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Most mesenchymal tumors found in the uterine corpus are benign tumors; however, uterine leiomyosarcoma is a malignant tumor with unknown risk factors that repeatedly recurs and metastasizes. In some cases, the histopathologic findings of uterine leiomyoma and uterine leiomyosarcoma are similar and surgical pathological diagnosis using excised tissue samples is difficult. It is necessary to analyze the risk factors for human uterine leiomyosarcoma and establish diagnostic biomarkers and treatments. Female mice deficient in the proteasome subunit low molecular mass peptide 2 (LMP2)/ß1i develop uterine leiomyosarcoma spontaneously. MATERIAL AND METHODS: Out of 334 patients with suspected uterine mesenchymal tumors, patients diagnosed with smooth muscle tumors of the uterus were selected from the pathological file. To investigate the expression status of biomarker candidate factors, immunohistochemical staining was performed with antibodies of biomarker candidate factors on thin-cut slides of human uterine leiomyosarcoma, uterine leiomyoma, and other uterine mesenchymal tumors. RESULTS AND DISCUSSION: In human uterine leiomyosarcoma, there was a loss of LMP2/ß1i expression and enhanced cyclin E1 and Ki-67/MIB1 expression. In human uterine leiomyomas and normal uterine smooth muscle layers, enhanced LMP2/ß1i expression and the disappearance of the expression of E1 and Ki-67/MIB1 were noted. The pattern of expression of each factor in other uterine mesenchymal tumors was different from that of uterine leiomyosarcoma. CONCLUSIONS: LMP2/ß1i, cyclin E1, and Ki-67/MIB1 may be candidate factors for biomarkers of human uterine leiomyosarcoma. Further large-cohort clinical trials should be conducted to establish treatments and diagnostics for uterine mesenchymal tumors.
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Biomarcadores Tumorais , Ciclina E , Leiomioma , Leiomiossarcoma , Proteínas Oncogênicas , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Leiomiossarcoma/diagnóstico , Leiomioma/metabolismo , Leiomioma/patologia , Leiomioma/diagnóstico , Leiomioma/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Ciclina E/metabolismo , Ciclina E/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Adulto , Cisteína EndopeptidasesRESUMO
We propose a data-driven technique to infer microscopic physical quantities from nuclear magnetic resonance (NMR) spectra, in which the data size and quality required for the Bayesian inference are investigated. The 59Co-NMR measurement of YbCo2Zn20 single crystal generates complex spectra with 28 peaks. By exploiting the site symmetry in the crystal structure, the isotropic Knight shift Kiso and nuclear quadrupole resonance (NQR) frequency νQ were respectively estimated to be Kiso=0.7822±0.0090% and νQ=2.008±0.016 MHz (T=20 K and H≃10.2 T) by analyzing only 30 data points from one spectrum. The estimated νQ is consistent with the precise value obtained in the NQR experiment. Our method can significantly reduce the measurement time and the computational cost of data analysis in NMR experiments.
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Periodontitis is a multifactorial disease that progresses via dynamic interaction between bacterial and host-derived genetic factors. The recent trend of omics analyses has discovered many periodontitis-related risk factors. However, how much the individual factor affects the pathogenesis of periodontitis is still unknown. This article aims to identify multiple key factors related to the pathogenesis of periodontitis and quantitatively predict the influence of each factor on alveolar bone resorption by omics analysis and mathematical modeling. First, we induced periodontitis in mice (n = 3 or 4 at each time point) by tooth ligation. Next, we assessed alveolar bone resorption by micro-computed tomography, alterations in the gene expression by RNA sequencing, and the microbiome of the gingivae by 16S ribosomal RNA sequencing during disease pathogenesis. Omics data analysis identified key players (bacteria and molecules) involved in the pathogenesis of periodontitis. We then constructed a mathematical model of the pathogenesis of periodontitis by employing ordinary differential equations that described the dynamic regulatory interplay between the key players and predicted the alveolar bone integrity as output. Finally, we estimated the model parameters using our dynamic experimental data and validated the model prediction of influence on alveolar bone resorption by in vivo experiments. The model predictions and experimental results revealed that monocyte recruitment induced by bacteria-mediated Toll-like receptor activation was the principal reaction regulating alveolar bone resorption in a periodontitis condition. On the other hand, osteoblast-mediated osteoclast differentiation had less impact on bone integrity in a periodontitis condition.
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Perda do Osso Alveolar , Periodontite , Camundongos , Animais , Microtomografia por Raio-X/efeitos adversos , Modelos Animais de Doenças , Perda do Osso Alveolar/metabolismo , Osteoclastos/metabolismo , Periodontite/microbiologiaRESUMO
BACKGROUND AND PURPOSE: Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. MATERIALS AND METHODS: 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. RESULTS: Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. CONCLUSIONS: Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Neoplasias Encefálicas/patologia , Astrocitoma/patologia , Glioma/patologia , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Assessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). PATIENTS AND METHODS: The subjects were 16 patients who underwent SBRT for solitary HCC ≤3cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8-43 (median: 28) months, ages from 59-85 (median: 65) years. RESULTS: Changes in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself. CONCLUSIONS: This is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.
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Biomarcadores/sangue , Antígeno CA-19-9/sangue , Carcinoma Hepatocelular/radioterapia , Hepatite C Crônica/complicações , Neoplasias Hepáticas/radioterapia , Precursores de Proteínas/sangue , alfa-Fetoproteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , ProtrombinaRESUMO
BACKGROUND: Dental professionals have so many opportunities to use injection needles and sharp instruments during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at the dental departments of Hiroshima University Hospital. OBJECTIVE: This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with antiretroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. METHODS: Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals from 2007 to 2018 were collected. RESULTS: Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell number and HIV-RNA load were 1176 (768-1898) /µl and less than 20 copies/ml, respectively, in all the patients. Two of the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests. CONCLUSION: ; These data might support the concept of "undetectable equals untransmittable", although HIV exposure in this study was not through sexual transmission.
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Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ferimentos Penetrantes Produzidos por Agulha/tratamento farmacológico , Exposição Ocupacional/prevenção & controle , Profilaxia Pós-Exposição/métodos , Adulto , Clínicas Odontológicas/estatística & dados numéricos , Odontólogos/estatística & dados numéricos , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Psoriatic arthritis (PsA) is a chronic and debilitating disease that can be managed by different clinical specialists. OBJECTIVES: The objective of the LOOP study was to evaluate the impact of clinical specialty setting on the time to diagnosis and treatment of patients with PsA. Clinical disease activity and disease burden were also compared between clinical settings. METHODS: LOOP was a cross-sectional, multicentre, observational study conducted in 17 countries in Western and Eastern Europe, the Middle East, Latin America and Asia. Adult patients (≥18 years) with a suspected or established diagnosis of PsA who were routinely visiting a rheumatologist, dermatologist or non-rheumatology/non-dermatology physician were enrolled. All patients were assessed by both a rheumatologist and a dermatologist. RESULTS: Of 1483 enrolled patients, a total of 1273 had a confirmed diagnosis of PsA. There was no significant difference in the median time from onset of inflammatory musculoskeletal symptoms to PsA diagnosis between patients enrolled by rheumatologists and dermatologists (6.0 vs. 3.9 months). However, the median time from diagnosis to first treatment with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) was significantly shorter in the rheumatology setting compared with the dermatology setting (0 vs. 2.0 months; P < 0.001). In addition, disease activity was significantly higher in the dermatology setting compared with the rheumatology setting. CONCLUSIONS: Differences in the management and clinical status of patients with PsA were observed between the rheumatology and dermatology settings. Importantly, median time from diagnosis to first csDMARD was significantly shorter in the rheumatology setting, and patients in the dermatology setting had higher disease activity. These data show the importance of improved collaboration between rheumatologists and dermatologists.
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Artrite Psoriásica , Dermatologia , Psoríase , Reumatologia , Adulto , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Ásia , Estudos Transversais , Gerenciamento Clínico , Europa Oriental , Humanos , Oriente MédioRESUMO
The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm3 than in the control group. It became clear that the patients taking anti-HIV drugs, especially the CD4+ count < 500/mm3 group, had a deteriorated oral environment and dysgeusia, suggesting that the management of oral hygiene is necessary to maintain oral health, which leads to systemic health.
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Infecções por HIV , Paladar , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Humanos , Japão/epidemiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS: Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS: The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION: Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.
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Biomarcadores/sangue , Glucuronidase/sangue , Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Insuficiência Renal/sangue , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Kidney transplantation is performed as a useful treatment to improve the quality of life (QOL) of patients with end-stage renal failure; however, the correlation between mood status and QOL among recipients post-kidney transplantation have yet to be clarified. METHODS: Sixty-eight post-kidney transplantation patients who visited our institution between March and December 2016 were enrolled in this study. The QOL of the participants as measured by the Short Form-36 Health Survey Version 2 (SF-36v2) questionnaire was compared to results gathered from hemodialysis patients in a previous study. To identify the factors associated with QOL, a multiple regression analysis was performed, including some physical, mental, and socioeconomic characteristics as well as the Profile of Mood States as independent variables. RESULTS: The QOL of the transplantation group was significantly higher for all 8 subscales of SF-36v2 compared to the hemodialysis group. Among the factors, greater age and higher Confusion levels were related to lower physical QOL. In addition, higher Vigor and lower Fatigue levels were related to higher mental QOL, while the condition of having an occupation was related to higher role/social QOL. CONCLUSION: The QOL of recipients after kidney transplantation was better than that of hemodialysis patients. It is important to pay attention to mood status, especially confusion and fatigue, in order to maintain and improve the QOL of the recipient after kidney transplantation. Kidney transplantation can be a beneficial treatment not only physically but also psychologically and socially.
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Transplante de Rim/psicologia , Qualidade de Vida , Transplantados/psicologia , Adulto , Fadiga , Feminino , Humanos , Falência Renal Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Inquéritos e QuestionáriosRESUMO
We show that blister-based-laser-induced forward-transfer can be used to cleanly desorb and transfer nano- and micro-scale particles between substrates without exposing the particles to the laser radiation or to any chemical treatment that could damage the intrinsic electronic and optical properties of the materials. The technique uses laser pulses to induce the rapid formation of a blister on a thin metal layer deposited on glass via ablation at the metal/glass interface. Femtosecond laser pulses are advantageous for forming beams of molecules or small nanoparticles with well-defined velocity and narrow angular distributions. Both fs and ns laser pulses can be used to cleanly transfer larger nanoparticles including relatively fragile monolayer 2D transition metal dichalcogenide crystals and for direct transfer of nanoparticles from chemical vapour deposition growth substrates, although the mechanisms for inducing blister formation are different.
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OBJECTIVE: To investigate the efficacy and safety of belimumab, a human immunoglobulin monoclonal antibody against B lymphocyte stimulator, in a subset of patients with systemic lupus erythematosus (SLE) who were hypocomplementemic (C3 <90 mg/dl and/or C4 <10 mg/dl) and anti-double-stranded DNA (anti-dsDNA) positive (≥30 IU/ml) at baseline. METHODS: In this phase III, double-blind, placebo-controlled study (BEL112341; ClinicalTrials.gov identifier: NCT01484496), patients with moderate to severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI] score ≥8) were randomized (2:1) to receive weekly subcutaneous (SC) belimumab 200 mg or placebo, plus standard SLE therapy, for 52 weeks. The primary end point was SLE Responder Index 4 (SRI-4) response rate at week 52. Secondary end points were time to severe flare and reduction in corticosteroid dose (weeks 40-52). Safety was assessed throughout. RESULTS: Of the 836 patients in the intent-to-treat (ITT) population, 356 were hypocomplementemic and anti-dsDNA positive at baseline (108 in the placebo group and 248 in the SC belimumab 200 mg group). Compared with placebo, the belimumab group contained more SRI-4 responders (47.2% versus 64.6%; P = 0.0014), had a lower incidence of severe flare according to the SELENA-SLEDAI flare index (31.5% versus 14.1%), and had a greater percentage of patients who reduced corticosteroid dosage by ≥25% to ≤7.5 mg/day during weeks 40-52 (11.4% versus 20.7%; P = 0.0844). Adverse events (AEs) were similar between treatment groups. CONCLUSION: Our findings indicate that in hypocomplementemic, anti-dsDNA-positive SLE patients, weekly SC belimumab 200 mg significantly improves SRI-4 response, decreases severe flare incidence, and reduces corticosteroid use versus placebo; a trend toward greater benefit compared with the overall ITT population was observed. AEs were consistent with the known safety profile of belimumab.
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Anticorpos Antinucleares/sangue , Anticorpos Monoclonais Humanizados/administração & dosagem , Complemento C3/deficiência , DNA/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Análise de Intenção de Tratamento , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the efficacy and safety of laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair in patients who have undergone robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: From July 2014 to December 2016, TAPP inguinal hernia repair was conducted in 40 consecutive patients who had previously undergone RALP. Their data were retrospectively analyzed as an uncontrolled case series. RESULTS: The mean operation time in patients who had previously undergone RALP was 99.5 ± 38.0 min. The intraoperative blood loss volume was small, and the duration of hospitalization was 2.0 ± 0.5 days. No intraoperative complications or major postoperative complications occurred. During the average 11.2-month follow-up period, no patients who had previously undergone prostatectomy developed recurrence. CONCLUSIONS: Laparoscopic TAPP inguinal hernia repair after RALP was safe and effective. TAPP inguinal hernia repair may be a valuable alternative to open hernioplasty.
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Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos RobóticosAssuntos
Dermatomiosite , Glucocorticoides , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais , Ribonucleosídeos , Tacrolimo , Autoanticorpos/sangue , Dermatomiosite/sangue , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/efeitos adversos , Índice de Gravidade de Doença , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA). She developed end-stage renal disease due to suspicious IgA nephropathy at age 33 years. Kidney transplantation was performed at age 35 years, and aHUS recurred 2 weeks later, leading to the progressive hemolytic anemia and renal dysfunction. Therefore, she underwent plasma therapy several times. Because it was difficult to continue to plasma therapy for severe allergy, eculizumab was proposed as an alternate therapy. Treatment with eculizumab was initiated 36 days after renal transplantation. After 3 years of eculizumab treatment, and without plasma therapy, schistocytes decreased, haptoglobin increased to within normal limits, creatinine levels stabilized, and no further episodes of diarrhea were reported. At protocol biopsy 1 year after transplantation, she was diagnosed with C4d-negative subclinical AMR. However, her pathologic findings at follow-up biopsy 3 years after transplantation were recovered. We conclude that eculizumab alone, without plasma therapy, is sufficient to treat recurrence of aHUS and AMR due to DSA after renal transplantation and to maintain long-term graft function.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Síndrome Hemolítico-Urêmica Atípica/complicações , Feminino , Glomerulonefrite por IGA/complicações , Rejeição de Enxerto/complicações , Rejeição de Enxerto/imunologia , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Recidiva , Tacrolimo/uso terapêutico , Doadores de Tecidos , Resultado do TratamentoRESUMO
AIM: Progranulin (PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel. METHODS: Isometric contraction of rat isolated superior mesenteric artery was measured. RESULTS: Pre-treatment with PGRN (10-100 ng mL-1 , 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL-1 ) augmented acetylcholine (ACh; 30 nm)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL-1 ) augmented ACh (10 µm)-induced nitric oxide (NO)-mediated relaxation in the presence of indomethacin (10 µm), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 mm), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh (10 µm, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL-1 ) augmented an NO donor, sodium nitroprusside (SNP; 30 nm-1 µm)- but not a membrane-permeable cGMP analogue, 8-bromo-cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 µm), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL-1 ) increased SNP (30 nm, 5 min)-induced cGMP production as determined by enzyme immunoassay. CONCLUSION: We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension.