RESUMO
Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.
Assuntos
Encéfalo/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Animais , Encéfalo/enzimologia , Humanos , FarmacocinéticaRESUMO
Adoptive immunotherapy requires the isolation of CD8+ T cells specific for tumor-associated antigens, their expansion in vitro and their transfusion to the patient to mediate a therapeutic effect. MUC1 is an important adenocarcinoma antigen immunogenic for T cells. The MUC1-derived SAPDTRPA (MUC1-8-mer) peptide is a potent epitope recognized by CD8+ T cells in murine models. Likewise, the T2 cell line has been used as an antigen-presenting cell to activate CD8+ T cells, but so far MUC1 has not been assessed in this context. We evaluated whether the MUC1-8-mer peptide can be presented by T2 cells to expand CD25+CD8+ T cells isolated from HLA-A2+ lung adenocarcinoma patients with stage III or IV tumors. The results showed that MUC1-8-mer peptide-loaded T2 cells activated CD8+ T cells from cancer HLA-A2+ patients when anti-CD2, anti-CD28 antibodies and IL-2 were added. The percentage of CD25+CD8+ T cells was 3-fold higher than those in the non-stimulated cells (P=0.018). HLA-A2+ patient cells showed a significant difference (2.3-fold higher) in activation status than HLA-A2+ healthy control cells (P=0.04). Moreover, 77.6% of MUC1-8-mer peptide-specific CD8+ T cells proliferated following a second stimulation with MUC1-8-mer peptide-loaded T2 cells after 10 days of cell culture. There were significant differences in the percentage of basal CD25+CD8+ T cells in relation to the cancer stage; this difference disappeared after MUC1-8-mer peptide stimulation. In conclusion, expansion of CD25+CD8+ T cells by MUC1-8 peptide-loaded T2 cells plus costimulatory signals via CD2, CD28 and IL-2 can be useful in adoptive immunotherapy.
Assuntos
Linfócitos T CD8-Positivos/citologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Epitopos de Linfócito T/metabolismo , Neoplasias Pulmonares/imunologia , Mucina-1/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Proliferação de Células , Feminino , Antígeno HLA-A2/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: We conducted a study evaluating the clinical and radiologic results of the open tibial shaft fractures using an external fixator as definitive treatment. METHODS: Clinical, observational, descriptive, prospective and longitudinal study. Forty-six patients were included, 40 males (87%) and 6 females (13%), whose age was 31.02 +/- 14.62 years; the time elapsed from the accident to admission in the Emergency Room was 1-16 hours, with a mean of 5.1 +/- 3.35 hours. Ten patients (21.74%) had a Gustilo grade I open fracture, and 36 patients (78.26%) a Gustilo grade II fracture. They were also classified according to the AO classification, with the following resulting groups: 13 (28.9%) patients were A3, 12 (26.1%) were B3, 8 (17.4%) B1, 8 (17.4%) were B2, and 5 (10.9%) were A2. The dynamization of the fixator was done at a mean of 11.56 +/- 1.10 weeks. RESULTS: Forty-three patients had healing at 23.51 +/- 3.62 weeks; Gustilo I fractures healed at 22.8 +/- 3.5 weeks; Gustilo II fractures at 23.7 +/- 3.7 weeks, with a P value of 0.48. In 3 patients (6.53%), due to absence of healing, the external fixator was exchanged for an intramedullary nail with a bone graft, with healing occurring at 18 weeks. Six infections (13%) were reported at the nail insertion site; angulations ranged from 0 degrees to 8 degrees, which is tolerable. CONCLUSIONS: This fixator is safe in properly selected patients, since the few complications that occurred are similar to other reports using different internal fixation methods.
Assuntos
Fixadores Externos , Fixação de Fratura/instrumentação , Fixação de Fratura/métodos , Fraturas Expostas/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas Expostas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fraturas da Tíbia/diagnóstico por imagem , Adulto JovemAssuntos
Colo do Útero/metabolismo , Fibronectinas , Glicoproteínas/análise , Trabalho de Parto Prematuro/diagnóstico , Vagina/metabolismo , Corticosteroides/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Peso ao Nascer , Feminino , Morte Fetal/diagnóstico , Morte Fetal/etiologia , Idade Gestacional , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/prevenção & controle , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade , Tocolíticos/uso terapêuticoAssuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Adulto , Colo do Útero , Glicoproteínas/análise , Trabalho de Parto Prematuro , Vagina , Corticosteroides , Antibacterianos/uso terapêutico , Peso ao Nascer , Morte Fetal , Idade Gestacional , Trabalho de Parto Prematuro , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tocolíticos/uso terapêuticoRESUMO
Glial glutamate receptors are likely to play a role in plasticity, learning, and memory and in a number of neuropathologies. An enhanced glutamate-dependent tyrosine phosphorylation has been detected in such processes. Using primary cultures of chick Bergmann glia cells and chick cerebellar slices, we addressed whether glial glutamate receptors can activate the nonreceptor tyrosine kinase pp125 focal adhesion kinase (pp125(FAK)). A dose- and time-dependent tyrosine phosphorylation of pp125(FAK) was found in both preparations upon glutamate treatment. This effect was mediated through alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)/kainate (KA) receptors, as shown by its inhibition by the specific antagonists 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7- sulfonamide (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the lack of effect of metabotropic agonists. FAK tyrosine phosphorylation was dependent on phosphatidylinositol 3-kinase activity. As expected, an increase in pp125(FAK) catalytic activity was found upon glutamate treatment. Immunprecipitation experiments demonstrated that FAK associates with ionotropic glutamate receptors. Taken together, these results suggest a role for glial glutamate receptors in cytoskeletal rearrengments and focal adhesion contact formation and provide new insight into the signaling transactions elicited by this neurotransmitter in glial cells.
Assuntos
Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Cerebelo/metabolismo , Ácido Glutâmico/metabolismo , Neuroglia/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptores de AMPA/metabolismo , Animais , Anticorpos/farmacologia , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/embriologia , Embrião de Galinha , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Relação Dose-Resposta a Droga , Proteína-Tirosina Quinases de Adesão Focal , Ácido Glutâmico/farmacologia , Immunoblotting , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Testes de Precipitina , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/efeitos dos fármacos , Receptores de AMPA/efeitos dos fármacos , Receptores de Ácido Caínico/efeitos dos fármacos , Receptores de Ácido Caínico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tirosina/metabolismoRESUMO
OBJECTIVE: To evaluate in a prospective trial two surgical technique routinely used for orbital decompression in Graves' disease ophthalmopathy. PATIENTS AND METHODS: Patients with Graves' disease exophthalmus (greater than 22 mm) that was euthyroid for at least six months after treatment were admitted to the study and randomly assigned to two groups, twenty six orbits in 17 patients were surgically decompressed with the Walsh and Ogura technique (group I) and 18 orbits in 18 patients were decompressed with Kennedy's surgical approach (group II). RESULTS: Both surgical techniques were equally effective in reducing the exophthalmus (p < 0.05). Morbility was significantly greater in terms of diplopia and infraorbital nerve lesion with Walsh and Ogura surgical approach. CONCLUSIONS: Due to reduced morbility, orbital surgical decompression with Kennedy's technique is recommended in patients with Graves' disease exofthalmus.
Assuntos
Descompressão Cirúrgica , Exoftalmia/etiologia , Exoftalmia/cirurgia , Doença de Graves/complicações , Órbita/cirurgia , Adulto , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
The objective of this article is to correlate a new biochemical method called fetal fibronectin (fFN) found in cervico-vaginal secretions (CVS) in pregnant woman with the presence or not of preterm labor. In this paper the patients studied had pregnancies of 24 up to 37 weeks of pregnancy. The were free of symptoms and without risk factors for preterm labor. The cervico-vaginal specimen was taken with special equipment designed for this purpose (Adeza Biomedical Collection Kit). The laboratory processed this for immunoassay. A positive fFN was considered above 0.05 microgram/dl. There were 263 patients enrolled for this study. Of these 232 had fFN negative (89%) and 31 were positive (12%). The weeks of gestation at birth were 38.6 for the negative group and 34.4 for the positive group (p < 0.0001). Only 5 neonates from the negative group were born before 37 weeks of gestation (2.2%) and in the positive fFN group this occurred in 22 case (71%) (p < 0.0001). The average weight at birth for the negative fibronectin group was 3152 g. for the positive group (p < 0.0001). The neonatal morbidity was more frequent and respiratory distress syndrome was more severe in the positive fibronectin group in comparison with the negative fFN with a significant p. The same tendency was observe with the Apgar score < 7 at 1 and 5 minutes (more frequent in the positive group) (p < 0.0001). The was one neonatal death in the negative group (0.43%) and 5 in the positive group (16%) p = 0.0001. The sensibility and positive predicitive value of positive fFN for the prediction of preterm labor was 81.4 and 71 respectively and the specificity and negative predictive value for negative fFN was 96.1 and 97.8. Finally the RR for prematurity when the fFN was positive on SCV was 32.9. The presence fFN in cervical-vaginal secretion between 24 and 37 weeks of gestation seems to be a good indicator of preterm labor. In this study positive results correlate with less weeks of pregnancy and lees weight at birth. Also with higher with more morbidity and mortality. These findings give the obstetrician a better chance of an opportune diagnosis with adequate treatment and improve perinatal results.
Assuntos
Colo do Útero/metabolismo , Feto/química , Fibronectinas/análise , Trabalho de Parto Prematuro/diagnóstico , Complicações na Gravidez/diagnóstico , Vagina/metabolismo , Adulto , Colo do Útero/química , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Vagina/química , Esfregaço VaginalRESUMO
Twins, specially those of monochorionic and monoamniotic pregnancies, are exposed to many perinatal risks and complications. The objective of this study was to evaluate the usefulness of ultrasonographic determination of the chorionicity of human placental by counting the number of layers in amniotic membranes. Thirty-eight patients with twin pregnancies were studied prospectively. The ultrasonographic evaluation of membranes layers was made only once, between the weeks and 16 and 30 of pregnancy. When two layers were identified, the placentation was determined as monochorionic, and when four layers were seen, the diagnosis of bichorionic placentation was made. The type of chorionicity was confirmed by histologic study of the placenta. With ultrasound, the chorionicity was correctly determined in 36 out of 38 cases, for a total predictive value of 94.6%. The capacity for diagnosing bichorionic (4 layers) placentation was 100% (22/22) and 87.6% (14/16) for monochorionic (2 layers) placentation. The ultrasonographic evaluation of the amniotic membranes number is an efficient method to recognize the chorionicity of placenta and constitutes an useful and simple method giving important information in perinatal prognosis.
Assuntos
Córion/diagnóstico por imagem , Gravidez Múltipla , Ultrassonografia Pré-Natal , Feminino , Idade Gestacional , Humanos , Placentação , Gravidez , Estudos Prospectivos , GêmeosRESUMO
The presence of oligohydramnios evaluated by accumulation or major pool technique in pre-term PMR is strongly correlated with maternal and perinatal infection. The objective of this study is to evaluate the usefulness of amniotic fluid volume rate (AFVR) in prediction of maternal and fetal-neonatal infection in patients with PMR before 37 weeks. Thirty patients with PMR were prospectively studied. AFVR was done in all the patients at the time of arrival and they were managed conservatively. None of them had utero-inhibitors and only antibiotics were used after chord clamping. In absence of intrauterine infection corticotherapy was allowed. The results of AFVR were correlated with maternal infection (chorioamnioitis) and perinatal (possible neonatal sepsis or neonatal sepsis). Twenty three out of 30 patients (76.6%) had a AFVR less than or equal to 5.0 cm. (Oligohydramnios) and seven (30.4%) showed a greater rate than 5.0 cm. The earliest pregnancy was 26.5 weeks and the greatest 34.4 weeks. Out of the total of patients 13 (43.3%) had chorioamnioitis and all correspond to the group with AFVI smaller or equal to 5.0 cm. In the group with oligohydramnios were 15 neonates (65.2%) with neonatal infection (six possible sepsis and nine neonatal sepsis). All neonates with positive cultures also corresponded to the group with smaller AFVR; the comparison among the cases with oligohydramnios with infection and the ones that had normal AFVR without infection has statistical significance (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)