Papers by Roberta Cysneiros

Keywords: C-reactive protein Cytokines Epileptogenesis Omega-3 fatty acid Temporal lobe epilepsy ... more Keywords: C-reactive protein Cytokines Epileptogenesis Omega-3 fatty acid Temporal lobe epilepsy Pilocarpine During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cyto-kines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures.

Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As many other spec... more Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As many other species of the genus, it shares the reputed folk use to treat heart failure, cough, asthma and bronchitis. The plant has been cultivated under controlled conditions and the 2% aqueous extract (AE) prepared with the dried leaves was standardized by its chemical contents on catechins, flavonoids and procyanidins. The present paper reports the antihypertensive activity of AE and of n-butanol fraction (BuF), an enriched semi-purified butanolic fraction used to isolate the main chemical constituents. Oral administration of AE and BuF induced hypotension in normotensive rats. The effect of AE (0.5 g/ kg/bi, p.o.) was time and dose-dependent peaking at 2–3 weeks after daily administration. BuF was faster but not more active than AE. Both extracts decreased the hypertension of spontaneous hypertensive rats, the hypertension induced in rats by L-NAME treatment and that induced by constriction of one renal artery. The antihypertensive effect was maintained for as long as 60 days of treatment and was reversible upon drug washout at the same rate of its establishment. Acute i.v. administration of BuF to anesthetized rats induced a fast short-lasting hypotension and inhibited the pressor responses to noradrenaline, angiotensin I and angiotensin II by 40%. These results were indirect indications that the hypotension induced by AE is not related to ACE inhibition, increased NO synthesis, or specific blockade of a1 and AT1 receptors. It can be suggested that BuF interferes with the calcium handling mechanisms in smooth muscle cells and neurons. Intravenous injection of five out of nine compounds isolated from BuF produced immediate but short-lasting hypotension that does not correlate with the onset of the hypotension after oral treatment. This finding suggests that they may not be the compounds directly responsible for the delayed and sustained hypotension after per os administration of AE. The many compounds isolated from AE are under evaluation to determine its pharmacokinetics, mechanisms of action and interactions necessary to yield the plant effect. Although its mechanism is still unknown, AE seems to be an effective and safe antihypertensive phytomedicine.br (A.J. Lapa).
Mechanisms and New Methods for Analyzing Risks, 2015

Journal of Neural Transmission, 2014
Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed... more Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality.
10. THE BRAZILIAN FOLK MEDICINE PROGRAM TO VALIDATE MEDICINAL PLANTS-A TOPIC IN NEW ANTIHYPERTENS... more 10. THE BRAZILIAN FOLK MEDICINE PROGRAM TO VALIDATE MEDICINAL PLANTS-A TOPIC IN NEW ANTIHYPERTENSIVE DRUG RESEARCH ANTONIO JOSE LAPA1-*, MARIA TERESA R. DE LIMA-LANDMAN1, ROBERTA M. CYSNEIROS1, ANTONIO CARLOS R. ...

The nanotechnology research progressed significantly over the past 30 years, allowing for the dev... more The nanotechnology research progressed significantly over the past 30 years, allowing for the development of new materials with applications that meet the interests of various sectors. In health, the pharmaceutical industry has used nanostructured materials to develop the release of drugs. Application of the nanoparticles offers numerous advantages compared to conventional release, such as progressive and controlled release of drugs from the matrix degradation, effective plasma levels with less fluctuation over time, less risk of toxicity, biological penetration through the barriers and targeting to specific tissue targets. In this study, the material used in drug delivery is pseudoboehmite. The pseudoboehmite consists in an advanced synthetic ceramic with enhanced characteristics of composition, morphology and desired particle size. It is based on an oxyhydroxide aluminum and its structure is similar to boehmite. Objectives: Analysis of the implementation of a pseudoboehmite obtained by the sol-gel process as pharmaceutical excipient for release of drug acyclovir in vitro and evaluation of their toxicity in rodents (Wistar rats). Methods: The pseudoboehmite was synthesized by solgel method and then subjected to aging treatment by wet process. The pseudoboehmite obtained was characterized by scanning electron microscopy (SEM), infrared absorption spectroscopy analysis (FTIR), by adsorption to a test dissolutor with gastrointestinal fluid and construction of the release profile by High Performance Liquid Chromatography (HPLC) to determine the kinetics of drug release by the tablet. Furthermore, acute toxicity tests in males albino rats were perfomed. These were treated with a single dose of pseudoboehmite (300mg/Kg e 2000mg/Kg) through oral administration by gavage and intraperitoneal injection -IP. The surviving animals were anesthetized by ketamine hydrochloride 10% intraperitoneally and then exsanguinated by the aorta to detecting the presence of aluminum in the systemic circulation by Atomic Absorption Spectroscopy. Blood samples were collected anticoagulant (EDTA 1mg/1ml) and centrifuged at 1500 rpm to obtain the plasma. The procedures described above were conducted individually and in isolated location to avoid any stress in other animals. All experimental procedures adopted for the study obeyed the rules established by the Research and Ethics Committee of Universidade Presbiteriana Mackenzie -process CEUA / UPM Nº 090/05/2012. Results: By SEM's analysis, it was observed that the pseudoboehmite is constituted by a highly porous surface and appears to have a homogeneous and fibrillar shape, which facilitates adsorption. Using FTIR analysis, it was observed that the pseudoboehmite has a high purity, without the presence of byproducts of the sol-gel process as contaminants. It was also observed, by characteristic absorption bands that through the high amorphous fraction, there is presence of nanocrystals in low amounts. In the adsorption test in a dissolutor with gastrointestinal fluid and construction of the release profile by HPLC, characteristics were observed on the release kinetics allowing the applying of pseudoboehmite the development of controlled release systems for drugs. With respect to acute toxicity, there were no deaths and no signs of toxicity after the administration of pseudoboehmite. In the analysis of plasma, there was no presence of aluminum in the systemic circulation of animals -below the limit of detection by equipment used atomic absorption spectrophotometry. Conclusion: The pseudoboehmite synthesized has a high porosity, with future expectations for its use as drug-releasing system. The absence of aluminum metal in samples of blood plasma of animals reveals the absence of absorption bodies, emphasizing the need for more detailed investigations such as the histological and biochemical parameters resulting from the administration of pseudoboehmite.
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Papers by Roberta Cysneiros