Nerve-ending examination

It is believed that the mechanism of action of amphetamines lies in their ability to release epinephrine (adrenaline) and dopamine from presynaptic nerve endings, which stimulate the corresponding receptors in the CNS. It is also possible that they reduce neuronal uptake of amines as well as inhibit their degradation by monoaminoxidase (MAO). Characteristic of this series of compounds is the effect on the respiratory center, on the satiation center located in the hypothalamus, which leads to suppression of feelings of hunger, thus allowing analog of the examined compounds to be used as anorectics. 

Figure 5. Electron microscopic examination of the "nerve ending fraction (X13,000) and of the synaptosomal membrane fraction (X.7150)...

Soudljn cc al. (281) examined the binding of [ H]benzetlmide to subcellular fractions of the rat caudate nucleus and found both in vitro and In vivo that the (+) isomer was bound to the particles in a fraction composed of membranes and nerve endings to the extent of 4-7 times the (-) isomer. Fractions composed more nearly exclusively of membranes or of nerve endings bound the labeled material less extensively than the fraction that contained both structures Binding of benzetlmlde In vitro vas reduced markedly by atropine and by carbachol, but only slightly. If at all, by d-tubocurarlne. 

Pharmacology. In order to assess the importance of conformational preferences in the action of amphetamine at the adrenergic nerve endings, the effect of the amphetamine and methamphetamine analogs (NH-X,-NH-N, NM-X and NM-N) on the uptake and release of JH-norepinephrine (NE) and H-dopamine (DA) in chopped tissues from various regions of rat brain was examined. NH-X and NM-X were nearly as potent as amphetamine in the inhibition of uptake of 3H-NE into chopped cortex... 

Isolated nerve endings (synaptosomes) in superfusion represent an ideal preparation for the study of neurotoxicant action. Indeed the use of such an approach to examine the interaction of pharmacological agents with ion channels in vertebrate synaptosomal preparations is well established ( 3), (40. It is only relatively recently that fractionation procedures for invertebrate synaptosomes have been optimized and superfusion techniques applied to the study of drug and toxin action in insects (J ), ( 5). In the present communication we have attempted to clarify the mode of action of certain insecticidal neurotoxicants by determining their effects on transmitter release in the presence and absence of channel specific modulators. 

If a DC source coupled to two skin surface electrodes is suddenly switched on, a transient sensation may be felt in the skin. The same thing happens when the DC current is switched off. This proves that many nerve endings are only sensitive to changes in a stimulus and not to a static stimulus. At the moment a DC is switched on, it is not only a DC, it also contains an AC component. DC must therefore be applied with a slow increase from zero up to the desired level, if the threshold of DC perception is to be examined. 

Very recent X-ray examination by Wilkins et al. (1971) of several membranes suspended in water has shown that their main structural feature is the lipid bilayer. The preparations examined included erythrocyte ghosts, nerve-ending membranes, sarcoplasmic reticulum, E. coli plasma membrane, and that of Halobacterium cutiru-brum. 

P-Homochelidonine was examined by Meyer and von Engel, and the results, as quoted by Sehmidt, indicate that in frogs -homoehelidonine behaves like ehelidonine, and that in mammals it eauses slight nareosis and a transitory fall in blood pressme, followed by eonvulsions of the type indueed by camphor, slowing of the pulse and, in large doses, paralysis of the vaso-motor centres. It also paralyses the ends of the sensory nerves. ... 

In the neurotoxicity study (OECD TG 424/EU Annex B.43), the animals are tested to allow the detection or the characterization of behavioral and/or neurological abnormalities. A range of behaviors that could be affected by neuro toxic ants is assessed during each observation period. At the end of the test, a subset of animals of each sex from each group are perfused in situ and sections of the brain, spinal cord, and peripheral nerves are prepared and examined. 

In the subchronic neurotoxicity study, end points measured are similar to those measured in the acute neurotoxicity study. However, the duration of dosing is 90 days and exposure to the test material is usually via the diet. As for the acute neurotoxicity study, these studies consist of three test groups and a control group. The functional observation battery and motor activity tests are conducted at selected intervals such as weeks 5, 9, and 13, as well as pretest. At test termination, at least 6 animals per group are perfused via the heart with fixative to ensure optimal fixation of nervous tissues for histopathology examination. Nervous tissues examined include brain, spinal cord (various segments), and selected nerves such as the optic, sciatic, tibial, and sural nerves. 

The role of the sympathetic nervous system in renal injury, end-stage renal disease, and renovascular hypertension are discussed through a literature review accompanying sympathetic nerve mechanisms in hypertension and obesity. Relevant studies of sympathetic nerve activity and 32-adrenoceptor polymorphism might contribute to the onset and maintenance of renal injury in healthy subjects and in patients with chronic heart failure and cardiovascular events in ESRD patients. A better understanding of the relationships of sympathetic nerve activity with renal injury might help clinical implications (treatment) for renal injury in hypertensive patients and hypertension in patients with ESRD. Recently, the role of denervation of renal sympathetic nerve in refractory hypertension has been examined and showed its efficacy in humans. The outcome from the study have not been established, but a number of animal studies show theoretical benefits for those patients in the acute phase. Further studies are needed to clarify the relationships between the sympathetic nerve activity and renal injury. 

To understand the physiological nature of muscle contractions, it is helpful to examine muscles microscopically. Muscle fibers have an outside membrane called the plasmalemma, an interior structure called a sar-colemma, transverse tubules across the fibers, and an inner network of muscle tissue called sarcoplasma. When a nerve impulse reaches the muscle, an action potential is set up and the current quickly travels in both directions from the motor end plate through the entire length of the muscle fiber. The whole inside of the muscle tissue becomes involved as the current spreads and, aided by calcium, the contractile protein called actin causes the muscle component (myosin) to contract. An enzyme, ATP-ase, helps provide the energy needed for the muscular filaments to slide past each other. Relaxation occurs promptly when Ca flows into the muscle tissue and the cycle is completed. The muscle fiber is now ready to be stimulated again by a nerve impulse. 

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