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1.
Proc Natl Acad Sci U S A ; 116(26): 12781-12786, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31186356

RESUMO

How do fundamental concepts from economics, such as individuals' preferences and beliefs, relate to equally fundamental concepts from psychology, such as relatively stable personality traits? Can personality traits help us better understand economic behavior across strategic contexts? We identify an antisocial personality profile and examine the role of strategic context (the "situation"), personality traits (the "person"), and their interaction on beliefs and behaviors in trust games. Antisocial individuals exhibit a specific combination of beliefs and preferences that is difficult to reconcile with a rational choice approach that assumes that beliefs about others' behaviors are formed rationally and therefore, independently from preferences. Variations in antisocial personality are associated with effect sizes that are as large as strong variations in strategic context. Antisocial individuals have lower trust in others unless they know that they can punish them. They are also substantially less trustworthy, believe that others are like themselves, and respond to the possibility of being sanctioned more strongly, suggesting that they anticipate severe punishment if they betray their partner's trust. Antisocial individuals are not simply acting in their economic self-interest, because they harshly punish those who do not reciprocate their trust, although that reduces their economic payoff, and they do so nonimpulsively and in a very calculated manner. Antisocial individuals honor others' trust significantly less (if they cannot be punished) but also, harshly punish those who betray their trust. Overall, it seems that antisocial individuals have beliefs and behaviors based on a view of the world that assumes that most others are as antisocial as they themselves are.


Assuntos
Transtorno da Personalidade Antissocial/psicologia , Confiança , Transtorno da Personalidade Antissocial/economia , Cultura , Economia Comportamental , Jogos Experimentais , Humanos , Psicologia Social , Punição
2.
Purinergic Signal ; 17(3): 481-492, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34282551

RESUMO

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.


Assuntos
Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Receptores Purinérgicos/biossíntese , Transcriptoma/fisiologia , Animais , Polaridade Celular/fisiologia , Células Cultivadas , Camundongos , Receptores Purinérgicos/genética
3.
Psychol Med ; 47(16): 2879-2891, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28587695

RESUMO

BACKGROUND: Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain. METHODS: Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex). RESULTS: Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies. CONCLUSIONS: Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.


Assuntos
Mapeamento Encefálico/métodos , Núcleo Caudado/fisiopatologia , Córtex Cerebral/fisiopatologia , Tomada de Decisões/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Recompensa , Adulto , Estudos de Casos e Controles , Núcleo Caudado/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Índice de Gravidade de Doença
4.
Psychol Med ; 45(6): 1241-51, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25277236

RESUMO

BACKGROUND: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. METHOD: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. RESULTS: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. CONCLUSIONS: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.


Assuntos
Núcleo Caudado/fisiopatologia , Transtorno Depressivo/fisiopatologia , Relações Interpessoais , Princípios Morais , Núcleo Accumbens/fisiopatologia , Adulto , Anedonia/fisiologia , Feminino , Jogos Experimentais , Humanos , Imageamento por Ressonância Magnética , Masculino , Recompensa , Adulto Jovem
5.
Transl Psychiatry ; 12(1): 268, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794104

RESUMO

Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients' response before treatment.


Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Antidepressivos/uso terapêutico , DNA , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Diabetes Mellitus Tipo 2/genética , Epigênese Genética , Epigenoma , Estudo de Associação Genômica Ampla/métodos , Humanos
6.
J Neurophysiol ; 104(4): 1955-68, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20685928

RESUMO

Weakly electric fish use electroreception for both active and passive electrolocation and for electrocommunication. While both active and passive electrolocation systems are prominent in weakly electric Mormyriform fishes, knowledge of their passive electrolocation ability is still scarce. To better estimate the contribution of passive electric sensing to the orientation toward electric stimuli in weakly electric fishes, we investigated frequency tuning applying classical input-output characterization and stimulus reconstruction methods to reveal the encoding capabilities of ampullary receptor afferents. Ampullary receptor afferents were most sensitive (threshold: 40 µV/cm) at low frequencies (<10 Hz) and appear to be tuned to a mix of amplitude and slope of the input signals. The low-frequency tuning was corroborated by behavioral experiments, but behavioral thresholds were one order of magnitude higher. The integration of simultaneously recorded afferents of similar frequency-tuning resulted in strongly enhanced signal-to-noise ratios and increased mutual information rates but did not increase the range of frequencies detectable by the system. Theoretically the neuronal integration of input from receptors experiencing opposite polarities of a stimulus (left and right side of the fish) was shown to enhance encoding of such stimuli, including an increase of bandwidth. Covariance and coherence analysis showed that spiking of ampullary afferents is sufficiently explained by the spike-triggered average, i.e., receptors respond to a single linear feature of the stimulus. Our data support the notion of a division of labor of the active and passive electrosensory systems in weakly electric fishes based on frequency tuning. Future experiments will address the role of central convergence of ampullary input that we expect to lead to higher sensitivity and encoding power of the system.


Assuntos
Potenciais de Ação/fisiologia , Peixe Elétrico/fisiologia , Células Ciliadas da Ampola/fisiologia , Neurônios Aferentes/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Células Ciliadas da Ampola/citologia , Masculino , Neurônios Aferentes/citologia , Distribuição Aleatória
7.
Med Klin Intensivmed Notfmed ; 115(3): 249-252, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30535900

RESUMO

Acute necrotizing esophagitis ("black esophagus") is defined as complete necrosis of the esophageal mucosa, which typically affects the entire circumference. We report a case of a healthy 62-year-old woman, who became hemodynamically unstable due to stress cardiomyopathy with acute right heart failure. Transfusion-dependent anemia occurred 24 h later and an upper gastrointestinal endoscopy revealed a black discoloured mucosa of the distal esophagus. After hemodynamic stabilization and treatment with proton pump inhibitors and sucralfate, complete healing of the esophageal mucosa was achieved.


Assuntos
Cardiomiopatias , Esofagite/diagnóstico , Esofagite/tratamento farmacológico , Esofagite/terapia , Cardiomiopatia de Takotsubo , Doença Aguda , Feminino , Humanos , Pessoa de Meia-Idade
9.
J Fish Biol ; 74(1): 54-76, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20735524

RESUMO

In this study, a first comparative investigation of all four species of Petrocephalus (P. bovei, P. bane, P. soudanensis and P. cf. pallidomaculatus) present in the Upper Volta system and their electric organ discharges (EOD) was conducted. It was found that P. bovei was the most widespread (in terms of habitat use), but in several places P. bovei, P. soudanensis and P. cf. pallidomaculatus occurred syntopically. All species emitted a triphasic signal, and with very few exceptions, the Petrocephalus species of the Upper Volta system could clearly be identified on the basis of their EOD waveforms. The most obvious differences between species in EOD waveforms were in amplitude of the last phase, total duration and fast Fourier transformation (FFT) peak frequency. No sexual dimorphism was present in the EOD of any species although external dimorphism, i.e. an indentation at the base of the anal fin of mature males, was common. The EOD waveform diversity in the Upper Volta principally resembled that found in four sympatric Petrocephalus species from the Ogooué system (Gabon) and might play a role in species recognition and speciation processes.


Assuntos
Peixe Elétrico/fisiologia , Órgão Elétrico/fisiologia , Animais , Burkina Faso , Masculino , Caracteres Sexuais , Especificidade da Espécie
10.
Ophthalmologe ; 116(4): 372-375, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-29881876

RESUMO

Self-injurious behavior (nonsuicidal self-injury, NNSI) is a common phenomenon and occurs in Germany, especially in adolescence, with a lifetime prevalence of 25-35%. In adulthood autoaggressive behavior is usually associated with mental illness, such as borderline personality disorder, as in the presented case. Eye injuries are rare. The treating physician is faced with the difficulty of correctly classifying the injury and clarifying suicidal intentions. Patient care requires a lot of patience, empathy and time and has to include psychosocial aspects.


Assuntos
Transtorno da Personalidade Borderline , Traumatismos Oculares , Comportamento Autodestrutivo , Alemanha , Humanos
11.
Micron ; 119: 1-7, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30639793

RESUMO

The ternary iron arsenide compound BaFe2As2 exhibits a structural phase transition from tetragonal to orthorhombic at a temperature of about 140 K. The twin lamellae arising below this transition temperature were studied in undoped single crystalline bulk and epitaxial thin film samples using electron backscatter diffraction in a scanning electron microscope equipped with a helium cryostat. Applying this technique on bulk single crystals a characteristic twin lamella size in the range of 0.1 µm up to a few µm was observed. In contrast, in epitaxially strained thin films the phase transition is not observed at temperatures above 19 K.

12.
J Physiol Paris ; 102(4-6): 233-45, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18992811

RESUMO

This study is concerned with the origin of backpropagating action potentials in GABAergic, medium ganglionic layer neurones (MG-cells) of the mormyrid electrosensory lobe (ELL). The characteristically broad action potentials of these neurones are required for the expression of spike timing dependent plasticity (STDP) at afferent parallel fibre synapses. It has been suggested that this involves active conductances in MG-cell apical dendrites, which constitute a major component of the ELL molecular layer. Immunohistochemistry showed dense labelling of voltage gated sodium channels (VGSC) throughout the molecular layer, as well as in the ganglionic layer containing MG somata, and in the plexiform and upper granule cell layers of ELL. Potassium channel labelling was sparse, being most abundant in the deep fibre layer and the nucleus of the electrosensory lobe. Intracellular recordings from MG-cells in vitro, made in conjunction with voltage sensitive dye measurements, confirmed that dendritic backpropagation is active over at least the inner half of the molecular layer. Focal TTX applications demonstrated that in most case the origin of the backpropagating action potentials is in the proximal dendrites, whereas the small narrow spikes also seen in these neurones most likely originate in the axon. It had been speculated that the slow time course of membrane repolarisation following the broad action potentials was due to a poor expression of potassium channels in the dendritic compartments, or to their voltage- or calcium-sensitive inactivation. However application of TEA and 4AP confirmed that both A-type and delayed rectifying potassium channels normally contribute to membrane repolarisation following dendritic and axonal spikes. An alternative explanation for the shape of MG action potentials is that they represent the summation of active events occurring more or less synchronously in distal dendrites. Coincidence of backpropagating action potentials with parallel fibre input produces a strong local depolarisation that could be sufficient to cause local secretion of GABA, which might then cause plastic change through an action on presynaptic GABA(B) receptors. However, STP depression remained robust in the presence of GABAB receptor antagonists.


Assuntos
Dendritos/fisiologia , Peixe Elétrico/fisiologia , Retroalimentação Fisiológica/fisiologia , Plasticidade Neuronal/fisiologia , Rombencéfalo/citologia , Sinapses/fisiologia , 4-Aminopiridina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Dendritos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estimulação Elétrica/métodos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/citologia , Neurônios/fisiologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/classificação , Canais de Potássio/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/classificação , Canais de Sódio/metabolismo , Tetraetilamônio/farmacologia , Tetrodotoxina/farmacologia
13.
Int J Artif Organs ; 30(1): 16-24, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17295189

RESUMO

BACKGROUND: Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency. METHODS: In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit ) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit. RESULTS: In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785+/-0.613 versus 0.695+/-0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185+/-0.554 versus 0.979+/-0.543 IME per treatment (P=0.004). The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8+/-26.7 versus -22.2+/-28.9 mmHg (P=0.007), diastolic BP: -7.8+/-14.8 versus -9.1+/-15.3 mmHg (P=0.064), heart rate: 1.8+/-10.4 versus 2.3+/-11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD. CONCLUSION: For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.


Assuntos
Diálise Renal/efeitos adversos , Diálise Renal/métodos , Idoso , Pressão Sanguínea , Volume Sanguíneo , Estudos Cross-Over , Hemodiafiltração , Humanos , Hipotensão/etiologia , Cãibra Muscular/etiologia , Ultrafiltração
14.
Int J Oral Maxillofac Surg ; 46(10): 1229-1236, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28579265

RESUMO

The primary objective of this study was to investigate the quality of life (QOL) of patients with oral squamous cell carcinoma (OSCC) undergoing curative neoadjuvant chemoradiotherapy followed by radical tumour resection and simultaneous oral cavity reconstruction, using two validated questionnaires. A secondary objective was to assess clinical variables predicting post-treatment dysfunction in chewing, saliva, and swallowing. Thirty-five patients with locally advanced OSCC who underwent preoperative chemoradiotherapy were recruited prospectively. All patients completed both the University of Washington Quality of Life version 4 questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy-Head & Neck version 4 questionnaire (FACT-H&N). UW-QOL and FACT-H&N items were associated with clinical variables. Nearly three-quarters of OSCC patients perceived good to excellent levels of overall QOL after preoperative chemoradiotherapy. Chewing difficulties, decreased salivary function, and swallowing dysfunction were the most frequent complaints of OSCC patients. Items related to food intake were significantly worse in OSCC patients older than 60 years and those with T4 tumours, as well as those without alcohol intake. Chewing, saliva, and swallowing are the most significant issues in patients with OSCC undergoing preoperative chemoradiotherapy. The results of this study may help guide treatment decisions for OSCC patients based on more accurate expectations of adverse effects of cancer treatment.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Transtornos de Deglutição/fisiopatologia , Neoplasias Bucais/fisiopatologia , Neoplasias Bucais/terapia , Qualidade de Vida , Salivação/fisiologia , Sistema Estomatognático/fisiopatologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Terapia Neoadjuvante , Procedimentos Cirúrgicos Bucais , Cuidados Pré-Operatórios , Estudos Prospectivos , Inquéritos e Questionários
15.
Dent Mater ; 22(6): 499-505, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16198408

RESUMO

OBJECTIVES: Oral and systemic cells are permanently exposed to various types of xenobiotics, such as dental restorative materials, which may subsequently cause adverse effects. Objective of the present investigation was to analyze the effects of three important resin monomers on the glutathione metabolism of human gingival fibroblasts after an incubation period of 4h. METHODS: Cells were exposed to various concentrations of 2-hydroxyethyl methacrylate (HEMA; 0.1-10 mM), triethylene-glycol dimethacrylate (TEGDMA; 0.05-2.5 mM), and urethane dimethacrylate (UDMA; 0.005-0.25 mM). Subsequently, cellular glutathione (GSH) concentrations were determined after a treatment period of 4h using the monobromobimane assay. Data were statistically evaluated using Tukey ANOVA with p<0.05. RESULTS: GSH depletion was dependent on the type of the resin monomer: UDMA>TEGDMA>HEMA. The concentrations for a 50%-reduction of cellular GSH varied between 0.1 mM (0.05 mM) (UDMA), 0.33 mM (0.09 mM) (TEGDMA), and 1.6 mM (0.8 mM) (HEMA). Simultaneously, no decrease of cell numbers was found at any tested concentration. SIGNIFICANCE: These data indicate that the investigated resins may cause cell damage due to depletion of intracellular GSH level even at low concentrations within a short period of time. The decrease of GSH is an early reaction, which is triggered prior to other cytotoxic alterations.


Assuntos
Resinas Compostas/farmacologia , Materiais Dentários/farmacologia , Fibroblastos/efeitos dos fármacos , Gengiva/efeitos dos fármacos , Glutationa/efeitos dos fármacos , Metacrilatos/farmacologia , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/farmacologia , Poliuretanos/farmacologia , Cimentos de Resina/farmacologia , Compostos Bicíclicos com Pontes , Contagem de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Corantes Fluorescentes , Gengiva/metabolismo , Glutationa/análise , Humanos , Teste de Materiais , Reagentes de Sulfidrila
16.
J Physiol Paris ; 110(3 Pt B): 190-199, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27815181

RESUMO

The Electrosensory Lateral Line lobe (ELL) is the first central target where the electrosensory information encoded in the spatiotemporal pattern electroreceptor afferent discharges is processed. These afferents encode the minute amplitude changes of the basal electric field through both a change in latency and discharge rate. In the ELL the time and rate-coded input pattern of the sensory periphery goes through the granular cell layer before reaching the main efferent cells of the network: large fusiform (LF) and large ganglion (LG) cells. The evidence until now shows that granular cells are inhibitory. Given that large fusiform cells are excited by the sensory input, it remains a mystery how the afferent input produce excitation through a layer composed by only inhibitory cells. We addressed this problem by modeling how the known circuitry of the ELL could produce excitation in LF cells with only inhibitory granular cells. Alternatively we show that a network composed of a mix of excitatory and inhibitory granular cell not only performs better, as expected, carrying excitation to LF cells but it does so robustly and at higher sensitivity by enhancing the contrast of the electric image between the periphery and the ELLs output. We then show with refined histological methods that a subpopulation of the granular cells indeed are excitatory, providing the necessary input for this contrast enhancing mechanism.


Assuntos
Peixe Elétrico/fisiologia , Órgão Elétrico/fisiologia , Reconhecimento Fisiológico de Modelo/fisiologia , Animais , Órgão Elétrico/citologia , Neurônios/fisiologia
17.
J Biomed Mater Res B Appl Biomater ; 75(2): 272-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16080163

RESUMO

Glutathione (GSH) is important for the self-protection of cells against oxidative stress and toxic xenobiotics, whereas reactive oxygen species (ROS) at elevated concentrations may cause detrimental alterations of cell membranes, DNA, and other cellular structures. The present investigation addressed the effects of triethylene-glycoldimethacrylate (TEGDMA) and camphorquinone (CQ) on glutathione metabolism and the formation of ROS in oral cells. Primary human pulp fibroblasts were exposed to various concentrations of TEGDMA and CQ (0.1-5 mM). Subsequently, GSH concentration and ROS formation were analyzed with the use of the monobromobimane assay (GSH) and 2',7'-dichlorofluorescein diacetate (DCFH-DA) (ROS). The endogenous ROS hydrogen peroxide (H2O2) was used as a positive control (0.02-2 mM). TEGDMA significantly decreased GSH at concentrations between 0.5 and 5 mM (p<0.05), but did not elevate ROS levels. Contrary, CQ increased ROS formation at concentrations>or=1 mM, but had only a moderate effect on GSH at the highest test concentration. Hydrogen peroxide increased ROS and simultaneously decreased GSH at concentrations of >or=0.2 mM. These data show that the investigated substances may cause cell damage due to various mechanisms, GSH decrease and/or ROS increase. As a consequence, TEGDMA and CQ released into an aqueous environment from resinous materials might interact, thus generating significant cytotoxic effects even at low concentrations.


Assuntos
Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Glutationa/metabolismo , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Terpenos/farmacologia , Células Cultivadas , Humanos
18.
Cancer Treat Rev ; 41(10): 960-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26604093

RESUMO

BACKGROUND: Plasma fibrinogen may be involved in several stages of cancer progression. Clinical studies have demonstrated that pretreatment plasma fibrinogen is associated with poor survival in various cancers. The aim of this meta-analysis was to examine the prognostic effect of circulating fibrinogen in solid tumors. MATERIALS AND METHODS: We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, and meeting proceedings to identify studies assessing the effect of pretreatment plasma fibrinogen on survival of cancer patients. Pooled multivariable-adjusted hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were estimated using random-effects models. RESULTS: Data from 52 observational studies and 15,371 patients were summarized. An elevated baseline plasma fibrinogen was significantly associated with worse OS (pooled HR = 1.69; 95% CI = 1.48­1.92). The highest negative effect of elevated plasma fibrinogen on OS was demonstrated in renal cell carcinoma (pooled HR = 2.22), followed by head and neck cancer (pooled HR = 2.02), and colorectal cancer (pooled HR = 1.89). The adverse prognostic impact of high plasma fibrinogen remained in both non-metastatic and metastatic disease and patients of different ethnicity. Patients with high baseline fibrinogen had a significantly shorter DFS (pooled HR = 1.52) and CSS (pooled HR = 2.50). CONCLUSIONS: An elevated pretreatment plasma fibrinogen significantly correlates with decreased survival in patients with solid tumors. Future clinical trials are warranted to determine whether plasma fibrinogen could be incorporated in cancer staging systems and whether fibrinogen-lowering therapies have a favorable effect on disease recurrence and mortality.


Assuntos
Fibrinogênio/metabolismo , Neoplasias/sangue , Progressão da Doença , Intervalo Livre de Doença , Humanos , Neoplasias/mortalidade , Prognóstico , Modelos de Riscos Proporcionais
19.
Biochimie ; 74(9-10): 941-8, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1334702

RESUMO

Two tumor cell lines (C6 glioma and N1E-115 neuroblastoma), primary glia and primary neurons (from rat) were incubated with 2-13C-pyruvate and 3-13C-pyruvate in culture dishes. 13C NMR spectra of the cell extracts were used to determine the ratio of pyruvate carboxylase to pyruvate dehydrogenase activity. Pyruvate carboxylase activity was found higher in primary glia cells than in neurons. Glial cells synthesized more amino acids, ie, their TCA cycle was used to a larger extent for biosynthesis than is the case of neurons, where it is preferentially used for the energy metabolism.


Assuntos
Ciclo do Ácido Cítrico/fisiologia , Espectroscopia de Ressonância Magnética/métodos , Neuroglia/metabolismo , Neurônios/metabolismo , Animais , Carbono , Células Cultivadas , Glioma/metabolismo , Neuroblastoma/metabolismo , Prótons , Piruvato Carboxilase/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Piruvatos/metabolismo , Ácido Pirúvico , Ratos , Reprodutibilidade dos Testes , Células Tumorais Cultivadas
20.
Biomaterials ; 17(15): 1481-8, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8853118

RESUMO

Transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13) from Streptoverticillium mobaraense has been used to stabilize immobilisates produced with beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) from Aspergillus oryzae and acid-processed gelatins of different qualities as support. The isopeptide level of N epsilon-(gamma-L-glutamyl)-L-lysine bonds formed by transglutaminase was determined to estimate their influence on the kinetic properties of the enclosed beta-galactosidase. An HPLC procedure using precolumn derivatization of the gelatin hydrolysates with FMOC-chloride was chosen which permits the analysis of cross-linked lysine with satisfactory precision. Depending on the gelatin quality, the degree of cross-links necessary for the transformation of gelatin into an insoluble protein was in the range 0.3-32.3% of the available lysine residues. beta-Galactosidase was entrapped in the gelatin matrices with a yield of 8-46% of the initial activity. Long reaction times for cross-linking were due to low yields rather than to the number of isopeptide bonds. Repeated use of the immobilisates did not lead to an appreciable loss of activity. The Vmax of beta-galactosidase were diminished by immobilization caused by a tighter package of the protein chains rather than by the extent of cross-links, while the obtained Km values of the free enzyme and the immobilisates were quite similar. Also, the pH and temperature of optima of the free enzyme and the gelatin immobilisates differ only slightly. The data suggest that the immobilization procedure only moderately affects the activity of enzymes catalysing the reaction of a small compound if gelatin with high jelly strength is cross-linked in a 10% solution with transglutaminase.


Assuntos
Reagentes de Ligações Cruzadas , Enzimas Imobilizadas/metabolismo , Gelatina , Transglutaminases/metabolismo , beta-Galactosidase/metabolismo , Aspergillus oryzae/enzimologia , Cromatografia Líquida de Alta Pressão , Colágeno , Indicadores e Reagentes , Cinética , Streptomycetaceae/enzimologia
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