Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Análise da Expressão de APE1 após Estresse Oxidativo Induzido em Células Proficientes e Deficientes na Via de Reparo por Excisão de Nucleotídeos

Riboflavin is a vitamin very important in aerobic organisms, as a precursor of many coenzymes involved in the electron transporter chain. However, after photosensitization of riboflavin with UV or visible light, it generates reactive oxygen species (ROS), which can oxidize the DNA. The repair of oxidative lesions on DNA occurs through the base excision repair pathway (BER), where APE1 endonuclease plays a central role. On the other hand, the nucleotide excision repair pathway (NER) repairs helix-distorting lesions. Recently, it was described the participation of NERproteins in the repair of oxidative damage and in stimulation of repair function fromAPE1. The aim of this research was to evaluate the cytotoxic effects of photosensitized riboflavin (RF*) in cells proficient and deficient in NER, correlating with APE1 expression. For this propose, the cells were treated with RF* and it was performed the cell viability assay, extraction of whole proteins, cells fractionation, immunoblotting, indirect immunofluorescence and analysis of polymorphisms of BER gens. The results evidenced that cells deficient in XPA and CSB proteins were more sensitive to RF*. However, XPC-deficient cells presented similar resistance to MRC5- SV cells, which is proficient in NER. These results indicate that XPA and CSB proteins have an important role on repair of oxidative lesions induced by RF*. Additionally, it was evidenced that single nucleotide polymorphisms (SNPs) in BER enzymes may influence in sensitivity of NER-deficient cell lines. Concerning the APE1 expression, the results showed that expression of this protein after treatment with RF* only changed in XPC-deficient cells. Though, it was observed that APE1 is recruited and is bound to chromatin in MRC5-SV and XPA cells after treatment with RF*. The results also showed the induction of DNA damage after treatment with RF*, through the analysis of-H2AX, since the treatment promoted an increase of endogenous levels of this phosphorylated protein, which acts signaling double strand-break on DNA. On the other hand, in XPC-deficient cells, regardless of resistance of RF*, the endogenous levels of APE1 are extremely reduced when compared with other cell lines and APE1 is not bound to chromatin after treatment with RF*. These results conclude that RF* was able to induce cell death in NERdeficient cells, where XPA and CSB cells were more sensitive when compared with MRC5-SV and XPC-deficient cells. This last result is potentially very interesting, since XPC-deficient cell line presents low levels of APE1. Additionally, the results evidenced that APE1 protein can be involved in the repair of oxidative damage induced by RF*, because APE1 is recruited and bound strongly to chromatin after treatment.

Avaliação de efeitos de um extrato aquoso de cinnamomum zeylanicum L. na marcação de constituintes sanguíneos com tecnécio-99m e na morfologia das hemácias de ratos wistar

Radiobiocomplexes are used to obtain images in nuclear medicine and employed in basic research. Blood constituents labeled with technetium-99m (99mTc) have also been employed as radiobiocomplexes and used also experimental model for evaluation of the biological effects of natural or synthetic drugs. The analysis of the morphology and the morphometrics parameters (perimeter/área ratio) can be used to evaluate the effects of drugs upon the structure of the membrane of red blood cells. Cinnamomum zeylanicum (cinnamon) is a spice used as herbal medicine to treat diseases. The aim of this study was to evaluate the effect of in vitro and in vivo treatment with an aqueous cinnamon extract on the labeling of blood constituents with 99mTc and on the morphology of red blood cells from Wistar rats. In the in vitro treatment, isolated blood sample from animals were incubated with cinnamon extract. In the in vivo treatment, blood samples were also withdrawn from animals treated with cinnamon extract. In both cases, the radiolabeling of blood constituents was done. The morphological analysis of red blood cells was also done. As control, blood or animals treated with NaCl 0.9%. The data obtained on the labeling of blood constituents with 99mTc experiments indicated that the in vitro treatment with cinnamon extract was capable to decrease signiicantly (p<0.05) the percentage of radioactivity in cellular compartments and on the fixation of cellular and plasma proteins. These effects were not observed on the in vivo treatment. The results obtained for the morphology of red blood cells suggest that the in vitro and in vivo treatments did not alter the morphology and the perimeter/area ratio. The in vitro treatment with aqueous cinnamon extract could affect the membrane structures related with the oxidation status of the stannous ion pertechnetate ion, altering the labeling of blood constituentes with 99mTc. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade do Estado do Rio de Janeiro

Estudo de efeitos de um extrato de Arctium lappa (Bardana) na marcação dos constituintes sangüíneos com Tecnécio-99m, na biodisponibilidade do radiofármaco pertecnatato de sódio e na morfologia de hemácias de ratos Wistar

Radionuclides have been used in Nuclear Medicine for diagnostic and treatment. In basic research, cellular and molecular structures are labeled with technetium-99m (99mTc) and used as radiobiocomplexes. Some natural or synthetic drugs are capable to alter the labeling of blood constituents with 99mTc, as well as in the biodistribution of radiobiocomplexes. Arctium lappa (Bardana) has been used to treat inflammatory processes. The aim of this work was to evaluate the effects of an extract of Bardana on the labeling of blood constituents with 99mTc, on the morphology of red blood cells, on the perimeter/area ratio of red blood cells and on the biodistribution of radiophamaceutical sodium pertechnetate in Wistar rats. Extract of Bardana was capable to alter the labeling of cellular compartment with 99mTc. Plasma and cellular proteins did not present alteration on the percentage of radioactivity (%ATI). Extract of Bardana was also capable to alter the morphology and the perimeter/area ratio of red blood cells. On the biodistribution of sodium pertechnetate in animals treated with the extract of Bardana, it was observed a small and significant uptake in liver, tooth and tongue, and a high and a significant uptake in stomach, lung and testis (p<0.05). In conclusion, these findings could be justified due to the effects of some chemical compounds in the Bardana extract. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade Estadual do Rio de Janeiro

IgA sérica, secretora, IgE total e estado nutricional em crianças com infecções por enteroparasitas

Infections for intestinal parasites are one of the main morbidade causes in humans and, its relationships with socioeconomic levels and hygiene conditions in countries in development are already very established. Many works, even so, they are being accomplished to elucidate the complex interactions among nutrition, these infections and answer imunológica, because it is seen that malnutrition commits the immunity increasing the susceptibilidade for infectious diseases and these for its time can harm the state human nutricional. It is known that sponge helmínticos they stimulate synthesis of IgE so much policlonal as specific for the same ones and that IgA secretora, main imunoglobulina of defense of the mucous ones, can act against protozoa as the Giardia lamblia and against helmintos as Trichuris tichiura and Strongyloides stercorales. Some studies show that the malnutrition energy protéica influences in the production of these answers, but some authors show results divergentes. In this work it was evaluated the levels of total IgE, IgA sérica and secretora, contagem of sanguine eosinófilos, levels of proteins séricas and state nutricional, in 103 children of low socioeconomic level, to discover a correlation between those and infection for enteroparasitas. They participated in the study children of both sexes, with age of 3 to 6 years, visitors of the same creche and residents in a neighborhood with precarious hygiene conditions and basic saneamento, in the city of Christmas. The obtained results showed that the faulty environmental and socioeconomic conditions favored to a high infection frequency for enteroparasitas, mainly Trichuris trichiura and Ascaris lumbricoides between the helmintos and Endolimax sleep and Giárdia lamblia among the protozoa. Light malnutrition without deficit protéico was observed in 30% of the children, which didn't also present significant deficiencies of IgA sérica and secretora. The sponged children

Obtenção de polímeros graftizados de quitosana e estudo das propriedades físico-químicas para aplicação na indústria do petróleo

Chitosan is a biopolymer derived from the shells of crustaceans, biodegradable, inexpensive and renewable with important physical and chemical properties. Moreover, the different modifications possible in its chemical structure generate new properties, making it an attractive polysaccharide owing to its range of potential applications. Polymers have been used in oil production operations. However, growing concern over environmental constraints has prompted oil industry to search for environmentally sustainable materials. As such, this study sought to obtain chitosan derivatives grafted with hydrophilic (poly(ethylene glycol), mPEG) and/or hydrophobic groups (n-dodecyl) via a simple (one-pot) method and evaluate their physicochemical properties as a function of varying pH using rheology, small-angle Xray scattering (SAXS), dynamic light scattering (DLS) and zeta potential. The chitosan derivatives were prepared using reductive alkylation under mild reaction conditions and the chemical structure of the polymers was characterized by nuclear magnetic resonance (1H NMR) and CHN elemental analysis. Considering a constant mPEG/Chitosan molar ratio on modification of chitosan, the solubility of the polymer across a wide pH range (acidic, neutral and basic) could only be improved when some of the amino groups were submitted to reacetylation using the one-pot method. Under these conditions, solubility is maintained even with the simultaneous insertion of n-dodecyl. On the other hand, the solubility of derivatives obtained only through mPEG incorporation using the traditional methodology, or with the ndodecyl group, was similar to that of its precursor. The hydrophilic group promoted decreased viscosity of the polymer solutions at 10 g/L in acid medium. However, at basic pH, both viscosity and thermal stability increased, as well as exhibited a pronounced pseudoplastic behavior, suggesting strong intermolecular associations in the alkaline medium. The SAXS results showed a polyelectrolyte behavior with the decrease in pH for the polymer systems. DLS analyses revealed that although the dilute polymer solutions at 1 g/L and pH 3 exhibited a high density of protonated amino groups along the polymer chain, the high degree of charge contributed significantly to aggregation, promoting increased particle size with the decrease in pH. Furthermore, the hydrophobic group also contributed to increasing the size of aggregates in solution at pH 3, whereas the hydrophilic group helped reduce their size across the entire pH range. Nevertheless, the nature of aggregation was dependent on the pH of the medium. Zeta potential results indicated that its values do not depend solely on the surface charge of the particle, but are also dependent on the net charge of the medium. In this study, water soluble associative polymers exhibit properties that can be of great interest in the petroleum industry

Avaliação das propriedades físico-químicas de sistemas a base de carboximetilcelulose e poli (N-isopropilacrilamida) em soluções aquosas para aplicação na indústria do petróleo

Sustainable development is a major challenge in the oil industry and has aroused growing interest in research to obtain materials from renewable sources. Carboxymethylcellulose (CMC) is a polysaccharide derived from cellulose and becomes attractive because it is water-soluble, renewable, biodegradable and inexpensive, as well as may be chemically modified to gain new properties. Among the derivatives of carboxymethylcellulose, systems have been developed to induce stimuli-responsive properties and extend the applicability of multiple-responsive materials. Although these new materials have been the subject of study, understanding of their physicochemical properties, such as viscosity, solubility and particle size as a function of pH and temperature, is still very limited. This study describes systems of physical blends and copolymers based on carboxymethylcellulose and poly (N-isopropylacrylamide) (PNIPAM), with different feed percentage compositions of the reaction (25CMC, 50CMC e 75CMC), in aqueous solution. The chemical structure of the polymers was investigated by infrared and CHN elementary analysis. The physical blends were analyzed by rheology and the copolymers by UV-visible spectroscopy, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS) and zeta potential. CMC and copolymer were assessed as scale inhibitors of calcium carbonate (CaCO3) using dynamic tube blocking tests and chemical compatibility tests, as well as scanning electron microscopy (SEM). Thermothickening behavior was observed for the 50 % CMC_50 % PNIPAM and 25 % CMC_75 % PNIPAM physical blends in aqueous solution at concentrations of 6 and 2 g/L, respectively, depending on polymer concentration and composition. For the copolymers, the increase in temperature and amount of PNIPAM favored polymer-polymer interactions through hydrophobic groups, resulting in increased turbidity of polymer solutions. Particle size decreased with the rise in copolymer PNIPAM content as a function of pH (3-12), at 25 °C. Larger amounts of CMC result in a stronger effect of pH on particle size, indicating pH-responsive behavior. Thus, 25CMC was not affected by the change in pH, exhibiting similar behavior to PNIPAM. In addition, the presence of acidic or basic additives influenced particle size, which was smaller in the presence of the additives than in distilled water. The results of zeta potential also showed greater variation for polymers in distilled water than in the presence of acids and bases. The lower critical solution temperature (LCST) of PNIPAM determined by DLS corroborated the value obtained by UV-visible spectroscopy. SAXS data for PNIPAM and 50CMC indicated phase transition when the temperature increased from 32 to 34 °C. A reduction in or absence of electrostatic properties was observed as a function of increased PNIPAM in copolymer composition. Assessment of samples as scale inhibitors showed that CMC performed better than the copolymers. This was attributed to the higher charge density present in CMC. The SEM micrographs confirmed morphological changes in the CaCO3 crystals, demonstrating the scale inhibiting potential of these polymers

Geologia, Geocronologia, Geoquímica e Petrogênese das Rochas Ígneas Cretácicas da Província Magmática do Cabo e suas Relações com as Unidades Sedimentares da Bacia de Pernambuco (NE do Brasil)

The area studied forms a thin NNE-directed belt situated south of Recife town (Pernambuco state), northeastern Brazil. Geologically, it comprises the Pernambuco Basin (PB), which is limited by the Pernambuco Lineament to the north, the Maragogi high to the south and the Pernambuco Alagoas massif to the west, all of them with Precambrian age. This thesis reports the results obtained for the Cabo Magmatic Province (CMP), aiming the characterization of the geology, stratigraphy, geochronology, geochemistry and petrogenesis of the Cretaceous igneous rocks presented in the PB. The PB is composed of the Cabo Formation (rift phase) at the base (polymictic conglomerates, sandstones, shales), an intermediate unit, the Estiva Formation (marbles and argillites), and, at the top, the Algodoais Formation (monomictic conglomerates, sandstones, shales). The CMP is represented by trachytes, rhyolites, pyroclastics (ignimbrites), basalts / trachy-andesites, monzonites and alkali-feldspar granite, which occur as dykes, flows, sills, laccoliths and plugs. Field observations and well descriptions show that the majority of the magmatic rocks have intrusive contacts with the Cabo Formation, although some occurrences are also suggestive of synchronism between volcanism and siliciclastic sedimentation. 40Ar/39Ar and zircon fission tracks for the magmatic rocks indicate an average age of 102 r 1 Ma for the CMP. This age represents an expressive event in the province and is detected in all igneous dated materials. It is considered as a minimum age (Albian) for the magmatic episode and the peak of the rift phase in the PB. The 40Ar/39Ar dates are about 10-14 Ma younger than published palynologic ages for this basin. Geochemically, the CMP may be divided in two major groups; i) a transitional to alkaline suite, constituted by basalts to trachy-andesites (types with fine-grained textures and phenocrysts of sanidine and plagioclase), trachytes (porphyrytic texture, with phenocrysts of sanidine and plagioclase) and monzonites; ii) a alkaline suite, highly fractionated, acidic volcano-plutonic association, formed by four subtypes (pyroclastic flows ignimbrites, fine-to medium-grained rhyolites, a high level granite, and later rhyolites). These four types are distinguished essentially by field aspects and petrographic and textural features. Compatible versus incompatible trace element concentrations and geochemical modeling based on both major and trace elements suggest the evolution through low pressure fractional crystallization for trachytes and other acidic rocks, whereas basalts / trachy-andesites and monzonites evolved by partial melting from a mantle source. Sr and Nd isotopes reveal two distinct sources for the rocks of the CMP. Concerning the acidic ones, the high initial Sr ratios (ISr = 0.7064-1.2295) and the negative HNd (-0.43 to -3.67) indicate a crustal source with mesoproterozoic model ages (TDM from 0.92 to 1.04 Ga). On the other hand, the basic to intermediate rocks have low ISr (0.7031-0.7042) and positive HNd (+1.28 to +1.98), which requires the depleted mantle as the most probable source; their model ages are in the range 0.61-0.66 Ga. However, the light rare earth enrichment of these rocks and partial melting modeling point to an incompatible-enriched lherzolitic mantle with very low quantity of garnet (1-3%). This apparent difference between geochemical and Nd isotopes may be resolved by assuming that the metasomatizing agent did not obliterate the original isotopic characteristics of the magmas. A 2 to 5% partial melting of this mantle at approximately 14 kbar and 1269oC account very well the basalts and trachy-andesites studied. By using these pressure and temperatures estimates for the generation of the basaltic to trachy-andesitic magma, it is determined a lithospheric stretching (E) of 2.5. This E value is an appropriated estimate for the sub-crustal stretching (astenospheric or the base of the lithosphere?) region under the Pernambuco Basin, the crustal stretching probably being lower. The integration of all data obtained in this thesis permits to interpret the magmatic evolution of the PB as follows; 1st) the partial melting of a garnet-bearing lherzolite generates incompatible-enriched basaltic, trachy-andesitic and monzonitic magmas; 2nd) the underplating of these basaltic magmas at the base of the continental crust triggers the partial melting of this crust, and thus originating the acidic magmas; 3rd) concomitantly with the previous stage, trachytic magmas were produced by fractionation from a monzonitic to trachy-andesitic liquid; 4th) the emplacement of the several magmas in superficial (e.g. flows) or sub-superficial (e.g. dykes, sills, domes, laccoliths) depths was almost synchronically, at about 102 r 1 Ma, and usually crosscutting the sedimentary rocks of the Cabo Formation. The presence of garnet in the lherzolitic mantle does not agree with pressures of about 14 kbar for the generation of the basaltic magma, as calculated based on chemical parameters. This can be resolved by admitting the astenospheric uplifting under the rift, which would place deep and hot material (mantle plume?) at sub-crustal depths. The generation of the magmas and their subsequent emplacement would be coupled with the crustal rifting of the PB, the border (NNE-SSW directed) and transfer (NW-SE directed) faults serving as conduits for the magma emplacement. Based on the E parameter and the integration of 40Ar/39Ar and palynologic data it is interpreted a maximum duration of 10-14 Ma for the rift phase (Cabo Formation clastic sedimentation and basic to acidic magmatism) of the PB