RESUMO
BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.
Assuntos
Betacoronavirus/isolamento & purificação , Pérnio/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Betacoronavirus/genética , Betacoronavirus/imunologia , Biópsia , COVID-19 , Teste para COVID-19 , Pérnio/sangue , Pérnio/imunologia , Pérnio/patologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , França/epidemiologia , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , SARS-CoV-2 , Testes Sorológicos , Pele/patologia , Adulto JovemRESUMO
Dermatomyositis is an idiopathic inflammatory myopathy with various clinical and serological profiles, including poor prognosis forms for which aggressive immunosuppressive treatment is warranted. We report the case of a 60-year-old woman referred to our hospital for an anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis (MDA5 DM) with rapidly progressive interstitial pneumonia, typical cutaneous features and muscular impairment. Treatment with high-dose methylprednisolone, cyclophosphamide and gamma globulin was performed, but the patient remained corticodependant. Blood detection of positive interferon signature justified the administration of an anti-JAK1/2, leading to the clinical remission and the regression of the interferon signature. After 12 months of follow up, a small cell carcinoma was discovered, raising the question of a paraneoplastic syndrome, for which the most recent datas are quite reassuring for this kind of MDA5 DM. The presentation of this case is of twofold interest: describing one of the first report of successful treatment of intereronopathy MDA5 DM with ruxolitinib and highlighting an association with a cancer, which is not expected for this phenotype of dermatomyositis.
Assuntos
Autoanticorpos/efeitos adversos , Dermatomiosite/tratamento farmacológico , Helicase IFIH1 Induzida por Interferon/imunologia , Inibidores de Janus Quinases/uso terapêutico , Síndromes Paraneoplásicas/tratamento farmacológico , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Evolução Fatal , Feminino , Humanos , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/imunologia , Índice de Gravidade de Doença , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
PURPOSE: The purpose of this study was to retrospectively compare microwave (MWA) and radiofrequency (RFA) ablation in the percutaneous treatment of primary and secondary lung tumors. MATERIAL AND METHODS: A total of 115 patients with a total of 160 lung tumors (primary, n=41; secondary, n=119) were retrospectively included. There were 56 men and 59 women with a mean age of 67.8±12.7 (SD) years (range: 42-89 years) who underwent either MWA (61 patients; 79 tumors) or RFA (54 patients; 81 tumors). The primary study endpoints were local recurrence during follow-up and the incidence of complications during and following thermal ablation. The MWA and RFA groups were compared in terms of treatment efficacy and complication rates. RESULTS: Demographics were similar in the two groups. Mean tumor diameter was smaller in RFA group (13.1±5.1 [SD] mm; range: 4-27mm) than in MWA group (17.1±8.3 [SD] mm; range: 5-36mm) (P<0.001). Ablation volumes at one month were 24.1±21.7 (SD) cm3 (range: 2-97.8 cm3) in RFA group and 30.2±35.9 (SD) cm3 (range: 1.9-243.8 cm3) in MWA group (P=0.195). During a mean overall follow-up duration of 488±407 (SD) days (range: 30-1508 days), 9/160 tumors (5.6%) developed local recurrence: six (6/79; 7.6%) in the RFA group and three (3/81; 3.7%) in the MWA group (P=0.32). Pneumothoraces were more frequent in the RFA group (32/79; 40.5%) than in the MWA group (20/81; 24.7%) (P=0.049). The mean length of hospital stay was 4.5±3.7 (SD) days (range: 1-25 days) in the RFA group and 4.7±4.6 (SD) days (range: 2-25 days) in the MWA group (P=0.76). CONCLUSIONS: MWA favorably compares with RFA and can be considered as an effective and safe thermal ablation technique for lung tumors, especially in situations where RFA has limited efficacy.
Assuntos
Técnicas de Ablação , Neoplasias Pulmonares/terapia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pneumotórax/etiologia , Estudos RetrospectivosRESUMO
Tumor heterogeneity in ovarian cancer has been reported at the histological and genetic levels and is associated with adverse clinical outcomes. Tumor evaluation using standard computed tomography or magnetic resonance imaging techniques does not account for the intra- or inter-tumoral heterogeneity in advanced ovarian cancer with peritoneal carcinomatosis. As such, computational approaches in assessing tumor heterogeneity have been proposed using radiomics and radiogenomics in order to analyze the whole tumor heterogeneity as opposed to single biopsy sampling. As part of radiomics, texture analysis, which includes the extraction of multiple data from images has been proposed recently to evaluate advanced ovarian tumor heterogeneity. In this short review, we explain the basics of radiomics, how to perform texture analysis, and its applications to ovarian cancer imaging.
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Aumento da Imagem/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Genômica , Humanos , Neoplasias Ovarianas/genéticaRESUMO
BACKGROUND: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. OBJECTIVE: Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. METHODS: Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. RESULTS: Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. CONCLUSION: In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Ritmo Delta/fisiologia , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Criança , Pré-Escolar , Diagnóstico Precoce , Eletroencefalografia , Feminino , Humanos , Masculino , Fenótipo , Estudos Retrospectivos , Convulsões/complicaçõesRESUMO
Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.
Assuntos
Ataxia/genética , Neoplasias Encefálicas/genética , Calcinose/genética , Cistos do Sistema Nervoso Central/genética , Leucoencefalopatias/genética , Espasticidade Muscular/genética , Doenças Retinianas/genética , Convulsões/genética , Proteínas de Ligação a Telômeros/genética , Adolescente , Ataxia/fisiopatologia , Neoplasias Encefálicas/fisiopatologia , Calcinose/fisiopatologia , Cistos do Sistema Nervoso Central/fisiopatologia , Retardo do Crescimento Fetal/genética , Hemorragia Gastrointestinal/etiologia , Genes Recessivos/genética , Humanos , Leucoencefalopatias/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Espasticidade Muscular/fisiopatologia , Mutação/genética , Doenças Retinianas/fisiopatologia , Convulsões/fisiopatologiaRESUMO
INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is little known to pediatricians and likely underdiagnosed. The child's vital and cognitive prognosis is at stake. The use of immunomodulatory drugs, such as rituximab has led to spectacular results, but many questions remain about its mode of action in this type of pathology. CASE REPORT: We report the case of a 6-year-old girl with no medical history, admitted for status epilepticus preceded by behavior symptoms and sleep disorders. Gradually, the child became bedridden, mute, and animated by predominantly orofacial dyskinesia. Examinations were normal (cerebrospinal fluid [CSF] analysis, brain MRI). The diagnosis was established by the presence of NMDA-R antibodies in the CSF. After exclusion of a tumor-associated syndrome, treatment was started initially by intravenous immunoglobulins, then by plasma exchange, and finally rituximab. The patient was cured with rituximab despite an unusually early recovery of the B-cell pool. DISCUSSION: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe but potentially reversible neurologic disorder only recently described, even in childhood. It may be reversible without sequelae if diagnosed and treated early. The use of immunomodulatory therapy, such as rituximab seemingly improves the outcome. Immunological monitoring is needed to better understand its mechanism of action in autoimmune diseases of the nervous system in childhood.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Anticorpos/líquido cefalorraquidiano , Anticorpos Monoclonais Murinos/uso terapêutico , Criança , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Troca Plasmática , Receptores de N-Metil-D-Aspartato/imunologia , RituximabRESUMO
OBJECTIVES: To differentiate onset of CNS involvement in primary hemophagocytic lymphohistiocytosis (HLH) from that of other CNS inflammatory diseases and to identify early symptoms linked to abnormal cognitive outcome. METHODS: Forty-six children with primary HLH who had neurologic evaluation within 2 weeks and brain MRI within 6 months of diagnosis were included. Initial symptoms, CSF study, brain MRI, and neurologic outcome were assessed. Brain MRIs were compared with those of 44 children with acute disseminated encephalomyelitis (ADEM). RESULTS: At disease onset, 29 children (63%) had neurologic symptoms and 7 (15%) had microcephaly. Twenty-three (50%) children had abnormal CSF study, but only 15 (33%) had abnormal brain MRI. The latter showed that patients with HLH, unlike patients with ADEM, had symmetric periventricular lesions, without thalamic and brainstem involvement and with infrequent hyposignal intensity on T1. At the end of follow-up (3.6 ± 3.6 years), 17 of the 28 (61%) surviving patients had normal neurologic status, 5 (18%) had a severe neurologic outcome, and 6 (21%) had mild cognitive difficulties. Abnormal neurologic outcome was not influenced by age or type of genetic defect, but by the presence of neurologic symptoms, MRI lesions, or abnormal CSF study at onset. Early clinical and MRI symptoms may regress after treatment. CONCLUSION: Neurologic symptoms are frequent at the onset of primary HLH and are mostly associated with abnormal CSF findings, but with normal brain MRI. In cases of abnormal brain MRI, the observed lesions differ from those of ADEM.
Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Adolescente , Líquido Cefalorraquidiano/metabolismo , Criança , Pré-Escolar , Transtornos da Consciência/etiologia , Diagnóstico Diferencial , Encefalomielite Aguda Disseminada/patologia , Encefalomielite Aguda Disseminada/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/líquido cefalorraquidiano , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/psicologia , Imageamento por Ressonância Magnética , Masculino , Prontuários Médicos , Meningismo/etiologia , Microcefalia/etiologia , Microcefalia/patologia , Microcefalia/fisiopatologia , Estudos Retrospectivos , Convulsões/etiologia , Resultado do TratamentoRESUMO
Since the discovery of the remarkable efficacy of imatinib in the metastatic GIST, several studies advanced our knowledge on the care of this pathology. In the localized GIST, the efficacy of the adjuvant treatment by imatinib was proved, but the duration, the indication and the management in case of relapse after imatinib are not still consensual. The imatinib is also used in neoadjuvant setting to optimize the quality of resection, the main treatment remaining the maximal tumor resection. In metastatic setting, imatinib remains the standard of care first-line treatment. It must be administered until progress or intolerance. Nevertheless, secondary resistance to imatinib is a substantial problem in routine clinical practice; in second line, sunitinib demonstrated its efficacy. Several inhibitors of tyrosine-kinases are ongoing evaluated in all the therapeutic lines. Clearly, a better knowledge of the molecular profile and the pharmacokinetics underlying the resistance to imatinib as well as the development of a new class of broad-spectrum tyrosine-kinase inhibitors may allow in the near future new individualized therapeutic strategies for GIST patients.
Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Antineoplásicos/farmacocinética , Benzamidas , Benzenossulfonatos/uso terapêutico , Quimioterapia Adjuvante , Resistencia a Medicamentos Antineoplásicos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Indóis/uso terapêutico , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piperazinas/farmacocinética , Piperidinas , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/farmacocinética , Pirróis/uso terapêutico , Sorafenibe , Sunitinibe , Tiazóis/uso terapêuticoRESUMO
Pediatric MS is better understood after a series of epidemiological studies including the French cohort following almost 500 children since more than 7 years. Pediatric MS may have an onset as early as 2 years but symptoms are different than those at adolescence. Its evolution towards a motor handicap is slower than in adults but cognitive impairment have to be evaluated carefully. Interferon beta treatment can be use, if needed, even before the age of 10. Several environmental factors might increase its risk, especially early EBV infection or passive smoking. HBV vaccination does not increase significantly its risk of occurrence.
Assuntos
Esclerose Múltipla/terapia , Adolescente , Encéfalo/patologia , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , França/epidemiologia , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologiaRESUMO
No effective treatment has been demonstrated for patients with acute transverse myelopathy. In a multicentre controlled study, 12 children with severe acute transverse myelopathy were treated with intravenous methylprednisolone (IVMP) and compared with a historical group of 17 patients. The treatment had a significant effect on the proportion of patients walking independently at 1 month and on the proportion with full recovery at 1 year, with no differences in the frequency of complications between the two groups.
Assuntos
Metilprednisolona/administração & dosagem , Mielite Transversa/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Metilprednisolona/efeitos adversosRESUMO
We observed a 17-month-old girl with profound and initially isolated episodes of hypothermia. Thereafter, she developed growth delay, repetitive corneal and bone lesions. Persistent hyperlactataemia in plasma and in CSF prompted us to investigate respiratory chain enzymes. A deficit in respiratory chain complexes III and IV was demonstrated in isolated skeletal muscle mitochondria, circulating lymphocytes and fibroblasts by spectrophotometric and polarographic studies. Moreover, UCP3 mRNA expression in muscle was decreased.
Assuntos
Proteínas de Transporte/genética , Deficiência de Citocromo-c Oxidase , Complexo III da Cadeia de Transporte de Elétrons/deficiência , Hipotermia/etiologia , Miopatias Mitocondriais/diagnóstico , RNA Mensageiro/genética , Biópsia , Pré-Escolar , Feminino , Fraturas Espontâneas/diagnóstico , Fraturas Espontâneas/enzimologia , Fraturas Espontâneas/genética , Humanos , Hipotermia/enzimologia , Hipotermia/genética , Lactente , Recém-Nascido , Canais Iônicos , Miopatias Mitocondriais/enzimologia , Miopatias Mitocondriais/genética , Proteínas Mitocondriais , Músculo Esquelético/patologia , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/enzimologia , Retinose Pigmentar/genética , Proteína Desacopladora 3RESUMO
Within the brain, HIV-1 targets the microglia and astrocytes. Previous studies have reported that viral entry into astrocytes is independent of CD4, in contrast to microglia. We aimed to determine whether chemokine receptors play a role in mediating CD4-independent HIV-1 entry into astrocytes. We found that embryonic astrocytes and microglial cells express CCR5, CCR3, and CXCR4 transcripts. Intracellular calcium levels in astrocytes were found to increase following application of RANTES, MIP-1beta (CCR5-agonist), SDF-1alpha (CXCR4-agonist), but not eotaxin (CCR3-agonist). In microglial cells, eotaxin was also able to modulate internal calcium homeostasis. CD4 was not present at the cell surface of purified astrocytes but CD4 mRNA could be detected by RT-PCR. Neither HIV-1(9533) (R5 isolate) nor HIV-1(LAI) (X4 isolate) penetrated into purified astrocytes. In contrast, mixed CNS cell cultures were infected by HIV-1(9533) and this was inhibited by anti-CD4 mAb in 4/4 tested cultures and by anti-CCR5 mAb in 2/4. Thus, the HIV-1 R5 strain requires CD4 to penetrate into brain cells, suggesting that CCR5 cannot be used as the primary receptor for M-tropic HIV-1 strains in astrocytes. Moreover, inconstant inhibition of HIV-1 entry by anti-CCR5 mAb supports the existence of alternative coreceptors for penetration of M-tropic isolates into brain cells.
Assuntos
Complexo AIDS Demência/virologia , Astrócitos/virologia , Encéfalo/virologia , HIV-1/patogenicidade , Receptores CCR5/genética , Receptores CXCR4/genética , Complexo AIDS Demência/metabolismo , Complexo AIDS Demência/fisiopatologia , Astrócitos/citologia , Astrócitos/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Antígenos CD4/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Células Cultivadas/citologia , Células Cultivadas/metabolismo , Células Cultivadas/virologia , Quimiocina CCL4 , Quimiocina CCL5/farmacologia , Quimiocina CXCL12 , Quimiocinas CXC/farmacologia , Técnicas de Cocultura , Feto , HIV-1/metabolismo , Humanos , Imuno-Histoquímica , Proteínas Inflamatórias de Macrófagos/farmacologia , Macrófagos/virologia , Microglia/citologia , Microglia/metabolismo , Microglia/virologia , Neurônios/citologia , Neurônios/metabolismo , Neurônios/virologia , RNA Mensageiro/metabolismo , Receptores CCR3 , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Linfócitos T/virologiaRESUMO
Despite the number of potential causes, most children with ischemic cerebrovascular disease are classified into a few major categories: 1) cardioembolic stroke; 2) moyamoya syndrome; 3) complication(s) connected with systemic disease, with a known risk of a cerebrovascular event; 4) cervicocephalic arterial dissection; and 5) transient cerebral arteriopathy of undefined origin (probable arteritis). The etiological diagnosis is rapidly established by complementary investigations based on the initial clinical and imaging findings: cardiac exploration, magnetic resonance imaging and angiography or echo-doppler of the cervical arteries if cervical dissection is suspected; intra-arterial catheter cerebral angiography and analysis of the cerebrospinal fluid to investigate an intracranial arteriopathy. The outcome and treatment depend on the type of stroke, on its accurate identification, and on prediction regarding the risk of recurrence. Although there is a constitutional predisposition to cerebrovascular accidents, environmental triggers such as trauma, infectious disease and cardiac surgery also play a major role.
Assuntos
Infarto Cerebral/diagnóstico , Infarto Cerebral/etiologia , Fatores Etários , Arterite/complicações , Dissecação da Artéria Carótida Interna/complicações , Angiografia Cerebral , Infarto Cerebral/classificação , Infarto Cerebral/epidemiologia , Infarto Cerebral/terapia , Criança , Progressão da Doença , Humanos , Imageamento por Ressonância Magnética , Doença de Moyamoya/complicações , Vigilância da População , Recidiva , Sistema de Registros , Acidente Vascular Cerebral/complicações , Análise de Sobrevida , Dissecação da Artéria Vertebral/complicaçõesRESUMO
OBJECTIVE: To compare astrocyte toxicity induced by plasma membrane-expressed gp120/41 and soluble gp120. DESIGN: Analysis of morphological alterations and lactate dehydrogenase (LDH) release from astrocytes in culture with monocytes infected with HIV-1, microglia expressing Env of a macrophage-tropic HIV-1 isolate or soluble Env. METHODS: Primary human embryonic astrocytes were cultured with: monocytes infected with two M-tropic HIV-1 isolates (HIV-1(9533), HIV-1(BX08)); human microglia infected with the defective Semliki Forest virus (SFV) vector coding for the env gene of HIV-1(BX08) isolate (SFVenvBX08); and soluble gp140 purified from baby hamster kidney cells transfected with the env gene of HIV-1(BX08) lacking the intracytoplasmic region of gp41 (SFVdelta envBX08). Gp120 mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction and the protein was detected by immunofluorescence in infected monocytes or microglia. RESULTS: Contact of HIV-infected monocytes induced morphological changes in astrocytes and a 137% increase in LDH release at day 2 of co-culture compared with controls (uninfected monocytes). Gp120/41(BX08)-expressing microglia induced a 170% increase in LDH release (relative to SFVLacZ-infected microglia). Pretreatment of co-cultures with an anti-gp120 monoclonal antibody (mAb; NEA-9305) directed against the V3 loop inhibited LDH release. Soluble purified gp140 from BX08 isolate induced only a weak LDH release (104%). Finally, cytotoxicity was not blocked by treatment of the co-culture with Bordetella pertussis toxin, an inhibitor of Gi alpha protein-dependent receptors. CONCLUSION: HIV envelope glycoprotein expressed at the plasma membrane induced astrocyte damage more efficiently than its soluble counterpart. The V3 loop was involved in toxicity induction through a pathway independent of the Gi alpha protein-coupled receptor.
Assuntos
Astrócitos/patologia , Membrana Celular/metabolismo , Efeito Citopatogênico Viral , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp41 do Envelope de HIV/metabolismo , HIV-1/patogenicidade , Macrófagos/virologia , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/isolamento & purificação , Proteína gp120 do Envelope de HIV/toxicidade , Proteína gp41 do Envelope de HIV/toxicidade , HIV-1/genética , HIV-1/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Microglia/citologia , Microglia/metabolismo , Microglia/patologia , Monócitos/citologia , Monócitos/metabolismo , Monócitos/virologia , Toxina Pertussis , RNA Viral/genética , RNA Viral/metabolismo , Vírus da Floresta de Semliki/genética , Solubilidade , Fatores de Virulência de Bordetella/farmacologiaAssuntos
Códon sem Sentido/genética , Hipopigmentação/genética , Deficiência Intelectual/genética , Melanossomas/patologia , Transtornos das Habilidades Motoras/genética , Hipotonia Muscular/genética , Criança , Análise Mutacional de DNA , Feminino , Humanos , Hipopigmentação/fisiopatologia , Deficiência Intelectual/fisiopatologia , Transtornos das Habilidades Motoras/fisiopatologia , Hipotonia Muscular/fisiopatologia , Miosinas/genética , SíndromeRESUMO
Microglial cells and astrocytes isolated from human embryonic proencephalon were compared to monocyte-derived macrophages (MDM) for their ability to replicate human cytomegalovirus (HCMV) in vitro. A specific cytopathic effect was observed in microglial cells and astrocytes, but not in MDM. A high percentage of glial cells but a low percentage of MDM expressed immediate-early and late viral antigens. The ability of HCMV-infected microglial cells and astrocytes to release viral particles in their supernatants was significantly higher than that of infected MDM. Human microglial cells and astrocytes at an early stage of development are highly susceptible to HCMV infection.
Assuntos
Astrócitos/virologia , Citomegalovirus/fisiologia , Macrófagos/virologia , Microglia/virologia , Replicação Viral , Antígenos Virais/análise , Células Cultivadas/virologia , Efeito Citopatogênico Viral , Imunofluorescência , Humanos , Microscopia Confocal , Fatores de Tempo , Eliminação de Partículas ViraisRESUMO
Oxidative stress is thought to be involved in the mechanism of nerve cell death in Parkinson's disease (PD). Among several toxic oxidative species, nitric oxide (NO) has been proposed as a key element on the basis of the increased density of glial cells expressing inducible nitric oxide synthase (iNOS) in the substantia nigra (SN) of patients with PD. However, the mechanism of iNOS induction in the CNS is poorly understood, especially under pathological conditions. Because cytokines and FcepsilonRII/CD23 antigen have been implicated in the induction of iNOS in the immune system, we investigated their role in glial cells in vitro and in the SN of patients with PD and matched control subjects. We show that, in vitro, interferon-gamma (IFN-gamma) together with interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) can induce the expression of CD23 in glial cells. Ligation of CD23 with specific antibodies resulted in the induction of iNOS and the subsequent release of NO. The activation of CD23 also led to an upregulation of TNF-alpha production, which was dependent on NO release. In the SN of PD patients, a significant increase in the density of glial cells expressing TNF-alpha, Il-1beta, and IFN-gamma was observed. Furthermore, although CD23 was not detectable in the SN of control subjects, it was found in both astroglial and microglial cells in parkinsonian patients. Altogether, these data demonstrate the existence of a cytokine/CD23-dependent activation pathway of iNOS and of proinflammatory mediators in glial cells and their involvement in the pathophysiology of PD.
Assuntos
Neuroglia/imunologia , Óxido Nítrico/metabolismo , Doença de Parkinson/imunologia , Doença de Parkinson/metabolismo , Receptores de IgE/metabolismo , Substância Negra/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Interferon gama/farmacologia , Interleucina-1/farmacologia , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Neuroglia/patologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Doença de Parkinson/patologia , Receptores de IgE/análise , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Substância Negra/metabolismo , Substância Negra/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Oxidative stress is suggested to be involved in several neurodegenerative diseases. One mechanism of oxidative damage is mediated by peroxynitrite, a neurotoxic reaction product of superoxide anion and nitric oxide. Expression of two cytokines and two key enzymes that are indicative of the presence of reactive oxygen intermediates and peroxynitrite was investigated in brain tissue of AIDS patients with and without AIDS dementia complex and HIV-seronegative controls. RNA expression of IL-1beta, IL-10, inducible nitric oxide synthase, and superoxide dismutase (SOD) was found to be significantly higher in demented compared with nondemented patients. Immunohistochemical analysis showed that SOD was expressed in CD68-positive microglial cells while inducible nitric oxide synthase was detected in glial fibrillary acidic protein (GFAP)-positive astrocytes and in equal amounts in microglial cells. Approximately 70% of the HIV p24-Ag-positive macrophages did express SOD, suggesting a direct HIV-induced intracellular event. HIV-1 infection of macrophages resulted in both increased superoxide anion production and elevated SOD mRNA levels, compared with uninfected macrophages. Finally, we show that nitrotyrosine, the footprint of peroxynitrite, was found more intense and frequent in brain sections of demented patients compared with nondemented patients. These results indicate that, as a result of simultaneous production of superoxide anion and nitric oxide, peroxynitrite may contribute to the neuropathogenesis of HIV-1 infection.