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.

Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury.

Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.

Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention.

Systematic review and meta-analysis of noninvasive cranial nerve neuromodulation for nervous system disorders.

Objective: To systematically review the medical literature and comprehensively summarize clinical research done on rehabilitation with a novel portable and noninvasive electrical stimulation device called the cranial nerve noninvasive neuromodulator in patients suffering from nervous system disorders.

Data Sources: PubMed, MEDLINE, and Cochrane Database of Systematic Reviews from 1966 to March 2013.

Study Selection: Studies were included if they recruited adult patients with peripheral and central nervous system disorders, were treated with the cranial nerve noninvasive neuromodulator device, and were assessed with objective measures of function.

Effect of combined nicotine and shrapnel exposure on pain measures and gait after nerve injury.

A significant fraction of military soldiers sustain nerve injury and use tobacco or nicotine containing products. Healing of nerve injuries is influenced by many factors, such as degree of original injury, healing potential of the nerve, and general health of patient. However, recently, it has been demonstrated that the presence of retained insoluble metal fragments decreases healing.

Role of growth factors in improved skin flap viability caused by phosphodiesterase-5 inhibitor.

Flap necrosis is one of the major complications of reconstructive surgery and sildenafil citrate has been shown to decrease flap necrosis in preclinical animal models. However, the mechanisms underlying sildenafil's therapeutic efficacy are not known. As with other phosphodiesterase 5 selective inhibitors, sildenafil causes vasodilation and enhanced blood flow.

The effect of high fat-induced obesity on cardiovascular and physical activity and opioid responsiveness in conscious rats.

Both obesity and increased endorphin production are associated with an increase in blood pressure. We have previously demonstrated that the acute and chronic central nervous system (CNS) administration of beta-endorphin can increase or decrease blood pressure, respectively. Also high fat (HF) diet-induced obesity is associated with increased hypothalamic mu opioid receptors and increased blood pressure in response to ss-endorphins.

The cardiovascular responses to mu opioid agonist and antagonist in conscious normal and obese rats.

Beta-endorphin decreases blood pressure in normal rats but increases blood pressure in obese rats. Since beta-endorphins can bind both mu opioid and kappa-opioid receptors we investigated the effect of a mu specific receptor agonist, D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and a mu specific antagonist, D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) on cardiovascular responses in conscious control and obese rats. Rats were also implanted with telemetry transmitters and intracerebroventricular (ICV) cannulas for recording and peptide administration.