RESUMO
OBJECTIVE: The aim of this study was to investigate the surface roughness of lithium disilicates (LS2s) polished using various polishing systems. MATERIALS AND METHODS: Two types of LS2 (A, Amber Mill and E, IPS e.max CAD) were polished using LS2-specific polishing systems (L-Edenta, L-Jota), a zirconia-specific polishing system (Z-Jota), and a conventional ceramic polishing system (P-Shofu) (n = 8 per group). The compositions of different polishing systems were analyzed using EDS. Surface roughness was measured using confocal laser scanning microscopy and analyzed using EDS and SEM. ANOVA and Tukey's tests were used for the statistical analyses (p = 0.05). RESULTS: The polishing systems were mainly composed of C, O, and Si. The L-Jota group exhibited rougher surfaces than the other groups. Amber Mill exhibited higher surface roughness than IPS e.max CAD (p⟨0.001). Among the polishing systems, the L-Jota group presented the highest roughness value (pp⟨0.001). The surface roughness of the AL-Jota group was higher than that of the other groups. CONCLUSIONS: A sufficiently smooth surface can be achieved without a LS2-specific polishing system. Further, the same polishing system can have different effects depending on the type of LS2.
Assuntos
Âmbar , Polimento Dentário , Cerâmica , Desenho Assistido por Computador , Porcelana Dentária , Teste de Materiais , Propriedades de SuperfícieRESUMO
AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.
Assuntos
Inteligência Artificial , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , TempoAssuntos
Adenocarcinoma/secundário , Neoplasias do Colo/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Parotídeas/secundário , Adenocarcinoma/cirurgia , Idoso , Colectomia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Parotídeas/cirurgiaRESUMO
The specific role of endogenous glutathione in response to neuronal degeneration induced by trimethyltin (TMT) in the hippocampus was examined in rats. A single injection of TMT (8 mg/kg, i.p.) produced a rapid increase in the formation of hydroxyl radical and in the levels of malondialdehyde (MDA) and protein carbonyl. TMT-induced seizure activity significantly increased after this initial oxidative stress, and remained elevated for up to 2 weeks post-TMT. Although a significant loss of hippocampal Cornus Ammonis CA1, CA3 and CA4 neurons was observed at 3 weeks post-TMT, the elevation in the level of hydroxyl radicals, MDA, and protein carbonyl had returned to near-control levels at that time. In contrast, the ratio of reduced to oxidized glutathione remained significantly decreased at 3 weeks post-TMT, and the glutathione-like immunoreactivity of the pyramidal neurons was decreased. However glutathione-positive glia-like cells proliferated mainly in the CA1, CA3, and CA4 sectors and were intensely immunoreactive. Double labeling demonstrated the co-localization of glutathione-immunoreactive glia-like cells and reactive astrocytes, as indicated by immunostaining for glial fibrillary acidic protein. This suggests that astroglial cells were mobilized to synthesize glutathione in response to the TMT insult. The TMT-induced changes in glutathione-like immunoreactivity appear to be concurrent with changes in the expression levels of glutathione peroxidase and glutathione reductase. Ascorbate treatment significantly attenuated TMT-induced seizures, as well as the initial oxidative stress, impaired glutathione homeostasis, and neuronal degeneration in a dose-dependent manner. These results suggest that ascorbate is an effective neuroprotectant against TMT. The initial oxidative burden induced by TMT may be a causal factor in the generation of seizures, prolonged disturbance of endogenous glutathione homeostasis, and consequent neuronal degeneration.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Epilepsia/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Epilepsia/induzido quimicamente , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Homeostase/efeitos dos fármacos , Radical Hidroxila/metabolismo , Malondialdeído/metabolismo , Degeneração Neural/induzido quimicamente , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Compostos de Trimetilestanho/toxicidadeRESUMO
A simple two stage assay was developed for the detection of IgM antibodies to either one of two microorganisms chosen arbitrarily for this study. Salmonella enteritidis and Trichinella spiralis. In the first stage, magnetic polystyrene beads (Dynabeads) coated with anti-mu (mouse) antibodies were incubated with the test material for 45 min to capture the IgM antibodies. In the second stage, indicator latex particles were incubated with the Dynabeads for 30 min and the results read following settlement of the Dynabeads under the influence of a magnet. Two types of indicator particles were used: blue-coloured (sensitized with Trichinella antigen) and red-coloured (sensitized with Salmonella antigen). These were mixed in suitable proportions to form a purple suspension. Reaction of either type of latex particles due to binding to the adsorbed IgM antibodies resulted in the settlement of that particle and hence a change of colour in the suspension to either red (if Trichinella-specific antibodies alone were present) or blue (if Salmonella-specific antibodies alone were present). When applied to the sera (used at 1/10 dilution) of both normal and immunized mice, the assay was positive for all but one (18) immune sera, and negative for all but one (9) normal sera.
Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Anti-Helmínticos/imunologia , Imunoensaio/métodos , Imunoglobulina M/análise , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Látex , Camundongos , Microesferas , Salmonella enteritidis/imunologia , Trichinella/imunologiaRESUMO
A simple two stage assay using latex particles as a reaction indicator has been developed for the detection of IgM antibodies to Trichinella spiralis. In the first stage, magnetic polystyrene beads (Dynabeads) coated with T. spiralis antigen were incubated for 30 min with the test serum. After washing, in the second stage, the assay was developed for 1 h using anti-mu-coated latex particles. After sedimentation of the Dynabeads the turbidity of the resultant latex suspension was measured spectrophotometrically at a wavelength of 400 nm. A decrease in turbidity of more than 20% from that of the control, unreacted, suspension was considered positive. Using an IgM phosphorylcholine-binding monoclonal antibody which was reactive with T. spiralis, the sensitivity of the assay was determined to be 110 ng/ml of antibody. This was 20-fold less than the sensitivity achieved in an indirect enzyme-linked immunosorbent assay (ELISA). When the assay was applied to sera obtained from CBA/N or BALB/c mice, which were either normal or immunized against T. spiralis, the expected results were obtained with titers up to 1/640 observed, and confirmed (r = 0.93, P less than 0.001) in the ELISA.
Assuntos
Imunoglobulina M/análise , Animais , Anticorpos/análise , Antígenos de Helmintos/análise , Testes de Fixação do Látex , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Nefelometria e Turbidimetria , Trichinella/imunologiaRESUMO
Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely prevents the increased death in glucose-deprived astrocytes exposed to 3-morpholinosydnonimine (SIN-1, a peroxynitrite-releasing reagent). The increased vulnerability was in good correlation with the peroxynitrite-evoked decrease of mitochondrial transmembrane potential (MTP) in astrocytes. A simultaneous exposure to glucose deprivation and SIN-1 rapidly depolarized MTP and depleted ATP in astrocytes. Inclusion of ciclopirox initially increased the MTP, maintained it high, and blocked the ATP depletion in glucose-deprived SIN-1-treated astrocytes. However, ciclopirox did not prevent the depletion of reduced glutathione in glucose-deprived SIN-1-treated astrocytes. Consistently, ciclopirox did not scavenge various kinds of oxidants including peroxynitrite, nitric oxide, superoxide anion, hydrogen peroxide and hydroxyl radical. Ciclopirox has been experimentally used as a cell cycle G1/S phase transition blocker (Hoffman et al., Cytometry 12 (1991) 26). Flow cytometry analysis, however, showed that the cytoprotective effect of ciclopirox was not attributed to its inhibition of the cell cycle progression. The present results indicate that ciclopirox protects astrocytes from peroxynitrite cytotoxicity by attenuating peroxynitrite-induced mitochondrial dysfunction.
Assuntos
Astrócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Molsidomina/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Ácido Peroxinitroso/antagonistas & inibidores , Ácido Peroxinitroso/toxicidade , Piridonas/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Cultivadas , Ciclopirox , Citometria de Fluxo , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , L-Lactato Desidrogenase/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Molsidomina/farmacologia , Óxido Nítrico/metabolismo , Oxirredução , Ratos , Ratos Sprague-Dawley , Rodaminas , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Superóxidos/metabolismo , Tirosina/metabolismoRESUMO
The present study shows that under glucose-deprived conditions immunostimulated astrocytes rapidly undergo death due to their increased susceptibility to endogenously produced peroxynitrite. Fe(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (FeTMPyP), but not the structurally related compounds ZnTMPyP and H(2)TMPyP, prevented the death in glucose-deprived immunostimulated astrocytes. Consistently, FeTMPyP, not ZnTMPyP and H(2)TMPyP, completely blocked the elevation of nitrotyrosine immunoreactivity (a marker of peroxynitrite) and the depolarization of the mitochondrial transmembrane potential in glucose-deprived immunostimulated astrocytes. The present data suggest that peroxynitrite may be associated with glial cell death during metabolic deterioration in the cerebral ischemic penumbra.
Assuntos
Astrócitos/efeitos dos fármacos , Compostos Férricos/farmacologia , Glucose/fisiologia , Metaloporfirinas/farmacologia , Porfirinas/farmacologia , Animais , Astrócitos/patologia , Morte Celular/efeitos dos fármacos , Interferon gama/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Nitratos/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
The present study investigates whether immunostimulated glial expression of inducible nitric oxide synthase influences the glucose deprivation-induced death of rat cerebellar granule cells (CGC). CGC/glia cocultures were immunostimulated by interferon-gamma (200 U/ml) and lipopolysaccharides (1 microg/ml) and 2 days later were challenged by glucose deprivation. Neurotoxicity was assessed by measuring the release of lactate dehydrogenase. Neither a 2-h glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly potentiated the glucose deprivation-induced death of CGC. The increased death of glucose-deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (SIN-1) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The increased death of glucose-deprived CGC either after immunostimulation or by SIN-1 was not altered by various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists. Because superoxide dismutase and catalase, which remove superoxide anion, decreased the augmented death of glucose-deprived immunostimulated CGC, the reaction of NO with superoxide to form peroxynitrite appears to be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated glial cells potentiate the death of glucose-deprived neurons in part through the expression of inducible NOS but not through NMDA receptor activation. Potentiation of glucose-deprived CGC death by immunostimulated glial cells may be clinically implicated in the tendency of recurrent ischemic insults to be more severe and fatal than an initial ischemic insult.
Assuntos
Cerebelo/citologia , Glucose/fisiologia , Neuroglia/citologia , Neurônios/citologia , Animais , Animais Recém-Nascidos , Morte Celular , Células Cultivadas , Cerebelo/fisiologia , Técnicas de Cocultura , Antagonistas de Aminoácidos Excitatórios/farmacologia , Proteína Glial Fibrilar Ácida/análise , Glucose/deficiência , Interferon gama/farmacologia , Cinética , Lipopolissacarídeos/farmacologia , Proteínas Associadas aos Microtúbulos/análise , Molsidomina/análogos & derivados , Molsidomina/farmacologia , Neuroglia/efeitos dos fármacos , Neuroglia/fisiologia , Neurônios/classificação , Neurônios/efeitos dos fármacos , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroarginina/farmacologia , Penicilamina/análogos & derivados , Penicilamina/farmacologia , Ratos , Ratos Sprague-Dawley , S-Nitroso-N-AcetilpenicilaminaRESUMO
AIM: To develop and test a new latex slide agglutination test (MPO-LSAT) to detect antimyeloperoxidase (anti-MPO) antibody in serum. METHODS: Latex bead coating was adjusted to give maximum sensitivity by attending to latex size, MPO to latex ratio for coupling, ratio of diluted serum to MPO-latex, reaction time and temperature for coupling, and reaction time for agglutination. Inhibition studies were performed using MPO, proteinase 3, bactericidal/permeability increasing protein, and lactoferrin. RESULTS: There was very good correlation between this test and the conventional anti-MPO enzyme linked immunosorbent assay (ELISA): 81% of sera positive in the ELISA were positive by MPO-LSAT. MPO-LSAT results correlated better with IgM anti-MPO than with IgG anti-MPO. CONCLUSIONS: MPO-LSAT is a simple diagnostic test that is potentially useful in the clinical laboratory as a rapid screening tool for vasculitic diseases.
Assuntos
Autoanticorpos/sangue , Peroxidase/imunologia , Vasculite/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Testes de Fixação do Látex/métodos , Sensibilidade e EspecificidadeRESUMO
AIMS/BACKGROUND: alpha-1 antitrypsin (alpha1AT) is an abundant protease inhibitor in human plasma. Its phenotypic variability has been reported to be associated with pulmonary emphysema and chronic liver diseases. However, alpha1AT deficiency is an uncommon condition in the Chinese population. The aim of this study was to describe the phenotypic distribution of alpha1AT in a southern Chinese population. METHODS: A total of 1085 healthy blood donors underwent alpha1AT phenotyping by isoelectric focusing. RESULTS: Two thirds (66.1%) were homozygous for either M1 or M2, whereas 32.6% were heterozygous for two different M phenotypes. The frequency of allelic variants was only 0.007, and deficiency variants were absent. Compared with earlier studies on southern Chinese populations, this study found a lower frequency of M2, and a higher number of allelic variants, including E, L, N, P, and S. This phenomenon can be attributed to population migration and mixing. CONCLUSIONS: An understanding of the alpha1AT pattern is important for evaluating the predisposition of the population to selected clinical diseases.
Assuntos
Povo Asiático/genética , alfa 1-Antitripsina/genética , Adolescente , Adulto , Alelos , Feminino , Heterozigoto , Homozigoto , Hong Kong , Humanos , Focalização Isoelétrica/métodos , Masculino , Pessoa de Meia-Idade , FenótipoRESUMO
Previous studies showed that heat-hyperalgesia and mechanical allodynia produced by chronic constrictive injury of the sciatic nerve were differentially sensitive to the NMDA receptor antagonist dextrorphan and to morphine and other opioid receptor agonists. These results support the hypothesis that different kinds of neuropathic pain symptoms are caused by different pathological mechanisms. In the present study we determined whether mechanical and thermal allodynia produced by unilateral transection of the 'superior' caudal trunk which innervates the tail in rats were differentially sensitive to the non-competitive NMDA receptor antagonist MK-801. Injection of MK-801 (0.3 mg/kg, i.p.) prior to nerve injury delayed the emergence of both types of allodynia; the antagonist-treated rats exhibited neither mechanical nor thermal allodynia at least for 4 days after the injury, whereas untreated control rats exhibited clear signs of allodynia from the first day after the injury. MK-801 injection on post-injury day 14, when the allodynia was near peak severity, suppressed temporarily both the mechanical and thermal allodynia. These results suggest that the mechanical and thermal allodynia from partial denervation of the tail are both dependent on NMDA receptors in their induction and maintenance. Thus, our results do not support the notion that different pathological mechanisms underlie different modalities of neuropathic pain from partial peripheral nerve injury.
Assuntos
Dor/fisiopatologia , Sistema Nervoso Periférico/lesões , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Modelos Animais de Doenças , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios , Masculino , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , TemperaturaRESUMO
Glucose deprivation has been shown to elicit neuronal death via extracellular glutamate accumulation. Here we report that immunostimulated glial expression of inducible nitric oxide synthase enhances the apoptotic death of glucose-deprived cerebellar granule cells (CGC) via the excitotoxicity-independent pathway. CGC cultures were immunostimulated by interferon-gamma (100 U/ml) and lipopolysaccharides (1 microg/ml) and 2 days later were challenged by glucose deprivation. Neither a 2-h Glucose deprivation nor a 2-day immunostimulation altered the viability of CGC. A 2-day immunostimulation, however, markedly enhanced the apoptotic death of CGC glucose-deprived for 1 h. The increased apoptotic death of glucose-deprived CGC after immunostimulation was mimicked by the nitric oxide (NO) releasing reagent 3-morpholinosydnonimine (200 microM, 30 min) and was partially prevented by the NO synthase (NOS) inhibitor N(G)-nitroarginine. The enhanced apoptotic death was not blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphovalerate (APV) and dizocilpine (MK-801) or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, the NO-induced enhanced apoptotic death occurred without a significant increase of the concentration of glutamate in the bathing medium. Our data indicate that immunostimulated glial cells potentiate the apoptotic death of glucose-deprived CGC in part through the expression of inducible NOS but not through NMDA receptor activation. Potentiation of glucose-deprived CGC death by immunostimulated glial cells may be clinically implicated in the tendency of recurrent ischemic insults to be more severe and fatal than an initial ischemic insult.
Assuntos
Apoptose/fisiologia , Sequestradores de Radicais Livres/farmacologia , Glucose/fisiologia , Neurônios/efeitos dos fármacos , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico/fisiologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Células Cultivadas , Cerebelo/efeitos dos fármacos , Cerebelo/fisiologia , Cicloeximida/farmacologia , Glucose/administração & dosagem , Ácido Glutâmico/metabolismo , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Neuroglia/efeitos dos fármacos , Neuroglia/fisiologia , Neurônios/fisiologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
BAY k-8644 (an L-type Ca(2+) channel agonist of the dihydropyridine class) is recognized as a potent convulsant agent. In this study, we used BAY k-8644 to explore the effects of dextromethorphan (DM) and its major metabolite, dextrorphan (DX), on the (pro)convulsant activity regulated by calcium channels. BAY k-8644 (2 mg/kg, s.c) potentiated seizures induced in rats by kainic acid (KA) (10 mg/kg, i.p.). DM appears more efficacious than DX in attenuation of KA-induced seizures. The anticonvulsant effect of a low dose (12.5 mg/kg, s.c.) of DM was reversed by BAY k-8644 (2 mg/kg) challenge. In contrast, BAY k-8644 (1 or 2 mg/kg) did not significantly affect an anticonvulsant effect from a higher dose (25 mg/kg) of either DM or DX. Intracerebroventricular injection of BAY k-8644 (37.5 microg) significantly induced seizures in mice. DM (12.5 or 25 mg/kg) pretreatment more significantly attenuated seizures evoked by BAY k-8644 than did DX (12.5 or 25 mg/kg). Furthermore, seizure activity induced by KA or BAY k-8644 was consistent with respective activator protein-1 DNA binding activity of the hippocampus. Therefore, our results suggest that the anticonvulsant effects of the morphinans involve, at least in part, the L-type calcium channel. They also suggest that DM is a more potent anticonvulsant than DX in the KA and BAY k-8644 seizure models.
Assuntos
Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Anticonvulsivantes/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Dextrometorfano/farmacologia , Dextrorfano/farmacologia , Agonistas de Aminoácidos Excitatórios , Ácido Caínico , Fármacos Neuroprotetores/farmacologia , Convulsões/prevenção & controle , Animais , Masculino , Camundongos , Camundongos Endogâmicos DBA , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Fator de Transcrição AP-1/metabolismoRESUMO
Norepinephrine turnover rates were estimated in the hypothalamus-thalamus, midbrain, pons-medulla and telencephalon of genetically epilepsy-prone rats (GEPR). In each of these 4 brain areas the endogenous norepinephrine levels were significantly lower in the GEPR than in control animals. In the hypothalamus-thalamus, midbrain and telencephalon the calculated norepinephrine turnover rates were also significantly lower in GEPRs than in control. These studies confirm and extend earlier observations relating seizures in the GEPR to decrements in central nervous system noradrenergic function.
Assuntos
Encéfalo/metabolismo , Epilepsia/metabolismo , Norepinefrina/metabolismo , Animais , Epilepsia/genética , Feminino , Masculino , Ratos , Ratos Mutantes , Distribuição TecidualRESUMO
Previous pharmacological studies have indicated the possible existence of functional interactions between opioidergic and dopaminergic neurons in the CNS. In this study, the expression of mRNAs encoding dopamine receptor D1/D2 was examined to investigate whether there is a change in the dopamine pathway of mice lacking the mu-opioid receptor by in situ hybridization technique. In the mu-opioid receptor knockout mice, the expression of dopamine receptor D1 mRNA was increased in the olfactory tubercle, nucleus accumbens, caudate putamen, and the layer VI of the neocortex compared with that of wild-type mice. The expression of dopamine receptor D2 mRNA was also increased in the olfactory tubercle, caudate putamen, and the nucleus accumbens of mu-opioid receptor knockout mice. These results indicate that there are compensational changes in the dopaminergic systems of mu-opioid receptor knockout mice.
Assuntos
Química Encefálica/genética , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores Opioides mu/genética , Animais , Expressão Gênica/fisiologia , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neocórtex/fisiologia , Neostriado/fisiologia , Núcleo Accumbens/fisiologia , Bulbo Olfatório/fisiologia , RNA Mensageiro/análiseRESUMO
Glucocorticoids have been implicated in the exacerbation of several types of neurotoxicity in various neuropathological situations. In this study, we investigated the effect of a glucocorticoid dexamethasone on glucose deprivation induced cell death of immunostimulated rat primary astrocytes, which is dependent on the production of peroxynitrite from the immunostimulated cells [Choi et al. Glia, 31(2001) 155-164; J. Neuroimmunol. 112 (2001) 55-62]. Glucose deprivation in immunostimulated rat primary astrocytes results in the release of lactate dehydrogenase (LDH) after 5 h and co-treatment with dexamethasone (1-1000 nM) dose-dependently increased LDH release. Treatment of the exogenous peroxynitrite generator SIN-1 (20 microM), plus glucose deprivation, also increased LDH release after 6 h and co-treatment with dexamethasone dose-dependently increased LDH release. A glucocorticoid receptor antagonist, RU-486, reversed the potentiation of cell death by dexamethasone. Glucose deprivation in immunostimulated cells decreased the intracellular ATP levels, which preceded LDH release from the cell, and co-treatment with dexamethasone dose-dependently potentiated the depletion of intracellular ATP levels. In addition, dexamethasone further deteriorated SIN-1 plus glucose deprivation-induced decrease in mitochondrial transmembrane potential in rat primary astrocytes, which was reversed by RU-486. The results from the present study suggest that glucocorticoids may be detrimental to astrocytes in situations where activation of glial cells are observed, including ischemia and Alzheimer's disease, by mechanisms involving depletion of intracellular ATP levels and deterioration of mitochondrial transmembrane potentials.
Assuntos
Astrócitos/citologia , Morte Celular/efeitos dos fármacos , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Glucose/farmacologia , Molsidomina/análogos & derivados , Ácido Peroxinitroso/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Morte Celular/fisiologia , Células Cultivadas , Antagonistas de Hormônios/farmacologia , Interferon gama/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mifepristona/farmacologia , Mitocôndrias/metabolismo , Molsidomina/farmacologia , Doadores de Óxido Nítrico/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Pretreatment of interferon-gamma and lipopolysaccharides made C6 glioma cells highly vulnerable to glucose deprivation. Neither 12 h of glucose deprivation nor 2-day treatment with interferon-gamma (100 U/ml) and lipopolysaccharides (1 microg/ml) altered the viability of C6 glioma cells. However, significant death of immunostimulated C6 glioma cells was observed after 5 h of glucose deprivation. The augmented death was prevented by dehydroepiandrosterone (DHEA) treatment during immunostimulation, but not by DHEA treatment during glucose deprivation. DHEA reduced the rise in nitrotyrosine immunoreactivity, a marker of peroxynitrite, and superoxide production in glucose-deprived immunostimulated C6 glioma cells. DHEA, however, did not protect glucose-deprived C6 glioma cells from the exogenously produced peroxynitrite by 3-morpholinosydnonimine. Further, DHEA did not alter the production of total reactive oxygen species and nitric oxide in immunostimulated C6 glioma cells. Superoxide dismutase (SOD) and the synthetic SOD mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin inhibited the death of glucose-deprived immunostimulated C6 glioma cells. In addition, a superoxide anion generator paraquat reversed the protective effect of DHEA on the augmented death. The data indicate that DHEA prevents the glucose deprivation-evoked augmented death by inhibiting the production of superoxide anion in immunostimulated C6 glioma cells.