Biological implications of selenium and its role in trypanosomiasis treatment.

Selenium (Se) is an essential trace element for several organisms and is present in proteins as selenocysteine (Sec or U), an amino acid that is chemically distinct from serine and cysteine by a single atom (Se instead of O or S, respectively). Sec is incorporated into selenoproteins at an in-frame UGA codon specified by an mRNA stem-loop structure called the selenocysteine incorporating sequence (SECIS) presented in selenoprotein mRNA and specific selenocysteine synthesis and incorporation machinery. Selenoproteins are presented in all domains but are not found in all organisms. Although several functions have been attributed to this class, the majority of the proteins are involved in oxidative stress defense. Here, we discuss the kinetoplastid selenocysteine pathway and how selenium supplementation is able to alter the infection course of trypanosomatids in detail. These organisms possess the canonical elements required for selenoprotein production such as phosphoseryl tRNA kinase (PSTK), selenocysteine synthase (SepSecS), selenophosphase synthase (SelD or SPS), and elongation factor EFSec (SelB), whereas other important factors presented in mammal cells, such as SECIS binding protein 2 (SBP) and SecP 43, are absent. The selenoproteome of trypanosomatids is small, as is the selenoproteome of others parasites, which is in contrast to the large number of selenoproteins found in bacteria, aquatic organisms and higher eukaryotes. Trypanosoma and Leishmania are sensitive to auranofin, a potent selenoprotein inhibitor; however, the probable drug mechanism is not related to selenoproteins in kinetoplastids. Selenium supplementation decreases the parasitemia of various Trypanosome infections and reduces important parameters associated with diseases such as anemia and parasite-induced organ damage. New experiments are necessary to determine how selenium acts, but evidence suggests that immune response modulation and increased host defense against oxidative stress contribute to control of the parasite infection.

Selenocysteine biosynthesis and insertion machinery in Naegleria gruberi.

Selenium (Se) is an essential trace element primarily found in selenoproteins as the 21st amino acid (selenocysteine, Sec, or U). Selenoproteins play an important role in growth and proliferation and are typically involved in cellular redox balance. Selenocysteine is encoded by an in-frame UGA codon specified by a stem-loop structure, the Sec insertion sequence element (SECIS), which, in eukaryotes, is located in the 3'-untranslated region (UTR). The availability of the Naegleria gruberi (ATCC 30224) genome sequence and the use of this organism as a model system for the pathogenic amoeba N. fowleri allowed us to investigate the Sec incorporation pathway in this primitive eukaryote. Using bioinformatics tools, we identified gene sequences encoding PSTK (O-phosphoseryl-tRNA(Sec) kinase), SepSecS (O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase), SelD/SPS2 (selenophosphate synthetase), EFSec (selenocysteine-specific elongation factor) and SBP (SECIS binding protein). These findings were confirmed by RT-PCR and by sequencing. A potential tRNA(Ser)Sec (SelC) gene and a putative selenoprotein with sequence similarity to a mitochondrial thioredoxin reductase (TR3) were also identified. Our results show that the selenocysteine incorporation machinery is indeed present in N. gruberi. Interestingly, the SelD/SPS2 gene is 2214 bp in length and contains two distinct domains. The N-terminal region shows sequence similarity to predicted methyltransferase proteins, and the C-terminal region is homologous to prokaryotic SelD/SPS2. Our results suggest the possibility of novel selenoproteins.

Cloning and molecular characterization of Trypanosoma cruzi U2, U4, U5, and U6 small nuclear RNAs.

Small nuclear RNAs (snRNAs) are important factors in the functioning of eukaryotic cells that form several small complexes with proteins; these ribonucleoprotein particles (U snRNPs) have an essential role in the pre-mRNA processing, particularly in splicing, catalyzed by spliceosomes, large RNA-protein complexes composed of various snRNPs. Even though they are well defined in mammals, snRNPs are still not totally characterized in certain trypanosomatids as Trypanosoma cruzi. For this reason we subjected snRNAs (U2, U4, U5, and U6) from T. cruzi epimastigotes to molecular characterization by polymerase chain reaction (PCR) and reverse transcription-PCR. These amplified sequences were cloned, sequenced, and compared with those other of trypanosomatids. Among these snRNAs, U5 was less conserved and U6 the most conserved. Their respective secondary structures were predicted and compared with known T. brucei structures. In addition, the copy number of each snRNA in the T. cruzi genome was characterized by Southern blotting.

Cloning and molecular characterization of Trypanosoma cruzi U2, U4, U5, and U6 small nuclear RNAs

Small nuclear RNAs (snRNAs) are important factors in the functioning of eukaryotic cells that form several small complexes with proteins; these ribonucleoprotein particles (U snRNPs) have an essential role in the pre-mRNA processing, particularly in splicing, catalyzed by spliceosomes, large RNA-protein complexes composed of various snRNPs. Even though they are well defined in mammals, snRNPs are still not totally characterized in certain trypanosomatids as Trypanosoma cruzi. For this reason we subjected snRNAs (U2, U4, U5, and U6) from T. cruzi epimastigotes to molecular characterization by polymerase chain reaction (PCR) and reverse transcription-PCR. These amplified sequences were cloned, sequenced, and compared with those other of trypanosomatids. Among these snRNAs, U5 was less conserved and U6 the most conserved. Their respective secondary structures were predicted and compared with known T. brucei structures. In addition, the copy number of each snRNA in the T. cruzi genome was characterized by Southern blotting.

Fencamfamine-induced changes in the parameters of the matching law and the effect of previous exposure to the drug.

The purpose of this study was to assess the effects of the psychomotor stimulant fencamfamine (FCF) on the operant response rate and on the parameters k and R(e) of Herrnstein's hyperbola. In the first experiment, rats were trained on a multiple variable interval (VI) schedule. Each rat was then given two i.p. injections of a randomly assigned FCF dose (0.0, 0.88, 1.75 and 3.5 mg/kg) at 48 h intervals. The overall response rate, the individual VI response rate, and the k and R(e) parameters of the hyperbola equation were calculated. In the second experiment, two groups of animals were trained drug-free on the same schedule. Afterwards, the animals in one group received six i.p. injections of 1.75 mg/kg FCF at 48 h intervals while subjects in the other group received vehicle injections, 15 min before each experimental session. Seven days after the last injection, a challenge dose (0.88 mg/kg) of FCF was administered and performance was measured. FCF increased overall response rate and decreased R(e) without changing k. Previous exposure to FCF did not induce sensitization of these measures. These results indicate that FCF has similar effects on k and R(e) as those produced by other indirect dopaminergic agents, and supports previous findings suggesting FCF as a potential drug of abuse.

Inibicao latente, um modelo experimental de Esquizofrenia / Latent inhibition, an experimental model of schizophrenia

Um dos modelos comportamentais mais utilizados na avaliacao de drogas antipsicoticas é o da pre-exposicao ao estímulo a ser condicionado, ou inibiçäo latente(LI). Na LI, a exposiçäo prévia a um estímulo sem consequencia retarda a aprendizagem, quando esse mesmo estímulo, numa fase posterior, é pareado com um reforçador. Neste artigo é feita, preliminarmente, uma revisäo da utilizaçäo da LI como modelo animal para avaliaçäo de drogas antipsicóticas, e de seu fundamento neuroquímico. A seguir, discutem-se os processos comportamentais implicados na pré-exposiçäo, e que explicariam o desempenho na fase de condicionamento. Duas teorias principais säo examinadas, à luz dos paradigmas respondentte e operante do comportamento: 1) a de Mackintosh, que considera que a aprendizagem deirrelevancia do estímulo ocorre quando esse näo sinaliza nenhuma mudança em um reforçador específico, e 2) a de Lubow, que defende a existencia de uma hipotética resposta de atençäo que decresceria aao longo de repetidas exposiçöes ao estímulo, o que diminuiria sua futura associabilidade quando na funçäo de estímulo condicional

Anxiogenic-like effect of acute and chronic fluoxetine on rats tested on the elevated plus-maze

The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely prescribed for depression and anxiety-related disorders. On the other hand, enhanced serotonergic transmission is known to be classically related to anxiety. In this study, the effects of acute (5.0 mg/kg) and chronic (5.0 mg/kg, 22 days) FLX were investigated in both food-deprived and non-deprived rats tested in the elevated plus-maze. Significant main effects of the three factors (drug, food condition and administration regimen) were observed, but no interaction between them. The administration of either acute or chronic FLX resulted in an anxiogenic effect, as detected by a significant reduction in the percentage of time spent in the open arms and in the percentage of open arm entries. Food deprivation yielded an anxiolytic-like profile, probably related to changes in locomotor activity. The administration regimen resulted in an anxiolytic profile in chronically treated rats, as would be expected after 22 days of regular handling. The anxiogenic action of acute FLX is consistent with both its neurochemical and clinical profile. The discrepancy between the anxiogenic profile of chronic FLX and its therapeutic uses is discussed in terms of possible differences between the type of anxiety that is measured in the plus-maze and the types of human anxiety that are alleviated by fluoxetine

Aterectomia coronária rotacional por ablaçäo e a assistência de enfermagem / Nurse assistance in rotational atherectomy

As indicaçöes no tratamento de lesöes coronárias complexas foram ampliadas com o avanço técnico e tecnológico da Cardiologia Intervencionista. Dentre as técnicas desenvolvidas para superar as limitaçöes no tratamento de lesöes coronárias, a aterectomia coronária rotacional é uma delas. Cabe à enfermagem a atualizaçào constante e, por meio da sistematizaçäo da assistência, prestar os cuidados no pé, no trans e no pós-procedimento, contribuindo assim para osucesso da nova técnica e para a boa evoluçädo paciente durante a fase hospitalar.