An Experimental Model of Prostatic Inflammation for Drug Discovery

There is increasing evidence to support a significant role for chronic non-bacterial, prostatic inflammation in the development of human voiding dysfunction and prostate cancer. Their increased prevalence with age suggests that the decrease of testosterone concentration and/or the ratio of testosterone-to-estradiol in serum may have a role in their development. The main objective of this study was to explore prostatic inflammation and its relationship with voiding dysfunction and prostate carcinogenesis by developing an experimental model. A novel selective estrogen receptor modulator (SERM), fispemifene, was tested for the prevention and treatment of prostatic inflammation in this model. Combined treatment of adult Noble rats with testosterone and estradiol for 3 to 6 weeks induced gradually developing prostatic inflammation in the dorsolateral prostatic lobes. Inflammatory cells, mainly T-lymphocytes, were first seen around capillaries. Thereafter, the lymphocytes migrated into the stroma and into periglandular space. When the treatment time was extended to 13 weeks, the number of inflamed acini increased. Urodynamical recordings indicated voiding dysfunction. When the animals had an above normal testosterone and estradiol concentrations but still had a decreased testosterone-to-estradiol ratio in serum, they developed obstructive voiding. Furthermore, they developed precancerous lesions and prostate cancers in the ducts of the dorsolateral prostatic lobes. Interestingly, inflammatory infiltrates were observed adjacent to precancerous lesions but not in the adjacency of adenocarcinomas suggesting that inflammation has a role in the early stages of prostate carcinogenesis. Fispemifene, a novel SERM tested in this experimental model, showed anti-inflammatory action by attenuating the number of inflamed acini in the dorsolateral prostate. Fispemifene exhibited also antiestrogenic properties by decreasing expression of estrogen-induced biomarkers in the acinar epithelium. These findings suggest that SERMs could be considered as a new therapeutic possibility in the prevention and in the treatment of chronic prostatic inflammation

Degradação de poluentes emergentes por processos Fenton e foto-Fenton

A continuous photochemical treatment system was developed for aiming the treatment of aqueous solutions containing relevant micro-pollutants (microcystin-LR, sulfamethoxazole and 17-b estradiol). The continuous photo-Fenton process provided high degradation efficiency. However, contact time between samples and the irradiated region is short relative to total treatment time, indicating that observed changes are predominantly due to the Fenton process. Higher degradation efficiency was observed in systems operated using two treatment cycles, the first involving a batch Fenton process and the second a continuous photo-Fenton treatment.

Ionic liquid mediated biomass deconstruction: from analysis challenges to fermentable sugars

Ionic liquids, ILs, have recently been studied with accelerating interest to be used for a deconstruction/fractionation, dissolution or pretreatment processing method of lignocellulosic biomass. ILs are usually utilized combined with heat. Regarding lignocellulosic recalcitrance toward fractionation and IL utilization, most of the studies concern IL utilization in the biomass fermentation process prior to the enzymatic hydrolysis step. It has been demonstrated that IL-pretreatment gives more efficient hydrolysis of the biomass polysaccharides than enzymatic hydrolysis alone. Both cellulose (especially cellulose) and lignin are very resistant towards fractionation and even dissolution methods. As an example, it can be mentioned that softwood, hardwood and grass-type plant species have different types of lignin structures leading to the fact that softwood lignin (guaiacyl lignin dominates) is the most difficult to solubilize or chemically disrupt. In addition to the known conventional biomass processing methods, several ILs have also been found to efficiently dissolve either cellulose and/or wood samples – different ILs are suitable for different purposes. An IL treatment of wood usually results in non-fibrous pulp, where lignin is not efficiently separated and wood components are selectively precipitated, as cellulose is not soluble or degradable in ionic liquids under mild conditions. Nevertheless, new ILs capable of rather good fractionation performance have recently emerged. The capability of the IL to dissolve or deconstruct wood or cellulose depends on several factors, (e.g. sample origin, the particle size of the biomass, mechanical treatments as pulverization, initial biomassto-IL ratio, water content of the biomass, possible impurities of IL, reaction conditions, temperature etc). The aim of this study was to obtain (fermentable) saccharides and other valuable chemicals from wood by a combined heat and IL-treatment. Thermal treatments alone contribute to the degradation of polysaccharides (e.g. 150 °C alone is said to cause the degradation of polysaccharides), thus temperatures below that should be used, if the research interest lies on the IL effectiveness. On the other hand, the efficiency of the IL-treatment can also be enhanced to combine other treatment methods, (e.g. microwave heating). The samples of spruce, pine and birch sawdust were treated with either 1-Ethyl-3-methylimidazolium chloride, Emim Cl, or 1-Ethyl-3-methylimidazolium acetate, Emim Ac, (or with ionized water for comparison) at various temperatures (where focus was between 80 and 120 °C). The samples were withdrawn at fixed time intervals (the main interest treatment time area lied between 0 and 100 hours). Double experiments were executed. The selected mono- and disaccharides, as well as their known degradation products, 5-hydroxymethylfurfural, 5-HMF, and furfural were analyzed with capillary electrophoresis, CE, and high-performance liquid chromatography, HPLC. Initially, even GC and GC-MS were utilized. Galactose, glucose, mannose and xylose were the main monosaccharides that were present in the wood samples exposed to ILs at elevated temperatures; in addition, furfural and 5-HMF were detected; moreover, the quantitative amount of the two latter ones were naturally increasing in line with the heating time or the IL:wood ratio.

Photocatalysis Studies under Visible Light Irradiation with TiO2 Obtained by Pulsed Electric Field Assisted Sol-Gel Method

The objective of this thesis was to study the effect of pulsed electric field on the preparation of TiO2 nanoparticles via sol-gel method under the visible light irradiation. The literature part introduces properties of different TiO2 crystal forms and principle of photocatalysis. It was expected that pulsed electric field would have an influence on degradation for oxalic acid and formic acid. TiO2 samples were prepared by using three frequencies (50Hz, 294Hz, and 963Hz) and two treatment times (12 minutes and 24 minutes) of pulsed electric field. The photocatalytic activities of TiO2 samples produced with sol-gel method were also compared with the TiO2 particles made by previous study and with the commercial TiO2 powder Aeroxide® (Evonic Degussa GmbH) at the same condition. Results show that pulsed electric field does have an effect on degradation for oxalic acid and formic acid. Generally, higher photocatalytic activities for oxalic acid and formic acid were obtained with lower frequency and longer treatment time of pulsed electric field.

Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

We showed that guaraná (Paullinia cupana Mart var. sorbilis) had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5) cells/animal) were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage) and the animals were treated with guaraná daily up to 14 days until euthanasia (total treatment time: 21 days). Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guaraná-treated (GUA) animals presented a 68.6% reduction in tumor burden area compared to control (CO) animals which were not treated with guaraná (CO: 0.84 ± 0.26, N = 6; GUA: 0.27 ± 0.24, N = 6; P = 0.0043), a 57.9% reduction in tumor proliferation index (CO: 23.75 ± 20.54, N = 6; GUA: 9.99 ± 3.93, N = 6; P = 0.026) and a 4.85-fold increase in apoptotic index (CO: 66.95 ± 22.95, N = 6; GUA: 324.37 ± 266.74 AB/mm², N = 6; P = 0.0152). In this mouse model, guaraná treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guaraná in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

Effect of osmotic predehydration on drying characteristics of banana fruits

Osmotic dehydration is considered to be a suitable preprocessing step to reduce the water content of foods. Such products can be dried further by conventional drying processes to lower their water activity and thus extend their shelf life. In this work, banana (Musa sapientum) fruits were initially treated by osmosis by varying several parameters of the processing conditions which included, besides the cutting format (longitudinal and round slices) of the fruit, temperature (28 and 49 ºC), syrup concentration (50, 60 and 67 ºBrix), treatment time (2, 4, 6, 10, 14, 16 and 18 hours), fruit and syrup ratio (1:1, 1:2, 1:3 and 1:4) and agitation effects. The best quality products were obtained by the use of the 67 ºBrix syrup, for 60 minutes of osmotic treatment, at 28 ºC, having a fruit and syrup ratio of 1:1 and agitation. The experimental data obtained on reduction in moisture content during the osmotic treatment were correlated with the experimental equation of M/Mo = Ae(-Kt), where A and K are the constants which represent the geometry and effective diffusivity of the drying process. This simplified mathematical model correlated well with the experimental results.

Cytotoxicity and mutagenicity of cola and grape flavored soft drinks in bone marrow cells of rodents

Due to the large consumption of soft drinks in Brazil and worldwide in recent years and considering that some of the components present in their composition pose potential risks to human health, the aim of this study was to evaluate the cytotoxic and mutagenic potential of specific cola and grape-flavored soft drink brands. Bone marrow cells of Wistar rats were initially treated by gavage with one single dose of Cola or Grape soft drink, which was next offered ad libitum (instead of water) for 24 hours. A negative control treatment was performed by administering one single dose of water and a positive control administering cyclophosphamide intraperitoneally. Statistical analysis showed that the Cola and Grape soft drinks studied were not cytotoxic. However, the Cola soft drink proved mutagenic in this experiment treatment time. Therefore, this study serves as a warning about the consumption of Cola-flavored soft drink and for the need for further subchronic and chronic studies on soft drinks in order to evaluate the long term mutagenic and cytotoxic effects of these substances.

Investigation of femtosecond laser technology for the fabrication of drug nanocrystals in suspension

La technique du laser femtoseconde (fs) a été précédemment utilisée pour la production de nanoparticules d'or dans un environnement aqueux biologiquement compatible. Au cours de ce travail de maîtrise, cette méthode a été investiguée en vue d'une application pour la fabrication de nanocristaux de médicament en utilisant le paclitaxel comme modèle. Deux procédés distincts de cette technologie à savoir l'ablation et la fragmentation ont été étudiés. L'influence de la puissance du laser, de point de focalisation, et de la durée du traitement sur la distribution de taille des particules obtenues ainsi que leur intégrité chimique a été évaluée. Les paramètres ont ainsi été optimisés pour la fabrication des nanoparticules. L’évaluation morphologique et chimique a été réalisée par microscopie électronique et spectroscopie infrarouge respectivement. L'état cristallin des nanoparticules de paclitaxel a été caractérisé par calorimétrie differentielle et diffraction des rayons X. L'optimisation du procédé de production de nanoparticules par laser fs a permis d'obtenir des nanocristaux de taille moyenne (400 nm, polydispersité ≤ 0,3). Cependant une dégradation non négligeable a été observée. La cristallinité du médicament a été maintenue durant la procédure de réduction de taille, mais le paclitaxel anhydre a été transformé en une forme hydratée. Les résultats de cette étude suggèrent que le laser fs peut générer des nanocristaux de principe actif. Cependant cette technique peut se révéler problématique pour des médicaments sensibles à la dégradation. Grâce à sa facilité d'utilisation et la possibilité de travailler avec des quantités restreintes de produit, le laser fs pourrait représenter une alternative valable pour la production de nanoparticules de médicaments peu solubles lors des phases initiales de développement préclinique. Mots-clés: paclitaxel, nanocristaux, laser femtoseconde, ablation, fragmentation

Influence d’un rince-bouche fluoré sur la corrosion galvanique entre un fil NiTi ou un fil CuNiTi et différents boîtiers orthodontiques : incidence sur les propriétés mécaniques des fils

Objectif : il a été rapporté que l’utilisation d’agents prophylactiques fluorés pouvait favoriser la corrosion galvanique au sein des alliages de titane. L’objectif de la présente étude était d’évaluer l’effet d’un rince-bouche fluoré sur les propriétés mécaniques de fils en nickel-titane (NiTi) et de fils en cuivre-nickel-titane (CuNiTi) lorsque ces derniers sont couplés à des boîtiers de compositions différentes (boîtiers de marques Smartclip, Clarity, et Sprint). Matériels et Méthodes : 90 segments de fils en NiTi et 90 segments de fils en CuNiTi ont été chacun couplés à 2 boîtiers de chaque marque. Chaque assemblage fil-boîtiers a été par la suite incubé pendant 3 heures à 37°C, soit dans une solution de fluore neutre (Fluorinse™ 0,05% NaF), soit dans une solution de salive artificielle (solution contrôle). Suite à l’incubation, les échantillons étaient nettoyés avec de l’eau déshydrogénée, les fils séparés des boîtiers et montés sur un support pour subir un test de pliage en trois points en milieu humide (salive artificielle) à 37°C. Les modules d’élasticité ainsi que les limites conventionnelles d’élasticité en activation et en désactivation ont été mesurés et comparés. Des analyses de Variance (ANOVA) et des comparaisons post-hoc avec la correction de Bonferronni ont été utilisées pour comparer les groupes entre eux (α = 0,05). Résultats : L’utilisation d’un rince-bouche fluoré a produit une réduction du module d’élasticité et de la limite conventionnelle d’élasticité en activation et en désactivation pour les fils en NiTi ; cependant, cet effet a été modulé par le type de boîtier auquel le fil a été couplé. Les propriétés mécaniques de fils en CuNiTi n’ont pas été affectées par le fluor, ou par le type de boîtier utilisé. Conclusions : L’utilisation d’un rince-bouche fluoré modifie les propriétés mécaniques des fils en NiTi seulement. Cet effet est modulé par le boîtier auquel le fil en NiTi est couplé. A la différence des autres études publiées dans la littérature, nos résultats ne nous permettent pas de conclure que la modification des propriétés mécaniques des fils en NiTi entrainerait obligatoirement un allongement de la durée du traitement orthodontique. Mots clés : Fluor, fils nickel-titane, boîtiers orthodontiques, corrosion galvanique, propriétés mécaniques.

Radiothérapie asservie à la respiration en combinaison avec l'utilisation d'un faisceau sans filtre égalisateur

La radiothérapie stéréotaxique corporelle (SBRT) est une technique couramment employée pour le traitement de tumeurs aux poumons lorsque la chirurgie n’est pas possible ou refusée par le patient. Une complication de l’utilisation de cette méthode provient du mouvement de la tumeur causé par la respiration. Dans ce contexte, la radiothérapie asservie à la respiration (RGRT) peut être bénéfique. Toutefois, la RGRT augmente le temps de traitement en raison de la plus petite proportion de temps pour laquelle le faisceau est actif. En utilisant un faisceau de photons sans filtre égalisateur (FFF), ce problème peut être compensé par le débit de dose plus élevé d’un faisceau FFF. Ce mémoire traite de la faisabilité d’employer la technique de RGRT en combinaison avec l’utilisation un faisceau FFF sur un accélérateur Synergy S (Elekta, Stockholm, Suède) avec une ceinture pneumatique, le Bellows Belt (Philips, Amsterdam, Pays-Bas), comme dispositif de suivi du signal respiratoire. Un Synergy S a été modifié afin de pouvoir livrer un faisceau 6 MV FFF. Des mesures de profils de dose et de rendements en profondeur ont été acquises en cuve à eau pour différentes tailles de champs. Ces mesures ont été utilisées pour créer un modèle du faisceau 6 MV FFF dans le système de planification de traitement Pinnacle3 de Philips. Les mesures ont été comparées au modèle à l’aide de l’analyse gamma avec un critère de 2%, 2 mm. Par la suite, cinq plans SBRT avec thérapie en arc par modulation volumétrique (VMAT) ont été créés avec le modèle 6 MV du Synergy S, avec et sans filtre. Une comparaison des paramètres dosimétriques a été réalisée entre les plans avec et sans filtre pour évaluer la qualité des plans FFF. Les résultats révèlent qu’il est possible de créer des plans SBRT VMAT avec le faisceau 6 MV FFF du Synergy S qui sont cliniquement acceptables (les crières du Radiation Therapy Oncology Group 0618 sont respectés). Aussi, une interface physique de RGRT a été mise au point pour remplir deux fonctions : lire le signal numérique de la ceinture pneumatique Bellows Belt et envoyer une commande d’irradiation binaire au linac. L’activation/désactivation du faisceau du linac se fait par l’entremise d’un relais électromécanique. L’interface comprend un circuit électronique imprimé fait maison qui fonctionne en tandem avec un Raspberry Pi. Un logiciel de RGRT a été développé pour opérer sur le Raspberry Pi. Celui-ci affiche le signal numérique du Bellows Belt et donne l’option de choisir les limites supérieure et inférieure de la fenêtre d’irradiation, de sorte que lorsque le signal de la ceinture se trouve entre ces limites, le faisceau est actif, et inversement lorsque le signal est hors de ces limites. Le logiciel envoie donc une commande d’irradiation au linac de manière automatique en fonction de l’amplitude du signal respiratoire. Finalement, la comparaison entre la livraison d’un traitement standard sans RGRT avec filtre par rapport à un autre plan standard sans RGRT sans filtre démontre que le temps de traitement en mode FFF est réduit en moyenne de 54.1% pour un arc. De la même manière, la comparaison entre la livraison d’un traitement standard sans RGRT avec filtre par rapport à un plan de RGRT (fenêtre d’irradiation de 75%) sans filtre montre que le temps de traitement de RGRT en mode FFF est réduit en moyenne de 27.3% par arc. Toutefois, il n’a pas été possible de livrer des traitements de RGRT avec une fenêtre de moins de 75%. Le linac ne supporte pas une fréquence d’arrêts élevée.

Characterisation of blends based on hydroxyethylcellulose and maleic acid-alt-methyl vinyl ether

Hydrophilic polymeric films based on blends of hydroxyethylcellulose and maleic acid-co-methyl vinyl ether were produced by casting from aqueous solutions. The physicochemical properties of the blends have been assessed using Fourier transform infrared spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, dielectric spectroscopy, etc. The pristine films exhibit complete miscibility due to the formation of intermacromolecular hydrogen bonding. The thermal treatment of the blend films leads to cross-linking via intermacromolecular esterification and anhydride formation. The cross-linked materials are able to swell in water and their swelling degree can be easily controlled by temperature and thermal treatment time. The formation of the crosslinks is apparent in the dynamic properties of the blends as observed through the mechanical relaxation and dielectric relaxation spectra. The dielectric characteristics of the material are influenced by the effects of change in the local structure of the blend on the ionic conduction processes and the rate of dipolar relaxation. Separation of these processes is attempted using the dielectric modulus method. Significant deviations from a simple additive rule of mixing on the activation energy are observed consistent with hydrogen bonding and crosslinking of the matrix. This paper indicates a method for the creation of films with good mechanical and physical characteristics by exposing the blends to a relatively mild thermal treatment.

Optimization in multi-implant placement for immediate loading in edentulous arches using a modified surgical template and prototyping: A case report

Immediate loading of dental implants shortens the treatment time and makes it possible to give the patient an esthetic appearance throughout the treatment period. Placement of dental implants requires precise planning that accounts for anatomic limitations and restorative goals. Diagnosis can be made with the assistance of computerized tomographic scanning, but transfer of planning to the surgical field is limited. Recently, novel CAD/CAM techniques such as stereolithographic rapid prototyping have been developed to build surgical guides in an attempt to improve precision of implant placement. The aim of this case report was to show a modified surgical template used throughout implant placement as an alternative to a conventional surgical guide.

Factorial design to optimize microwave-assisted synthesis of FDU-1 silica with a new triblock copolymer

The synthesis of FDU-1 silica with large cage-like mesopores prepared with a new triblock copolymer Vorasurf 504 (R) (Eo)(38)(BO)(46)(EO)(38) was developed. The hydrothermal treatment temperature, the dissolution of the copolymer in ethanol, the HCl concentration, the solution stirring time and the hydrothermal treatment time in a microwave oven were evaluated with factorial design procedures. The dissolution in ethanol is important to produce a material with better porous morphology. Increases in the hydrothermal temperature (100 degrees C) and HCl concentration (2 M) improved structural, textural and chemical properties of the cubic ordered mesoporous silica. Also, longer times induced better physical and chemical property characteristics. (C) 2010 Elsevier Inc. All rights reserved.

Synthesis and structure of cage-like mesoporous silica using different precursors

In this work the synthesis of cubic, FDU-1 type, ordered mesoporous silica (OMS) was developed from two types of silicon source, tetraethyl orthosilicate (TEOS) and a less expensive compound, sodium silicate (Na(2)Si(3)O(7)), in the presence of a new triblock copolymer template Vorasurf 504 (EO(38)BO(46)EO(38)). For both silicon precursors the synthesis temperature was evaluated. For TEOS the effect of polymer dissolution in methanol and the acid solution (HCl and HBr) on the material structure was analyzed. For Na(2)Si(3)O(7) the influence of the polymer mass and the hydrothermal treatment time were the explored experimental parameters. The samples were examined by Small Angle X-ray Scattering (SAXS) and Nitrogen Sorption. For both precursors the decrease on the synthesis temperature from ambient, -25 degrees C, to -15 degrees C improved the ordered porous structure. For TEOS, the SAXS results showed that there is an optimum amount of hydrophobic methanol that contributed to dissolve the polymer but did not provoke structural disorder. The less electronegative Br-ions, when compared to Cl-, induced a more ordered porous structure, higher surface areas and larger lattice parameters. For Na(2)Si(3)O(7) the increase on the hydrothermal treatment time as well as the use of an optimized amount of polymer promoted a better ordered porous structure. (C) 2011 Elsevier B.V. All rights reserved.

Low levels of methylmercury induce DNA damage in rats: protective effects of selenium

In this study we examined the possible antigenotoxic effect of selenium (Se) in rats chronically exposed to low levels of methylmercury (MeHg) and the association between glutathione peroxidase (GSH-Px) activity and DNA lesions (via comet assay) in the same exposed animals. Rats were divided into six groups as follows: (Group I) received water; (Group II) received MeHg (100 mu g/day); (Group III) received Se (2 mg/L drinking water); (Group IV) received Se (6 mg/L drinking water); (Group V) received MeHg (100 mu g/day) and Se (2 mg/L drinking water); (Group VI) received MeHg (100 mu g/day) and Se (6 mg/L drinking water). Total treatment time was 100 days. GSH-Px activity was determined spectrophotometrically and DNA damage was determined by comet assay. Mean GSH-Px activity in groups I, II, III, IV, V and VI were, respectively: 40.19 +/- A 17.21; 23.63 +/- A 6.04; 42.64 +/- A 5.70; 38.50 +/- A 7.15; 34.54 +/- A 6.18 and 41.39 +/- A 11.67 nmolNADPH/min/gHb. DNA damage was represented by a mean score from 0 to 300; the results for groups I, II, III, IV, V and VI were, respectively: 6.87 +/- A 3.27; 124.12 +/- A 13.74; 10.62 +/- A 3.81; 13.25 +/- A 1.76; 86.87 +/- A 11.95 and 76.25 +/- A 7.48. There was a significant inhibition of GSH-Px activity in group II compared with group I (P < 0.05). Groups V and VI did not show a difference in enzyme activity compared with groups III and IV, showing the possible protective action of Se. Comet assay presented a significant difference in DNA migration between group II and group I (P < 0.0001). Groups V and VI showed a significant reduction in MeHg-induced genotoxicity (P < 0.001) when compared with group II. A negative correlation (r = -0.559, P < 0.05) was found between GSH-Px activity and DNA lesion, showing that the greater the DNA damage, the lower the GSH-Px activity. Our findings demonstrated the oxidative and genotoxic properties of MeHg, even at low doses. Moreover, Se co-administration reestablished GSH-Px activity and reduced DNA damage.