Showing papers by "V. Wee Yong published in 2011"

Predominance of Th2 polarization by Vitamin D through a STAT6-dependent mechanism

Abstract: Background Vitamin D has several reported immunomodulatory properties including the reduced generation of pro-inflammatory CD4+ T helper 1 (Th1) cells and the increase in levels of the anti-inflammatory Th2 subset. Less clear has been the impact of vitamin D on the pro-inflammatory Th17 subset, and whether and how vitamin D may preferentially drive the polarization of one of the T helper subsets.

Inflammatory and structural biomarkers in acute traumatic spinal cord injury

Abstract: The paralysis of an acute spinal cord injury (SCI) remains a catastrophic condition for which there are currently no effective treatments. While the diagnosis of acute traumatic SCI is typically quite easy to make, distinguishing the exact degree of severity and prognosticating the extent of neurologic recovery are challenging. Functional neurologic measures are currently used to stratify injury severity and predict neurologic outcome. However, these measures are often impossible to determine in acutely injured patients. Additionally, for patients deemed to be of a specific injury severity, the variability in spontaneous neurologic recovery is high. Both of these issues severely impair the ability to perform clinical trials in novel therapies for SCI. Biomarkers that could more precisely define the severity of injury and better predict neurologic outcome would be extremely valuable. Furthermore, biological surrogate outcomes measures would be very useful in small preliminary clinical trials of novel therapies if they could inform decisions around the therapeutic regimen for subsequent larger clinical trials. This review highlights our ongoing work in establishing biomarkers for SCI using cerebrospinal fluid samples from acutely injured patients.

A quantitative analysis of suspected environmental causes of MS.

Abstract: Contexte: La sclerose en plaques (SP) est une maladie consideree comme ayant des causes environnementales. Des correlations concordantes ont ete etablies dans differents contextes pour la latitude, l'exposition au tabagisme, la lumiere du soleil et le deficit en vitamine D. Nous avons analyse la contribution de differents facteurs environnementaux au risque de developper la SP a partir d'une perspective populationnelle. Methodes: Nous avons collige les donnees globales de 54 etudes sur la prevalence de la SP au cours des 10 annees anterieures et nous avons calcule le degre de risque attribuable a la latitude, la longitude, la radiation ultraviolette (UV) (donnees obtenues par satellite de la NASA et adaptees selon les heures d'ensoleillement) les taux de tabagisme des populations (donnees de l'OMS), le sexe, la date de l'etude, les donnees demographiques de l'etude ainsi que plusieurs facteurs socioeconomiques. Nous rapportons une correlation negative tres significative entre la prevalence de la SP et la radiation UV. Resultats: Le manque de radiation UV a plus d'influence que les autres facteurs dans une proportion d'au moins 20 fois (p < 10^-8) a l'analyse de regression univariee. L'analyse de regression multiple a montre que la latitude et la longitude sont egalement des facteurs significatifs et que le tabagisme peut jouer un role minime. Les huit etudes de prevalence scandinaves ont revele des prevalences plus faibles que prevu etant donne la position geographique. Conclusions: La radiation UV disponible est un facteur environnemental significatif qui est plus important que tous les autres facteurs examines.

Targeting progressive neuroaxonal injury: lessons from multiple sclerosis.

Abstract: Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuroaxonal injury, suggesting a common pathophysiological pathway. Identification and development of neuroprotective therapies for such diseases has proven a major challenge, particularly because of an already substantial neuroaxonal compromise at the time of initial onset of clinical symptoms. Methods for early identification of neurodegeneration are therefore vital to ensure that neuroprotective therapies are applied as early as possible. Recent investigations have enhanced our understanding of the role of neuroaxonal injury in multiple sclerosis (MS). As MS generally manifests earlier in life and can be diagnosed much earlier in the course of the disease than the above-mentioned 'classic' neurodegenerative diseases, it is possible that MS could be used as a model disease to study degeneration and regeneration of the CNS. The mechanism of neuroaxonal injury in MS is believed to be inflammation-led neurodegeneration; however, the reverse may also be true (i.e. neuroaxonal degeneration may precede inflammation). Animal models of PD, AD and ALS have shown that it is likely that most cases of disease are due to initial inflammation, followed by a degenerative process, providing a parallel between MS and the classic neurodegenerative diseases. Other common factors between MS and the neurodegenerative diseases include iron and mitochondrial dysregulation, abnormalities in α-synuclein and tau protein, and a number of immune mediators. Conventional MRI techniques, using markers such as T2-weighted lesions, gadolinium-enhancing lesions and T1-weighted hypointensities, are readily available and routinely used in clinical practice; however, the utility of these MRI measures to predict disease progression in MS is limited. More recently, MRI techniques that provide more pathology-specific data have been applied in MS studies, including magnetic resonance spectroscopy, magnetization transfer ratio and myelin water imaging. Optical coherence tomography (OCT) is a non-MRI technique that quantifies optic nerve integrity and retinal ganglion cell loss as markers of neuroaxonal injury; more research is needed to evaluate whether information obtained from OCT is a reliable marker of axonal injury and long-term disability in MS. Using these advanced techniques, it may become possible to follow degeneration and regeneration longitudinally in patients with MS and to better differentiate the effects of drugs under investigation. Currently available immune-directed therapies that are approved by the US FDA for the first-line treatment of MS (interferon-β and glatiramer acetate) have been shown to decelerate the inflammatory process in MS; however, such therapy is less effective in preventing the progression of the disease and neuroaxonal injury. The use of MS as a clinical model to study modulation of neuroaxonal injury in the brain could have direct implications for the development of treatment strategies in neurodegenerative diseases such as AD, PD and ALS.