RESUMEN

A 41 year-old man, recently returned from Thailand, presented with bilateral shoulder pain and weakness, fever greater than 38 degrees and coryzal symptoms. He had no significant past medical history. He had abnormal liver function tests and an abnormal electromyogram of his right upper limb. He was diagnosed with acute Epstein Barr virus infection, however cerebrospinal fluid was negative for the virus. At follow up after three months, the patient had persistent weakness of his right upper limb. The literature suggests neurological features present in up to 7.5% of patients with Epstein Barr virus, although argues this is underestimated with the virus often being overlooked as a cause of neurological symptoms.

RESUMEN

We used modeling to predict the energy and cost savings associated with the air-based, hybrid membrane-biofilm reactor (hybrid MfBR). This process is obtained by replacing fine-bubble diffusers in conventional activated sludge with air-supplying, hollow-fiber membrane modules. Evaluated processes included removal of chemical oxygen demand (COD), combined COD and total nitrogen (TN) removal, and hybrid growth (biofilm and suspended). Target concentrations of COD and TN were based on high-stringency water reuse scenarios. Results showed reductions in power requirements as high as 86%. The decrease mainly resulted from the dramatically lower air flows for the MBfR, resulting from its higher oxygen-transfer efficiencies. When the MBfR was used for COD and TN removal, savings up to US$200/1,000 m(3) of treated water were predicted. Cost savings were highly sensitive to the costs of the membrane modules and electrical power. The costs were also very sensitive to membrane oxidation flux for ammonia, and the membrane life. These results suggest the hybrid MBfR may provide significant savings in energy and costs. Further research on the identified key parameters can help confirm these modeling predictions and facilitate scale-up.

Asunto(s)

Aire , Biopelículas , Conservación de los Recursos Energéticos , Membranas Artificiales , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua , Purificación del Agua/métodos

RESUMEN

Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury.

Asunto(s)

Aspergillus fumigatus/fisiología , Lesión Pulmonar/etiología , Lesión Pulmonar/microbiología , Irradiación Corporal Total/efectos adversos , Animales , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Transferencia Lineal de Energía , Lesión Pulmonar/fisiopatología , Ratones , Ratones Endogámicos C57BL , Dosis de Radiación , Esporas Fúngicas/fisiología

RESUMEN

Pulmonary damage after radiotherapy is typically characterized by an initial alveolar inflammation (pneumonitis) followed by chronic fibrosis. In the present study, changes in lung architecture were measured in the pneumonitis phase after whole-body low-dose X irradiation of C57BL/6 mice. Radiation damage was evaluated at 24 h and 1-8 weeks postirradiation. Three distinct scoring systems were used: ( 1 ) manually evaluating alveolar distortion and infiltration of inflammatory cells into the alveolar space using a continuous numerical scale across an entire lung section, ( 2 ) physically measuring the average thickness of the alveolar septa from multiple representative microscope fields, and ( 3 ) a new rapid automated mathematical algorithm based on image segmentation of alveolar space across an entire section. Each scoring method detected significant changes in alveolar architecture at the earliest times compared with sham-treated controls and gave comparable evaluations of injury. The results from the automated mathematical algorithm correlated significantly with both the manual evaluation method (Spearman's correlation coefficient rho = 0.044) and the direct physical measurement of septa thickness (rho = 0.002). These data demonstrate that evaluating alveolar space by segmentation analysis provides a reliable method for scoring early pulmonary radiation damage that is consistent with more established methodologies but is more rapid and is independent of potential operator and selection bias.

Asunto(s)

Algoritmos , Interpretación de Imagen Asistida por Computador/métodos , Pulmón/patología , Pulmón/efectos de la radiación , Reconocimiento de Normas Patrones Automatizadas/métodos , Neumonitis por Radiación/patología , Animales , Inteligencia Artificial , Ratones , Ratones Endogámicos C57BL , Dosis de Radiación

RESUMEN

Bromate is a carcinogenic disinfection by-product formed from bromide during ozonation or advanced oxidation. We previously observed bromate reduction in a hydrogen-based, denitrifying hollow fiber membrane biofilm reactor (MBfR). In this research, we investigated the potential existence of specialized bromate-reducing bacteria. Using denaturing gradient gel electrophoresis (DGGE), we compared the microbial ecology of two denitrifying MBfRs, one amended with nitrate as the electron acceptor and the other with nitrate plus bromate. The DGGE results showed that bromate exerted a selective pressure for a putative, specialized bromate-reducing bacterium, which developed a strong presence only in the reactor with bromate. To gain further insight into the capabilities of specialized, bromate-reducing bacteria, we explored bromate reduction in a control MBfR without any primary electron acceptors. A grown biofilm in the control MBfR reduced bromate without previous exposure, but the rate of reduction decreased over time, especially after perturbations resulting in biomass loss. The decrease in bromate reduction may have been the result of the toxic effects of bromate. We also used batch tests of the perchlorate-reducing pure culture, Dechloromonas sp. PC1 to test bromate reduction and growth. Bromate was reduced without measurable growth. Based on these results, we speculate bromate's selective pressure for the putative, specialized BRB observed in the DGGE was not growth related, but possibly based on resistance to bromate toxicity.

Asunto(s)

Betaproteobacteria/metabolismo , Bromatos/metabolismo , Percloratos/metabolismo , Biopelículas , Reactores Biológicos , Carcinógenos/metabolismo , Diseño de Equipo , Cinética , Nitratos/metabolismo , Oxidación-Reducción , Purificación del Agua/métodos

RESUMEN

We report on a novel process for total nitrogen (TN) removal, the hybrid membrane biofilm process (HMBP). The HMBP uses air-supplying hollow-fibre membranes inside an activated sludge tank, with suppressed aeration, to allow concurrent nitrification and denitrification. We hypothesised that a nitrifying biofilm would form on the membranes, and that the low bulk-liquid BOD concentrations would encourage heterotrophic denitrifying bacteria to grow in suspension. A nitrifying biofilm was initially established by supplying an influent ammonia concentration of 20 mgN/L. Subsequently, 120 mg/L acetate was added to the influent as BOD. With a bulk-liquid SRT of only 5 days, nitrification rates were 0.85 gN/m(2) per day and the TN removal reached 75%. The biofilm thickness was approximately 500 lim. We used DGGE to obtain a microbial community fingerprint of suspended and attached growth, and prepared a clone library. The DGGE results, along with the clone library and operating data, suggest that nitrifying bacteria were primarily attached to the membranes, while heterotrophic bacteria were predominant in the bulk liquid. Our results demonstrate that the HMBP is effective for TN removal, achieving high levels of nitrification with a low bulk-liquid SRT and concurrently denitrifying with BOD as the sole electron donor.

Asunto(s)

Biopelículas , Nitrógeno/metabolismo , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Secuencia de Bases , Biopelículas/clasificación , ADN Bacteriano/genética , Ecología , Membranas Artificiales , ARN Ribosómico 16S/genética , Aguas del Alcantarillado

RESUMEN

Medical mistakes is an issue that challenges many healthcare providers and organizations. The challenges are professional, personal, systemswide, financial, and morally compelling; and a fully fitting response may depend on the answer to questions that H. Richard Niebuhr used to divide all ethical considerations: what is going on here; and what is the fitting response. Heartland Regional Medical Center in St. Joseph, Missouri, asked these questions about medication errors. The response model they developed, although it is very much a work in progress, shows how a facility can go from an ethical analysis to fixing the problem.

Asunto(s)

Administración Hospitalaria , Errores de Medicación/prevención & control , Revelación , Humanos , Administración de la Seguridad

RESUMEN

This study characterizes the echogenicity of experimentally induced venous thrombosis. Venous duplex imaging (Diasonics Spectra) was performed of the rat (n 12) and primate (n 3) inferior vena cava (IVC). Thrombosis was induced by IVC ligation at the level of the renal veins (rat, baboon) or balloon occlusion (baboon) of the IVC at the renal vein and iliac vein bifurcation level. Sham-treated rats served as controls. B-mode images were stored for off-line computer analysis. Fixed depth gain control curves allowed for measuring gain-corrected echogenicity units over the IVC in both a longitudinal and transverse orientation. In rat studies, thrombus was removed at time of euthanasia and dissolved, allowing for fibrin monomer determination using a chromogenic assay. Echogenicity values generally increased over time in both rat and primate studies. Significant differences between ligated and sham-treated rats were noted at each time point measured (6 h, 2 days, and 6 days after IVC ligation) and fibrin monomer values correlated (p < 0.05) with echogenicity units. In primate studies, echogenicity values significantly were different from baseline values at all time points measured (6 h, 2 days, 6 days, and 13 days after thrombus induction). Duplex ultrasound can be used to quantitate thrombus echogenicity, which correlates to fibrin content. Such measurement may potentially allow for improved thrombus age determination and the noninvasive quantitation of thrombus progression/resolution.

Asunto(s)

Ultrasonografía Doppler Dúplex , Vena Cava Inferior/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Animales , Cateterismo , Modelos Animales de Enfermedad , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Ligadura , Papio , Ratas , Ratas Sprague-Dawley , Trombosis de la Vena/sangre , Trombosis de la Vena/etiología

RESUMEN

PURPOSE: Venous thrombosis results in a vein wall inflammatory response initiated by thrombus. Although anticoagulation with standard heparin (SH) and low-molecular-weight heparin (LMWH) is known to limit further thrombosis, their anti-inflammatory properties are poorly defined. The anti-inflammatory properties of these heparins were studied. METHODS: Sprague-Dawley rats were divided into groups and underwent inferior vena caval (IVC) ligation just below the renal level producing IVC thrombosis. One hour before ligation, animals received subcutaneous SH or LMWH at either high or low dose; normal saline (NS) was used as control. Six hours after ligation, animals were killed, and the IVCs were analyzed for clot presence, vein wall morphometrics, and vein wall permeability (VP) to define injury. RESULTS: Animals in both low-dose groups had no measurable anticoagulation, whereas those in both high-dose groups were adequately anticoagulated. There were statistically less IVC neutrophils for all groups compared with the control group, with low-dose LMWH showing the least cells (low-dose LMWH, 16 +/- 3; high-dose LMWH, 37 +/- 10; low-dose SH, 37 +/- 6; high-dose SH, 32 +/- 9; NS control, 63 +/- 2). Similar results were noted for total inflammatory cells. The lowest VP was noted for low-dose LMWH. CONCLUSION: Although both SH and LMWH inhibited vein wall neutrophils and total inflammatory cells, low-dose LMWH was most effective limiting neutrophil extravasation and was the only intervention to decrease VP below control levels. This occurred without preventing thrombus formation or causing a state of anticoagulation. Low-dose LMWH possesses anti-inflammatory properties distinct from its anticoagulant properties.

Asunto(s)

Antiinflamatorios/farmacología , Anticoagulantes/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Trombosis de la Vena/tratamiento farmacológico , Animales , Estudios de Evaluación como Asunto , Inflamación , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Venas/patología , Trombosis de la Vena/patología

RESUMEN

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.

Asunto(s)

Interleucina-10/fisiología , Tromboflebitis/inmunología , Tromboflebitis/patología , Animales , Constricción Patológica , Relación Dosis-Respuesta Inmunológica , Esquema de Medicación , Sueros Inmunes/administración & dosificación , Inflamación/inmunología , Inflamación/prevención & control , Inyecciones Intravenosas , Interleucina-10/administración & dosificación , Interleucina-10/genética , Interleucina-10/inmunología , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Tromboflebitis/prevención & control , Trombosis/inmunología , Vena Cava Inferior/patología

RESUMEN

PURPOSE: Venous thrombosis is associated with a significant inflammatory response, which can be visualized by gadolinium magnetic resonance venography (MRV). Gadolinium extravasates into tissue during inflammation, producing perithrombus enhancement on magnetic resonance scanning. This study determines (1) whether gadolinium enhancement occurs during deep venous thrombosis (DVT); and (2) whether this enhancement changes with time and can therefore establish the age of thrombus. METHODS: Patients with a diagnosis of iliofemoral DVT by duplex ultrasound who were referred for MRV to document central thrombus extent were studied. T1 weighted images were obtained before and after gadolinium injection (0.1 mmol/kg); repeat scans were obtained up to 3 months thereafter. At the level of maximum thrombus, measurements of signal intensity were made at the periphery (rim), and the center of the thrombosed vein, as well as the contralateral normal vein, on images after gadolinium enhancement. Rim-center vein signal intensity ratios were then calculated and followed. RESULTS: A total of 39 scans were obtained in 14 patients (eight men, six women). The thrombosed veins were enlarged, with a peripheral rim of enhancement ("bull's-eye" sign). The rim-center ratio for thrombosed veins (2.16 +/- 0.18) was different from that of normal veins (0.66 +/- 0.10; n = 39; p < 0.001). For all acute studies (< or = 14 days) the rim-center ratio was 2.38 +/- 0.17 (n = 31), whereas for all chronic studies (> 14 days) the rim-center ratio was 1.29 +/- 0.44 (n = 8; p = 0.001). Among patients who underwent both early and late studies, the rim-center ratio dropped significantly, from 2.33 +/- 0.20 acutely to 1.29 +/- 0.44 in chronic studies (n = 8; p = 0.03). One patient with active malignancy had a paradoxic increase in rim-center ratio over time and a clinical recurrence of symptoms, suggesting active thrombosis. CONCLUSIONS: We conclude that (1) a pattern of peripheral gadolinium enhancement (bull's-eye sign) is seen around acutely thrombosed veins on gadolinium-enhanced MRV, facilitating DVT diagnosis; and (2) the ratio of signal intensity at the rim versus the center of the thrombosed vein may be a good discriminator of acute compared with chronic DVT, which may help direct therapy.

Asunto(s)

Medios de Contraste , Vena Femoral/patología , Gadolinio DTPA , Vena Ilíaca/patología , Imagen por Resonancia Magnética , Tromboflebitis/diagnóstico , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo

RESUMEN

PURPOSE: Venous thrombosis and inflammation are interrelated. P-selectin contributes to activation of leukocyte-mediated inflammation. Therefore, we hypothesized that the neutralization of P-selectin would decrease vein wall inflammation and thrombosis. METHODS: Twelve baboons underwent infrarenal inferior vena caval balloon occlusion to induce thrombosis. Two groups of four baboons received neutralizing intravenous anti-P-selectin antibody (PSab) GA6 or CY1748 before occlusion and at days 2 and 4. Four baboons received saline control injections. One baboon per group was killed at days 2, 6, and 13, and at 2 months. Analysis included phlebography, ultrasound, gadolinium (Gd)-enhanced magnetic resonance venography (reflecting vein wall inflammation), and histologic, morphometric, and protein evaluation of the vein wall. Thrombus presence or absence was assessed. RESULTS: By day 2 in PSab baboons, vein wall Gd enhancement was decreased in the mid-inferior vena cava and the right iliac vein (p < 0.05; GA6 vs control baboons), normalizing by 2 months. The mid-inferior vena cava revealed fewer neutrophils and total leukocytes in PSab baboons; however, for GA6 in the right iliac vein these decreases were not present despite the absence of Gd enhancement; they were decreased with CY1748. PSab baboons demonstrated significantly less thrombus than control baboons (p < 0.01, GA6 and CY1748 vs control baboons). CONCLUSIONS: Anti-P-selectin antibody decreases vein wall inflammation and thrombus formation. Inhibition of P-selectin may be useful in venous thrombosis prophylaxis.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Vena Ilíaca , Selectina-P/inmunología , Trombosis/tratamiento farmacológico , Vasculitis/tratamiento farmacológico , Vena Cava Inferior , Enfermedad Aguda , Animales , Anticuerpos/sangre , Enfermedad Crónica , Medios de Contraste , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Gadolinio , Vena Ilíaca/diagnóstico por imagen , Vena Ilíaca/patología , Angiografía por Resonancia Magnética , Papio , Radiografía , Trombosis/diagnóstico , Trombosis/inmunología , Trombosis/patología , Factores de Tiempo , Ultrasonografía , Vasculitis/diagnóstico , Vasculitis/inmunología , Vasculitis/patología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología

RESUMEN

Using the dog as an animal model, we developed an experimental preparation to compare hemodynamic and hematologic toxicity of anticoagulation reversal. Currently, protamine sulfate reversal of standard unfractionated heparin and low-molecular-weight heparin (LMWH) anticoagulation causes adverse side effects, including decreased systemic mean arterial pressure (MAP), decreased cardiac output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In addition, standard protamine is only marginally effective at reversing the factor Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides to decrease the adverse responses attributed to standard protamine. The hemodynamic, hematologic, and coagulation effects of standard protamine and the protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation in anesthetized dogs. Flow probes and vascular catheters were surgically implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and heart rate (HR). Hematologic studies (platelet and white blood cell counts) and coagulation studies (activated clotting time [ACT], activated partial thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and antifactor IIa values) also were performed. The protamine variant +18RGD was less toxic, induced less thrombocytopenia, and was more effective in anticoagulation reversal than was standard protamine sulfate. Results of this study indicate that the dog may be a useful model for investigating important hemodynamic, hematologic, and coagulation parameters during reversal of LMWH anticoagulation by use of synthetic protamine variants.

Asunto(s)

Anticoagulantes/administración & dosificación , Enfermedades Cardiovasculares/inducido químicamente , Modelos Animales de Enfermedad , Enfermedades Hematológicas/inducido químicamente , Heparina de Bajo-Peso-Molecular/administración & dosificación , Péptidos/toxicidad , Protaminas/toxicidad , Animales , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Perros , Inhibidores del Factor Xa , Heparina de Bajo-Peso-Molecular/uso terapéutico , Consumo de Oxígeno/efectos de los fármacos , Péptidos/uso terapéutico , Protaminas/uso terapéutico

RESUMEN

Venous thrombosis and thrombophlebitis have long been observed to result in painful inflammation around the affected veins. The full extent of the synergistic interaction between thrombosis and the inflammatory response and how this leads to the later sequelae of chronic venous insufficiency is only now beginning to be understood. Venous thrombosis is known directly to elicit an inflammatory response in the thrombus and vein wall. Leukocytes including neutrophils and monocytes roll, adhere, activate and extravasate into the vein wall based on a vein wall cytokine/chemokine gradient producing an inflammatory response. Such a response leads to amplification of thrombus formation through mechanisms such as the elaboration of tissue factor on the surface of monocytes and the release of cathespin G from activated neutrophils (distrupting the endothelial cell barrier), exposing the thrombogenic subendothelial vein wall collagen. Selectins such as P-selectin and the proinflammatory cytokine tumor necrosis factor appear important in this vein wall response. Inhibition of inflammation before the initiation of the thrombotic event may decrease the detrimental vein wall changes that contribute to vein wall and vein valve damage and thrombus formation.

Asunto(s)

Tromboflebitis/inmunología , Quimiocinas/fisiología , Citocinas/fisiología , Endotelio Vascular/inmunología , Humanos , Activación Neutrófila/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/inmunología , Insuficiencia Venosa/inmunología

RESUMEN

Venous thrombosis and inflammation are interrelated. The authors hypothesized that inferior vena cava thrombosis results in a predictable vein wall inflammatory response, characterized by early neutrophil infiltration. Thrombosis was induced in rats by placement of an inferior vena cava ligature with branch ligation. Animals were killed at baseline, 6 hrs, day 2, and day 6. Analysis included vein wall morphometrics, myeloperoxidase activity, and fluorescence activated cell sorting. At 6 hrs, there was an increase in neutrophils and lymphocytes as compared to sham animals (p < 0.0001 for neutrophils, p < 0.05 for lymphocytes). By day 2, only neutrophils were elevated in the experimental groups (experimental = 75.5 cells/5 high power fields vs. 9.6 cells/ 5 high power fields in shams, p < 0.0001). Myeloperoxidase activity in the experimental group was greater than shams on day 2(34.7 delta optical density/min vs. 5.9 delta optical density/ min, p < 0.0001). Fluorescence activated cell sorting of the neutrophil marker at 6 hrs confirmed the increase in neutrophils (experimental = 63.1%, shams = 39.1%, p < 0.0001), and peaked on day 2 (71.9%). This study suggests that 1) neutrophils are elevated early during the inflammatory response due to thrombus initiation, and 2) neutrophils, because of their early predominance, likely contributed to vein wall injury during venous thrombosis.

Asunto(s)

Neutrófilos/patología , Tromboflebitis/complicaciones , Tromboflebitis/patología , Vasculitis/etiología , Vasculitis/patología , Animales , Separación Celular , Modelos Animales de Enfermedad , Citometría de Flujo , Neutrófilos/enzimología , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Tromboflebitis/enzimología , Vasculitis/enzimología , Vena Cava Inferior

RESUMEN

Venous thrombosis induces a detrimental inflammatory response in the vein wall. The cytokine tumor necrosis factor-alpha (TNF) and the adhesion molecules, selectins, have been found to be important in mediating inflammatory cell stimulation and leukocyte-endothelial cell adhesion, respectively. This study assesses the role of TNF and P-selectin in the inflammatory events associated with venous thrombosis. Rats were passively immunized with neutralizing anti-TNF serum alone, anti-TNF plus anti-P-selectin antibody, anti-P-selectin antibody alone, control serum, or control anti-P-selectin antibody. Antibodies or control sera were given prior to occlusion and at Days 2 and 4 postocclusion. Rats were sacrificed at Days 1-6 and Day 13 after occlusion for inferior vena caval (IVC) wall histopathology and TNF analysis. Differences in the extent of inflammatory cell infiltrate into the vein wall were found on Days 2, 6, and 13. TNF levels were elevated in the vein wall of the three groups not given anti-TNF antibody. The levels of TNF at Day 6 positively correlated with both total inflammatory cell (r = 0.53, P < 0.05) and neutrophil presence (r = 0.72, P < 0.01). The lowest IVC wall neutrophil and total inflammatory cell count at Days 2 and 6 and the lowest neutrophil count at Day 13 were found in the anti-TNF plus anti-P-selectin antibody group. Monocyte influx was also inhibited at Day 13 in this group. These results suggest a role for combined neutralization of TNF and P-selectin in the attenuation of inflammation induced by venous thrombosis.

Asunto(s)

Selectina-P/metabolismo , Tromboflebitis/complicaciones , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Vasculitis/etiología , Vasculitis/patología , Animales , Anticuerpos/inmunología , Recuento de Células , Monocitos/patología , Neutrófilos/patología , Selectina-P/inmunología , Ratas , Factores de Tiempo , Factor de Necrosis Tumoral alfa/inmunología , Vena Cava Inferior/patología

RESUMEN

The preference for parallelism of the two chains in tropomyosin coiled coils is thought to result from interchain salt bridges. To examine this idea, studies are presented of tropomyosin molecules reassembled from chaotropic solvents in acid solution, where cross-links cannot exist. The acid-reassembled molecules are appreciably less disulfide cross-linkable in acid than native molecules, a result explainable if some antiparallel dimers indeed form at low pH. Physical studies (backbone- and tyrosine-region CD and intrinsic viscosity) indicate that refolding in acid yields a molecular population demonstrably different in tyrosine-region CD from native, but having comparable (but not identical) helix content, thermal stability, and dimensions. Moreover, the refolding in acid after either thermal or chaotropic-solvent denaturation yields the same final state, arguing that it is an equilibrium state. All these results are consistent with, but do not prove, that the acid-reassembled population includes an appreciable fraction (2/3) of antiparallel coiled-coil dimers.

Asunto(s)

Estructura Secundaria de Proteína , Tropomiosina/química , Animales , Reactivos de Enlaces Cruzados , Concentración de Iones de Hidrógeno , Desnaturalización Proteica , Conejos

Asunto(s)

Educación Médica , Atención Primaria de Salud , Facultades de Medicina/tendencias , Especialización , Estudios de Cohortes , Femenino , Fuerza Laboral en Salud , Humanos , Kansas , Masculino , Distribución por Sexo , Estudiantes de Medicina/estadística & datos numéricos

RESUMEN

The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.

Asunto(s)

Moléculas de Adhesión Celular Neuronal/biosíntesis , Proteínas/metabolismo , Factor de Crecimiento Transformador beta/fisiología , Animales , Sangre , Proteínas Morfogenéticas Óseas , Bovinos , Sustancias de Crecimiento/fisiología , Humanos , Complejo de Antígeno L1 de Leucocito , Familia de Multigenes , Ratas , Factor de Crecimiento Transformador beta/genética , Células Tumorales Cultivadas

RESUMEN

Modulation of alpha 2-adrenergic and opioid neurotransmission may contribute to ethanol intoxication, tolerance, and physical dependence. We showed previously that ethanol increased the expression of functional delta-opioid receptors in NG108-15 cells (Charness, M. E., Querimit, L. A., and Diamond, I. (1986) J. Biol. Chem. 261, 3164-3169). Here we report that long-term (2 days) treatment of NG108-15 cells with ethanol increased the binding of the alpha 2-adrenergic receptor (alpha 2AR) antagonist [3H]rauwolscine and the muscarinic acetylcholine receptor (mAChR) antagonist [3H]quinuclidinyl benzilate by 2.8- and 1.4-fold, respectively. Increased receptor expression was associated with a proportionate increase in the potency of oxymetazoline and carbachol in inhibiting cAMP accumulation. Ethanol did not change the expression of G alpha i2 and reduced levels of G alpha s. Pertussis toxin pretreatment did not prevent the ethanol-induced increase in alpha 2AR, mAChR, and delta-opioid receptor expression. Ethanol caused a large (3.6-fold), dose-dependent increase in the abundance of alpha 2BAR mRNA (rat cDNA probe RNG, 4.1-kb transcript). Ethanol-induced increases in alpha 2BAR and alpha 2CAR (rat probe RG10, 2.5-kb transcript) mRNAs were first detected after 6 h of exposure to 100 mM ethanol, became maximal after 24 h, and persisted for up to 5 days. In contrast, ethanol caused only a small (1.3-fold) increase in the abundance of hm4 mAChR mRNA and did not change levels of G alpha i2 and G alpha s mRNAs. Our data indicate that clinically attainable concentrations of ethanol regulate alpha 2AR gene expression within the time frame of a single session of drinking.

Asunto(s)

Etanol/farmacología , Receptores Adrenérgicos alfa/genética , Receptores Muscarínicos/genética , Animales , Línea Celular , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Proteínas de Unión al GTP/metabolismo , Expresión Génica/efectos de los fármacos , Toxina del Pertussis , ARN Mensajero/genética , Ratas , Receptores Adrenérgicos alfa/clasificación , Factores de Tiempo , Distribución Tisular , Regulación hacia Arriba/efectos de los fármacos , Factores de Virulencia de Bordetella/farmacología