Avaliação bioquímica e hostológica de fígado de ratas wistar diabéticas e tratadas com tamoxifeno

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this multidisciplinary study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin (H&E), Masson s trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in 2 non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism

Efeito pró-inflamatório de uma lectina purificada da esponja marinha Cliona varians

A galactose and sucrose specific lectin from the marine sponge Cliona varians named CvL was purified by acetone fractionation followed by Sepharose CL 4B affinity chromatography. Models of leukocyte migration in vivo were used to study the inflammatory activity of CvL through of mouse paw oedema and peritonitis. Effect of CvL on peritoneal macrophage activation was analyzed. Effects of corticoids and NSAIDS drugs were also evaluated on peritonitis stimulated by CvL. Results showed that mouse hind-paw oedema induced by sub plantar injections of CvL was dependent dose until 50µg/paw. This CvL dose when administered into mouse peritoneal cavities induced maxima cell migration (9283 cells/µL) at 24 hours after injection. This effect was preferentially inhibited by incubation of CvL with the carbohydrates D-galactose followed by sucrose. Pre-treatment of mice with 3% thioglycolate increases the peritoneal macrophage population 2.3 times, and enhanced the neutrophil migration after 24h CvL injection (75.8%, p<0.001) and no significant effect was observed in presence of fMLP. Finally, Pre-treatment of mice with dexamethason (cytokine antagonist) decreased 65.6%, (p<0.001), with diclofenac (non-selective NSAID) decreased 34.5%, (p<0.001) and Celecoxib (selective NSAID) had no effect on leukocyte migration after submission at peritonitis stimulated by CvL, respectively. Summarizing, data suggest that CvL shows pro-inflammatory activity, inducing neutrophil migration probably by pathway on resident macrophage activation and on chemotaxis mediated by cytokines

Mutagênese induzida por flavonóides presentes do decocto das cascas da aroeira (Schinus terebinthifolius, Raddi)

The decoction of Brazilian pepper tree barks (Schinus terebinthifolius, Raddi), is used in medicine as wound healing and antiinflamatory. Once extracts from this plant are used for acceleration of scar s process, it is important to study their mutagenic and genotoxic potential. In previous works in our laboratory, it was observed mutagenicity caused by the decoction when in high concentrations. Among the chemical compounds of this plant that could be able to induce mutation, the flavonoids were the only group that was referred to have either an oxidant or antioxidant potential. The flavonoids were isolated, purified and quantified by adsorptive column chromatography under silica gel, bacterial and in vitro genotoxic tests were realized to determine if the flavonoids were the responsible agents for this mutagenicity found. The tests realized with plasmidial DNA were indicative that the flavonoids are probably genotoxic, due to the presence of correlation between increase of the flavonoid concentration and in plasmidial DNA double strand breakage visualized in agarose gel, as well as they were capable to generated abasic sites shown by the in vitro treatment with exonuclease III. The same tests with plasmidial DNA in the presence of copper [10 µM] and of a Tris-HCl pH 7.5 [10 µM] buffer were realized with the isolated flavonoids to determine if there would be or not participation of reactive oxygen species (ROS). The transformation of plasmidial DNA in different bacterial strains proficient and deficient in DNA repair enzymes in the presence or not of a Tris-HCl buffer, suggests that the enzymes that repair oxidative lesions are necessary to repair the lesions generated by the flavonoids and that ROS are generated and are necessary to promote the lesions. Bacterial tests with Escherichia coli strains of the CC collection (deficient or not for DNA repair enzymes), showed that the flavonoids are able to increase the frequency of mutations, mainly in strains mutated in repair enzymes (MutM, MutY-glicosylases and double mutant), suggesting that these agents are responsible for the enhancement in the mutation rate. In order to determine the mutation spectrum caused by the flavonoids of the Brazilian pepper tree stem bark, plasmidial DNA previously treated with the flavonoids were transformed in bacterial strains deficient and proficient in the DNA repair enzymes, followed by a blue-white selection with X-gal, DNA amplification by PCR and sequencing the positive mutant clones. Analysis of the mutants obtained from strains CC104, CC104mutM, CC104mutY, CC104mutMmutY, BW9101, BW9109 indicated a predominance of some mutations like G:C to C:G that can be correlated with the origin of 8-oxoG, due to oxidative lesions caused by the flavonoids. So it can concluded that the flavonoid isolated or in fractions enriched on them are genotoxic and mutagenic, and their mutations are predominantly oxidative, mediated by ROS, and the lesions are recognized by the BER system. In this way it is proposed that the flavonoids can act in two different ways to generate the DNA lesion: 1. in a Fenton-like reaction, when the flavonoid are in the presence of metal ions and that together with the water generate ROS that promotes the DNA lesions; 2. in another way the lesions can be generated by the formation of ROS due to the internal chemical structure of the flavonoid molecule due to the quantity and location of hydroxyl groups, and so producing the DNA lesions, those lesions can be directly (suggested by the in vitro experiments) or indirectly done (supported by the experiments using the CC bacterial strains)

Relação entre estresse oxidativo e oesteopenia diabética em ratas pré-menopausadas

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship between lipid peroxidation index, antioxidant defense parameter and bone metabolism in a premenopausal diabetic model by measurements such as thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes mellitus was induced by alloxan and confirmed by glycemia 250 mg/dL. The experimental period understood 1 and 5 after days induction and 45, 75 and 120 days after the installation of diabetes mellitus.The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to animals control. However, the antioxidant parameter, measured by GSH content, was significantly decrease (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significant decrease (p<0.05) in diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats

IL-10 na patogênese da infecção por Leishmania infantum

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1

Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM

Iniqüidade em saúde: uma extensão das desigualdades sociais no sistema público de saúde do Brasil (2003-2006)

This issue analises the unevenness in the brazilian system of public health care as an extension of socials inequities. It is a theoretical study based in a historical method, using empirical camp from academic, corporation and institution researchs, along the period 2002-2006. Equality and effectiveness in health systems are analitical basic cathegories grap in the root of the doctrine, principles and organization of the Unique Health System, in which sectorial actions are inserted. Discuss the estructural prodution and determined those inequalities through some social determiners of health system: income, land, food securitiy, nutritional situation, basic sanitation, epidemiological inequities and public management policy. Carry out a thematic review over health social production, it formlation and the goals of social policies, as well as the insertion of the equality principle in the assistance system, in the frame of the running public health regulations. It uses reflections that enlighted the correlation between the process of political-institutional actions and equity on health assistance. Analized the pertinency of sectorial reorganizational strategies on basic attendance, confronting the hipothesis that those strategies reinforce social inequities in health system, because it organize diferential assistance levels over not equal baselines. The results show up that social inequalities, even remaining, have had a small decrease; that the selectiviness of actual public policies and the duplication of the health system, increases the differences within and between the social classes and configures the assistance as inequal. The basic care system has great shortages that also appeares in middle and complex assistance levels. As conclusion, it remarks that the health assintance system, even with it integrality has limits; structural problems on material conditions of living and health system could not be reversed only with institutional legal arragements; by the contrary, in border conditions, these strategies produce policies that reinforce inequities, neglecting the equity principle of the system in which frame, they work. One patina of this tim

Normas tributárias indutoras na concretização do princípio constitucional da redução das desigualdades sociais e regionais

The Federal Constitution states that the reduction of social and regional inequalities is one of the goals to be achieved by the Brasilian State. The economic constitution states that the national economy must be developed so as to achieve, amongst other objectives, the reduction of those inequalities. In this paper, we aim to demonstrate the duty, imposed by the Constitution to the State, of acting in the national economy so as to promote the achievement of the constitutional goals, among wich we highlight the reduction of inequalities. One of the instruments that can be used by the State to achieve this objective is its fiscal policy. It is also an aim in this paper to demonstrate that inducing tax norms can be used by the State, because it can encourage the economic agents to bring about the reduction of social and regional inequalities. Therefore, after bibliographic and jurisprudential research, we conclude that the duty, imposed to the State, of acting in the national economy so as to promote the achievement of the constitutional goals exists. We also conclude that this acting must be planed and constant, because the consequences are slow and that, within the limits of the constitution, the inducing tax norms can be an instrument for the State in order to reduct the social and regional inequalities

O princípio constitucional da redução das desigualdades regionais e o transporte de gás natural

In a country of continental dimensions as Brazil, one of the top challenges to its economic growth is the logistic related to energetical demand supply. We live now in the era of environmental protection and, in this new context of priorizations, it passes trough the search for alternative energies for the energetic matrix, due the petroleum elevated costs in the global market (and its finitude), but also due its pollution over the environment. This attempt of substitution needs solutions related to the national reality, into a national long term developing plan and based at a juridical-economic analysis of its realization. This study will look for, also based in an economical analysis, the juridical legitimity of choosing natural gas as the new protagonist of national economic growth (as a substitute of petroleum) and the necessary boost that must be done by law, based on an economic policy focused strictly for that fact, as a modifying agent of this reality. This study, therefore, will always be turned to a constitutional aspect, respecting the principles of economic order and the goal of reducing regional inequalities, which must influence the making off of a developing plan. At the end, it will try to demonstrate the juridical viability of such undertaking, tuned in jus-economical criteria. Another goal is related to the analysis of the natural gas industry, due the regulation of its transport has a major importance for national energetic integration, not only because this activity be characterized as a net industry, still under control of a natural monopoly, but also because the competitive or cooperative profile that should be priorized at the beginning of the economic planning for this activity (such as investment policies and its own rules that will submit private agents)

As zonas de processamento de exportação como instrumento de desenvolvimento e redução das desigualdades regionais

The existence of inequalities among the Brazilian regions is an indeed fact along the country s history. Before this reality the constitutional legislator inserted into the Federal Constitution of 1988, as a purpose of the Federative Republic of Brazil, the reduction of regional inequalities. The development has also been included as a purpose from the State, because there is an straight relation with the reduction of regional inequalities. In both situations is searched the improvement of people s living conditions. . In pursuit of this achievement, the State must implement public policy, and, for this to happen, it needs the ingress of income inside of the public coffers and support of economic agents, therefore the importance of constitucionalization of the economic policy. The 1988 s Constitution adopted a rational capitalism regime consentaneous with current legal and social conceptions, that s why it enabled the State s intervention into economy to correct the so-called market failures or to make the established objectives fulfilled. About this last one, the intervention may happen by induction through the adoption of regulatory Standards of incentive or disincentive of economic activity. Among the possible inductive ways there are the tax assessments that aim to stimulate the economic agents behavior in view of finding that the development doesn t occur with the same intensity in all of the country s regions. Inside this context there are the Export Processing Zones (EPZs) which are special areas with different customs regime by the granting of benefits to the companies that are installed there. The EPZs have been used, by several countries, in order to develop certain regions, and economic indicators show that they promoted economic and social changes in the places where they are installed, especially because, by attracting companies, they provide job creation, industrialization and increased exports. In Brazil, they can contribute decisively to overcome major obstacles or decrease the attraction of economic agents and economic development of the country. In the case of an instrument known to be effective to achieve the goals established by the Constitution, it is duty of the Executive to push for the law that governs this customs regime is effectively applied. If the Executive doesn t fulfill this duty, incurs into unjustifiable omission, correction likely by the Judiciary, whose mission is to prevent acts or omissions contrary to constitutional order

Contribuição ao estudo da isonomia na tributação sob a perspectiva da ordem econômica

The study aims to investigate the limits of state intervention via induction on Economic Order, especially in cases regarding tax equality, through the analysis of their effects on economic development and on free competition from the perspective of economic efficiency and the Constitution. Thus, the work seeks to demonstrate that the achievement of equality in taxation is important in that it strengthens the economic relations in terms of efficiency, protects competition and fosters economic development to reduce regional and social inequalities and other constitutional desiderata. A dissertation is characterized by interdisciplinarity and was divided into two parts. The first is to discuss the legal meaning of equality from the doctrinal analysis of the principle and the relationship between equality and justice in the economic sense without rejecting its philosophical content. It is noteworthy that hermeneutics and the philosophy of language are useful tools for achieving equality in presenting the pragmatic methodologies applicable to the subject in terms of corrective justice. Based on these general assumptions, is going to study the tax equality and their characteristics, the corollary of the ability to pay and its relation to the economic capacity and the issue of progressivity in taxation as an ideal of distributive justice. The second part concerns the legal foundations of Economic Order and its relation to extrafiscality as a means of economic regulation in order to investigate the efficiency of this induction in order to promote economic development, free competition and tax equality itself to reduce inequalities and distributing wealth. Within this context, we investigated the scope of the constitutional principles of economic order, free enterprise and free competition, and favored differential treatment for small and medium enterprises, the issue of regional development for the reduction of regional and social inequalities, the problem the "fiscal war" and finally the efficiency from the perspective of Economic Analysis of Law

Trajetória de mulheres e a participação masculina no processo de aborto provocado

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Avaliação de robustez, desempenho e aplicação do controlador adaptativo por posicionamento de pólos e estrutura variável

In this work, the variable structure adaptive pole placement controller (VS-APPC) robustness and performance are evaluated and this algorithm is applied in a motor control system. The controller robustness evaluation will be done through simulations, where will be introduced in the system the following adversities: time delay, actuator response boundeds, disturbances, parametric variation and unmodeled dynamics. The VS-APPC will be compared with PI control, pole placement control (PPC) and adaptive pole placement controller (APPC). The VS-APPC will be simulated to track a step and a sine reference. It will be applied in a three-phase induction motor control system to track a sine signal in the stator reference frame. Simulation and experimental results will prove the efficiency and robustness of this control strategy

Dinâmica da Plasticidade Sináptica em neurônios do hipocampo durante ciclos de sono: um estudo computacional

Several research lines show that sleep favors memory consolidation and learning. It has been proposed that the cognitive role of sleep is derived from a global scaling of synaptic weights, able to homeostatically restore the ability to learn new things, erasing memories overnight. This phenomenon is typical of slow-wave sleep (SWS) and characterized by non-Hebbian mechanisms, i.e., mechanisms independent of synchronous neuronal activity. Another view holds that sleep also triggers the specific enhancement of synaptic connections, carrying out the embossing of certain mnemonic traces within a lattice of synaptic weights rescaled each night. Such an embossing is understood as the combination of Hebbian and non-Hebbian mechanisms, capable of increasing and decreasing respectively the synaptic weights in complementary circuits, leading to selective memory improvement and a restructuring of synaptic configuration (SC) that can be crucial for the generation of new behaviors ( insights ). The empirical findings indicate that initiation of Hebbian plasticity during sleep occurs in the transition of the SWS to the stage of rapid eye movement (REM), possibly due to the significant differences between the firing rates regimes of the stages and the up-regulation of factors involved in longterm synaptic plasticity. In this study the theories of homeostasis and embossing were compared using an artificial neural network (ANN) fed with action potentials recorded in the hippocampus of rats during the sleep-wake cycle. In the simulation in which the ANN did not apply the long-term plasticity mechanisms during sleep (SWS-transition REM), the synaptic weights distribution was re-scaled inexorably, for its mean value proportional to the input firing rate, erasing the synaptic weights pattern that had been established initially. In contrast, when the long-term plasticity is modeled during the transition SWSREM, an increase of synaptic weights were observed in the range of initial/low values, redistributing effectively the weights in a way to reinforce a subset of synapses over time. The results suggest that a positive regulation coming from the long-term plasticity can completely change the role of sleep: its absence leads to forgetting; its presence leads to a positive mnemonic change

Desenvolvimento de uma ferramenta computacional para aplicação em métodos de elevação por bombeio centrífugo submerso

The Electrical Submersible Pump (ESP) has been one of the most appropriate solutions for lifting method in onshore and offshore applications. The typical features for this application are adverse temperature, viscosity fluids and gas environments. The difficulties in equipments maintenance and setup contributing to increasing costs of oil production in deep water, therefore, the optimization through automation can be a excellent approach for decrease costs and failures in subsurface equipment. This work describe a computer simulation related with the artificial lifting method ESP. This tool support the dynamic behavior of ESP approach, considering the source and electric energy transmission model for the motor, the electric motor model (including the thermal calculation), flow tubbing simulation, centrifugal pump behavior simulation with liquid nature effects and reservoir requirements. In addition, there are tri-dimensional animation for each ESP subsytem (transformer, motor, pump, seal, gas separator, command unit). This computer simulation propose a improvement for monitoring oil wells for maximization of well production. Currenty, the proprietaries simulators are based on specific equipments manufactures. Therefore, it is not possible simulation equipments of another manufactures. In the propose approach there are support for diverse kinds of manufactures equipments