Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.     

Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.     

A controlled, longitudinal study of dementia in Parkinson''s disease.

Serial assessments of cognition, mood, and disability were carried out at nine month intervals over a 54 month period on a cohort of 87 patients with Parkinson's disease (PD) and a matched cohort of 50 control subjects. Dementia was diagnosed from data by rigorously applying DSM-III-R criteria. Initially, 6% (5/87) PD patients were demented, compared with none of the 50 control subjects. A further 10 PD patients met the dementia criteria during the follow up period; this was equivalent, with survival analysis, to a cumulative incidence of 19%. With the number of person years of observation as the denominator, the incidence was 47.6/1000 person years of observation. None of the control subjects fulfilled dementia criteria during the follow up period. The patients with PD who became demented during follow up were older at onset of Parkinson's disease than patients who did not become demented, had a longer duration of Parkinson's disease, and were older at inclusion to the study.     

Evidence-based management practice: reducing falls in hospital

This paper reports on a falls prevention and management program at one regional Western Australian hospital. The report focuses on the processes and outcomes of a quality management initiative to reduce falls in hospital to illustrate the nexus between research and quality improvement in clinical practice. The Falls Prevention program was based on statistical evidence of the level of risk in the hospital and development of an evidence-based multidimensional, multidisciplinary program to reduce the risks of falling and the number of falling events. Evaluative data demonstrate the effectiveness of the program in terms of a substantial reduction in falls. The program illustrates the value of evidence-based practice, particularly in relation to evidence-based management practice. It supports the merits of creating an organisational climate where all clinicians are encouraged to use research data to plan strategies for quality improvement and risk management and, in the process, advance clinical nursing knowledge development.     

Protecting kidneys in liver transplant patients:A pathway to preventive interventions

Acute kidney injury(AKI) is a frequent postoperative complication after liver transplantation. The etiology is multifactorial,including perioperative renal status,surgery related events,and postoperative immunosuppression therapy. The role of renal hypoperfusion and hepatic ischemia-reperfusion injury as causes of early AKI are now being increasingly recognized. Further studies should focus on therapies that would attenuate this injury.     

Comparison of the plaque assay and 50% tissue culture infectious dose assay as methods for measuring filovirus infectivity

Two common methods of quantifying filovirus infectivity, a plaque assay and 50% cell culture infectious dose (TCID₅₀) endpoint dilution assay, were compared. The two assays were performed side by side using the same virus stock sample to determine the correlation between the results of the two assays. The TCID₅₀ assay appeared to be more sensitive but slightly more variable, and there was a tenfold difference in the numerical results of these methods of enumeration. The advantages and disadvantages of both assays are discussed. Both methods are useful and practicable in filovirus research, and this comparison will be hugely beneficial to the filovirus research community as it seeks to become more united. Further work in this area should be performed to ensure consistency in filovirus research.     

Sodium ions and the secretion of catecholamines

1. Perfusion of bovine adrenal glands with a potassium-free Tyrode solution results in an increased spontaneous release of catecholamines and an increased response to stimulation with carbamylcholine.2. Perfusion with a Tyrode solution containing 70 mM-KCl causes a marked secretion of catecholamines and a subsequent inhibition of secretion in response to stimulation with carbamylcholine.3. Perfusion with sodium-free media abolishes or severely reduces the secretory response of the gland to carbamylcholine and to 70 mM-KCl although the basal secretion shows an initial rise.4. Perfusion with sodium-deficient media permits some retention of the secretory response.5. A possible role for intracellular sodium ions in the secretion of catecholamines is discussed.