RESUMO
OBJECTIVE: The objective of this study was to clarify the efficacy and safety of factor Xa inhibitors for antiphospholipid syndrome patients in real world utilization. METHODS: This is a retrospective cohort study comprised of all consecutive patients with antiphospholipid syndrome in our department over a period of 28 years. Patients treated with factor Xa inhibitors were extracted from the cohort. As a control group, patients treated with warfarin were selected from the same cohort with matched age, gender, coexistence of systemic lupus erythematosus, and the presence of antiplatelet therapy, after which we used a propensity score for each of the risk factors as an additional covariate in multivariate Cox proportional hazard regression. The primary endpoint was set as thrombotic and hemorrhagic event-free survival for five years. RESULTS: Among 206 patients with antiphospholipid syndrome, 18 had a history of anti-Xa therapy (five rivaroxaban, 12 edoxaban, one apixaban). Fourteen out of 18 patients on anti-Xa therapy had switched to factor Xa inhibitors from warfarin. Event-free survival was significantly shorter during anti-Xa therapy than that during warfarin therapy (hazard ratio: 12.1, 95% confidence interval: 1.73-248, p = 0.01) ( Figure 1(a) ). Similarly, event-free survival in patients treated with factor Xa inhibitors was significantly shorter compared with controls (hazard ratio: 4.62, 95% confidence interval: 1.54-13.6, p = 0.0075). In the multivariate Cox proportional hazard model, event-free survival in patients with anti-Xa therapy remained significantly shorter (hazard ratio: 11.9, 95% confidence interval: 2.93-56.0, p = 0.0005). CONCLUSIONS: Factor Xa inhibitors may not be recommended for antiphospholipid syndrome.
Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Trombose/prevenção & controle , Adulto , Síndrome Antifosfolipídica/complicações , Estudos de Coortes , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose/etiologiaRESUMO
OBJECTIVES: We aimed to evaluate the obstetric complications and the risk factors for these events in pregnant women with rheumatic diseases (RDs). METHODS: A single-center retrospective study of women with RDs at Hokkaido University Hospital between 2007 and 2016 was conducted. Clinical features and maternal and fetal outcomes were retrospectively collected. The rate of pregnancy complications was compared with the general obstetric population (GOP) in Japan. RESULTS: Overall, 132 pregnancies in 95 women with RDs were recorded. Underlying RDs were systemic erythematosus (SLE) (n = 57), antiphospholipid syndrome (APS) (n = 35), rheumatoid arthritis (n = 9), and other RDs (n = 31). Antiphospholipid antibodies (aPL) were detected in 44 pregnancies (32%). Glucocorticoid was used in 82 pregnancies (62%), and tacrolimus in 20 pregnancies (15%). There were 24 disease flares (18%), but no RD-related death was documented. We recorded 112 live births, 6 abortions, 8 miscarriages, and 6 stillbirths. Pregnancies with RDs appeared to have frequent, emergency cesarean sections and preterm deliveries compared with GOP (30% vs 15% and 21% vs 14%, respectively). The median [interquartile range] birthweight in SLE and APS was lower than GOP (2591 [2231-2958] g and 2600 [2276-2920] g vs 2950 [2650-3250] g, respectively). In pregnancies with SLE, low complement levels presented the risk of maternal complications (odds ratio [95% CI]; 3.9 [1.0-14.9], p = 0.046) and anti-DNA antibody positivity was significantly correlated with the risk of fetal complications (3.5 [1.1-11.2], p = 0.036). In pregnancies with APS, maternal age over 35 years and duration of disease longer than 9 years (7.4 [1.3-40.8], p = 0.021, and 11.16 [1.1-118.8], p = 0.046, respectively) were significantly correlated with the risk of fetal complications. CONCLUSION: Pregnancies with RDs were at increased risk of having both maternal complications and adverse neonatal outcomes, indicating these pregnancies should be closely monitored.
Assuntos
Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Doenças Reumáticas/complicações , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Cesárea/efeitos adversos , Cesárea/estatística & dados numéricos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Recém-Nascido , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Mortalidade Perinatal , Gravidez , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Fatores de Risco , Tacrolimo/uso terapêuticoRESUMO
The objective of this study is to identify the effects of statins and risk factors for thrombosis in patients with new onset of systemic lupus erythematosus (SLE) with or without antiphospholipid antibodies (aPL). Consecutive patients with SLE without history of thrombotic events were retrospectively enrolled from April 1997 to February 2014. The development of first thrombosis and death caused by thrombosis were defined as the study endpoint. Risk and protective factors for developing thrombosis were analyzed. A total of 152 patients, 80 positive and 72 negative for aPL, were included. In aPL-positive patients, 15 developed arterial ( n = 6) and venous ( n = 9) thrombosis (median follow-up period 69 months). Cox's proportional hazards model showed that older age at SLE onset and IgG-anticardiolipin antibodies (aCL) were statistically significant risks for thrombosis. Statin therapy was identified as a statistically significant protective factor against thrombosis (hazard ratio 0.12, 95% confidence interval 0.01-0.98). In aPL-negative patients (median follow-up period 46 months), seven patients developed thrombosis (five arterial and two venous). No risk factors for thrombosis were found in this group. In aPL-positive patients with SLE, the late disease onset and the presence of IgG-aCL represented additional risk factors for thrombosis. Statin treatment appeared as a protective factor for thrombosis.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lúpus Eritematoso Sistêmico/complicações , Trombose/tratamento farmacológico , Trombose/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/prevenção & controleRESUMO
Essentials Thrombotic risk stratification is an unmet need in antiphospholipid antibody carriers. Platelet count and antiphospholipid score (aPL-S) were combined to predict thrombotic events. Patients with high aPL-S are at high thrombotic risk regardless of platelet count. If platelet count is low, patients with low aPL-S are also on high thrombotic risk. SUMMARY: Background Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome. However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers, and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titers. Patients/methods A single-center, retrospective, longitudinal study comprising 953 consecutive patients who were suspected of having autoimmune disease between January 2002 and December 2006 was performed. Low platelet count was defined as a count of < 150 × 103 µL-1 at the time of aPL testing. Results A negative correlation was observed between aPL-S and platelet count (r = - 0.2477). Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.11-7.88). Among aPL-negative patients, no difference was found in the predictive value of thrombosis regardless of platelet count. Patients with aPLs were further divided into two subgroups according to aPL-S. Among low-aPL-S patients, those with low platelet counts developed thrombosis more frequently than those without (HR 3.44, 95% CI 1.05-11.2). In contrast, high-aPL-S patients developed thrombosis frequently regardless of platelet count. Conclusions aPL carriers with low platelet counts are at high risk of developing thrombosis. In particular, 'low-aPL-S carriers' may be stratified by platelet count in terms of predicting future thrombotic events.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Plaquetas , Contagem de Plaquetas , Trombocitopenia/sangue , Trombose/epidemiologia , Adulto , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Biomarcadores/sangue , Técnicas de Apoio para a Decisão , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombose/sangue , Trombose/diagnósticoRESUMO
The serine threonine kinase checkpoint kinase 2 (CHK2) is a DNA damage checkpoint protein important for the ATM-p53 signaling pathway. In addition to its phosphorylation, CHK2 is also ubiquitylated, and both post-translational modifications are important for its function. However, although the mechanisms that regulate CHK2 phosphorylation are well established, those that control its ubiquitylation are not fully understood. In this study, we demonstrate that the ubiquitin E3 ligase PIRH2 (p53-induced protein with a RING (Really Interesting New Gene)-H2 domain) interacts with CHK2 and mediates its polyubiquitylation and proteasomal degradation. We show that the deubiquitylating enzyme USP28 forms a complex with PIRH2 and CHK2 and antagonizes PIRH2-mediated polyubiquitylation and proteasomal degradation of CHK2. We also provide evidence that CHK2 ubiquitylation by PIRH2 is dependent on its phosphorylation status. Cells deficient in Pirh2 displayed accumulation of Chk2 and enhanced hyperactivation of G1/S and G2/M cell-cycle checkpoints. This hyperactivation was, however, no longer observed in Pirh2-/-Chk2-/- cells, providing evidence for the importance of Chk2 regulation by Pirh2. These findings indicate that PIRH2 has central roles in the ubiquitylation of Chk2 and its turnover and in the regulation of its function.
Assuntos
Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Quinase do Ponto de Checagem 2 , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
BACKGROUND: Systemic sclerosis (SSc) is accompanied by abnormalities in humoral and cellular immune systems. OBJECTIVE: To determine the genes specifically expressed in the immune system in SSc by analysis of the gene expression profile of peripheral blood mononuclear cells (PBMC) from patients with SSc, including those treated with haematopoietic stem cell transplantation (HSCT). Additionally, to investigate the clinical significance of the up regulation of tumour necrosis factor alpha (TNFalpha) converting enzyme (TACE). METHODS: PBMC from patients with SSc (n = 23) and other autoimmune diseases (systemic lupus erythematosus (SLE, n = 16), rheumatoid arthritis (RA, n = 29)), and from disease-free controls (n = 36) were examined. Complementary DNA arrays were used to evaluate gene expression of PBMC, in combination with real time quantitative polymerase chain reactions. TACE protein expression in PBMC was examined by fluorescence activated cell sorter (FACS). RESULTS: In patients with SSc 118 genes were down regulated after HSCT. Subsequent comparative analysis of SSc without HSCT and healthy controls indicated SSc-specific up regulation for three genes: monocyte chemoattractant protein-3 (p = 0.0015), macrophage inflammatory protein 3alpha (p = 0.0339), and TACE (p = 0.0251). In the FACS analysis, TACE protein was mainly expressed on CD14(+) monocytes both in patients with SSc and controls. TACE expression on CD14(+) cells was significantly increased in patients with early SSc (p = 0.0096), but not in those with chronic SSc, SLE, or RA. TACE protein levels in SSc monocytes correlated with the intracellular CD68 levels (p = 0.0016). CONCLUSIONS: Up regulation of TACE expression was a unique profile in early SSc, and may affect the function of TNFalpha and other immunoregulatory molecules.
Assuntos
Metaloendopeptidases/sangue , Monócitos/enzimologia , Escleroderma Sistêmico/enzimologia , Regulação para Cima , Proteínas ADAM , Proteína ADAM17 , Adulto , Idoso , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Diferenciação Celular , Membrana Celular/enzimologia , DNA Complementar/genética , Progressão da Doença , Feminino , Perfilação da Expressão Gênica/métodos , Transplante de Células-Tronco Hematopoéticas , Humanos , Lúpus Eritematoso Sistêmico/enzimologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Metaloendopeptidases/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/terapiaRESUMO
BACKGROUND: CD34+ cell-selected autologous PBSC transplantation (CD34+ APBSCT) is a procedure used for the treatment of patients with malignant disease that is intended to eliminate residual tumor cells from autologous grafts. However, frequent infectious complications after CD34+ APBSCT can occur. A delay of recovery of the absolute number of CD4+ T cells after transplantation was reported to be one disadvantageous factor. As data on T-cell function after CD34+ APBSCT are scanty, we analyzed changes in T-helper cell 1 (Th1) and T-helper cell 2 (Th2) after CD34+ APBSCT to evaluate immune reconstitution. METHODS: Twelve patients underwent APBSCT (CD34+APBSCT group, n=4, and unselected APBSCT, n=8). Peripheral blood (PB) samples were obtained at 2, 4, 8, 12 and 16 weeks after the transplantation. The dynamics of the Th1 and Th2 were analyzed at a single-cell level, using flow cytometry. RESULTS: In the CD34+ APBSCT group, not only the absolute count of CD4+ T cells but also the proportion of Th1 cells in CD4+ T cells and the ratio of Th1 to Th2 after transplantation were significantly decreased at 2 and 4 weeks after transplantation compared with findings in the unselected APBSCT group. DISCUSSION: We suggest that higher rates of infectious complications after CD34+ APBSCT may be due to the inability of residual T cells from the CD34+ cell selection to generate mature T cells that function adequately against infection. Although further study would be required, our preliminary data provide some information on the immune reconstitution after CD34+ APBSCT and differentiation of T lymphocytes into Th1 and Th2 in vivo.
Assuntos
Antígenos CD34/metabolismo , Transplante de Células-Tronco de Sangue Periférico , Células Th1/patologia , Células Th2/patologia , Adulto , Feminino , Citometria de Fluxo , Rejeição de Enxerto , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/terapia , Células Th1/metabolismo , Células Th2/metabolismo , Transplante AutólogoRESUMO
A 78-year-old man presented with a generalized erythematous papular rash. Such skin lesions were not painful, tender or pruritic, and spread over the truncus. He was admitted to our hospital for examination of the skin lesions. Laboratory tests indicated microcytic hypochromatic anemia and thrombocytopenia, although gave a normal leukocyte count with normal differentiation. His bone marrow showed hypercellularity, with 43% peroxidase positive blasts that displayed positive immunophenotypes for CD4, CD13, CD33, CD41a, KP-1 (CD68), and HLA-DR. His skin specimen revealed infiltration in the dermis and subcutaneous fat tissue by leukemic cells that were positive for the leukocyte common antigen (LCA, CD45), CD15, CD33, CD68, and HLA-DR. He was diagnosed as having M4 subtype of acute myelogeneous leukemia (AML) with leukemia cutis. After three courses of low dose cytosine arabinoside (LDAC), combined with low dose etoposide, he achieved complete remission (CR). He remained well, with no evidence of relapse nine months later. LDAC should be considered as initial treatment for such cases of leukemia cutis with poor general condition.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Leucemia/tratamento farmacológico , Idoso , Medula Óssea/patologia , Exantema/etiologia , Humanos , Imunofenotipagem , Leucemia/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , MasculinoRESUMO
Abstract A 24-year-old woman suffered from blurred vision and periorbital edema with remittent fever. She was diagnosed as having systemic lupus erythematosus (SLE), complicated with myopia and retinopathy and severe chemosis. Antiphospholipid syndrome (APS), hemophagocytic syndrome, and liver involvement were also proven. We considered that APS might cause chemosis as a result of thrombosis-induced perfusion failure in the conjunctiva. In such cases, APS should be considered and anticoagulation therapy associated with steroid therapy should be initiated. In systemic lupus erythematosus (SLE), chemosis, severe hepatitis, and hemophagocytic syndrome (HPS) are rare complications. It is well known that many cases of SLE are complicated with antiphospholipid syndrome (APS), which causes arteriovenous thrombosis. We report a case of SLE with transient myopia and severe chemosis complicated with severe hepatitis and HPS. As this patient had antiphospholipid antibodies, these ocular complications were considered to be related to APS.
RESUMO
The purpose of this study was to analyze changes in the T-helper cell 1/T-helper cell 2 (Th1/Th2) balance of peripheral T-helper cells after autologous peripheral blood stem cell transplantation (auto-PBSCT) for non-Hodgkin's lymphoma (NHL) and to evaluate the effects of chemotherapy and granulocyte colony-stimulating factor (G-CSF) on the Th1/Th2 balance. A series of peripheral blood samples from four patients with NHL were collected before peripheral blood stem cell harvest and after auto-PBSCT. Using flow cytometry, Th1 and Th2 cells were identified by their intracellular cytokines: interleukin (IL)-4-/interferon (IFN)-gamma+ and IL-4+/IFN-gamma-, respectively. The Th1/Th2 balance was estimated as the ratio of IL4-/IFN-gamma+ cells to IL-4+/IFN-gamma- cells. Although the Th1/Th2 balance decreased initially, it increased markedly 28 days after the cessation of G-CSF, following auto-PBSCT, in parallel with an increase in lymphocytes. This increase was mainly due to an increase in the proportion of Th1 cells. The Th1/Th2 balance did not change appreciably before PBSC harvest. Serum IFN-gamma increased after auto-PBSCT in three patients. These preliminary data demonstrate that, after auto-PBSCT for NHL, the Th1/Th2 balance decreases initially and then increases after 1 month to levels above pretreatment levels and that the effects of chemotherapy and G-CSF on the Th1/Th2 balance are negligible before PBSC harvest. Further evaluation of the Th1/Th2 balance after allogeneic PBSCT at the single-cell level should be undertaken using this method.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Contagem de Linfócitos , Linfoma não Hodgkin/terapia , Células Th1/imunologia , Células Th2/imunologia , Idoso , Antineoplásicos/uso terapêutico , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Interferon gama/sangue , Interleucina-12/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Transplante AutólogoRESUMO
A 45-year-old Japanese woman with splenomegaly and thrombocytopenia was referred to our hospital. The diagnosis of Osler-Weber-Rendu disease (Osler's disease) was made because of spotty telangiectasia on her tongue, recurrent epistaxis since childhood, and a diathesis indicated by her family history. The patient's laboratory examination revealed anemia, thrombocytopenia, and other data consistent with chronic disseminated intravascular coagulation (DIC). Bone marrow examination was normal. Abdominal computed tomography showed marked enlargement of the spleen with deformity and calcified plaque, not homogeneously enhancing. Hypersplenism was not observed. Platelet scintigraphy indicated a remarkable uptake in the spleen. She was diagnosed as having chronic DIC associated with vascular lesions of Osler's disease in the spleen. Splenectomy was performed and the subsequent pathological findings indicated that fragility of the fine vascular architecture of the splenic red pulp might have been responsible for pathogenesis. The large pooling of blood with coagulation was thought to be secondary.
Assuntos
Coagulação Intravascular Disseminada/complicações , Esplenomegalia/complicações , Telangiectasia Hemorrágica Hereditária/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The water decoction of leaves of kumis kucing, Orthosiphon aristatus (BL.) MIQ (Lamiaceae) which has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension etc., was partitioned into a mixture of chloroform and water. The chloroform-soluble portion showed an inhibitory effect on the contractile responses on rat thoracic aorta smooth muscle stimulated with KCl beforehand, while the water-soluble portion showed no effect. The chloroform-soluble portion was separated to afford a new benzochromene [orthochromene A (7)], two new isopimarane-type diterpenes [orthosiphonone A (10), orthosiphonone B (11)], and two novel migrated pimarane-type diterpenes [neoorthosiphol A (12), neoorthosiphol B (13)], together with eight known compounds (1-6, 8, 9). Among those thirteen substances, it was found that a major constituent in the water decoction of leaves, methylripariochromene A (5), exhibited a continuous decrease in systolic blood pressure after subcutaneous administration in conscious stroke-prone spontaneously hypertensive rats (SHRSP).
Assuntos
Anti-Hipertensivos/farmacologia , Benzopiranos/farmacologia , Lamiaceae/química , Animais , Anti-Hipertensivos/isolamento & purificação , Aorta Torácica/efeitos dos fármacos , Benzopiranos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Clorofórmio , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Folhas de Planta/química , Ratos , Ratos Endogâmicos SHR , Solubilidade , SístoleRESUMO
We studied two autopsy cases, each with a low titre of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated with systemic vasculitis. It was difficult to distinguish these cases from classic polyarteritis nodosa. The patients had suffered from continuous fever, malaise, and weight loss: however, their renal insufficiency was clinically mild over the course of their disease. The patients were diagnosed initially as having MPO-ANCA-associated vasculitis and were treated with prednisolone. Their clinical status improved, but unfortunately, they died of an infectious disease. Autopsies revealed systemic vasculitis in small arteries with no signs of necrotizing and crescentic glomerulonephritis. Our pathologist subsequently diagnosed both cases as classic polyarteritis nodosa. Systemic vasculitis associated with MPO-ANCA is usually considered to be a microscopic polyarteritis. However, classic polyarteritis nodosa should always be considered as a possibility for those patients with mild renal insufficiency and a low titre of MPO-ANCA.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Peroxidase/imunologia , Poliarterite Nodosa/diagnóstico , Vasculite/diagnóstico , Idoso , Anti-Inflamatórios/uso terapêutico , Betametasona/administração & dosagem , Biomarcadores/sangue , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Masculino , Prednisolona/administração & dosagem , Vasculite/tratamento farmacológicoRESUMO
Two novel migrated pimarane-type diterpenes named neoorthosiphols A (1) and B (2) were isolated from the water decoction of the leaves of Orthosiphon aristatus (Lamiaceae), which has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension, etc. The absolute chemical structures have been elucidated on the basis of physicochemical properties. It has been found that two migrated pimarane-type diterpenes (1, 2), four isopimarane-type diterpenes (3, 4, 5, 6), three benzochromenes (7, 8, 9) and two flavones (12, 13) exhibit a suppressive effect on contractile responses in rat thoracic aorta, among thirteen chemical constituents (1-13) isolated from the leaves.
Assuntos
Aorta Torácica/efeitos dos fármacos , Diterpenos/química , Lamiaceae/química , Músculo Liso Vascular/efeitos dos fármacos , Plantas Medicinais/química , Animais , Fenômenos Químicos , Físico-Química , Diterpenos/farmacologia , Endotélio Vascular/fisiologia , Técnicas In Vitro , Indonésia , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Conformação Molecular , Contração Muscular/efeitos dos fármacos , Folhas de Planta/química , Potássio/farmacologia , Ratos , Ratos WistarRESUMO
We report on a 23-year-old Japanese female with a 13-year history of systemic lupus erythematosus (SLE), and two episodes of deterioration followed by treatment with high dose prednisolone. Although she had been recently treated with prednisolone (12.5 mg daily), her liver function became worse in July 1998. Results of a liver biopsy revealed multi-focal hepatic cell death in a severe fatty liver, without any inflammatory cell invasion. The biopsy also showed a positive TUNEL (Tdt-catalysed DNA nick end labelling) reaction indicating apoptosis. Her liver function recovered rapidly following steroid pulse therapy. Serum soluble Fas ligand (sFasL) was found to be elevated to a concentration of 0.395 ng/ml at the time of liver damage, but was less than 0.03 ng/ml before liver damage and after prednisolone treatment. The liver damage in this case appeared to be involved with apoptosis induced by sFasL. Although hepatitis associated with SLE is rare, apoptosis directly related to elevated sFasL levels might cause this complication.
Assuntos
Apoptose , Hepatite/etiologia , Fígado/patologia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Biópsia , Proteína Ligante Fas , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hepatite/sangue , Hepatite/tratamento farmacológico , Hepatite/patologia , Humanos , Marcação In Situ das Extremidades Cortadas , Ligantes , Testes de Função Hepática , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Glicoproteínas de Membrana/sangue , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Receptor fas/sangueRESUMO
A 67-year-old man with a 7-month history of dilated cardiomyopathy was admitted to our hospital because of general fatigue, shortness of breath, and anemia on laboratory examination. Increased blasts were observed in the bone marrow. The blasts were characterized by large cells with abundant, intensely basophilic, vacuolated cytoplasm, round nuclei, and prominent nucleoli. Chromosome analysis revealed a nonrandom t(8;22)(q24;q11) chromosomal abnormality, and surface-marker analysis disclosed a positive immunophenotype for CD10, CD19, CD20, CD38, HLA-DR, FMC7, and IgM-lambda. These findings yielded a diagnosis of L3 acute lymphoblastic leukemia. The patient was treated with chemotherapeutic agents. On the 39th hospital day, during hematologic recovery after induction therapy, abdominal pain developed. Abdominal X-ray films disclosed ileus with dilatation of the small bowel and Kerckring's folds. Conservative treatment was begun but the patient died. At autopsy, intestinal perforations were observed at a site 55 cm proximal to the ileocecal junction. A specimen of perforated tissue revealed a diffuse infiltration of leukemic cells through the small bowel wall. However, bone marrow specimens showed no signs of aggravation of leukemia.
Assuntos
Linfoma de Burkitt/patologia , Doenças do Íleo/etiologia , Perfuração Intestinal/etiologia , Intestino Delgado/patologia , Infiltração Leucêmica/complicações , Idoso , Linfoma de Burkitt/sangue , Linfoma de Burkitt/diagnóstico , Humanos , Masculino , Indução de RemissãoRESUMO
Abstract A 57-year-old man presented with palpitations, shortage of breath on exertion, and rapidly progressive scleroderma. On admission, a computed tomographic scan of his lung showed active interstitial pneumonia. We treated him with d-penicillamine and intravenous pulse methylprednisolone. After this treatment, severe abdominal pain, microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal involvement appeared. We diagnosed him as having systemic sclerosis (SSc) complicated by thrombotic thrombocytopenic purpura. At postmortem, thromboses of capillaries, arterioles, and small arteries were found in several organs. As well as the differential diagnosis of SSc with thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and renal involvement, we diagnosed scleroderma renal crisis (SRC), normotensive renal crisis (NRC), and SSc complicated by TTP. Typical SRC and NRC were excluded because his blood pressure was in the normal range without elevation of plasma renin activity or azotemia over his clinical course. Although distinguishing TTP from renal crisis is difficult, an evaluation of ultra-large multimers of von Willebrand factor (UL-vWF) concentration may be helpful in these situations.
RESUMO
Methylripariochromene A (MRC) was isolated from the leaves of Orthosiphon aristatus (Lamiaceae) and subjected to the examination of several pharmacological actions related to antihypertensive activity. The following four findings were revealed from the present study: 1) MRC caused a continuous decrease in systolic blood pressure and a decrease in heart rate after subcutaneous administration in conscious male SHRSP, 2) MRC exhibited the concentration-dependent suppression of contractions induced by high K+, l-phenylephrine or prostaglandin F2alpha in endothelium-denuded rat thoracic aorta, 3) MRC showed a marked suppression of contractile force without a significant reduction in the beating rate in isolated bilateral guinea pig atria, and 4) MRC increased urinary volume and the excretion of Na+, K+ and Cl- for 3 h after oral administration with a load of saline in fasted rats. These findings indicate that MRC possesses some actions related to a decrease in blood pressure, i.e. vasodilating action, a decrease in cardiac output and diuretic action. Furthermore, it is presumed that the traditional use of this plant in the therapy of hypertension may be partially supported by these actions with MRC.