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PURPOSE: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. METHODS: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. RESULTS: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. CONCLUSION: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.
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Células Dendríticas , Linfadenite Histiocítica Necrosante , Interferon-alfa , Linfonodos , Humanos , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/sangue , Linfadenite Histiocítica Necrosante/imunologia , Masculino , Interferon-alfa/sangue , Feminino , Criança , Adolescente , Adulto , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Pré-Escolar , Linfonodos/patologia , Proteínas de Resistência a Myxovirus/genética , Proteínas de Resistência a Myxovirus/metabolismo , Proteínas de Resistência a Myxovirus/sangue , Adulto Jovem , Pessoa de Meia-Idade , Linfoma/diagnóstico , Linfoma/imunologia , Linfoma/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/sangue , Biomarcadores/sangue , Citocinas/sangue , Citocinas/metabolismoRESUMO
OBJECTIVE: Recently, the Pediatric Rheumatology International Trials Organization (PRINTO) has proposed revisions to the current International League of Associations for Rheumatology (ILAR) criteria for systemic juvenile idiopathic arthritis (s-JIA). Interleukin (IL)-18 overproduction plays a significant role in the pathogenesis of s-JIA. This study aimed to evaluate the performance of the PRINTO criteria compared with the ILAR criteria and determine whether serum IL-18 levels improve their diagnostic performances. METHODS: Overall, 90 patients with s-JIA and 27 patients with other febrile disease controls presenting with a prolonged fever of > 14 days and arthritis and/or erythematous rash were enrolled. The ILAR and PRINTO classification criteria were applied to all patients and examined with expert diagnoses. Enzyme-linked immunosorbent assay was used for measuring serum IL-18 levels. RESULTS: The PRINTO criteria had higher sensitivity but lower specificity than the ILAR criteria (sensitivity: PRINTO 0.856, ILAR 0.533; specificity: PRINTO 0.259, ILAR 0.851). With the addition of serum IL-18 levels ≥ 4,800 pg/mL, the sensitivity of the ILAR criteria and specificity of the PRINTO criteria were improved to 1.000 and 1.000, respectively. PRINTO plus serum IL-18 levels ≥ 4,800 pg/mL showed the highest value in Youden's index (sensitivity - [1 - specificity]). CONCLUSION: Serum IL-18 levels could improve the diagnostic performance of the PRINTO and ILAR criteria for s-JIA. The PRINTO criteria plus serum IL-18 levels ≥ 4,800 pg/mL could be the best diagnostic performance for s-JIA.
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Artrite Juvenil , Interleucina-18 , Humanos , Artrite Juvenil/sangue , Artrite Juvenil/diagnóstico , Interleucina-18/sangue , Masculino , Feminino , Criança , Pré-Escolar , Sensibilidade e Especificidade , Adolescente , Lactente , Ensaio de Imunoadsorção Enzimática/métodos , Reumatologia/métodosRESUMO
Adult T-cell leukemia/lymphoma (ATL) occurs after human T-cell leukemia virus type-1 (HTLV-1) infection with a long latency period exceeding several decades. This implies the presence of immune evasion mechanisms for HTLV-1-infected T cells. Although ATL cells have a CD4+CD25+ phenotype similar to that of regulatory T cells (Tregs), they do not always possess the immunosuppressive functions of Tregs. Factors that impart effective immunosuppressive functions to HTLV-1-infected cells may exist. A previous study identified a new CD13+ Treg subpopulation with enhanced immunosuppressive activity. We, herein, describe the paired CD13- (designated as MT-50.1) and CD13+ (MT-50.4) HTLV-1-infected T-cell lines with Treg-like phenotype, derived from the peripheral blood of a single patient with lymphoma-type ATL. The cell lines were found to be derived from HTLV-1-infected non-leukemic cells. MT-50.4 cells secreted higher levels of immunosuppressive cytokines, IL-10 and TGF-ß, expressed higher levels of Foxp3, and showed stronger suppression of CD4+CD25- T cell proliferation than MT-50.1 cells. Furthermore, the CD13 inhibitor bestatin significantly attenuated MT-50.4 cell growth, while it did not for MT-50.1 cells. These findings suggest that CD13 expression may be involved in the increased Treg-like activity of MT-50.4 cells. Hence, MT-50.4 cells will be useful for in-depth studies of CD13+Foxp3+ HTLV-1-infected cells.
Assuntos
Antígenos CD13 , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfócitos T Reguladores , Humanos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucemia-Linfoma de Células T do Adulto/imunologia , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/virologia , Leucemia-Linfoma de Células T do Adulto/patologia , Antígenos CD13/metabolismo , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Linhagem CelularRESUMO
OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.
Assuntos
Citocinas , Síndrome de Linfonodos Mucocutâneos , Choque Séptico , Síndrome de Resposta Inflamatória Sistêmica , Infecções por Yersinia pseudotuberculosis , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Citocinas/sangue , Humanos , Interleucina-6/sangue , Quimiocina CXCL9/sangue , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Choque Séptico/sangue , Choque Séptico/diagnóstico , Infecções por Yersinia pseudotuberculosis/sangue , Infecções por Yersinia pseudotuberculosis/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnósticoRESUMO
We had a case of Listeria monocytogenes (LM) meningitis complicated with hypercytokinemia and hemophagocytic lymphohistiocytosis in a healthy 22-month-old boy. He was admitted to our hospital with a fever, vomiting, mild consciousness disturbances, and extraocular muscle paralysis. Magnetic resonance imaging (MRI) revealed bilateral deep white matter lesions. After receiving ampicillin, meropenem, and gentamicin, his cerebrospinal fluid (CSF) culture results turned negative on the third day of hospitalization. However, the fever intermittently persisted, and it took approximately 40 days to completely resolve. During this period, various inflammatory cytokine levels, particularly neopterin, in the blood and CSF remained elevated. Therefore, long-term administration of corticosteroids in addition to antibiotics was required. The use of dexamethasone appeared to be effective for neurological disorders such as consciousness disturbance and extraocular muscle paralysis associated with abnormal brain MRI findings. LM meningitis may present with encephalopathy and persistent fever due to hypercytokinemia. In such cases, corticosteroid therapy should be considered.
Assuntos
Listeria monocytogenes , Meningite por Listeria , Corticosteroides/uso terapêutico , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Síndrome da Liberação de Citocina , Citocinas , Dexametasona/uso terapêutico , Gentamicinas/uso terapêutico , Humanos , Lactente , Masculino , Meningite por Listeria/líquido cefalorraquidiano , Meningite por Listeria/diagnóstico , Meningite por Listeria/tratamento farmacológico , Meropeném/uso terapêutico , Neopterina/uso terapêutico , Paralisia/tratamento farmacológicoRESUMO
There has been increasing interest in colloidal particles adsorbed at the air-water interface, which lead to stabilization of aqueous foams and liquid marbles. The wettability of the particles at the interface is known to play an important role in determining the type of air/water dispersed system. Foams are preferably formed using relatively hydrophilic particles, and liquid marbles tend to be formed using relatively hydrophobic particles. In this study, submicrometer-sized polystyrene particles carrying poly(N,N-diethylaminoethyl methacrylate) hairs (PDEA-PS particles), which are synthesized by dispersion polymerization, are demonstrated to work as a particulate stabilizer for both aqueous foams and liquid marbles. A key point for the hydrophilic PDEA-PS particles to stabilize both aqueous foams and liquid marbles, which have been generally stabilized with hydrophilic and hydrophobic particles, respectively, is the wetting mode of the particles with respect to water. The flocculates of PDEA-PS particles adsorb to the air-water interface from the aqueous phase to stabilize foam in a Wenzel mode, and the dried PDEA-PS particles adsorb to the interface as aggregates from the air phase to stabilize liquid marbles in a metastable Cassie-Baxter mode. On the basis of the difference in the wetting mode, stabilization of an air-in-water-in-air multiple gas-liquid dispersed system, named "foam marble", is realized. After the evaporation of water from the foam marble, a porous sphere is successfully obtained with pore sizes of a few tens of micrometers (reflecting the bubble sizes) and a few tens of nanometers (reflecting the gap sizes among the PDEA-PS particles).
RESUMO
A 9-year-old boy, diagnosed with double outlet right ventricle after birth, suffered sinus node dysfunction and non-sustained junctional tachycardia after an extracardiac total cavopulmonary connection (TCPC). Spontaneous atrial tachycardia appeared 3 years after an extracardiac TCPC. Sotalol was administered but the bradycardia was obvious. It was difficult to increase sotalol and atrial tachycardia was uncontrollable. Atrial tachycardia continued with symptoms; direct current (DC) cardioversion was frequently required. Five years after extracardiac TCPC, we implanted a pacemaker with atrial antitachycardia pacing (ATP) using epicardial leads. On day 2 post operation, wide QRS tachycardia appeared. Due to decreased blood pressure, DC cardioversion was immediately performed, but it recurred from atrial premature contraction. We judged this was atrial tachycardia with 1:1 atrioventricular conduction based on an intracardiac electrogram and it was terminated by burst atrial pacing from the pacemaker. After changing atrial pacing rate to 150 ppm, atrial tachycardia could be suppressed. Due to atrial pacing and increasing sotalol gradually, junctional tachycardia terminated spontaneously, and atrial tachycardia was not induced after pacemaker implantation. In conclusion, implantation of a pacemaker with ATP and intensification of antiarrhythmic drugs is an effective treatment strategy for pediatric patients with bradycardia-tachycardia syndrome after extracardiac TCPC.
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Asfixia Neonatal , Asfixia , Asfixia Neonatal/complicações , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Concomitant therapy with acetaminophen (APAP) and low-dose aspirin is often used in clinical settings; however, it is unclear whether this combination is involved in the progression of chronic kidney disease (CKD). We hypothesized that concomitant therapy with APAP and low-dose aspirin may cause CKD progression. We carried out a retrospective 6-year cohort study that included all patients who received low-dose aspirin from January 2011 to December 2016 at Kaetsu Hospital. Primary outcome was defined as CKD progression at the end of the study compared with baseline. Among the 441 patients treated during the study period, we identified 89 cases of CKD progression. Multivariate regression analysis showed that exposure to APAP>50 g [odds ratio (OR), 2.68, 95% confidence interval (CI), 1.08-6.70], age increase by 1 year (OR, 1.05, 95% CI, 1.02-1.08), and diabetes mellitus (OR, 2.40, 95% CI, 1.41-4.08) had positive associations with CKD progression. Our findings suggested that concomitant therapy with APAP and low-dose aspirin increased the risk of CKD progression. Therefore, we recommend more thorough monitoring of serum creatinine when patients are on such concomitant therapy. Moreover, it is important to advise users of low-dose aspirin to avoid unnecessary use of APAP, in order to reduce the risk of CKD progression.
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Acetaminofen/efeitos adversos , Aspirina/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Acetaminofen/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Biomarcadores , Creatinina/sangue , Complicações do Diabetes , Progressão da Doença , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/prevenção & controle , Estudos Retrospectivos , Fatores de RiscoRESUMO
Patients with autosomal recessive (AR) disorders are usually born to parents both of whom are heterozygous carriers of the disease. However, in some instances only one of the parents is a carrier and a mutation is segregated to the patient through uniparental isodisomy (UPiD). Recently, an increasing number of such case reports has been published, and it has become clear that there are several different UPiD patterns that cause AR disorders. In this article, we report 3 remarkable patients with different patterns of UPiD. We then review 85 cases collected in the literature. We realized that they can be classified into 3 patterns: UPiD of the whole chromosome, segmental UPiD with uniparental heterodisomy (UPhD), and segmental UPiD caused by post-zygotic mitotic recombination (MiRe). Whole chromosomal UPiD accounted for the majority of cases, with paternal origin accounting for approximately twice as many cases as maternal origin. Most cases of segmental UPiD with UPhD were of maternal origin, with a dominancy of nondisjunction in meiosis I, while segmental UPiD through MiRe is the smallest pattern with equal parental origin. These differences in proportion and parental origin in each pattern can be explained by considering nondisjunction during oogenesis as the starting point and UPiD as subsequent events.
Assuntos
Transtornos Cromossômicos/genética , Dissomia Uniparental , Pré-Escolar , Transtornos Cromossômicos/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Herança Paterna , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations and a 22q partial tetrasomy were identified in one family each. All patients identified with causative genes suffered from hearing loss. Second branchial arch anomalies, including a cervical fistula or cyst, preauricular pits, and renal anomalies, were frequently identified (>60%) in patients with EYA1 aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1 aberrations. Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients.
Assuntos
Síndrome Brânquio-Otorrenal/diagnóstico , Síndrome Brânquio-Otorrenal/genética , Estudos de Associação Genética , Variação Genética , Genótipo , Fenótipo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Feminino , Marcadores Genéticos , Humanos , Lactente , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Tirosina Fosfatases/genética , Adulto JovemRESUMO
OBJECTIVE: To determine the utility of capillary blood ketone levels as an indicator of inadequate intake of breast milk in the early postnatal period. STUDY DESIGN: Levels of capillary blood beta-hydroxybutyrate (ßOHB), the main ketone body in the blood, were measured with a bedside ketone meter in 585 full-term neonates aged 48-95 hours who were breastfed exclusively. Relationships between weight-loss percentage, blood sodium, glucose, pH, partial pressure of carbon dioxide, base-deficit levels, and ßOHB levels were investigated. The diagnostic accuracy of ßOHB for predicting excessive weight loss (weight loss ≥10% of birth weight) and hypernatremic dehydration (blood sodium level ≥150 mEq/L) was determined. RESULTS: ßOHB levels were correlated positively with weight-loss percentage and blood sodium levels and were correlated negatively with blood glucose levels. The diagnostic accuracy of ßOHB was 0.846 (optimal cut off, 1.55 mmol/L; sensitivity, 80.9%, specificity, 74.0%) for predicting excessive weight loss and 0.868 (optimal cut off, 1.85 mmol/L; sensitivity, 94.3%; specificity, 69.9%) for predicting hypernatremic dehydration according to the area under the receiver operating characteristic curve. Multiple logistic analysis revealed that ßOHB and weight loss percentage were the only independent predictors of hypernatremic dehydration. Increases in ßOHB levels also were associated with worsening metabolic acidosis and hypocapnia. CONCLUSION: High ßOHB levels were associated with inadequate intake of breast milk in the early postnatal period. The use of bedside capillary blood ketone levels may be clinically useful as an indicator of dehydration, energy depletion, and acid-base imbalance in breastfeeding infants in the early postnatal period.
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Ácido 3-Hidroxibutírico/sangue , Desequilíbrio Ácido-Base/diagnóstico , Aleitamento Materno , Desidratação/diagnóstico , Desnutrição/diagnóstico , Desequilíbrio Ácido-Base/sangue , Desequilíbrio Ácido-Base/etiologia , Biomarcadores/sangue , Capilares , Desidratação/sangue , Desidratação/etiologia , Feminino , Humanos , Cuidado do Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Desnutrição/sangue , Desnutrição/etiologia , Testes Imediatos , Sensibilidade e Especificidade , Redução de PesoRESUMO
Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1ß, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Rim/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Apoptose , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Dieta Hiperlipídica , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , Transdução de Sinais , Estreptozocina/administração & dosagemRESUMO
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1ß and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.
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Carcinoma Hepatocelular/prevenção & controle , Curcumina/uso terapêutico , Proteína HMGB1/metabolismo , Neoplasias Hepáticas/prevenção & controle , Fígado/efeitos dos fármacos , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Carcinoma Hepatocelular/etiologia , Modelos Animais de Doenças , Fibrose , Humanos , Fígado/patologia , Neoplasias Hepáticas/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/complicações , Estresse Oxidativo/efeitos dos fármacos , EstreptozocinaRESUMO
A set of new theoretical equations for apparent contact angles is proposed. The equations are derived from an equilibrium of interfacial tensions of a three-phase contact line pinned at the edges of a fine structure. These equations are validated by comparison with contact-angle measurement results for 2 µL water droplets on poly(methyl methacrylate) microstructured samples with square pillars or holes. The equilibrium contact angles predicted by the new equations reasonably agree with the experimental results. In contrast, the values predicted by the Cassie-Baxter equation or the Wenzel equation do not qualitatively agree with the experimental results in pillar pattern cases because the Cassie-Baxter equation and the Wenzel equation do not account for the pinning effect.
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Le Carbone (LC) is a charcoal supplement, which contains a large amount of dietary fibers. Several studies suggested that charcoal supplement may be beneficial for stomach disorders, diarrhea, gas and indigestion. But no studies address whether LC intake would suppress inflammation, cell proliferation or disease progression in colitis. In the present study, the effect of LC on experimental colitis induced by dextran sulfate sodium (DSS) in mice and its possible mechanism of action were examined. A study was designed for 8days, using C57BL/6 female mice that were administered with 3% DSS in drinking water for 7days followed by another 1day consumption of normal water with or without treatment. LC suspension was administered daily for 7days via oral gavage using 5mg/mouse in treatment group and normal group was supplied with drinking water. LC suspension significantly attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic changes were significantly reduced by LC treatment. The inflammatory mediators TNFα, IL-1ß, p-STAT3 and p-NF-κB induced in the colon by DSS were markedly suppressed by LC. The increased activation of AMPKα in the colon was also detected in LC group. Furthermore, the apoptotic marker protein cleaved caspase 3 was down-regulated and anti-apoptotic proteins Bcl2 and Bcl-xL were significantly up-regulated by LC treatment. Taken together, our results demonstrate the ability of LC to inhibit inflammation, apoptosis and give some evidence for its potential use as adjuvant treatment of inflammatory bowel disease.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Anti-Inflamatórios/uso terapêutico , Caspase 3/metabolismo , Carvão Vegetal/uso terapêutico , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Colite/induzido quimicamente , Colo/patologia , Sulfato de Dextrana , Feminino , Humanos , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: Post-hepatectomy liver failure is one of the most serious complications liver surgeons must overcome. We previously examined olprinone, a selective phosphodiesterase III inhibitor, and demonstrated its hepatoprotective effects in rats and pigs. We herein report the results of a phase I clinical trial of olprinone in liver surgery (UMIN000004975). METHODS: Twenty-three patients who underwent hepatectomy between 2011 and 2015 were prospectively registered. In the first 6 cases, olprinone (0.1 µg/kg/min) was administered for 24 h from the start of surgery. In the remaining 17 cases, olprinone (0.05 µg/kg/min) was administered from the start of surgery until just before the transection of the liver parenchyma. The primary endpoint was safety, and the secondary endpoint was efficacy. For the evaluation of efficacy, the incidence of post-hepatectomy liver failure in 20 hepatocellular carcinoma patients was externally compared with 20 propensity score-matched patients. RESULTS: No intraoperative side effects were observed, and the morbidity rates in the analyzed cohorts were acceptable. The rate of post-hepatectomy liver failure frequency tended to be lower in the olprinone group. CONCLUSIONS: The safety of olprinone in liver surgery was confirmed. The efficacy of olprinone will be re-evaluated in clinical trials.
Assuntos
Hepatectomia , Imidazóis/administração & dosagem , Falência Hepática/prevenção & controle , Inibidores da Fosfodiesterase 3/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Piridonas/administração & dosagem , Idoso , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Incidência , Falência Hepática/epidemiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Pesquisa Translacional Biomédica , Resultado do TratamentoRESUMO
We report the patient with MPC who developed fulminant respiratory failure that leads to death with no predisposing factors after successful renal transplantation. In addition to infectious diseases, MPC should be kept in mind when post-transplantation patients develop pulmonary symptoms. The majority of the patients with MPC are asymptomatic; however, some patients develop fulminant respiratory failure and may progress to death. MPC can develop or progress in patients with no predisposing factors after successful renal transplantation.