RESUMO
INTRODUCTION: Studies on metabolomics and CKD have primarily addressed CKD incidence defined as a decline on eGFR or appearance of albuminuria in the general population, with very few evaluating hard outcomes. In the present study, we investigated the association between metabolites and mortality and ESRD in a CKD cohort. SETTING AND METHODS: Data on 454 participants of the Progredir Cohort Study, Sao Paulo, Brazil were used. Metabolomics was performed by GC-MS (Agilent MassHunter) and metabolites were identified using Agilent Fiehn GC/MS and NIST libraries. After excluding metabolites present in <50% of participants, 293 metabolites were analyzed. An FDR q value <0.05 criteria was applied in Cox models on the composite outcome (mortality or incident renal replacement therapy) adjusted for batch effect, resulting in 34 metabolites associated with the outcome. Multivariable-adjusted Cox models were then built for the composite outcome, death, and ESRD incident events. Competing risk analysis was also performed for ESRD. RESULTS: Mean age was 68±12y, mean eGFR-CKDEPI was 38.4±14.6 ml/min/1.73m2 and 57% were diabetic. After adjustments (GC-MS batch, sex, age, DM and eGFR), 18 metabolites remained significantly associated with the composite outcome. Nine metabolites were independently associated with death: D-malic acid (HR 1.84, 95%CI 1.32-2.56, p = 0.0003), acetohydroxamic acid (HR 1.90, 95%CI 1.30-2.78, p = 0.0008), butanoic acid (HR 1.59, 95%CI 1.17-2.15, p = 0.003), and docosahexaenoic acid (HR 0.58, 95%CI 0.39-0.88, p = 0.009), among the top associations. Lactose (SHR 1.49, 95%CI 1.04-2.12, p = 0.03), 2-O-glycerol-α-D-galactopyranoside (SHR 1.76, 95%CI 1.06-2.92, p = 0.03), and tyrosine (SHR 0.52, 95%CI 0.31-0.88, p = 0.02) were associated to ESRD risk, while D-threitol, mannitol and myo-inositol presented strong borderline associations. CONCLUSION: Our results identify specific metabolites related to hard outcomes in a CKD population. These findings point to the need of further exploration of these metabolites as biomarkers in CKD and the understanding of the underlying biological mechanisms related to the observed associations.
Assuntos
Biomarcadores/análise , Falência Renal Crônica/patologia , Metabolômica , Insuficiência Renal Crônica/patologia , Idoso , Estudos de Coortes , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Taxa de Filtração Glomerular , Humanos , Ácidos Hidroxâmicos/análise , Falência Renal Crônica/metabolismo , Falência Renal Crônica/mortalidade , Malatos/análise , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Álcoois Açúcares/análise , Taxa de SobrevidaRESUMO
The aim of this study was to assess the prevalence of toothache, associated factors and impact of this condition on the Child Oral Health Related Quality of Life (COHRQoL) in preschoolers. The study was carried out in Santa Maria, Brazil, during the National Children's Vaccination Day, and 534 children aged 0 to 5 years were included. Clinical variables included dental caries and dental trauma. A questionnaire was responded by the parents and provided information about several socioeconomic indicators, dental service use and toothache. Toothache was collected by the question: "Has your child ever had a toothache - Yes or no?". Data on COHRQoL were assessed using the Brazilian version of the Early Childhood Oral Health Impact Scale (ECOHIS). Multivariable Logistic regression models were performed to assess the association between the predictor variables and outcomes. The prevalence of toothache was 10.11% (95% CI: 7.55% - 12.68%). Older children had a higher chance of presenting dental pain (OR 2.72; 95% CI: 1.01 - 7.56), as well as children with caries experience (OR 3.43; 95% CI: 1.81 - 6.52). Moreover, children who had not visited the dental service in the last 6 months were less likely to present toothache (OR 0.51; 95% CI: 0.28 - 0.95). The presence of dental pain negatively affects the COHRQoL; those with toothache presented a higher chance of having higher impact on the total scores of ECOHIS (OR 4.18; 95% CI: 1.76 - 9.95) than those without toothache. Similar observation was found for the child section of the questionnaire (OR 5.54; 95% CI: 2.15 - 14.24). Toothache negatively affects COHRQoL and is associated with caries experience, age and use of dental service.
O objetivo deste estudo foi avaliar a prevalência de dor dentaria, os fatores associados e seu impacto na qualidade de vida relacionada a saúde bucal de crianças pré-escolares. Esse estudo foi realizado em Santa Maria, Brasil, durante o dia nacional de vacinação infantil, e 534 crianças de 0 a 5 anos foram incluídas. As variáveis clinicas incluídas foram carie dental e traumatismo dentário. Um questionário foi respondido pelos pais, fornecendo informações sobre as condições socioeconômicas, uso de serviços odontológicos e dor dentaria. Dor de dente foi coletada através da pergunta: "Seu filho já teve dor de dente - Sim ou Não?". Os dados sobre qualidade de vida relacionada a saúde bucal foram obtidos através da versão brasileira do questionário "Early Childhood Oral Health Impact Scale" (ECOHIS). Modelos multivariáveis de regressão logística foram utilizados para avaliar a associação entre as variáveis preditoras e os desfechos. A prevalência de dor dentaria foi 10,11% (95% IC: 7,55% - 12,68%). Crianças mais velhas apresentaram uma maior chance de ter tido dor dentaria (OR 2,72; 95% IC: 1,01 - 7,56), assim como crianças com experiência de carie (OR 3,43; 95% IC: 1,81 - 6,52). Além disso, as crianças que não tinham visitado o dentista nos últimos 6 meses foram menos propensas a apresentar dor dentária (OR 0,51; 95% IC: 0,28 - 0,95). A presença de dor dentária afeta negativamente a qualidade de vida relacionada a saúde bucal das crianças; aquelas que tiveram dor de dente apresentaram uma maior chance de ter piores impactos nos escores totais do ECOHIS (OR 4,18; 95% IC: 1,76 - 9,95) quando comparadas àquelas que não tiveram dor dentária. O mesmo se pode observar para a seção do questionário correspondente aos impactos na criança (OR 5,54; 95% IC: 2,15 - 14,24. Dor dentaria afeta negativamente a qualidade de vida relacionada a saúde bucal e esta associada com experiência de carie, idade e uso de serviços odontológicos.
Assuntos
Anti-Inflamatórios não Esteroides/análise , Benzenoacetamidas , Ácidos Hidroxâmicos/análise , Anti-Inflamatórios não Esteroides/síntese química , Fenômenos Químicos , Química , Cromatografia Líquida de Alta Pressão , Ácidos Hidroxâmicos/síntese química , Espectroscopia de Ressonância MagnéticaRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to determine the role of host factors and bacterial virulence genes in the development of pyelonephritis caused by Escherichia coli in renal transplant (Tx) recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 328 E. coli isolates from cases of cystitis (Cys; n=239) or pyelonephritis (PN; n=89), with 169 from renal Tx recipients, were subjected to molecular analyses to identify P-fimbria subunits (PapC, PapG II, and PapGIII), G- and M-fimbriae, and aerobactin. The presence of antibiotic resistance was also determined. Parameters such as gender, age, immunosuppression regimens, causes of ESRD, kidney donor, intraoperative anastomosis, use of double J stent, trimethoprim/sulfamethoxazole (TMP/SMZ) prophylaxis, and time after Tx were evaluated. RESULTS: A multivariate analysis showed a significant association between PN and renal Tx. In renal Tx recipients, the risk of occurrence of PN was significantly higher among males and for those no longer receiving TMP/SMZ prophylaxis. E. coli strains isolated from PN presented a lower prevalence of papGIII and lower rates of resistance to pipemidic acid. Although papGII was more prevalent in PN than in Cys, it was not independently associated with PN. CONCLUSIONS: These findings suggested that renal Tx increases the risk for PN, and the male sex represented a host factor independently associated with risk, whereas the prophylaxis with TMP/SMZ was protective. The lack of papGIII and low resistance to first-generation quinolones were bacterial-independent risk factors for PN in Tx.
Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Transplante de Rim/efeitos adversos , Pielonefrite/microbiologia , Fatores de Virulência/genética , Adesinas de Escherichia coli/genética , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Brasil , Distribuição de Qui-Quadrado , Combinação de Medicamentos , Farmacorresistência Bacteriana , Escherichia coli/patogenicidade , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/genética , Feminino , Proteínas de Fímbrias/genética , Humanos , Ácidos Hidroxâmicos/análise , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Porinas/genética , Estudos Prospectivos , Pielonefrite/prevenção & controle , Medição de Risco , Fatores de Risco , Fatores Sexuais , Sulfadoxina/uso terapêutico , Trimetoprima/uso terapêutico , Virulência/genética , Adulto JovemRESUMO
The aim of the study was to determine the occurrence of virulence genes expressing fimbriae, production of hemolysin, colicin and aerobactin among a hundred Escherichia coli isolates obtained from in-and outpatients of a tertiary-care teaching hospital, between July and August 2000, showing clinical and laboratory signs of urinary tract infection (UTI). The presence of genes (pap, afa, sfa) for fimbriae expression was assayed using specific primers in a polymerase chain reaction. Among the isolates studied, the prevalence of the virulence factors was 96.0%, 76.0%, 24.0%, for hemolysin, aerobactin and colicin, respectively; the prevalence of genes coding for fimbrial adhesive systems was 32.0%, 19.0% and 11.0% for pap, sfa and afa respectively. The strains isolated from the outpatients displayed a greater number of virulence factors compared to those from hospitalized subjects, emphasizing the difference between these two kinds of patients.
Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Infecções Urinárias/microbiologia , Fatores de Virulência/biossíntese , Adolescente , Adulto , Criança , Pré-Escolar , Colicinas/biossíntese , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Escherichia coli/genética , Feminino , Fímbrias Bacterianas/genética , Proteínas Hemolisinas/biossíntese , Humanos , Ácidos Hidroxâmicos/análise , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Óperon/genética , Reação em Cadeia da Polimerase , Virulência , Fatores de Virulência/análise , Fatores de Virulência/genéticaRESUMO
The aim of the study was to determine the occurrence of virulence genes expressing fimbriae, production of hemolysin, colicin and aerobactin among a hundred Escherichia coli isolates obtained from in-and outpatients of a tertiary-care teaching hospital, between July and August 2000, showing clinical and laboratory signs of urinary tract infection (UTI). The presence of genes (pap, afa, sfa) for fimbriae expression was assayed using specific primers in a polymerase chain reaction. Among the isolates studied, the prevalence of the virulence factors was 96.0 percent, 76.0 percent, 24.0 percent, for hemolysin, aerobactin and colicin, respectively; the prevalence of genes coding for fimbrial adhesive systems was 32.0 percent, 19.0 percent and 11.0 percent for pap, sfa and afa respectively. The strains isolated from the outpatients displayed a greater number of virulence factors compared to those from hospitalized subjects, emphasizing the difference between these two kinds of patients.
O objetivo do trabalho foi determinar a ocorrência de fatores de virulência, tais como, a expressão de fímbrias, produção de hemolisina, colicina e aerobactina em 100 cepas de Escherichia coli isoladas de pacientes ambulatoriais e hospitalizados de um hospital universitário de nível de atendimento terciário, entre os meses de julho e agosto de 2000, que apresentavam sinais clínicos e laboratoriais de infecção do trato urinário (ITU). Foram pesquisados os genes pap, afa e sfa responsáveis pela expressão de fímbrias através da técnica de PCR. A freqüência dos fatores de virulência entre as cepas estudadas foi de 96,0 por cento, 76,0 por cento e 24,0 por cento para hemolisina, aerobactina e colicina respectivamente, e a prevalência dos genes para os sistemas de adesinas fimbriais foi de 32,0 por cento, 19,0 por cento e 11,0 por cento para os genes pap, sfa e afa respectivamente. As cepas isoladas dos pacientes ambulatoriais exibiram um número maior de fatores de virulência quando comparadas com aquelas provenientes de indivíduos hospitalizados.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Ácidos Hidroxâmicos/análise , Infecções Urinárias/microbiologia , Fatores de Virulência/biossíntese , Colicinas/biossíntese , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Escherichia coli/genética , Fímbrias Bacterianas/genética , Proteínas Hemolisinas/biossíntese , Óperon/genética , Reação em Cadeia da Polimerase , Virulência , Fatores de Virulência/análise , Fatores de Virulência/genéticaRESUMO
AIMS: The antagonistic activity of the Escherichia coli strain H22 against enteric bacteria was studied both in vitro and in vivo. METHODS AND RESULTS: In vitro, bacterial strains belonging to seven of nine genera of the family Enterobacteriaceae (Enterobacter, Escherichia, Klebsiella, Morganella, Salmonella, Shigella and Yersinia) were inhibited by the strain H22. Six days after simultaneous oral inoculation in germ-free mice, E. coli strain H22 reduced the faecal population of Shigella flexneri 4 to undetectable levels (P < 0.05). In ex vivo assay, inhibitory zones against Sh. flexneri 4 were observed around faecal samples from mice inoculated with E. coli strain H22. The in vitro inhibition of Sh. flexneri 4 was shown to be mediated by microcin C7. In addition to microcin C7, strain H22 was shown to produce aerobactin, new variants of colicins E1 and Ib, and bacteriophage particles with morphology similar to the phages of the family Myoviridae. CONCLUSIONS: Altogether, the properties of E. coli H22, observed both under in vitro and in vivo conditions, suggest its potential use as a probiotic strain for livestock and humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The strain H22 was shown to produce several antimicrobial compounds with inhibitory capabilities against pathogenic or potentially pathogenic enterobacteria.
Assuntos
Enterobacteriaceae/fisiologia , Escherichia coli/fisiologia , Administração Oral , Animais , Antibacterianos/análise , Bacteriocinas/análise , Bacteriófagos/metabolismo , Colicinas/análise , Enterobacter/fisiologia , Escherichia/fisiologia , Fezes/microbiologia , Feminino , Ácidos Hidroxâmicos/análise , Klebsiella/fisiologia , Masculino , Camundongos , Microscopia Eletrônica/métodos , Morganella/fisiologia , Myoviridae , Plasmídeos/ultraestrutura , Salmonella/fisiologia , Shigella/fisiologia , Shigella flexneri/fisiologia , Sideróforos/análise , Yersinia/fisiologiaRESUMO
Mechanisms of fragmentation of hydroxamic siderophores are proposed comparing deuterated and nondeuterated samples. Standard siderophores (e.g. deferoxamine and coprogen) were directly injected into both ion trap and linear quadrupole mass spectrometers with electrospray ionization (ESI). Four and two fragmentation steps were carried out for deferoxamine and coprogen (analyzed by positive and negative ESI, respectively). Deferoxamine cleavages occurred in both peptide and hydroxamic bonds while the coprogen fragmentation pattern is more elaborate, since it contains Fe(III) in its structure.
Assuntos
Cromatografia Líquida/métodos , Desferroxamina/análise , Ácidos Hidroxâmicos/análise , Sideróforos/análise , Sideróforos/química , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
An extracellular low-molecular mass component (LMMC) with catalytic properties was isolated from liquid cultures containing wheat bran of ascomycete thermophilic Thermoascus aurantiacus. The partially purified LMMC showed very high activity with typical phenoloxidase substrates in the absence of hydrogen peroxide at acidic pH (2.8). However, in this pH range, the phenoloxidase (PO) activity was quickly lost. The LMMC showed a high optimum temperature (80 degrees C) and an elevated thermostability. The molecular mass of the component estimated by gel filtration chromatography was 530 Da. IR and 1H- and 13C-NMR spectra indicated the presence of hydroxamic acid moiety. Qualitative determination of metal ions by several techniques revealed the presence of mainly iron associated with this structure. Iron may be the responsible for the ability for catalyze oxidation reactions, such as o-dianisidine oxidation, by the LMMC. These results suggested the existence of a hydroxamate-type metal-binding component, most likely hydroxamate siderophore. In addition, the chrome azurol S (CAS) universal assay for noncomplexed siderophores detection revealed the production of these compounds by T.aurantiacus in solid and liquid media.
Assuntos
Ascomicetos/enzimologia , Monofenol Mono-Oxigenase/metabolismo , Ascomicetos/química , Catálise , Cromatografia em Gel , Dianisidina/metabolismo , Fibras na Dieta/metabolismo , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Ácidos Hidroxâmicos/análise , Hidroxibenzoatos , Ferro/análise , Ferro/metabolismo , Cinética , Peso Molecular , Oxidantes/química , Oxidantes/isolamento & purificação , Oxidantes/metabolismo , Sideróforos/química , Sideróforos/isolamento & purificação , Sideróforos/metabolismo , Análise Espectral , TemperaturaRESUMO
Thirty one Escherichia coli strains isolated from pigs with urinary tract infections were investigated for presence of virulence factors and plasmid DNA profile. The most frequent virulence factors presented by these strains were mannose-resistant fimbriae, including P. fimbriae (54.8%) and aerobactin production (45.2%). The pap) operon, detected by PCR, was found in 54.8% of the strains, which is similar to its frequency in human strains. Other characteristics such as the presence of mannose-sensitive hemagglutinin (16.1%), indicative of type 1 pili, and production of hemolysin (25.8%), colicin (38.7%) and toxins (22.6% for LT and for VT) were less frequent. No strains were positive for STa production. Plasmid profiles were variable among isolates from either the same or different farms.
Assuntos
Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli , Escherichia coli/patogenicidade , Doenças dos Suínos/microbiologia , Doenças Urológicas/veterinária , Animais , Toxinas Bacterianas/urina , Brasil , Colicinas/urina , Primers do DNA/química , DNA Bacteriano/química , Enterotoxinas/urina , Ensaio de Imunoadsorção Enzimática/veterinária , Escherichia coli/classificação , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Fímbrias Bacterianas/imunologia , Testes de Hemaglutinação/veterinária , Proteínas Hemolisinas/urina , Ácidos Hidroxâmicos/análise , Óperon , Plasmídeos , Reação em Cadeia da Polimerase/veterinária , Sorotipagem/veterinária , Toxina Shiga I , Suínos , Doenças Urológicas/microbiologia , VirulênciaRESUMO
30 strains isolated from clinical cases and a laboratory induced R-mutant or S typhi were studied. The synthesis of Colicin V, Siderophores, hydroxamate and phenolate (Aerobactin and Enterochelin) were investigated using biological assays. All strains were positive for Enterochelin but only strains 6586 and 4448 were positive for Aerobactin. An 80 kD receptor for enterochelin was found in the outer membrane of strains. Only strains 4448, 635 and 4693 produced Colicin V. Plasmid related antibiotic resistance was demonstrated in 7 strains and was considered "cryptic" in 3 others. The LD50 for mice ranged from 2.7 x 10(4) to 1 x 10(9) bacteria per ml. The presence of pathogenic factors was not related to the LD50.