Effects of cognitive-behavioral therapy on neurotrophic factors in patients with major depressive disorder

Objective: To correlate neurotrophic factors - brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and beta-nerve growth factor (beta-NGF) - and severity of depressive symptoms in patients diagnosed with major depressive disorder (MDD) undergoing cognitive-behavioral therapy (CBT). Methods: In this quasi-experimental study, participants were selected by convenience and received 16 sessions of CBT. The outcomes of interest were severity of depressive symptoms and changes in neurotrophic factor levels after CBT. The differences between variables before and after treatment (deltas) were analyzed. Results: Patients had significant changes in symptom severity after treatment. No significant associations were found between Beck Depression Inventory II (BDI-II) scores and any independent variable. No correlations were observed between BDNF or GDNF levels and BDI scores before or after treatment, although there was a trend toward significant differences in beta-NGF levels. Conclusion: BDNF, beta-NGF, and GDNF were not influenced by the effects of CBT on depressive symptoms.

Circulating levels of neurotrophic factors are unchanged in patients with Parkinson's disease / Os níveis circulantes de fatores neurotróficos não estão alterados em pacientes com doença de Parkinson

ABSTRACT There is great evidence linking neurotrophic factor (NF) dysfunction with Parkinson's disease (PD) pathophysiology. This study was conducted to evaluate plasma levels of NFs and their possible associations with clinical symptoms in PD. For this purpose, 40 PD patients and 25 controls were subjected to a clinical evaluation and peripheral blood draw. Plasma levels of brain-derived neurotrophic factor (BDNF), pro-BDNF, neurotrophin 3, neurotrophin 4, nerve growth, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were measured by enzyme-linked immunosorbent assay. There was no significant difference between PD patients and controls regarding the plasma levels of the evaluated NFs. In addition, NF levels were not associated with disease duration, degree of motor or functional impairment, cognitive performance or severity of depressive symptoms. In conclusion, although NFs may play relevant roles in the pathophysiology of PD, the circulating levels of these molecules are not necessarily changed in patients with PD.

RESUMO Há evidências de que alteracões nas ações exercidas por fatores neurotróficos (FNs) estejam associadas à fisiopatologia da doença de Parkinson (DP). O presente estudo foi conduzido para avaliar os níveis plasmáticos de FNs e suas possíveis associações com sintomas clínicos na DP. Para este fim, 40 pacientes com DP e 25 controles foram submetidos à avaliação clínica e coleta de sangue periférico. Os níveis plasmáticos do fator neurotrófico derivado do cérebro (BDNF), pro-BDNF, neurotrofina 3, neurotrofina 4, fator de crescimento do nervo, fator neurotrófico derivado da glia e fator neurotrófico ciliar foram avaliados por ensaio de imunoadsorção enzimática. Não houve diferença significativa entre pacientes com DP e controles quanto aos níveis plasmáticos dos FNs avaliados. Além disso, não encontramos associação entre os níveis dos FNs e duração da doença, grau de comprometimento motor ou funcional, desempenho cognitivo e gravidade dos sintomas depressivos. Em conclusão, embora os FNs possam desempenhar papéis relevantes na fisiopatologia da DP, os níveis circulantes dessas moléculas não estão necessariamente alterados em pacientes com DP.

Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania

Objective: To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Methods: Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). Results: BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. Conclusion: These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD. .

Comparison of S100β levels, and their correlation with hemodynamic indices in patients undergoing coronary artery bypass grafting with three different anesthetic techniques.

Cardiac surgery with aid of cardiopulmonary bypass (CPB) is associated with neurological dysfunction. The presence of cerebrospecific protein S100β in serum is an indicator of cerebral damage. This study was designed to evaluate the influence of three different anesthesia techniques, on S100β levels, in patients undergoing coronary artery bypass grafting on CPB. A total of 180 patients were divided into three groups - each of who received sevoflurane, isoflurane and total intravenous anesthesia as part of the anesthetic technique, respectively. S100 were evaluated from venous sample at following time intervals - prior to induction of anesthesia (T1), after coming off CPB (T2); 12 h after aortic cross clamping (T3) and 24 h after aortic cross clamping (T4). In all three groups, maximal rise in S100β levels occurred after CPB which gradually declined over next 24 h, the levels at 24 h post-AOXC being significantly higher than baseline levels. Significantly low levels of S100β were noted at all postdose hours in the sevoflurane group, as compared to the total intravenous anesthesia (TIVA) group, and at 12 and 24 h postaortic cross clamp, in comparison to the isoflurane group. Comparing the isoflurane group with the TIVA group, the S100 levels were lower in the isoflurane group only at 24 h postaortic cross clamp. It was concluded that maximum rise in S100β levels occurs immediately after CPB with a gradual decline in next 24 h. The rise in S100β levels is significantly less in patients administered sevoflurane in comparison to isoflurane or TIVA. Hemodynamic parameters had no influence on the S100β levels during the first 24 h after surgery.

Brain injury markers (S100B and NSE) in chronic cocaine dependents

OBJECTIVE: Studies have shown signs of brain damage caused by different mechanisms in cocaine users. The serum neuron specific enolase and S100B protein are considered specific biochemical markers of neuronal and glial cell injury. This study aimed at comparing blood levels of S100B and NSE in chronic cocaine users and in volunteers who did not use cocaine or other illicit drugs. METHOD: Twenty subjects dependent on cocaine but not on alcohol or marijuana, and 20 non-substance using controls were recruited. Subjects were selected by consecutive and non-probabilistic sampling. Neuron specific enolase and S100B levels were determined by luminescence assay. RESULTS: Cocaine users had significantly higher scores than controls in all psychiatric dimensions of the SCL-90 and had cognitive deficits in the subtest cubes of WAIS and the word span. Mean serum S100B level was 0.09 ± 0.04 µg/l among cocaine users and 0.08 ± 0.04 µg/l among controls. Mean serum neuron specific enolase level was 9.7 ± 3.5 ng/l among cocaine users and 8.3 ± 2.6 ng/l among controls. CONCLUSIONS: In this first study using these specific brain damage markers in cocaine users, serum levels of S100B and neuron specific enolase were not statistically different between cocaine dependent subjects and controls.

OBJETIVO: Estudos têm demonstrado sinais de lesão cerebral causadas por diferentes mecanismos em usuários de cocaína. A enolase sérica neurônio-específica e a proteína S100B são consideradas marcadores bioquímicos específicos de lesão neuronal e glial. Este estudo objetivou comparar os níveis sangüíneos de S100B e enolase sérica neurônio-específica em usuários crônicos de cocaína e em voluntários que não usam cocaína ou outras drogas ilícitas. MÉTODO: Vinte sujeitos dependentes de cocaína, mas não dependentes de álcool, maconha ou outra droga, e 20 sujeitos controles não usuários de drogas foram recrutados. Os sujeitos foram selecionados por amostragem consecutiva e não-probabilística e os níveis de enolase neurônio-específica e S100B foram determinados por ensaio de luminescência. RESULTADOS: Os usuários de cocaína tiveram escores significativamente maior que os controles em todas as dimensões psiquiátricas do SCL-90 e apresentaram prejuízos cognitivos no subteste cubos do WAIS e no span de palavras. Os níveis de S100B foram em média 0,09 ± 0,04 µg/l nos usuários de cocaína e 0,08 ± 0,04 µg/l nos controles. Os níveis de enolase neurônio-específica foram em média 9,7 ± 3,5 ng/l nos usuários e 8,3 ± 2,6 ng/l nos controles. CONCLUSÃO: Neste primeiro estudo utilizando esses marcadores específicos de lesão cerebral em usuários de cocaína, os níveis séricos de S100B e enolase específica do neurônio não foram significativamente diferentes entre dependentes de cocaína e controles.

S100B protein related neonatal hypoxia

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B é de particular importância neste campo. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadro de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém nascidos a termo que desenvolveram encefalopatia hipóxico-isquêmica no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Observou-se correlação positiva entre as duas substâncias, assim como quando comparadas entre si nas suas respectivas dosagens, obteve-se significância estatística.

Measurement of S-100B for risk classification of victims sustaining minor head injury: first pilot study in Brazil

INTRODUÇÃO: A liberação da proteína neuronal S-100B na circulação tem sido sugerida como indicadora de dano neuronal. Foi testada a hipótese de que a S-100B é um marcador útil e custo efetivo para a triagem de pacientes com trauma craniano leve. MÉTODO: Cinqüenta pacientes consecutivos com trauma craniano isolado foram prospectivamente avaliados na sala de emergência de um Centro de Trauma brasileiro pela tomografia computadorizada de crânio e por amostras de sangue venoso, para a medida no soro da proteína S-100B utilizando um teste recentemente desenvolvido; 21 pessoas normais foram utilizadas como controles negativos. Os resultados são apresentados como mediana e percentis 25-75. RESULTADOS: Os pacientes chegaram ao Centro de Trauma em média 45 min (30-62) após o trauma craniano leve. Seis dos 50 pacientes tiveram lesões pós-traumáticas relevantes segundo a tomografia computadorizada de crânio inicial (12%) e foram considerados como positivos. A concentração mediana de S-100B nestes pacientes foi de 0,75µg/L (0,66-6,5), significativamente maior (U-teste, p<0,05) do que a concentração mediana de 0,26µg/L (0.12-0.65) dos pacientes sem lesões pós-traumáticas, segundo a tomografia computadorizada de crânioCCT-. O cálculo para a detecção dos pacientes com lesões intra-cranianas revelou sensibilidade de 100%, especificidade de 20%, valor preditivo positivo de 15% and valor preditivo negativo de 100%. CONCLUSÃO: A proteína S-100B tem altas taxas de sensibilidade e valor preditivo negativo, podendo ter um importante papel para descartar a necessidade de tomografia de crânio após trauma craniano leve. Acreditamos que este achado é de relevância clínica, principalmente em países onde o trauma é muito frequente e os recursos médicos limitados.

Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis

The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

Determination of serum interleukin-13 and nerve growth factor in patients with systemic lupus erythematosus and clinical significance / 华中科技大学学报（医学）（英德文版）

The changes in the levels of serum interleukin-13 (IL-13) and nerve growth factor (NGF) in patients with systemic lupus erythematosus (SLE) and their clinical significance were investigated. Sandwich ELISA was used to determine the levels of serum IL-13 and NGF in 35 SLE patients and 15 normal controls. The results showed that the levels of serum IL-13 (92.69+/-9.87 pg/ml) and NGF (339.69+/-25.60 pg/ml) in active SLE patients were significantly higher than those in inactive SLE patients (IL-13, 54.22+/-9.31 pg/ml; NGF, 300.89+/-33.51 pg/ml) (P<0.01). The inactive patients also had significantly increased serum levels of IL-13 and NGF as compared with normal controls (IL-13, 35.20+/-12.70 pg/ml; NGF, 111.40+/-32.54 pg/ml; P<0.05 and P<0.01, respectively). Spearman correlation analysis revealed that the serum IL-13 levels were correlated with disease activity index of SLE (SLEDAI), ESR and serum levels of C3 (r= 0. 813, 0.504, -0.605, respectively). The serum NGF levels were also correlated with above markers (r=0.442, 0.338, -0.463, respectively). The serum levels of IL-13 and NGF had a positive correlation (r=0.506, P<0.01). It was suggested that IL-13 and NGF might be involved in the pathogenesis of SLE and closely correlated with disease activity.

The research progression of S100beta as a neurochemistry maker / 法医学杂志

S100beta is one kind of the calcium binding proteins. As growth factor of neuraxon, it is excreted by neuroglial cell, and distributing in nerve tissue extensively. Although S100beta has very important values neurophysiological, it also has neurotoxicity with excreting overmuch. Concentration of S100beta changes regularity in serum after the brain injury. In addition, it has a close relations with the degree of brain damage, which can be regarded as the neural new marker of biochemistry after brain damage. The advances of S100beta protein, in the research on neurophysiological values and its application for nerve tissue injury, disease were reviewed.

Effect of a submaxillary gland extract on Ehrlich tumor growth in mice

Ablation of host submaxillary glands modifies Ehrlich tumor growth and tumor-infiltrating leukocytes, possibly by modifications in the serum level of growth factors produced by this gland. To extend this research, 7-month-old male EPM-1 mice (N = 30) were divided into two groups: 1) inoculated with tumor cells previously incubated with submaxillary salivary gland extract (SGE) in PBS for 30 min at 37 percent; 2) inoculated with tumor cells previously incubated with PBS, under the same conditions. Animals were inoculated into the footpad with 40 µl of a suspension containing 4.5 x 107 tumor cells/ml, and footpad thickness was measured daily for 10 days. Sections and smears of tumor cells were prepared from the tumor mass to determine mitosis frequency, percent of tumor cells immunopositive to nerve (NGF) and epidermal (EGF) growth factors and percent of tumor-infiltrating leukocytes. The incubation of tumor cells with SGE produced a tumor reduction of about 30 percent in size. This effect was not related to loss of cell viability during incubation, but a 33 percent increase 0.05 in the percentage of dead or dying tumor cells and a 15 percent increase in the percent of NGF/EGF-positive tumor cells 0.01 were observed in vivo at the end of experiment. Tumor-infiltrating lymphocytes and mitosis frequency did not differ between groups. These data suggest a direct effect of factors present in SGE on tumor cells, which induce degeneration of tumor cells