Drugs and the autonomic nervous system

The nervous systems can initially be divided up into the central and peripheral nervous systems. The central nervous system is the brain and spinal cord and drugs that modify the central nervous system are considered as a subject in systematic pharmacology (therapeutics) section. Everything neural, other that the central nervous system, can be considered peripheral nervous systems. The peripheral nervous systems can be divided into the autonomic(involuntary) nervous system, which is the system that performs without your conscious help, and the somatic or voluntary nervous system, which you can consciously control(Figure 7.1). In addition the autonomic nervous system is divided into the sympathetic and parasympathetic nervous systems...

A generative nervous system for the planet

Generative systems are now being proposed for addressing major ecological problems. The Complex Urban Systems Project (CUSP) founded in 2008 at the Queensland University of Technology, emphasises the ecological significance of the generative global networking of urban environments. It argues that the natural planetary systems for balancing global ecology are no longer able to respond sufficiently rapidly to the ecological damage caused by humankind and by dense urban conurbations in particular as evidenced by impacts such as climate change. The proposal of this research project is to provide a high speed generative nervous system for the planet by connecting major cities globally to interact directly with natural ecosystems to engender rapid ecological response. This would be achieved by active interactions of the global urban network with the natural ecosystem in the ecological principle of entropy. The key goal is to achieve ecologically positive cities by activating self-organising cities capable of full integration into natural eco-systems and to netowork the cities globally to provide the planet with a nervous system.

Drugs and the somatic nervous system

Drugs and the somatic nervous system 8.1 The somatic nervous system 8.2 Anticholinesterases 8.3 Neuromuscular blockers 8.4 Botox

Variability in odour reception in the peripheral sensory system of Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

Mixtures of single odours were used to explore the receptor response profile across individual antennae of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae). Seven odours were tested including floral and green-leaf volatiles: phenyl acetaldehyde, benzaldehyde, β-caryophyllene, limonene, α-pinene, 1-hexanol, 3Z-hexenyl acetate. Electroantennograms of responses to paired mixtures of odours showed that there was considerable variation in receptor tuning across the receptor field between individuals. Data from some moth antennae showed no additivity, which indicated a restricted receptor profile. Results from other moth antennae to the same odour mixtures showed a range of partial additivity. This indicated that a wider array of receptor types was present in these moths, with a greater percentage of the receptors tuned exclusively to each odour. Peripheral receptor fields show variation in the spectrum of response within a population (of moths) when exposed to high doses of plant volatiles. This may be related to recorded variation in host choice within moth populations as reported by other authors.

EdU, a new thymidine analogue for labelling proliferating cells in the nervous system

The standard method of labelling proliferating cells uses the thymidine analogue, bromodeoxyuridine (BrdU), which incorporates into the DNA during S-phase of the cell cycle. A disadvantage of this method is that the immunochemical processing requires pre-treatment of the cells and tissue with heat or acid to reveal the antigen. This pre-treatment reduces reliability of the method and degrades the specimen, reducing the ability for multiple immuno-fluorescence labelling at high resolution. We report here the utility of a novel thymidine analogue, ethynyl deoxyuridine (EdU), detected with a fluorescent azide via the “click” chemistry reaction (the Huisgen 1,3-dipolar cycloaddition reaction of an organic azide to a terminal acetylene). The detection of EdU requires no heat or acid treatment and the incorporated EdU is covalently conjugated to fluorescent probe. The reaction is quick and compatible with fluorescence immunochemistry and other fluorescent probes. We show here that EdU is non-toxic in vitro and in vivo and can be used in place of BrdU to label cells during neurogenesis and the progeny identified at least 30 days later. The fluorescent labelling of EdU, markedly improves the detection of proliferating cells and allows concurrent high resolution fluorescence immunochemistry.

Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Semaphorin–plexin signalling genes associated with human breast tumourigenesis

Introduction Gene expression profiling has enabled us to demonstrate the heterogeneity of breast cancers. The potential of a tumour to grow and metastasise is partly dependant on its ability to initiate angiogenesis or growth and remodelling of new blood vessels, usually from a pre-existing vascular network, to ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells along with access to the systemic circulation. Cell–cell signalling of semaphorin ligands through interaction with their plexin receptors is important for the homeostasis and morphogenesis of many tissues and has been widely studied for a role in neural connectivity, cancer, cell migration and immune responses. This study investigated the role of four semaphorin/plexin signalling genes in human breast cancers in vivo and in vitro. Materials and methods mRNA was extracted from formalin fixed paraffin embedded archival breast invasive ductal carcinoma tissue samples of progressive grades (grades I–III) and compared to tissue from benign tumours. Gene expression profiles were determined by microarray using the Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays and validated by Q-PCR using a Corbett RotorGene 6000. Following validation, the gene expression profile of the identified targets was correlated with those of the human breast cancer cell lines MCF-7 and MDA-MD-231. Results The array data revealed that 888 genes were found to be significantly (p ≤ 0.05) differentially expressed between grades I and II tumours and 563 genes between grade III and benign tumours. From these genes, we identified four genes involved in semaphorin–plexin signalling including SEMA4D which has previously been identified as being involved in increased angiogenesis in breast cancers, and three other genes, SEMA4F, PLXNA2 and PLXNA3, which in the literature were associated with tumourigenesis, but not directly in breast tumourigenesis. The microarray analysis revealed that SEMA4D was significantly (P = 0.0347) down-regulated in the grade III tumours compared to benign tumours; SEMA4F, was significantly (P = 0.0159) down-regulated between grades I and II tumours; PLXNA2 was significantly (P = 0.036) down-regulated between grade III and benign tumours and PLXNA3 significantly (P = 0.042) up-regulated between grades I and II tumours. Gene expression of SEMA4D was validated using Q-PCR, demonstrating the same expression profile in both data sets. When the sample set was increased to incorporate more cases, SEMA4D continued to follow the same expression profile, including statistical significance for the differences observed and small standard deviations. In vitro the same pattern was present where expression for SEMA4D was significantly higher in MDA-MB-231 cells when compared to MCF-7 cells. The expression of SEMA4F, PLXNA2 and PLXNA3 could not be validated using Q-PCR, however in vitro analysis of these three genes revealed that both SEMA4F and PLXNA3 followed the microarray trend in expression, although they did not reach significance. In contrast, PLXNA2 demonstrated statistical significance and was in concordance with the literature. Discussion We, and others, have proposed SEMA4D to be a gene with a potentially protective effect in benign tumours that contributes to tumour growth and metastatic suppression. Previous data supports a role for SEMA4F as a tumour suppressor in the peripheral nervous system but our data seems to indicate that the gene is involved in tumour progression in breast cancer. Our in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. Finally, our in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours. Conclusions Semaphorins and their receptors, the plexins, have been implicated in numerous aspects of neural development, however their expression in many other epithelial tissues suggests that the semaphorin–plexin signalling system also contributes to blood vessel growth and development. These findings warrant further investigation of the role of semaphorins and plexins and their role in normal and tumour-induced angiogenesis in vivo and in vitro. This may represent a new front of attack in anti-angiogenic therapies of breast and other cancers.

Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers - Duffy (Fy), antithrombin III (AT3), renin (REN), β-nerve growth factor (NGFB), and salivary amylase (AMY1) - in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate that possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

Acetylcholine receptor antibody in the diagnosis of myasthenia gravis

The acetylcholine receptor (AchR) antibody assay has a key role in the diagnosis of myasthenia gravis. In this article, the role of AchR antibody assay in the diagnosis of ocular and generalized myasthenia gravis is reviewed, and compared to standard means of diagnosing the disease by clinical and electrophysiological methods.