RESUMO
The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system.
Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia Tipo Ausência/induzido quimicamente , Guanosina/efeitos adversos , Receptor A2A de Adenosina/metabolismo , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Inibidores de Ciclo-Oxigenase/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletroencefalografia , Análise de Fourier , Indometacina/farmacologia , Lipopolissacarídeos/toxicidade , Antagonistas de Receptores Purinérgicos P1/farmacologia , Pirimidinas/farmacologia , Ratos , Ratos Wistar , Teofilina/farmacologia , Fatores de Tempo , Triazóis/farmacologiaRESUMO
The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFN gamma+ T(h)1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFN gamma and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFN gamma and the observed decrease of Foxp3+ Tregs. The shift toward T(h)1 with increased IFN gamma production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.
Assuntos
Doenças do Tecido Conjuntivo/imunologia , Ativação Linfocitária/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Linhagem Celular Tumoral , Doenças do Tecido Conjuntivo/sangue , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/fisiopatologia , Citocinas/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th2/metabolismoRESUMO
We aimed at investigating the distribution of various types of immunoregulatory T cells in the peripheral blood of patients with Hodgkin's lymphoma (HL) (n = 94) being in the state of long-lasting complete remission using flow cytometry. Healthy patients (n = 41) as 'negative' and patients in complete remission with breast cancer (n = 47) as 'positive' controls were investigated in the study. We found significant elevations in the number of CD4+ CD25high naturally occurring regulatory T cells, CD4+/intracellular IL-10+ (Tr1) and CD8+/intracellular IL-10+ T cells in HL compared to the healthy controls. In carcinoma patients, however, the number of Tr1 and CD8+/IL-10+ T cells was higher than that in the other two groups. The increase in the number of CD4+ CD25high T cells seems to be characteristic of HL compared to the two other types of regulatory T cells. This change exists for a long time and it seems to be a characteristic of HL and independent of the types of therapy and the duration of time since therapy.
Assuntos
Doença de Hodgkin/imunologia , Subpopulações de Linfócitos/citologia , Linfócitos T Reguladores/citologia , Adulto , Idoso , Contagem de Linfócito CD4 , Antígenos CD8/análise , Feminino , Doença de Hodgkin/sangue , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/análiseRESUMO
The immune system has several mechanisms to fight against developing malignant cell clones in the host, one of them is the activated T-cell response. Both CD4+ helper and CD8+ cytotoxic T-cells bear HLA-DR molecules as important surface activation markers. Our aim was to determine, how the ratio of activated T cells change in the peripheral blood of non-Hodgkin's lymphoma (NHL) patients during the periods of polychemotherapy. Using the methods of immunofluorescence staining and flow cytometry, we found the ratio of CD3+/HLA-DR+ cells significantly higher in NHL patients before treatment compared to healthy controls (10.63% versus 2.97%, P<0.001). During the period of polychemotherapy, this ratio began to increase significantly (10.63% versus 16.94%, P=0.006). After treatment, the ratio of activated T cells decreased, however, we detected significantly higher rate of CD3+/HLA-DR+ lymphocytes in patients who relapsed within 1 year than in those who stayed in remission (9.55% versus 20.62%, P<0.001). We suppose that investigation of CD3+/HLA-DR+ activated T cells might be a promising method to determine the prognostics of lymphoma patients.
Assuntos
Complexo CD3/imunologia , Antígenos HLA-DR/imunologia , Linfoma não Hodgkin/diagnóstico , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
AIM: The availability of several biological therapy options is rapidly growing in the field of malignant lymphomas. This emphasizes the need to understand the precise interaction of the host immune system with the malignant disease. We measured the intracellular cytokine responses in lymphoma patients' lymphocytes, to characterize the polarization changes in their immune system. METHODS: Patients with B cell non-Hodgkin's lymphoma were involved in the study. Peripheral lymphocytes were labeled with anti-CD4 or anti-CD8 antibodies and intracellular accumulation of IL-4 or IFN-gamma was detected after in vitro incubation the cells with activating cocktail. The frequency of different T-cell subsets were measured within the lymphocyte population. RESULTS: Significantly increased CD4+, IFN-gamma producing (Th1) cell percentage were found in untreated lymphoma cases (28.8% vs. 21.8%). CD8+ IL-4 and IFN-gamma producing (Tc0) T cell frequency is significantly higher in untreated lymphoma patients compared with normal controls (1.3% vs. 0.47%). The frequency of CD4+ IL-4 producing (Th2) cells is significantly lower in untreated patients (0.96% vs. 1.19%). Patients in long-term remission have lower frequency of CD4+, IL4 producing (Th2) cell ratio (0.31% vs. 1.19%) and increased CD4+ IFN-gamma producing (Th1) cell frequency (30.1% vs. 21.8%), compared with healthy normal controls. CONCLUSION: Our results demonstrate that there is a sustained increase in the CD4+ IFN-gamma producing cell frequency in lymphoma patients. The frequency of CD4+ IL-4 producing cells is decreasing by treatment. These may contribute to strong polarization toward Th1 type response, needed for lymphoma clearance and remission.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Interferon gama/biossíntese , Interleucina-4/biossíntese , Linfoma de Células B/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Líquido Intracelular/metabolismo , Contagem de Linfócitos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Indução de Remissão , Células Th1/metabolismo , Células Th2/metabolismo , Vincristina/administração & dosagemRESUMO
Dermatomyositis is a systemic autoimmune disease which belongs to the group of idiopathic inflammatory myopathies. The disease is rare with an incidence of 0.1-1/100,000 and a prevalence of 1-6/100,000. Women are affected twice as often as men. In some patients the disease presents with dermatologic changes weeks to months before the myopathy arises. It was observed that in some patients the myositis develops much later and sometimes not at all. Therefore, the term of dermatomyositis sine myositis used in earlier literature has been changed to amyopathic dermatomyositis. The most important question is whether the patient needs systemic therapy with its possible side effects yet possibly preventing the appearance of myositis or only local therapy for the skin manifestations is necessary. The goal of this article is to summarize the latest findings in amyopathic dermatomyositis.