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They have been described in the retina (where r1is expressed) but relatively little is known of their function in the brain although they are widely expressed (Bormann 2000) cheap 120mg orlistat with mastercard. For example 120mg orlistat otc, all three r subunits are found in cerebellar Purkinje cells. Native GABAC receptors may be homomeric pentamers of a single r subunit or heteromeric pentamers of more than one of the r subunits. GABAC receptor dose±response curves have Hill slopes around 3 or greater, unlike GABAA receptor dose±response curves where the Hill slope is usually around 2. When expressed alone, 5-HT3-A subunits form functional homomeric receptors but these have a much smaller single channel conductance (less than 1. Native 5-HT3 receptors are likely to be pentameric heteromers of 5-HT3-A and 5-HT3-B subunits. Synaptic transmission mediated by 5-HT3 receptors has been 66 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION described in only a few places in the brain, such as in the locus coeruleus and it has been suggested that most 5-HT3 receptors are located presynaptically on nerve terminals where their calcium permeability may be important in potentiating transmitter release. GLUTAMATE RECEPTORS Glutamate receptors mediate fast synaptic transmission throughout the nervous system. They have been classified pharmacologically as three main types according to their sensitivity to three specific agonists: kainate, AMPA and NMDA. The NMDA receptors are unique among the ion channel receptors in requiring the binding of two separate agonists, glutamate and glycine in order to activate the receptor. Selective antagonists for both the glutamate binding site (AP5) and the glycine binding site (7-chloro- kynurenate) have been developed. AMPA and kainate receptors are often referred to as non-NMDA receptors and are blocked by the non-NMDA receptor antagonists CNQX and DNQX. Gene cloning has identified five kainate receptor subunits, four AMPA receptor subunits and six NMDA receptor subunits (Table 3. Kainate receptors Kainate receptors may be formed by homomeric combination of GluR5, GluR6 or GluR7 or by heteromeric combination of any of GluR5±7 with the kainate binding proteins, KA1 or KA2. AMPA receptors AMPA receptors can be formed by homomeric or heteromeric combinations of GluR1± 4. However, most native AMPA receptors are more likely to be heteromeric assemblies Table 3. Between different a subunits in any family there is around 60±70% amino-acid sequence homology whereas between a and b subtypes, for example, there is normally around only 40% sequence homology. Mouse NMDA receptor subunits are denoted by the Greek letters x and e while rat and human are indicated as shown. NEUROTRANSMITTER RECEPTORS 67 of GluR2 with one or more of the other AMPA receptor subunits. The main evidence for this came from the discovery that the mRNA for GluR2 is edited at the position coding for a glutamine residue in the TM2 region. This change in the GluR2 subunit dominates the functional properties of the receptor when heteromeric combinations of GluR subunits are expressed in oocytes or cell lines. Thus, wherever GluR2 subunits are expressed, the AMPA receptors so formed have a linear current±voltage relation and are Na‡ permeable but not Ca2‡ permeable. This is the case at most synapses which have been investigated in the brain but interestingly, does not appear to be so at excitatory synapses onto interneurons where the AMPA receptors are probably heteromeric assemblies of GluR1, GluR3 and GluR4. The mRNAs for GluR5 and GluR6 are also edited at the equivalent position to that of GluR2 but the extent of editing varies between 50% and 90% in different brain regions. Thus kainate receptors are likely to be more hetero- geneous than AMPA receptors in terms of their calcium permeability. NMDA receptors The NMDA receptors come in four main flavours depending on which NR2 subunit (or subunits) is involved in forming the receptor (Table 3. Functional NMDA receptors result from the co-assembly of one or more members of three different subfamilies of subunits: NR1, NR2 and NR3. The NR1 family is composed of one subunit with nine different alternatively spliced variants. Block by NMDA channel blockers such as ketamine, MK-801 and phencyclidine is affected by which splice variant of the NR1 subunit is involved, probably because the NR1 splice variant affects the kinetics of channel activation (the effectiveness of any channel blocker being dependent on how much the channel is open).

Coping proven orlistat 120 mg, conflictural social interactions orlistat 60mg without prescription, social support, and mood Bartlett, J. Staying on the roller coaster with clients: Implications of the new HIV/AIDS med- Kilby, J. Journal of individuals who are HIV+ and individuals with Black Psychology, 25(3), 316–335. Hemophilia and pain condition: Implications of a biopsychosocial related conditions. New England Journal of Medicine, the lives of people living with HIV disease and 348(22), 2171–2172. Home management research in hematologic disorders: Sickle cell dis- of haemophilia. American Journal of Pediatrics and templating returning to work for people living Oncology, 15, 87–91. New Eng- problem of pain in adolescents with sickle cell dis- land Journal of Medicine, 341(2), 99–109. C HAPTER 9 Endocrine Conditions NORMAL STRUCTURE AND • hypothalamus, a area of the brain that FUNCTION OF THE ENDOCRINE coordinates functions of the nervous SYSTEM system and endocrine system. The endocrine tem is regulatory, with different hormones system is composed of ductless glands altering various body processes so that the (endocrine glands) scattered throughout the body’s internal balance (homeostasis) is body (Figure 9–1). Although each endocrine produce chemical substances called hor- gland has its own unique and independ- mones that are secreted directly into the ent function, endocrine glands often bloodstream and act as messengers on tar- work in concert. Endo- by the endocrine system control and inte- crine glands include the: grate a variety of body activities, establish- • thyroid gland, located in the neck, in ing a delicate chain of communication front of and on either side of the tra- between various body systems and influ- chea (windpipe). Each adrenal • Reproductive maturity and function gland has two parts, the medulla and • Metabolism the cortex. Each part has a different • Adjustment to internal and external function. Overproduction or underproduction of It is divided into two parts, the ante- one hormone can affect a number of oth- rior and the posterior lobes. Insufficient amounts of the parathy- function of regulating the production and roid hormone in the blood can cause spasm secretion of another hormone. If parathyroid hormone is to ed by the thyroid gland, regulates the rate be effective, vitamin D must be present. When the level of thy- (medulla) secretes the hormones epineph- roxine in the blood is high, metabolism rine and, to a lesser extent, norepinephrine speeds up; when it is low, metabolism slows at times of stress to enable the body to pre- down. These Parathyroid hormone, which regulates the hormones increase the heart rate, increase concentrations of calcium and phosphate muscle tone, and constrict blood vessels in the body, is secreted by the parathyroid in times of stress. Excessive amounts of the parathy- adrenal glands (cortex) secretes hormones roid hormone in the blood can result in the called steroids, which regulate many essen- demineralization of bone, causing bones to tial functions, such as electrolyte and become fragile so that they are easily bro- water balance, metabolism, immune re- Pituitary Thyroid Parathyroid glands Adrenal gland Kidney Pancreas Ovaries (female) Testes (male) Figure 9–1 Endocrine System. Conditions of the Endocrine System 261 sponses, and inflammatory reactions. The Hyperthyroidism (Graves’ Disease, adrenal cortex is essential to life. If it is dys- Thyrotoxicosis) functional, death will occur within a few days unless the hormones that it normal- Manifestations of Hyperthyroidism ly secretes are replaced. Hyperthyroidism is the overproduction The anterior lobe of the pituitary secretes of thyroid hormone because of hyperfunc- thyroid-stimulating hormone (TSH) (which tion of the thyroid gland. Hyperthyroid- is necessary for thyroid function), growth ism results in an increased metabolic rate. The posterior lobe of the pituitary ingestion of the hormone or inflammation gland stores hormones produced in the of the thyroid gland (thyroiditis) rather hypothalamus. Antidiuretic hormone (ADH), than from an overactive thyroid gland which increases water reabsorption by the (Woeber, 2000). Other Special cells within the islets of Langer- symptoms of hyperthyroidism include hans in the pancreas produce the hormones restlessness, irritability, nervousness, and insulin and glucagon, which are necessary weight loss. The increased rate of metab- for the metabolism of carbohydrates, pro- olism causes intolerance to heat; thus, teins, and fats.

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Blood plasma constitutes approximately 55% of a given volume of Objective 8 Describe the structure and functions of the blood generic orlistat 60 mg without a prescription. These proteins remain within the blood and interstitial fluid and assist in maintaining body homeostasis cheap orlistat 120mg overnight delivery. The three types of plasma Objective 11 Describe the location of the conduction proteins are albumins, globulins, and fibrinogen. They are produced by the liver and provide the blood with carrier molecules and with the viscos- Location and General Description ity needed to maintain and regulate blood pressure. The The hollow, four-chambered, muscular heart is roughly the size three types of globulins are alpha globulins, beta globulins, and of a clenched fist. The heart contracts an estimated 42 mil- the liver and function in transporting lipids and fat-soluble vita- lion times a year, pumping 700,000 gallons of blood. Gamma globulins are produced by lymphoid tissues and are The heart is located in the thoracic cavity between the lungs antibodies of immunity. Fibrinogens are large molecules that are synthesized in the ing downward and resting on the diaphragm. The base of the heart liver and, together with platelets, play an important role in clot- is the broad superior end, where the large vessels attach. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 546 Unit 6 Maintenance of the Body FIGURE 16. The parietal pericardium is actually The wall of the heart is composed of three distinct layers composed of an outer fibrous pericardium and an inner serous (table 16. It is the serous pericardium that produces the lu- visceral pericardium. The space between this layer and the parietal bricating pericardial fluid that allows the heart to beat in a pericardium is the pericardial cavity, just described. It is composed of cardiac muscle tissue (see chapter 4) and arranged Pericarditis is an inflammation of the parietal pericardium in such a way that the contraction of the muscle bundles results that results in an increased secretion of fluid into the pericar- dial cavity. Because the tough, fibrous portion of the parietal peri- in squeezing or wringing of the heart chambers. The thickness of cardium is inelastic, an increase in fluid pressure impairs the the myocardium varies in accordance with the force needed to movement of blood into and out of the chambers of the heart. Thus, the thickest por- Some of the pericardial fluid may be withdrawn for analysis by in- tion of the myocardium surrounds the left ventricle and the atrial jecting a needle to the left of the xiphoid process to pierce the pari- etal pericardium. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 16 Circulatory System 547 TABLE 16. In- separated from each other by the thin, muscular interatrial sep- flammation of the endocardium is called endocarditis. Atrioventricular valves (AV valves) lie between the atria and ventricles, and semilunar valves are located at the bases of the two large vessels leaving the heart. The atria contract and empty simultaneously into vessels that supply blood to the muscular wall of the heart. The most prominent groove is the coronary sulcus that encircles the walls of the atria are reinforced with latticelike pestinate mus- heart and marks the division between the atria and ventricles. Contraction of these modified cardiac muscles ejects blood The partition between the right and left ventricles is denoted by from the atria to the ventricles. Each atrium has an ear-shaped, two (anterior and posterior) interventricular sulci. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 548 Unit 6 Maintenance of the Body TABLE 16. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 16 Circulatory System 549 Left common carotid artery Left subclavian artery Brachiocephalic trunk Aortic arch Superior vena cava Descending aorta Left pulmonary artery Azygos vein Branches of left Right pulmonary artery pulmonary artery Branches of right pulmonary artery Left pulmonary veins Left atrium Right pulmonary veins Posterior cardiac vein Right atrium Coronary sinus Inferior vena cava Left ventricle Right ventricle (b) Aortic arch Superior vena cava Left pulmonary artery Pulmonary trunk Right pulmonary veins Left pulmonary veins Left atrium Pulmonary valve Aortic valve Right atrium Left atrioventricular valve Right atrioventricular valve Papillary muscle Chordae tendineae Interventricular septum Left ventricle Inferior vena cava Trabeculae carneae Right ventricle (c) FIGURE 16. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 550 Unit 6 Maintenance of the Body The following discussion shows the sequence in which The walls of the left ventricle are thicker than those of blood flows through the atria, ventricles, and valves. It is impor- the right ventricle because the left ventricle bears a greater tant to keep in mind that the right side of the heart (right atrium workload, pumping blood through the entire body. The endo- and right ventricle) receives deoxygenated blood (blood low in cardium of both ventricles is characterized by distinct ridges oxygen) and pumps it to the lungs. The aortic valve (also called the aortic semilunar valve), located at the base of the ascending portion of Right Atrium the aorta, closes as a result of the pressure of the blood when the left ventricle relaxes, and thus prevents the backflow of blood The right atrium receives systemic venous blood from the superior into the relaxed ventricle. The coronary sinus is an additional opening into the right atrium that receives venous blood from the myocardium of the heart itself. Cardiac catheterization is a procedure used in the diagnosis of certain heart disorders.

There- Acquired hearing loss occurs after birth or fore buy orlistat 120 mg lowest price, increasing the loudness of sound later in life orlistat 120mg for sale. There are a number of causes does not correct the hearing problem and of acquired hearing loss. Noise-induced hearing loss is a com- Conditions of the Outer Ear mon but preventable type of acquired hearing loss. Avoiding loud noises or wear- Conditions of the outer ear can con- ing ear protectors when exposed to loud tribute to hearing loss when there is an noise could drastically reduce the inci- obstruction that disrupts the mechanical dence of noise-induced hearing loss. Although conditions of injury or disease, such as from traumatic the outer ear may not have a major impact brain injury or from multiple sclerosis on hearing or may be correctable, they affecting the auditory pathway. Presby- may also be disfiguring, causing cosmetic cusis (hearing loss associated with aging) concerns. The extent to the outer ear can result from congenital which degeneration of portions of the au- conditions or from trauma. Other condi- ditory system is due to the aging process tions of the outer ear that may impede Hearing Loss and Deafness 149 hearing are buildup of earwax (cerumen), Because of the proximity of the mastoid foreign bodies in the ears, or growths (e. Com- as it once was because of the earlier detec- plete occlusion, however, generally results tion of otitis media and treatment with in a low to moderate conductive loss. Con- antibiotics; however, chronic mastoiditis ditions of the outer ear that cause tempo- and associated complications can result if rary conductive hearing impairments can previous ear infections are left untreated. Otosclerosis Conditions of the Middle Ear Otosclerosis is a hardening of the ossi- cles (incus, stapes, and malleus of the mid- Conditions of the middle ear may cause dle ear), which transmit sound impulses temporary or permanent hearing loss. Early symptoms may in- clude trouble hearing on the telephone Perforated Tympanic Membrane but not in crowds. It causes conduc- A thickened or perforated tympanic mem- tive hearing loss because hardening of the brane (ruptured eardrum) may or may not ossicles reduces the efficiency of the trans- impair hearing. Some individuals may also have vestibular symptoms such as ver- Otitis Media tigo (dizziness) or impaired equilibrium. Individuals with otosclerosis often hear Otitis media (inflammation and fluid amplified speech well and without distor- buildup in the middle ear) can cause con- tions; consequently, they are usually good ductive hearing losses because of collec- candidates for hearing aids. Hearing can tion of fluid in the middle ear or because also often be restored or improved with of damage to the tympanic membrane (ear- surgical intervention; however, surgery drum) as a result of infection or rupture. When de- Usually, with appropriate treatment, per- termining if surgery is appropriate, indi- manent hearing loss will not result. If not viduals’ lifestyle and occupation are con- treated promptly, however, otitis media sidered. Since surgery may affect vestibu- can lead to mastoiditis (Hendley, 2002). If individuals’ hob- Mastoiditis is an infection of the mas- bies or occupations expose them to large toid cells within the mastoid process locat- and rapid changes in barometric pressure, ed in the temporal bone of the skull. A number of therapies, including group Conditions of the Inner Ear cognitive therapy, have been used to help people cope with tinnitus. Adjustment to Many conditions of the inner ear cause tinnitus does not appear to be related to permanent hearing loss. Labyrinthitis Meniere’s Disease Labyrinthitis (inflammation of the labyrinth of the inner ear) may be acute Meniere’s disease is a disorder of the without resulting in permanent hearing inner ear that encompasses the triad of loss. Labyrinthitis may occur as a compli- recurrent severe vertigo, sensorineural hear- cation of otitis media, influenza, or upper ing loss, and tinnitus (noise or ringing in respiratory infections. The cause of Meniere’s disease ear is involved, symptoms of vertigo (diz- is unknown. One or both ears may be ziness), nausea, and vomiting frequently affected. When attacks do occur, Tinnitus they are dramatic, often debilitating indi- viduals during the episode. Tinnitus (ringing or noise in the ears) Vertigo usually appears suddenly and is may or may not be accompanied by hear- often accompanied by nausea and vomit- ing loss. Tinnitus may be intermittent or may be loud noise or can be a symptom of a more constant between attacks, becoming worse serious condition, such as tumor, high during an attack.

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