Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration

The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.     

A-FABP and Oxidative Stress Underlie the Impairment of Endothelium-Dependent Relaxations to Serotonin and the Intima-Medial Thickening in the Porcine Coronary Artery with Regenerated Endothelium

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Surgical Outcomes and Complications after Occipito-Cervical Fusion Using the Screw-Rod System in Craniocervical Instability

Objective

Although there is no consensus on the ideal treatment of the craniocervical instability, biomechanical stabilization and bone fusion can be induced through occipito-cervical fusion (OCF). The authors conducted this study to evaluate efficacy of OCF, as well as to explore methods in reducing complications.

Methods

A total of 16 cases with craniocervical instability underwent OCF since the year 2002. The mean age of the patients was 51.5 years with a mean follow-up period of 34.9 months. The subjects were compared using lateral X-ray taken before the operation, after the operation, and during last follow-up. The Nurick score was used to assess neurological function pre and postoperatively.

Results

All patients showed improvements in myelopathic symptoms after the operation. The mean preoperative Nurick score was 3.1. At the end of follow-up after surgery, the mean Nurick score was 2.0. After surgery, most patients'' posterior occipito-cervical angle entered the normal range as the pre operation angle decresed from 121 to 114 degree. There were three cases with complications, such as, vertebral artery injury, occipital screw failure and wound infection. In two cases with cerebral palsy, occipital screw failures occurred. But, reoperation was performed in one case.

Conclusion

OCF is an effective method in treating craniocervical instability. However, the complication rate can be quite high when performing OCF in patients with cerebral palsy, rheumatoid arthritis. Much precaution should be taken when performing this procedure on high risk patients.     

Impact of Chronic Simulated Snoring on Carotid Atherosclerosis in Rabbits

Background and Purpose

Chronic simulated snoring was induced in rabbits to determine the impact of snoring on the development of atherosclerosis.

Methods

The pressure wave of induced snoring at the carotid bifurcation of rabbits was acquired by gently pressing the airway. This wave was then simulated using custom-made mechanical devices. Twelve rabbits were used in this study, seven of which were assigned to the experimental group and the remaining five formed the control group. All of the rabbits were raised on a 1% high-cholesterol diet. Either working or sham devices were positioned at the ventral center of the neck in each rabbit. At the end of a 2-month observation period, all of the rabbits were sacrificed by perfusion fixation, the carotid arteries harvested, and the carotid atherosclerosis histology reviewed.

Results

All of the rabbits survived to the end of the experimental period. Blood sampling revealed the presence of hypercholesterolemia in both groups, with no significant difference between them. The presence and degree of atherosclerosis did not differ significantly between the groups.

Conclusions

The findings of this study show the feasibility of making a chronic simulated snoring rabbit model. However, the causative role of snoring in carotid atherosclerosis was not detected in this animal study.     

Altered immune function associated with disordered neural connectivity and executive dysfunctions: A neurophysiological study on children with autism spectrum disorders

Previous studies have shown that children with autism spectrum disorders (ASDs) have impaired executive function, disordered neural connectivity, and abnormal immunologic function. The present study examined whether these abnormalities were associated. Seventeen high-functioning (HFA) and 17 low-functioning (LFA) children with ASD, aged 8–17 years, participated voluntarily in the study. The two groups of children were compared on their general intelligence in terms of IQ; executive function as measured by the Hong Kong List Learning Test, D2 Test of Concentration, Five Point Test, Children's Color Trail Test, Tower of California Test, and Go/No-Go task; a non-executive task as measured by the Picture Completion Task; neural connectivity as measured by theta coherence in the anterior and posterior regions; and immunologic function as measured by the level of circulating CD3+ CD8+ suppressor/cytotoxic T lymphocytes in a blood sample. Results on executive function showed that LFA children performed significantly poorer than HFA children as shown on their lower Executive Composite as well as individual executive function scores. However, there was no group difference on the Picture Completion Task. Results on neural connectivity showed that LFA children demonstrated a different pattern of electroencephalography (EEG) coherence from HFA children as shown in the significantly elevated theta coherence in the anterior network, as well as at the left intra-hemispheric (LA-LP) and right-to-left inter-hemisphere (RA-LP) connections of LFA children. In immunologic function, results showed that LFA children had significantly elevated level of suppressor/cytotoxic T lymphocytes (CD3+ CD8+) (p < 0.05). In addition, the executive dysfunction, disordered neural connectivity, and abnormal immunologic function were found to be associated. These results provided some initial evidence to support the notion that immunologic factors are associated with neuronal damage, measureable by EEG coherence and manifested as executive dysfunctions.     

The Management of Mycotic Aortic Aneurysms: Is there a Role for Endoluminal Treatment?

Background : Mycotic aneurysms are rare. Conventional surgical options include ligation or excision with in-situ or extra-anatomical reconstruction. The use of endoluminal stenting for mycotic aneurysms in the presence of sepsis is controversial, but may be a temporising measure, or sometimes the only option in the management of critically ill patients who are not fit for surgery.

Methods : A literature review was undertaken using Medline, all relevant papers on endoluminal management of mycotic aneurysm were taken into account.

Results : Open surgical repair of mycotic aortic aneurysm is associated with considerable peri-and post-operative morbidity and mortality. Endoluminal treatment with stent-grafts has been introduced as an alternative, and early results are promising.

Conclusion : No level I evidence for the endoluminal treatment of mycotic aneurysms exists. Ideally a randomised controlled trial of open surgery versus endoluminal treatment should be performed but this may be difficult to perform because of the low incidence of infected aneurysms.     

Surgical suture assembled with polymeric drug-delivery sheet for sustained,local pain relief

Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical strength of the suture itself – strength that is essential for successful wound closure. Thus, it is not easy to control drug delivery with sutures, and the drug-delivery surgical sutures available for clinical use are now limited to anti-infection roles. Here, we demonstrate a surgical suture enabled to provide controlled delivery of a pain-relief drug and, more importantly, we demonstrate how it can be fabricated to maintain the mechanical strength of the suture itself. For this purpose, we separately prepare a drug-delivery sheet composed of a biocompatible polymer and a pain-relief drug, which is then physically assembled with a type of surgical suture that is already in clinical use. In this way, the drug release profiles can be tailored for the period of therapeutic need by modifying only the drug-loaded polymer sheet without adversely influencing the mechanical strength of the suture. The drug-delivery sutures in this work can effectively relieve the pain at the surgical site in a sustained manner during the period of wound healing, while showing biocompatibility and mechanical properties comparable to those of the original surgical suture in clinical use.     

Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage

Efficient derivation of neural cells from human embryonic stem cells (hESCs) remains an unmet need for the treatment of neurological disorders. The limiting factors for current methods include being labor-intensive, time-consuming and expensive. In this study, we hypothesize that the substrate topography, with optimal geometry and dimension, can modulate the neural fate of hESCs and enhance the efficiency of differentiation. A multi-architectural chip (MARC) containing fields of topographies varying in geometry and dimension was developed to facilitate high-throughput analysis of topography-induced neural differentiation in vitro. The hESCs were subjected to “direct differentiation”, in which small clumps of undifferentiated hESCs were cultured directly without going through the stage of embryoid body formation, on the MARC with N2 and B27 supplements for 7 days. The gene and protein expression analysis indicated that the anisotropic patterns like gratings promoted neuronal differentiation of hESCs while the isotropic patterns like pillars and wells promoted the glial differentiation of hESCs. This study showed that optimal combination of topography and biochemical cues could shorten the differentiation period and allowed derivation of neurons bearing longer neurites that were aligned along the grating axis. The MARC platform would enable high-throughput screening of topographical substrates that could maximize the efficiency of neuronal differentiation from pluripotent stem cells.     

The Significance of Keratinized Mucosa on Implant Health: A Systematic Review

Background: Whether a minimal width of keratinized mucosa (KM) is required to maintain peri‐implant tissue health has been a topic of interest. This systematic review and meta‐analysis aims to investigate the effect of KM on various peri‐implant health‐related parameters. Methods: An electronic search of five databases (from 1965 to October 2012) and a hand search of peer‐reviewed journals for relevant articles were performed. Human cross‐sectional or longitudinal studies with data on the relationship between the amount of KM around dental implants and various peri‐implant parameters, with a follow‐up period of at least 6 months, were included. Results: Eleven studies, seven cross‐sectional and four longitudinal, were included. Weighted mean difference (WMD) and confidence interval (CI) were calculated with meta‐analyses for each clinical parameter. The results showed statistically significant differences in plaque index (PI) and modified PI (WMD = ?0.27, 95% CI = ?0.43 to ?0.11), modified gingival index (mGI) (WMD = ?0.48, 95% CI = ?0.70 to ?0.27), mucosal recession (MR) (WMD = ?0.60 mm, 95% CI = ?0.85 to ?0.36 mm), and attachment loss (AL) (WMD = ?0.35 mm, 95% CI = ?0.65 mm to ?0.06 mm), all favoring implants with wide KM. However, comparisons of other parameters (bleeding on probing, modified bleeding index, GI, probing depth, and radiographic bone loss) did not reach statistically significant differences. The result of heterogeneity test showed only one parameter (AL, P value for the χ² test = 0.30 and I² test = 18%) had a low degree of heterogeneity among analyzed studies; meta‐analyses of other parameters presented moderate‐to‐high degree of heterogeneity. Limitations of the present review include limited number of selected studies (n = 11), existence of heterogeneity and publication bias, and only English‐written articles searched. Conclusion: Based on current available evidence, a lack of adequate KM around endosseous dental implants is associated with more plaque accumulation, tissue inflammation, MR, and AL.