F proveniente da ingestão de água ou de alimentos preparados com água fluoretada. O estudo foi in vivo (n=20), cruzado, duplo cego, e realizado em 4 fases experimentais, nas quais os voluntários ingeriram: água não fluoretada (< 0,01 µg F/mL), água fluoretada (1 µg F/mL), refeição preparada com água não fluoretada ou refeição preparada com água fluoretada. A refeição foi composta por arroz, feijão, carne, vagem, cenoura, suco e gelatina, e o tempo para ingestão foi padronizado em 15 minutos. A dose de F ingerida foi baseada no peso corporal para atingir 0,8 µg F/kg peso corporal, quando da ingestão água ou da refeição preparada com água não fluoretada (dose correspondente ao F residual presente nos alimentos), e 12 µg F /Kg de peso corporal, quando da ingestão de água ou refeição preparada com água fluoretada. Imediatamente antes e 5, 10, 15, 30, 45, 60, 120 e 180 minutos após a ingestão, amostras de sangue e saliva não estimulada foram coletadas para determinação da concentração de F. As amostras de sangue (de 1 a 10 µL) foram obtidas por punção digital e a concentração de F foi determinada no plasma sanguíneo por eletrodo íon-específico, adaptado para microanálise. Na saliva, a concentração de F foi determinada após microdifusão facilitada com hexametildisiloxano. A biodisponibilidade de F foi estimada a partir da área sob a curva (ASC) das concentrações plasmática e salivar de F em função do tempo. Os grupos foram comparados utilizando análise de variância, seguida de teste de Tukey. Significativo aumento na ASC da concentração de F no plasma e saliva foi observado quando da ingestão de água e da refeição preparada com água fluoretada em comparação com os grupos controles (p<0,05), sem diferença entre as formas de utilização (p>0,05). Conclui-se que tanto a ingestão de água quanto de alimento fluoretado aumentam a biodisponibilidade de F no plasma e na saliva e podem contribuir para seu benefício anticárie / Abstract: There is clear evidence of the importance of fluoridated water as a public measure of fluoride (F) use, being responsible for the decrease in dental caries incidence. Nevertheless, its mechanism of action, whether related to the increase in salivary F concentration by the immediate contact with fluoridated water or by the return of the ion to the oral cavity by salivary secretion after its absorption, is still under discussion. Moreover, not only the ingestion of fluoridated water, but also of food cooked with it, has anticaries potential, but it is unknown whether there are differences between these two ways in respect to the ability to elevate salivary F concentration. Thus, the aim of this study was to evaluate the F bioavailability from drinking water or foods prepared with fluoridated water. The study was in vivo (n = 20), crossover, double blind, conducted in 4 experimental phases, in which volunteers ingested: non-fluoridated water (< 0.01 µg F / ml), fluoridated water (1 µg F / ml), meal prepared with non-fluoridated water and meal prepared with fluoridated water. The meal consisted of rice, beans, meat, beans, carrot, juice and gelatin, and the time for intake was standardized in 15 minutes. The dose of ingested F was based on body weight to achieve 0.8 µg F/kg body weight, considering the intake of the water or meal prepared with non-fluoridated water (corresponding to the residual F dose present in foods), and 12 µg F/kg of body weight, considering the intake of water or food prepared with fluoridated water. Immediately before and 5, 10, 15, 30, 45, 60, 120 and 180 minutes after ingestion, unstimulated saliva and blood samples were collected to determine the F concentration. Blood samples (1 to 10 µL) were obtained from finger draws and F concentration in blood plasma was determined by ion-specific electrode, adapted for microanalysis. In saliva, the F concentration was determined after microdiffusion with hexamethyldisiloxane. The F bioavailability was estimated from the area under the curve (AUC) of plasma and salivary F concentrations as a function of time. Groups were compared using analysis of variance followed by Tukey test. Significant increase in the AUC of plasma F and saliva concentrations were observed when both water and meal prepared with fluoridated water were compared to control groups (p<0.05), with no difference between the forms of use (p>0.05). We conclude that both the intake of fluoridated water or foods prepared with it increase the F bioavailability in plasma and saliva and can have anticaries potential / Doutorado / Cariologia / Doutora em Odontologia

Vitamin D deficiency is an epidemic issue in all age groups in Western countries and that affects both skeletal and non-skeletal functions. Even with the wide application of food fortification, vitamin D deficiency tends to increase continuously. Being hydrophobic in nature, vitamin D has poor solubility; thereby it negatively affects its absorption and bioavailability when compared to other hydrophilic dietary compounds. The need to develop a novel strategy is of greater importance to enhance its bioavailability and thereby improving vitamin D level in the body. In this study, lipid-based delivery of oil-in-water nanoemulsion (diameter < 200nm) was utilized to improve the bioaccessibility and oral bioavailability of vitamin D3. First, we examined the in vitro relative bioaccessibility of nanoencapsulated vitamin D3 using a simulated gastrointestinal system. The study results showed that nanoemulsion-based delivery system significantly increased the relative bioaccessibility by 3.94 fold when compared to the coarse emulsion (diameter >200nm), as indicated by the concentration of vitamin D3 in the mixed micelles. To evaluate the in vivo bioavailability of vitamin D3 an animal study was conducted. Mice were assigned randomly to three groups: vitamin D3 nanoemulsion (n=6), coarse emulsion (diameter > 200nm) (n=6) and vehicle (nanoemulsion without vitamin D3) (n=3), which is the control group. After 3-days of feeding emulsion by mixing in drinking water, the serum 25(OH)D3, a biomarker of vitamin D availability, was measured using immunoassay. We found that serum 25(OH)D3 level in animals fed with vitamin D3 nanoemulsion was significantly higher than in those animals fed with coarse emulsion (22.7 ± 1.10 ngmL-1 vs 17.92 ± 2.82 ngmL-1). It indicated that nanoemulsion improved the in vivo bioavailability by 28%. These results showed that the nano-based delivery systems can be utilized to improve vitamin D level, and further human studies are warranted for its application to the human population in order to improve the vitamin D status.

Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symtoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.

Methadone hydrochloride is an old drug that has been in vogue off and on. It has complex pharmacodynamics and can be potentially fatal in inexperienced settings. Drug switching from an opioid to methadone or vice versa requires knowledge of equianalgesic dosing. It is critical when using the drug to monitor for signs and symptoms of toxicity so that overdosing or toxicity can be identified in a timely manner. This review discusses these important topics so that methadone can be used safely and effectively.

Soil pollution in recent years has emerged as an issue of great environmental concern. Contamination of soil by improper disposal or spillage of petrochemicals and products containing petroleum hydrocarbons is one of such pollution cases highly reported. To remediate petroleum contaminated soil, A DC powered electrokinetic reactor was used with biosurfactants as an enhancement for the remediation process. To begin with, studies were made under voltage variations of 10 V and 30 V with an electrode spacing of 185 mm. Biosurfactant with its producing microbes and biosurfactant free cells were introduced in the soil chamber after which the reactor was left to run for 10 days under the electric field. The technology was able to achieve the highest oil recovery of 75.15 % from the soil in 96 hours at 30 V. With other factors remaining constant, the reactor was also operated under a constant voltage of 30 V with configurations of fixed electrodes spacings of 335 mm, 260 mm,185 mm and continuous approaching electrodes at 335 mm, 260 mm and 185 mm. The current in the electrolyte was highest with the least electrode distance of 185 mm. The increase in current led to a direct proportional increase in the electroosmotic flow towards the cathode leading to increased coalescence of the oil from the soil as compared to the other electrode distances. The analysis of the results showed reduction in the total carbon content in the soil with viable oil recovery rates for all the electrode distances with 185 mm being the most effective in both oil recovery and degradation. The reactor was further operated with amended biosurfactant concentrations of 28 g/L, 56 g/L and 84 g/L to enhance the recovery of oil from the soil and aid in biodegradation of the remaining oil by hydrocarbon degrading microbes. The highest oil recovery of 83.15 % was obtained with the biosurfactant concentration of 56 g/L showing that the hyper increase in concentration of the biosurfactants is not necessary to have an efficient process. In all experiments the microorganisms were able to survive under the electro-halo-thermal environment in the reactor and degraded the remaining hydrocarbons to acceptable amounts in the environment. The bacteria were however affected by the constantly changing pH in all experiments. The presence of biosurfactants was so significant in aiding oil recovery and increasing bioavailability of hydrocarbons to the microbes. Production of biosurfactants in the reactor followed up by kinetic suggestions of the processes in the bioelectrokinetic reactor should be studied in future. / Dissertation (MEng (Environmental Engineering))--University of Pretoria, 2019. / Chemical Engineering / MEng (Environmental Engineering) / Unrestricted

Arsenic is a notorious poison due to its high toxicity, worldwide distribution, and lack of any taste and colour once dissolved. The abundance of arsenic in Earth’s crust makes that it can naturally find its way into food and drinking water. Rapid and reliable detection of arsenic, directly in the field, is critical to support evidence-based decision-making in choosing irrigation or drinking water sources. Current cost-effective colourimetric techniques are associated with poor accuracy, health risks, and unacceptable levels of false negatives. Arsenic-specific cellular sensors, or biosensors, may present an inexpensive, safe, and renewable alternative, yet they have long been criticized for unsatisfactory sensing performance, and inconsistency of the outcome. This, in addition to the lack of suitable instruments capable of measuring the signals produced by these biosensors, has led to very few solutions reaching market. The goal of my thesis research was to test hypotheses that improve our fundamental understanding of As species biogeochemistry in simple and complex environmental matrices to then develop a new arsenic monitoring interface, one that would be both simple and accessible to the general public. Using a combination of wild-type and mutant strains, I managed to detail both the internal regulation of arsenic, and the external drivers of arsenic bioavailability. I started by designing a defined exposure protocol that achieved, for the first time, equimolar uptake of over 94% of the added As(III) and As(V) into the cells. By developing this control early into my thesis, I then worked to reintroduce commonly found constituents of environmental waters that are thought to impact arsenic uptake. This direct testing approach uncovered fundamentals of environmental arsenic redox chemistry such as As(III) photooxidation in solution, environmental ligand exchanges, and biological transport pathways. Simplifying a complex exposure protocol for use by the general public required automation of the data analysis steps. This consists of several hundred lines of code, capable of analyzing, normalizing and stabilizing biosensor output to improve the consistency and robustness of this system. These algorithms were then integrated into a new arsenic monitoring interface, one that was built and designed specifically for dehydrated biosensors. This portable, low-cost spectrometer achieved a fluorescent detection range that rivals expensive and sophisticated laboratory equipment at a fraction of the price, and without the need for a computer to compile the measurements. In contrast to highly criticized colorimetric techniques, the biosensor exposure protocol exceeds in operational use, reliability and detection limit. At its core, my thesis research provides a new and complete arsenic testing solution, one capable of measuring both As(III) and As(V) at levels relevant to the World Health Organization and Canadian guidelines for arsenic content in water (10 µg/L). It also provides a new method capable of selectively discriminating between arsenic species, thereby providing an inexpensive and high-throughput arsenic speciation method. I hope this work will help kickstart development of a marketable solution that empowers individuals to test and to monitor the quality of their water sources.

Methods currently used to determine iron bioavailability have disadvantages for both the subjects and researchers involved. One safe and simple method that needs further evaluation, the serum iron absorption method, involves an initial blood drawing, dosage s of iron, and blood drawings taken at intervals thereafter. Generally, the rise in serum iron or area under the curve is used to determine iron uptake. Two experiments were conducted using the serum iron absorption method in an effort to improve the utility of this method for the measurement of iron bioavailability. With this effort in mind, an equation adjusting for dose of iron (0.5-8 mg) and blood volume was used to estimate serum iron absorption and allow for adequate comparisons of other iron absorption data obtained with this method and others. One very significant result was that low serum ferritin was found to be a predictor of high serum estimated iron absorption (SEIA). Similarly, low serum ferritin levels were also highly correlated to iron absorption when radioiron methods were used. In Experiment I, college-aged women (n=11) with low serum ferritin levels (average 11 ng/ml) participated in four serum iron trials in which four iron sources were used as iron dosages. Ferrous sulfate in orange juice (2.2 mg iron), ground beef (0.62 mg iron), cereal (6.6 mg iron), and ground beef and cereal together (3.6 mg iron) were used. Comparisons were made between the results obtained using this serum iron absorption data and other radioiron absorption data for similar iron sources, and the results were quite similar to iron absorption levels reported in the literature. In Experiment I, the ferrous sulfate (40%) and ground beef treatments (46%) had the highest serum estimated iron absorption (SEIA) and the cereal/ground beef (5%) and cereal treatments (3%) had significantly less. Experiment II involved 28 college-aged women who participated in four serum iron absorption trials. For these four trials the iron dose was the same (2 mg iron as ferrous sulfate in orange juice). However, pre-trial supplements containing either (1) 30 mg iron, 60 mg ascorbic acid, (2) 30 mg iron, no ascorbic acid, (3) no iron, 60 mg ascorbic acid, or (4) a placebo were given (one per day) on each of the three days prior to the weekly serum iron absorption trials. During each pre-trial supplementation period, three daily diet records were kept by subjects to determine if the previous intake of nutrients (from food or pre-trial supplements) influenced the outcome of the serum iron absorption trial. Pre-trial supplementation of 30 mg iron, no ascorbic acid caused a significantly lower SEIA. Dietary nutrients did not cause a significant effect on SEIA. Mean SEIA following combined iron supplements was lower (p=0.081) 16% vs. 23% following non-iron containing supplements. For this experiment, the SEIA was higher in subjects with low serum ferritin (20 ng/ml).

Vitamin E TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate), the water-soluble derivative of the naturally occurring d-a-tocopherol, was used initially to overcome malabsorption and correct severe vitamin E deficiency in cholestatic children. The observation that its administration increased the absorption of vitamin D focused attention on its amphiphilic properties as nonionic surfactant and applications in solubilizing lipophilic and poorly soluble compounds and enhancing their absorption and bioavailability. Further research has evaluated its safety and efficacy which combines solubilization and formation of micelle-like particles with inhibition of P-glycoprotein-mediated efflux, the key mechanism to the development of drug resistance. These properties expanded its applications in pharmaceuticals and dietary, disease-specific, supplements for malabsorbing patients. Emerging research on major nutraceuticals and the developing field of cannabinoids have shown that poor water solubility and extensive first-pass metabolism cause poor absorption and bioavailability. This chapter describes the properties, safety, and efficacy of vitamin E TPGS with a focus on its applications in nutraceuticals and cannabinoids.

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