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AIM: To differentiate between growing and non-growing intracranial meningiomas using magnetisation transfer ratio (MTR) values with amide proton transfer (APT) and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventeen patients with suspected intracranial meningiomas who underwent APT-CEST MRI from November 2020 to April 2021 were evaluated retrospectively. MTR values on APT-CEST imaging as well as conventional MRI features were evaluated. These parameters were compared in growing meningiomas versus non-growing meningiomas and the findings compared with previous MRI examinations. ROC curve analysis was also performed to determine the diagnostic cut-offs for MTR. RESULTS: The cohort comprised 10 patients with growing meningiomas (two men [20%], eight women [80%]; mean age [standard deviation (SD)]: 59.9 years [16]) and seven patients with non-growing meningiomas (seven women [100%]; mean age [SD]: 63.9 years [18.6]). Significant differences were found in MTR values (0.0198 ± 0.0003 versus 0.0131 ± 0.0002; p<0.0001) between the growing meningiomas and non-growing meningiomas groups, respectively. The receiver operating characteristic (ROC) curve analysis showed that MTR values clearly differentiated between growing and non-growing meningiomas. At an area under the ROC curve (AUC) threshold of 0.0151, diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR were 100%, 85.7%, 90.9%, and 100%, respectively. CONCLUSION: Patients with growing meningiomas could be discriminated from patients with non-growing meningiomas, using the MTR values on post-growth tumour APT-CEST imaging.
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Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Amidas , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Pessoa de Meia-Idade , Projetos Piloto , Prótons , Estudos RetrospectivosRESUMO
OBJECTIVE: Serum interleukin-18 (IL-18) levels are increased in patients with interstitial lung disease (ILD). In addition, IL-18 levels are increased in patients with rheumatoid arthritis (RA) and are associated with arthritis activity. We determined whether increased IL-18 levels are associated with ILD in RA. METHOD: RA patients were enrolled using an RA cohort database. Plasma IL-18 levels were measured by enzyme-linked immunosorbent assay. ILD was determined by a pulmonologist and a radiologist based on chest radiography and computed tomography findings. IL-18 levels for RA with ILD and RA without ILD were compared. Associations between ILD and various markers including IL-18 and confounding factors (e.g. smoking history) were investigated by logistic regression analysis. Diagnostic values of IL-18 for the presence of ILD were investigated using receiver operating characteristics curve analysis. RESULTS: ILD was complicated in 8.2% (n = 26) of the study population (N = 312). Plasma IL-18 levels were higher for RA patients with ILD than for RA patients without ILD (721.0 ± 481.4 vs 436.8 ± 438.9 pg/mL, p < 0.001). IL-18, Krebs von den Lungen-6, and anti-cyclic citrullinated peptide antibody titre and glucocorticoid doses were independently associated with the presence of ILD during multivariate logistic regression analysis. Sensitivity and specificity of IL-18 levels for the detection of ILD in RA patients were 65.3% and 76.3%, respectively (area under the curve = 0.73). CONCLUSION: Plasma IL-18 levels were higher for RA patients with ILD than for those without ILD. Increased IL-18 levels were associated with the presence of ILD.
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Artrite Reumatoide/complicações , Interleucina-18/sangue , Doenças Pulmonares Intersticiais/complicações , Idoso , Artrite Reumatoide/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Halitosis is caused by volatile sulphur compounds including methyl mercaptan (CH3 SH) in the oral cavity and is a serious problem that limits interpersonal social communication. The aim of study was to evaluate the effects of reuterin-related compounds (RRCs) on halitosis-related periodontopathic bacteria in vitro. MATERIALS AND METHODS: RRC-01, RRC-02 and RRC-03 (32 and 64 µg ml-1 ) in culture media containing Fusobacterium nucleatum JCM8523 and Porphyromonas gingivalis ATCC33277 were used. The effects of RRCs on CH3 SH production and detectable odour by F. nucleatum and P. gingivalis were examined by CH3 SH production assay and organoleptic test, respectively. The number of bacterial cells was also measured using an ATP assay. In P. gingivalis treated with RRCs, the expression of mgl gene, which is responsible for CH3 SH production, was examined by qRT-PCR. RESULTS: CH3 SH production and the score of detectable odour from F. nucleatum and P. gingivalis culture media containing RRCs were significantly lower than that without RRCs (P < 0.05). The expression of mgl gene in P. gingivalis was significantly downregulated by RRC-01 (P < 0.01), but not by RRC-02 or RRC-03. CONCLUSIONS: RRCs are potent oral care products for preventing halitosis via reducing CH3 SH production.
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Antibacterianos/farmacologia , Fusobacterium nucleatum/efeitos dos fármacos , Gliceraldeído/análogos & derivados , Halitose/microbiologia , Odorantes/análise , Porphyromonas gingivalis/efeitos dos fármacos , Propano/farmacologia , Antibacterianos/uso terapêutico , Biomarcadores/metabolismo , Fusobacterium nucleatum/metabolismo , Gliceraldeído/farmacologia , Gliceraldeído/uso terapêutico , Halitose/prevenção & controle , Humanos , Porphyromonas gingivalis/metabolismo , Propano/uso terapêutico , Compostos de Sulfidrila/metabolismoRESUMO
Candida albicans is a commonly found member of the human microflora and is a major human opportunistic fungal pathogen. A perturbation of the microbiome can lead to infectious diseases caused by various micro-organisms, including C. albicans. Moreover, the interactions between C. albicans and bacteria are considered to play critical roles in human health. The major biological feature of C. albicans, which impacts human health, resides in its ability to form biofilms. In particular, the extracellular matrix (ECM) of Candida biofilm plays a multifaceted role and therefore may be considered as a highly attractive target to combat biofilm-related infectious diseases. In addition, extracellular DNA (eDNA) also plays a crucial role in Candida biofilm formation and its structural integrity and induces the morphological transition from yeast to the hyphal growth form during C. albicans biofilm development. This review focuses on pathogenic factors such as eDNA in Candida biofilm formation and its ECM production and provides meaningful information for future studies to develop a novel strategy to battle infectious diseases elicited by Candida-formed biofilm.
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Biofilmes , Candida albicans/fisiologia , Candida/classificação , Candida/fisiologia , Candida albicans/patogenicidade , Candidíase/microbiologia , DNA/metabolismo , Humanos , Hifas/fisiologia , Percepção de Quorum , Infecções Respiratórias/microbiologia , Fatores de Virulência/metabolismoRESUMO
AIMS: Quaternary ammonium compounds (QACs), including benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC) are cationic surfactants and have been used widely as general disinfectants in the medical field due to their strong antibacterial effects and low cytotoxicity to human cells. 4,4'-(α,ω-hexametylenedithio) bis (1-octylpyridinium bromide) (4DTBP-6,8) is one of the potent bis-QACs synthesized to improve the antimicrobial activities of mono-QACs such as BAC. This study aimed to assess the effectiveness of 4DTBP-6,8 against Pseudomonas aeruginosa, a prevalent hospital pathogen. METHODS AND RESULTS: The minimum inhibitory concentrations of 4DTBP-6,8, CPC and BAC against P. aeruginosa were measured. 4DTBP-6,8 exhibited strong antibacterial activity. We assessed the bactericidal effects of QACs against P. aeruginosa under certain conditions and their cytotoxicities in human epithelial cells using lactate dehydrogenase (LDH) release. 4DTBP-6,8 exerted excellent bactericidal effects against high concentrations of bacteria, biofilm cells and even in the presence of contaminated proteins. Cellular LDH was not released by the treatment with 4DTBP-6,8. CONCLUSIONS: 4DTBP-6,8 exhibited the strongest bactericidal activity against P. aeruginosa among the three QACs tested without any cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The potent bis-QAC, 4DTBP-6,8 has the potential to be an effective disinfectant in preventing hospital infections caused by P. aeruginosa.
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Antibacterianos/farmacologia , Desinfetantes/farmacologia , Niacinamida/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos de Piridínio/farmacologia , Biofilmes/efeitos dos fármacos , Linhagem Celular , Humanos , Niacinamida/farmacologiaRESUMO
CONTEXT: Autoimmune thyroid disease is considered a multifactorial disorder in which autoimmunity against thyroid antigens is facilitated by exposure to endogenous and environmental factors. We present here a rare case of identical female twins who developed consecutively Graves' disease within a few months and had three HLA susceptibility alleles for the development of Graves' disease. SUBJECTS: A 28-year-old woman was referred to our hospital complaining of thirst, sweating, palpitations, tremor and skin rash. Laboratory data showed hyperthyroidism with antibodies against the thyroid stimulating hormone receptor and ultrasonography of the thyroid revealed enlargement with hypervascularity. Her identical twin was referred to our hospital because of similar symptoms. RESULT: We diagnosed them with Graves' disease and both were treated with methimazole. Human leukocyte antigen genotyping showed that both twins possessed the DRB1*04:05, DQB1*04:01:01, DPB1*05:01 haplotype, which confers susceptibility to Graves' disease. CONCLUSIONS: This case supports the hypothesis that interaction of multiple human leukocyte antigen susceptibility alleles as well as genetic background and environmental factors might synergistically contribute the close timing in Graves' disease onset.
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BACKGROUND AND AIMS: Whether low-volume, high-intensity, interval training (HIIT) is an adequate exercise method for improving metabolic risk factors is controversial. Moreover, it is not known if performing a short-term, low-calorie diet intervention (LCDi) after a HIIT program affects risk factors. This study investigated how an 8-week, 3 times/week exercise intervention (EXi) incorporating either HIIT or moderate-intensity continuous training (MICT) followed by a 4-week LCDi affects risk factors. METHODS AND RESULTS: Twenty-six male workers with metabolic risk factors (47.4 ± 7.1 years; cardiorespiratory capacity (VO2peak) of 28.5 ± 3.9 ml/kg/min) were randomly assigned to either the HIIT (3 sets of 3-min cycling with a 2-min active rest between sets, 180 kcal) or MICT (45 min, 360 kcal) group. After the EXi, all subjects participated in a 4-week LCDi (4 counseling sessions). During the EXi, VO2peak improved more (P < 0.05) through HIIT (25.4 ± 14.6%) than through MICT (14.9 ± 12.8%), whereas improvements in body fat and HDL cholesterol were similar. During the LCDi, some risk factors improved further (P < 0.05) without any group differences, while VO2peak in the HIIT group decreased (P < 0.05) to the same level as in the MICT group. CONCLUSION: VO2peak increased more with HIIT than with MICT during the EXi despite HIIT having a lower exercise volume than MICT, but this advantage of HIIT promptly disappeared through detraining. An intervention strategy consisting of 8 weeks of either HIIT or MICT followed by a 4-week LCDi has a positive effect on metabolic risk factors. CLINICAL TRIAL REGISTRATION: UMIN11352.
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Restrição Calórica , Exercício Físico , Síndrome Metabólica/prevenção & controle , Tecido Adiposo/metabolismo , Adulto , Povo Asiático , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Consumo de Oxigênio , Fatores de RiscoRESUMO
INTRODUCTION: Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear. MATERIALS AND METHODS: The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC + R, n = 79). RESULTS: Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC + R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC + R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC + R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%). CONCLUSIONS: IAC + R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/terapia , Neoplasias da Bexiga Urinária/terapia , Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma de Células de Transição/patologia , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cistectomia , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante/métodos , Invasividade Neoplásica , Tratamentos com Preservação do Órgão , Peplomicina/administração & dosagem , Prognóstico , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologiaRESUMO
AIM: To investigate the effect of catechins on vascular endothelial growth factor (VEGF) production and cyclooxygenase-2 (COX-2) expression in human dental pulp cells (HDPC) stimulated with bacteria-derived factors or pro-inflammatory cytokines. METHODOLOGY: Morphologically fibroblastic cells established from explant cultures of healthy human dental pulp tissues were used as HDPC. HDPC pre-treated with catechins, epigallocatechin-3-gallate (EGCG) or epicatechin gallate (ECG), were exposed to lipopolysaccharide (LPS), peptidoglycan (PG), interlukin-1ß (IL-1ß) or tumour necrosis factor-α (TNF-α). VEGF production was examined by enzyme-linked immunosorbent assay, and COX-2 expression was assessed by immunoblot. RESULTS: EGCG and ECG significantly reduced LPS- or PG-mediated VEGF production in the HDPC in a dose-dependent manner. EGCG also prevented IL-1ß-mediated VEGF production. Although TNF-α did not enhance VEGF production in the dental pulp cells, treatment of 20 µg mL(-1) of EGCG decreased the level of VEGF. In addition, the catechins attenuated COX-2 expression induced by LPS and IL-1ß. CONCLUSIONS: The up-regulated VEGF and COX-2 expressions in the HDPC stimulated with these bacteria-derived factors or IL-1ß were diminished by the treatment of EGCG and ECG. These findings suggest that the catechins may be beneficial as an anti-inflammatory tool of the treatment for pulpal inflammation.
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Catequina/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Western Blotting , Catequina/análogos & derivados , Células Cultivadas , Polpa Dentária/citologia , Ensaio de Imunoadsorção Enzimática , Fibroblastos/efeitos dos fármacos , Humanos , Interleucina-1beta/farmacologia , Lipopolissacarídeos/farmacologia , Peptidoglicano/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
PURPOSE: Cell-free and concentrated ascites reinfusion therapy (CART) is intended to treat patients by ultrafiltration and reinfusion of their refractory ascites. In the CART system, bacteria and cancer cells in removed massive ascites are filtrated. Then, water is removed in the condenser, resulting in a higher protein concentration. The purpose of this study was to assess the clinical usefulness of CART in the treatment of refractory massive ascites in patients with cancerous peritonitis. MATERIALS AND METHODS: CART was performed 13 times in four patients with ovarian and endometrial cancer. RESULTS: Autologous protein with a higher concentration was intravenously administered. The amount of aspirated and condensed ascites was 3,190 +/- 1,086 ml (975 4,500 ml) and 538 +/- 249 ml (100 - 860 ml), respectively. Condensed albumin, albumin concentration, and concentration time were 43.2 +/- 25.8 g, 8.2 +/- 3.3 g/dl, and 73.3 +/- 24.8 min (28 - 122 min), respectively. CART was effective in maintaining serum albumin concentrations, and it is possible to repeat infusion. During CART, patients performance status was 1-2 and vital signs were stable except for mild elevations in body temperature. Daily life was maintained without serious side-effects. CONCLUSIONS: The use of CART for gynecological cancer patients with refractory massive ascites due to cancerous peritonitis contributes to improvements in quality of life and relief of symptoms. With autologous infusion of condensed ascites, patients can avoid infection, allergic reactions, and administration of expensive blood products.
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Ascite/terapia , Neoplasias do Endométrio/terapia , Neoplasias Ovarianas/terapia , Peritonite/terapia , Neoplasias do Endométrio/sangue , Feminino , Humanos , Neoplasias Ovarianas/sangue , Albumina Sérica/análiseRESUMO
AIMS: The aim of this study was to investigate the effects of genomic DNA purified from Candida albicans and pneumonia-related pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, on in vitro biofilm formation and morphological change of 3 Candida species (C. albicans, C. glabrata, and C. tropicalis). METHODS AND RESULTS: Biofilm formation was evaluated by the crystal violet assay and colony-forming unit counts. Morphological characteristics of biofilms were evaluated by scanning electron microscopy and fluorescence microscopy. Addition of DNA at a low concentration (<1·0 µg ml(-1)) significantly increased biofilm mass of all three Candida species. In contrast, the addition of DNA at a high concentration (10 µg ml(-1)) decreased the biofilm mass. Interestingly, the formation of hyphae in a dense network of yeast cells was observed in C. albicans biofilms exposed to a low concentration of DNA (<1·0 µg ml(-1)). CONCLUSIONS: These findings demonstrated that extracellular DNA (eDNA) plays a crucial role in Candida biofilm formation and suggested that eDNA may induce the morphological transition from yeast to hyphal growth form during C. albicans biofilm development. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel therapy targeting eDNA may be applicable for Candida infection to decrease biofilm formation and hyphal formation.
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Biofilmes/crescimento & desenvolvimento , Candida/crescimento & desenvolvimento , DNA Fúngico/metabolismo , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Desoxirribonuclease I/farmacologia , Hifas/crescimento & desenvolvimento , Viabilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia de FluorescênciaRESUMO
AIMS: The aim of this study was to clarify the effects of homologous and heterologous extracellular DNAs (eDNAs) and histone-like DNA-binding protein (HLP) on Streptococcus intermedius biofilm development and rigidity. METHODS AND RESULTS: Formed biofilm mass was measured with 0·1% crystal violet staining method and observed with a scanning electron microscope. The localizations of eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining with 7-hydoxyl-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) and anti-HLP antibody without fixation, respectively. DNase I treatment (200 U ml(-1)) markedly decreased biofilm formation and cell density in biofilms. Colocalization of eHLP and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 µg ml(-1)) purified from Strep. intermedius, other Gram-positive bacteria, Gram-negative bacteria, or human KB cells into the Strep. intermedius culture increased the biofilm mass of all tested strains of Strep. intermedius, wild-type, HLP-downregulated strain and control strains. In contrast, the addition of eDNA (>1 µg ml(-1)) decreased the biofilm mass of all Strep. intermedius strains. CONCLUSIONS: These findings demonstrated that eDNA and eHLP play crucial roles in biofilm development and its rigidity. SIGNIFICANCE AND IMPACT OF THE STUDY: eDNA- and HLP-targeting strategies may be applicable to novel treatments for bacterial biofilm-related infectious diseases.
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Biofilmes/crescimento & desenvolvimento , Proteínas de Ligação a DNA/metabolismo , DNA/farmacologia , Streptococcus intermedius/fisiologia , Biofilmes/efeitos dos fármacos , Linhagem Celular Tumoral , DNA/análise , Proteínas de Ligação a DNA/análise , Desoxirribonuclease I , Humanos , Streptococcus intermedius/efeitos dos fármacos , Streptococcus intermedius/crescimento & desenvolvimentoRESUMO
Fallow field biotopes that develop from abandoned rice fields are man-made wetlands that provide new habitats for various aquatic animals. Although consideration of such biotopes generally focuses on their positive aspects, this study evaluated the negative aspects of establishing fallow field biotopes with regard to mosquito breeding sites. To determine whether fallow field biotopes become breeding habitats for vector mosquitoes, we evaluated mosquito fauna in fallow field biotopes and adjacent rice fields. We found larvae of Anopheles lesteri, Anopheles sinensis and Culex tritaeniorhynchus (all: Diptera: Culicidae) in the biotopes. Although abundances of mosquito larvae in the biotopes and rice fields were statistically similar, mosquito abundances in rice fields increased dramatically in August when the water level reduced after the rainy season. The abundance and variety of the mosquitoes' natural predators were greater in biotopes than in rice fields because the former are a permanent and stable aquatic environment. A generalized linear mixed model showed a negative effect of predator diversity on mosquito larvae abundance in both habitats. Although fallow field biotopes become breeding habitats for vector mosquitoes, establishing biotopes from fallow fields in order to protect various aquatic animals, including mosquito insect predators, may help to control mosquito breeding.
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Culicidae/fisiologia , Cadeia Alimentar , Insetos Vetores/fisiologia , Insetos/fisiologia , Agricultura , Animais , Culicidae/classificação , Culicidae/crescimento & desenvolvimento , Ecossistema , Insetos/classificação , Japão , Larva/classificação , Larva/fisiologia , Controle de Mosquitos , Oryza , Densidade Demográfica , Estações do AnoRESUMO
BACKGROUND/OBJECTIVE: Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue (VAT), but there is no clear consensus as to a standardized protocol. We compared the ability of two commonly used imaging protocols (multiple slice versus single slice) to detect changes in VAT with diet or exercise. SUBJECTS/METHODS: We utilized data from the participants who completed our diet (n=22) or exercise (n=35) based weight-loss interventions. The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks. Multiple-slice images obtained from T9 to S1 and a single-slice image at L4-L5 were compared using the effect size of the VAT change. In addition, we calculated the sample size needed to compare the two imaging protocols' ability to detect significant changes in VAT. RESULTS: VAT and subcutaneous adipose tissue volumes and areas, and other anthropometry decreased significantly after both the diet and exercise interventions. For VAT, a single-slice image had a lower effect size (diet: 1.23; exercise: 0.49) than the multiple-slice images (diet: 1.81; exercise: 0.90). The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions. CONCLUSIONS: The different image protocols may lead to different results in relative VAT changes. Furthermore, single-slice imaging required a substantially larger sample size than multiple-slice imaging, and for researchers to detect smaller changes in VAT with single-slice imaging, a larger sample size would be needed. Thus, multiple-slice imaging has advantages for assessing VAT change in future clinical research.
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Gordura Intra-Abdominal/patologia , Imageamento por Ressonância Magnética/métodos , Obesidade/terapia , Redução de Peso , Adulto , Dieta Redutora , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/patologia , Reprodutibilidade dos Testes , Gordura Subcutânea/patologiaRESUMO
AIMS: The aim of this work was to clarify the effects of electromagnetic wave irradiation (EMWI) on oral bacterial pathogens. METHODS AND RESULTS: A Gram-negative (Porphyromonas gingivalis) or Gram-positive (Streptococcus mutans, S. intermedius, Enterococcus faecalis) bacterial suspension was irradiated by EMW apparatus (500-1000 kHz, 5-15 times, 1 s time(-1) ). Quantification of survival bacteria by CFU counting revealed that EMWI exhibited marked bactericidal activity against all tested bacteria and bactericidal activity at 500 kHz increased in an irradiation number-dependent manner. After EMWI at 500 kHz, scanning electron microscopic observations showed that the chain of S. mutans cells was shortened after 5 irradiations and the outlines of bacterial cells (S. mutans and P. gingivalis) were unclear after 5-10 irradiations. EMWI inhibited the inductive effect of S. mutans on pro-inflammatory cytokine production in human monocytes and this inhibitory effect was comparable with that of heat-killed bacteria. Furthermore, using an enzyme activity assay, EMWI partially inactivated the activities of gingipains from P. gingivalis. CONCLUSIONS: These findings demonstrated that EMWI has inactivation and bactericidal activities against single microbial species among four kinds of oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Electromagnetic wave irradiation may be applicable for medical disinfection and sterilization, such as refractory periapical periodontitis.
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Desinfecção/métodos , Campos Eletromagnéticos , Porphyromonas gingivalis/crescimento & desenvolvimento , Streptococcus mutans/crescimento & desenvolvimento , Adesinas Bacterianas/metabolismo , Linhagem Celular , Cisteína Endopeptidases/metabolismo , Enterococcus faecalis/crescimento & desenvolvimento , Cisteína Endopeptidases Gingipaínas , Humanos , Testes de Sensibilidade Microbiana , Boca/microbiologia , TemperaturaRESUMO
BACKGROUND AND OBJECTIVE: As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin-1 and E-cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated chemokine secretion and E-cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions. MATERIAL AND METHODS: We examined the permeability, and the expression of claudin-1 and E-cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)-α, with or without IM. RESULTS: TNF-α increased the permeability of HGECs, and IM abolished the increase. TNF-α reduced the expression of E-cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF-α disrupted claudin-1 expression in HGECs, and IM reversed this effect. CONCLUSION: The results suggest that IM reverses the TNF-α-induced disruption of the gingival epithelial barrier by regulating E-cadherin and claudin-1.
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Gengiva/efeitos dos fármacos , Triazinas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Adulto , Western Blotting , Caderinas/efeitos dos fármacos , Técnicas de Cultura de Células , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Claudina-1 , Impedância Elétrica , Inserção Epitelial/citologia , Inserção Epitelial/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Fluoresceína , Imunofluorescência , Corantes Fluorescentes , Gengiva/citologia , Gengiva/imunologia , Humanos , Masculino , Proteínas de Membrana/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Junções Íntimas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. METHODS: The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. RESULTS: A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. CONCLUSION: Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Adulto , Idoso , Determinação da Pressão Arterial , Creatinina/urina , Combinação de Medicamentos , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hiperuricemia , Japão , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Resultado do Tratamento , Ácido Úrico/sangue , Adulto JovemRESUMO
Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adiponectina/sangue , Endotélio Vascular/metabolismo , Resistência à Insulina/imunologia , Síndrome Metabólica/sangue , Óxido Nítrico/sangue , Estresse Oxidativo/imunologia , Antioxidantes/metabolismo , Índice de Massa Corporal , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Inflamação/sangue , Peroxidação de Lipídeos , Síndrome Metabólica/imunologia , Obesidade/sangue , Ácido Úrico/sangueRESUMO
Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman's rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.