Axonal regeneration and physiological activity following transection and immunological disruption of myelin within the hatchling chick spinal cord

Transections of the chicken spinal cord after the developmental onset of myelination at embryonic day (E) 13 results in little or no functional regeneration. However, intraspinal injection of serum complement proteins with complement-binding GalC or 04 antibodies between E9-E12 results in a delay of the onset of myelination until E17. A subsequent transection of the spinal cord as late as E15 (i.e., during the normal restrictive period for repair) results in neuroanatomical regeneration and functional recovery. Utilizing a similar immunological protocol, we evoked a transient alteration of myelin structure in the posthatching (P) chicken spinal cord, characterized by widespread "unravelling" of myelin sheaths and a loss of MBP immunoreactivity (myelin disruption). Myelin repair began within 7 d of cessation of the myelin disruption protocol. Long term disruption of thoracic spinal cord myelin was initiated after a P2-P10 thoracic transection and maintained for > 14 d by intra-spinal infusion of serum complement proteins plus complement-binding GalC or 04 antibodies. Fourteen to 28 d later, retrograde tract tracing experiments, including double-labeling protocols, indicated that approximately 6-19% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked peripheral nerve activity in paralyzed preparations, as well as leg muscle activity patterns typical of stepping in unparalyzed animals. This indicated that a transient alteration of myelin structure in the injured adult avian spinal cord facilitated brainstem-spinal axonal regrowth resulting in functional synaptogenesis with target neurons.     

Comparison of three-dimensional surface scanning techniques for capturing the external ear

Congenital facial anomalies, such as microtia (malformation of the external ear), lead to significant psychosocial effects starting from early childhood. Three-dimensional (3D) scanning and advanced manufacturing are being investigated as a cheaper and more personalised method of fabricating reconstructive treatments for patients compared to traditional approaches. To date, most case studies have used expensive 3D scanners, yet, there is potential for low-cost devices to provide comparable results. This study aimed to investigate these different approaches. Both ears of 16 adult participants were scanned with three devices: Artec Spider (Artec Group), Intel^® RealSense? (Intel), and the Apple iPhone^® 7 (Apple Inc.) combined with photogrammetry using 90, 60 and 30 photographs. The scanning time, processing time, accuracy, completeness, resolution and repeatability of each technique were assessed using the Artec Spider as a reference scanner. Our results show that the iPhone had the longest processing time however, this decreased nine-fold when reducing the number of photos from 90 to 30. There was no significant difference in the accuracy, completeness or repeatability of the iPhone scans with 90 photographs (1.4?±?0.6?mm, 79.9%, 1.0?±?0.1?mm), 60 photographs (1.2?±?0.2, 79.3%, 0.9?±?0.2?mm) or 30 photographs (1.2?±?0.3?mm, 74.3%, 1.0?±?0.2?mm). The Intel RealSesne performed significantly worse in each parameter (1.8?±?03?mm; 46.6%, 1.4?±?0.5). Additionally, the RealSense had significantly lower resolution with not enough detail captured for the application. These results demonstrate that the ear can be accurately 3D scanned using iPhone photographs. We would recommend capturing between 30 and 60 photographs of the ear to create a scan that is accurate but without the downfall of long processing time. Using these methods we aim to provide a more comfortable setting for the patient and a lower-cost and more personalised ear prosthesis.     

K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.     

Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

The effect of nitric oxide (NO) donors on high-voltage-activated Ca2+ channels in insulin-secreting RINm5F cells was investigated using the patch-clamp technique in the whole-cell configuration. Sodium nitroprusside (SNP, 2-400 microM) induced a dose-dependent reduction in Ba2+ currents with maximal inhibition of 58%. The IC50 for SNP was 45 microM. A different NO donor, (+/-)S-nitroso-N-acetylpenicillamine (SNAP, 500 microM), also produced a 50% decrease in current amplitude. When 200 microM SNP was administered together with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidozoline-1-oxyl-3-oxide (carboxy-PTIO, 300 microM), the Ba2+ current inhibition was lowered to 7%. Administration of 500 microM 8-bromoguanosine 3':5'-cyclic monophosphate sodium salt (8-Br-cGMP) mimicked the effects of SNP, causing a comparable decrease (56%) in peak-current amplitude. When soluble guanylyl cyclase was blocked by 10 microM 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), the inhibitory effect of 200 microM SNP was reduced from 39% to 15%. The SNP-induced current decrease was 36% of controls after the blockade of L-type Ca2+ channels and 30% in the presence of 2.5 microM omega-conotoxin-MVIIC. These data indicate that NO inhibits both L-type and P/Q-type Ca2+ channels in RINm5F cells, probably by an increase in the intracellular levels of cGMP. NO may then significantly influence the Ca2+-dependent release of hormones from secretory cells as well as that of neurotransmitters from nerve terminals.     

Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain

Adenovirus-mediated gene transfer into the brain is associated with significant inflammation and activation of anti-vector and anti-transgene immune responses that curtail the gene delivery of adenoviruses and therapeutic efficacy. Elucidating the molecular mediators of inflammatory and immune responses to adenoviruses injected into the brain should allow us to inhibit their inflammatory actions, thereby reducing vector clearance and enhance adenoviral-mediated gene transfer into the CNS. Cytokines are primary mediators of the immune response and are released during inflammation. Here we report for the first time that injection of replication-deficient adenovirus vectors into the cerebral ventricles of rats causes a rapid increase in body temperature. This fever response precedes any vector-encoded transgene expression and occurs with vectors encoding no transgene, as well as with vectors encoding a therapeutic transgene i.e., HSV1-thymidine kinase. No fever is detected after infection of the striatum, an important brain target in studies on neurodegeneration. After infection of the brain ventricles, CSF levels of immunoreactive tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta increase significantly (up to 300-fold). In the hypothalamus, the locus of thermoregulation in the brain, only IL-1beta and IL-6 are significantly elevated. A neutralizing TNF-alpha antibody has no effect on adenovirus-induced fever. However, pretreatment with either the IL-1 receptor antagonist or the cyclooxygenase inhibitor flurbiprofen completely abolishes adenovirus-induced fever, suggesting that IL-1 and prostaglandins are direct mediators of this response. These results are the first to demonstrate that IL-1, but not TNF-alpha, is the main mediator of a very early inflammatory response to adenovirus in the brain.     

Regulation of a Physiological Parameter or In Vivo Drug Concentration by Integral Pulse Frequency Modulated Bolus Drug Injections

This paper describes the designs for two novel, nonlinear, discrete, drug injection controllers. The basis for these controllers is integral pulse frequency modulation (IPFM). An IPFM controller injects small boluses of a drug into a pharmacokinetic (PK) plant to achieve regulation of the plant output. Bolus injections are advantageous because they provide a precise knowledge of the times and the cumulative amount of drug injected, and they require a discrete-action pump suitable for digital control, miniaturization, and implantation.     

Lesions of the dorsal spinal cord decrease the duration of contact defensive immobility (animal hypnosis) in the rabbit.

22 male New Zealand albino rabbits received either bilateral dorsal or unilateral dorsolateral spinal cord lesions. The duration and incidence of contact defensive immobility (CDI) were tested in these Ss and in 10 intact controls. Neither of the spinal cord lesions affected the number of CDI inductions, but Ss with lesions of the dorsal spinal cord exhibited significantly shorter durations of CDI than either of the other groups, which did not differ from each other. Results indicate that the somesthetic systems that ascend in the dorsal spinal cord are important for the maintenance, but not the initiation, of CDI. It is suggested that the reduction of excitatory drive to neurons of the reticular zones of the dorsal column nuclei produced by transection of the dorsal spinal cord provides the physical basis for the reduction of CDI duration. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)