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Thousands of these dead cells shed the ultraviolet radiation in sunlight cheap 500mg meldonium overnight delivery. Tactile cells are sparse from the skin surface each day order meldonium 500 mg on-line, only to be replaced by new compared to keratinocytes and melanocytes. This surface layer is cornified; it is receptor cells aid in tactile (touch) reception. Cornifica- mented granular dendrocytes are scattered throughout the tion, brought on by keratinization, is the drying and flat- stratum basale. They are protective macrophagic cells that tening of the stratum corneum and is an important ingest bacteria and other foreign debris. Integumentary System © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 5 Integumentary System 109 TABLE 5. The specific characteristics of each epidermal layer are de- scribed in table 5. Tattooing colors the skin permanently because dyes are in- jected below the mitotic basal layer of the epidermis into the underlying dermis. In nonsterile conditions, infectious organisms may be introduced along with the dye. Small tattoos can be removed by skin grafting; for large tattoos, mechanical abrasion of the skin is preferred. 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.

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Unfortunately generic 500 mg meldonium amex, the change(s) in the benzodiazepine receptor or its coupling to the rest of the GABAA receptor are unknown buy meldonium 500 mg on-line, as are the stimuli that could explain this functional change. Recent studies suggest that the binding of [11C]flumazenil is abnormally low in panic patients (Malizia et al. However, this is the only tested theory so far to connect panic anxiety directly with a disorder of the GABAA receptor. The receptor shift theory could also explain why benzodiazepines are ineffective in treating panic disorder but, because these drugs do effectively relieve generalised anxiety, it seems that the theory might explain the origin of the former, but not the latter disorder, and that they have different causes. He went on to stimulate the locus coeruleus of (chair- restrained) monkeys and showed that this caused behavioural changes, some of which resembled a cluster of behaviours displayed by the animals when under threat. This work led to the proposal that anxiety was due to (or exacerbated by) excessive ANXIETY 411 Figure 19. This proposes that patients with panic disorder have dysfunctional GABAA receptors such that the actions of drugs that behave as antagonists in normal subjects are expressed as inverse agonism in panic patients. It is unlikely that this theory extends to generalised anxiety disorder (GAD), for which benzodiazepine agonists are highly effective treatments, but it could explain why these drugs are relatively ineffective at treating panic disorder. This is an a2-adrenoceptor antagonist that increases the firing rate of, and release of noradrena- line from, noradrenergic neurons by blockade of presynaptic a2-adrenoceptors on the neuronal cell bodies and terminals, respectively. Increases in noradrenaline release, inferred from measurement of the noradrenaline metabolite, 3-methoxy, 4-hydroxy- phenylglycol (MHPG), in plasma, have shown that the noradrenergic response in panic patients who experience a panic attack with yohimbine is greater than that in either panic patients who do not express this response or in normal patients (Bremner et al. Unfortunately, the noradrenergic response to yohimbine is not exaggerated in patients with GAD, suggesting that the aetiology of this form of anxiety could differ from that of panic disorder. Nevertheless, the a2-adrenoceptor agonist, clonidine, which has the opposite effect to yohimbine on noradrenergic neurons, is sometimes used to relieve anxiety, especially that associated with alcohol and opiate withdrawal. However, it is not a viable long-term treatment for anxiety because of its effects on the cardio- vascular system. One complication with the above concept is that, in some brain regions, the majority of a2-adrenoceptors are postsynaptic and so a reduction in a2-adrenoceptor-mediated noradrenergic transmission, after treatment with yohimbine, cannot be ruled out as a causal factor for the anxiety induced by this drug. Another problem is that yohimbine is also a 5-HT1A receptor agonist, a 5-HT1D partial agonist and a 5-HT2B antagonist; all these receptors could be involved in anxiety (see below). Furthermore, a finding that argues against excessive noradrenergic transmission as a cause of anxiety is that stimulating the locus coeruleus in humans induces a pleasant sensation, rather than anxiety (Libet and Gleason 1994) and that not all anxiogenic challenges increase plasma MHPG (Silverstone et al. Measurements of noradrenaline release in animals have not helped to resolve this confusion. Microdialysis studies in vivo have confirmed that anxiogenic doses of 412 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION yohimbine do increase the extracellular concentration of noradrenaline in the frontal cortex of rats but an anxiogenic dose of the benzodiazepine inverse agonist, FG 7142, does not. These observations question the role of noradrenaline as an initiator of anxiety as does the finding that the anti-anxiety drug, buspirone (see Chapter 9), increases the concentration of noradrenaline in the extracellular fluid in the frontal cortex of freely- moving rats (Done and Sharp 1994). Whether this is because buspirone is metabolised to 1-(2-pyrimidinyl)-piperazine (1-PP), which is an a2-adrenoceptor antagonist, is uncertain. Unfortunately, no studies have investigated the effects of chronic administration of this drug on noradrenergic transmission; this could be important because, unlike benzodiazepines, buspirone is effective therapeutically only after several weeks of treatment. The finding that infusion of the b-adrenoceptor agonist, isoprenaline, has an anxiogenic effect in humans implicates this receptor subytype also but little (if any) isoprenaline crosses the blood±brain barrier and so any anxiogenic effects are likely to be an indirect consequence of the autonomic arousal it will cause (i. Of course, this alone does not rule out a role for these receptors in the psychological component of anxiety. However, one complication is that propranolol, like many other b-adrenoceptor antagonists, is also a 5-HT1A receptor antagonist which could contribute to its anti-anxiety effects (see below). Indeed, subjects claim that, whereas these drugs relieve the peripheral manifestations of anxiety, they have no appreciable effects on its psychological component. This is supported by evidence that these drugs are of little, if any, long-term benefit in GAD (Nutt 1990) and that they can even exacerbate this condition. If excessive noradrenergic transmission is a causal factor in anxiety, then it would be predicted that a lesion of central noradrenergic neurons would have an anti-anxiety effect in behavioural models of this condition. Unfortunately, the behavioural effects of such lesions are notoriously inconsistent and there are many reports of negative findings (e.

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Semen samples with low sperm motility can attained during puberty buy 500 mg meldonium with amex, at approximately 12 years of age discount meldonium 250mg with visa. The onset of puberty requires changes in the sensitivity, ac- There is no evidence for chemotactic interactions be- tivity, and function of several endocrine organs, including tween the egg and sperm, although evidence exists for spe- those of the hypothalamic-pituitary-gonadal axis. Sperm arrive in the vicinity of the egg at random, and some exit into the abdominal cavity. Although sperm remain OVUM AND SPERM TRANSPORT, motile for up to 4 days, their fertilizing capacity is limited FERTILIZATION, AND IMPLANTATION to 1 to 2 days in the female reproductive tract. Sperm can be cryopreserved for years, if agents such as glycerol are Sperm deposited in the female reproductive tract swim up used to prevent ice crystal formation during freezing. During maturation in the epididymis, the sperm ac- enters the uterus, and implants into the endometrium. To bind to and penetrate the zona pellucida, the sperm must undergo ca- The Egg and Sperm Enter the Oviduct pacitation, an irreversible process that involves an increase A meiotically active egg is released from the ovary in a in sperm motility, the removal of surface proteins, a loss of cyclical manner in response to the LH surge. For a suc- lipids, and merging of the acrosomal and plasma mem- cessful fertilization, fresh sperm must be present at the branes of the sperm head. To increase the proba- branes and change in acrosomal structure is called the acro- bility that the sperm and egg will meet at an optimal time, some reaction. The reaction occurs when the sperm cell the female reproductive tract facilitates sperm transport binds to the zona pellucida of the egg. It involves a redis- during the follicular phase of the menstrual cycle, prior to tribution of membrane constituents, increased membrane ovulation (see Chapter 38). However, during the luteal fluidity, and a rise in calcium permeability. Capacitation phase, after ovulation, sperm survival and access to the takes place along the female genital tract and lasts 1 hour to oviduct are decreased. Sperm can be capacitated in a chemically de- egg and sperm begin to exhibit signs of degeneration fined medium, a fact that has enabled in vitro fertilization within 24 hours after release. In vitro fertilization may be The volume of semen (ejaculatory fluids and sperm) in used in female infertility as well. The liquid component of the semen, called semi- The ovum is grasped by the fimbria, ciliated finger-like nal plasma, coagulates after ejaculation but liquefies projects of the oviducts. The grasping of the egg is facili- within 20 to 30 minutes from the action of proteolytic en- tated by ciliary movement and muscle contractions, under zymes secreted by the prostate gland. The coagulum the influence of estrogen secreted during the periovulatory forms a temporary reservoir of sperm, minimizing the ex- period. Because the oviduct opens into the peritoneal cav- pulsion of semen from the vagina. During intercourse, ity, eggs that are not picked up by the oviducts can enter some sperm cells are immediately propelled into the cer- the abdominal cavity. Those remaining in the vagina do not survive an abdominal ovum is fertilized. The cervical canal constitutes a more on the presence of granulosa cells surrounding the egg. Oocyte maturity is judged from the Candidates for in vitro fertilization (IVF) are women with dis- morphology of the cumulus (granulosa) cells and the pres- ease of the oviducts, unexplained infertility, or endometrio- ence of the germinal vesicle and first polar body. The ma- sis (occurrence of endometrial tissue outside the endome- ture oocytes are then placed in culture media. About Follicular development is induced with one or a combina- 100,000 spermatozoa are added for each oocyte. After 24 tion of GnRH analogs, clomiphene, recombinant FSH, and hours, the eggs are examined for the presence of two menopausal gonadotropins (a combination of LH and FSH). Embryos are grown to the Follicular growth is monitored by measuring serum estra- four- to eight-cell stage, about 60 to 70 hours after their re- diol concentration and by ultrasound imaging of the devel- trieval from the follicles. When the leading follicle is 16 to 17 mm in di- often deposited in the uterine lumen in order to increase ameter and/or the estradiol level is greater than 300 pg/mL, the chance for a successful pregnancy. To ensure a recep- hCG is injected to mimic an LH surge and induce final follic- tive endometrium, daily progesterone administrations be- ular maturation, including maturation of the oocyte. A successful pregnancy rate of proximately, 34 to 36 hours later, oocytes are retrieved from 15 to 25% has been reported by many groups, which com- the larger follicles by aspiration using laparoscopy or a pares favorably with that of natural human pregnancy. The fertilizable life of the human ovum is about 24 head becomes anchored to the membrane surface of the hours, and fertilization occurs usually by 2 days after ovu- egg, and microvilli protruding from the oolemma (plasma lation. The fertilized ovum remains in the oviduct for 2 to membrane of the egg) extend and clasp the sperm.

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