Increased plasma levels of brain derived neurotrophic factor (BDNF) in patients with fibromyalgia.

Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system. BDNF appears to modulate nociceptive sensory inputs and pain hypersensitivity and has been studied in pathological situations, including chronic pain conditions and major depression. Increased serum BDNF levels have been recently reported in fibromyalgia (FM). In the present study, we assessed plasma BDNF levels in patients with FM and controls. Plasma BDNF was measured from 30 female patients with FM and 30 healthy age- and gender-matched volunteers using an enzyme immunoassay. FM patients showed higher levels of BDNF (FM = 167.1 +/- 171.2 pg/mL) when compared with the control group (control = 113.8 +/- 149.6 pg/mL) (P = 0.049; Mann-Whitney test). Six out of 30 controls presented superior values to the medium (15/15) of the patients with fibromyalgia (129 pg/mL) (P = 0.029, Fisher exact test). There was no correlation between plasma BDNF levels and age, disease duration, pain score, number of pain points and HAM-D score. Our results confirm previous findings of increased plasma BDNF levels in patients with FM, suggesting that BDNF may be involved in the pathophysiology of Fibromyalgia, despite high levels of depression.

Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model.

Quinolinic acid (QA) is an N-methyl-D-aspartate receptor agonist that also promotes glutamate release and inhibits glutamate uptake by astrocytes. QA is used in experimental models of seizures studying the effects of overstimulation of the glutamatergic system. The guanine-based purines (GBPs), including the nucleoside guanosine, have been shown to modulate the glutamatergic system when administered extracellularly. GBPs were shown to inhibit the binding of glutamate and analogs, to be neuroprotective under excitotoxic conditions, as well as anticonvulsant against seizures induced by glutamatergic agents, including QA-induced seizure. In this work, we studied the electrophysiological effects of guanosine against QA-induced epileptiform activity in rats at the macroscopic cortical level, as inferred by electroencephalogram (EEG) signals recorded at the epidural surface. We found that QA disrupts a prominent basal theta (4-10 Hz) activity during peri-ictal periods and also promotes a relative increase in gamma (20-50 Hz) oscillations. Guanosine, when successfully preventing seizures, counteracted both these spectral changes. MK-801, an NMDA-antagonist used as positive control, was also able counteract the decrease in theta power; however, we observed an increase in the power of gamma oscillations in rats concurrently treated with MK-801 and QA. Given the distinct spectral signatures, these results suggest that guanosine and MK-801 prevent QA-induced seizures by different network mechanisms.

Increased S100B serum levels in dilated cardiomyopathy patients.

BACKGROUND: The S100B protein is considered a biochemical marker for brain injuries. However, our group demonstrated that the isolated rat heart releases S100B. In this study, we investigated the serum levels of S100B in dilated cardiomyopathy (DCM) patients to evaluate its levels in heart disease. METHODS AND RESULTS: We selected DCM patients, excluding any condition that could influence S100B serum levels. Control individuals were sex and age matched. Both groups were submitted to clinical evaluation and echocardiography. We measured the S100B and NT-proBNP serum levels (expressed as median [interquartile range]). NT-proBNP levels in patients group (1462 pg/mL [426-3591]) were higher than in controls (35 pg/mL [29-55]), P < .001. S100B serum levels were higher in patients group (0.051 microg/L [0.022-0.144]) than in controls (0.017 microg/L [0.003-0.036]), P = .009. Additionally, we found a positive correlation between S100B and NT-proBNP serum levels only in patients group (Spearman's coefficient r = 0.534; P = .013). CONCLUSIONS: Although we cannot rule out the influence of S100B from brain, the positive correlation between S100B and NT-proBNP levels in DCM patients points to the myocardium as the main source for the rise in S100B serum levels.

The ischemic rat heart releases S100B.

S100B is an astrocytic protein assessed in cerebrospinal fluid and serum as a biochemical marker of cerebral injuries. However, increasing evidences suggest the influence of extra cerebral sources on its serum levels. Since it was reported that the injured myocardium expresses S100B, we investigated whether the isolated heart releases this protein. The rat hearts were excised and perfused by the Langendorff technique of isolated heart perfusion. After stabilization, 10 hearts (ischemic group) were submitted to 20 minutes of ischemia and 30 minutes of reperfusion, and 5 hearts (control group) were submitted to 50 minutes of perfusion. The perfusion fluid was collected at pre-ischemia, and 0, 5, 10, 15 and 30 min after ischemia (or equivalent in controls) for S100B and cardiac troponin T (a heart injury marker) assays. In the ischemic group, S100B and troponin T levels increased significantly at time 0 min: S100B values [mug/L, median (IQ25/IQ75)] increased from < or = 0.02 (< or = 0.02/0.03) to 0.38 (0.22/0.84), while troponin T values [mug/L, median (IQ25/IQ75)] increased from 0.31 (0.15/0.45) to 2.84 (2.00/3.63). Our results point to the ischemic heart as an extra cerebral source of S100B.

S100B and NSE serum concentrations in Machado Joseph disease.

BACKGROUND: NSE and S100B are considered as neuronal and glial peripheral markers of central nervous system pathologies, respectively. We evaluated the potential use of S100B and NSE serum concentrations as peripheral markers of symptomatic patients with Machado Joseph disease (MJD). METHODS: We measured S100B and NSE peripheral concentrations of 22 MJD patients and compared with healthy subjects concentrations. The correlations of both markers with CAG repeat size, age of onset, disease duration, and the scores of the Extended Disability Status Scale of Kurtzke, Unified Parkinson's Disease Rating Scale, and the Montgomery-Asberg depression rating scale were also assessed. RESULTS: S100B serum concentrations between control and MJD subjects were not statistically different, whereas NSE serum concentrations were higher in MJD patients than in control subjects (p=0.00001). S100B presented a moderate correlation with disease duration and depression score, whereas NSE presented a moderate correlation with depression score and a good negative correlation with EDSS score. CONCLUSIONS: Symptomatic MJD patients present increased concentrations of NSE and normal concentrations of S100B in blood.

S100B and NSE serum levels in patients with Parkinson's disease.

We evaluated S100B protein and neuron-specific enolase (NSE) serum levels in Parkinson's disease (PD) patients and their correlation with the severity of disease. The levels of S100B (P=0.16) and NSE (P=0.39) between PD and controls were similar. However, S100B levels correlated positively with the Hoehn and Yahr scale (r=0.368; P=0.02) and negatively with the Activities of Daily Living (ADL) scale (r=-0.431; P=0.006). Therefore, S100B and NSE may not have a diagnostic role in PD, but S100B may have a potential role as a marker of disease progression. The study of S100B may also contribute to elucidate the controversial role of glial cells in PD.

Antidepressivos tricíclicos: uma revisão sobre os aspectos farmacológicos e a importância do monitoramento terapêutico / Tricycles antidepressants: a review about pharmacological characteristics and therapeutic dry monitoring importance

O monitoramento terapêutico é fundamental no acompanhamento de diversos tratamentos, pois permite avaliar se os níveis plasmáticos dos fármacos estão dentro do intervalo terapêutico possibilitando a melhora da resposta clínica e a diminuição da morbidez dos pacientes. Os antidepressivos tricíclicos (ADT) são exemplo de fármacos que necessitam monitoramento terapêutico, pois apresentam estreita faixa terapêutica, risco de toxicidade, metabólitos ativos e baixa correlação entre a dose administrada e níveis plasmáticos. Além disso, fatores como idade, outras patologias associadas e interações medicamentosas podem interferir nos níveis plasmáticos dos ADT. O objetivo deste trabalho foi revisar algumas características farmacológicas dos ADT assim como demonstrar a importância do monitoramento terapêutico para essa classe de fármacos

Anticonvulsant effect of GMP depends on its conversion to guanosine.

Studies on the purinergic system normally deal with adenine-based purines, namely, adenine nucleotides and adenosine. However, a guanine-based purinergic system may also have important neuromodulatory roles. Guanine-based purines exert trophic effects on neural cells, protect brain slices in a model of hypoxia and stimulate glutamate uptake. In vivo, both guanosine 5'-monophosphate (GMP) and guanosine (GUO) protected against seizures. In this study, we investigated if the anticonvulsant effect of GMP is mediated by guanosine and if guanosine or GMP treatments were able to increase adenosine levels. Intraperitoneal (i.p.) treatments with 7.5 mg/kg GMP or guanosine prevented 50% of seizures by quinolinic acid (QA) and increased guanosine cerebrospinal fluid (CSF) levels around twofold and threefold, respectively; GMP and adenosine levels remained unchanged. Intracerebroventricular treatment with 960 nmol GMP prevented 80% of seizures and the 5'-nucleotidase inhibitor alpha-beta-methyleneadenosine 5'-diphosphate (AOPCP), when injected 3 min before, reduced this anticonvulsant effect to 30% protection as well as significantly decreased the conversion of GMP into guanosine measured in the CSF. This study shows that the previously reported effect of GMP as an anticonvulsant seems to be related to its ability to generate guanosine through the action of ecto-5'-nucleotidase.

Influence of anticoagulants on the measurement of S100B protein in blood.

OBJECTIVE: Evaluate anticoagulants influence on blood S100B levels. DESIGN AND METHODS: Blood from 18 healthy adult subjects were collected using: no anticoagulants; EDTA; heparin; and citrate. S100B levels were determined using LIA-mat assay. RESULTS: Heparin and citrate increased S100B levels (p<0.001), whereas EDTA had no effect (p=0.24). Heparin samples were highly (r2=0.97, p<0.001), citrate samples were moderately (r2=0.49, p<0.001), and EDTA samples were not (r2=0.22, p=0.059) correlated with serum samples. CONCLUSION: When anticoagulant is required, heparin should be the primary choice.

Influence of anticoagulants on the measurement of S100B protein in blood.

OBJECTIVE: Evaluate anticoagulants influence on plasma S100B levels. DESIGN AND METHODS: Blood were collected from 18 healthy adult subjects using: no anticoagulants, EDTA, heparin, and citrate. S100B levels were determined using LIA-mat assay. RESULTS: Heparin plasma and citrate increased plasma S100B levels (p < 0.001), whereas EDTA had no effect (p = 0.24). Heparin plasma samples were highly (r2 = 0.97, p < 0.001), citrate samples were moderately (r2 = 0.49, p < 0.001), and EDTA samples were not (r2 = 0.22, p = 0.059) correlated with serum samples. CONCLUSIONS: When anticoagulant is required, heparin plasma should be the primary choice for measurement of S100 B levels.

Proteína S100B no lúpus eritematoso sistêmico com envolvimento neuropsiquiátrico / S100B protein in systemic lupus erythematosus with neuropsychiatric involvement

Não existem bons marcadores de dano e atividade de doença no envolvimento neuropsiquiátrico do lúpus eritematoso sistêmico. Níveis elevados da proteína S100B no soro e no liquor têm sido estudados como marcadores de dano cerebral. Objetivo: Estudar os níveis séricos da proteína S100B no lúpus neuropsiquiátrico e correlacioná-los com achados de exames de imagem. Métodos: Concentrações da proteína S100B no soro foram avaliadas por meio de quimiluminescência em 48 pacientes lúpicos (LESNPS) com ou sem sintomas neurosiquiátricos (LES). Vinte e três pacientes foram estudados usando ressonância magnética (RM) e tomografia computadorizada de emissão fotônica única (SPECT). Resultados: Pacientes com LESNP apresentaram um número aumentado de lesões de substância branca (LSB) maiores ou iguais a 6 mm, comparado aos pacientes com LES sem envolvimento neuropsiquiátrico (p= 0,028). Todos os pacientes com lúpus eritematoso sistêmico (com ou sem sitomas neuropsiquiátricos) apresentaram níveis séricos elevados da proteína S100B em comparação com os controles normais. Pacientes com LESNPS apresentaram níveis significativamente mais elevados da proteína S100B do que os pacientes com LES (p < 0,0001). Foi encontrada correlação entre o índice de atividade da doença (SLEDA), a concentração sérica da proteína S100B e o número de LSB 6 mm (p= 0,0082). Conclusões: Os achados demonstraram níveis séricos elevados da proteína S100B no envolvimento neuropsiquiátrico do LES. Será necessário estudar um número maior de pacientes para correlacionar estes níveis elevados com as diversas formas de apresentação desta complicação e com os achados dos exames de imagem.

Serum S100B levels in patients with lupus erythematosus: preliminary observation.

S100B is an astrocytic calcium-binding protein which has been proposed as a biochemical marker of brain damage or dysfunction in acute and chronic diseases. We investigated whether serum S100B levels could be related to systemic lupus erythematosus (SLE) activity. Patients were grouped as having inactive SLE (ISLE), active SLE without central nervous system (CNS) involvement (ASLE), or active SLE with unequivocal neurologic or psychiatric manifestation (NPSLE). The control group consisted of age- and sex-matched healthy blood donors. S100B levels were determined using a luminescence immunoassay. All SLE groups had higher levels of serum S100B than the control group. Among the SLE groups, significantly higher levels of serum S100B protein were found in the NPSLE group than in the ISLE and ASLE groups, and there was no significant difference in S100B levels between the ISLE and ASLE groups. These preliminary results point to a putative relevance of serum S100B protein levels in SLE patients, specifically concerning CNS involvement present in this disease.