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1.
Artículo en Inglés | MEDLINE | ID: mdl-29109162

RESUMEN

Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (Cmax), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (P = 0.005); time to Cmax (Tmax) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (P = 0.003); half-life (t1/2), 9.1 ± 3.6 versus 8.9 ± 2.2 h (P = 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC p ), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter (P = 0.004). The tissue area under the concentration-time curve (AUC t ) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter (P = 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (P = 0.351). Despite lower plasma Cmax and delayed Tmax values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.


Asunto(s)
Antibacterianos/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Oxazolidinonas/uso terapéutico , Tetrazoles/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/metabolismo , Administración Oral , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Estudios de Casos y Controles , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/microbiología , Líquido Extracelular/microbiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Microdiálisis/métodos , Persona de Mediana Edad
2.
Arch Pediatr ; 24(9): 811-816, 2017 Sep.
Artículo en Francés | MEDLINE | ID: mdl-28801118

RESUMEN

The objective of this study was to evaluate the value of direct examination and culture of gastric fluid in the treatment of early neonatal bacterial infections (INBP) in pre-term infants. MATERIALS AND METHODS: Observational study conducted over 6 months in a Type III center. All hospitalized premature babies who had routine gastric fluid sampling at birth during the period of the study were included. They were classified into two groups: premature infants with probable or suspected infection and treated as such (Group 1) and premature infants with no infection or only having colonization (Group 2). RESULTS AND DISCUSSION: In total, 255 pre-term infants were included in the study. Group 1 consisted of 127 newborns and group 2 consisted of 128 newborns. The direct gastric fluid examination was positive in 51 newborns in Group 1 and in 46 newborns in group 2. The culture was positive in 25 newborns in group 1 and eight newborns in group 2. Direct examination of gastric fluid of the 255 children studied had low sensitivity (40.1%) and low specificity (64%) of INBP, with 52.6% positive predictive value (PPV) and 51.8% negative predictive value (NPV). The gastric fluid culture was specific (93.7%) of the INBP, sensitivity was low (19.6%), with PPV at 75.7% and NPV at 54%. CONCLUSION: These results undermine the relevance of the direct examination of gastric fluid in the delicate diagnosis of INBP. This direct examination has a low PPV and NPV. It is advisable not to start or stop antibiotic therapy solely on this argument; however, it can guide the choice of antibiotic therapy and remains useful for this reason. The culture of gastric fluid has very good specificity (93.7%).


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Líquido Extracelular/microbiología , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/microbiología , Bacterias/aislamiento & purificación , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino
3.
Phys Rev E ; 95(1-1): 012408, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28208370

RESUMEN

Collective behavior of bacterial colonies plays critical roles in adaptability, survivability, biofilm expansion and infection. We employ an individual-based model of an interstitial biofilm to study emergent pattern formation based on the assumptions that rod-shaped bacteria furrow through a viscous environment and excrete extracellular polymeric substances which bias their rate of motion. Because the bacteria furrow through their environment, the substratum stiffness is a key control parameter behind the formation of distinct morphological patterns. By systematically varying this property (which we quantify with a stiffness coefficient γ), we show that subtle changes in the substratum stiffness can give rise to a stable state characterized by a high degree of local order and long-range pattern formation. The ordered state exhibits characteristics typically associated with bacterial fitness advantages, even though it is induced by changes in environmental conditions rather than changes in biological parameters. Our findings are applicable to a broad range of biofilms and provide insights into the relationship between bacterial movement and their environment, and basic mechanisms behind self-organization of biophysical systems.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Biopelículas/crecimiento & desarrollo , Líquido Extracelular/microbiología , Modelos Biológicos , Animales , Simulación por Computador , Elasticidad , Fimbrias Bacterianas/fisiología , Movimiento/fisiología , Viscosidad
4.
Antimicrob Agents Chemother ; 58(12): 7520-6, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25288076

RESUMEN

Staphylococcus aureus, including methicillin-susceptible (MSSA) and -resistant (MRSA) strains, is an important pathogen of bacterial pneumonia. As antibiotic concentrations at the site of infection are responsible for killing, we investigated the activity of human-simulated epithelial lining fluid (ELF) exposures of three antibiotics (ceftaroline, ceftriaxone, and vancomycin) commonly used for treatment of S. aureus pneumonia. An in vitro pharmacodynamic model was used to simulate ELF exposures of vancomycin (1 g every 12 h [q12h]), ceftaroline (600 mg q12h and q8h), and ceftriaxone (2 g q24h and q12h). Four S. aureus isolates (2 MSSA and 2 MRSA) were evaluated over 72 h with a starting inoculum of ∼ 10(6) CFU/ml. Time-kill curves were constructed, and microbiological response (change in log10 CFU/ml from 0 h and the area under the bacterial killing and regrowth curve [AUBC]) was assessed in duplicate. The change in 72-h log10 CFU/ml was largest for ceftaroline q8h (reductions of >3 log10 CFU/ml against all strains). This regimen also achieved the lowest AUBC against all organisms (P < 0.05). Vancomycin produced reliable bacterial reductions of 0.9 to 3.3 log10 CFU/ml, while the activity of ceftaroline q12h was more variable (reductions of 0.2 to 2.3 log10 CFU/ml against 3 of 4 strains). Both regimens of ceftriaxone were poorly active against MSSA tested (0.1 reduction to a 1.8-log10 CFU/ml increase). Against these S. aureus isolates, ELF exposures of ceftaroline 600 mg q8h exhibited improved antibacterial activity compared with ceftaroline 600 mg q12h and vancomycin, and therefore, this q8h regimen deserves further evaluation for the treatment of bacterial pneumonia. These data also suggest that ceftriaxone should be avoided for S. aureus pneumonia.


Asunto(s)
Antibacterianos/farmacocinética , Ceftriaxona/farmacocinética , Cefalosporinas/farmacocinética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Modelos Estadísticos , Vancomicina/farmacocinética , Antibacterianos/farmacología , Área Bajo la Curva , Materiales Biomiméticos , Ceftriaxona/farmacología , Cefalosporinas/farmacología , Recuento de Colonia Microbiana , Líquido Extracelular/efectos de los fármacos , Líquido Extracelular/microbiología , Humanos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/microbiología , Vancomicina/farmacología , Ceftarolina
5.
Adv Immunol ; 121: 191-211, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24388216

RESUMEN

The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.


Asunto(s)
Antígenos CD/fisiología , Antígenos de Superficie/fisiología , Interacciones Huésped-Patógeno/inmunología , Receptores de Superficie Celular/fisiología , Transducción de Señal/inmunología , Animales , Líquido Extracelular/inmunología , Líquido Extracelular/microbiología , Líquido Extracelular/virología , Interacciones Huésped-Patógeno/genética , Humanos , Inmunoglobulinas/fisiología , Inflamación/genética , Inflamación/microbiología , Inflamación/virología , Gripe Humana/genética , Gripe Humana/inmunología , Gripe Humana/virología , Lectinas Tipo C/fisiología , Ratones , Receptores de Orexina , Infecciones por Orthomyxoviridae/genética , Infecciones por Orthomyxoviridae/inmunología , Receptores de Superficie Celular/deficiencia , Receptores KIR/administración & dosificación , Receptores KIR/genética , Transducción de Señal/genética
6.
J Invertebr Pathol ; 109(1): 83-90, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22019387

RESUMEN

In the present study, lysozyme-like activity against Micrococcus luteus was detected in the coelomic fluid, the extract from coelomocytes, intestine and in the homogenates from cocoons of Dendrobaena veneta. Four hours after immunization with Escherichia coli, the lysozyme activity in the coelomic fluid increased about three times and in the extract of coelomocytes - four times, in comparison to the control. In three cases: of the coelomic fluid, the homogenates from cocoons and the extract from coelomocytes, the antibody against HEWL (hen egg white lysozyme) recognized only one protein with a molecular mass of about 14.4 kDa. In the coelomic fluid, apart from the protein with molecular mass of 14.4 kDa the antibody directed against human lysozyme recognized an additional protein of 22 kDa. Using the bioautography technique after electrophoretic resolution of native proteins in acidic polyacrylamide gels, two lytic zones of M. luteus were observed in the case of the coelomic fluid and three after the analysis of the extract of coelomocytes and the egg homogenates. The results indicated the existence of several forms of lysozyme with a different electric charge in the analyzed D. veneta samples. The highest lysozyme activity in the intestine of D. veneta was observed in the midgut. The antibody directed against human lysozyme indicated a strong positive signal in epidermal and midgut cells of earthworm.


Asunto(s)
Antibacterianos/metabolismo , Antiinfecciosos/metabolismo , Enterocitos/enzimología , Muramidasa/metabolismo , Oligoquetos/enzimología , Animales , Antiinfecciosos/análisis , Electroforesis en Gel Bidimensional , Enterocitos/citología , Escherichia coli/inmunología , Líquido Extracelular/enzimología , Líquido Extracelular/microbiología , Intestinos/citología , Intestinos/enzimología , Muramidasa/análisis , Oligoquetos/inmunología , Oligoquetos/microbiología , Óvulo/enzimología , Óvulo/inmunología , Óvulo/microbiología
7.
J Leukoc Biol ; 89(2): 205-19, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20689098

RESUMEN

Ubiquitin is a post-translational protein modifier and plays essential roles in all aspects of biology. Although the discovery of ubiquitin introduced this highly conserved protein as a molecule with extracellular actions, the identification of ubiquitin as the ATP-dependent proteolysis factor 1 has focused subsequent research on its important intracellular functions. Little attention has since been paid to its role outside of the cell. During recent years, multiple observations suggest that extracellular ubiquitin can modulate immune responses and that exogenous ubiquitin has therapeutic potential to attenuate exuberant inflammation and organ injury. These observations have not been integrated into a comprehensive assessment of its possible role as an endogenous immune modulator. This review recapitulates the current knowledge about extracellular ubiquitin and discusses an emerging facet of its role in biology during infectious and noninfectious inflammation. The synopsis of these data along with the recent identification of ubiquitin as a CXCR4 agonist suggest that extracellular ubiquitin may have pleiotropic roles in the immune system and functions as an endogenous opponent of DAMPs. Functions of extracellular ubiquitin could constitute an evolutionary conserved control mechanism aimed to balance the immune response and prevent exuberant inflammation. Further characterization of its mechanism of action and cellular signaling pathways is expected to provide novel insights into the regulation of the innate immune response and opportunities for therapeutic interventions.


Asunto(s)
Líquido Extracelular/inmunología , Líquido Extracelular/microbiología , Inmunomodulación/inmunología , Receptores de Reconocimiento de Patrones/fisiología , Ubiquitina/fisiología , Animales , Líquido Extracelular/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Inflamación/metabolismo , Inflamación/patología , Inflamación/prevención & control , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/fisiología , Ubiquitina/agonistas
8.
J Immunol ; 184(11): 6386-95, 2010 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-20421641

RESUMEN

We previously demonstrated that extracellular bacterial DNA activates neutrophils through a CpG- and TLR9-independent mechanism. Biofilms are microbial communities enclosed in a polymeric matrix that play a critical role in the pathogenesis of many infectious diseases. Because extracellular DNA is a key component of biofilms of different bacterial species, the aim of this study was to determine whether it plays a role in the ability of biofilms to induce human neutrophil activation. We found that degradation of matrix extracellular DNA with DNase I markedly reduced the capacity of Pseudomonas aeruginosa biofilms to induce the release of the neutrophil proinflammatory cytokines IL-8 and IL-1beta (>75%); reduced the upregulation of neutrophil activation markers CD18, CD11b, and CD66b (p < 0.001); reduced the number of bacteria phagocytosed per neutrophil contacting the biofilm; and reduced the production of neutrophil extracellular traps. Consistent with these findings, we found that biofilms formed by the lasI rhlI P. aeruginosa mutant strain, exhibiting a very low content of matrix extracellular DNA, displayed a lower capacity to stimulate the release of proinflammatory cytokines by neutrophils, which was not decreased further by DNase I treatment. Together, our findings support that matrix extracellular DNA is a major proinflammatory component of P. aeruginosa biofilms.


Asunto(s)
Biopelículas/crecimiento & desarrollo , ADN Bacteriano/inmunología , Activación Neutrófila/inmunología , Neutrófilos/inmunología , Pseudomonas aeruginosa/fisiología , Citocinas/biosíntesis , Líquido Extracelular/química , Líquido Extracelular/microbiología , Humanos , Microscopía Confocal , Neutrófilos/metabolismo
9.
J Immunol ; 181(4): 2705-12, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18684961

RESUMEN

Extracellular nucleic acids play important roles in human immunity and hemostasis by inducing IFN production, entrapping pathogens in neutrophil extracellular traps, and providing procoagulant cofactor templates for induced contact activation during mammalian blood clotting. In this study, we investigated the functions of extracellular RNA and DNA in innate immunity and hemolymph coagulation in insects using the greater wax moth Galleria mellonella a reliable model host for many insect and human pathogens. We determined that coinjection of purified Galleria-derived nucleic acids with heat-killed bacteria synergistically increases systemic expression of antimicrobial peptides and leads to the depletion of immune-competent hemocytes indicating cellular immune stimulation. These activities were abolished when nucleic acids had been degraded by nucleic acid hydrolyzing enzymes prior to injection. Furthermore, we found that nucleic acids induce insect hemolymph coagulation in a similar way as LPS. Proteomic analyses revealed specific RNA-binding proteins in the hemolymph, including apolipoproteins, as potential mediators of the immune response and hemolymph clotting. Microscopic ex vivo analyses of Galleria hemolymph clotting reactions revealed that oenocytoids (5-10% of total hemocytes) represent a source of endogenously derived extracellular nucleic acids. Finally, using the entomopathogenic bacterium Photorhabdus luminescens as an infective agent and Galleria caterpillars as hosts, we demonstrated that injection of purified nucleic acids along with P. luminescens significantly prolongs survival of infected larvae. Our results lend some credit to our hypothesis that host-derived nucleic acids have independently been co-opted in innate immunity of both mammals and insects, but exert comparable roles in entrapping pathogens and enhancing innate immune responses.


Asunto(s)
ADN/administración & dosificación , Hemolinfa/inmunología , Inmunidad Celular , Inmunidad Innata , Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/inmunología , Photorhabdus/inmunología , ARN/administración & dosificación , Animales , Apolipoproteínas/fisiología , Líquido Extracelular/inmunología , Líquido Extracelular/microbiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/prevención & control , Hemolinfa/microbiología , Hemostasis/inmunología , Humanos , Inmunidad Celular/genética , Inmunidad Innata/genética , Larva/genética , Larva/crecimiento & desarrollo , Larva/inmunología , Larva/microbiología , Mariposas Nocturnas/microbiología , Photorhabdus/genética , Photorhabdus/patogenicidad , Proteoma/inmunología , Proteínas de Unión al ARN/fisiología
10.
J Proteome Res ; 6(7): 2874-83, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17539673

RESUMEN

The pathophysiology of vaginal conditions is still ill-defined at a molecular level. Because the proteome of the human cervical-vaginal fluid (CVF) has not been reported to date, we undertook the identification of proteins present in the cell-free fraction of these fluids. Proteins were separated bidimensionally (2-D) by isoelectrofocusing (pH 3-11) followed by SDS-polyacrylamide electrophoresis. The proteins of 147 spots were identified by matrix-assisted laser desorption/ ionization-time-of-flight-mass spectrometry (MALDI-TOF/TOF). This approach was supplemented by immunoassays for markers of neutrophils (myeloperoxidase, MPO; neutrophil gelatinase-associated lipocalin, NGAL/HNL) and eosinophils (eosinophil cationic protein: ECP) and by immunoblotting (lactoferrin, calgranulins A and B and annexins A1 and A3. Nearly half of the proteins (69/147) and protein fragments detected were found to be plasma components, on the basis of which the human CVF can be broadly considered a plasma transudate. Although the pattern of protein spots was very similar for all fluids analyzed, a relative overabundance of major plasma proteins such as albumin, transferrin, immunoglobulins, apolipoproteins, alpha-1-acid glycoprotein 1, and calgranulins was associated with the presence of a high number of polymorphonuclear leukocytes in the lavages from which those cell-free fluids had been obtained. Instead, fluids from women experiencing vulvovaginal candidiasis did not show differences in the protein maps compared with asymptomatic individuals. Neutrophil and eosinophil granule secretion proteins were also detected in variable amounts in the lavage fluids by both immunoassay and immunoblotting, indicating polymorphonuclear cell activation.


Asunto(s)
Candidiasis Vulvovaginal/metabolismo , Moco del Cuello Uterino/química , Líquido Extracelular/química , Proteínas/análisis , Proteómica , Vagina/química , Sistema Libre de Células/química , Sistema Libre de Células/microbiología , Moco del Cuello Uterino/metabolismo , Electroforesis en Gel de Poliacrilamida , Proteínas en los Gránulos del Eosinófilo/análisis , Eosinófilos/metabolismo , Líquido Extracelular/metabolismo , Líquido Extracelular/microbiología , Femenino , Humanos , Inmunoproteínas/análisis , Neutrófilos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Vagina/microbiología
11.
Diagn Microbiol Infect Dis ; 54(2): 121-6, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16406184

RESUMEN

To evaluate the diagnostic performance of a commercially available Mycobacterium tuberculosis PCR assay (Amplicor MTB-ROCHE), 2296 respiratory and nonrespiratory specimens from 2296 patients with suspected tuberculosis (TB) were collected prospectively in an 8-year period. Clinical data for each patient were abstracted, and all samples were examined blindly by direct microscopy, culture, and PCR. M. tuberculosis DNA was detected in 93 of 113 culture-positive samples and in 29 of 38 samples from patients with probable TB. The lowest sensitivity was observed in pleural fluid and abscess aspirates. The sensitivity, specificity, and positive predictive value of the assay were 97.2%, 100%, and 100% for smear-positive specimens and 75.3%, 97.0%, and 47.5% for smear-negative specimens, respectively. The PCR cost per additional correct clinical decision was Euro 2826 but would have declined to Euro 308 if the test was applied only to smear-positive specimens. The overall performance of Amplicor MTB test was excellent for smear-positive, but suboptimal for smear-negative specimens.


Asunto(s)
ADN Bacteriano/análisis , Líquido Extracelular/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Tuberculosis/diagnóstico , Líquidos Corporales/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Humanos , Sensibilidad y Especificidad , Esputo/microbiología , Estómago/microbiología
12.
Infect Immun ; 74(1): 703-10, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16369027

RESUMEN

Porphyromonas gingivalis, an important periodontal pathogen, is an effective colonizer of oral tissues. The organism successfully invades, multiplies in, and survives for extended periods in primary gingival epithelial cells (GECs). It is unknown whether P. gingivalis resides in the cytoplasm of infected cells throughout the infection or can spread to adjacent cells over time. We developed a technique based on flow cytofluorometry and fluorescence microscopy to study propagation of the organism at different stages of infection of GECs. Results showed that P. gingivalis spreads cell to cell and that the amount of spreading increases gradually over time. There was a very low level of propagation of bacteria to uninfected cells early in the infection (3 h postinfection), but there were 20-fold and 45-fold increases in the propagation rate after 24 h and 48 h, respectively, of infection. Immunofluorescence microscopy of infected cells suggested that intercellular translocation of P. gingivalis may be mediated through actin-based membrane protrusions, bypassing the need for release of bacteria into extracellular medium. Consistent with these observations, cytochalasin D treatment of infected cells resulted in significant inhibition of bacterial spreading. This study shows for the first time that P. gingivalis disseminates from cell to cell without passing through the extracellular space. This mechanism of spreading may allow P. gingivalis to colonize oral tissues without exposure to the humoral immune response.


Asunto(s)
Células Epiteliales/microbiología , Líquido Extracelular/microbiología , Encía/microbiología , Porphyromonas gingivalis , Actinas/metabolismo , Infecciones por Bacteroidaceae/microbiología , Infecciones por Bacteroidaceae/transmisión , Células Cultivadas , Citoesqueleto/microbiología , Células Epiteliales/metabolismo , Citometría de Flujo , Encía/citología , Encía/metabolismo , Humanos , Cinética , Microscopía Fluorescente
13.
Pediatr Pulmonol ; 39(2): 127-34, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15573391

RESUMEN

Considerable heterogeneity exists in the management of parapneumonic pleural disease. A randomized controlled trial (RCT) demonstrated the effectiveness of small-catheter drainage with fibrinolysis, but surgical devotees suggest this may only be applicable to "early" cases. We examined evidence-based medical management in "all-comers." We performed a retrospective database analysis of the management of all children with complex pleural effusion admitted to the John Radcliffe Hospital over the 7-year period 1996-2003. One hundred and ten children were admitted. Ten were excluded as they were part of a multicenter RCT and had received intrapleural saline instead of urokinase. Of the remaining 100, 51 were female and 49 male. Median age on admission was 5.8 years (range, 0.3-16.5). Symptoms preadmission averaged 11 days, with December the most common month for presentation. Ninety-six underwent chest ultrasound, confirming an effusion in all, described as loculated/septated (68) or echogenic (11). In 17 cases, no specific comment was made regarding the nature of the fluid seen on ultrasound. Ninety-five had subsequent chest tube drainage and then received intrapleural fibrinolysis with urokinase. An etiological organism was identified in 21 cases (21%) (Streptococcus pneumoniae in 10, group A Streptococcus in 5, Staphylococcus aureus in 4, Haemophilus influenzae in 1, and coliform in 1). In a further 9 cases (9%), Gram-positive organisms were seen on pleural fluid microscopy, but did not grow on culture. Two (2%) required surgery due to the persistence of symptoms and an inadequate response to medical management. Median duration of admission was 7 days (range, 2-21 days); median duration of stay from intervention was 5 days (range, 2-19 days). At median follow-up of 8 weeks (range, 3-20 weeks), all children were symptom-free, with minimal pleural thickening on chest X-ray. In conclusion, antibiotic therapy with chest drain insertion and intrapleural urokinase is effective in treating complex parapneumonic effusion and is associated with a good long-term outcome.


Asunto(s)
Drenaje/instrumentación , Empiema Pleural/terapia , Activadores Plasminogénicos/administración & dosificación , Neumonía Bacteriana/complicaciones , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Adolescente , Antibacterianos/administración & dosificación , Cefuroxima/administración & dosificación , Tubos Torácicos , Niño , Preescolar , Método Doble Ciego , Empiema Pleural/diagnóstico , Empiema Pleural/etiología , Líquido Extracelular/microbiología , Femenino , Estudios de Seguimiento , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/terapia , Humanos , Lactante , Inyecciones Intravenosas , Instilación de Medicamentos , Tiempo de Internación , Masculino , Cavidad Pleural/diagnóstico por imagen , Derrame Pleural/diagnóstico , Derrame Pleural/microbiología , Derrame Pleural/terapia , Neumonía Bacteriana/diagnóstico por imagen , Radiografía Torácica , Estudios Retrospectivos , Toracotomía , Resultado del Tratamiento , Ultrasonografía
14.
Biochem J ; 384(Pt 2): 263-70, 2004 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-15260802

RESUMEN

Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.


Asunto(s)
Adhesión Bacteriana/fisiología , Mucinas Gástricas/metabolismo , Helicobacter pylori/metabolismo , Mucinas/metabolismo , Centrifugación por Gradiente de Densidad/métodos , Líquido Extracelular/química , Líquido Extracelular/microbiología , Mucinas Gástricas/química , Mucosa Gástrica/química , Mucosa Gástrica/microbiología , Glicosilación , Infecciones por Helicobacter/patología , Humanos , Concentración de Iones de Hidrógeno , Mucina 5AC
15.
Can J Vet Res ; 67(3): 229-31, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12889731

RESUMEN

During infection, nutrient deprivation can alter bacterial phenotype. This, in turn, may have implications for pathogenesis and prophylaxis. Actinobacillus pleuropneumoniae (biotype 1) and Haemophilus parasuis, respiratory tract pathogens of swine, are both V-factor-dependent. The concentrations of V factor in the extracellular fluids of pigs are unknown and may limit the growth of these bacteria in vivo. The aim of this study was to determine the concentrations of nicotinamide adenine dinucleotide (NAD) in select porcine body fluids and to compare the availability of NAD in vivo with the affinities of the organisms for this compound. Levels in plasma, tissue fluids (peritoneal, pleural, synovial, and cerebrospinal), and laryngeal, tracheal, and lung washings were determined with an enzymatic cycling assay. We concluded that, although the NAD supply in the respiratory tract is probably not growth-limiting, it may become limiting if the organisms are disseminated.


Asunto(s)
Actinobacillus pleuropneumoniae/crecimiento & desarrollo , Haemophilus/crecimiento & desarrollo , NAD/metabolismo , Infecciones del Sistema Respiratorio/veterinaria , Enfermedades de los Porcinos/microbiología , Infecciones por Actinobacillus/microbiología , Infecciones por Actinobacillus/veterinaria , Actinobacillus pleuropneumoniae/aislamiento & purificación , Actinobacillus pleuropneumoniae/patogenicidad , Animales , Líquido Extracelular/química , Líquido Extracelular/microbiología , Haemophilus/aislamiento & purificación , Haemophilus/patogenicidad , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/veterinaria , Pulmón/microbiología , Fenotipo , Infecciones del Sistema Respiratorio/microbiología , Porcinos
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