Otimização do perfil farmacocinético e farmacodinâmico de fármacos anticancerígenos através da sua veiculação em nanossistemas lipídicos

Dissertação de mestrado em Biofísica e Bionanossistemas

Riqueza em óleo nas sementes, amêndoas e cascas das bagas de mamona

This paper is a joined publication of the Depts. of Genetics and of Technology, of the E. S. A. "Luiz de Queiroz", Universidade de São Paulo, and deals with the variation of the percentage oil content in the whole seeds, the embryos and the seed-coat of 28 varieties of castor-beans (Ricinus communis, L.). Primarily, the authors, as a justification of this paper, make reference to the applications which castor-oil has in industry, medicine, etc. In accordance with the weight of 100 seeds, the varieties of castor-beans were classified into 3 classes : small seeds (100 seeds less than 30 g), medium seeds (100 seeds between 30 g and 60) and large seeds (100 seeds more than 60 g). The percentage of oil in the seed, embryo and seed-coat, the dimensions of the seeds and the weight of 100 seeds are given for every variety in table 1. In order to obtain an estimate of the variability for the methods of determination of the oil percentage, in the 3 differents parts of the seeds and also in the 3 groups of seeds, the coefficient of variability was calculate (table 2). It is showed that the variation in the seed and embryo is low and that in the seed-coat is very high. The analysis of variance, with regard to the difference among the 3 types of seeds (small, medium and large), among the 3 parts of the seed (whole seed, embryo and seed-coat) and residual error, is given in table 3. Only, the oil content of whole seeds among types of seeds was significant at the 5% level. The t test among the correspondent means is not significant for the difference between medium and large seeds is significant between both these types (medium and large) and small seeds. The fiducial limits in relation to the mean of the oil percentage in the 3 differents types of seed, show that there is one variety (n. 1013-2), which has a percentage of oil, in the medium type of seed, significantly at the 5% level (table 4), higher than the general mean. Since the distribution of the percentage of oil in the seedcoat is discontinuous, 5 groups were established (table 5). All the differences between groups are significant (table 6). For practical purposes, when we have to remove the seed coat, one should eliminate those varieties which loose at least 3% of oil by this procedure. There is a significant linear correlation at 5% level between the percentage of oil in the seed and in the embryo, of the smali and medium type of seeds (table 7), and also, when taking the 3 types together (lower part of table 7), one finds that the same is true. Also, the correlation between the percentages of oil in the embryo and in the seed-coat of the 3 types together is significant at 5% level. According to the results obtained in relation to the percentage in 28 varieties studied, it can be recommended, for breeding purposes, to work only with those varieties which belong to the medium and the large types of seeds.

Protection of aouts monkeys after immunization with recombinant antigens of Plasmodium falciparum

The genus Aotus spp. (owl monkey) is one of the WHO recommended experimental models for Plasmodium falciparum blood stage infection, especially relevant for vaccination studies with asexual blood stage antigens of this parasite. For several immunization trials with purified recombinant merozoite/schizont antigens, the susceptible Aouts kenotypes II, III, IV and VI were immunized with Escherichia coli derived fusion proteins containg partial sequences of the proteins MSAI (merozoite surface antigen I), SERP (serine-strech protein) and HRPII (histidine alanine rich protein II) as well as with a group of recombinant antigens obtained by an antiserum raised against a protective 41 kD protein band. The subcutaneous application (3x) of the antigen preparations was carried out in intact animals followed by splenectomy prior to challange, in order to increase the susceptibility of the experimental hosts to the parasite. A partial sequence of HRPII, the combination of three different fusion proteins of the 41 kD group and mixture of two sequences of SERP in the presence of the modified Al(OH)3 adjuvant conferred significant protection against a challange infection with P. falciparum blood stages (2-5 x 10 (elevado a sexta potência) i. RBC). Monkey immunized with the MS2-fusion protein carrying the N-terminal part of the 195 kD precursor of the major merozoite surface antigens induced only marginal protection showing some correlation between antibody titer and degree of parasitaemia. Based on the protective capacity of these recombinant antigens we have expressed two hybrid proteins (MS2/SERP/HRPII and SERP/MSAI/HRPII) in E. coli containing selected partial sequences of SERP, HRPII and MSAI. Antibodies raised against both hybrid proteins in rabbits and Aotus monkeys recognize the corresponding schizont polypeptides. In two independent immunization trials using 13 animals (age 7 months to 3 years) we could show that immunization of Aotus monkeys with either of the two hybrid proteins administered in an oil-based well tolerated formulation protected the animals frm a severe experimental P. falciparum (strain Palo Alto) infection.

Effect of brushwood transposition on the leaf litter arthropod fauna in a cerrado area

The results of ecological restoration techniques can be monitored through biological indicators of soil quality such as the leaf litter arthropod fauna. This study aimed to determine the immediate effect of brushwood transposition transferred from an area of native vegetation to a disturbed area, on the leaf litter arthropod fauna in a degraded cerrado area. The arthropod fauna of four areas was compared: a degraded area with signal grass, two experimental brushwood transposition areas, with and without castor oil plants, and an area of native cerrado. In total, 7,660 individuals belonging to 23 taxa were sampled. Acari and Collembola were the most abundant taxa in all studied areas, followed by Coleoptera, Diptera, Hemiptera, Hymenoptera, and Symphyla. The brushwood transposition area without castor oil plants had the lowest abundance and dominance and the highest diversity of all areas, providing evidence of changes in the soil community. Conversely, the results showed that the presence of castor oil plants hampered early succession, negatively affecting ecological restoration in this area.

The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice.

ABSTRACT: BACKGROUND: Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) of marine origin exert multiple beneficial effects on health. Our previous study in mice showed that reduction of adiposity by LC n-3 PUFA was associated with both, a shift in adipose tissue metabolism and a decrease in tissue cellularity. The aim of this study was to further characterize the effects of LC n-3 PUFA on fat cell proliferation and differentiation in obese mice. METHODS: A model of inducible and reversible lipoatrophy (aP2-Cre-ERT2 PPARgammaL2/L2 mice) was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor gamma in response to i.p. injection of tamoxifen. Before the injection, obesity was induced in male mice by 8-week-feeding a corn oil-based high-fat diet (cHF) and, subsequently, mice were randomly assigned (day 0) to one of the following groups: (i) mice injected by corn-oil-vehicle only, i.e."control" mice, and fed cHF; (ii) mice injected by tamoxifen in corn oil, i.e. "mutant" mice, fed cHF; (iii) control mice fed cHF diet with 15% of dietary lipids replaced by LC n-3 PUFA concentrate (cHF+F); and (iv) mutant mice fed cHF+F. Blood and tissue samples were collected at days 14 and 42. RESULTS: Mutant mice achieved a maximum weight loss within 10 days post-injection, followed by a compensatory body weight gain, which was significantly faster in the cHF as compared with the cHF+F mutant mice. Also in control mice, body weight gain was depressed in response to dietary LC n-3 PUFA. At day 42, body weights in all groups stabilized, with no significant differences in adipocyte size between the groups, although body weight and adiposity was lower in the cHF+F as compared with the cHF mice, with a stronger effect in the mutant than in control mice. Gene expression analysis documented depression of adipocyte maturation during the reconstitution of adipose tissue in the cHF+F mutant mice. CONCLUSION: Dietary LC n-3 PUFA could reduce both hypertrophy and hyperplasia of fat cells in vivo. Results are in agreement with the involvement of fat cell turnover in control of adiposity.

Toimintamalli asuinkiinteistö öljyvahingon hoitamiseksi

Pienkiinteistöjen öljyvahingot ovat viime vuosina lisääntyneet. Tämän työn tarkoituksena on luoda öljyvahingon torjuntaan ja jälkihoitoon osallistuvalle urakoitsijalle toimintamalli asuinkiinteistön öljyvahingon hoitamiseksi. Mallin halutaan erityisesti kuvaavan öljyvahingon hoitoon osallistuvien viranomaisten ja muiden tahojen vastuita ja velvollisuuksia. Työn tavoitteena on myös tunnistaa pienkiinteistöissä tapahtuvat öljyvahinkotyypit sekä niille altistavat riskitekijät. Öljyn päästäminen ympäristöön sekä öljyn käsittely ja varastointi niin, että siitä aiheutuu öljyvahingon vaara, kielletään laissa. Vahinkojen torjumiseksi on annettu määräyksiä muun muassa öljylämmityslaitteistojen turvallisuutta koskien. Asuinkiinteistöjen öljyvahingot liittyvät yleensä öljysäiliön täyttötilanteisiin. Vahinkojen syynä on usein säiliön ja sen varusteiden puutteellisuus tai huono kunto. Asuinrakennusten lämmitykseen käytetään kevyttä polttoöljyä. Maahan joutuessaan polttoöljy imeytyy sora- ja hiekkamaahan nopeasti, jolloin vaarana on öljyn kulkeutuminen pohjaveteen ja vesistöihin. Asuinkiinteistön öljyvahingossa öljyä joutuu usein myös rakenteisiin. Öljyvahingosta tulee ilmoittaa aina hätäkeskukseen. Vastuu öljyvahinkojen torjunnasta kuuluu alueelliselle pelastustoimelle. Torjuntatoimiin osallistuu usein myös urakoitsija. Jos vahinkokohdetta ei torjuntatoimin saada kunnostettua, alueellinen ympäristökeskus voi määrätä puhdistamisesta vastuussa olevan selvittämään pilaantuneen alueen laajuuden ja puhdistamistarpeen sekä toteuttamaan mahdollisen kunnostuksen. Pilaantuneen maaperän kunnostus voidaan toteuttaa massan vaihtona tai paikan päällä maata kaivamatta. Likaantuneiden rakenteiden saneerausta tarvitaan sisäilman hajuhaittojen poistamiseksi. Öljyvahingon kustannukset voivat nousta hyvinkin suuriksi. Ensisijainen vastuu niistä kuuluu vahingonaiheuttajalle.

Epoxidação do óleo de mamona e derivados empregando o sistema catalítico VO(acac)2/TBHP

The alternative system VO(acac)2/TBHP was investigated for the epoxidation reaction of castor oil and its derivatives. Results of 88% of conversion, 73% of epoxidation and 82% of selectivity were obtained for the system containing 20% excess of TBHP and 1% of VO(acac)2 catalyst, during 3 h under toluene reflux. The product was characterized by GC/MS as methyl-cis-9, 10-epoxi, 12-hydroxystearate and quantitative ¹H NMR was used to calculate the data above. Preliminary results indicate that the heterogeneous system VO(acac)2 grafted on K10 clay can also promote epoxidation of castor oil.

Sintesis de poliuretanos a partir de polioles obtenidos a partir del aceite de higuerilla modificado por transesterificación con pentaeritritol

Castor oil was reacted by transesterification with various percentages in mass of pentaerythritol to obtain different esters of pentaerythritol. Alternatively, glycerol was also used instead of pentaerythritol for the same reaction in order to establish comparative reference products. The products of the reactions were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy in order to detect and quantify (in terms of the molecular mass and structural information) the components of the products obtained. Analysis for hydroxyl value, acid value, viscosity and specific gravity were used to complete the characterization of the polyols obtained and also of the original castor oil. The polymer characterization was accomplished by tensile stress-strain tests, Shore A hardness, thermogravimetric analysis and chemical resistance to solvents.

Modificação química de argilas: desafios científicos e tecnológicos para obtenção de novos produtos com maior valor agregado

Chemical modification of clays is possible due to their ion-exchange and adsorption capacities, which allows the adjustment of the physicochemical properties of the surfaces of their layers. This modification makes possible the use of clays to produce a great number of new materials, which range from coarse applications such as oil based drilling fluids to refined applications such as pharmaceutical products. This article intends to expose where there is still space for research and investment aiming at the performance improvement of clay-based materials.

Estudo da fermentação do hidrolisado de batata-doce utilizando diferentes linhagens de Saccharomyces cerevisiae

Ethanol is the most suitable substitute for oil-based fuels. The performance of the fermentation is affected by several factors, therefore the aim of this work was to evaluate the efficiency of the fermentation of a hydrolyzed must of sweet potato using three strains of the Saccharomyces cerevisiae. It was also evaluated the effect of three forms of the processes conduction in the fermentation yield, efficiency and viability of yeast at the end process. Among the parameters evaluated, only the cell viability showed significant difference. The strain PE-2 would be the most suitable for the fermentation of the hydrolysed sweet potato.

Desenvolvimento de tecnologia de pré-polímeros na síntese de poliuretanos empregados em combustíveis sólidos

The aim of this work was to synthesize a polyurethane polymer matrix using polyols as a raw material to obtain a binder such as the hydroxyl terminated polybutadiene (HTPB) pre-polymer in energetic material formulation. The soybean-based polyol was the best starting raw material for producing a binder for solid fuel formulation in rocket motor applications. Characterization of the obtained soybean-based polyurethane binder was carried out by employing FT-IR analysis and thermo analytical techniques that showed similar HTPB binder thermo decomposition behaviors, confirming their potential for use as polymer matrix composites.

Poliuretanos obtenidos a partir de aceite de higuerilla modificado y poli-isocianatos de lisina: síntesis, propiedades mecánicas y térmicas y degradación in vitro

Biodegradable polyurethanes (PUR) were prepared from polyols derived from castor oil by transesterification of pentaerythritol-modified castor oil and lysine polyisocyanates (LDI and LTI). The polyurethanes obtained were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA). The mechanical behavior of the polyurethanes was measured by Shore A hardness and tensile testing (stress-strain curves). The biodegradable nature of the material was determined by contact angle, water absorption tests, and in vitro degradation in PBS solution. This study aims to examine the effect of the structure and functionality of diisocyanate on the mechanical properties and in vitro degradation of the material. The results were compared with homologous materials obtained from isophorone diisocyanate (IPDI) used in previous works. The objective was to evaluate candidate materials that can be potentially used in tissue engineering.

Influence of plasma modification on surface properties and offset printability of coated paper

The properties of the paper surface play a crucial role in ensuring suitable quality and runnability in various converting and finishing operations, such as printing. Plasma surface modification makes it possible to modify the surface chemistry of paper without altering the bulk material properties. This also makes it possible to investigate the role of the surface chemistry alone on printability without influencing the porous structure of the pigment-coated paper. Since the porous structure of a pigment coating controls both ink setting and optical properties, surface chemical changes created by a plasma modification have a potential to decouple these two effects and to permit a better optimization of them both. The aim of this work was to understand the effects of plasma surface modification on paper properties, and how it influences printability in the sheet-fed offset process. The objective was to broaden the fundamental understanding of the role of surface chemistry on offset printing. The effects of changing the hydrophilicity/ hydrophobicity and the surface chemical composition by plasma activation and plasma coatings on the properties of coated paper and on ink-paper interactions as well as on sheet-fed offset print quality were investigated. In addition, the durability of the plasma surface modification was studied. Nowadays, a typical sheet-fed offset press also contains units for surface finishing, for example UVvarnishing. The role of the surface chemistry on the UV-varnish absorption into highly permeable and porous pigment-coated paper was also investigated. With plasma activation it was possible to increase the surface energy and hydrophilicity of paper. Both polar and dispersion interactions were found to increase, although the change was greater in the polar interactions due to induced oxygen molecular groups. The results indicated that plasma activation takes place particularly in high molecular weight components such as the dispersion chemicals used to stabilize the pigment and latex particles. Surface composition, such as pigment and binder type, was found to influence the response to the plasma activation. The general trend was that pilot-scale treatment modified the surface chemistry without altering the physical coating structure, whereas excessive laboratory-scale treatment increased the surface roughness and reduced the surface strength, which led to micro-picking in printing. It was shown that pilot-scale plasma activation in combination with appropriate ink oils makes it possible to adjust the ink-setting rate. The ink-setting rate decreased with linseed-oil-based inks, probably due to increased acid-base interactions between the polar groups in the oil and the plasma-treated paper surface. With mineral-oil-based inks, the ink setting accelerated due to plasma activation. Hydrophobic plasma coatings were able to reduce or even prevent the absorption of dampening water into pigmentcoated paper, even when the dampening water was applied under the influence of nip pressure. A uniform hydrophobic plasma coating with sufficient chemical affinity with ink gave an improved print quality in terms of higher print density and lower print mottle. It was also shown that a fluorocarbon plasma coating reduced the free wetting of the UV-varnish into the highly permeable and porous pigment coating. However, when the UV-varnish was applied under the influence of nip pressure, which leads to forced wetting, the role of the surface chemical composition seems to be much less. A decay in surface energy and wettability occurred during the first weeks of storage after plasma activation, after which it leveled off. However, the oxygen/carbon elemental ratio did not decrease as a function of time, indicating that ageing could be caused by a re-orientation of polar groups or by a contamination of the surface. The plasma coatings appeared to be more stable when the hydrophobicity was higher, probably due to fewer interactions with oxygen and water vapor in the air.

FRUIT MORPHOLOGY AND PRODUCTIVITY OF BABASSU PALMS IN NORTHERN MINAS GERAIS STATE, BRAZIL1

ABSTRACT The objectives of this study were to morphologically characterize fruits of the babassu palm tree (Attalea vitrivir) and to estimate their productivity in the north of Minas Gerais State, Brazil. Twenty mature fruits were collected from 10 plants in three different areas in Januária, Minas Gerais. Eighteen biometric parameters of the fruits were measured, the oil contents of the seeds was determined, the adherence to normal distribution was evaluated, distribution frequencies were evaluated and the effects of individuals and areas on the variables and the correlations between them were analyzed. The production of fruit bunches per plant and the number of fruits per bunch from 10 plants were quantified in three areas and the potential production under both natural harvesting and cultivation conditions were estimated. Significant differences were found among all of the biometric parameters examined between the different individuals and the different areas, which shows wide morphological variability in the fruits. The average oil content was 45.7%, but with significant differences among individuals. The observed variability favors the selection of productive individuals in genetic improvement programs. The potential productivity of endocarps and oil based on a density of 400/plants per hectare would be respectively 6.4 and 1.2 tons/ha, which indicates the possibility of using A. vitrivir for producing charcoal, bio fuels, and for carbon fixation.

Immunogenicity of an inactivated bovine herpesvirus type 5 strain defective in thymidine kinase and glycoprotein E

The immunogenicity of an inactivated, experimental vaccine based on a bovine herpesvirus type 5 strain defective in thymidine kinase and glycoprotein E (BoHV-5 gE/TKΔ) was evaluated in cattle and the results were compared with a vaccine containing the parental BoHV-5 strain (SV507/99). To formulate the vaccines, each virus (wildtype SV507/99 and BoHV-5 gE/TK∆) was multiplied in cell culture and inactivated with binary ethyleneimine (BEI). Each vaccine dose contained approximately of 10(7.5) TCID50 of inactivated virus mixed with an oil-based adjuvant (46:54). Forty calves, 6 to 9-months-old, were allocated into two groups of 20 animals each and vaccinated twice (days 0 and 22pv) by the subcutaneous route with either vaccine. Serum samples collected at day 0 and at different intervals after vaccination were tested for virus neutralizing (VN) antibodies against the parental virus and against heterologous BoHV-5 and BoHV-1 isolates. The VN assays demonstrated seroconversion to the respective homologous viruses in all vaccinated animals after the second vaccine dose (mean titers of 17.5 for the wildtype vaccine; 24.1 for the recombinant virus). All animals remained reagents up to day 116 pv, yet showing a gradual reduction in VN titers. Animals from both vaccine groups reacted in similar VN titers to different BoHV-1 and BoHV-5 isolates, yet the magnitude of serological response of both groups was higher against BoHV-5 field isolates. Calves vaccinated with the recombinant virus did not develop antibodies to gE as verified by negative results in a gE-specific ELISA, what would allow serological differentiation from naturally infected animals. Taken together, these results indicate that inactivated antigens of BoHV-5 gE/TK recombinant virus induced an adequate serological response against BoHV-5 and BoHV-1 and thus can be used as an alternative, differential vaccine candidate.