Immunopathology of terminal complement activation and complement C5 blockade creating a pro-survival and organ-protective phenotype in trauma.

Background And Purpose: Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo.

HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma.

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 h after admission.

An Open-Globe Porcine Injury Platform for Assessing Therapeutics and Characterizing Biological Effects.

Open-globe injuries can result in permanent vision loss, partly due to extended delays between injury and medical intervention. Even with early intervention, the management of open-globe injuries remains a challenge for ophthalmologists, mostly due to inadequate or suboptimal current therapies. To aid in the development of novel therapeutics and track toxicological and pathophysiological changes, this article details an open-globe injury platform capable of inducing injuries in enucleated porcine eyes.

Development and Characterization of a Benchtop Corneal Puncture Injury Model.

During recent military operations, eye-related injuries have risen in frequency due to increased use of explosive weaponry which often result in corneal puncture injuries. These have one of the poorest visual outcomes for wounded soldiers, often resulting in blindness due to the large variations in injury shape, size, and severity. As a result, improved therapeutics are needed which can stabilize the injury site and promote wound healing.

Blast Exposure Induces Ocular Functional Changes with Increasing Blast Over-pressures in a Rat Model.

: Blast-related brain and ocular injuries can lead to acute and chronic visual dysfunction. The chronic visual consequences of blast exposure and its progression remain unclear. The goal of this study is to analyze ocular functional response to four levels of blast exposure and identify a threshold of blast exposure leading to acute and chronic visual dysfunction.

Early Complement and Fibrinolytic Activation in a Rat Model of Blast-Induced Multi-Organ Damage.

Objective: Blast injury is associated with multi-organ failure (MOF), causing significant morbidity and mortality in trauma patients. However, the pathogenesis of blast-induced MOF still remains obscure. In this study, we evaluate the pathophysiological changes related to blast-induced MOF in a clinically relevant rat model of blast injury.

Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-μs pulses.

The laser-induced retinal injury thresholds for repetitive-pulse exposures to 100-μs-duration pulses at a wavelength of 532 nm have been determined for exposures of up to 1000 pulses in an in vivo model. The ED50 was measured for pulse repetition frequencies of 50 and 1000 Hz. Exposures to collimated beams producing a minimal retinal beam spot and to divergent beams producing a 100-μm-diameter retinal beam spot were considered.

Damage threshold from large retinal spot size repetitive-pulse laser exposures.

The retinal damage thresholds for large spot size, multiple-pulse exposures to a Q-switched, frequency doubled Nd:YAG laser (532 nm wavelength, 7 ns pulses) have been measured for 100 μm and 500 μm retinal irradiance diameters. The ED50, expressed as energy per pulse, varies only weakly with the number of pulses, n, for these extended spot sizes. The previously reported threshold for a multiple-pulse exposure for a 900 μm retinal spot size also shows the same weak dependence on the number of pulses.

Variation of laser-induced retinal injury thresholds with retinal irradiated area: 0.1-s duration, 514-nm exposures.

The retinal injury threshold dose for laser exposure varies as a function of the irradiated area on the retina. Zuclich reported thresholds for laser-induced retinal injury from 532 nm, nanosecond-duration laser exposures that varied as the square of the diameter of the irradiated area on the retina. We report data for 0.

Retinal injury thresholds for blue wavelength lasers.

The interaction mechanism leading to laser-induced retinal alteration can be thermal or non-thermal, depending upon the wavelength of the laser radiation and the duration of the exposure. To investigate the effect of exposure duration on the interaction mechanism, retinal injury thresholds in the rhesus monkey were experimentally measured for exposure to laser radiation at wavelengths of 441.6, 457.

Near-UV/blue light-induced fluorescence in the human lens: potential interference with visual function.

Irradiation of the ocular lens of numerous species by near-UV or short-visible wavelengths induces a blue-green fluorescence, which can be a source of intraocular veiling glare. Wavelengths longer than the approximately 365-nm lens absorption peak induce progressively weaker but also progressively more red-shifted fluorescence emission. The more red-shifted emission has a higher luminous efficiency and, in fact, earlier studies in this laboratory have demonstrated that the lens fluorescence in the nonhuman primate yields an approximately constant luminous efficiency when excited by equal radiant exposures over the wavelength range from 350 to 430 nm.