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1.
Eur Rev Med Pharmacol Sci ; 24(9): 5140-5147, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32432778

RESUMO

OBJECTIVE: Sesamin is a functional ingredient in sesame (Sesamum indicum) seeds and has many physiological effects. This study investigated whether sesame lignans, sesamin and episesamin (1:1), can suppress age-related disorders of the kidney. MATERIALS AND METHODS: Twenty-month-old mice were divided into three groups, and each group received a regular diet (O-C), diet containing sesame lignans (O-SE), and diet containing sesame lignans and α-tocopherol (VE; O-SE+VE), respectively, for 5 months. Six-month-old young mice (Y-C) were compared to the older mice. RESULTS: Renal lipofuscin deposition was increased in the O-C group compared to that in the Y-C group and its deposition with aging was significantly decreased in both O-SE and O-SE+VE groups. Plasma blood urea nitrogen levels in the O-C group increased compared to those in the Y-C group; however, those in both O-SE and O-SE+VE groups did not differ from those in the Y-C group. The number of podocytes in the O-C group decreased compared to that in the Y-C group and this effect was attenuated in the O-SE and O-SE+VE groups. The effect was strongest in the O-SE+VE group. Histological examinations showed that glomerular hypertrophy accompanied by mesangial hyperplasia and renal tubular degeneration was less severe in the O-SE and O-SE+VE groups than in the O-C group. Moreover, age-related increases in the mRNA expression of NADPH oxidase- and inflammation-related genes, including p67phox, p40phox, TNFα, and IL-6, in the kidney were suppressed in the O-SE and O-SE+VE groups. CONCLUSIONS: Sesame lignans might be useful to suppress age-related kidney disorders, and these effects could be enhanced with VE.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Dioxóis/farmacologia , Nefropatias/tratamento farmacológico , Lignanas/farmacologia , alfa-Tocoferol/farmacologia , Animais , Antioxidantes/administração & dosagem , Dieta , Dioxóis/administração & dosagem , Nefropatias/metabolismo , Lignanas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sesamum/química , alfa-Tocoferol/administração & dosagem
2.
J Nutr Health Aging ; 21(5): 573-578, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28448089

RESUMO

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.


Assuntos
Deficiência de Ácido Ascórbico/complicações , Ácido Ascórbico/biossíntese , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/etiologia , Proteínas de Ligação ao Cálcio/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Absorciometria de Fóton , Envelhecimento , Animais , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Deficiência de Ácido Ascórbico/metabolismo , Peso Corporal/efeitos dos fármacos , Doenças Ósseas Metabólicas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Fêmur/patologia , Masculino , Mandíbula/efeitos dos fármacos , Mandíbula/metabolismo , Mandíbula/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia
3.
J Dent Res ; 95(12): 1381-1386, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27470067

RESUMO

Periodontal disease is characterized by chronic inflammation in subgingival areas, where a vast array of inflammation-associated metabolites are likely produced from tissue breakdown, increased vascular permeability, and microbial metabolism and then eventually show a steady flow into saliva. Thus, prolonged periodontal inflammation is a key feature of disease activity. Although salivary metabolomics has drawn attention for its potential use in diagnosis of periodontal disease, few authors have used that to investigate periodontal inflammation detection. In this pilot study, the authors explored the use of salivary metabolites to reflect periodontal inflammation severity with a recently proposed parameter-periodontal inflamed surface area (PISA)-used to quantify the periodontal inflammatory burden of individual patients with high accuracy. Following PISA determination, whole saliva samples were collected from 19 subjects before and after removal of supragingival plaque and calculus (debridement) with an ultrasonic scaler to assess the influence of the procedure on salivary metabolic profiles. Metabolic profiling of saliva was performed with gas chromatography coupled to time-of-flight mass spectrometry, followed by multivariate regression analysis with orthogonal projections to latent structures (OPLS) to investigate the relationship between PISA and salivary metabolic profiles. Sixty-three metabolites were identified. OPLS analysis showed that postdebridement saliva provided a more refined model for prediction of PISA than did predebridement samples, which indicated that debridement may improve detection of metabolites eluted from subgingival areas in saliva, thus more accurately reflecting the pathophysiology of periodontitis. Based on the variable importance in the projection values obtained via OPLS, 8 metabolites were identified as potential indicators of periodontal inflammation, of which the combination of cadaverine, 5-oxoproline, and histidine yielded satisfactory accuracy (area under the curve = 0.881) for diagnosis of periodontitis. The authors' findings identified potential biomarkers that may be useful for reflecting the severity of periodontal inflammation as part of monitoring disease activity in periodontitis patients.


Assuntos
Doenças Periodontais/metabolismo , Doenças Periodontais/patologia , Saliva/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Desbridamento Periodontal , Doenças Periodontais/terapia , Valor Preditivo dos Testes , Saliva/química , Índice de Gravidade de Doença
4.
J Cardiovasc Surg (Torino) ; 56(3): 455-62, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25729918

RESUMO

Aim. The aim of this study was to evaluate the performance of the new European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). This study also evaluated the performance of the EuroSCORE II in high-risk patients. Methods. Three hundred and six consecutive adult patients underwent AVR with or without coronary artery bypass grafting at our institution from August 2002 to June 2012. The cut-off value of 6% for the EuroSCORE II and 10% for the STS score was used to identify high-risk in this study. Results. Operative mortality was 3.5% (N.=11). The mean expected mortality for all patients was 3.1% (O/E ratio=1.12) for the EuroSCORE II and 5.1% (O/E ratio=0.68) for the STS score. Observed versus expected mortality for the high-risk patients was 17.2% versus 11.9% (O/E ratio=1.44) for the EuroSCORE II (N.=29) and 19.3% versus 18.5% (O/E ratio=1.04) for the STS score (N.=31), and that for the low-risk was 2.1% versus 2.2% (O/E ratio=0.95) for the EuroSCORE II and 1.8% versus 3.5% (O/E ratio=0.51) for the STS score. Discrimination power of the STS score was good (area under the receiver operating characteristics curve [AUC] 0.74), but that of the EuroSCORE II was suboptimal (AUC 0.66). Conclusion. Good calibration ability of the EuroSCORE II for low-risk patients and that of the STS score for high-risk are observed. However, the EuroSCORE II underestimates the operative mortality in high-risk patients and the STS score overestimates the risk in low-risk patients.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Técnicas de Apoio para a Decisão , Implante de Prótese de Valva Cardíaca , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Perfusion ; 30(8): 653-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25721457

RESUMO

BACKGROUND: We designed a non-invasive, observational, real-time study, using near-infrared spectroscopy (NIRS) to assess the in vivo effects of cardiopulmonary bypass (CPB) on patients' skeletal muscle as well as the effects of hemodilution and hypothermia on tissue oxygen delivery during CPB. METHODS: The study included 20 consecutive adult patients undergoing open-heart surgery with CPB. Evaluation parameters for peripheral circulation were measured using the NIRO-200NX and recorded every 30 seconds. To assess how hemodilution influences peripheral circulation parameters, we compared data between a group of patients with hematocrit (Hct) values >22% (high Hct group) and those with Hct values ⩽22% (low Hct group). RESULTS: Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L), which flows into the skeletal muscle, was an important factor for deciding the tissue oxygenation index (TOI%), showing the tissue oxygen saturation. The low Hct group showed a significant increase in the normalized tissue hemoglobin index (nTHI), showing the percentage change in the amount of initial hemoglobin and TOI compared to the high Hct group. Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L) and deoxygenated hemoglobin (ΔHHb, µmol/L) were significantly less in the low Hct group than in the high Hct group, thus, showing good peripheral circulation despite the low hematocrit levels. CONCLUSION: Our study indicated the presence of a compensatory mechanism in which increased blood flow of the microcirculation is in compensation for the lack of oxyhemoglobin delivery caused by hemodilution.


Assuntos
Ponte Cardiopulmonar/métodos , Hemodiluição/métodos , Microcirculação/fisiologia , Músculo Esquelético/metabolismo , Adulto , Idoso , Hematócrito , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho
7.
Prog Biophys Mol Biol ; 116(1): 11-24, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25192800

RESUMO

It has long been suggested that the Ca(2+)-mechanisms are largely involved in generating the early afterdepolarization (EAD) as well as the delayed afterdepolarization (DAD). This view was examined in a quantitative manner by applying the lead potential analysis to a new human ventricular cell model. In this ventricular cell model, the tight coupled LCC-RyR model (CaRU) based on local control theory (Hinch et al. 2004) and ion channel models mostly based on human electrophysiological data were included to reproduce realistic Ca(2+) dynamics as well as the membrane excitation. Simultaneously, the Ca(2+) accumulation near the Ca(2+) releasing site was incorporated as observed in real cardiac myocytes. The maximum rate of ventricular repolarization (-1.02 mV/ms) is due to IK1 (-0.55 mV/ms) and the rest is provided nearly equally by INCX (-0.20 mV/ms), INaL (-0.16 mV/ms) and INaT (-0.13 mV/ms). These INaL and INaT components are due to closure of the voltage gate, which remains partially open during the plateau potential. DADs could be evoked by applying high-frequency stimulations supplemented by a partial Na(+)/K(+) pump inhibition, or by a microinjection of Ca(2+). EADs was evoked by retarding the inactivation of INaL. The lead potential (VL) analysis revealed that IK1 and IKr played the primary role to reverse the AP repolarization to depolarizing limb of EAD. ICaL and INCX amplified EAD, while the remaining currents partially antagonized dVL/dt. The maximum rate of rise of EAD was attributable to the rapid activation of both ICaL (45.5%) and INCX (54.5%).


Assuntos
Potenciais de Ação/fisiologia , Sinalização do Cálcio/fisiologia , Potenciais da Membrana/fisiologia , Modelos Cardiovasculares , Miócitos Cardíacos/fisiologia , Função Ventricular/fisiologia , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Simulação por Computador , Ventrículos do Coração/citologia , Humanos , Ativação do Canal Iônico/fisiologia , Miócitos Cardíacos/citologia
8.
Aust Dent J ; 59(4): 497-503, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25091293

RESUMO

BACKGROUND: Bacterial resistance to antibiotics is a health problem in many parts of the world. The aim of this study was to identify bacteria from dental infections and determine bacterial resistance to antibiotics used in dental care in the primary dentition. METHODS: This cross-sectional study comprised 60 children who presented for dental treatment for active dental infections in the primary dentition. Samples from dental infections were collected and bacteria were identified by polymerase chain reaction (PCR) assay. Bacterial resistance to antibiotics was determined by colony forming units on agar plates containing amoxicillin, clindamycin and amoxillicin-clavulanic acid (A-CA) tested at 8 µg/ml or 16 µg/ml. RESULTS: Clindamycin in both concentrations tested (8 µg/ml and 16 µg/ml) showed the highest bacterial resistance (85.9%), followed by amoxicillin (43.7%) and A-CA (12.0%). All comparisons among the three antibiotics used in the study exhibited statistical significance (p = <0.05) in both concentrations tested (8 µg/ml and 16 µg/ml), and under aerobic and anaerobic conditions. The most prevalent resistant species identified by PCR in primary dentition infections were: Streptococcus oralis and Prevotella intermedia (75.0%); Treponema denticola and Porphyromonas gingivalis (48.3%); Streptococcus mutans (45.0%); Campylobacter rectus; and Streptococcus salivarius (40%). CONCLUSIONS: This study demonstrated that A-CA exhibited the lowest bacterial resistance for clinical isolates in primary dentition infections.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Clindamicina/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Doenças Dentárias/tratamento farmacológico , Doenças Dentárias/microbiologia , Dente Decíduo/microbiologia , Biofilmes/crescimento & desenvolvimento , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Estudos Transversais , Placa Dentária/microbiologia , Humanos
9.
Adv Dent Res ; 26(1): 15-22, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24736700

RESUMO

Periodontal disease is caused by a group of bacteria that utilize a variety of strategies and molecular mechanisms to evade or overcome host defenses. Recent research has uncovered new evidence illuminating interesting aspects of the virulence of these bacteria and their genomic variability. This paper summarizes some of the strategies utilized by the major species - Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis - implicated in the pathogenesis of periodontal disease. Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has revealed variations in their genetic content (ranging between 0.4% and 19.5%) and organization. Strikingly, isolates from human periodontal sites showed no genomic changes during persistent colonization. T. forsythia manipulates the cytokine responses of macrophages and monocytes through its surface glycosylation. Studies have revealed that bacterial surface-expressed O-linked glycans modulate T-cell responses during periodontal inflammation. Periodontal pathogens belonging to the "red complex" consortium express neuraminidases, which enables them to scavenge sialic acid from host glycoconjugates. Analysis of recent data has demonstrated that the cleaved sialic acid acts as an important nutrient for bacterial growth and a molecule for the decoration of bacteria surfaces to help evade the host immune attack. In addition, bacterial entry into host cells is also an important prerequisite for the lifestyle of periodontal pathogens such as P. gingivalis. Studies have shown that, after its entry into the cell, this bacterium uses multiple sorting pathways destined for autophagy, lysosomes, or recycling pathways. In addition, P. gingivalis releases outer membrane vesicles which enter cells via endocytosis and cause cellular functional impairment.


Assuntos
Bactérias/patogenicidade , Doenças Periodontais/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Transporte Biológico , Genoma Bacteriano , Glicosilação , Humanos , Neuraminidase/metabolismo
10.
J Clin Pediatr Dent ; 37(3): 289-95, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23855174

RESUMO

UNLABELLED: The aim of this study was to characterize the main periodontal bacterial species in Down syndrome (DS) patients with and without periodontitis. METHOD: This cross-sectional study involved 75 DS patients, 45 with and 30 without periodontitis. Informed consent, health and dental questionnaires and periodontitis diagnosis were performed PCR and LAMP assays were performed on subgingival dental plaque sample. RESULTS: Tannerella forsythia was the most frequent bacteria detected in the group with and without periodontitis (95.5 and 63.3%) followed by Treponema denticola (88.8 and 50%) and Porphyromonas gingivalis (53.3 and 25% respectively). There were statistical differences between groups (p < 0.05). Pg fimA type I was the most frequent Porphyromonas gingivalis genotype. Two different sets of primers (Aa-F/Aa-R and ltx3/ltx4) were used to detect Aggregatibacter actinomycetemcomitans and different frequencies were obtained, (68% and 14.6% respectively), they had a weak correlation (Cohen Kappa = 0.16). After sequencing of PCR products, ltx3/ltx4 showed more specificity. JP2 clone of A. actinomycetemcomitans was not detected in any sample. CONCLUSIONS: The composition of oral biofilm is fundamental for the development of periodontal disease independently of immunological alterations associated with DS. The frequency of detection of A. actinomycetemcomitans reported in the literature has a wide range, because the primers and probes applied


Assuntos
Biofilmes/classificação , Placa Dentária/microbiologia , Síndrome de Down/microbiologia , Periodontite/microbiologia , Aggregatibacter actinomycetemcomitans/classificação , Aggregatibacter actinomycetemcomitans/genética , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Toxinas Bacterianas/genética , Bacteroides/isolamento & purificação , Estudos Transversais , Primers do DNA , DNA Bacteriano/análise , Exotoxinas/genética , Feminino , Proteínas de Fímbrias/análise , Genótipo , Humanos , Masculino , Consórcios Microbianos , Perda da Inserção Periodontal/classificação , Perda da Inserção Periodontal/microbiologia , Bolsa Periodontal/classificação , Bolsa Periodontal/microbiologia , Periodontite/classificação , Periodonto/microbiologia , Pili Sexual/genética , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/isolamento & purificação , Perda de Dente/classificação , Treponema denticola/isolamento & purificação , Adulto Jovem
11.
Mol Oral Microbiol ; 28(6): 435-51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23890177

RESUMO

The effects of sugar alcohols such as erythritol, xylitol, and sorbitol on periodontopathic biofilm are poorly understood, though they have often been reported to be non-cariogenic sweeteners. In the present study, we evaluated the efficacy of sugar alcohols for inhibiting periodontopathic biofilm formation using a heterotypic biofilm model composed of an oral inhabitant Streptococcus gordonii and a periodontal pathogen Porphyromonas gingivalis. Confocal microscopic observations showed that the most effective reagent to reduce P. gingivalis accumulation onto an S. gordonii substratum was erythritol, as compared with xylitol and sorbitol. In addition, erythritol moderately suppressed S. gordonii monotypic biofilm formation. To examine the inhibitory effects of erythritol, we analyzed the metabolomic profiles of erythritol-treated P. gingivalis and S. gordonii cells. Metabolome analyses using capillary electrophoresis time-of-flight mass spectrometry revealed that a number of nucleic intermediates and constituents of the extracellular matrix, such as nucleotide sugars, were decreased by erythritol in a dose-dependent manner. Next, comparative analyses of metabolites of erythritol- and sorbitol-treated cells were performed using both organisms to determine the erythritol-specific effects. In P. gingivalis, all detected dipeptides, including Glu-Glu, Ser-Glu, Tyr-Glu, Ala-Ala and Thr-Asp, were significantly decreased by erythritol, whereas they tended to be increased by sorbitol. Meanwhile, sorbitol promoted trehalose 6-phosphate accumulation in S. gordonii cells. These results suggest that erythritol has inhibitory effects on dual species biofilm development via several pathways, including suppression of growth resulting from DNA and RNA depletion, attenuated extracellular matrix production, and alterations of dipeptide acquisition and amino acid metabolism.


Assuntos
Biofilmes/efeitos dos fármacos , Eritritol/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/crescimento & desenvolvimento , Streptococcus gordonii/efeitos dos fármacos , Streptococcus gordonii/crescimento & desenvolvimento , Biofilmes/crescimento & desenvolvimento , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica , Porphyromonas gingivalis/metabolismo , Sorbitol/farmacologia , Streptococcus gordonii/metabolismo , Xilitol/farmacologia
12.
Transplant Proc ; 44(4): 1067-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22564626

RESUMO

Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2(k)) that underwent transplantation of C57BL/6 (B6, H2(b)) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4(+) cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4(+) cells.


Assuntos
Danazol/farmacologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/imunologia , Fatores Imunológicos/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Transferência Adotiva , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Danazol/administração & dosagem , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/imunologia , Histocompatibilidade , Fatores Imunológicos/administração & dosagem , Injeções Intraperitoneais , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Fatores de Tempo
13.
Transplant Proc ; 44(4): 1076-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22564629

RESUMO

In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Coração/imunologia , Música , Linfócitos T Reguladores/imunologia , Estimulação Acústica , Transferência Adotiva , Animais , Proliferação de Células , Citocinas/metabolismo , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/imunologia , Histocompatibilidade , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Transplante de Pele/imunologia , Linfócitos T Reguladores/transplante , Fatores de Tempo , Perfuração da Membrana Timpânica/imunologia , Perfuração da Membrana Timpânica/fisiopatologia
14.
Oral Dis ; 17(4): 370-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21029263

RESUMO

OBJECTIVE: Porphyromonas gingivalis was recently shown to cause intimal hyperplasia in a mouse model by a novel cholesterol-independent mechanism, suggesting to be a pathogen-specific feature of cardiovascular diseases. The aim of this study was to characterize the clinical and histopathological features of aortic aneurysms in cardiovascular disease patients harboring oral P. gingivalis. SUBJECT AND METHODS: Aortic aneurysm specimens were collected from 76 Japanese patients who underwent surgery, of whom dental plaque specimens were also collected from 31 patients. Bacterial DNA was extracted from each specimen to detect P. gingivalis by polymerase chain reaction. Histopathological analyses of the aortic aneurysm specimens, including immunohistochemical staining for embryonic myosin heavy chain isoform (SMemb) and S100 calcium-binding protein A9 (S100A9), were also performed. RESULTS: The number of aneurysms occurring in the distal aorta was significantly higher in subjects positive for P. gingivalis in dental plaque compared with those who were negative. The expressions of S100A9 and SMemb were also significantly greater in the subjects positive for P. gingivalis in dental plaque. On the other hand, there were no significant differences in adipocellular accumulation between the groups. CONCLUSIONS: These results suggest that aortic aneurysms in patients harboring oral P. gingivalis have greater expression of S100A9 and proliferative smooth muscle cells, which was different from the present patients without oral P. gingivalis.


Assuntos
Aneurisma Aórtico/patologia , Doenças Cardiovasculares/patologia , Placa Dentária/microbiologia , Porphyromonas gingivalis/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/microbiologia , Aneurisma da Aorta Abdominal/microbiologia , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Torácica/microbiologia , Aneurisma da Aorta Torácica/patologia , Calgranulina B/análise , Doenças Cardiovasculares/microbiologia , Proliferação de Células , DNA Bacteriano/análise , Dilatação Patológica/patologia , Feminino , Proteínas de Fímbrias/genética , Humanos , Hiperplasia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/patologia , Cadeias Pesadas de Miosina/análise , Pili Sexual/genética , Reação em Cadeia da Polimerase , Porphyromonas gingivalis/genética , Isoformas de Proteínas/análise
15.
J Periodontal Res ; 45(3): 337-44, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19909399

RESUMO

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis infection is thought to be a significant etiological factor in the development of cardiovascular diseases. However, scant definitive evidence has been presented concerning the pathological molecular mechanisms of these disorders. In the present study, we performed a molecular analysis of the developmental mechanisms of aortic intimal hyperplasia induced by P. gingivalis. MATERIAL AND METHODS: The effects of P. gingivalis-induced bacteremia on intimal hyperplasia were evaluated using a mouse model of aortic hyperplasia created by photochemical-induced endothelial cell injury. Alterations of gene expression profiles in injured blood vessels of the mice were extensively analyzed using DNA microarray assays to identify the key molecules involved in P. gingivalis-induced hyperplasia. In addition, human aneurismal specimens from patients with or without P. gingivalis infection were analyzed histochemically. RESULTS: Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model. Concomitantly, S100 calcium-binding protein A9 (S100A9) and embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients. CONCLUSION: We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.


Assuntos
Aorta/microbiologia , Infecções por Bacteroidaceae/patologia , Endotélio Vascular/lesões , Porphyromonas gingivalis/patogenicidade , Túnica Íntima/microbiologia , Animais , Aorta/patologia , Aneurisma Aórtico/microbiologia , Aneurisma Aórtico/patologia , Aterosclerose/microbiologia , Aterosclerose/patologia , Bacteriemia/microbiologia , Biomarcadores/análise , Calgranulina B/análise , Quimiocinas CC/análise , Modelos Animais de Doenças , Endotélio Vascular/microbiologia , Artéria Femoral/lesões , Artéria Femoral/microbiologia , Humanos , Hiperplasia , Proteínas Inflamatórias de Macrófagos/análise , Masculino , Camundongos , Camundongos Endogâmicos ICR , Músculo Liso Vascular/patologia , Cadeias Pesadas de Miosina/análise , Análise de Sequência com Séries de Oligonucleotídeos , Isoformas de Proteínas/análise , Infecções Estreptocócicas/patologia , Streptococcus mutans/patogenicidade , Túnica Íntima/patologia
16.
Oral Microbiol Immunol ; 24(6): 478-84, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19832800

RESUMO

INTRODUCTION: The fimA-encoded fimbriae of the periodontal pathogen Porphyromonas gingivalis display genetic diversity. Type I fimbriated P. gingivalis (Pg-I) has been most widely studied at the molecular level, whereas Pg-II is the most frequent isolate from severe periodontitis. METHODS: To investigate virulence differences between Types I and II fimbriae, we examined strains 33277 (Pg-I) and OMZ314 (Pg-II), reciprocal swap mutants (i.e. expressing the heterologous fimbrial type), and their respective FimA-deficient derivatives. These organisms were tested in a mouse periodontitis model and in interactions with mouse macrophages, a cell type that plays important roles in chronic infections. RESULTS: Strain 33277 induced significantly more periodontal bone loss than OMZ314 and substitution of Type II fimbriae with Type I in OMZ314 resulted in a more virulent strain than the parent organism. However, the presence of Type II fimbriae was associated with increased proinflammatory and invasive activities in macrophages. CONCLUSION: The inverse relationship between proinflammatory potential and ability to cause experimental periodontitis may suggest that an aggressive phenotype could provoke a host response that would compromise the persistence of the pathogen.


Assuntos
Proteínas de Fímbrias/genética , Fímbrias Bacterianas/genética , Periodontite/microbiologia , Porphyromonas gingivalis/genética , Fatores de Virulência/genética , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/microbiologia , Animais , Células Cultivadas , Fímbrias Bacterianas/imunologia , Imunidade Inata/genética , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Periodontite/imunologia , Fagocitose , Porphyromonas gingivalis/imunologia
17.
Kyobu Geka ; 62(11): 990-4, 2009 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-19827554

RESUMO

Aortic root replacement (ARR) after aortic valve replacement (AVR) or ARR is often a major challenge. We performed 12 cases (7 men and 5 women) of ARR as redo operation from July 2002 to June 2009 in our institution. There was no mortality. Among them. ARR was performed in 5 cases, and AVR in 6 cases, at the previous operation. The age at the redo operation was 59.6 +/- 12.7 years. The mean interval between the previous and the redo operations was 6.8 years. In the cases of previous AVR, enlargement of the aortic root or the Valsalva sinus was recognized in 3, artificial valve failure with pannus formation below the valve was in 2, and perivalvular and regurgitation with infection was in 1. In the cases of previous ARR, surgical site infection was seen in 4, among which pseudoaneurysm formation or bleeding from the suture line at the aortic root was the reason for the redo operation in 3 cases. Pseudoaneurysm formation and artificial valve failure may be involved in some type of infection. ARR may be necessary in patients with aortitis.


Assuntos
Aorta/cirurgia , Adulto , Idoso , Aorta/patologia , Valva Aórtica/cirurgia , Prótese Vascular , Procedimentos Cirúrgicos Cardiovasculares/métodos , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Fatores de Tempo
18.
Kyobu Geka ; 62(6): 500-3, 2009 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-19522214

RESUMO

We report a 27-year-old woman who underwent off-pump coronary artery bypass grafting (OPCAB) for angina pectoris with coronary artery aneurysm due to Kawasaki disease. At the age of 3, she was diagnosed as Kawasaki disease with coronary artery aneurysms in the right coronary artery and the left anterior descending artery. She was medically followed-up since then Because an enlarged aneurysm and a stenotic lesion were recognized in the right coronary artery, operation was indicated. In operation, the right coronary artery was ligated at the inflow and the outflow of the aneurysm. OPCAB was also conducted with the right internal thoracic artery anastomosed to the right coronary artery. Postoperative course was uneventful, and she was discharged at the day 5 after operation. Revascularization using arterial grafts, especially the internal thoracic arteries, may be the choice for young patients to expect a good patency rate in the long-term.


Assuntos
Angina Pectoris/etiologia , Angina Pectoris/cirurgia , Ponte de Artéria Coronária sem Circulação Extracorpórea , Ponte de Artéria Coronária , Síndrome de Linfonodos Mucocutâneos/complicações , Adulto , Anastomose Cirúrgica , Aneurisma Coronário/etiologia , Aneurisma Coronário/cirurgia , Vasos Coronários/cirurgia , Feminino , Humanos , Artéria Torácica Interna/cirurgia
19.
Oral Microbiol Immunol ; 24(3): 260-3, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19416458

RESUMO

INTRODUCTION: Porphyromonas gingivalis is a periodontal pathogen whose long fimbriae (FimA) are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes. FimA variations were previously shown to be related to the onset and development of adult periodontitis in a general population, while FimA were recently found to be critical mediators of initial biofilm formation. However, it is unclear if FimA variations have effects on biofilm features. Here, we compare the characteristic structures of homotypic biofilms developed by P. gingivalis strains with different FimA types. METHODS: Biofilms were formed on saliva-coated glass bottom wells in phosphate-buffered saline and their structures were analysed using confocal laser scanning microscopy. Furthermore, the biovolumes of the biofilms were quantified with a three-dimensional fluorophotometric method. RESULTS: Biofilm structures formed by the six representative FimA-type strains apparently differed. Type I and Ib P. gingivalis formed biofilms with a dense basal monolayer and dispersed microcolonies, whereas those formed by types II, III and IV strains had markedly luxuriant biofilms filled with widely clumped and tall colonies, and their biovolumes were significantly greater than those of types I and Ib. These characteristic features were confirmed to be closely related to FimA type in assays that utilized fimA-substituted mutants from type I to II and those from type II to I. CONCLUSION: Our results suggest that FimA variations have effects on the structures of biofilms formed by P. gingivalis, which may be an important factor in the pathogenesis of periodontitis.


Assuntos
Biofilmes/classificação , Fímbrias Bacterianas/classificação , Porphyromonas gingivalis/fisiologia , Técnicas Bacteriológicas , Biofilmes/crescimento & desenvolvimento , Proteínas de Fímbrias/genética , Fímbrias Bacterianas/genética , Genótipo , Humanos , Imageamento Tridimensional/métodos , Microscopia Confocal/métodos , Mutação/genética , Pili Sexual/genética , Porphyromonas gingivalis/ultraestrutura , Saliva
20.
Kyobu Geka ; 62(1): 19-23, 2009 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-19195181

RESUMO

We report the clinical results of 799 cases of isolated coronary artery bypass grafting (CABG) performed during the recent 5 years. We performed off-pump CABG (OPCAB) as standard operation, in which arterial grafts were mainly used. The mean number of distal anastomoses was 3.6 +/- 1.4 per patient Four hundred and fifty-five cases (57.0%) were done only with arterial grafts. Bilateral internal thoracic arteries were used in 326 cases. The mean number of saphenous vein grafts was 1.6 +/- 0.8 per patient. Continuous hemodiafiltraion (CHDF) was performed in 22 cases (2.8%) postoperatively. Among the OPCAB cases, 10 cases (1.3%) were converted to on-pump CABG. There were 7 cases (0.9%) of hospital death. The mean length of postoperative hospital stay was 10.2 +/- 5.3 days. The ratio of the patients with left main trunk disease and that of the patients who required postoperative CHDF increased year by year. The mean length of postoperative hospital stay decreased every year, and the reduced length was 2.7 days in the 5 years (8.7+/- 3.6 days in 2007). It is expected that patients who have severe calcified lesions or who are on hemodialysis may increase in the near future. In such cases, CABG rather than percutaneous catheter intervention may be suitable for revascularization. Therefore, not only appropriate choice of treatment strategies, but also accurate surgical techniques may become more importance.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Idoso , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Resultado do Tratamento
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