Human cytomegalovirus (HCMV) is an important, ubiquitous pathogen that causes severe clinical disease in immunocompromised individuals, such as organ transplant recipients and infants infected in utero. Antiviral chemotherapy remains problematic due to toxicity of the available compounds and the emergence of viruses resistant to available antiviral therapies. Antiviral antibodies could represent a valuable alternative strategy to limit the clinical consequences of viral disease in patients. The envelope glycoprotein B (gB) of HCMV is a major antigen for the induction of virus neutralizing antibodies. However, the role of anti-gB antibodies in the course of the infection in-vivo remains unknown. We have used a murine CMV (MCMV) model to generate and study a number of anti-gB monoclonal antibodies (mAbs) with differing virus-neutralizing capacities. The mAbs were found to bind to similar antigenic structures on MCMV gB that are represented in HCMV gB. When mAbs were used in immunodeficient RAG-/- hosts to limit an ongoing infection we observed a reduction in viral load both with mAbs having potent neutralizing capacity in-vitro as well as mAbs classified as non-neutralizing. In a therapeutic setting, neutralizing mAbs showed a greater capacity to reduce the viral burden compared to non-neutralizing antibodies. Efficacy was correlated with sustained concentration of virus neutralizing mAbs in-vivo rather than their in-vitro neutralizing capacity. Combinations of neutralizing mAbs further augmented the antiviral effect and were found to be as potent in protection as polyvalent serum from immune animals. Prophylactic administration of mAbs before infection was also protective and both neutralizing and non-neutralizing mAbs were equally effective in preventing lethal infection of immunodeficient mice. In summary, our data argue that therapeutic application of potently neutralizing mAbs against gB represent a strategy to modify the outcome of CMV infection in immunodeficient hosts. When present before infection, both neutralizing and non-neutralizing anti-gB exhibited protective capacity.
The provision of sufficient chest compression is among the most important factors influencing patient survival during cardiopulmonary resuscitation (CPR). One approach to optimize the quality of chest compressions is to use mechanical-resuscitation devices. The aim of this study was to compare a new device for chest compression (corpuls cpr) with an established device (LUCAS II). We used a mechanical thorax model consisting of a chest with variable stiffness and an integrated heart chamber which generated blood flow dependent on the compression depth and waveform. The method of blood-flow generation could be changed between direct cardiac-compression mode and thoracic-pump mode. Different chest-stiffness settings and compression modes were tested to generate various blood-flow profiles. Additionally, an endurance test at high stiffness was performed to measure overall performance and compression consistency. Both resuscitation machines were able to compress the model thorax with a frequency of 100/min and a depth of 5 cm, independent of the chosen chest stiffness. Both devices passed the endurance test without difficulty. The corpuls cpr device was able to generate about 10-40% more blood flow than the LUCAS II device, depending on the model settings. In most scenarios, the corpuls cpr device also generated a higher blood pressure than the LUCAS II. The peak compression forces during CPR were about 30% higher using the corpuls cpr device than with the LUCAS II. In this study, the corpuls cpr device had improved blood flow and pressure outcomes than the LUCAS II device. Further examination in an animal model is required to prove the findings of this preliminary study.
Tissue response to three types of vascular prosthetic materials was evaluated by correlation of scanning electron microscopy and light microscopy. Two clinically established materials, woven dacron and woven teflon, and an experimental material, expanded polytetrafluoroethylene (Goretex) were employed. They were implanted in the subcutaneous tissue of rats and removed at time intervals ranging from 48 hours to 30 days. Half of the retrieved material was fixed in 10% formalin and examined by routine light microscopy. The other half was glutaraldehyde fixed and acetone/CO2 critical point dried, then examined by scanning electron microscopy.Prior to this study, the three materials were evaluated by scanning electron microscopy to establish topographic landmarks. The woven dacron had bundles of relatively large, rough fibers; the woven teflon had fibers of similar size but with a smooth surface; the PTFE, however, had a surface composed of fibers and pores only a few micra in diameter.
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