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Small tattoos can be removed by skin grafting; for large tattoos order zithromax 500mg free shipping antibiotic resistance news, mechanical abrasion of the skin is preferred 500mg zithromax otc bacteria science fair projects. Coloration of the Skin Normal skin color is the expression of a combination of three pigments: melanin, carotene, and hemoglobin. Melanin is a brown- black pigment produced in the melanocytes of the stratum basale FIGURE 5. All individuals of similar size have approximately the arrow) produce melanin. Commonly called “liver spots,” these pigmented patches are benign growths of pigment-producing melanocytes. Excessive exposure to sunlight can cause skin cancer (see Clinical Considerations and fig. In sunlight, the skin ab- sorbs two wavelengths of ultraviolet rays known as UVA and UVB. The DNA within the basal skin cells may be damaged as the sun’s (a) (b) more dangerous UVB rays penetrate the skin. Although it was once believed that UVA rays were harmless, findings now indicate that ex- cessive exposure to these rays may inhibit the DNA repair process that follows exposure to UVB. Therefore, individuals who are ex- posed solely to UVA rays in tanning salons are still in danger of basal cell carcinoma, because they will later be exposed to UVB rays of sunlight when they go outdoors. It was once thought to account for the yellow-tan skin of people of (c) (d) Asian descent, but this coloration is now known to be caused by variations in melanin. Oxygenated blood flowing through the dermis gives the skin its pinkish tones. Certain physical conditions or diseases cause symptomatic discoloration of the skin. In jaundice, the skin appears yellowish be- palms and the shallow flexion lines that can be seen on the cause of an excess of bile pigment in the bloodstream. Furrows on the fore- usually symptomatic of liver dysfunction and sometimes of liver im- head and face are acquired from continual contraction of facial maturity, as in a jaundiced newborn. Surface Patterns The science known as dermatoglyphics is concerned with the classification and identification of fingerprints. Every individ- The exposed surface of the skin has recognizable patterns that ual’s prints are unique, including those of identical twins. All other primates have ridges) are congenital patterns that are present on the finger and fingerprints, and even dogs have a characteristic “nose print” that is toe pads, as well as on the palms and soles. The designs formed used for identification in the military canine corps and in certain dog kennels. They are formed by the pull of elastic fibers within the dermis and are well established prenatally. The Dermis ridges of fingerprints function to prevent slippage when grasping objects. Because they are precise and easy to reproduce, finger- The dermis is deeper and thicker than the epidermis (see prints are customarily used for identifying individuals. Elastic and collagenous fibers within the dermis are arranged in definite patterns, producing lines of tension in the skin and providing skin tone (fig. Integumentary System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 5 Integumentary System 111 FIGURE 5. Stretch marks generally fade with time but may leave permanent markings. Innervation of the Skin The dermis of the skin has extensive innervation (nerve supply). Specialized integumentary effectors consist of smooth muscles or glands within the dermis that respond to motor impulses trans- mitted from the central nervous system to the skin by autonomic FIGURE 5. Surgical incisions Several types of sensory receptors respond to various tactile made parallel to the lines of tension heal more rapidly and create less (touch), pressure, temperature, tickle, or pain stimuli. Certain areas of the body, such as the palms, soles, lips, and external genitalia, have a Layers of the Dermis greater concentration of sensory receptors and are therefore more The dermis is composed of two layers. Chapter 15 includes a detailed discussion of stratum papillarosum (papillary layer), is in contact with the epi- the structure and function of the various sensory receptors. Papillae Blood vessels within the dermis supply nutrients to the mitoti- form the base for the friction ridges on the fingers and toes. Fibers within this layer blood vessels play an important role in regulating body tempera- are more dense and regularly arranged to form a tough, flexible ture and blood pressure. It is quite distensible, as is evident in pregnant tion responses can either shunt the blood away from the women or obese individuals, but it can be stretched too far, caus- superficial dermal arterioles or permit it to flow freely throughout ing “tearing” of the dermis. Fever or shock can be detected by the color and leaves a white streak called a stretch mark, or linea albicans temperature of the skin. Lineae albicantes are frequently found on the sodilation of dermal blood vessels. It is important to maintain good blood circulation in people It is the strong, resilient reticular layer of domestic mammals who are bedridden to prevent bedsores, or decubitus (de- that is used in making leather and suede.

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It could unfold a whole new requirement and dimension to our understanding of synaptic physiology and pharmacology and the use of drugs generic zithromax 500 mg amex infection gums. On the other hand discount zithromax 100 mg with amex antimicrobial pillows, it may be of little significance in some cases for although cholinergic-mediated nicotinic and muscarinic responses as well as dopamine and peptide effects are observed in sym- pathetic ganglia, it is only nicotinic antagonists that actually reduce transmission, acutely anyway. The brain could be likened to a television set in which the amino acids are providing the basic positive and negative power lines, while the other NTs (the multi-coloured wires) control the colour, contrast and brightness. All are required for a perfect picture but some are obviously more important than others. FUNCTIONAL SYNAPTIC NEUROCHEMISTRY To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 mmol/mg) just as ACh is at the neuromuscular junction. By contrast, the peptides are not even synthesised in the terminal but are split from a larger precurser protein in the cell body or during transit down the axon. They are consequently only found in low concentrations (100 pmol/g) and after acting are broken down by peptidases into fragments that cannot be re-used. It is perhaps not surprising that they have a supporting rather than a primary role. In between the above two extremes are the monoamines (1±10 nmol/g) which are preformed and stored in terminals but at much lower concentrations than the amino acids and when released are removed primarily by reuptake for re-use, or intraneuronal metabolism to inactive metabolites. Thus the appropriate synaptic organisation, biochemistry and receptor pharmacology of the NTs also varies in keeping with their function. It is often assumed, incorrectly, that the NTs found in the highest concentra- tion are the most potent. Those like the amino acids while having high affinity for their receptors have low potency while the peptides found at much lower concentration have high potency but low affinity. It perhaps goes without saying that the proposed transmitter must be shown to be present in the CNS and preferably in the area and at the synapses where it is thought to act. Stimulation of the appropriate nerves should evoke a measurable release of NT. The proposed NT must produce effects postsynaptically which are identical physiologically (appropriate membrane potential changes) and pharmacologically (sensitivity to antagonists) to that produced by neuronal stimulation and the relased endogenous NT. As guidelines they provide a reasonable scientific framework of the type of investigations that must be undertaken to establish the synaptic role of a substance. As rigid rules they could preclude the discovery of more than one type of neurotransmitter or one form of neurotransmission. Nevertheless, the criteria have been widely employed and often expanded to include other features which will be considered as subdivisions of the main criteria. PRESENCE Distribution and concentration It is generally felt that a substance is more likely to be a NT if it is unevenly distributed in the CNS although if it is widely used it will be widely distributed. Certainly the high concentration (5±10 mmol/g) of dopamine, compared with that of any other monoamine in the striatum or with dopamine in other brain areas, was indicative of its subsequently established role as a NT in that part of the CNS. This does not mean it cannot have an important function in other areas such as the mesolimbic system and parts of the cerebral cortex where it is present in much lower concentrations. In fact the concentra- tion of the monoamines outside the striatum is very much lower than that of the amino acids but since the amino acids may have important biochemical functions that necessitate their widespread distribution, the NT component of any given level of amino acid is difficult to establish. Nevertheless, useful information can be deduced from patterns of distribution. Glycine is concentrated more in the cord than cortex and in ventral rather than dorsal grey or white matter. This alone would be indicative of a NT role for glycine in the ventral horn, where it is now believed to be the inhibitory transmitter at motoneurons. GABA, on the other hand, is more concentrated in the brain than in the cord and in the latter it is predominantly in the dorsal grey so that although it is an inhibitory transmitter like glycine it must have a different pattern of activity. Section of dorsal roots and degeneration of afferent fibres produces a reduction in glutamate and substance P which can then be associated with sensory inputs. Temporary reduction of the blood supply to the cord causes preferential destruction of interneurons and a greater loss of asparate and glycine, compared with other amino acids and so links NEUROTRANSMITTER SYSTEMS AND FUNCTION: OVERVIEW 27 those amino acids with interneurons. Intrinsic neurons can also be destroyed through overactivity caused by kainic acid injections.

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The dis- fusal muscle fibers buy 500 mg zithromax amex antimicrobial drugs antimicrobial agents, about 300 m long zithromax 100mg on line infection 8 weeks after giving birth, have contractile fil- tal pole of a GTO is anchored in collagen fibers of the ten- aments at both ends. The proximal pole is attached to the ends of the tains the cell nuclei (Fig. There are two types of in series with the extrafusal muscle fibers such that con- intrafusal fibers: nuclear bag fibers, named for the large tractions of the muscle stretch the GTO. There are about twice as many nuclear chain eter than the type Ia variety, which innervate the muscle fibers as nuclear bag fibers per spindle. Muscle contraction stretches the GTO and gener- type fibers are further classified as bag1 and bag2, based on ates action potentials in type Ib axons. The GTO output whether they respond best in the dynamic or static phase of provides information to the central nervous system about muscle stretch, respectively. Sensory axons surround both the noncontractile mid- Information entering the spinal cord via type Ia and Ib portion and paracentral region of the contractile ends of axons is directed to many targets, including the spinal in- the intrafusal fiber. The sensory axons are categorized as terneurons that give rise to the spinocerebellar tracts. The axons of These tracts convey information to the cerebellum about both types are myelinated. Type Ia axons are larger in di- the status of muscle length and tension. Alpha motor neurons innervate shaped endings that wrap around the middle of the intra- the extrafusal muscle fibers, and gamma motor neurons in- fusal muscle fiber (see Fig. Cells bodies of both alpha and clear chain fibers are innervated by type Ia axons. Type II gamma motor neurons reside in the ventral horns of the axons innervate mainly nuclear chain fibers and have nerve spinal cord and in nuclei of the cranial motor nerves. This high number reflects the com- ings of both primary and secondary sensory axons of the plex role of the spindles in motor system control. Intrafusal muscle spindles respond to stretch by generating action po- muscle fibers likewise constitute a significant portion of the tentials that convey information to the central nervous sys- total number of muscle cells, yet they contribute little or tem about changes in muscle length and the velocity of nothing to the total force generated when the muscle con- 94 PART II NEUROPHYSIOLOGY A R Ia Response Passive stretch of muscle fibers from resting length Tension Wt. T Passive stretch B Ia response ceases R Stimulate alpha Ia Response motor neuron Tension Wt. T Stimulate C Ia responsiveness is maintained Stimulate alpha R and Ia Response gamma motor neurons Tension Wt. A, The Ia C, Concurrent alpha and gamma motor neuron activation, as oc- sensory endings from the muscle spindles discharge at a slow rate curs in normal, voluntary muscle contraction, shortens the muscle when the muscle is at its resting length and show an increased fir- spindle along with the extrafusal fibers, maintaining the spindle’s ing rate when the muscle is stretched. Rather, the contractions of intrafusal fibers play a spindle were reinstituted, the Ia nerve endings would re- modulating role in sensation, as they alter the length and, sume their sensitivity to stretch. This is accomplished by coordinated activation discharge of action potentials. Contraction of the muscle of the alpha and gamma motor neurons during muscle con- increases the firing rate in type Ib axons from Golgi tendon traction (see Fig. Ia endings report both the velocity and the length of stretch, type Ia endings show a greater firing rate increase, while muscle stretch; type II endings report length. B, With the release CHAPTER 5 The Motor System 95 types of endings, each located distal to the sensory endings on the striated poles of the spindle’s muscle fibers (see Fig. The nerve terminals are either plate endings or trail endings; each intrafusal fiber has only one of these two types of endings. Plate endings occur predominantly on bag1 fibers (dynamic), whereas trail endings, primarily on chain fibers, are also seen on bag2 (static) fibers. This arrangement allows for largely independent control of the nuclear bag and nuclear chain fibers in the spindle. Gamma motor neurons with plate endings are designated dynamic and those with trail endings are designated static. This functional distinction is based on experimental find- ings showing that stimulation of gamma neurons with plate endings enhanced the response of type Ia sensory axons to stretch, but only during the dynamic (muscle length chang- ing) phase of a muscle stretch. During the static phase of the stretch (muscle length increase maintained) stimulation of the gamma neurons with trail endings enhanced the re- sponse of type II sensory axons. Static gamma neurons can affect the responses of both types Ia and II sensory axons; dynamic gamma neurons affect the response of only type Ia axons. These differences suggest that the motor system has the ability to monitor muscle length more precisely in some muscles and the speed of contraction in others. THE SPINAL CORD IN THE CONTROL OF MOVEMENT Muscles interact extensively in the maintenance of posture and the production of coordinated movement. The circuitry of the spinal cord automatically controls much of this inter- FIGURE 5. Sensory feedback from muscles reaches motor neu- rons controlling axial, girdle, and limb muscles rons of related muscles and, to a lesser degree, of more dis- are grouped in pools oriented in a medial-to-lateral fashion. In addition to activating local circuits, muscles flexor and extensor motor neurons also segregate into pools. This information is processed and can be re- layed back to influence spinal cord circuits. A zone between the medial and lateral pools contains in- The Structural Arrangement of Spinal terneurons that project to limb motor neuron pools ipsilat- Motor Systems Correlates With Function erally and axial pools bilaterally.

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Drugs that increase dopaminergic transmission zithromax 250 mg without a prescription antibiotic resistance meat, initiating voluntary movements (see Chapter 5) order zithromax 250 mg on-line antibiotics list. The such as cocaine, which inhibits dopamine reuptake, and tuberoinfundibular system of dopaminergic neurons is lo- amphetamine, which promotes dopamine release and in- cated entirely within the hypothalamus, with cell bodies in hibits its reuptake, lead to repeated administration and the arcuate nucleus and periventricular nuclei and terminals abuse presumably because they stimulate the brain’s reward in the median eminence on the ventral surface of the hypo- system. The tuberoinfundibular system is responsible for tem is also the site of action of neuroleptic drugs, which 128 PART II NEUROPHYSIOLOGY Cingulate gyrus Anterior nucleus of thalamus Fornix Corpus callosum Stria medullaris Longitudinal stria Habenula Septal nuclei Prefrontal cortex Olfactory bulb Stria terminalis FIGURE 7. The fiber tracts that interconnect the structures of the limbic system are also shown. Noradrenergic neurons (containing norepinephrine) Noradrenergic neurons innervate all parts of the limbic are located in cell groups in the medulla and pons (Fig. The medullary cell groups project to the spinal cord, role in setting mood (sustained emotional state) and affect where they influence cardiovascular regulation and other (the emotion itself; e. Cell groups in the pons include the Drugs that alter noradrenergic transmission have profound lateral system, which innervates the basal forebrain and hy- effects on mood and affect. For example, reserpine, which depletes brain norepinephrine (NE), induces a state of de- pression. Drugs that enhance NE availability, such as monoamine oxidase inhibitors (MAOIs) and inhibitors of Prefrontal reuptake, reverse this depression. Amphetamines and co- cortex caine have effects on boosting noradrenergic transmission Motivational processing similar to those described for dopaminergic transmission; Association they inhibit reuptake and/or promote the release of norepi- Memory cortex nephrine. Increased noradrenergic transmission results in processing an elevation of mood, which further contributes to the po- Cingulate gyrus Mesolimbic/ Cingulate gyrus mesocortical system Basal ganglia Anterior Thalamus thalamic Frontal Hippocampus cortex Nigrostriatal nuclei system Mammillary Fornix Mammillothalamic tract body Hypothalamus Substantia Tuberoinfundibular nigra Rest ot system hypothalamus Ventral tegmental area Midbrain Medulla Pons Brainstem The origins and projections of the three FIGURE 7. Experimental studies be- ginning early in the last century demonstrated that stimu- lating the limbic system or creating lesions in various parts of the limbic system can alter emotional states. Most of our knowledge comes from animal studies, but emotional feel- ings are reported by humans when limbic structures are Hypothalamus stimulated during brain surgery. The brain has no pain sen- Midbrain sation when touched, and subjects awakened from anesthe- Locus ceruleus sia during brain surgery have communicated changes in Pons emotional experience linked to electrical stimulation of specific areas. Medulla To spinal cord Electrical stimulation of various sites in the limbic sys- tem produces either pleasurable (rewarding) or unpleasant FIGURE 7. To study these findings, researchers use cell groups of noradrenergic neurons of the electrodes implanted in the brains of animals. The Human rent to the electrodes by pressing a bar, repeated and Brain and Spinal Cord. The sites that pro- voke the highest rates of electrical self-stimulation are in tential for abusing such drugs, despite the depression that the ventral limbic areas, including the septal nuclei and nu- follows when drug levels fall. Extensive studies of electrical self-stimu- quences of cocaine or amphetamine-like drugs reflect the latory behavior indicate that dopaminergic neurons play a increased noradrenergic transmission, in both the periph- major role in mediating reward. This can result in a hypertensive crisis, thought to be the site of action of addictive drugs, includ- myocardial infarction, or stroke, in addition to marked ing opiates, alcohol, nicotine, cocaine, and amphetamine. A fight-or-flight re- Serotonergic neurons also innervate most parts of the sponse, including the autonomic components (see Chapter 6) CNS. Cell bodies of these neurons are located at the mid- and postures of rage and aggression characteristic of fight- line of the brainstem (the raphe system) and in more later- ing behavior, can be elicited by electrical stimulation of ally placed nuclei, extending from the caudal medulla to the sites in the hypothalamus and amygdala. Serotonin plays a major role in the de- tical connections to the limbic system are severed, rage fect underlying affective disorders (discussed later). Drugs postures and aggressiveness become permanent, illustrating the importance of the higher centers in restraining aggres- sion and, presumably, in invoking it at appropriate times. Cingulate gyrus By contrast, bilateral removal of the amygdala results in a Basal ganglia placid animal that cannot be provoked. The biological basis of human sexual ac- tivity is poorly understood because of its complexity and be- cause findings derived from nonhuman animal studies can- not be extrapolated. The major reason for this limitation is that the cerebral cortex, uniquely developed in the human brain, plays a more important role in governing human sex- Hypothalamus ual activity than the instinctive or olfactory-driven behav- Midbrain iors in nonhuman primates and lower mammalian species. Nevertheless, several parallels in human and nonhuman sex- Pons ual activities exist, indicating that the limbic system, in gen- Medulla eral, coordinates sex drive and mating behavior, with higher To spinal cord centers exerting more or less overriding influences. The depicted groups originate in the caudal medulla, pons, ulation reflexes and engorgement of female erectile tissues, and midbrain and send projections to most regions of the brain. Copulatory behaviors and postures can be elicited in ani- New York: Springer-Verlag, 1983. Ablation studies have shown that sexual and serotonergic neurons serving the limbic system. A ther- behavior also requires an intact connection of the limbic apeutic response to these treatments ensues only after treat- system with the frontal cortex. Similarly, when treatment stops, Olfactory cues are important in initiating mating activity symptoms may not reappear for several weeks. Driven by the hypothalamus’ endoge- in treatment response is presumably due to alterations in the nous seasonal clock, the anterior and preoptic areas of the long-term regulation of receptor and second messenger sys- hypothalamus initiate hormonal control of the gonads. Hormonal release leads to the secretion of odorants The most effective long-term treatment for mania is (pheromones) by the female reproductive tract, signaling lithium, although antipsychotic (neuroleptic) drugs, which the onset of estrus and sexual receptivity to the male.

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