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Also not all the animals show memory loss and that tends to precede the amyloid disposition buy discount levitra extra dosage 60mg on line. Three distinct forms of ApoE purchase 60mg levitra extra dosage otc, E2 60 mg levitra extra dosage mastercard, E3 and E4 are encoded on chromosome 19 but it is the ApoE generic levitra extra dosage 60mg overnight delivery, E4 allele that occurs at a much higher frequency in late-onset AzD patients (50%) compared with controls (16%) and binds to and possibly increases the formation of b-amyloid. The precise physiological role of these 463 and 448 amino-acid transmembrane proteins is unclear but plasma and brain tissue from patients with PS mutations contain above-normal levels of the b-amyloid protein as do transgenic mice expressing PS mutations and cells transfected with mutant PS. Thus all the above genetic mutations can lead to increased amyloid deposition and possibly AzD (see Smith 1998). Unfortunately familial AzD represents only the minority of cases and so other causes need to be considered. HEAD INJURIES It has been estimated that up to 15% of head injuries may lead to AzD with dementia being common among boxers (dementia pugilistica). Certainly such trauma is associated with diffuse amyloid deposits (not plaques) and a number of neurofibrillary tangles apparently identical to those in AzD. ALUMINIUM Reported positive associations between AzD and a high aluminium level in drinking water promoted that element as a risk factor for, or cause of, AzD. Since then aluminium in silicate form has been found in plaques and tangles and shown to impair the axonal transport of neurofilament. However, the occurrence of high brain levels of aluminium, either through environmental exposure or dialysis encephalopathy, is not associated with a greater incidence of AzD and the neurofibrillary changes it produces appear different from those of AzD. Currently while aluminium is accepted to be neurotoxic, it is thought to be a more likely cause of neurological impairments than AzD. INFLAMMATION The finding that patients treated with non-steroidal anti-inflammatory drugs (NSAIDs) like asprin were less likely to develop AzD stimulated the suggestion that AzD may have an inflammatory component and indeed NSAIDs have been shown to have a protective effect against AzD. It remains to be seen whether this is a true anti- inflammatory effect or whether the NSAIDs are protecting by reducing free radical production. SUMMARY Even if there is a link between the presence of tangles and plaques and the emergence of AzD, it is by no means certain how those markers could be responsible for all the symptoms. They do not seem to be sufficiently numerous or widely spread to disrupt brain function to the extent that eventually occurs in AzD, although their preferential location in the hippocampus and the known association of that area with memory processing could explain the loss of that faculty. Since therapy for AzD, like that for the other major neurodegenerative disorder Parkinsonism, could depend on establishing to what extent its pathology is associated 380 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION with the loss of neurotransmitter function, it is important to consider NT changes in AzD. NEUROTRANSMITTER CHANGES IN AzD The NT most consistently implicated in AzD is ACh. ACETYLCHOLINE It is 20 years since a 50% reduction was noted in the level of choline acetyltransferase (ChAT), the enzyme responsible for ACh synthesis, in the frontal cortex and hippocampus of AzD patients (Bowen et al. ACh itself was not easily measured at that time but a reduced synthesis of ACh from 14C glucose was observed in brain tissue from AzD patients. There is in fact a significant correlation between the reduction in ChAT and both the increased number of plaques and tangles at death and the severity of mental impairment six months before death (Perry et al. ACh loss is not global, no change being found in the striatum or some parts of the cortex. Recently reduced ACh levels have been reported in CSF obtained by lumbar puncture, though it is surprising that it survived degradation (Tohgi et al. Since ACh is mostly synthesised in nerve terminals, the reduction in cortical ChAT must reflect a loss of cholinergic nerve terminals and as there are few cholinergic neurons in the cortex, these must be the endings of axons that come from cholinergic neurons in the subcortical nucleus basalis (Fig. In fact there is a dramatic loss (570%) of such neurons in AzD, especially in younger patients, although there is some evidence that the loss of cortical ChAT is greater than the cell loss and that degeneration starts in the cortical terminals and proceeds retrogradely to the cell bodies. Plaques and tangles are also found in the nucleus basalis but lesion of it does not induce their formation in the cortex and their cortical location does not just coincide with cholinergic innervation. No overall reduction in cholinergic muscarinic receptors was found but recent studies with relatively specific ligands show a loss of presynaptic M2 receptors, in keeping with the loss of terminals, but no reduction in postsynaptic M1 receptors. ACh AND b-AMYLOID Low concentrations of solubilised b-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of Ab below those generally neurotoxic. Since b-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism). To what extent these events can occur in vivo, let alone with insoluble b-amyloid, which forms the plaques, is not clear but soluble b-amyloid itself is also increased significantly in AzD brain and when infused into the ventricles of rats reduces ChAT activity.

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The cubital fossa is the depression on the anterior surface Antebrachium of the elbow region safe levitra extra dosage 40mg, where the median cubital vein links the Contained within the antebrachium (forearm) are two parallel cephalic and basilic veins order levitra extra dosage 60mg fast delivery. These veins are subcutaneous and be- bones (the ulna and radius) and the muscles that control the come more conspicuous when a proximal compression is applied purchase 60 mg levitra extra dosage with amex. The muscles of the forearm taper dis- For this reason discount levitra extra dosage 40mg online, they are an important location (particularly the tally over the wrist, where their tendons attach to various bones median cubital) for the removal of venous blood for analyses and of the hand. Several muscles of the forearm can be identified as transfusions or for intravenous therapy (fig. Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 Chapter 10 Surface and Regional Anatomy 321 Triceps brachii m. The ulna can be palpated along its entire length from Tendon of palmaris longus m. Nerves, tendons, and vessels are close to the surface at the Styloid process of ulna wrist, making cuts to this area potentially dangerous. Tendons Thenar eminence from four flexor muscles can be observed as surface features if Hypothenar eminence the anterior forearm muscles are strongly contracted while mak- ing a fist. The tendons that can be observed along this surface, from lateral to medial, are from the following muscles: flexor carpi radialis, palmaris longus, superficial digital flexor, and flexor carpi ulnaris. The median nerve going to the hand is located under the tendon of the palmaris longus muscle (see FIGURE 10. Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 322 Unit 4 Support and Movement Tendon of extensor Nail pollicis brevis m. Distal Styloid process interphalangeal of ulna joints Anatomical Proximal snuffbox interphalangeal Tendon of extensor joints pollicis longus m. The radial artery lies along the Hand surface of the radius, immediately lateral to the tendon of the Much of the surface anatomy of the hand, such as flexion creases, flexor carpi radialis muscle. This is the artery commonly used fingerprints, and fingernails, involves features of the skin discussed when monitoring the pulse. Other surface features are the extensor tendons from also be detected in the ulnar artery, lateral to the tendon of the the extensor digitorum muscle, which can be seen going to each of flexor carpi ulnaris. The knuckles of the hand are the distal ends of the posterior surface of the wrist as the thumb is extended the second through the fifth metacarpal bones. The tendon of the extensor pollicis brevis muscle of the fingers and the individual phalanges can be palpated. The depression created between these two tendons as they are pulled taut is referred to as the anatomical snuffbox. Pulsations of the radial artery can be detected in Internal Anatomy this depression. The internal anatomy of the shoulder and upper extremity in- The median nerve, which serves the opponens pollicis muscle cludes the structures of the shoulder, brachium, cubitus (elbow), of the thumb, is the nerve most commonly injured by stab antebrachium, and hand. The principal structures of these re- wounds or the penetration of glass into the wrist or hand. Severing of this nerve paralyzes a major muscle of the thumb; it wastes away, re- gions are shown in the cadaver dissections in figures 10. Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 Chapter 10 Surface and Regional Anatomy 323 Flexion creases Tendon of superficial on digits digital flexor m. Hypothenar eminence Thenar eminence Tendon of flexor carpi Flexion creases ulnaris m. Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 324 Unit 4 Support and Movement 1 8 2 9 3 4 10 5 11a 11b 6 11c 7 1 Supraspinatus m. Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 Chapter 10 Surface and Regional Anatomy 325 1 1 2 12 3 2 13 4 3 14 14 5 15 4 15 16 6 5 17 7 18 16 6 8 19 7 20 8 9 9 10 10 11 17 11 18 12 19 20 13 21 1 Flexor carpi ulnaris m. List the clinically important structures that can be ob- 8 Radius 19 Tendon of extensor digiti minimi m. Describe the locations of the axilla, brachium, cubital radialis longus m. Which of the two bones of the forearm is the more station- ary as the arm is rotated? Surface and Regional © The McGraw−Hill Anatomy, Sixth Edition Anatomy Companies, 2001 326 Unit 4 Support and Movement Iliac crest Coccyx Site for intramuscular injection Natal cleft Gluteus maximus m. Greater trochanter of femur Fold of buttock Hamstring group of muscles Popliteal fossa FIGURE 10.

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The pinna levitra extra dosage 60 mg discount, the visible portion of the outer water are greater than those in air cheap 40mg levitra extra dosage fast delivery, the speed of sound in ear discount 40 mg levitra extra dosage otc, is not critical to hearing in humans discount 60mg levitra extra dosage with mastercard, although it does water is about 4 times as great, and the wavelength is cor- respondingly increased. Since the wavelength depends on the elasticity of the medium (which varies according to temperature and pressure), it is more convenient to TABLE 4. Sound fre- Common Sounds quency is usually expressed in units of Hertz (Hz or cy- Sound cles per second). Pressure Pressure Relative Another fundamental characteristic of a sound wave is 2 (dynes/cm ) Level (dB) Sound Source Pressure its intensity or amplitude. This may be thought of as the relative amount of compression or rarefaction present as 0. Be- 200 120 Loud thunder 1,000,000 cause the human ear is sensitive to sounds over a million- 2,000 140 Pain and damage 10,000,000 fold range of sound pressure levels, it is convenient to ex- press the intensity of sound as the logarithm of a ratio Modified from Gulick WL, Gescheider GA, Frisina RD. New referenced to the absolute threshold of hearing for a tone York: Oxford University Press, 1989, Table 2. The superior and lateral lig- Vestibular nerve Incus aments lie roughly in the plane of the ossicular chain and an- Facial nerve chor the head and shaft of the malleus. The anterior ligament Cochlear attaches the head of the malleus to the anterior wall of the nerve middle ear cavity, and the posterior ligament runs from the head of the incus to the posterior wall of the cavity. The sus- pensory ligaments allow the ossicles sufficient freedom to function as a lever system to transmit the vibrations of the tympanic membrane to the oval window. This mechanism is especially important because, although the eardrum is sus- pended in air, the oval window seals off a fluid-filled cham- ber. Transmission of sound from air to liquid is inefficient; if Pinna sound waves were to strike the oval window directly, 99. Al- though it varies with frequency, the ossicular chain has a Outer ear Middle Inner ear ear lever ratio of about 1. The brane is coupled to the smaller area of the oval window (ap- structures of the middle and inner ear are en- proximately a 17:1 ratio). These conditions result in a pres- cased in the temporal bone of the skull. Although the efficiency depends on the fre- slightly emphasize frequencies in the range of 1,500 to quency, approximately 60% of the sound energy that 7,000 Hz and aids in the localization of sources of sound. Wax-secreting glands line the canal, and its inner end is sealed by the tympanic membrane or eardrum, Approximate Stapedius axis of Superior muscle a thin, oval, slightly conical, flexible membrane that is an- rotation ligament chored around its edges to a ring of bone. An incoming Temporal bone pressure wave traveling down the external auditory canal causes the eardrum to vibrate back and forth in step with Scala vestibuli the compressions and rarefactions of the sound wave. Oval window Lateral The overall acoustic effect of the outer ear structures is to ligament produce an amplification of 10 to 15 dB in the frequency range broadly centered around 3,000 Hz. The next portion of the auditory sys- Basilar tem is an air-filled cavity (volume about 2 mL) in the mas- Incus membrane toid region of the temporal bone. The tube Eardrum opens briefly during swallowing, allowing equalization of Tensor tympani Round the pressures on either side of the eardrum. During rapid muscle window external pressure changes (such as in an elevator ride or during takeoff or descent in an airplane), the unequal Eustachian tube Scali forces displace the eardrum; such physical deformation tympani may cause discomfort or pain and, by restricting the mo- tion of the tympanic membrane, may impair hearing. Outer Middle Inner Blockages of the eustachian tube or fluid accumulation in ear ear ear the middle ear (as a result of an infection) can also lead to difficulties with hearing. Vibrations from the eardrum are transmitted by the lever system Bridging the gap between the tympanic membrane and formed by the ossicular chain to the oval window of the scala the inner ear is a chain of three very small bones, the ossi- vestibuli. The malleus (hammer) is attached to the pensory system for the ossicles, are not shown. The combination eardrum in such a way that the back-and-forth movement of the four suspensory ligaments produces a virtual pivot point of the eardrum causes a rocking movement of the malleus. The stapedius and tensor tympani muscles third bone, the stapes (stirrup). This last bone, through its modify the lever function of the ossicular chain.

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Upright posture imposes other diagnostic structural features trusted levitra extra dosage 40mg, such as the sigmoid (S-shaped) curvature of the FIGURE 2 generic levitra extra dosage 60 mg with visa. Body Organization and © The McGraw−Hill Anatomy purchase levitra extra dosage 60 mg online, Sixth Edition Organization cheap levitra extra dosage 60 mg with visa, and the Anatomical Nomenclature Companies, 2001 Human Organism 26 Unit 2 Terminology, Organization, and the Human Organism Creek Tarsier Aye-aye Gorilla Human FIGURE 2. Cerebrum Optic lobe Cerebellum Cerebrum Codfish Frog Chimpanzee Cerebellum Alligator Goose Human Creek Horse FIGURE 2. Body Organization and © The McGraw−Hill Anatomy, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism Chapter 2 Body Organization and Anatomical Nomenclature 27 (a) (b) (c) (d) (e) (f) FIGURE 2. The human thumb is structurally Taxon Grouping Characteristics adapted for tremendous versatility in grasping objects. Kingdom Animalia Eucaryotic cells without walls, plastids, The saddle joint at the base of the thumb allows a wide or photosynthetic pigments range of movement (see fig. All primates have op- Phylum Chordata Dorsal hollow nerve cord; notochord; posable thumbs. Humans, like no other Subphylum Vertebrata Vertebral column animals, have developed articulated speech. The anatomi- Class Mammalia Mammary glands; hair; convoluted cal structure of our vocal organs (larynx, tongue, and lips), cerebrum; heterodont dentition and our well-developed brain have made this possible. Order Primates Well-developed brain; prehensile hands Family Hominidae Large cerebrum, bipedal locomotion 5. Although this characteristic is well de- veloped in several other animals, it is also keen in humans. Genus Homo Flattened face; prominent chin and nose with inferiorly positioned nostrils Our eyes are directed forward so that when we focus on an Species sapiens Largest cerebrum object, we view it from two angles. Stereoscopic vision gives us depth perception, or a three-dimensional image. Body Organization and © The McGraw−Hill Anatomy, Sixth Edition Organization, and the Anatomical Nomenclature Companies, 2001 Human Organism 28 Unit 2 Terminology, Organization, and the Human Organism We also differ from other animals in the number and The human body contains many distinct kinds of cells, arrangement of our vertebrae (vertebral formula), the kinds and each specialized to perform specific functions. Examples of spe- number of our teeth (tooth formula), the degree of development cialized cells are bone cells, muscle cells, fat cells, blood cells, of our facial muscles, and the structural organization of various liver cells, and nerve cells. The human characteristics just described account for the splendor of our cultural achievements. As bipedal animals, we have our hands free to grasp and manipulate objects with our op- Tissue Level posable thumbs. We can store information in our highly developed brain, make use of it at a later time, and even share our learning Tissues are layers or groups of similar cells that perform a com- through oral or written communication. The entire body is composed of only four princi- pal kinds of tissues: epithelial, connective, muscular, and nervous Knowledge Check tissue. An example of a tissue is the muscle within the heart, whose function it is to pump the blood through the body. Why are humans considered members outer layer of skin (epidermis) is a tissue because it is composed of the phylum Chordata? Organ Level An organ is an aggregate of two or more tissue types that per- BODY ORGANIZATION forms a specific function. Examples of organs are the Structural and functional levels of organization characterize the heart, spleen, pancreas, ovary, skin, and even any of the bones human body, and each of its parts contributes to the total organism. Each organ usually has one or more primary tis- Objective 4 Identify the components of a cell, tissue, organ, sues and several secondary tissues. In the stomach, for example, and system, and explain how these structures relate to one the inside epithelial lining is considered the primary tissue be- another in constituting an organism. Secondary tissues of the stomach are the con- Objective 5 Describe the general function of each system. Cellular Level The cell is the basic structural and functional component of System Level life. Humans are multicellular organisms composed of 60 to The systems of the body constitute the next level of structural 100 trillion cells. A body system consists of various organs that have such vital functions of life as metabolism, growth, irritability similar or related functions. Examples of systems are the circula- (responsiveness to stimuli), repair, and replication are car- tory system, nervous system, digestive system, and endocrine sys- ried on. For example, the Cells are composed of atoms—minute particles that pancreas functions with both the endocrine and digestive sys- are bound together to form larger particles called molecules tems and the pharynx serves both the respiratory and digestive (fig.

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