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Lipitor

By K. Taklar. Mercy College.

What the overall physiological consequences of either an increase or decrease in 5-HT transmission in any brain region might be is beyond the scope of this chapter order 40 mg lipitor with visa. However purchase 20 mg lipitor visa, it is certain that the diverse cocktail of 5-HT receptors in every brain region gives scope for flexibility and refinement in the 5-HT response that would not be possible if there were only the two receptors identified by Gaddum purchase 10mg lipitor with mastercard. This flexibility applies not only to the qualitative features of the response but also its duration buy lipitor 40mg on-line. Another dimension of sophistication is added by the different affinities of 5-HT for each of its receptors and differences in their rates of desensitisation. An interesting discussion of how all these variables could affect overall 5-HT transmission in the brain can be found in Uphouse (1997). This is not easy because the actions of drugs that target specific receptors leads us to believe that 5-HT helps to regulate: mood, anxiety, sleep, body temperature, appetite, sexual behaviour, movement, intestinal motility, cardiovascular function (central and peripheral) and nociception, at least. While a detailed explanation of the physiology of each of these functions is not possible here, and many are covered in appropriate chapters of this book, two topics are of particular interest. One is the general role of 5-HT during the waking state: this is discussed below because, in the light of recent discoveries, we might have to modify the currently accepted view. A second is the role of 5-HT in feeding, a subject to which this chapter has referred to some extent already. This will be covered here because the regulation of body weight is becoming an increasingly important research area, reflecting the growing concern about the serious health problems linked with obesity. THE ROLE OF 5-HT IN THE WAKING STATE One puzzle concerning 5-HT transmission in the brain, and a defining feature of 5-HT neurons in the DRN and MRN, is their slow, rhythmic firing rate of 1±2 spikes/s. Certainly, electrophysiolo- gical studies in vivo have shown that neurons in the DRN do respond to environmental stimuli but, unlike noradrenergic neurons, they do not seem to have a role in homeostasis or the response to aversive stimuli. This is deduced from findings that the single-unit response of neurons in the DRN is not affected by a range of aversive stimuli such as environmental heat or systemic pyrogens; drug-induced changes in systemic blood pressure or glucoregulatory challenge. In all these cases, the activity of these neurons during the 5-HYDROXYTRYPTAMINE 205 stimulus is no greater than that expressed during active waking (Jacobs and Azmitia 1992). In fact, it is generally thought that the only consistent change in response of these neurons is that reflecting changes in the sleep±waking cycle such that these neurons are maximally active during waking but can become totally quiescent during rapid eye movement (REM) sleep (see Chapter 22). As a result of such findings, it has been suggested that 5-HT neurons in the brain are concerned merely with regulation of motor responses. In so doing, they could be responsible for gating motor output and coordinating homeostatic and sensory function (Jacobs and Azmitia 1992; Jacobs and Fornal 1999). This would be consistent with evidence that increases in the firing rate of neurons in the DRN precede an increase in arousal (see Chapter 22). This could mean that the frequency of discharge codes the state of arousal and primes target cells for forthcoming changes in the motor response to sensory inputs. It has even been claimed that 5-HT neurons projecting to the primary visual cortex are involved more in the interpretation of movement in the visual field than its qualitative features. Evidence deemed to support this theory comes from the discovery of a population of neurons in the DRN that, unlike the majority, do not show any increase on waking and some may even reduce their firing during orientation to environmental stimuli. However, they do increase their activity during vegetative motor behaviours involving oral±buccal movements (chewing, grooming). Some are even active during anticipation of food, suggesting that they are capable of developing responses to conditioned environmental cues. To some extent, this proposal is supported by microdialysis studies of changes in 5-HT efflux in the terminal fields of 5-HT neurons. A single swim stress also fails to increase 5-HT efflux in the medial prefrontal cortex of rats. Indeed, it would be interesting to know whether this reflects any long-term influence of 5-HT-moduline on regulation of 5-HT release (see above). Also, 5-HT efflux is increased in the Raphe nuclei and their terminal fields after handling of rats (Adell, Casanovas and Artigas 1997), hypo- glycaemic shock (Vahabzadeh, Boutelle and Fillenz 1995) and even during a conditioned fear response in which animals actually freeze (i. Finally, there is compelling evidence that 5-HT transmission in the amygdala affects emotional, rather than merely motor, components of anxiety (see Chapter 19).

Upon examination by her physician generic lipitor 40 mg otc, she is found Clotting factors buy 20mg lipitor free shipping, mostly produced in the liver purchase 5 mg lipitor with visa, have a series to have a distended abdomen that is tender in the area of glutamic acid residues that must be carboxylated by a vi- between her ribs at the top of her abdomen lipitor 5 mg. The reduced form of vitamin K is a necessary cofac- edly shows no significant abnormalities. During carboxylation of the clot- reasons, the patient is later taken for a venogram and ting factor, vitamin K becomes an epoxide. Warfarin is was found to have thrombosis of her hepatic veins, thought to disrupt the vitamin K cycle, thereby preventing Budd-Chiari syndrome. She is subsequently referred to a the necessary carboxylation of clotting factors. Initially, the patient is treated with di- continues to synthesize these factors, but they lack effect uretic medication (spironolactone and furosemide to in- and therefore clotting is limited. Temperature Regulation PART 8 and Exercise Physiology CHAPTER The Regulation of Body Temperature* C. The control of thermoregulatory responses is accom- temperature is relatively uniform in the core and is regu- plished through reflex signals generated in the CNS ac- lated within narrow limits, while shell temperature is per- cording to the level of the thermoregulatory set point, as mitted to vary. The body produces heat through metabolic processes and and nerve endings elsewhere, chiefly in the skin. The re- exchanges energy with the environment as mechanical sponse of sweat glands and superficial blood vessels to work and heat; it is in thermal balance when the sum of these signals is modified by local skin temperature. Acclimatization to heat can dramatically increase the vironment equals energy loss to the environment. In humans, the chief physiological thermoregulatory re- homeostasis in hot temperatures, and conserve salt while sponses are the secretion of sweat, which removes heat from sweating profusely. Acclimatization to cold has only mod- the skin as it evaporates; the control of skin blood flow, which est effects, depending on how the acclimatization was pro- governs the flow of heat to the skin from the rest of the body; duced, and may include increased tissue insulation and and increasing metabolic heat production in the cold. Adverse systemic effects of excessive heat stress include “thermostat”) varies cyclically with the circadian rhythm circulatory instability, fluid-electrolyte imbalance, exer- and the menstrual cycle, and is elevated during fever. Core and whole-body skin temperatures govern the reflex and heatstroke involve organ and tissue injury produced in control of physiological thermoregulatory responses, several ways, some of which are not well understood. The which are graded according to disturbances in the body’s primary adverse systemic effect of excessive cold stress is thermal state. As a water-based solution Hwarm-blooded animals, and regulate their internal freezes, ice crystals consisting of pure water form, so that all body temperatures within a narrow range near 37 C, in dissolved substances in the solution are left in the unfrozen spite of wide variations in environmental temperature liquid. Internal body temperatures of poikilotherms, or comes more and more concentrated. Freezing damages cells cold-blooded animals, by contrast, are governed by envi- through two mechanisms. In addition, the increase in solute concen- ing cells and tissues can tolerate without harm extends from tration of the cytoplasm as ice forms denatures the proteins just above freezing to nearly 45 C—far wider than the lim- by removing their water of hydration, increasing the ionic its within which homeotherms regulate body temperature. As we shall see, tissue Second, temperature changes profoundly alter biologi- temperature is important for two reasons. High functions as electrical properties and fluidity of cell mem- temperatures alter the configuration and overall structure of branes, and through a general effect on most chemical re- protein molecules, even though the sequence of amino action rates. Such alteration of protein structure is reaction rates vary approximately as an exponential func- called denaturation. A familiar example of denaturation by tion of temperature (T); increasing T by 10 C increases the heat is the coagulation of albumin in the white of a cooked reaction rate by a factor of 2 to 3. Since the biological activity of a protein molecule de- tion, the ratio of the rates at two temperatures 10 C apart is pends on its configuration and charge distribution, denatu- called the Q for that reaction, and the effect of tempera- 10 ration inactivates a cell’s proteins and injures or kills the ture on reaction rate is called the Q effect. Injury occurs at tissue temperatures higher than about Q may be generalized to apply to a group of reactions 10 45 C, which is also the point at which heating the skin be- that have some measurable overall effect (such as O con- 2 comes painful. The severity of injury depends on the tem- sumption) in common and are, thus, thought of as com- perature to which the tissue is heated and how long the prising a physiological process. A com- monly used rule is that a patient’s fluid and calorie needs are Upper limit increased 13% above normal for each 1 C of fever. The profound effect of temperature on biochemical re- Temperature action rates is illustrated by the sluggishness of a reptile regulation Heatstroke, that comes out of its burrow in the morning chill and be- seriously impaired brain lesions comes active only after being warmed by the sun.

C lipitor 5 mg mastercard, fined as electromagnetic radiation between the wave- A series of prisms can bring parallel rays to a point cheap 10 mg lipitor with amex. The familiar ing case of this arrangement is a convex (converging) lens generic lipitor 5mg with visa. F cheap lipitor 20 mg line, Plac- range of intensities, from a single photon to the direct light ing two such lenses together produces a shorter focal length. H, A negative As with all such radiation, light rays travel in a straight lens can effectively increase the focal length of a positive lens. The amount of bending is determined by the angle at which the ray strikes the surface; if the an- algebraically. External lenses (eyeglasses or contact lenses) gle is 90 , there is no bending, while successively more are used to compensate for optical defects in the eye. An appropriately chosen spherical organ, consisting of several layers and structures pair of prisms can turn parallel rays to a common point (Fig. A convex lens may be thought of as a series of such white, connective tissue layer, the sclera, and a transparent prisms with increasingly more bending power (Fig. Six extraocular muscles that control the D), and such a lens, called a converging lens or positive direction of the eyeball insert on the sclera. The next layer lens, will bring an infinite number of parallel rays to a com- is the vascular coat; its rear portion, the choroid, is pig- mon point, called the focal point. A converging lens can mented and highly vascular, supplying blood to the outer form a real image. The front portion contains the iris, a is its focal length (FL), which may be expressed in meters. Often the diopter (D), which is the inverse of ted to the interior of the eye. The iris also gives the eye its the focal length (1/FL), is used to describe the power of a characteristic color. An advantage of this system is that dioptric held in place by a radial arrangement of zonule fibers, sus- powers are additive; two convex lenses of 25 D each will pensory ligaments that attach it to the ciliary body, which function as a single lens with a power of 50 D when placed contains smooth muscle fibers that regulate the curvature of next to each other (Fig. The lens is composed A concave lens causes parallel rays to diverge (Fig. A concave lens placed Between the cornea and the iris/lens is the anterior before a positive lens lengthens the focal length (Fig. However, because the two eyes are mirror im- Anterior chamber Canal of Schlemm ages of each other, information from the overlapping vi- Iris sual field of one eye “fills in” the missing part of the image Posterior Ciliary body chamber from the other eye. The image that falls on the retina fibers is real and inverted, as in a camera. Neural processing re- stores the upright appearance of the field of view. The im- age itself can be modified by optical adjustments made by Vitreous humor the lens and the iris. Most of the refractive power (about 43 D) is provided by the curvature of the cornea, with the lens providing an additional 13 to 26 D, depending on the focal distance. The muscle of the ciliary body has primarily a Optic disc parasympathetic innervation, although some sympathetic Fovea (blind spot) innervation is present. When it is fully relaxed, the lens is at its flattest and the eye is focused at infinity (actually, at Retina anything more than 6 meters away) (Fig. When the Choroid Optic nerve ciliary muscle is fully contracted, the lens is at its most Sclera curved and the eye is focused at its nearest point of distinct vision (Fig. The near point of vision for view from above, showing the relative positions the eye of a young adult is about 10 cm. This con- dition is called presbyopia; supplemental refractive power, fluid. This liquid is continuously secreted by the epithelium of the ciliary processes, located behind the iris. As the fluid accumulates, it is drained through the canal of Schlemm into the venous circulation. If too much pressure builds up in the anterior cham- ber, the internal structures are compressed and glaucoma, a condition that can cause blindness, results.

Magnetic resonance imaging of the brainstem and cra- Williams & Wilkins discount lipitor 20 mg otc, 1972 cheap 10mg lipitor mastercard. The Human Brain and Spinal Cord: Functional Neuroanatomy Magnusson KR discount 20mg lipitor with amex, Clements JR order lipitor 20 mg, Larson AA, Madl JE, Beitz AJ. Cholecystokinin-, galamin-, and corticotropin- combined retrograde transport-immunohistochemical study. So- releasing factor-like immunoreactive projections from the nucleus matosens Res 1987;4:177–190. Stanford, CT: Ap- nerve: A cyto-and chemoarchitectonic study in the human. On the naming of clinical disorders, with particular ref- Wilkins, 1998. Cerebellar nuclear projections from the basilar pontine Jones SL, Light AR. Serotoninergic medullary raphespinal projection nuclei and nucleus reticularis tegmenti pontis as demonstrated with to the lumbar spinal cord in the rat: A retrograde immunohisto- PHA-L tracing in the rat. Atlas of the Central Nervous System in Man, 3rd Kandel ER, Schwartz JH, Jessell TM. Monaghan PL, Beitz AJ, Larson AA, Altschuler RA, Madl JE, Mullett Keirman JA. Immunocytochemical localization of glutamate-, glutaminase- Viewpoint, 7th Ed. Immunocytochemical identification of long ascending, pep- Adv Anat Embryol Cell Biol 1987;103:1–62. Neuroanatomy: Magnetic Resonance Imaging and Computed To- Nelson BJ, Mugnaini E. The Comparative Anatomy and Histology of the Exp Brain Res Ser 17:86–107). Cerebellum: The Human Cerebellum, Cerebellar Connections, and Newman DB, Hilleary SK, Ginsberg CY. The Central Nervous Sys- Schnitzlein HN, Hartley EW, Murtagh FR, Grundy L, Fargher JT. Computed Tomography of the Head and Spine: A Photographic Noback CR, Strominger NL, Demarest RJ. The Human Brain: An Introduction to its Functional A Photographic Color Atlas of MRI, CT, Gross, and Microscopic Anatomy, 5th ed. Inter- and intra-laminar dis- to the hippocampus mediated by stellate cells in the entorhinal cor- tribution of tectospinal neurons in 23 mammals. Baltimore: Urban & projections in primate as studied by retrograde double-labeling Schwarzenberg, 1981. Pernkopf Atlas of Topographic and Applied Human neurones of the substantia nigra receive a GABA-containing input Anatomy, 3rd ed. Atlas of Cross Section Anatomy of the Brain: Guide to anterograde tracing method. J Comp Neurol 1990;294: the Study of the Morphology and Fiber Tracts of the Human Brain. New York: Blakiston Division, McGraw-Hill Book Company, Inc, Strata P (ed). Illustrated Guide to the Central bulbospinal axons that contain serotonin and either enkephalin or Nervous System. Localization of enkephalin- Tatu L, Moulin T, Bogousslavsky J, Duvernoy H. Arterial territories ergic neurons in the dorsolateral pontine tegmentum projecting to of human brain: Brainstem and cerebellum. The posterior cranial fossa: Microsurgical anatomy and Terzian H, Ore GD. Neurosurgery 2000; 47 (Supplement); by bilateral removal of the temporal lobes. The supratentorial cranial space: Microsurgical Tieman SB, Butler K, Neale JH.

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