Energy Losses (Gains) of Massive Coloured Particles in Stochastic Colour Medium

The propagation of massive coloured particles in stochastic background chromoelectric field is studied using the semiclassical equations of motion. Depending on the nature of the stochastic background we obtain the formulae for the energy losses of heavy coloured projectile in nonperturbative hadronic medium and for the energy gains in the stochastic field present, e.g., in the turbulent plasma. The result appears to be significantly dependent on the form of the correlation function of stochastic external fieldComment: 9 pages, BI-TP 94/15, plain LaTe

Development, characterization, and in vivo validation of a humanized C6 monoclonal antibody that inhibits the membrane attack complex

Damage and disease of nerves activates the complement system. We demonstrated that activation of the terminal pathway of the complement system leads to the formation of the membrane attack complex (MAC) and delays regeneration in the peripheral nervous system. Animals deficient in the complement component C6 showed improved recovery after neuronal trauma. Thus, inhibitors of the MAC might be of therapeutic use in neurological disease. Here, we describe the development, structure, mode of action, and properties of a novel therapeutic monoclonal antibody, CP010, against C6 that prevents formation of the MAC in vivo. The monoclonal antibody is humanized and specific for C6 and binds to an epitope in the FIM1-2 domain of human and primate C6 with sub-nanomolar affinity. Using biophysical and structural studies, we show that the anti-C6 antibody prevents the interaction between C6 and C5/C5b by blocking the C6 FIM1-2:C5 C345c axis. Systemic administration of the anti-C6 mAb caused complete depletion of free C6 in circulation in transgenic rats expressing human C6 and thereby inhibited MAC formation. The antibody prevented disease in experimental autoimmune myasthenia gravis and ameliorated relapse in chronic relapsing experimental autoimmune encephalomyelitis in human C6 transgenic rats. CP010 is a promising complement C6 inhibitor that prevents MAC formation. Systemic administration of this C6 monoclonal antibody has therapeutic potential in the treatment of neuronal disease.Molecular Epidemiolog

A review of diagnostic and functional imaging in headache

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache — the posterior hypothalamic grey matter — and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally

Optical coherence tomography in acute optic neuritis: a population-based study

OBJECTIVES: To measure early structural damage caused by autoimmune inflammatory optic neuritis (ON) by optical coherence tomography (OCT) in a population-based cohort. METHODS: In a prospective population-based study over 24 months in Southern Denmark, patients diagnosed with acute ON and without prior diagnosis of a chronic neuroinflammatory disorder were included and examined with OCT, visual evoked potentials (VEP), visual fields, high contrast visual acuity (HCVA), and low contrast letter acuity (LCLA). Structural and functional outcomes were determined at 6-month follow-up based on interocular differences. RESULTS: The 50 included patients had on average 16.9 μm peripapillary retinal nerve fiber layer loss, 10.6 μm ganglion cell and inner plexiform layer (GCIP) loss, and an average HCVA decrease of 0.22 dec. Based on a linear regression model, average GCIP loss amounted to -0.2 μm per day and started 8 days after onset. OCT outcomes but not VEP correlated well with all visual function measurements at follow-up. Structural and functional damage in 20 patients (40%) diagnosed de novo with multiple sclerosis (MS) and in 2 patients (4%) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) test did not differ from patients with idiopathic ON. CONCLUSIONS: Optic neuritis causes substantial retinal damage and vision loss independent of the underlying disease. Our study supports that GCIP damage starts closely to clinical onset. Good structure-function correlations between OCT and vision support the importance of OCT in monitoring acute ON

Systematic mechanism-orientated approach to chronic pancreatitis pain

Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders

Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial

Item does not contain fulltextBACKGROUND & AIMS: Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain disorders. We investigated whether agents used to treat patients with neuropathic pain are effective in CP. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the effects of the gabapentoid pregabalin as an adjuvant analgesic. We measured pain relief, health status, quality of life, and tolerability in 64 patients with pain from CP; they were randomly assigned to groups given increasing doses of pregabalin or placebo (control) for 3 consecutive weeks. The primary end point was pain relief, based on a visual analogue scale documented by a pain diary. Secondary end points included Patients' Global Impression of Change (PGIC) score, changes in physical and functional scales, pain character, quality of life, and tolerability. RESULTS: Pregabalin, compared with placebo, caused more effective pain relief after 3 weeks of treatment (36% vs 24%; mean difference, 12%; 95% confidence interval, 22%-2%; P = .02). The percentage of patients with much or very much improved health status (PGIC score) at the end of the study was higher in the pregabalin than the control group (44% vs 21%; P = .048). Changes in physical and functional scales, pain character, quality of life, and number of serious adverse events were comparable between groups. CONCLUSIONS: In a placebo-controlled trial, pregabalin is an effective adjuvant therapy for pain in patients with CP