Antioxidant activity of ß-selenoamines and their capacity to mimic different enzymes.

The antioxidant properties of organoselenium compounds have been extensively investigated because oxidative stress is a hallmark of a variety of chronic human diseases. Here, we reported the influence of substituent groups in the antioxidant activity of ß-selenoamines. We have investigated whether they exhibited glutathione peroxidase-like (GPx-like) activity and whether they could be substrate of thioredoxin reductase (TrxR). In the DPPH assay, the ß-selenium amines did not exhibit antioxidant activity. However, the ß-selenium amines with p-methoxy and tosyl groups prevented the lipid peroxidation. The ß-selenium amine compound with p-methoxy substituent group exhibited thiol-peroxidase-like activity (GPx-like activity) and was reduced by the hepatic TrxR. These results contribute to understand the influence of structural alteration of non-conventional selenium compounds as synthetic mimetic of antioxidant enzymes of mammalian organisms.

Hippocampal PKA/CREB pathway is involved in the improvement of memory induced by spermidine in rats.

Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D-aspartate (NMDA) receptor function, and has been reported to facilitate memory formation. In the current study we determined whether or not the PKA/CREB signaling pathway is involved in SPD-induced facilitation of memory of inhibitory avoidance task in adult rats. The post-training administration of the cAMP-dependent protein kinase (PKA) inhibitor, N-[2-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide [H-89, 0.5 ρmol intrahippocampal (ih)] or the antagonist of the NMDA receptor polyamine-binding site (arcaine, 0.02 nmol ih) with SPD (0.2 nmol ih) prevented memory improvement induced by SPD. Intrahippocampal administration of SPD (0.2 nmol) facilitated PKA and cAMP response element-binding protein (CREB) phosphorylation in the hippocampus 180 min, but not 30 min, after administration, and increased translocation of the catalytic subunit of PKA into the nucleus. Arcaine (0.02 nmol) and H-89 (0.5 ρmol) prevented the stimulatory effect of SPD on PKA and CREB phosphorylation. These results suggest that memory enhancement induced by the ih administration of SPD involves the PKA/CREB pathways in rats.

Contribution of peripheral vanilloid receptor to the nociception induced by injection of spermine in mice.

Polyamines (putrescine, spermidine and spermine) are important endogenous regulators of ion channels, such as vanilloid (TRPV1), glutamatergic (NMDA or AMPA/kainate) and acid-sensitive (ASIC) receptors. In the present study, we have investigated the possible nociceptive effect induced by polyamines and the mechanisms involved in this nociception in vivo. The subcutaneous (s.c.) injection of capsaicin (as positive control), spermine, spermidine or putrescine produced nociception with ED(50) of 0.16 (0.07-0.39)nmol/paw, 0.4 (0.2-0.7) µmol/paw, 0.3 (0.1-0.9) µmol/paw and 3.2 (0.9-11.5) µmol/paw, respectively. The antagonists of NMDA (MK801, 1 nmol/paw), AMPA/kainate (DNQX, 1 nmol/paw) or ASIC receptors (amiloride, 100 nmol/paw) failed to reduce the spermine-trigged nociception. However, the TRPV1 antagonists capsazepine or SB366791 (1 nmol/paw) reduced spermine-induced nociception, with inhibition of 81 ± 10 and 68 ± 9%, respectively. The previous desensitization with resiniferatoxin (RTX) largely reduced the spermine-induced nociception and TRPV1 expression in the sciatic nerve, with reductions of 82 ± 9% and 67 ± 11%, respectively. Furthermore, the combination of spermine (100 nmol/paw) and RTX (0.005 fmol/paw), in doses which alone were not capable of inducing nociception, produced nociceptive behaviors. Moreover, different concentrations of spermine (3-300 µM) enhanced the specific binding of [(3)H]-RTX to TRPV1 receptor. Altogether, polyamines produce spontaneous nociceptive effect through the stimulation of TRPV1, but not of ionotropic glutamate or ASIC receptors.

Clinical relevance and frequency of cytoplasmic and nuclear dense fine speckled patterns observed in ANA-HEp-2.

OBJECTIVES: This study aimed to determine the frequency and antibody titers of nuclear dense fine and cytoplasmic patterns with possible clinical correlation. METHODS: From 2007 to 2009, the results of 2,788 autoantibody serological tests were assessed by indirect immunofluorescence (IIF) at LAC-HUSM/UFSM, using as substrate HEp-2. RESULTS: Among the analyzed samples, 1,998 of them were negative for autoantibodies. Among the positive samples (n = 790), we found 57 (7.2%) showing reactivity pattern described as dense fine speckled (DFS) (3.8%), or cytoplasmic (Cit) fluorescence (3.4%). In samples with standard DFS (n = 29), nine had titers of 1/160, and only one patient had autoimmune disease (AID). Among patients with titers > 1/160, only one patient did not have AID. Among samples with standard Cit (n = 27), 20 had titers of 1/160, and only eight were not associated with AID. The other seven patients with titers > 1/160 reported AID. CONCLUSION: The results confirm the value of 1/160 as the best cut-off point for defining AID presence, for any of the fluorescence assessed patterns. However, attention should be given to lower titers, especially for Cit IIF, since only 40% did not report the presence of AID.

Relevância clínica e frequência de padrões citoplasmático e pontilhado fino denso observados em FAN-HEp-2 / Clinical relevance and frequency of cytoplasmic and nuclear dense fine speckled patterns observed in ANA-HEp-2

OBJETIVOS: O presente estudo procurou determinar a frequência e relacionar o título sorológico dos padrões de imunofluorescência para citoplasma celular e nuclear pontilhado fino denso com possível correlação clínica. MÉTODOS: No período entre 2007 a 2009 foram avaliados os resultados de 2.788 testes sorológicos para pesquisa de autoanticorpos pela técnica de imunofluorescência indireta (IFI), utilizando como substrato células HEp-2, realizados no LAC-HUSM/UFSM. RESULTADOS: Entre as amostras analisadas, 1.998 resultaram não reagentes para a pesquisa de autoanticorpos. Entre as amostras reagentes (n = 790) foram encontradas 57 (7,2 por cento) amostras apresentando padrão de reatividade descrita como pontilhado fino denso (SFD) (3,8 por cento) ou fluorescência citoplasmática (Cit) (3,4 por cento). Nas amostras com padrão SFD (n = 29), nove apresentaram título < 1/160, onde apenas um paciente apresentava doença autoimune (DAI). Entre os pacientes com título > 1/160 apenas um não apresentava DAI. Entre as amostras com padrão Cit (n = 27), 20 apresentavam título < 1/160, onde apenas oito não tinham DAI associada. Todos os outros 7 pacientes com título > 1/160 tinham relato de DAI. CONCLUSÃO: Os resultados encontrados ratificam o valor de 1/160 como melhor ponto de corte para definição de presença de DAI, para qualquer um dos padrões de fluorescência avaliados. Contudo, deve-se prestar atenção a títulos inferiores, principalmente para IFI Cit, uma vez que apenas 40 por cento não apresentavam relato de DAI presente.

OBJECTIVES: This study aimed to determine the frequency and antibody titers of nuclear dense fine and cytoplasmic patterns with possible clinical correlation. METHODS: From 2007 to 2009, the results of 2,788 autoantibody serological tests were assessed by indirect immunofluorescence (IIF) at LAC-HUSM/UFSM, using as substrate HEp-2. RESULTS: Among the analyzed samples, 1,998 of them were negative for autoantibodies. Among the positive samples (n = 790), we found 57 (7.2 percent) showing reactivity pattern described as dense fine speckled (DFS) (3.8 percent), or cytoplasmic (Cit) fluorescence (3.4 percent). In samples with standard DFS (n = 29), nine had titers of 1/160, and only one patient had autoimmune disease (AID). Among patients with titers > 1/160, only one patient did not have AID. Among samples with standard Cit (n = 27), 20 had titers of 1/160, and only eight were not associated with AID. The other seven patients with titers > 1/160 reported AID. CONCLUSION: The results confirm the value of 1/160 as the best cut-off point for defining AID presence, for any of the fluorescence assessed patterns. However, attention should be given to lower titers, especially for Cit IIF, since only 40 percent did not report the presence of AID.