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OBJECTIVE: This study aimed to evaluate the in vitro antibacterial effects of lysozyme-chitosan oligosaccharide conjugates (LYZOX) against Streptococcus gordonii and Porphyromonas gingivalis. MATERIALS AND METHODS: Planktonic S. gordonii and P. gingivalis were treated with various concentrations of LYZOX for 10 min. The treated bacteria were incubated on trypticase soy agar plates, and colony-forming unit (CFU) was calculated. The antibacterial effect of LYZOX was compared with that of lysozyme, chitosan, physiological saline, and benzalkonium chloride solution. Cell morphology before and after LYZOX treatment was observed using a scanning electron microscope (SEM). The antibacterial effect of LYZOX with decanoic acid against the biofilm-like bacteria was also examined via crystal violet staining. The Kruskal-Wallis test and post hoc Dunn tests were performed to compare the difference in antibacterial activity of each treatment. RESULTS: Bacterial CFU numbers were reduced after LYZOX treatment in a concentration-dependent manner. The reduction in CFUs was smaller for corresponding concentrations of chitosan or lysozyme alone. SEM analyses revealed bacterial cells shrank following LYZOX treatment. The combined use of LYZOX and decanoic acid yielded an even higher antibacterial effect against bacterial biofilms. CONCLUSION: LYZOX exhibits antibacterial activity against two periodontal bacteria and may be a promising plaque control agent.
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BACKGROUND: Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction. CASE PRESENTATION: A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare. CONCLUSIONS: This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite Membranoproliferativa , Glomerulonefrite Membranosa , Glomerulonefrite , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Idoso , Humanos , Masculino , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Anticorpos Anticitoplasma de Neutrófilos , Glomerulonefrite/patologia , Glomerulonefrite Membranoproliferativa/complicações , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Imunoglobulina G , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Espectrometria de Massas , N-AcetilglucosaminiltransferasesRESUMO
Recently, the comprehensive concept of "infection-related glomerulonephritis (IRGN)" has replaced that of postinfectious glomerulonephritis (PIGN) because of the diverse infection patterns, epidemiology, clinical features, and pathogenesis. In addition to evidence of infection, hypocomplementemia particularly depresses serum complement 3 (C3), with endocapillary proliferative and exudative GN developing into membranoproliferative glomerulonephritis (MPGN); also, C3-dominant or co-dominant glomerular immunofluorescence staining is central for diagnosing IRGN. Moreover, nephritis-associated plasmin receptor (NAPlr), originally isolated from the cytoplasmic fraction of group A Streptococci, is vital as an essential inducer of C3-dominant glomerular injury and is a key diagnostic biomarker for IRGN. Meanwhile, "C3 glomerulopathy (C3G)", also showing a histological pattern of MPGN due to acquired or genetic dysregulation of the complement alternative pathway (AP), mimics C3-dominant IRGN. Initially, C3G was characterized by intensive "isolated C3" deposition on glomeruli. However, updated definitions allow for glomerular deposition of other complement factors or immunoglobulins if C3 positivity is dominant and at least two orders of magnitude greater than any other immunoreactant, which makes it challenging to quickly distinguish pathomorphological findings between IRGN and C3G. As for NAPlr, it was demonstrated to induce complement AP activation directly in vitro, and it aggravates glomerular injury in the development of IRGN. A recent report identified anti-factor B autoantibodies as a contributing factor for complement AP activation in pediatric patients with PIGN. Moreover, C3G with glomerular NAPlr deposition without evidence of infection was reported. Taken together, the clinico-pathogenic features of IRGN overlap considerably with those of C3G. In this review, similarities and differences between the two diseases are highlighted.
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Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Humanos , Criança , Glomerulonefrite/patologia , Glomerulonefrite Membranoproliferativa/etiologia , Glomérulos Renais/patologia , AutoanticorposRESUMO
BACKGROUND: Glycolipids on cell membrane rafts play various roles by interacting with glycoproteins. Recently, it was reported that the glycolipid GM3 is expressed in podocytes and may play a role in podocyte protection. In this report, we describe the correlation between changes in GM3 expression in glomeruli and proteinuria in minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) patients. METHODS: We performed a case-control study of the correlation between nephrin/GM3 expression levels and proteinuria in MCNS and FSGS patients who underwent renal biopsy at our institution between 2009 and 2014. Normal renal tissue sites were used from patients who had undergone nephrectomy at our institution and gave informed consent. RESULTS: Both MCNS and FSGS had decreased GM3 and Nephrin expression compared with the normal (normal vs. MCNS, FSGS; all p < 0.01). Furthermore, in both MCNS and FSGS, GM3 expression was negatively correlated with proteinuria (MCNS: r = - 0.61, p < 0.01, FSGS: r = - 0.56, p < 0.05). However, nephrin expression had a trend to correlate with proteinuria in FSGS (MCNS: r = 0.19, p = 0.58, FSGS: r = - 0.48, p = 0.06). Furthermore, in a simple linear regression analysis, GM3 expression also correlated with proteinuric change after 12 months of treatment (MCNS: r = 0.40, p = 0.38, FSGS: r = 0. 68, p < 0.05). CONCLUSION: We showed for the first time that decreased GM3 expression correlates with proteinuria in MCNS and FSGS patients. Further studies are needed on the podocyte-protective effects of GM3.
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Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Podócitos , Estudos de Casos e Controles , Glomerulosclerose Segmentar e Focal/patologia , Glicolipídeos , Humanos , Nefrose Lipoide/patologia , Síndrome Nefrótica/patologia , Podócitos/metabolismo , Proteinúria/patologiaRESUMO
We describe two cases of type 2 autoimmune pancreatitis (AIP). A 39-year-old man presented to our hospital with complaints of epigastric and back pain. Pancreatic enzyme levels were elevated, but serum levels of immunoglobulins G and G4 (IgG and IgG4) were normal. Computed tomography (CT) showed diffuse pancreatic enlargement, and endoscopic retrograde pancreatography revealed diffuse narrowing of the pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed granulocytic epithelial lesions and very few IgG4-positive cells. Colonoscopy revealed ulcerative colitis. Type 2 AIP was diagnosed, and 5-aminosalicylic acid (5-ASA) and prednisolone were administered. The clinical course has since been favorable, and the prednisolone dose is currently being reduced. A 47-year-old woman presented to our hospital with complaints of bloody stools. Colonoscopy revealed ulcerative colitis. CT depicted diffuse pancreatic enlargement with a capsule-like rim. Pancreatic enzyme levels were elevated, but serum levels of IgG and IgG4 were normal. On magnetic resonance cholangiopancreatography, the pancreatic duct could not be delineated. No pathological findings of type 2 AIP were obtained on EUS-FNA. Type 2 AIP was suspected, and 5-ASA and steroid enemas were administered. To date, recurrence has not been observed, and 5-ASA management continues. The two cases differed with regard to sex of patient, clinical course, pathological findings, and treatment.
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Doenças Autoimunes , Pancreatite Autoimune , Pancreatite , Adulto , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pancreatite/diagnóstico por imagem , Pancreatite/tratamento farmacológicoRESUMO
[Purpose] Recently, a photo-based smartphone application for angle measurement-"Grid line imaging application Professional"-was developed to evaluate joint disease treatments. The aim of this study was to determine the accuracy and reliability of the application. [Participants and Methods] We measured the knee joint of a mannequin using an application and a universal goniometer. Twelve examiners measured eight knee joints of mannequins at different arbitrary angles using the application and a universal goniometer. Correlations between the application and universal goniometer measurements were examined using scatter plots and correlation coefficients. Systematic errors of the application were visually confirmed using the Bland-Altman method. Intra-class correlation coefficients were used to evaluate the inter-examiner reliability of the application. [Results] The application and universal goniometer measurements showed a good correlation (r=0.99) and no systematic error. The intra-class correlation coefficient for inter-examiner reliability was 0.999. Furthermore, to evaluate intra-examiner reliability, six examiners measured six different knee joints twice using the application on a 2-day interval. The intra-class correlation coefficient for intra-examiner reliability was 0.982. [Conclusion] The accuracy of the application was equivalent to that of a universal goniometer, and both the inter- and intra-examiner reliabilities of the application were almost perfect.
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AIM: The purpose of this study was to investigate the accuracy of the measurement of palatal mucosa thickness using cone beam computed tomography (CBCT) and to create a conversion formula to evaluate palatal mucosa thickness more accurately. We then evaluated the palatal mucosa thickness in a Japanese population using CBCT and the conversion formula. MATERIALS AND METHODS: We evaluated palatal mucosa thickness in 10 healthy subjects at 15 sites using CBCT, digital impression, and K file. Multiple regression analysis was performed to create a conversion formula to measure thickness accurately. We then obtained CBCT data from 174 patients retrospectively, applied the conversion formula, and evaluated palatal mucosa thickness. RESULTS: Sites of measurement affected measurement error. Measurement using CBCT was 0.34 ± 0.04 mm smaller than actual measurement; therefore, a conversion formula was created. Male, age ≥60 years, and probing pocket depth ≥4 mm had significant and positive associations with palatal mucosa thickness; however, no association was observed between bleeding on probing and palatal mucosa thickness. CONCLUSION: CBCT is useful for the noninvasive and accurate measurement of palatal mucosa thickness.
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Tomografia Computadorizada de Feixe Cônico , Palato , Humanos , Masculino , Mucosa , Palato/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Tetralogy of Fallot is the most common cyanotic congenital heart disease. Patients with the condition have a high risk of developing chronic kidney disease. Treatment of kidney disease in patients with complex hemodynamics presents unique challenges. However, there are very few reports on the treatment of end-stage renal failure in patients with tetralogy of Fallot. CASE PRESENTATION: We present a rare case of peritoneal dialysis in a 47-year-old man with tetralogy of Fallot who had not undergone intracardiac repair. Peritoneal dialysis successfully removed fluids and solutes without adversely affecting the patient's hemodynamics. Our patient was managed with peritoneal dialysis for 5 years before he succumbed to sepsis secondary to digestive tract perforation. CONCLUSIONS: In this paper, we discuss the importance of monitoring acid-base balance, changes in cyanosis, and hyperviscosity syndrome during peritoneal dialysis in patients with tetralogy of Fallot. Lower leg edema and B-type natriuretic peptide level were useful monitoring parameters in this case. This case illustrates that with attention to the patient's unique requirements, peritoneal dialysis can provide successful renal replacement therapy without compromising hemodynamics in patients with tetralogy of Fallot.
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Hemodinâmica , Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Tetralogia de Fallot/fisiopatologia , Procedimento de Blalock-Taussig , Cianose/fisiopatologia , Edema , Cefaleia/fisiopatologia , Hemoglobinas/metabolismo , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Oxigenoterapia , Flebotomia , Policitemia/sangue , Policitemia/etiologia , Policitemia/terapia , Tetralogia de Fallot/sangue , Tetralogia de Fallot/complicações , Tetralogia de Fallot/terapiaRESUMO
The present study aimed to identify and compare the microbial signatures between periodontally healthy and periodontitis subjects using 454 sequences of 16S rRNA genes. Subgingival plaque samples were collected from ten periodontally healthy subjects and ten matched chronic periodontitis patients. Bacterial DNA was extracted and next-generation sequencing of 16S rRNA genes was performed. The microbial composition differed between healthy subjects and periodontitis patients at all phylogenetic levels. Particularly, 16 species, including Lautropia mirabilis and Neisseria subflava predominated in healthy subjects, whereas nine species, including Porphyromonas gingivalis and Filifactor alocis predominated in periodontitis. UniFrac, a principal coordinate and network analysis, confirmed distinct community profiles in healthy subjects and periodontitis patients. Using predicted function profiling, pathways involved in phenylpropanoid, GPI-anchor biosynthesis, and metabolism of alanine, arginine, aspartate, butanoate, cyanoamino acid, fatty acid, glutamate, methane, proline, and vitamin B6 were significantly over-represented in periodontitis patients. These results highlight the oral microbiota alterations in microbial composition in periodontitis and suggest the genes and metabolic pathways associated with health and periodontitis. Our findings help to further elucidate microbial composition and interactions in health and periodontitis.
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Periodontite Crônica , Microbiota , Humanos , Japão , Filogenia , RNA Ribossômico 16SRESUMO
Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67.1 years (women) and 66.8 years (men). Frailty was defined based on criteria set forth by the Cardiovascular Health Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and 43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound, broadband ultrasound attenuation, stiffness index) of the calcaneus were measured. The association between frailty and QUS parameters was determined separately for women and men using multivariate analysis of covariance (ANCOVA), with adjustments for clinical characteristics including age, body mass index, hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate, corrected calcium, intact parathyroid hormone, and medication for CKD-MBD (vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS parameters declined significantly with increasing levels of frailty in both sexes (P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be considered a risk factor for bone loss in patients undergoing hemodialysis.
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Reabsorção Óssea/complicações , Fragilidade/complicações , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Reabsorção Óssea/diagnóstico por imagem , Estudos Transversais , Feminino , Fragilidade/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , UltrassonografiaRESUMO
OBJECTIVES: Increasing evidence suggests that periodontitis can exacerbate diabetes, and gut bacterial dysbiosis appears to be linked with the diabetic condition. The present study examined the effects of oral administration of the periodontopathic bacterium, Porphyromonas gingivalis, on the gut microbiota and systemic conditions in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: Diabetes was induced by streptozotocin injection in C57BL/6J male mice (STZ). STZ and wild-type (WT) mice were orally administered P. gingivalis (STZPg, WTPg) or saline (STZco, WTco). Feces were collected, and the gut microbiome was examined by 16S rRNA gene sequencing. The expression of genes related to inflammation, epithelial tight junctions, and glucose/fatty acid metabolism in the ileum or liver were examined by quantitative PCR. RESULTS: The relative abundance of several genera, including Brevibacterium, Corynebacterium, and Facklamia, was significantly increased in STZco mice compared to WTco mice. The relative abundances of Staphylococcus and Turicibacter in the gut microbiome were altered by oral administration of P. gingivalis in STZ mice. STZPg mice showed higher concentrations of fasting blood glucose and inflammatory genes levels in the ileum, compared to STZco mice. CONCLUSIONS: Oral administration of P. gingivalis altered the gut microbiota and aggravated glycemic control in streptozotocin-induced diabetic mice.
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Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/microbiologia , Microbioma Gastrointestinal , Porphyromonas gingivalis , Aerococcaceae/isolamento & purificação , Animais , Glicemia/metabolismo , Brevibacterium/isolamento & purificação , Claudina-1/genética , Corynebacterium/isolamento & purificação , Disbiose , Fezes/microbiologia , Expressão Gênica , Íleo , Inflamação/genética , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/genética , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Análise de Sequência de RNA , Staphylococcus/isolamento & purificação , Estreptozocina , Proteína da Zônula de Oclusão-1/genéticaRESUMO
OBJECTIVES: This study aimed to define the comprehensive bacterial flora of the healthy oral cavity by identifying and comparing bacterial species in different subgingival sites using 454 sequencing of 16S rRNA genes. MATERIALS AND METHODS: Subgingival plaque samples were taken from six target teeth (central incisor, first premolar, and first molar in both the maxilla and mandible) of 10 periodontally healthy patients. Bacterial DNA was extracted and next-generation sequencing of 16S rRNA genes was performed. RESULTS: Bacterial composition in phylum level was similar for all sites within the same individual irrespective of tooth location. Unweighted UniFrac distance values of microbiome also showed that average distance was significantly larger between subjects than between tooth locations of the same subjects. CONCLUSIONS: The present results clarify the lack of effect of tooth location in the healthy subgingival microbiota. Results may suggest that any subgingival site can demonstrate similar subject-specific microbiota. CLINICAL RELEVANCE: This investigation offers a better understanding of the uniqueness of the oral microbiome. The present study will facilitate sampling in future subgingival microbiological studies.
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Bactérias/classificação , Gengiva/microbiologia , Microbiota , DNA Bacteriano , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , RNA Ribossômico 16S/genéticaRESUMO
Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry-sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM. Stem Cells 2017;35:989-1002.
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Citoproteção , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Acetilcisteína/farmacologia , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Medula Óssea/patologia , Microambiente Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Indicadores e Reagentes , Inflamação/patologia , Camundongos Endogâmicos C57BL , Fatores de TempoRESUMO
OBJECTIVE: Greater physical activity is associated with lower risk of mortality in persons with kidney disease; however, little is known about the appropriate dose of physical activity among hemodialysis patients. Here detected the minimum level of habitual physical activity to help inform interventions aimed at improving outcomes in the dialysis population. DESIGN: The design was prospective cohort study. SUBJECTS: Clinically stable outpatients in a hemodialysis unit from October 2002 to March 2014 were assessed for their eligibility to be included in this 7-year prospective cohort study. We used the Youden index to determine the optimal cutoff points for physical activity. The prognostic effect of physical activity on survival was estimated by Cox proportional hazards regression analysis. The number of steps per nondialysis day was recorded by accelerometer at study entry. MAIN OUTCOME MEASURE: The main outcome measure was all-cause mortality. RESULTS: There were 282 participants who had a mean age of 65 ± 11 years and 45% were female. A total of 56 deaths occurred during the follow-up period (56 months [interquartile range: 29-84 months]). The cutoff value for the physical activity discriminating those at high risk of mortality was 3,752 steps. After adjustment for the effect of confounders, the hazard ratio in the group of <4,000 steps was 2.37 (95% confidence interval: 1.22-4.60, P = .01) compared with the others. CONCLUSIONS: Engaging in physical activity is associated with decreased mortality risk among hemodialysis patients. Our findings of a substantial mortality benefit among those who engage in at least 4,000 steps provide a basis for as a minimum initial recommendation kidney health providers can provide for mobility disability-free hemodialysis patients.
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Exercício Físico , Falência Renal Crônica/mortalidade , Diálise Renal , Idoso , Índice de Massa Corporal , Metabolismo Energético , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Albumina Sérica/metabolismoRESUMO
OBJECTIVES: The combined effects of reduced functional mobility, muscle weakness, and low serum albumin on mortality in hemodialysis patients have not been clarified. Here, we examined the associations of reduced functional mobility, muscle weakness, and low serum albumin-both alone and in combination-with all-cause mortality in hemodialysis patients. METHODS: A total of 490 patients treated between July 2010 and October 2016 were enrolled retrospectively in this study. The independent prognostic effect of the combination of reduced functional mobility, muscle weakness, and low serum albumin on survival was estimated by Cox proportional hazard regression analysis. We calculated the increases in predictive capacity by combining the associations of reduced functional mobility, muscle weakness, and low serum albumin in comparison to each component alone based on the receiver-operating characteristic curves, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The final study population consisted of 314 hemodialysis patients, and 56 patients died during the 6.5-year follow-up period. The high Combined score group showed a significantly lower cumulative survival rate than the low Combined score group (hazard ratio, 3.30; 95% confidence interval, 1.59-6.87; P = .001). Both NRI and IDI suggested that the addition of Combined score to patient characteristics improved discrimination of patients at high risk of mortality (NRI, 0.038 95% CI: 0.096 - 0.064, P < .001 IDI, 0.029 95% CI: 0.004 - 0.055, P = .025). CONCLUSIONS: The combined assessment of reduced functional mobility, muscle weakness, and low serum albumin was associated with poorer prognosis in patients on hemodialysis. The results presented here indicated that the combination of reduced functional mobility, muscle weakness, and low serum albumin is useful for accurate prediction of prognosis in hemodialysis patients.
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Limitação da Mobilidade , Debilidade Muscular/mortalidade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade , Albumina Sérica/análise , Idoso , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: Growing evidence indicates an association between periodontitis and delivery outcome; however, the mechanism is unclear. This study aimed to investigate the influence of Porphyromonas gingivalis (Pg) infection on delivery outcome in mice. MATERIALS AND METHODS: Bacteremia was induced in pregnant Slc:ICR mice (8 weeks old) by intravenous injection of Pg. Mice were randomly divided into a control group (CO), and those receiving Pg injection at gestational day 1 (GD1), gestational day 15 (GD15) or every day (ED). Delivery outcome, Pg infection, and gene expression in the placenta and umbilical cord were evaluated. RESULTS: Birth weight was lower in the ED and GD15 groups than in the CO group. A remarkable increase in anti-Pg IgG antibody was observed in the ED and GD1 groups, although Pg was not detected in the placenta or umbilical cord. mRNA expression of Tnfα and Il6 in the placenta, and Hif1α in the umbilical cord, was significantly increased in the ED group. Microarray analysis of the umbilical cord revealed increased expression of several genes including Orm1, Mgl2, Rps6ka3 and Trim15 in the ED group. CONCLUSIONS: Pg infection during the third trimester caused low birth weight and inflammation in the placenta and umbilical cord.
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Peso ao Nascer , Periodontite/metabolismo , Placenta/microbiologia , Porphyromonas gingivalis/metabolismo , Prenhez/metabolismo , Cordão Umbilical/microbiologia , Animais , Feminino , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: A previous cohort study indicated a significant association of lower baseline level of physical activity in hemodialysis patients with elevated risks of mortality. However, there have been no reports regarding the association between changes in physical activity over time and mortality in hemodialysis patients. This study was performed to examine the prognostic significance of physical activity changes in hemodialysis patients. METHODS: This retrospective cohort study was performed in 192 hemodialysis patients with a 7-year follow-up. The average number of steps taken per non-dialysis day was used as a measure of physical activity. Forty (20.8%) patients had died during the follow-up period. The percentage change in physical activity between baseline and 12 months was determined, and patients were divided into three categories according to changes in physical activity. A decrease or increase in physical activity > 30% was defined as becoming less or more active, respectively, while decrease or increase in physical activity < 30% were classified as stable. RESULTS: Forty seven (24.5%), 51 (26.6%), and 94 (49.0%) patients were classified as becoming less active, becoming more active, and stable, respectively. The hazard ratio on multivariate analysis in patients with decreased physical activity was 3.68 (95% confidence interval, 1.55-8.78; P < 0.01) compared to those with increased physical activity. CONCLUSIONS: Reductions in physical activity were significantly associated with poor prognosis independent of not only patient characteristics but also baseline physical activity. Therefore, improved prognosis in hemodialysis patients requires means of preventing a decline in physical activity over time.
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Exercício Físico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/mortalidade , Diálise Peritoneal Ambulatorial Contínua/estatística & dados numéricos , Distribuição por Idade , Idoso , Estudos de Coortes , Feminino , Humanos , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Resultado do TratamentoRESUMO
In an attempt to discover inhibitory compounds against pore-forming toxins, some of the major toxins produced by bacteria, we herein examined the effects of four kinds of indolo[3,2-b]quinoline derivatives on hemolysis induced by the aerolysin-like hemolysin (ALH) of Aeromonas sobria and also by the alpha-hemolysin of Staphylococcus aureus. The results showed that hemolysis induced by ALH was significantly reduced by every derivative, while that induced by alpha-hemolysis was significantly reduced by three out of the four derivatives. However, the degrees of reduction induced by these derivatives were not uniform. Each derivative exhibited its own activity to inhibit the respective hemolysin. Compounds 1 and 2, which possessed the amino group bonding the naphthalene moiety at the C-11 position of indolo[3,2-b]quinoline, had strong inhibitory effects on the activity of ALH. Compound 4 which consisted of benzofuran and quinoline had strong inhibitory effects on the activity of alpha-hemolysin. These results indicated that the amino group bonding the naphthalene moiety of compounds 1 and 2 assisted in their ability to inhibit ALH activity, while the oxygen atom at the 10 position of compound 4 strengthened its interaction with alpha-hemolysin. These compounds also suppressed the hemolytic activity of the supernatant of A. sobria or A. hydrophila, suggesting that these compounds were effective at the site of infection of these bacteria.
Assuntos
Aeromonas/metabolismo , Toxinas Bacterianas/toxicidade , Eritrócitos/efeitos dos fármacos , Proteínas Hemolisinas/toxicidade , Quinolinas/farmacologia , Animais , Toxinas Bacterianas/metabolismo , Proteínas Hemolisinas/metabolismo , Hemólise , Estrutura Molecular , Quinolinas/química , OvinosRESUMO
Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity.