RESUMO
Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Idoso , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Guanina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Resultado do TratamentoRESUMO
A Gram-stain-positive, rod-shaped and non-motile strain, designated PAMC 27367(T), was isolated from rainwater collected on the Bering Sea. Analysis of the 16S rRNA gene sequence of the strain showed an affiliation with the genus Rhodococcus. Phylogenetic analyses revealed that strain PAMC 27367(T) formed a robust clade with the type strains of Rhodococcus rhodnii, Rhodococcus aetherivorans and Rhodococcus ruber with 16S rRNA gene sequence similarities of 96.3 %, 95.8 % and 95.5 %, respectively. Cells of the strain grew optimally at 25 °C and at pH 6.5-7.0 in the presence of 0-2 % (w/v) sea salts. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and three unknown phospholipids. The major cellular fatty acids (>10 %) were iso-C16 : 0, C17 : 1ω8c and 10-methyl C17 : 0. Cell wall analysis showed that strain PAMC 27367(T) contained meso-diaminopimelic acid. The genomic DNA G+C content was 77.1 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic data presented here, we propose a novel species with the name Rhodococcus aerolatus sp. nov., with PAMC 27367(T) (â= KCTC 29240(T)â= JCM 19485(T)) as the type strain.
Assuntos
Filogenia , Chuva/microbiologia , Rhodococcus/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Dados de Sequência Molecular , Oceanos e Mares , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rhodococcus/genética , Rhodococcus/isolamento & purificação , Análise de Sequência de DNARESUMO
BACKGROUND: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. METHODS: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. RESULTS: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. CONCLUSION: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.
Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Paclitaxel/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Análise por Conglomerados , Cistadenocarcinoma Seroso/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , MicroRNAs/fisiologia , Análise em Microsséries , Neoplasias Ovarianas/mortalidade , Análise de Sobrevida , TranscriptomaRESUMO
Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P < 0.001), prothrombin time (PT) (International normalized ratio, median 1.72 vs 1.10, P < 0.001), and total bilirubin level (median: 9.6 mg/dL vs 6.3 mg/dL, P = 0.04) were significantly higher in the ARF than in the non-ARF group. Twelve patients (80%) recovered completely with haemodialysis (seven patients, 46.7%) or only conservative management (five patients, 33.3%), while one patient underwent liver transplantation because of fulminant hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.
Assuntos
Injúria Renal Aguda/patologia , Vírus da Hepatite A Humana/isolamento & purificação , Hepatite A/complicações , Hepatite A/patologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Adolescente , Adulto , Alanina Transaminase/sangue , Bilirrubina/sangue , Biópsia , Criança , Feminino , Hematúria , Hepatite A/mortalidade , Histocitoquímica , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Estudos Retrospectivos , Urina/química , Urina/citologia , Adulto JovemRESUMO
Hydrotalcite (HTAL-Cl), an inorganic anion exchanger, is of use as an adsorbent for the removal of arsenate (As(V)) in water systems. The adsorption properties of HTAL-Cl for As(V) and the effects of co-existing anions on the As(V) removal performance were investigated in this work. Under the conditions of pH>or=4, the adsorption capacity for As(V) gradually decreased with an increase of pH, but As(V) was removed effectively within the range of pH = 5-8. Co-existing anions interfered As(V) removal, and the effect decreased in the order of HPO(4)(2-) > HCO(3)(-) > SO(4)(2-) > Cl(-). In binary solute systems containing phosphate and As(V), the maximum adsorption capacity of HTAL-Cl was 0.95 mmol g(-1) for phosphate and 0.65 mmol g(-1) for As(V): the total of these values corresponded to the maximum adsorption capacity for As(V) in single solute systems. The adsorption isotherms in these binary solute systems were approximated by the following modified Langmuir equations:As(V): q(As) = 18.7 radicalC(As)/(1 + 21.5 radicalC(P) + 12.8 radicalC(As)), phosphate : q(P) = 33.1 radicalC(P)/(1 + 21.5 radicalC(P) + 12.8 radicalC(As)). The column adsorption experiments showed that the adsorbed As(V) was released by the phosphate adsorption, because phosphate was adsorbed more strongly on HTAL-CL than As(V).
Assuntos
Hidróxido de Alumínio/química , Arseniatos/isolamento & purificação , Hidróxido de Magnésio/química , Purificação da Água/métodos , Adsorção , Ânions , Arseniatos/química , Arsênio/química , Concentração de Íons de Hidrogênio , Resinas de Troca Iônica/química , Modelos Teóricos , Fosfatos/química , Pós , Propriedades de Superfície , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
OBJECTIVE: To evaluate the value of the QuantiFERON-TB Gold (QFT-G) assay and chest computed tomography (CT), in addition to the conventional use of the tuberculin skin test (TST) and chest radiography (CXR), in a contact investigation of a tuberculosis (TB) outbreak. DESIGN: In a contact investigation of a TB outbreak in a high school, TST and CXR were performed on all 1044 employees and students. QFT-G was performed on TST-positive subjects, and CT on QFT-G-positive subjects and students with TST > or =20 mm. RESULTS: TST was positive in 388 subjects (37.2%), while QFT-G was positive in 7.6% (30/394). CXR showed abnormal findings suggestive of TB in 10 (1.0%) subjects, all of whom were TST-positive and six of whom were QFT-G-positive. Findings suggestive of active TB were noted in 17 (32.7%) of 52 subjects by CT. Collectively, among 21 (1.1%) TB patients, all were TST-positive, 12 (57.1%) were QFT-G-positive and active TB was diagnosed by CT, and not by CXR, in 11 subjects. CONCLUSION: Compared to the conventional approach, the additional use of QFT-G in TST-positive subjects and chest CT in subgroups with a high probability of infection was found to be more effective in the differentiation between active TB, latent TB and non-infected subjects in a contact investigation.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Teste Tuberculínico/métodos , Tuberculina , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
We investigated the growth kinetics and morphological changes in acid-stressed Salmonella Typhimurium as well as the antimicrobial effects of epsilon-polylysine (SAVE-ORY GL610) and combined potassium lactate (PL) and sodium diacetate (SDA) (PURASAL Opti.Form PD Plus) on acid-stressed S. Typhimurium. Exposure to 0.5% acetic or lactic acid injured over 90% of the S. Typhimurium population. Although the lag time of the injured S. Typhimurium was extended, the injured cells were recovered at 10 degrees C and 24 degrees C, indicating a risk of using 10 degrees C as a storage temperature. Additionally, 4.5% PL/SDA mixture or 2% epsilon-polylysine completely inhibited the growth of acid-stressed S. Typhimurium in broth at 10, 24, or 35 degrees C. Although 3% PL/SDA mixture inhibited the growth of lactic acid-stressed S. Typhimurium at 10 degrees C, it did not inhibit the growth of unstressed S. Typhimurium at the same temperature. This finding indicates a different antimicrobial effect due to the physiological status of the pathogen. Furthermore, acid-stressed S. Typhimurium was not resistant to epsilon-polylysine or the PL/SDA mixture, although the antimicrobial effect of these compounds was enhanced at a lower storage temperature. TEM analysis revealed that most of the stressed cells lost their cellular integrity and membranes partially. Both dead and doubling cells were observed after recovery at 30 degrees C for 12 h. The addition of 2% epsilon-polylysine or 4.5% PL/SDA mixture resulted in the collapse of the structure of S. Typhimurium cells and cytoplasmic materials being released. These results provide valuable information regarding the morphological and physiological responses of acid-stressed S. Typhimurium cells in broth and chicken patties followed by antimicrobial stress with epsilon-polylysine or PL/SDA mixture.
Assuntos
Manipulação de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Lactatos/farmacologia , Produtos Avícolas/microbiologia , Salmonella typhimurium/crescimento & desenvolvimento , Acetato de Sódio/farmacologia , Animais , Galinhas , Contagem de Colônia Microbiana , Relação Dose-Resposta a Droga , Microbiologia de Alimentos , Conservação de Alimentos/métodos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Polilisina , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/ultraestrutura , Estresse Fisiológico , Temperatura , Fatores de TempoRESUMO
The purposes of this study were to evaluate the efficiency of acetone removal by electron beam irradiation in groundwater and the effect of various conditions. According to the results, the removal kinetics of acetone were pseudo first-order, and the removal efficiencies were expressed to the (%) removal and G-values. By adding sulfite, it was confirmed that acetone was mainly degraded by the reaction with the hydrated electrons. The presence of nitrate caused the removal of acetone to decrease. But there was no significant effect of alkalinity on the removal of acetone. The effect of the initial pH values (pH 5 to 9) on the acetone removal efficiency was negligible, but the pH value decreases due to the formation of acidic compounds after irradiation. Consequently, the radiation-induced removal reactions of acetone followed the pseudo-first-order kinetic model; in addition to the initial concentration of acetone, nitrate and the absorbed dose were important factors in removing acetone from an aqueous solution using electron beam irradiation. The effects of general pH and alkalinity on the degrading acetone were negligible.
Assuntos
Acetona/química , Elétrons , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Purificação da Água/métodosRESUMO
BACKGROUND: The non-essential amino acid, l-glutamine (Gln), is abundant in the human body. Gln exhibits beneficial effects on endotoxic shock through the inhibition of cytosolic phospholipase A(2) (cPLA(2)) activity. cPLA(2) has been reported to be implicated in the pathogenesis of asthma, but the effects of Gln on asthma have not yet been defined. OBJECTIVE: To investigate the effects of Gln on allergic bronchial inflammation and airway hyperresponsiveness (AHR), and to determine the possible action mechanisms of Gln in a murine model of asthma. METHODS: cPLA(2) phosphorylation was assessed by immunoprecipitation and Western blotting. Smears of bronchoalveolar lavage cells were stained with Diff-Quik solution for differential cell counting. Airway levels of the proteins [T-helper type-1 (Th1) and Th2 cytokines, and mucin] were measured by ELISA. mRNA expression of cytokines was assessed by real-time RT-PCR. AHR was assessed as a change in airway resistance (RL). Histological studies were performed to assess the levels of mucin and pulmonary inflammation. RESULTS: Systemic Gln administration inhibited cPLA(2) phosphorylation and its enzymatic activity in the lungs. Additionally, Gln effectively suppressed the key features of Th2-dependent asthmatic features, such as airway eosinophilia, mucus formation, and airway type 2 cytokine production, as well as late AHR. CONCLUSION: Gln was found to be effective in the suppression of Th2-dependent phenotypes and late AHR, and this effect of Gln appeared to be at least partially attributable to its ability to suppress cLPA(2) activity in the airway. Our results suggest that clinical use of Gln for patients with asthma may be beneficial.
Assuntos
Asma/tratamento farmacológico , Hiper-Reatividade Brônquica/tratamento farmacológico , Bronquite/tratamento farmacológico , Glutamina/farmacologia , Fosfolipases A2 Citosólicas/antagonistas & inibidores , Células Th2/efeitos dos fármacos , Animais , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/imunologia , Bronquite/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Glutamina/análise , Glutamina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Muco/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fosforilação , Células Th2/imunologiaRESUMO
Vibrio parahaemolyticus is recognized as the leading cause of human gastroenteritis associated with the consumption of seafood. The objective of this study was to model the growth kinetics of pathogenic and nonpathogenic V. parahaemolyticus in broth and oyster slurry. Primary growth models of V. parahaemolyticus in broth and oyster slurry fit well to a modified Gomperz equation (broth R(2)=0.99; oyster slurry R(2)=0.96). The lag time (LT), specific growth rate (SGR), and maximum population density (MPD) of each primary model were compared. The growth of nonpathogenic V. parahaemolyticus was found to be more rapid than that of pathogenic V. parahaemolyticus, regardless of the model medium. In addition, significant (P<0.05) differences in the growth kinetics between pathogenic and nonpathogenic V. parahaemolyticus in broth were observed at 10 degrees C. When compared to growth in broth, the growth of V. parahaemolyticus was delayed in oyster slurry, and growth was not observed at 10 or 15 degrees C. The Davey and square root models were identified as appropriate secondary models for predicting the LT and SGR, respectively. For the broth model, the average B(f) and A(f) values for LT were found to be 0.97 and 1.3, respectively, whereas the average B(f) and A(f) values for SGR were 1.05 and 1.11, respectively. The model generated in this study predicted an LT that was shorter and an SGR that was similar to those that were actually observed, which indicates that these models provide a reliable and safe prediction of V. parahaemolyticus growth.
Assuntos
Modelos Biológicos , Ostreidae/microbiologia , Frutos do Mar/microbiologia , Temperatura , Vibrio parahaemolyticus/crescimento & desenvolvimento , Animais , Contagem de Colônia Microbiana , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Humanos , Cinética , Coreia (Geográfico) , Vibrio parahaemolyticus/patogenicidadeRESUMO
This study was aimed at exploring the reclamation of sewage treatment plant effluent water (SEW) as an alternative water resource. For the oxidation of SEW, an ozone-UV system, based on the results of the combined ozone/UV process performed in our previous study, was set up under practical conditions, including a series type, continuous mode, semi-pilot scale operation (1.5 m3/d). As a result, the serial contact of the ozone and UV reactors showed lower CODCr and TOC removal efficiencies. However, these were greatly enhanced by recycling the water flow of the ozone-UV system at 40Q, as a result of the improvements in the transferred ozone dose in the ozone reactor and the contact efficiency between photons and ozone in the UV reactor, which approached that achieved in the combined ozone/UV process. For the disinfection of SEW, carried out in a syringe-type batch reactor, the increase of instantaneous ozone demand (ozone ID) led to a higher inactivation efficiency, an increased UV transmittance due to ozonation, and an enhanced inactivation rate of E. coli in the UV reactor. Additionally, it was concluded that the ozone/UV process could overcome the limitations of the ozone alone and UV alone processes for the reclamation of sewage effluent water.
Assuntos
Desinfetantes/administração & dosagem , Desinfecção/métodos , Ozônio/administração & dosagem , Esgotos/microbiologia , Raios Ultravioleta , Eliminação de Resíduos Líquidos , Purificação da Água/métodos , Desinfetantes/farmacologia , Oxirredução , Ozônio/farmacologia , Esgotos/químicaRESUMO
The aim of this study was to investigate some aspects of the performance of electrochemical process as an alternative disinfection strategy, while minimising DBPs, for water purification. The study of electrochemical processes has shown free chlorine to be produced, but smaller amounts of stronger oxidants, such as ozone, hydrogen peroxide and OH radicals (*OH), were also generated. The formation of mixed oxidants increased with increasing electric conductivity, but was limited at conductivities greater than 0.6 mS/cm. Using several microorganisms, such as E. coli and MS2 bacteriophage, inactivation kinetic studies were performed. With the exception of free chlorine, the role of mixed oxidants, especially OH radicals, was investigated for enhancement of the inactivation rate. Additionally, the formation and reduction of DBPs was studied by monitoring the concentration of haloacetic acids (HAAs) during the process.
Assuntos
Cloro/química , Desinfecção/métodos , Butanóis/farmacologia , Condutividade Elétrica , Eletroquímica , Eletrólitos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Peróxido de Hidrogênio/química , Hidróxidos/química , Levivirus/efeitos dos fármacos , Levivirus/fisiologia , Oxidantes/química , Oxirredução , Ozônio/químicaRESUMO
Tannerella forsythia is a major periodontal pathogen, and T. forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2 ) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. forsythia GroEL and IL-17 synergistically increased PGE2 production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. forsythia GroEL injection, and simultaneous injection of T. forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.
Assuntos
Reabsorção Óssea/microbiologia , Chaperonina 60/metabolismo , Inflamação , Interleucina-17/imunologia , Tannerella forsythia/imunologia , Tannerella forsythia/patogenicidade , Animais , Reabsorção Óssea/imunologia , Reabsorção Óssea/patologia , Chaperonina 60/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/genética , Dinoprostona/imunologia , Ensaio de Imunoadsorção Enzimática , Fibroblastos/microbiologia , Gengiva/citologia , Gengiva/imunologia , Gengiva/microbiologia , Interleucina-1/genética , Interleucina-1/imunologia , Interleucina-17/farmacologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Camundongos , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Periodontite/imunologia , Crânio/imunologia , Crânio/patologia , Fatores de Virulência , Microtomografia por Raio-XRESUMO
BACKGROUND: In patients with lesions at the eloquent areas, the aim of surgical interventions should be a more radical removal of the lesions with preservation of brain function. In this retrospective study, our techniques for localizing lesion and the postoperative results of 26 patients with cavernous angiomas (CA) located at the eloquent areas are summarized. METHOD: The MR based 3D-rendering images were reconstructed from the 2D MR images by using a computerized program. These images were obtained in all patients for the localization of their lesion. Following craniotomy, to verify the actual location of lesions, we compared the 3D-image to the exposed cortical surface. Simultaneously, intraoperative ultrasonogram (IOUS) was used for the accurate localization of the lesion. In order to minimize the damage to the eloquent area, the minimal corticotomy was planned at the margin of the sulcus nearest to the lesion. FINDINGS: An accurate localization of the lesion was possible in all 26 patients and the eloquent areas near the lesions were identified on the operation field. Complete removal of the CAs was done in all cases. One patient developed temporary monoparesis postoperatively, but the patient fully recovered in a month. Fourteen patients presented with preoperative seizures, and all patients had excellent seizure outcome after their surgery. The mean duration of the follow-up period was 27 months. CONCLUSIONS: We could localize the lesion accurately using MRI 3D-rendering images and IOUS during the operation for CA. We planned minimal corticotomy to the lesion and we completely removed the lesion without causing any additional neurological deficit. Although CA can be located in eloquent areas, surgical removal of these lesions is a safe and effective treatment option for lowering the risk of developing symptoms and controlling the seizure.
Assuntos
Neoplasias Encefálicas/cirurgia , Hemangioma Cavernoso/cirurgia , Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/patologia , Humanos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
In the pathogenesis of periodontitis, Porphyromonas gingivalis plays a role as a keystone pathogen that manipulates host immune responses leading to dysbiotic oral microbial communities. Arg-gingipains (RgpA and RgpB) and Lys-gingipain (Kgp) are responsible for the majority of bacterial proteolytic activity and play essential roles in bacterial virulence. Therefore, gingipains are often considered as therapeutic targets. This study investigated the role of gingipains in the modulation by P. gingivalis of phagocytosis of Tannerella forsythia by macrophages. Phagocytosis of T. forsythia was significantly enhanced by coinfection with P. gingivalis in a multiplicity of infection-dependent and gingipain-dependent manner. Mutation of either Kgp or Rgp in the coinfecting P. gingivalis resulted in attenuated enhancement of T. forsythia phagocytosis. Inhibition of coaggregation between the two bacterial species reduced phagocytosis of T. forsythia in mixed infection, and this coaggregation was dependent on gingipains. Inhibition of gingipain protease activities in coinfecting P. gingivalis abated the coaggregation and the enhancement of T. forsythia phagocytosis. However, the direct effect of protease activities of gingipains on T. forsythia seemed to be minimal. Although most of the phagocytosed T. forsythia were cleared in infected macrophages, more T. forsythia remained in cells coinfected with gingipain-expressing P. gingivalis than in cells coinfected with the gingipain-null mutant or infected only with T. forsythia at 24 and 48 h post-infection. Collectively, these results suggest that P. gingivalis, mainly via its gingipains, alters the clearance of T. forsythia, and provide some insights into the role of P. gingivalis as a keystone pathogen.
Assuntos
Adesinas Bacterianas/imunologia , Cisteína Endopeptidases/imunologia , Macrófagos/microbiologia , Fagocitose , Porphyromonas gingivalis/imunologia , Tannerella forsythia/imunologia , Adesinas Bacterianas/genética , Linhagem Celular , Técnicas de Cocultura , Cisteína Endopeptidases/genética , Cisteína Endopeptidases Gingipaínas , Humanos , Macrófagos/imunologia , Macrófagos/ultraestrutura , Microscopia Confocal , Mutação , Periodontite/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidadeRESUMO
Although enolases are cytosolic enzymes involved in the glycolytic pathway, they can also be secreted or expressed on the surface of a variety of eukaryotic cells and bacteria. Surface-exposed enolases of eukaryotes and bacteria can function as plasminogen receptors. Furthermore, antibodies raised against bacterial enolases can react with host enolases, suggesting molecular mimicry between bacterial and host enzymes. In this study, we analyzed an enolase of the major periodontopathogen Tannerella forsythia, which is either secreted or present on the cell surface, via matrix-assisted laser desorption ionization time-of-flight mass spectrometry and immunofluorescence, respectively. The T. forsythia enolase retained the enzymatic activity converting 2-phosphoglycerate to phosphoenolpyruvate and showed plasminogen binding and activating ability, which resulted in the degradation of fibronectin secreted from human gingival fibroblasts. In addition, it induced proinflammatory cytokine production, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumour necrosis factor-α (TNF-a) in the human THP-1 monocytic cell line. Taken together, our results demonstrate that T. forsythia enolase plays a role in pathogenesis in the host by plasminogen activation and proinflammatory cytokine induction, which has the potential to exaggerate inflammation in periodontitis.
Assuntos
Fosfopiruvato Hidratase/metabolismo , Tannerella forsythia/enzimologia , Tannerella forsythia/patogenicidade , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular , Células Cultivadas , Citocinas/biossíntese , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Gengiva/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucinas/biossíntese , Interleucinas/imunologia , Monócitos , Periodontite/metabolismo , Periodontite/microbiologia , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/imunologia , Plasminogênio/análise , Tannerella forsythia/genética , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The tumor suppressor gene p16INK4A is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16INK4A protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16INK4A is more toxic in cancer cells which express mutant forms of p16INK4A compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay and DAPI staining following infection of MDA-MB 231 breast cancer cells with Adp16 indicate that p16INK4A-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating a decrease in cpp32 and cyclinB1 protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage following infection of MDA-MB-231 cells with Adp16. These results suggest that gene therapy using Adp16 may be a promising treatment option for human cancers containing alterations in p16 expression.
Assuntos
Apoptose , Proteínas de Transporte/biossíntese , Adenoviridae , Proteínas de Transporte/genética , Caspase 3 , Caspases/metabolismo , Linhagem Celular , Inibidor p16 de Quinase Dependente de Ciclina , Expressão Gênica , Vetores Genéticos , Humanos , Mutagênese , Poli(ADP-Ribose) Polimerases/metabolismo , Células Tumorais CultivadasRESUMO
BACKGROUND: Vertebral compression fracture (VCF) is frequent in chronic obstructive pulmonary disease (COPD) patients. However, little is known about whether VCF affects mortality in COPD patients. OBJECTIVE: To investigate whether VCFs might increase death in COPD patients. METHODS: In this retrospective cohort study, we enrolled 254 COPD patients with a recent history of hospitalisation due to respiratory problems. Patients were assessed for VCF using quantitative morphometric analyses of lateral chest radiographs; 211 patients received follow-up examinations for 2 years. RESULTS: Of the 211 COPD patients analysed, 60 (28.4%) had VCF at enrolment. During the follow-up period, 33/60 (55.0%) patients with and 46/151 patients (30.5%) without VCF died (P = 0.003, log-rank test). Cox proportional hazard analysis revealed that VCF is an independent risk factor for death after adjusting for age, sex, body mass index, smoking, dyspnoea scale, forced expiratory volume in 1 sec (FEV1) and comorbidities (hazard ratio for VCF = 1.79, 95%CI 1.11-2.89, P = 0.02). CONCLUSION: VCF might be an independent risk factor for death in male COPD patients.
Assuntos
Causas de Morte , Fraturas por Compressão/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Vértebras Torácicas/lesões , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Fraturas por Compressão/diagnóstico por imagem , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Radiografia , República da Coreia , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Fraturas da Coluna Vertebral/diagnóstico por imagem , Estatísticas não Paramétricas , Análise de SobrevidaRESUMO
Liver cirrhosis is a predominant risk factor for hepatocellular carcinoma (HCC). However, the exact mechanism of the progression from cirrhosis to cancer remains unclear. The uptake of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is widely used as a marker of increased glucose metabolism to monitor the progression of cancer with positron emission tomography (PET)/computed tomography (CT). Here we investigated the feasibility of using (18)F-FDG PET/CT in the diethylnitrosamine (DEN) mediated experimental hepatocellular carcinoma model. Rats received weekly intraperitoneal injections of DEN for 16 weeks for induction of HCC. We recorded starting from 0 days or 0 weeks after the last DEN injection. The weight and survival rate of rats were then measured. Also, an (18)F-FDG PET scan and serum analysis were performed at minus 2, 0, plus 2, and plus 4 weeks after the last DEN injection. The body weight of rats was maintained between 350 g and 370 g during 14 and 20 weeks, and the rats were euthanized at 35 days after the last DEN injection. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphate (ALP) were significantly higher at zero weeks after the last DEN injection. The (18)F-FDG uptake for the quantitative evaluation of HCC was done by measuring the region of interest (ROI). At minus two weeks after the last DEN injection, the ROI of rats had significantly increased compared to the normal group, in a time-dependent manner. These results suggest that FDG uptake serves as a good screening test to evaluate the feasibility of DEN-induced HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Fluordesoxiglucose F18/farmacocinética , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/diagnóstico , Dietilnitrosamina , Estudos de Viabilidade , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Masculino , Taxa de Depuração Metabólica , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição TecidualRESUMO
Deregulation of the cell cycle by overexpression of G1 cyclins, cyclin E and cyclin D1 genes, has been demonstrated to be a prerequisite for the development of human cancer. Recently, cyclin E is proposed to be sufficient for the progression of the G1 cell cycle without cyclin D1. Here we show that the proposed model system was specifically present in human hepatocellular carcinoma (HCC) unlike other human cancers. Of 31 HCC tissues analyzed, 21 (67.7%) exhibited an overexpression of cyclin E protein. In contrast to cyclin E gene expression, cyclin D1 expression was strongly downregulated in 19 (61.2%) HCCs. Interestingly, 65% of HCC tissues with overexpression of the cyclin E gene exhibited downregulation of cyclin D1, suggesting reciprocal deregulation of these cyclins in the G1 progression of the cell cycle. Southern blot analysis proved the amplification of cyclin E gene in HCC with a high level of overexpression. The present findings suggest that the reciprocal deregulation of cyclin E lacking cyclin D1 expression might play a role in G1 progression and the development of HCC.