System nervous

The nervous systems of helminths, including cestodes, have been reviewed by Falkmer et al. (207), Gustafsson (278), Halton (289), Rohde (707) Shisov (758) Sukhdeo Mettrick (828) and Lumsden Hildreth (458). It has been stressed that the borderline between the nervous system and the endocrine system has become indistinct and the two parts are now dealt with under the common name neuroendocrine system (278). 

Representative species investigated by these and other techniques such as TEM include the following Dipylidium caninum (755, 756), Diphyllobothrium dendriticum (277,280-283), Echinococcus granulosus (570), Hymenolepis diminuta (462,966), H. microstoma (936, 937, 941, 943), H. nana (202, 206, 966), Mesocestoides sp. (304), 

Moniezia expartsa (408), Oochoristica sigmoides (411), Pelichnobothrium spedosum (260), and Raillietina spp. (411, 717). 

The gross anatomy of the nervous system is known for very few species. That of adult H. nana (206, 966) is shown in Fig. 2.9 and that of larval Mesocestoides sp. (304) in Fig. 2.8. 

In cestodes, most, perhaps all, of the neural elements are found in the ganglia of the scolex and the main nerve tracts. In these, the cell bodies are arranged peripherally around a core made up of a tangled mass of neuronal processes often referred to as neurites because it is impossible to distinguish between axons and dendrites. This mass constitutes the so-called neuropile . Like all differentiated cells in cestodes - and probably in all invertebrates - nerve cells are incapable of mitosis and hence new nerve cells must arise directly from the germinative ( = stem) cells (276). In D. dendriticum, the neuropile is composed of a dense network of unmyelinated nerve fibres with no extracellular stroma between the fibres (277). The fibres differ mainly in the content of different types of vesicles, which can be dense-core, small clear or large clear vesicles. The structure of synapses is discussed further on pp. 25—7. 

The central nervous system arises from a thickened area of the ectoderm called the neural plate on day 19 in the human embryo. This process is referred to as induction. The neural plate then differentiates into the neural tube (providing the origins for the brain and spinal cord) and the neural crest (forming the basis of the peripheral nervous system). The process by which the neural tube arises from the neural plate is referred to as neurulation. To form the neural tube, the neural plate changes shape and forms a pronounced groove, closing from the cranial end to the caudal end. The neural tube has openings on both ends that close on about day 25 and day 27, respectively. 

During the fourth week of development, the brain is growing quickly and bends ventrally with the head fold to produce the midbrain flexure and the cervical flexure. The formation of the flexures allows for significant changes in the shape of the developing brain and the distribution of the grey and white matter. By day 30, 

Changes in the central nervous system may occur with or without actual anemia (100, 115), although they are always associated with achylia gaslrica. The essential lesion is a primaiy degeneration of the myelin sheath with no glia reaction, most often affecting the posterior columns and the pyramidal tracts. 

Radioautography at the cellular level was applied to the study of brain lipids after injection of various precursors, such as acetate, labeled either with H or with in position 1 or 2, serine-3- C or cholesterol- H (Torvik and Sidman, 1965). Since some of these precursors were incorporated into proteins, lipid activity was determined by subtracting the radioautographic reaction observed over sections derived from tissue fixed in Carnoy s fluid (which will extract most lipids) from that seen over formalin-flxed frozen sections. The authors attempted to localize more closely the site of lipid formation in the brain and concluded that the rate of uptake was most 

Akaike et al. have examined the neuroprotective properties of serofendic acid, a substance isolated from serum. The compound was found to protect neuronal cells from both glutamate and NO. This was attributed to the scavenging of OH radicals (from the decomposition of ONOO-) rather than NO itself.320 Indeed, Ueda and colleagues have demonstrated the formation of both NO and OH in neuronal cells upon stimulation of the NMDA receptor.321 These workers also trapped lipid radicals in the brains of rats undergoing seizures induced by the stimulation of a subset of glutamate receptors with kainic acid. Polyphenols have been shown to exacerbate the neurotoxicity of NO.322 

2 Dopamine oxidation. In Parkinson s disease, cell death is localised to the dopamine-producing cells of the substantia nigra. Radicals are produced during the oxidation of DA, but whether the formation of these species is responsible for neuronal cell death or occurs as a consequence of cell turnover has not been established. Haque et al. have observed semiquinones from DA and is meta- 

4 Other phenomena. Prion proteins, the mutated forms of which cause Creutzfeldt-Jacob disease, also appear to interact with metal ions. Spectra of Cu(H) bound to various mutant proteins have indicated anomalous binding behaviour.331 Hydroxyl radical generation during the interaction of mutant forms of a prion protein fragment with Fe(II) has also been reported.332 

Despite extensive research, there are major experimental design difficulties in quantitatively correlating the time course relationship between drug plasma concentrations and PD effects of CNS agents. Suitable PD effects, which should possess most of the following characteristics, are listed below  

Benzodiazepines have been extensively used in the treatment of anxiety. However, the untoward CNS impairment effects of benzodiazepines are much more readily quantified using cognitive neuromotor testing than measures of anxiolytic effects due to lack of effective PD markers. Psychometric tests (hand-eye coordination, memory, body sway, and psychomotor speed), anesthetic effects (sleeping time), eye movement, and neurophysiological effects have been used as the PD end points to model the PK/PD relationships of benzodiazepines. 

The time course changes in the CNS impairment on psychomotor and cognitive skills related changes to the plasma lorazepam concentrations in a PK/PD model in healthy subjects. The PD end points included computerized continuous tracking, body sway with eyes opened, and digit symbol substimtion (DSS) tests. ° 

Alcohol and drug abuse disorders Steroid hormones Anti-inflammatory agents 

Plasma and tissue ACE, angiotensin II, PRA, angiotensin I, urine Na+/K, aldosterone 

The brain is prone to suffer oxidant damage due to its relatively low content of antioxidant enzymes (Carrillo et al. 1992) and its high content of iron, as shown in neuromelanin by Laser microprobe mass analysis (LAMMA) (Good et al. 1992). Immu-noreactive catalase protein decreased in the hypothalamus and the prefrontal cortex of the ageing rat brain (3 vs. 12 months) by 63 and 55 %, respectively (CiRiOLO et al. 1997). Iron will be easily released when the cells are injured and cannot be safely bound as cerebrospinal fluid has not any significant iron binding capacity. The toxicity of 02 has been 

Iron overload within the mitochondria confers cellular sensitivity to oxidant stress and may play an important role in the pathogenesis of Friedreich s ataxia, which might be treated by iron chelators to mobilise mitochondrial iron (Smith et al. 1999, Richardson et al. 2001). However, desferrioxamine cannot efficiently mobilise iron from cells (Bottomley et al. 1985, Richardson et al. 1994), and it is not effective at mobilising Fe from Fe-loaded mitochondria (Ponka et al. 1979, 1984). Pyridoxal isonicotinoyl hydrazone showed high affinity at mobilising Fe from an experimental model of mitochondrial Fe overload in reticulocytes (Ponka et al. 1979), and so did several of its analogues (Richardson et al. 2001). 

Copper toxicoses may be of genetic origin as in Wilson s disease in man (Underwood 1974) and copper toxicosis in the Bedlington terrier (Johnson et al. 1980). 

The phospholipid mixture isolated from brain was employed as a model system to study the free-radical oxidation chemistry using Cu(II) and H2O2 (Hall and Murphy 1998) to generate a hydroxyl radical by the Fenton reaction. The distribution of plasmenyl phosphohpids present in brain is somewhat different from that observed in erythrocyte membranes with the former having a high abundance of plasmenyl species with 18 1, 20 1, and 22 1 fatty acyl groups at the sn-2 position, which is comparable in abundance to those molecular species with 20 4, 22 4, and 22 6 fatty acyl groups at sn-2 (Khaselev and Murphy 1999). 

Copper deficiency in Menke s disease, an X-linked genetic disorder characterised by rapidly progressive cerebral degeneration was reported by Banks et al. (1972). 

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Cocaine is the oldest of the local anaesthetics. It is a central nervous system stimulant and is habit-forming. See ecgonine. 

Crystallizes from water in large colourless prisms containing 2H2O. It is poisonous, causing paralysis of the nervous system m.p. 101 C (hydrate), 189°C (anhydrous), sublimes 157°C. It occurs as the free acid in beet leaves, and as potassium hydrogen oxalate in wood sorrel and rhubarb. Commercially, oxalic acid is made from sodium methanoate. This is obtained from anhydrous NaOH with CO at 150-200°C and 7-10 atm. At lower pressure sodium oxalate formed from the sodium salt the acid is readily liberated by sulphuric acid. Oxalic acid is also obtained as a by-product in the manufacture of citric acid and by the oxidation of carbohydrates with nitric acid in presence of V2O5. 

Base, it stimulates all parts of the nervous system and in large doses produces convulsions. It is used for killing vermin. 

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

Kohonen networks, also known as self-organizing maps (SOMs), belong to the large group of methods called artificial neural networks. Artificial neural networks (ANNs) are techniques which process information in a way that is motivated by the functionality of biological nervous systems. For a more detailed description see Section 9.5. 

The nervous systems and especially the brains of animals and humans work very fast, efficiently, and highly in parallel. They consist of networked neurons which work together and interchange signals with one another. This section describes the functionality of a biological neuron and explains the model of an artificial neuron. 

Artificial Neural Networks (ANNs) are information processing imits which process information in a way that is motivated by the functionality of the biological nervous system. Just as the brain consists of neurons which are connected with one another, an ANN comprises interrelated artificial neurons. The neurons work together to solve a given problem. 

Concerning the distribution of a drug, models have been published for log BB blood/brain partition coefficient) for CNS-active drugs (CNS, central nervous system) crossing the blood-brain barrier (BBB) [38-45] and binding to human serum albumin (HSA) [46]. 

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

II Ceiiliiil nervous system depressants and anli-liypcrlcnsivcs 1618... 

H Airpclilc depressant and central nervous. system stimulant 876... 

Barbituric acid is the parent of a group of compounds known as barbiturates The bar biturates are classified as sedative-hypnotic agents meaning that they decrease the responsiveness of the central nervous system and promote sleep Thousands of deriva lives of the parent ring system of barbituric acid have been tested for sedative-hypnotic activity the most useful are the 5 5 disubstituted derivatives... 

A central nervous system stimulant obtained from the leaves of the coca plant)... 

The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters, substances that carry messages across a synapse from one neuron to another Several of these neurotransmitters arise from l tyrosine by structural modification and decarboxylation as outlined m Figure 27 5... 

Parylene s use in the medical field is linked to electronics. Certain pacemaker manufacturers use it as a protective conformal coating on pacemaker circuitry (69). The coated circuitry is sealed in a metal can, so that the parylene coating serves only as a backup should the primary barrier leak. There is also interest in its use as an electrode insulation in the fabrication of miniature electrodes for long-term implantation to record or to stimulate neurons in the central or peripheral nervous system, as the "front end" of experimental neural prostheses (70). One report describes the 3-yr survival of functioning parylene-coated electrodes in the brain of a monkey (71). 

Full eye protection should be worn whenever handling acryhc monomers contact lenses must never be worn. Prolonged exposure to Hquid or vapor can result in permanent eye damage or blindness. Excessive exposure to vapors causes nose and throat irritation, headaches, nausea, vomiting, and dizziness or drowsiness (solvent narcosis). Overexposure may cause central nervous system depression. Both proper respiratory protection and good ventilation are necessary wherever the possibiHty of high vapor concentration arises. 

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

Taste-active chemicals react with receptors on the surface of sensory cells in the papillae causing electrical depolarization, ie, drop in the voltage across the sensory cell membrane. The collection of biochemical events that are involved in this process is called transduction (15,16). Not all the chemical steps involved in transduction are known however, it is clear that different transduction mechanisms are involved in different taste quaUties different transduction mechanisms exist for the same chemical in different species (15). Thus the specificity of chemosensory processes, ie, taste and smell, to different chemicals is caused by differences in the sensory cell membrane, the transduction mechanisms, and the central nervous system (14). 

Loperamide is similar ia action and use to diphenoxylate however, it does not need to be formulated with atropiae and is available by prescription and OTC. It is reported to have fewer central nervous system side effects than diphenoxylate. 

Effects of repeated ethylene glycol peroral overexposure in treated rats and mice can result in kidney, Hver, and nervous system damage. The most sensitive indicators of ethylene glycol toxicity are disturbances in acid—base balance and nephrotoxic (kidney) effects. Effects of repeated chronic peroral overexposure of diethylene glycol in treated rats result in kidney and Hver damage (48). 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

In humans, the hypothalamic-derived protein and the hormone noncovalent complexes are packaged in neurosecretory granules, then migrate along axons at a rate of 1 4 mm/h until they reach the posterior pituitary where they are stored prior to release into the bloodstream by exocytosis (67). Considerable evidence suggests that posterior pituitary hormones function as neurotransmitters (68) vasopressin acts on the anterior pituitary to release adrenocorticotropic hormone [9002-60-2] (ACTH) (69) as well as on traditional target tissues such as kidneys. Both hormones promote other important central nervous system (CNS) effects (9,70). 

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