RESUMO
Background: The ligation of intersphincteric fistula fract (LIFT) technique avoids postoperative anal continence disturbances and preserves quality of life. Methods: A total of 70 patients with anal fistula (AF) were treated in the Day Surgery Unit. The LIFT technique was the primary treatment in 63 patients. The other had previously undergone placement of a loose seton (two-step approach). The mean follow-up was 66.8 months. Statistical analysis was performed using contingency tables, the chi-square test, and the Student T-test. Results: The use of LIFT was successful in 40 patients (57.1%). However, 6 patients (8.6%) presented persistence of postoperative intersphincteric fistula, being successfully treated by fistulotomy. There were no differences in this technique's success rate between high and low AF (p = 0.45). The success rate of one-step LIFT, however, was significantly higher (p = 0.03). No disturbances of continence were observed. Conclusions: The LIFT technique has a role in the treatment of AF, is suitable for ambulatory surgery, and has a low complications rate. A two-step approach is not always needed. (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fístula Retal/cirurgia , Complicações Pós-Operatórias , Recidiva , Seguimentos , Incontinência Fecal/prevenção & controleRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.
Assuntos
Apirase/metabolismo , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunomodulação , Adenosina/metabolismo , Apirase/genética , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Linfócitos B Reguladores/imunologia , Linfócitos B Reguladores/metabolismo , Estudos de Casos e Controles , Citocinas/biossíntese , Gerenciamento Clínico , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Ativação Linfocitária , Contagem de Linfócitos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do TratamentoAssuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hiper-Reatividade Brônquica , Rinite Alérgica , Imunoterapia , AsmaRESUMO
Animal and technical models often require repeated anaesthetic administrations for surgical procedures. As there is evidence for immunomodulatory effects of anaesthesia, the effects of repeated exposure to sevoflurane anaesthesia on the immune response in mice were studied. Sevoflurane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevoflurane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevoflurane anaesthesia, peripheral blood leukocyte counts, the composition and in vitro function of spleen cells (lymphocytes and macrophages) and the in vivo immune response to a conventional T-dependent antigen were assessed. In addition, liver, spleen and kidney histopathology and also hepatic and renal function were studied. Three days after the latest anaesthetic procedure, the absolute number of both leukocyte and lymphocyte counts were reduced in peripheral blood. Splenic cell composition (LB, LTCD3(+), LTCD4(+) and LTCD8(+)), macrophage function and the mitogen-induced lymphoprolipherative response were preserved. Yet, the in vivo humoral response to a conventional antigen was augmented following the antigenic challenge. Assessment at day 9 after the last anaesthetic procedure revealed the persistence of the humoral response alteration. Nevertheless, sevoflurane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.
Assuntos
Anestesia , Anestésicos Inalatórios/efeitos adversos , Imunidade/efeitos dos fármacos , Éteres Metílicos/efeitos adversos , Animais , Linfócitos B , Rim/anatomia & histologia , Rim/efeitos dos fármacos , Rim/fisiologia , Contagem de Leucócitos , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/fisiologia , Contagem de Linfócitos , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sevoflurano , Baço/citologia , Linfócitos T , Timo/anatomia & histologia , Timo/efeitos dos fármacosRESUMO
OBJECTIVE: Given that anesthesia and surgery are known by their immunomodulatory effects, we aimed to compare the immune response after 1 or 3 anesthetic exposures to sevoflurane in a murine model without surgery. MATERIAL AND METHODS: Young adult male mice, non-controlled for body conformation, were exposed 1 (group S1) or 3 times (group S3) to 3% sevoflurane in oxygen (1.2 maximum alveolar concentration) for 40 minutes. Untreated animals were used as controls. Three days after in vivo exposure to sevoflurane, the cellular composition of peripheral blood and of the spleen were studied. We also studied the in vivo response to exogenous (sheep red blood cells: SRBC) and endogenous antigens (heat shock proteins: HSP 65 and HSP 70) as well as biomarkers of toxicity. RESULTS: The number of leukocytes in peripheral blood decreased in S3 animals, and the number of lymphocytes decreased in both groups. B cells in spleen decreased only in the S1 group, but an increased in vivo response to SRBC was seen in both S1 and S3 mice in comparison with the control animals. Re-exposure to sevoflurane led to a decrease in immunoglobulin G response only to HSP 70. Plasma markers of liver and kidney function did not change after anesthetic exposure. CONCLUSION: Changes in leukocyte populations in peripheral blood and in antibody-producing capacity occur after either a single exposure or repeated exposures to sevoflurane. However no changes occur in biomarkers of toxicity.
Assuntos
Anestésicos Inalatórios/farmacologia , Formação de Anticorpos/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Éteres Metílicos/farmacologia , Anestésicos Inalatórios/administração & dosagem , Animais , Biomarcadores , Esquema de Medicação , Eritrócitos/imunologia , Imunoglobulina A/biossíntese , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Rim/anatomia & histologia , Rim/efeitos dos fármacos , Testes de Função Renal , Contagem de Leucócitos , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Testes de Função Hepática , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Éteres Metílicos/administração & dosagem , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Sevoflurano , Ovinos , Baço/anatomia & histologia , Baço/citologia , Baço/efeitos dos fármacosRESUMO
Phosphorylation of phospholamban (PLB) at Ser16 (protein kinase A site) and at Thr17 [Ca2+/calmodulin kinase II (CaMKII) site] increases sarcoplasmic reticulum Ca2+ uptake and myocardial contractility and relaxation. In perfused rat hearts submitted to ischemia-reperfusion, we previously showed an ischemia-induced Ser16 phosphorylation that was dependent on beta-adrenergic stimulation and an ischemia and reperfusion-induced Thr17 phosphorylation that was dependent on Ca2+ influx. To elucidate the relationship between these two PLB phosphorylation sites and postischemic mechanical recovery, rat hearts were submitted to ischemia-reperfusion in the absence and presence of the CaMKII inhibitor KN-93 (1 microM) or the beta-adrenergic blocker dl-propranolol (1 microM). KN-93 diminished the reperfusion-induced Thr17 phosphorylation and depressed the recovery of contraction and relaxation after ischemia. dl-Propranolol decreased the ischemia-induced Ser16 phosphorylation but failed to modify the contractile recovery. To obtain further insights into the functional role of the two PLB phosphorylation sites in postischemic mechanical recovery, transgenic mice expressing wild-type PLB (PLB-WT) or PLB mutants in which either Thr17 or Ser16 were replaced by Ala (PLB-T17A and PLB-S16A, respectively) into the PLB-null background were used. Both PLB mutants showed a lower contractile recovery than PLB-WT. However, this recovery was significantly impaired all along reperfusion in PLB-T17A, whereas it was depressed only at the beginning of reperfusion in PLB-S16A. Moreover, the recovery of relaxation was delayed in PLB-T17A, whereas it did not change in PLB-S16A, compared with PLB-WT. These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr17 appears to play a major role.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Miocárdio Atordoado/metabolismo , Miocárdio Atordoado/fisiopatologia , Substituição de Aminoácidos , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Contração Miocárdica/fisiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Fosforilação , Ratos , Ratos WistarRESUMO
Based on the immunomodulatory effects of anesthesia and surgery, a study was undertaken to assess the effect of sevoflurane anesthesia on the immune system in a murine model without surgery. Adult male mice were anesthetized with 3% sevoflurane (1.2 minimal alveolar concentration, MAC) in oxygen for 40 min, whereas nontreated animals served as controls. After sevoflurane anesthesia, peripheral blood leukocyte counts, the splenic composition and in vitro macrophage phagocytic activity and lymphoproliferative response were assessed. The in vivo specific immune response to sheep red blood cells (SRBC), a conventional T-dependent antigen was determined. In addition, liver, spleen, thymus and kidney histopathology and also hepatic and renal functions after anesthesia were studied. Sevoflurane diminished the number of peripheral blood lymphocytes and splenic B-cell counts, enhancing CD4+ lymphocytes in spleen. The in vitro functionality of macrophages and the mitogen-induced lymphoproliferative response were preserved, while the in vivo immune response to SRBC was enhanced in treated animals. Microscopic studies revealed conserved architecture of the spleen, thymus, lymph node, liver and kidney, and there were no differences in serum parameters of hepatic and renal functions between treated and control groups. Our results suggest that 3 days after the anesthetic exposure, animals treated with sevoflurane modulated their peripheral blood leukocyte counts, splenic lymphoid composition and the characteristics of the specific response to SRBC, while there was no evidence of hepatic or renal toxicity.