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2.
J Med Ultrason (2001) ; 48(4): 439-448, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34410547

RESUMO

PURPOSE: We aimed to investigate whether low-intensity continuous and pulsed wave ultrasound (US) irradiation can inhibit the formation of Staphylococcus epidermidis biofilms, for potential application in the treatment of catheter-related bloodstream infections (CRBSI). METHODS: S. epidermidis biofilms that formed on the bottom surfaces of 6-well plates were irradiated on the bottom surface using the sound cell incubator system for different intervals of time. RESULTS: US irradiation with continuous waves for 24 h notably inhibited biofilm formation (p < 0.01), but the same US irradiation for 12 h had no remarkable effect. Further, double US irradiation with pulsed waves for 20 min inhibited biofilm formation by 33.6%, nearly two-fold more than single US irradiation, which reduced it by 17.9%. CONCLUSION: US irradiation of a lower intensity (ISATA = 6-29 mW/cm2) than used in a previous study and lower than recommended by the Food and Drug Administration shows potential for preventing CRBSI caused by bacterial biofilms.


Assuntos
Infecções Estafilocócicas , Staphylococcus epidermidis , Biofilmes , Humanos , Infecções Estafilocócicas/prevenção & controle , Ondas Ultrassônicas
3.
Intern Med ; 60(13): 2047-2053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193774

RESUMO

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Piridinas , Sorafenibe/uso terapêutico
4.
J Med Ultrason (2001) ; 48(3): 353-359, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34014426

RESUMO

PURPOSE: This study aimed to evaluate the positive rate and prognostic significance of superb microvascular imaging (SMI) in rheumatoid arthritis (RA) patients in remission with normal C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). METHODS: The study enrolled 112 RA patients, and ultrasound (US) assessment was performed on 28 joints of each patient. RESULTS: The SMI signal-positive rates for each joint were: metacarpophalangeal (MCP) joints: 20.5%, wrist joints: 43.8%, metatarsophalangeal (MTP) joints: 17.0%, and other foot joints: 25.0%. Investigation of the prognostic significance of the SMI signal in each joint revealed that only in the MTP joints was the total score of the SMI signal in the patients with relapse significantly higher than that in the patients with remission (P = 0.01). Comparison of the receiver operating characteristics curves for predicting relapse showed that the area under the curve (AUC) of the MTP joints was the highest (AUC = 0.66) of the investigated joints. The optimal threshold for the total MTP SMI score was 1 (accuracy = 83.3%). Positive/negative data of the SMI signal in the MTP joints were not significantly associated with the values of conventional disease activity markers. CONCLUSION: In RA patients in remission with normal CRP and ESR levels, the percentage of positive SMI signal was highest in the wrist joints. However, the accuracy of the SMI signal for predicting relapse was greatest for the MTP joints, suggesting that US assessment of the MTP joints by SMI is useful for predicting relapse in these patients.


Assuntos
Artrite Reumatoide , Artrite Reumatoide/diagnóstico por imagem , Sedimentação Sanguínea , Proteína C-Reativa , Humanos , Prognóstico , Articulação do Punho/diagnóstico por imagem
5.
Mod Rheumatol ; : 1-9, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-33851898

RESUMO

OBJECTIVES: We aimed to clarify the clinical implication of ultrasound (US)-detected foot joint inflammation in tightly controlled patients with rheumatoid arthritis (RA). METHODS: We evaluated bilateral foot joints (second to fifth metatarsophalangeal joints of forefoot; tarsometatarsal, cuneonavicular and midtarsal joints of midfoot) of 430 RA patients for synovitis using Power Doppler (PD) imaging by US. We made a cross-sectional and a 3-year longitudinal analysis about the associations of US-detected synovitis with clinical, laboratory and radiographic data as well as foot-specific outcomes using a self-administered foot evaluation questionnaire (SAFE-Q). RESULTS: The US-detected foot synovitis was seen in 28% of patients. The US-detected synovitis was closely related to 28 joint-disease activity score (DAS28) more in the forefoot than in the midfoot, while related to joint destruction in both. Multiple regression analyses showed significant associations between midfoot PD positivity and SAFE-Q in the remission group. SAFE-Q was worsened after the 3-year interval, but PD positivity at baseline did not contribute to the changes. On the other hand, destruction of the joints with US-detected synovitis significantly progressed in 3 years than with not. CONCLUSIONS: US-detected synovitis on foot joints were related to systemic inflammation, clinical symptoms, and future joint destruction with region specificity.

6.
Mod Rheumatol ; 31(2): 334-342, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32243209

RESUMO

OBJECTIVE: Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. METHODS: In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2-5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. RESULTS: A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. CONCLUSIONS: While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Articulação do Tornozelo/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Sinovite/tratamento farmacológico , Sinovite/patologia , Ultrassonografia Doppler/normas , Articulação do Punho/diagnóstico por imagem
7.
Eur J Pharmacol ; 882: 173238, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32561292

RESUMO

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) play a crucial role in the pathogenesis of RA. RA-FLS display passive pro-inflammatory responses and self-directed aggressive responses, such as pro-inflammatory mediator production, reduced apoptosis and formation of a thickened synovial lining. Evidence suggests a role for Janus kinase (JAK)-signal transducer and transcriptional activator (STAT) signaling in the passive response but the aggressive behavior of RA-FLS is poorly understood. The pharmacologic effects of the novel JAK inhibitor, peficitinib, on cytokine-induced intracellular signaling and self-directed aggressive behavior of RA-FLS (e.g., increased expression of apoptosis-resistant genes and sodium nitroprusside-induced apoptosis) were investigated and compared with approved JAK inhibitors. RA-FLS assembly to form a lining-like structure and pro-inflammatory mediator production was investigated in three-dimensional (3D)-micromass culture. Peficitinib inhibited STAT3 phosphorylation in RA-FLS following induction by interferon (IFN)-α2b, IFN-γ, interleukin (IL)-6, oncostatin M, and leukemia inhibitory factor in a concentration-related manner, and was comparable to approved JAK inhibitors, tofacitinib and baricitinib. Peficitinib and tofacitinib suppressed autocrine phosphorylation of STAT3 and expression of apoptosis-resistant genes, and promoted cell death. In 3D-micromass culture, peficitinib reduced multi-layered RA-FLS cells to a thin monolayer, an effect less pronounced with tofacitinib. Both compounds attenuated production of vascular endothelial growth factor-A, matrix metalloproteinases, IL-6 and tumor necrosis factor superfamily-11. This study confirmed the pathogenic role of uncontrolled JAK-STAT signaling in the aggressive and passive responses of RA-FLS that are critical for RA progression. The novel JAK inhibitor peficitinib suppressed the pro-inflammatory behavior of RA-FLS, accelerated cell death and abrogated thickening of the synovium.


Assuntos
Adamantano/análogos & derivados , Artrite Reumatoide/metabolismo , Inibidores de Janus Quinases/farmacologia , Janus Quinases/metabolismo , Niacinamida/análogos & derivados , Fator de Transcrição STAT3/metabolismo , Sinoviócitos/metabolismo , Adamantano/farmacologia , Apoptose/efeitos dos fármacos , Azetidinas/farmacologia , Células Cultivadas , Citocinas/metabolismo , Humanos , Janus Quinases/antagonistas & inibidores , Niacinamida/farmacologia , Fosforilação/efeitos dos fármacos , Piperidinas/farmacologia , Purinas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Sinoviócitos/efeitos dos fármacos
8.
Clin J Gastroenterol ; 13(5): 839-843, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31974811

RESUMO

We report a 46-year-old male patient with functional liver damage due to hepatitis B virus infection. A 12 cm hepatocellular carcinoma (HCC) in the left lobe and portal venous tumor thrombosis (PVTT) with vp4 (portal vein tumor thrombosis in the main trunk) were detected by computed tomography (CT). He underwent hepatic arterial infusion chemotherapy (HAIC) with cisplatin 100 mg for HCC and received radiation therapy (39 Gy/13 Fr) for PVTT with vp4. Follow-up CT showed reduction of HCC and reduced PVTT volume after 1 month of treatment. He then initiated lenvatinib therapy at 12 mg/day. One month later, follow-up CT showed no change in HCC size and a reduction in PVTT volume. Two months after initiating lenvatinib, follow-up CT showed no change in HCC, but further reduction in contrast effect and volume of PVTT. Three months after HAIC, he underwent drug-eluting-bead transcatheter arterial chemoembolization (DEB-TACE) with 100 mg of cisplatin (CDDP) for the HCC. After DEB-TACE, he received 12 mg/day with 5-days-on/2-days-off due to vomiting. One month after DEB-TACE, blood evaluation showed decreased tumor markers, and CT revealed that the HCC had grown slightly with no change in PVTT. Five months after HAIC, he underwent DEB-TACE with 100 mg of cisplatin for the HCC. A total of 150 days have passed since the start of lenvatinib treatment, and his Child-Pugh A status has been maintained.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trombose , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia , Veia Porta , Quinolinas , Trombose/terapia , Resultado do Tratamento
9.
J Med Ultrason (2001) ; 47(1): 131-138, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31555946

RESUMO

PURPOSE: Ultrasound is commonly used to assess the degree of synovitis in patients with rheumatoid arthritis (RA); however, it is unclear which joints are optimal for evaluating and predicting recurrence and remission. PATIENTS AND METHODS: In 293 RA patients enrolled in the KURAMA cohort, 28 joints were assessed by ultrasound. RESULTS: Results from patients in remission in both 2015 and 2017 (Group 1, n = 152) were compared with those from patients in remission in 2015 and non-remission in 2017 (Group 2, n = 60). The SMI scores for total (3.1 vs. 6.3, P = 0.004), MCP2-5 (1.1 vs. 2.4, P = 0.03), wrist (0.9 vs. 2.1, P = 0.0003), MTP2-5 (0.4 vs. 1.0, P = 0.03), and Lisfranc joints (0.07 vs. 0.25, P = 0.04) were significantly higher for Group 2. When those in non-remission in 2015 and remission in 2017 (Group 3, n = 27) were compared with those in remission in 2015 and non-remission in both 2015 and 2017 (Group 4, n = 54), the GS-SMI combined score (3.0 vs. 5.0, P = 0.04) and SMI score (1.5 vs. 2.9, P = 0.04) for MCP2-5 joints were significantly higher for Group 4. Multivariate logistic regression analysis identified "wrist SMI score ≧ 1" as an independent prognostic factor for recurrence (odds ratio 3.08, P = 0.001) and "MCP2-5 GS-SMI combined score ≦ 4" as an independent prognostic factor for remission (odds ratio 3.25, P = 0.048). CONCLUSION: We identified the optimal joint cut-off scores for predicting recurrence and remission in RA patients. Risk-stratification therapy based on the ultrasound scores may improve outcome and quality of life for patients with RA.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Qualidade de Vida , Recidiva , Ultrassonografia , Articulação do Punho/diagnóstico por imagem
10.
Mod Rheumatol ; 30(6): 975-981, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612758

RESUMO

Objective: Ultrasonography (US) is a useful tool for evaluating the activity of rheumatoid arthritis (RA) patients. As the systemic evaluation of many joints is time-consuming, a method to evaluate this activity with a smaller number of joints is needed. The aim of this study was to clarify whether the number of joints assessed may be reduced using patient-oriented joint selection.Methods: A total of 492 RA patients were recruited at Kyoto University Hospital. Bilateral metacarpophalangeal (MCP), (proximal) interphalangeal (PIP/IP), and wrist joints were evaluated by US. Gray scale and power Doppler imaging findings were scored by a 0-3 semi-quantitative method. Clinical assessments were performed by physicians who were blind to US results, and a questionnaire on subjective symptoms was collected from each patient.Results: The correlation between the US score of all 22 joints (US22) and patient-oriented painful joints (PtUS) or physician-oriented tender and/or swollen joints were moderate (Spearman's ρ = 0.435) and weak (ρ = 0.383), respectively. These correlations were weaker than that between the total US score of 5 preselected joints (unilateral 2MCP, 3MCP, 2PIP, 3PIP, and the wrist) and US22 (ρ = 0.813). However, when focusing on patients whose painful joints were 5 and more, the correlation between PtUS and US22 was markedly stronger (ρ = 0.757).Conclusion: Patient-oriented joint selection reflected actual joint inflammation to some extent. However, excessive reductions in the number of joints assessed need to be avoided even if patients do not have arthralgia because of the potential for underestimations.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Articulação do Punho/diagnóstico por imagem
11.
Rheumatology (Oxford) ; 59(8): 1957-1968, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764973

RESUMO

OBJECTIVES: Peficitinib, a novel Janus kinase (JAK) inhibitor, demonstrated promising results in treating RA in phase 3 clinical trials. This in vitro study was undertaken to characterize the pharmacological properties of peficitinib and investigate the involvement of JAK and signal transducer and activator of transcription (STAT) pathways in the pathological processes of SSc, which is also an autoimmune disease. METHODS: Phosphorylation levels of STAT molecules were assessed in peripheral blood mononuclear cells collected from patients with RA or SSc and healthy subjects, and in skin specimens obtained from 19 patients with SSc. In vitro inhibition of STAT phosphorylation and cytokine/chemokine production by peficitinib, tofacitinib and baricitinib were also characterized. RESULTS: Higher spontaneous STAT1 or STAT3 phosphorylation was observed in peripheral T-cells and monocytes from patients with RA and SSc compared with healthy subjects. In skin sections from patients with SSc, phosphorylated STAT3-positive cells were found in almost all cases, irrespective of disease subtype or patient characteristics. Conversely, phosphorylated STAT1-positive cells were observed only in samples from untreated patients with diffuse disease of short duration. Peficitinib inhibited STAT phosphorylation induced by various cytokines, with comparable efficacy to tofacitinib and baricitinib. Peficitinib also suppressed cytokine and chemokine production by peripheral blood mononuclear cells and skin fibroblasts. CONCLUSION: Our results suggest that JAK/STAT pathways are constitutively activated in SSc and RA, and that the JAK inhibitor may represent a novel therapeutic option for SSc.


Assuntos
Adamantano/análogos & derivados , Artrite Reumatoide/metabolismo , Inibidores de Janus Quinases/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Niacinamida/análogos & derivados , Escleroderma Sistêmico/metabolismo , Adamantano/farmacologia , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Niacinamida/farmacologia , Fosforilação/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo
12.
Clin J Gastroenterol ; 13(3): 421-427, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31782114

RESUMO

A 76-year-old man was diagnosed with multiple hepatocellular carcinomas (HCCs). He underwent right lobectomy and partial resection of the liver after transcatheter arterial embolization at our hospital. The pathology report was moderately differentiated HCC (fT4N0M0 Stage Iva, Vp1, Vv0). Follow-up CT revealed a lesion in the right ventricle 3 years after surgery. Moderately differentiated HCC was determined on myocardial biopsy, and the lesion was diagnosed as cardiac metastasis of HCC. No recurrence of HCC was observed in the liver. Radiation therapy (39 Gy/13 fr) was performed for the cardiac metastasis, and oral lenvatinib 8 mg/day was started. Evaluation by mRECIST on contrast-enhanced CT indicate a partial response (PR). Lenvatinib has been continued for 7 months. Cardiac metastasis of HCC is extremely rare; herein, we have also provided a literature reviews.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Cardíacas/secundário , Neoplasias Hepáticas/patologia , Idoso , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino
13.
Int J Rheum Dis ; 22(7): 1312-1318, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099177

RESUMO

AIM: Previous studies have reported that patients with rheumatoid arthritis (RA) have a higher risk of developing cardiovascular disease (CVD) than the general population. A major cause of CVD is atherosclerosis, which can be evaluated with carotid ultrasonography (US). As far as we know, there have been no large-scale carotid artery US studies in Japanese patients with RA. The aim of this study was to identify the risk factors for atherosclerosis in Japanese patients with RA. METHODS: The study subjects underwent physical examinations, laboratory tests and US examination, and answered a questionnaire about their lifestyle. Carotid US was performed to measure the maximum carotid intima media thickness (max cIMT) and to detect plaques. RESULTS: Atherosclerosis was detected in 238 patients (52%). Age, hypertension, and total/high-density lipoprotein cholesterol ratio were positively related to max cIMT. Presence of plaques was related to age, Disease Activity Score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR), smoking, and any biological treatment. DAS28-ESR correlated positively not with cIMT but with the development of plaques in our patients with low disease activity (average DAS28-ESR of 2.7). CONCLUSION: Disease Activity Score of 28 joints-erythrocyte sedimentation rate was related to the size and number of plaques, whereas only traditional risk factors were related to max cIMT. This indicated that the inflammatory conditions of RA could affect the formation of atherosclerotic plaques. For the management of CVD in patients with RA, it may be important to control not only traditional risk factors, but also RA disease activity.


Assuntos
Artrite Reumatoide/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Doenças das Artérias Carótidas/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Adulto Jovem
14.
Rheumatol Int ; 38(9): 1679-1689, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29974186

RESUMO

Rheumatoid arthritis (RA) patients often have altered body composition including reduced muscle mass and increased fat mass. Some RA patients are likely to increase visceral fat without obesity [Body Mass Index (BMI) ≥ 25]. The objective of the study was to determine the association between obesity and/or visceral adiposity and the risk for atherosclerosis in Japanese RA patients. Obesity was evaluated using the BMI, with visceral adiposity evaluated using the visceral fat area (VFA) and the visceral/subcutaneous fat ratio (V/S ratio), quantified using the dual bioelectrical impedance method. Atherosclerosis was evaluated based on the intima-media thickness (IMT) and Plaque score (PS) of the carotid artery, measured using ultrasonography. Multivariate analysis was performed to determine the factors associated with IMT and PS. IMT and PS were compared among groups of patients sub-classified according to BMI and VFA levels. The V/S ratio was higher in RA patients than healthy controls, after adjustment for age, BMI, and waist circumference. On multivariate analysis, the V/S ratio, but not the BMI, was independently associated with the IMT and PS. Among the sub-classifications for BMI and VFA, non-obese patients with a high visceral adiposity (18.5 ≤ BMI < 25 kg/m2 and VFA ≥ 100 cm2) had the highest IMT (mean IMT, 0.93 ± 0.29 mm; maximum IMT, 1.44 ± 0.71 mm) and PS (1.43 ± 0.61), compared to all other BMI and VFA subgroups. RA patients have increased visceral adiposity, which is associated with a high prevalence of atherosclerotic of plaques. Non-obese RA patients who have visceral adiposity have a specifically higher risk for atherosclerosis.


Assuntos
Adiposidade , Artrite Reumatoide/epidemiologia , Aterosclerose/epidemiologia , Gordura Intra-Abdominal/metabolismo , Obesidade/epidemiologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Distribuição da Gordura Corporal , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/patologia , Fatores de Risco
15.
J Med Ultrason (2001) ; 45(1): 25-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28836084

RESUMO

PURPOSE: The purpose of this study was to clarify the effect of ultrasonic irradiation on biofilm produced by Staphylococcus epidermidis (S. epidermidis), which causes central venous catheter-related infections. MATERIALS AND METHODS: Staphylococcus epidermidis (S. epidermidis, ATCC 35984 RP 62A) was used in this study. First, biofilm was prepared from S. epidermidis on the bottom of the upper left well of a 6-well plate. Next, the biofilm was irradiated for 24 h with 1-MHz ultrasound (US) in the continuous wave mode to serve as the US irradiation group. The acoustic power irradiated below the bottom of the well was 3.8 mW. As a control (non-US irradiation group), non-irradiated biofilm on the bottom of a 6-well plate was incubated at 37 °C in an atmosphere of 5.0% CO2. After US irradiation, the bottoms of the wells were stained with 0.1% crystal violet for 60 s. To extract the crystal violet, 99.5% ethanol was added to the wells, and the extracted solutions were measured at an absorbance of 595 nm. RESULT: The absorbance of the US irradiation group was significantly less than that of the non-US irradiation group (p < 0.01). CONCLUSION: US irradiation can decrease the amount of S. epidermidis biofilm when the duration of US irradiation is sufficiently long even if the acoustic intensity is low.


Assuntos
Biofilmes/efeitos da radiação , Staphylococcus epidermidis/efeitos da radiação , Ondas Ultrassônicas , Humanos , Modelos Teóricos , Staphylococcus epidermidis/fisiologia
16.
Transplantation ; 100(12): 2611-2620, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27861289

RESUMO

BACKGROUND: Blockade of CD28-mediated T cell costimulation by a modified cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig), belatacept, is a clinically effective immunosuppressive therapy for the prevention of renal allograft rejection. Use of belatacept-based calcineurin inhibitor-free immunosuppression, however, has demonstrated an increased frequency of cellular rejection episodes and immunosuppression-related safety issues relative to conventional regimens. Furthermore, belatacept typically requires infusion for its administration chronically, which may present an inconvenience to patients. To address these issues, a novel CTLA4-Ig variant, ASP2409, with improved CD86 binding selectivity and affinity relative to belatacept was created using DNA shuffling directed evolution methods. METHODS: We evaluated the immunosuppressive effect of ASP2409 on in vitro alloimmune T cell responses, in vivo tetanus toxoid (TTx)-induced immunological responses and renal transplantation in cynomolgus monkeys. RESULTS: ASP2409 had 6.1-fold higher and 2.1-fold lower binding affinity to monkey CD86 and CD80 relative to belatacept, respectively. ASP2409 was 18-fold more potent in suppressing in vitro alloimmune T cell responses relative to belatacept. In a cynomolgus monkey TTx immunization model, ASP2409 inhibited anti-TTx immune responses at a 10-fold lower dose level than belatacept. In a cynomolgus monkey renal transplantation model, subcutaneous injection of 1 mg/kg ASP2409 prevented allograft rejection through complete CD86 and partial CD80 receptor occupancies and dramatically prolonged renal allograft survival in combination with tacrolimus or mycophenolate mofetil/methylprednisolone. CONCLUSIONS: These results support the potential of ASP2409 as an improved CTLA4-Ig for maintenance immunosuppression in organ transplantation.


Assuntos
Abatacepte/farmacologia , Antígeno B7-2/imunologia , Imunoconjugados/farmacologia , Imunossupressores/farmacologia , Transplante de Rim , Animais , Antígeno B7-1/imunologia , Antígenos CD28/imunologia , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunoconjugados/imunologia , Imunoglobulina G/imunologia , Imunossupressão , Cinética , Macaca fascicularis , Masculino , Linfócitos T/imunologia , Toxoide Tetânico/farmacologia
17.
Int Immunopharmacol ; 40: 310-317, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27662596

RESUMO

The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods. Here we evaluated the effect of ASP2408 in vitro using cynomolgus monkey and rat T cell proliferation assays and in vivo using cynomolgus monkey tetanus toxoid (TTx) immunization and a rat rheumatoid arthritis model. ASP2408 was 290-fold and 21-fold more potent in suppressing in vitro monkey T cell proliferation than abatacept and belatacept, respectively. ASP2408 inhibited anti-TTx immunological reactions in cynomolgus monkey at a 10-fold lower dose level than belatacept, through complete CD86 and partial CD80 receptor occupancies, and also suppressed inflammation in the rat collagen-induced arthritis model. Overall, improved immunosuppressive potency of ASP2408 relative to abatacept and belatacept correlated well with improved CD86 binding affinity. These results may support the advantage of preferential enhancement of CD86 binding affinity to inhibit T cell-mediated immune response and improved dosing convenience in humans relative to abatacept or belatacept.


Assuntos
Antígeno B7-2/imunologia , Imunossupressores , Abatacepte/sangue , Abatacepte/farmacologia , Abatacepte/uso terapêutico , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Antígeno B7-1/imunologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo II/imunologia , Feminino , Pé/patologia , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Macaca fascicularis , Masculino , Ratos , Linfócitos T/efeitos dos fármacos , Toxoide Tetânico/imunologia
18.
Pharmacology ; 91(3-4): 207-13, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23486212

RESUMO

The effect of CP-690550 (tofacitinib), a new Janus kinase (JAK) inhibitor, was evaluated in chronic allergic dermatitis. Allergic contact dermatitis was induced in rat ears by repeated application of oxazolone. This dermatitis was accompanied by sustained ear swelling and marked epidermal hyperplasia. In the induced ear, a lot of inflammatory cells infiltrated into the dermis site and the amounts of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-22 were elevated. Orally administered CP-690550 significantly suppressed ear swelling as well as epidermal thickening, and the effect at 10 mg/kg was comparable to that of cyclosporin A and etanercept. These results suggest a great potential of CP-690550, a JAK inhibitor, as a treatment for chronic dermatitis featuring epidermal hyperplasia (in the pathogenesis of which IFN-γ, TNF-α and IL-22 play a role) such as psoriasis and chronic atopic dermatitis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Alérgica de Contato/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Animais , Citocinas/imunologia , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/patologia , Orelha , Feminino , Hiperplasia/etiologia , Hiperplasia/imunologia , Hiperplasia/patologia , Janus Quinases/antagonistas & inibidores , Oxazolona , Ratos , Ratos Sprague-Dawley , Pele/patologia
19.
J Med Ultrason (2001) ; 40(1): 1-2, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27276917
20.
J Med Ultrason (2001) ; 39(1): 29-31, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27278703

RESUMO

Sister Mary Joseph's nodule (SMJN), which is known as a malignant tumor metastasized to the umbilicus, is a rare condition. We report ultrasonic findings of SMJN secondary to ovarian cancer in a 66-year-old woman. The umbilical tumor was observed as a hypoechoic mass with punctate hyperechoic foci. A pathological specimen obtained by needle biopsy confirmed adenocarcinoma with psammoma bodies. A comparison of the ultrasonographic findings with the pathological findings of the resected specimen suggested that the hyperechoic foci corresponded to psammoma bodies. When hyperechoic foci are observed inside SMJN by ultrasonography, adenocarcinoma from ovarian cancer should be included in the differential diagnosis.

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