Effects of Pegorgotein on Neurologic Outcome of Patients With Severe Head Injury

Young, Byron; Runge, Jeffrey W; Waxman, Kenneth; Harrington, Timothy; Wilberger, Jack E.; Muizelaar, J. Paul; Boddy, Alex; Kupiec, James W.

doi:10.1001/jama.1996.03540070034027

Cited by 145 publications

(13 citation statements)

References 12 publications

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“…Administration of SOD-mimics has been evaluated in clinical TBI. A large clinical trial with polyethylene glycol (PEG)-conjugated SOD showed no improvement in survival or neurological outcome after moderate to severe TBI (Young et al, 1996), although an earlier small phase II study reported a positive trend (Muizelaar, 1993). …”

Section: Therapeutic Strategies Targeting Lipid Peroxidationmentioning

confidence: 99%

Therapies targeting lipid peroxidation in traumatic brain injury

2016

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Lipid peroxidation can be broadly defined as the process of inserting a hydroperoxy group into a lipid. Polyunsaturated fatty acids present in the phospholipids are often the targets for peroxidation. Phospholipids are indispensable for normal structure of membranes. The other important function of phospholipids stems from their role as a source of lipid mediators – oxygenated free fatty acids that are derived from lipid peroxidation. In the CNS, excessive accumulation of either oxidized phospholipids or oxygenated free fatty acids may be associated with damage occurring during acute brain injury and subsequent inflammatory responses. There is a growing body of evidence that lipid peroxidation occurs after severe traumatic brain injury in humans and correlates with the injury severity and mortality. Identification of the products and sources of lipid peroxidation and its enzymatic or non-enzymatic nature is essential for the design of mechanism-based therapies. Recent progress in mass spectrometry-based lipidomics/oxidative lipidomics offers remarkable opportunities for quantitative characterization of lipid peroxidation products, providing guidance for targeted development of specific therapeutic modalities. In this review, we critically evaluate previous attempts to use non-specific antioxidants as neuroprotectors and emphasize new approaches based on recent breakthroughs in understanding of enzymatic mechanisms of lipid peroxidation associated with specific death pathways, particularly apoptosis. We also emphasize the role of different phospholipases (calcium-dependent and -independent) in hydrolysis of peroxidized phospholipids and generation of pro- and anti-inflammatory lipid mediators.

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Section: Therapeutic Strategies Targeting Lipid Peroxidationmentioning

confidence: 99%

Therapies targeting lipid peroxidation in traumatic brain injury

2016

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“…As overall 28-day mortality was high (58%), a substantial part of the data were probably analysed without consent. In another trial [4], diligent attempts to contact the relative were made and an independent physician was consulted before it was deemed necessary to waive consent. If attempts to contact relatives continued to be unsuccessful, or if the patient died before relatives could be contacted, the institutional review board was notified, and data were used.…”

Section: Previous Experience In Patients Who Died Before Obtained Defmentioning

confidence: 99%

“…If attempts to contact relatives continued to be unsuccessful, or if the patient died before relatives could be contacted, the institutional review board was notified, and data were used. Summarizing, in these studies [1, 2, 4], data were used if the patient died before deferred consent was obtained, and reasonable efforts were made to obtain permission from a patient representative.…”

Section: Previous Experience In Patients Who Died Before Obtained Defmentioning

confidence: 99%

“…Deferred consent involves randomization at the investigator's discretion according to criteria that have been explicit during ethical review of the protocol, followed by the request for patient's (deferred subject consent) or representative's (deferred proxy consent) informed consent in a later phase. Several emergency trials have used deferred consent [1, 2, 3, 4]. …”

Section: Introductionmentioning

confidence: 99%

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Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not?

et al. 2007

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“…The relatively long therapeutic time window of eight hours in the administration of the drug may explain the failure of SOD to exhibit protective effect in this clinical trial. [64]…”

Section: Human Superoxide Dismutase (Sod)/superoxide Dismutase Like Mmentioning

confidence: 99%

Antioxidants: The new frontier for translational research in cerebroprotection

Tewari

Mahendru

Bilotta

2014

J Anaesthesiol Clin Pharmacol

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It is important for the anesthesiologist to understand the etiology of free radical damage and how free-radical scavengers attenuate this, so that this knowledge can be applied to diverse neuro-pathological conditions. This review will concentrate on the role of reactive species of oxygen in the pathophysiology of organ dysfunction, specifically sub arachnoid hemorrhage (SAH), traumatic brain injury (TBI) as well as global central nervous system (CNS) hypoxic, ischemic and reperfusion states. We enumerate potential therapeutic modalities that are been currently investigated and of interest for future trials. Antioxidants are perhaps the next frontier of translational research, especially in neuro-anesthesiology.

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Effects of Pegorgotein on Neurologic Outcome of Patients With Severe Head Injury

Cited by 145 publications

References 12 publications

Therapies targeting lipid peroxidation in traumatic brain injury

Therapies targeting lipid peroxidation in traumatic brain injury

Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not?

Antioxidants: The new frontier for translational research in cerebroprotection

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