RESUMEN
Introduction: Drug-induced tubulointerstitial injury is a common cause of renal impairment. Since the mechanisms of drug-induced tubular injury are diverse, various treatment approaches are needed according to the pathogenesis. Renal biopsy is indispensable to determine not only the pathological diagnosis, but also the underlying mechanism, and to guide appropriate treatment. Most recently, one of the red yeast supplements has been widely highlighted as a novel cause of tubular damage, mainly in Japan and Asia. However, neither detailed pathological findings nor the mechanism of renal impairment has been sufficiently reported. Case Presentation: Two cases of renal impairment after taking red yeast supplement internally are presented. Both cases showed renal dysfunction with low uric acid, potassium, and phosphorus levels, characteristic features of Fanconi syndrome. The renal biopsy findings of both cases showed severe injury to the proximal tubules with mild inflammatory cell infiltration. The proximal tubules exhibited diffuse loss of the brush border, flattening, and tubular lumen dilation. Immunofluorescence showed no deposition of immunoglobulin and complement in the glomeruli and tubules. Electron microscopic findings indicated proximal tubular damage without crystal deposition. Moreover, immunohistochemistry using the proximal tubular marker CD10 and a marker for distal tubules including the loop of Henle, E-cadherin, collectively demonstrated that the focus of renal injury in both cases was mainly the proximal tubules. Conclusions: The red yeast rice supplement itself, its metabolized product, or other unknown contaminant components might directly induce proximal tubulopathy rather than an allergic reaction-related tubulointerstitial nephritis.
RESUMEN
Clinical studies have shown that Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1ß secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans. This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A. actinomycetemcomitans.
Asunto(s)
Aggregatibacter actinomycetemcomitans , Artritis Experimental , Caspasas Iniciadoras , Inflamasomas , Macrófagos , Animales , Ratones , Macrófagos/inmunología , Artritis Experimental/microbiología , Artritis Experimental/inmunología , Interleucina-1beta/metabolismo , Artritis Reumatoide , Ratones Endogámicos C57BL , Lipopolisacáridos , Infecciones por Pasteurellaceae/microbiologíaRESUMEN
Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are induced by dysbiotic microbiota resulting in the inflammatory destruction of peri-implant tissue. Nonetheless, there has yet to be an established protocol for the treatment of these diseases in a predictable manner, although many clinicians and researchers have proposed various treatment modalities for their management. With the increase in the number of reports evaluating the efficacy of various treatment modalities and new materials, the use of multiple decontamination methods to clean infected implant surfaces is recommended; moreover, the use of hard tissue laser and/or air abrasion techniques may prove advantageous in the future. Limited evidence supports additional effects on clinical improvement in antimicrobial administration for treating peri-implantitis. Implantoplasty may be justified for decontaminating the implant surfaces in the supracrestal area. Surgical treatment is employed for advanced peri-implantitis, and appropriate surgical methods, such as resection therapy or combination therapy, should be selected based on bone defect configuration. This review presents recent clinical advances in debridement methods for contaminated implant surfaces and regenerative materials for treating peri-implant bone defects. It also proposes a new flowchart to guide the treatment decisions for peri-implant disease.
RESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0292267.].
RESUMEN
Recently, several target antigens of membranous nephropathy (MN), such as phospholipase A2 receptor (PLA2R) and exostosin 1/exostosin 2 (EXT1/2), have been discovered. A 30-year-old woman was referred to our hospital with nephrotic range proteinuria and microscopic hematuria. She was first noted to have proteinuria before pregnancy, and her proteinuria worsened in the postpartum period. A renal biopsy showed MN. Immunofluorescence microscopy showed IgG, IgA, IgM, C3, C4, and C1q depositions in the mesangial area and glomerular capillary walls (GCWs). Regarding the IgG subclass, IgG1 and IgG3 were detected on glomeruli. Electron microscopy showed subepithelial electron-dense deposits (EDDs). EDDs were also detected in paramesangial and subendothelial areas. The diagnosis of membranous lupus nephritis (MLN) was suspected, but she did not fulfill the criteria for systemic lupus erythematosus. Neither anti-nuclear antibody nor hypocomplementemia were detected. We further evaluated glomerular EXT1/2 expressions, which were evident on GCWs. In addition, PLA2R was also detected on GCWs, although serum antibody for PLA2R was negative. She responded to immunosuppressive therapy with decreased proteinuria. In the present case, glomerular PLA2R expression implied the possibility of primary MN. However, pathological findings with a full-house staining pattern and glomerular EXT1/2 expressions were very similar to those of lupus-associated MN. Glomerular PLA2R expression appeared not to reflect immunocomplexes of PLA2R and autoantibody when considering the results for glomerular IgG subclass and the absence of serum anti-PLA2R antibody. Collectively, it is plausible that this was a case of a relatively young postpartum female who developed latent MLN rather than primary MN.
RESUMEN
Therapeutic light has been increasingly used in clinical dentistry for surgical ablation, disinfection, bio-stimulation, reduction in inflammation, and promotion of wound healing. Photodynamic therapy (PDT), a type of phototherapy, has been used to selectively destroy tumor cells. Antimicrobial PDT (a-PDT) is used to inactivate causative bacteria in infectious oral diseases, such as periodontitis. Several studies have reported that this minimally invasive technique has favorable therapeutic outcomes with a low probability of adverse effects. PDT is based on the photochemical reaction between light, a photosensitizer, and oxygen, which affects its efficacy. Low-power lasers have been predominantly used in phototherapy for periodontal treatments, while light-emitting diodes (LEDs) have received considerable attention as a novel light source in recent years. LEDs can emit broad wavelengths of light, from infrared to ultraviolet, and the lower directivity of LED light appears to be suitable for plaque control over large and complex surfaces. In addition, LED devices are small, lightweight, and less expensive than lasers. Although limited evidence exists on LED-based a-PDT for periodontitis, a-PDT using red or blue LED light could be effective in attenuating bacteria associated with periodontal diseases. LEDs have the potential to provide a new direction for light therapy in periodontics.
RESUMEN
Objective: This study investigated the suppressive effects of blue light-emitting diode (LED) irradiation on bone resorption and changes in the oral microbiome of mice with ligature-induced periodontitis. Background: Wavelength of blue light has antimicrobial effects; however, whether blue LED irradiation alone inhibits the progression of periodontitis remains unclear. Methods: Nine-week-old male mice ligated ligature around the right maxillary second molar was divided into ligation alone (Li) and ligation with blue LED irradiation (LiBL) groups. The LiBL group underwent blue LED (wavelength, 455 nm) irradiation four times in a week at 150 mW/cm2 without a photosensitizer on the gingival tissue around the ligated tooth at a distance of 5 mm for 5 min. The total energy density per day was 45 J/cm2. Bone resorption was evaluated using micro-computed tomography at 8 days. Differences in the oral microbiome composition of the collected ligatures between the Li and LiBL groups were analyzed using next-generation sequencing based on the 16S rRNA gene from the ligatures. Results: Blue LED irradiation did not suppress bone resorption caused by ligature-induced periodontitis. However, in the LiBL group, the α-diversity, number of observed features, and Chao1 were significantly decreased. The relative abundances in phylum Myxococcota and Bacteroidota were underrepresented, and the genera Staphylococcus, Lactococcus, and Lactobacillus were significantly overrepresented by blue LED exposure. Metagenomic function prediction indicated an increase in the downregulated pathways related to microbial energy metabolism after irradiation. The co-occurrence network was altered to a simpler structure in the LiBL group, and the number of core genera decreased. Conclusions: Blue LED irradiation altered the composition and network of the oral microbiome of ligature-induced periodontitis in mice.
Asunto(s)
Pérdida de Hueso Alveolar , Microbiota , Periodontitis , Ratones , Masculino , Animales , Fármacos Fotosensibilizantes/farmacología , Microtomografía por Rayos X/efectos adversos , ARN Ribosómico 16S , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/metabolismo , Periodontitis/terapia , Periodontitis/complicaciones , Periodontitis/metabolismoRESUMEN
BACKGROUND: In recent years, light has been used for bacterial control of periodontal diseases. This in vitro study evaluated the effects of light-emitting diode (LED) irradiation at different wavelengths on both Porphyromonas gingivalis and human gingival fibroblasts (HGF-1). METHODS: P. gingivalis suspension was irradiated with LEDs of 365, 405, 450, 470, 565, and 625 nm at 50, 100, 150, and 200 mW/cm2 for 3 min (radiant exposure: 9, 18, 27, 36 J/cm2, respectively). Treated samples were anaerobically cultured on agar plates, and the number of colony-forming units (CFUs) was determined. Reactive oxygen species (ROS) levels were measured after LED irradiation. The viability and damage of HGF-1 were measured through WST-8 and lactate dehydrogenase assays, respectively. Gene expression in P. gingivalis was evaluated through quantitative polymerase chain reaction. RESULTS: The greatest reduction in P. gingivalis CFUs was observed on irradiation at 365 nm with 150 mW/cm2 for 3 min (27 J/cm2), followed by 450 and 470 nm under the same conditions. While 365-nm irradiation significantly decreased the viability of HGF-1 cells, the cytotoxic effects of 450- and 470-nm irradiation were comparatively low and not significant. Further, 450-nm irradiation indicated increased ROS production and downregulated the genes related to gingipain and fimbriae. The 565- and 625-nm wavelength groups exhibited no antibacterial effects; rather, they significantly activated HGF-1 proliferation. CONCLUSIONS: The 450- and 470-nm blue LEDs showed high antibacterial activity with low cytotoxicity to host cells, suggesting promising bacterial control in periodontal therapy. Additionally, blue LEDs may attenuate the pathogenesis of P. gingivalis.
Asunto(s)
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/farmacología , Porphyromonas gingivalis , FibroblastosRESUMEN
Cold atmospheric plasma (CAP) has been studied and clinically applied to treat chronic wounds, cancer, periodontitis, and other diseases. CAP exerts cytotoxic, bactericidal, cell-proliferative, and anti-inflammatory effects on living tissues by generating reactive species. Therefore, CAP holds promise as a treatment for diseases involving chronic inflammation and bacterial infections. However, the cellular mechanisms underlying these anti-inflammatory effects of CAP are still unclear. Thus, this study aimed to elucidate the anti-inflammatory mechanisms of CAP in vitro. The human acute monocytic leukemia cell line, THP-1, was stimulated with lipopolysaccharide and irradiated with CAP, and the cytotoxic effects of CAP were evaluated. Time-course differentiation of gene expression was analyzed, and key transcription factors were identified via transcriptome analysis. Additionally, the nuclear localization of the CAP-induced transcription factor was examined using western blotting. The results indicated that CAP showed no cytotoxic effects after less than 70 s of irradiation and significantly inhibited interleukin 6 (IL6) expression after more than 40 s of irradiation. Transcriptome analysis revealed many differentially expressed genes (DEGs) following CAP irradiation at all time points. Cluster analysis classified the DEGs into four distinct groups, each with time-dependent characteristics. Gene ontology and gene set enrichment analyses revealed CAP-induced suppression of IL6 production, other inflammatory responses, and the expression of genes related to major histocompatibility complex (MHC) class II. Transcription factor analysis suggested that nuclear factor erythroid 2-related factor 2 (NRF2), which suppresses intracellular oxidative stress, is the most activated transcription factor. Contrarily, regulatory factor X5, which regulates MHC class II expression, is the most suppressed transcription factor. Western blotting revealed the nuclear localization of NRF2 following CAP irradiation. These data suggest that CAP suppresses the inflammatory response, possibly by promoting NRF2 nuclear translocation.
Asunto(s)
Leucemia Monocítica Aguda , Gases em Plasma , Humanos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Células THP-1 , Gases em Plasma/farmacología , Interleucina-6 , Antiinflamatorios/farmacología , Línea Celular , LipopolisacáridosRESUMEN
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.
RESUMEN
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.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glomerulonefritis Membranoproliferativa , Glomerulonefritis Membranosa , Glomerulonefritis , Lupus Eritematoso Sistémico , Nefritis Lúpica , Anciano , Humanos , Masculino , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/complicaciones , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Inmunoglobulina G , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Espectrometría de Masas , N-AcetilglucosaminiltransferasasRESUMEN
Oral health screening is important for maintaining and improving quality of life. The present study aimed to determine whether patients with a certain level of alveolar bone resorption could be screened by salivary bacterial test along with their background information. Saliva samples were collected from 977 Japanese patients, and the counts of each red-complex, that is, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, were measured using quantitative polymerase chain reaction analysis. Mean bone crest levels (BCLs) were measured using a full-mouth periapical radiograph. Multiple logistic regression analysis was used to determine associations between BCLs (1.5-4.0 mm in 0.5 mm increments) and explanatory variables, such as the number of each red-complex bacteria and the patients' age, sex, number of teeth, stimulated saliva volume, and smoking habits. When the cutoff BCL value was set at 3.0 mm, the area under the curve, sensitivity, and specificity values were optimal at 0.86, 0.82, and 0.76, respectively. In addition, all tested explanatory variables, except sex and T. denticola count, were significantly associated with BCLs according to a likelihood ratio test (p < 0.05). Additionally, the odds ratio (OR) was substantially increased when a patient was >40 years old and the bacterial count of P. gingivalis was >107 cells/µL (OR: >6). Thus, P. gingivalis count and patients' background information were significantly associated with the presence of a certain amount of bone resorption, suggesting that it may be possible to screen bone resorption without the need for radiography or oral examination.
RESUMEN
The optimal method for decontamination of implant surfaces for peri-implantitis treatment remains controversial. In recent years, erbium-doped yttrium aluminum garnet (Er:YAG) laser irradiation and implantoplasty (IP) (i.e. mechanical modification of the implant) have been reported to be effective in decontaminating implant surfaces during the surgical treatment. Also, a lack of adequate keratinized mucosa (KM) around the implant is known to be associated with more plaque accumulation, tissue inflammation, attachment loss, and mucosal recession, increasing the risk of peri-implantitis. Therefore, free gingival graft (FGG) has been recommended for gaining adequate KM around the implant. However, the necessity of acquiring KM for the treatment of peri-implantitis using FGG remains unclear. In this report, we applied the apically positioned flap (APF) as resective surgery for peri-implantitis treatment in conjunction with IP and Er:YAG laser irradiation to polish/clean the implant surface. Furthermore, FGG was conducted simultaneously to create additional KM, which increased the tissue stability and contributed to the positive results. The two patients were 64 and 63 years old with a history of periodontitis. The removal of granulation tissue and debridement of contaminated implant surfaces were performed with Er:YAG laser irradiation post flap elevation and then modified smooth surfaces mechanically using IP. Er:YAG laser irradiation was also utilized to remove the titanium particles. In addition, we performed FGG to increase the width of KM as a vestibuloplasty. Peri-implant tissue inflammation and progressive bone resorption were not observed, and both patients maintained good oral hygiene conditions until the 1-year follow-up appointment. Bacterial analysis via high-throughput sequencing revealed proportional decreases in bacteria associated with periodontitis (Porphyromonas, Treponema, and Fusobacterium). To the best of our knowledge, this study is the first to describe peri-implantitis management and bacterial change before and after procedures by resective surgery combined with IP and Er:YAG laser irradiation for peri-implantitis treatment, accompanied by FGG for increasing KM around the implants.
RESUMEN
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.
Asunto(s)
Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Humanos , Niño , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/etiología , Glomérulos Renales/patología , AutoanticuerposRESUMEN
BACKGROUND: This study evaluated the effectiveness of a novel pocket therapy (Er:YAG laser-assisted comprehensive periodontal pocket therapy [Er-LCPT]) for residual pocket treatment, compared with conventional mechanical treatment alone, in a randomized controlled clinical trial. METHODS: Two sites in 18 patients having residual periodontal pockets of ≥5 mm depth, extant following initial active therapy, or during supportive therapy, were randomized into two groups in a split mouth design: the control group received scaling and root planing (SRP) by curette, and the test group received Er-LCPT using curette and laser. With Er-LCPT, after root debridement, inflamed connective tissue on the inner gingival surface and on the bone surface/within extant bone defects was thoroughly debrided. Furthermore, removal of proximate oral epithelium and coagulation of the blood clot in the pocket entrance were performed with laser. Clinical parameters were evaluated, before and after treatment, through 12 months. RESULTS: Both groups showed significant improvements in clinical parameters. With Er-LCPT, pocket debridement was thoroughly and safely performed, without any adverse side effects and complications, and favorable healing was observed in most of the cases. At 12 months, Er-LCPT demonstrated significantly higher probing pocket depth reduction (2.78 mm vs. 1.89 mm on average; p = 0.012, Wilcoxon signed-rank test), clinical attachment gain (1.67 mm vs. 1.06 mm; p = 0.004) as primary outcomes, and reduced BOP value (0.89 vs. 0.56; p = 0.031), compared with SRP alone. CONCLUSION: The results of this study indicate that Er-LCPT is more effective for residual pocket treatment, compared with SRP alone.
Asunto(s)
Láseres de Estado Sólido , Humanos , Bolsa Periodontal/cirugía , Láseres de Estado Sólido/uso terapéutico , Estudios de Seguimiento , Aplanamiento de la Raíz/métodos , Raspado Dental/métodos , Resultado del Tratamiento , Pérdida de la Inserción Periodontal/cirugíaRESUMEN
Objective Allergic reactions are a severe complication of plasma exchange (PEx). Few reports have analyzed allergic reactions during PEx using fresh-frozen plasma (FFP) as a replacement solution. We therefore clarified the relationship between risk and exacerbation factors that lead to the onset of PEx-related allergic reactions, particularly PEx, using FFP, and examined whether or not allergic reactions were predictable. Methods This retrospective study included 88 consecutive patients who underwent PEx with FFP as a replacement solution at Kitasato University Hospital. The patients were grouped according to the presence of allergic reactions and compared. Data were analyzed using the χ2 test, Mann-Whitney U test, and a binomial logistic analysis. Statistical analyses were performed using EZR software program, version 1.54, with p<0.05 considered statistically significant. Results There were 44 allergic reaction cases. The average time to the onset of an allergic reactions was 63.5 (45-93) minutes. The allergic reaction-onset group had significantly higher average albumin (Alb) levels than did the non-allergic reaction-onset group. The binomial logistic analysis identified Alb levels as independent risk factors for allergic reactions. The receiver operating characteristic analysis identified an Alb level ≥3.4 g/dL as a risk factor for allergic reactions (area under the curve: 0.731; 95% confidence interval: 0.622-0.84). Conclusion Allergic reaction onset occurred approximately one hour after PEx initiation in the critical period. A serum Alb level ≥3.4 g/dL was identified as a risk factor for predicting allergic reactions. Patients with Alb levels ≥3.4 g/dL at the first PEx should be monitored for allergic reaction symptoms.
Asunto(s)
Hipersensibilidad , Intercambio Plasmático , Humanos , Intercambio Plasmático/efectos adversos , Intercambio Plasmático/métodos , Estudios Retrospectivos , Plasma , Hipersensibilidad/epidemiología , Hipersensibilidad/etiología , Factores de RiesgoRESUMEN
DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 ≤ 100 nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , Epigénesis Genética , Animales , Humanos , Ratones , Transformación Celular Neoplásica/genética , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , Metilasas de Modificación del ADN/metabolismo , ADN Metiltransferasa 3BRESUMEN
BACKGROUND: A delay in muscle repair interferes with the effect of training or exercise; therefore, it is important to identify the factors that delay muscle repair. P. gingivalis, one of the most common periodontal disease pathogens, has the potential to inhibit muscle repair after training, as inferred from a previous study. To assess the expression of satellite cells in this in vivo study, we evaluated the relationship between P. gingivalis and muscle regeneration after training. METHODS: A total of 20 male Wistar rats (eight weeks in age) were randomly divided into two groups: one orally administered sonicated P. gingivalis four times per week for six weeks (PG group) and one given no treatment (NT group). After four weeks of training using a treadmill, the gastrocnemius was evaluated using histology of the cross-sectional area (CSA) of myotubes and immunohistochemistry of the expression of skeletal muscle satellite cells. In addition, an endurance test was performed a day before euthanization. RESULTS: The CSA and expression of Pax7+/MyoD- and Pax7+/MyoD+ cells were not significantly different between the groups. However, the expression of Pax7-/MyoD+ cells and running time until exhaustion were significantly lower in the PG group. CONCLUSIONS: Infection with P. gingivalis likely interferes with muscle repair after training.
Asunto(s)
Condicionamiento Físico Animal , Células Satélite del Músculo Esquelético , Animales , Masculino , Ratas , Administración Oral , Fibras Musculares Esqueléticas , Músculo Esquelético/metabolismo , Ratas Wistar , Células Satélite del Músculo Esquelético/metabolismoRESUMEN
Podocytopathy, which is characterized by injury to podocytes, frequently causes proteinuria or nephrotic syndrome. There is currently a paucity of effective therapeutic drugs to treat proteinuric kidney disease. Recent research suggests the possibility that glycosphingolipid GM3 maintains podocyte function by acting on various molecules including nephrin, but its mechanism of action remains unknown. Here, various analyses were performed to examine the potential relationship between GM3 and nephrin, and the function of GM3 in podocytes using podocytopathy mice, GM3 synthase gene knockout mice, and nephrin injury cells. Reduced amounts of GM3 and nephrin were observed in podocytopathy mice. Intriguingly, this reduction of GM3 and nephrin, as well as albuminuria, were inhibited by administration of valproic acid. However, when the same experiment was performed using GM3 synthase gene knockout mice, valproic acid administration did not inhibit albuminuria. Equivalent results were obtained in model cells. These findings indicate that GM3 acts with nephrin in a collaborative manner in the cell membrane. Taken together, elevated levels of GM3 stabilize nephrin, which is a key molecule of the slit diaphragm, by enhancing the environment of the cell membrane and preventing albuminuria. This study provides novel insight into new drug discovery, which may offer a new therapy for kidney disease with albuminuria.