RESUMO
Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.
Assuntos
Antígenos CD8/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Fatores de Transcrição Forkhead/imunologia , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Tolerância a Radiação/imunologia , Adolescente , Adulto , Idoso , Quimiorradioterapia/métodos , Metilação de DNA , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Microambiente Tumoral/imunologia , Proteínas Virais/imunologia , Adulto JovemAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Eosinofilia/induzido quimicamente , Eritema/induzido quimicamente , Pneumonia Viral/complicações , Idoso , COVID-19 , Infecções por Coronavirus/virologia , Humanos , Masculino , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/radioterapia , Modelos Teóricos , Radioterapia Adjuvante , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Intervalo Livre de Progressão , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Multiple Sclerosis (MS) is one of the leading causes of disability in young adults. Its prevalence varies according to different countries. In Argentina there is a wide heterogeneity regarding data published in different areas of the country. Prevalence established in most studies is 17 cases per 100,000 inhabitants; however, most of the available data comes from studies that took place in Buenos Aires. There is little or no information from other provinces, especially from Northwest of Argentina (NOA), where there are no studies of the disease prevalence. The aim of this study is to investigate MS prevalence, phenotypes and epidemiological characteristics in Salta, Argentina, in order to contribute to the current knowledge of MS epidemiology and distribution in our country. METHODS: A descriptive, observational, transversal study was carried out in the capital city of Salta. Researchers from all public and private hospitals with a Neurology Department have participated. Private researchers who are well known leaders in demyelinating diseases in the city provided valuable information. Patients who did not have medical control for the past two years as well as patients whose last address was not registered in Salta were excluded. RESULTS: 120 registries were obtained from the four hospitals that participated and from the 12 private researchers. Ten patients were excluded due to overlapping data. The population of the area based on 2010 census was 535,310, so we estimated an MS prevalence 23.8 cases per 100,000 inhabitants (95% CI 20.1-27.4), 24.1 cases per 100,000 inhabitants in female population (95% CI 21.2-28.6) and 18.2 cases per 100,000 inhabitants (95% CI 15.2-21.1) in male population. In our analysis, 64 (58.2%) were female and the average age was 42.1 years. 81.8% are recurrent remitting forms, 16.4% secondary progressive and 1.8% primary progressive. CONCLUSION: This is the first study that provides epidemiological data on the prevalence and clinical forms of MS in Salta City as well as in the entire Northwest Region of Argentina(NOA). We estimate a prevalence of 23.8 cases per 100,000 inhabitants, which establishes a moderate risk area for MS.
Assuntos
Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Argentina/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
PURPOSE: To assess kinetics of plasmatic cytokines during radiation therapy (RT) for locally advanced and early-stage non-small cell lung cancer (NSCLC). METHODS: This prospective study was conducted on 15 early-stage NSCLC underwent to extreme hypofractionated regimen (52 Gy in 8 fractions) with stereotactic body RT (SBRT), and 13 locally advanced NSCLC underwent to radical moderated hypofractionated regimen (60 Gy in 25 fractions) with intensity modulated RT (IMRT). For patients undergoing SBRT, peripheral blood samples were collected on the first day of SBRT (TFd), the last day (TLd) and 45 days (T45d) after the end of SBRT. For patients undergoing IMRT, blood samples were collected at: TFd, 2 weeks (T2w), 4 weeks (T4w), TLd, and T45d. The following cytokines were measured: IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, EGF, FGF-2, INF-γ, MIP-1α, MIP-1ß, TGF-α, TNF-α, and VEGF. Cytokine levels measured in different RT time and compared. RESULTS: No difference in baseline levels of cytokines was documented between patient radiation approaches (except for MIP-1α). For SBRT patients, a mean reduction of IL-10 and IL-17 plasma level was documented between TLd and TFd, respectively (p < 0.05). For IMRT patients, a statistically significant (p < 0.05) mean plasma level reduction was documented between T4w and TFd for all the following cytokines: IL-1, IL-1ra, IL-2, IL-12, FGF-2, MIP-1α, MIP-1ß, TGF-α, TNF-α, VEGF. CONCLUSIONS: SBRT and IMRT induce different plasmatic cytokine changes in NSCLC patients, supporting hypothesis that RT regimes of dose schedules and techniques have different impacts on the host immune response.
Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Citocinas/sangue , Neoplasias Pulmonares/sangue , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: To derive Normal Tissue Complication Probability (NTCP) models for severe patterns of early radiological radiation-induced lung injury (RRLI) in patients treated with radiotherapy (RT) for lung tumors. Second, derive threshold doses and optimal doses for prediction of RRLI to be used in differential diagnosis of tumor recurrence from RRLI during follow-up. METHODS AND MATERIALS: Lyman-EUD (LEUD), Logit-EUD (LogEUD), relative seriality (RS) and critical volume (CV) NTCP models, with DVH corrected for fraction size, were used to model the presence of severe early RRLI in follow-up CTs. The models parameters, including α/ß, were determined by fitting data from forty-five patients treated with IMRT for lung cancer. Models were assessed using Akaike information criterion (AIC) and area under receiver operating characteristic curve (AUC). Threshold doses for risk of RRLI and doses corresponding to the optimal point of the receiver operating characteristic (ROC) curve were determined. RESULTS: The α/ßs obtained with different models were 2.7-3.2 Gy. The thresholds and optimal doses curves were EUDs of 3.2-7.8 Gy and 15.2-18.1 Gy with LEUD, LogEUD and RS models, and µd of 0.013 and 0.071 with the CV model. NTCP models had AUCs significantly higher than 0.5. Occurrence and severity of RRLI were correlated with patients' values of EUD and µd. CONCLUSIONS: The models and dose levels derived can be used in differential diagnosis of tumor recurrence from RRLI in patients treated with RT. Cross validation is needed to prove prediction performance of the model outside the dataset from which it was derived.
Assuntos
Lesão Pulmonar Aguda/etiologia , Neoplasias Pulmonares/radioterapia , Modelos Estatísticos , Lesões por Radiação/etiologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Risco , SegurançaRESUMO
Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with underlying systemic diseases. Treatment usually consists of topics and sometimes systemic immunosuppression. We present the case of a 32-year-old female patient undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in which immunosuppressive measures were ineffective to control the disease. Treatment outcome was favourable with only mild side effects in the irradiated areas. Localized radiation therapy hence is a potential effective palliation for refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive systemic immunosuppression.
Assuntos
Braquiterapia , Pioderma Gangrenoso/radioterapia , Radioterapia de Alta Energia , Adulto , Anticorpos Monoclonais/uso terapêutico , Doenças do Sistema Nervoso Autônomo/complicações , Braquiterapia/instrumentação , Braquiterapia/métodos , Cicatriz/patologia , Cicatriz/radioterapia , Terapia Combinada , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Relação Dose-Resposta à Radiação , Resistência a Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Infliximab , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/tratamento farmacológico , Espondilite Anquilosante/complicações , Resultado do TratamentoRESUMO
Tolosa-Hunt syndrome (THS) is characterized by unilateral painful ophthalmoplegia with oculomotor paresis, associated with an idiopathic granulomatous inflammation involving the cavernous sinus, with a typical relapsing-remitting course. We report a case of an 8-year-old girl who was admitted because of an ophthalmoplegia with exotropia and ptosis of the left eyelid, accompanied by diplopia and left sovraorbital pain. The clinical data, neuroradiological findings and response to steroid treatment suggested THS, as defined by the 2004 International Classification of Headache Disorders (ICHD)-II criteria. THS must be considered a possible cause of painful ophthalmoplegia in childhood, as well as in adults, and confirmed with a focused neuroradiological investigation. The few paediatric cases described in the literature that meet the 2004 ICHD-II criteria are not sufficient to identify possible differences between the paediatric and the adult forms. Every new paediatric case should therefore be reported in order to gather and compare further information.
Assuntos
Síndrome de Tolosa-Hunt/fisiopatologia , Anti-Inflamatórios/uso terapêutico , Blefaroptose/etiologia , Seio Cavernoso/patologia , Criança , Dexametasona/uso terapêutico , Diplopia/etiologia , Exotropia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Oftalmoplegia/etiologia , Síndrome de Tolosa-Hunt/complicações , Síndrome de Tolosa-Hunt/tratamento farmacológicoRESUMO
Sodium phosphate enemas and laxatives are widely used for the treatment of constipation, even if a number of cases of significant toxicity due to alterations of the fluid and electrolyte equilibria (hypernatremia, hyperphosphatemia, and hypocalcemia) have been reported. We present the case of an 83-year-old man who died of fecal and chemical peritonitis secondary to an iatrogenic colon perforation (produced performing a Fleet enema through the patient's iliac colostomy) with peritoneal absorption of sodium phosphate. Environmental scanning electron microscopy coupled with an X-ray fluorescence energy dispersive spectrometry discovered multiple bright crystals formed of calcium, phosphorus, and oxygen in the brain, heart, lung, and kidney sections of the victim. The absence of these kinds of precipitates in two control samples chronically treated with Fleet enemas led us to assume that the deceased had adsorbed a great quantity of phosphorus ions from the peritoneal cavity with subsequent systemic dissemination and precipitation of calcium phosphate bindings.
Assuntos
Catárticos/farmacocinética , Enema/efeitos adversos , Microscopia Eletrônica de Varredura , Fosfatos/farmacocinética , Espectrometria por Raios X , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Cálcio/metabolismo , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Colo/lesões , Cristalização , Patologia Legal , Humanos , Doença Iatrogênica , Perfuração Intestinal/etiologia , Rim/metabolismo , Rim/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Oxigênio/metabolismo , Peritonite/etiologia , Fosfatos/administração & dosagem , Fosfatos/efeitos adversos , Fósforo/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate beta(1)-adrenoceptors (beta(1)-AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease. MATERIAL AND METHODS: Flow cytometry and enzyme-linked immunosorbent assay using cell culture-adherent gingival fibroblasts and/or their purified membranes and/or a synthetic peptide corresponding to the second extracellular loop of human beta(1)-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE(2) generation and CD40 expression were also tested. RESULTS: Circulating immunoglobulin G (IgG) from chronic periodontal disease patients (but not from normal individuals) interacted with the fibroblast surface, activating beta(1)-AR. Atenolol or CGP 20712 (beta 1-AR antagonists) and beta(1) synthetic peptide inhibited the interaction of IgG with beta(1)-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific beta(1)-AR activation, increasing PGE(2) generation and CD40 overexpression. The corresponding affinity-purified anti-beta(1)-AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo-oxygenase. CONCLUSION: This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE(2) and CD40 expression) is induced as a consequence of antibody-beta(1)-AR interaction. The PGE(2)-CD40-IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.
Assuntos
Autoanticorpos/imunologia , Antígenos CD40/biossíntese , Periodontite Crônica/imunologia , Dinoprostona/metabolismo , Receptores Adrenérgicos beta 1/imunologia , Formação de Anticorpos , Biofilmes , Membrana Celular/imunologia , Células Cultivadas , Periodontite Crônica/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/imunologia , Fibroblastos/metabolismo , Citometria de Fluxo , Gengiva/citologia , Gengiva/imunologia , Humanos , Imunoglobulina G/imunologia , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular/imunologia , Regulação para CimaRESUMO
BACKGROUND AND AIM: Acute hepatitis B course may be significantly modified by underlying chronic hepatitis C. The aim of this study was to compare clinical and virological characteristics of acute hepatitis B in patients with or without chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS: Twenty-seven patients with symptomatic acute hepatitis B were enrolled: 14 with underlying chronic HCV (Group A) and 13, matched by age and gender, with single hepatitis B (Group B). All patients were followed-up until HBsAg negativization. RESULTS: Group A patients were HCV-RNA-negative on hospital admission and all but one remained negative during follow-up. HBeAg tested positive in 92.9% and 84.6% of Groups A and B patients, respectively. ALT, bilirubin, prothrombin time values and HBsAg titer were similar in both groups. Nevertheless, lower mean HBV-DNA levels (p=0.03), a shorter duration of HBsAg positivity (p<0.01) and of symptoms before ALT peak (p=0.014), and significantly lower peak ALT values (p=0.03) were observed in Group A compared to Group B patients. CONCLUSIONS: Acute HBV infection suppressed HCV replication. Conversely, the underlying HCV infection exerted a modulatory effect on HBV replication which influenced the course, though not the outcome, of the acute disease. Although acute hepatitis B showed a mild clinical course in both groups of patients, HBV vaccination should be suggested to risk subjects.
Assuntos
Anticorpos Anti-Hepatite B/imunologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite C/imunologia , Hepatite C Crônica/imunologia , RNA Viral/análise , Superinfecção/virologia , Replicação Viral , Doença Aguda , DNA Viral/imunologia , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/complicações , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Masculino , RNA Viral/imunologia , Estudos Soroepidemiológicos , Superinfecção/epidemiologiaRESUMO
Oligodendroglioma cells are detectable in the cerebro-spinal fluid in up to 14% of patients [10] and cerebellar and/or spinal cord involvement is a well known phenomenon [3]. Distant spread of oligodendroglioma is exceptional, probably due to the presence of the blood-brain barrier, the absence of lymphatic vessels and the short survival of patients. A review of the worldwide literature yielded 32 previously reported examples since 1951 to the present (Tab1e 1). This review was performed using NCBI-PubMed and "oligodendroglioma, oligodendrogliomas, metastatic, metastasis, metastases, extraneural", in different combinations, as key words and reviewing the bibliography of the consequent selected articles. New therapeutic approaches are prolonging the overall survival of patients with primitive brain tumours and in particular of those with high grade oligodendroglioma which is a chemo-sensitive disease. A longer overall survival could increase the risk of extracranial dissemination of gliomas that in the future might become a less rare clinical complication.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Hepáticas/secundário , Lobo Occipital , Oligodendroglioma/secundário , Lobo Parietal , Adulto , Evolução Fatal , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Oligodendroglioma/diagnóstico , Oligodendroglioma/patologiaRESUMO
AIM: To investigate the role of muscarinic acetylcholine receptor (mAChR) subtype activity in the regulation of endothelial- (e) and neuronal- (n) nitric oxide synthase (NOS) expression and activity. METHODOLOGY: Rat dental pulp tissue was used throughout the study. The e-nos and n-nos mRNA levels were specifically measured using reverse transcriptase polymerase chain reaction procedures that involve simultaneous co-amplification of both target cDNA and a reference template with a single set of primers. NOS activity was measured by the production of [U-(14)C]-citrulline from [U-(14)C]-arginine. RESULTS: Stimulation of M(1)/M(2) and M(3)/M(4) mAChRs with pilocarpine caused an increase in e-nos and n-nos mRNA levels and NOS activity in the dental pulp. The specific mAChR subtype antagonists, L-NMMA, l-NIO and N(2)-propyl-L-arginine but not aminoguanidine attenuated all these effects. Inhibitors of phospholipase C (PLC), protein kinase C (PKC) and calcium/calmodulin (CaM) prevented the pilocarpine-dependent increase in n-nos and e-nos mRNA levels and NOS activity. CONCLUSIONS: Activation of mAChR subtypes stimulated NOS activity by increasing the production of NO through e-nos and n-nos gene expression and NOS activity. The mechanism appears to occur secondarily to stimulation of CaM and PKC enzymatic activity.
Assuntos
Polpa Dentária/metabolismo , Neurotransmissores/análise , Óxido Nítrico Sintase/análise , Óxido Nítrico/análise , Receptores Muscarínicos/fisiologia , Transdução de Sinais/fisiologia , Animais , Arginina/farmacologia , Calmodulina/antagonistas & inibidores , Polpa Dentária/enzimologia , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Masculino , Agonistas Muscarínicos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/análise , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/análise , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Ornitina/análogos & derivados , Ornitina/farmacologia , Pilocarpina/farmacologia , Proteína Quinase C/antagonistas & inibidores , Ratos , Ratos Wistar , Receptores Muscarínicos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/antagonistas & inibidores , ômega-N-Metilarginina/farmacologiaRESUMO
Psidium guajava 'Paluma' saplings were exposed to carbon filtered air (CF), ambient non-filtered air (NF), and ambient non-filtered air+40ppb ozone (NF+O(3)) 8h per day during two months. The AOT40 values at the end of the experiment were 48, 910 and 12 895ppbh(-1), respectively for the three treatments. After 5 days of exposure (AOT40=1497ppbh(-1)), interveinal red stippling appeared in plants in the NF+O(3) chamber. In the NF chamber, symptoms were observed only after 40 days of exposure (AOT40=880ppbh(-1)). After 60 days, injured leaves per plant corresponded to 86% in NF+O(3) and 25% in the NF treatment, and the average leaf area injured was 45% in NF+O(3) and 5% in the NF treatment. The extent of leaf area injured (leaf injury index) was explained mainly by the accumulated exposure of ozone (r(2)=0.91; p<0.05).
Assuntos
Oxidantes Fotoquímicos/análise , Ozônio/análise , Psidium/química , Brasil , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental/métodos , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Psidium/efeitos dos fármacos , Clima TropicalRESUMO
The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.
Assuntos
Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Açúcares de Nucleosídeo Difosfato/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismo , Sequência de Aminoácidos , Animais , Transporte Biológico , Glicosilação , Humanos , Dados de Sequência Molecular , Açúcares de Nucleosídeo Difosfato/química , Açúcares de Nucleosídeo Difosfato/genética , Proteínas de Transporte de Nucleotídeos/química , Proteínas de Transporte de Nucleotídeos/genética , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.
Assuntos
Humanos , Animais , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Açúcares de Nucleosídeo Difosfato/metabolismo , Proteínas de Transporte de Nucleotídeos/metabolismo , Sequência de Aminoácidos , Transporte Biológico , Glicosilação , Dados de Sequência Molecular , Açúcares de Nucleosídeo Difosfato/síntese química , Açúcares de Nucleosídeo Difosfato/genética , Proteínas de Transporte de Nucleotídeos/química , Proteínas de Transporte de Nucleotídeos/genética , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
1 The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChR) on DNA synthesis and CD40 expression in human fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with carbachol in presence or absence of specific antagonists and the following parameters were measured: identification of mAChR subtypes, DNA synthesis, inositol phosphates (InsP) production and CD40 expression. 2 Human fibroblasts express mAChR with Kd 0.47 +/- 0.11 nm and Bmax 236 +/- 22 fmol mg protein(-1). Carbachol stimulates DNA synthesis, InsP and the expression of CD40. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine but not by AF-DX 116 and tropicamide, indicating that M3 and M1 mAChR are implicated in carbachol action. The relative Ki of the antagonists obtained by competition binding assay was in parallel to the relative potency for blocking both carbachol-stimulated InsP accumulation and DNA synthesis. 3 The intracellular pathway leading to carbachol-induced biological effects involved phospholipase C and calcium/calmodulin, as U-73122 and trifluoroperazine blocked carbachol effects, respectively. Calphostin C, a protein kinase C inhibitor, had no effect, indicating that this enzyme does not participate in the system. 4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function.
Assuntos
Antígenos CD40/biossíntese , DNA/biossíntese , Fibroblastos/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Atropina/farmacologia , Calmodulina/antagonistas & inibidores , Calmodulina/metabolismo , Carbacol/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Estrenos/farmacologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Fosfatos de Inositol/metabolismo , Antagonistas Muscarínicos/farmacologia , Pirenzepina/farmacologia , Pirrolidinonas/farmacologia , Quinuclidinil Benzilato , Ensaio Radioligante , Receptor Muscarínico M1/análise , Receptor Muscarínico M1/efeitos dos fármacos , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M3/análise , Receptor Muscarínico M3/efeitos dos fármacos , Receptor Muscarínico M3/metabolismo , Receptores Muscarínicos/análise , Receptores Muscarínicos/metabolismo , Trifluoperazina/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismoRESUMO
PURPOSE: The purpose of this study was to evaluate cortical activation patterns in patients with Parkinson's disease during a relatively complex motor task. MATERIALS AND METHODS: Seven patients (six men and one woman) with lateralised akinetic-rigid Parkinson's disease underwent functional magnetic resonance imaging (MRI) of the brain with a 1.5-T magnet. Finger tapping was chosen as a motor task. The control group included 11 volunteers (six men and five women) with no neurological disease. RESULTS: Patients showed hyperactivity of the ipsilateral and contralateral motor cortex associated with bilateral over-activation of the parietal cortex during movement of the affected hand. In some cases, there was a lack of activation of the pre-motor and supplementary motor areas whereas, when present, activation in these areas was greater during movement of the healthy hand. Finally, activation of the occipital cortex was found in all patients as a result of their tendency to control movement visually. CONCLUSIONS: Results of this study confirm a re-organisation of cortical circuits due to subcortical damage in patient's with Parkinson's disease.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Imageamento por Ressonância Magnética , Doença de Parkinson/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Córtex Motor/fisiopatologia , Desempenho PsicomotorRESUMO
Psidium guajava L., Psidium cattleyanum Sabine and Mangifera indica L. were tested under field conditions as possible tropical bioindicators of industrial air pollution. The study was performed around the industrial complex of Cubatão, SE Brazil, which comprises 23 industries, including fertilizer, cement, chemical, petrochemical, and steel plants, with 110 production units and 260 emission sources of pollutants. Saplings were exposed to environmental conditions during four periods of 16 weeks each (September 1994-September 1995), at four different sites in the coastal mountains near the industrial complex: the Valley of Pilões River (VP), the reference area; the Valley of Mogi River (VM), with high contamination of particulate matter, fluorides (F), sulfur (S) and nitrogen (N) compounds; Caminho do Mar (CM1, CM2), mainly affected by organic pollutants, S and N compounds, and secondary pollutants; and Paranapiacaba (PP), affected by secondary pollutants, such as ozone. M. indica did not adapt to the climatic conditions at the exposure sites. In the two Psidium species, the presence of visible symptoms, root/shoot ratio, foliar contents of F, S and N, amounts of ascorbate (AA) and water-soluble thiols (-SH), as well as peroxidase activity (POD) were determined. P. guajava showed higher foliar accumulation of F, S and N, more pronounced alterations of biochemical indicators, and less visible leaf injury than P. cattleyanum. P. guajava may be used as an accumulative indicator in tropical climates, while further studies will be needed before P. cattleyanum might be applied as a sensitive species in biomonitoring programs.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Monitoramento Ambiental/métodos , Mangifera , Psidium , Poluentes Atmosféricos/análise , Brasil , Indústrias , Mangifera/fisiologia , Folhas de Planta/química , Psidium/fisiologia , Sensibilidade e Especificidade , Clima TropicalRESUMO
The present study was designed to investigate the putative anxiolytic effects of moclobemide (MOC), a reversible inhibitor of type A monoamine oxidase enzyme (RIMA) antidepressant, in an experimental model of anxiety in mice. The test selected was the light/dark aversion test. In the present investigation, an anxiogenic-like behavior was induced by light, alone as the stimulus (standard version of the test) or by pretreatment with a subconvulsant dose of pentylenetetrazole (PTZ) (15 mg/kg IP) 45 min before testing ("enhanced" version of the test). In mice, the effect of repeated administration for 2 weeks of MOC (0.5, 1, and 5 mg/kg IP) was compared with those of selegiline (SEL) (5, 10, and 20 mg/kg IP), an irreversible and selective MAO-B inhibitor. For comparative purpose, the chronic effect of an established reference anxiolytic, such as lorazepam (LOR) (0.025, 0.05, and 0.10 mg/kg IP), was also evaluated. Results demonstrated that PTZ-treated mice showed a decrease in the number of transitions as well as in the time spent in the lit area, when compared with vehicle controls, an effect characteristic of an anxiogenic response. This anxiogenic-like behavior was reduced by chronic administration of LOR as well as MOC, suggesting an anxiolytic-like effect (as shown in the "standard" version of the test). In addition, the increased aversion of mice for the light compartment of the light/dark box was significantly reduced compared to PTZ-treated mice or vehicle controls. SEL failed to significantly alter the anxiogenic-like behavior induced by subconvulsant doses of PTZ. These data provide additional evidence for the anxiolytic-like effects of MOC administered chronically in the mouse.