RESUMEN
In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients' macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1ß secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-ß (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1ß and/or IFN-I signaling could represent a therapeutic approach for these patients.
Asunto(s)
Fascitis Necrotizante , Interferón Tipo I , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inmunidad Innata , Inflamación/metabolismo , Subunidad p50 de NF-kappa BRESUMEN
PURPOSE: To investigate the biocompatibility of silver nanoparticle (AgNP)-doped Ti-6Al-4V surfaces by evaluating the viability and proliferation rate of human gingival fibroblasts (HGFs)-as the dominant cells of peri-implant soft tissues-seeded on the modified surfaces. MATERIALS AND METHODS: AgNPs (sizes 8 nm and 30 nm) were incorporated onto Ti-6Al-4V specimen surfaces via electrochemical deposition, using colloid silver dispersions with increasing AgNP concentrations of 100 ppm, 200 ppm, and 300 ppm. One control and six experimental groups were included in the study: (1) control (Ti-6Al-4V), (2) 8 nm/100 ppm, (3) 8 nm/200 ppm, (4) 8 nm/300 ppm, (5) 30 nm/100 ppm, (6) 30 nm/200 ppm, and (7) 30 nm/300 ppm. HGF cell primary cultures were isolated from periodontally healthy donor patients and cultured in direct contact with the group specimens for 24 and 72 hours. The cytotoxicity of AgNP-doped Ti-6Al-4V specimens toward HGF was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and BrdU (5-bromo-2'-deoxyuridine) assay tests. Calcein AM and ethidium homodimer (EthD-1) fluorescent stains were used to determine the live and dead cells. The morphology and attachment properties of the HGFs were determined via scanning electron microscopy (SEM). RESULTS: Energy dispersive x-ray (EDX) analysis confirmed the presence of AgNPs on the specimens. The MTT test revealed that AgNPs of both sizes and all concentrations presented a decreased cellular metabolic activity compared to the control discs. All concentrations of both sizes of AgNPs affected the cell proliferation rate compared to the control group, as revealed by the BrdU assay. Overall, cytotoxicity of the modified Ti-6Al-4V surfaces depended on cell exposure time. Observation via confocal microscopy confirmed the results of the MTT and BrdU assay tests. Specifically, most cells remained alive throughout the 72-hour culture period. SEM images revealed that adjacent cells form bonds with each other, creating confluent layers of conjugated cells. CONCLUSIONS: The findings of the present study indicate that Ti-6Al-4V surfaces modified with 8 nm and 30 nm AgNPs at concentrations of 100 ppm, 200 ppm, and 300 ppm do not produce any serious cytotoxicity toward HGFs. The initial arrest of the HGF proliferation rate recovered at 72 hours. These results on the antibacterial activity against common periodontal pathogens, in combination with the results found in a previous study by the same research group, suggest that AgNP-doped Ti-6Al-4V surfaces are potential candidates for use in implant abutments for preventing peri-implant diseases.
Asunto(s)
Aleaciones , Proliferación Celular , Supervivencia Celular , Fibroblastos , Encía , Nanopartículas del Metal , Plata , Propiedades de Superficie , Tiazoles , Titanio , Humanos , Fibroblastos/efectos de los fármacos , Titanio/toxicidad , Titanio/química , Encía/citología , Encía/efectos de los fármacos , Plata/química , Plata/toxicidad , Proliferación Celular/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Aleaciones/toxicidad , Ensayo de Materiales , Aleaciones Dentales/química , Aleaciones Dentales/toxicidad , Microscopía Electrónica de Rastreo , Colorantes , Materiales Biocompatibles/química , Sales de TetrazolioRESUMEN
PURPOSE: To identify differences between three-phase bone scan and SPECT/CT (TBS) and WBC SPECT/CT (WS) and compare diagnostic accuracies of each modality in patients with suspicious post-traumatic osteomyelitis (OM). METHODS: Twenty-one patients with suspicious post-traumatic OM were enrolled. All patients performed TBS and WS within 1 week. Foci of MDP and WBC accumulation were divided into three categories: bone (OM), soft tissue (soft tissue inflammation; STI), negative for inflammation (NI). Confirmative diagnosis was made upon operative pathology or long-term clinical follow-up. RESULTS: Of 21 patients, four OM, eight STI, nine NI were finally diagnosed. TBS diagnosis was correct in three of four positive cases and nine of 17 negative cases. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) of TBS were 75 %, 52.9 %, 57.1 %, 27.3 %, 90 %. WS diagnosis was correct in two of four positive cases and 17 of 17 negative cases. Sensitivity, specificity, accuracy, PPV, NPV were 50 %, 100 %, 81.0 %, 100 %, 89.5 %. Twelve of 21 cases showed agreement between TBS and WS. TBS misdiagnosed nine cases (six STI and two NI as eight OM; one OM as one STI), while WS misdiagnosed four cases (two OM as two STI; two STI as two NI). Combining results from TBS and WS led to better diagnostic accuracy (91.7 %) than either TBS or WS alone. CONCLUSION: TBS and WS showed moderate agreement in assessment of clinically suspected post-traumatic OM. WS better evaluated inflammation than TBS. WS tended to underestimate inflammation whereas TBS tended to overestimate inflammation. Combining TBS and WS enhanced diagnostic accuracy.
RESUMEN
With its long-lasting effectiveness, octenidine is an agent of first choice for antiseptic wound treatment. However, the manufacturer advises against instillation of the agent under pressure. A 50-year-old patient presented with erythema and extensive soft tissue induration after wound cleansing with octenidine under pressure. Due to the lack of resorption of the agent, this caused long-lasting interstitial soft tissue edema. This case demonstrates the importance of following the manufacturer's instructions for use. Advantages of the agent such as lack of systemic toxicity or broad spectrum efficacy can only be achieved if the agent is applied correctly.
Asunto(s)
Eritema/etiología , Terapia de Presión Negativa para Heridas/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Antiinfecciosos Locales/efectos adversos , Diagnóstico Diferencial , Eritema/patología , Eritema/prevención & control , Femenino , Humanos , Iminas , Persona de Mediana Edad , Infección de Heridas/complicacionesRESUMEN
PURPOSE: To identify differences between three-phase bone scan and SPECT/CT (TBS) and WBC SPECT/CT (WS) and compare diagnostic accuracies of each modality in patients with suspicious post-traumatic osteomyelitis (OM).METHODS: Twenty-one patients with suspicious post-traumatic OM were enrolled. All patients performed TBS and WS within 1 week. Foci ofMDP andWBC accumulation were divided into three categories: bone (OM), soft tissue (soft tissue inflammation; STI), negative for inflammation (NI). Confirmative diagnosis was made upon operative pathology or long-term clinical follow-up.RESULTS: Of 21 patients, four OM, eight STI, nine NI were finally diagnosed. TBS diagnosis was correct in three of four positive cases and nine of 17 negative cases. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) of TBS were 75 %, 52.9 %, 57.1 %, 27.3 %, 90 %. WS diagnosis was correct in two of four positive cases and 17 of 17 negative cases. Sensitivity, specificity, accuracy, PPV, NPV were 50 %, 100 %, 81.0 %, 100 %, 89.5 %. Twelve of 21 cases showed agreement between TBS and WS. TBS misdiagnosed nine cases (six STI and two NI as eight OM; one OM as one STI), while WS misdiagnosed four cases (two OM as two STI; two STI as two NI). Combining results from TBS and WS led to better diagnostic accuracy (91.7 %) than either TBS or WS alone.CONCLUSION: TBS and WS showed moderate agreement in assessment of clinically suspected post-traumatic OM. WS better evaluated inflammation than TBS. WS tended to underestimate inflammation whereas TBS tended to overestimate inflammation. Combining TBS and WS enhanced diagnostic accuracy.
Asunto(s)
Humanos , Diagnóstico , Diagnóstico Diferencial , Estudios de Seguimiento , Inflamación , Osteomielitis , Patología , Sensibilidad y Especificidad , Enfermedades de Transmisión SexualRESUMEN
The effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of pain in osteoarthritis and other musculoskeletal diseases is well documented. The role of NSAIDs is less clear in the treatment of conditions involving soft tissue inflammation, including the airways, ear-nose-throat (ENT) system and urogenital tract. These conditions are often treated inappropriately with antibiotics. Morniflumate, the ß-morpholinoethyl ester of niflumic acid, is a member of the fenamate family of NSAIDs indicated for the treatment of inflammatory conditions (with or without pain) affecting airways, the ENT system, urogenital tract and the osteoarticular system. Morniflumate has a 30-year history of clinical use, particularly for the treatment of pain associated with paediatric ENT infection. This article reviews evidence supporting the efficacy and safety of morniflumate. Based on available evidence and the favourable tolerability profile emerging from extensive clinical use, morniflumate appears to be a valid and well-tolerated alternative to other NSAIDs, or to antibiotics, for the treatment of pain and other symptoms of soft tissue inflammation.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Miositis/tratamiento farmacológico , Ácido Niflúmico/análogos & derivados , Osteítis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Ciclooxigenasa 2/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Ratones , Ácido Niflúmico/efectos adversos , Ácido Niflúmico/farmacocinética , Ácido Niflúmico/uso terapéutico , Osteoartritis/tratamiento farmacológico , RatasRESUMEN
OBJECTIVE: The purpose of this study was to compare the bacterial flora at the peri-implant sulcus of the orthodontic mini-implant placed in the alveolar mucosa with the bacterial flora at the adjacent healthy gingival sulcus. METHODS: Two plaque samples from 7 patients were collected by inserting paper points into the sulcus between the mini-implant and ligature wire connected to the mini-implant head and inflamed alveolar mucosa, and from the gingival sulcus of a healthy tooth adjacent to the mini-implant. RESULTS: Using 16S rDNA clone library, the 24 kinds of bacteria including Haemophilus aphrophilus, Sphingomonas species, Capnocytophaga species, Prevotella melaninogenica, Lachnospiraceae species, Porphyromonas species, Neisseria flava were identified only from the sulcus around the mini-implant. These bacteria constituted only 9.2% of total clones, and the bacteria identified from both the sulcus around mini-implants and the gingival sulcus constituted 80.4% of total clones. Of these bacteria, clones of Prevotella species, Atopobium rimae, Veillonella species, Streptococcus intermedius/constellatus, Streptococcus salivarius were more frequently isolated from the peri-implant sulcus. CONCLUSION: This study suggests that a broad epidemiological study is needed to find causative bacteria which induce inflammation from the peri-implant sulcus.