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Differentiation along The presence or absence of SRY in the genome determines the male line requires active 5 -reductase proven viagra plus 400 mg, the enzyme whether male or female gonadal differentiation takes place generic 400mg viagra plus overnight delivery. Without DHT viagra plus 400 mg on line, re- Thus discount viagra plus 400 mg without a prescription, in normal XX (female) fetuses purchase viagra plus 400 mg on-line, which lack a Y chro- gardless of the genetic, gonadal, or hormonal sex, the ex- mosome, ovaries, rather than testes, develop. The Whether possessing the XX or the XY karyotype, every structures that develop from the primordial structures are embryo goes initially through an ambisexual stage and has illustrated in Figure 39. A 4- to 6-week-old human embryo possesses in- gen-dependent differentiation occurs only during fetal life different gonads, and undifferentiated pituitary, hypothal- and is thereafter irreversible. Testicular descent into the rived from coelomic epithelium and underlying mes- scrotum, which occurs during the third trimester, is also enchyme, and primordial germ cells, which migrate from controlled by androgens. In many species, a sharp decline in the circulating levels of progesterone and The duration of pregnancy in women averages 270 14 a concomitant rise in estrogen precede birth. Parturition or the onset progesterone does not fall significantly before delivery. Uncoordinated uterine contractions start about rise in placental progesterone-binding protein or by a de- 1 month before the end of gestation. The termination of cline in the number of myometrial progesterone receptors. They increase intracellular calcium ine muscle is regulated by hormones and by mechanical concentrations of myometrial cells and activate the actin- factors. The hormones include progesterone, estrogen, myosin contractile apparatus. The mechanical fac- parturition, the concentration of prostaglandins in amni- tors include distension of the uterine muscle and stretching otic fluid rises abruptly. Aspirin and in- Progesterone hyperpolarizes myometrial cells, lowers domethacin, inhibitors of prostaglandin synthesis, delay or their excitability, and suppresses uterine contractions. Estrogen, in gen- tions, and its release from both maternal and fetal pitu- eral, has the opposite effects. Oxytocin is used clinically to CHAPTER 39 Fertilization, Pregnancy, and Fetal Development 697 Indifferent drogen precursors. Injections of ACTH and cortisol in late stages pregnancy do not induce labor. Interestingly, the adminis- tration of estrogens to the cervix causes ripening, probably by increasing the secretion of prostaglandins. Genital fold Genital swelling POSTPARTUM AND PREPUBERTAL PERIODS Genital tubercle Lactation is controlled by pituitary and ovarian hormones, requires suckling for continued milk production, and is the major source of nutrition for the newborn. As the child grows, puberty will occur around age 10 to 11 because the hypothalamus activates secretion of pituitary hormones Male Female that cause secretion of estrogens and androgens from the Glans gonads and adrenals during that time. Alterations in hor- Fused Glans mone secretion lead to abnormal onset of puberty and go- urogenital Urethral groove nadal development. Several hormones participate in Prepuce mammogenesis, the differentiation and growth of the mam- Body of mary glands, and in the production and delivery of milk. Galac- Urethral orifice Scrotal topoiesis, the maintenance of lactation, is regulated by PRL. The mammary glands begin to differentiate in the pectoral region as an ectodermal thickening on the epidermal ridge during weeks 7 to 8 of induce labor (see Clinical Focus Box 39. The prospective mammary glands lie along bilat- significance of oxytocin is that it helps expel the fetus from eral mammary ridges or milk lines extending from axilla to the uterus, and by contracting uterine muscles, it reduces groin on the ventral side of the fetus. Most of the ridge dis- uterine bleeding when bleeding may be significant after de- integrates except in the axillary region. Interestingly, oxytocin levels do not rise at the time mals with serially repeated nipples, a distinct milk line with of parturition. Mam- corpus luteum and the decidua, assists parturition by soft- mary buds are derived from surface epithelium, which in- ening the cervix, permitting the eventual passage of the vades the underlying mesenchyme. However, the the buds elongate, branch, and sprout, eventually forming relative role of relaxin in parturition in humans is unclear, the lactiferous ducts, the primary milk ducts. The ducts unite, laxin reaches its peak during the first trimester, declines to grow, and extend to the site of the future nipple.

The subunit composition of the GABAA receptor could be one confounding factor in resolving this question buy viagra plus 400mg otc. For instance purchase 400mg viagra plus, flumazenil has been reported to augment the action of GABA at cloned receptors comprising a4 b2 g2 subunits generic viagra plus 400 mg without a prescription. Apparent effects of the antagonist in vivo could also depend on whether there is any tonic activation of the benzodiazepine receptor by an endogenous ligand generic viagra plus 400 mg online. Flumazenil is available in the clinic for intravenous infusion to reverse benzodiazepine-induced sedation (e order viagra plus 400 mg on-line. However, because it has a half-life of only 1 h in humans, it is only of realistic benefit in reversing the actions of agonist benzodiazepines with a short half-life, such as midazolam. The potential benefits of benzodiazepine partial agonists are as non-sedative, anti- anxiety agents. Because of their low efficacy, it was predicted that a partial agonist should not induce sedation even if their receptor occupancy exceeds that normally required for an anti-anxiety effect when using a full agonist. One such compound, bretazenil, has been developed but failed to reach the clinic because it displayed some sedative activity and, more problematic, there were end-of-dose rebound effects that were undoubtedly exacerbated by its short half-life. Currently, the partial agonist, abecarnil (a b-carboline), is undergoing clinical trials. For the current status of the development of partial agonists and other promising benzodiazepine receptor ligands see Cheetham and Heal (2000). Even benzodiazepine inverse agonists might yet find some useful applications such as in the relief of cognitive deficits (which are increased by benzodiazepine full agonists) (Abe, Takeyama and Yoshimura 1998). With the rapidly expanding understanding of different combinations of subunits that comprise the GABAA receptor, it is hoped to develop compounds that target specific subunit combinations and improve cognitive function in dementia but which lack any proconvulsant or anxiogenic actions. However, three candidates have been given prominent attention, albeit for different reasons, and are worthy of mention. Although subsequently found to be an artefact of the extraction process, this compound turned out to be a ligand for the benzodiazepine receptor, nonetheless, and was the first inverse agonist to be identified. The anxiogenic effects in humans of its more stable congener, FG 7142, are described graphically in a report by Dorow et al. Both these peptides are neuroactive and ODN turns out to have inverse agonist activity at GABAA receptors both in vivo and in vitro and to have marked effects on behaviour (e. However, there is scepticism as to whether the brain can manufacture sufficient peptide to regulate the ubiquitous GABAA receptor on a moment-to-moment basis. Currently, the binding of TTN to the peripheral benzodiazepine site, and its effect on neurosteroid synthesis, is attracting greater interest (Do Rego et al. Finally, the presence in human post-mortem brain tissue of the active metabolite of diazepam, desmethyldiazepam, raised some curiosity and frank alarm (Sangameswaran et al. At the time of its discovery in the brain it was thought that there was no enzyme system capable of producing such halogenated compounds and that its presence in the brain reflected dietary intake from an environment contaminated by overuse of its parent compound. However, its discovery in stored brain tissue which had been obtained before the synthesis of the benzodiazepines allayed these fears. It is now thought possible that some benzodiazepines, including desmethyl- diazepam, occur naturally and that they are taken in as part of a normal diet (Table 19. Although, by analogy with the opioids, one would expect there to be an endogenous ligand for the widely distributed benzodiazepine receptor, its existence remains uncertain and we must be alert to the possibility that any such ligand(s) could have either agonist or inverse agonist activity. Chrysin Wheat grain Diazepam, desmethyldiazepam, lormetazepam Potato Diazepam, desmethyldiazepam, lormetazepam Karmelitter Geist Amentoflavon 410 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION ENDOGENOUS LIGANDS AND BENZODIAZEPINE RECEPTORS: AN EXPLANATION FOR THE CAUSE OF ANXIETY The undisputed efficacy of benzodiazepines in relief of anxiety led to the question of whether this disorder could arise from abnormal concentrations in the brain of an endogenous ligand or a malfunction of the benzodiazepine/GABA receptor system. An important study, aimed at distinguishing between these possibilities, has been carried out in humans (Nutt et al. In this case, the administration of the antagonist, flumazenil, should induce anxiety in normal subjects and exacerbate anxiety in anxious patients. In this case, the administration of flumazenil should relieve anxiety in anxious patients and have no, or sedative, effects in healthy subjects. In this case, flumazenil (which normally has zero efficacy) should induce anxiety in anxious patients but have no effects in healthy subjects because they have normal receptors. To distinguish between these possibilities, flumazenil was administered to panic patients and control subjects. The results of the experiment were consistent with the third possibility: flumazenil induced panic attacks in 8 of 10 patients but not in control subjects (Fig. Unfortunately, the change(s) in the benzodiazepine receptor or its coupling to the rest of the GABAA receptor are unknown, 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.

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Physical therapy generic 400 mg viagra plus with mastercard, a major com- changes for affected individuals may make ponent of the treatment program discount 400 mg viagra plus, can it more difficult for them to cope purchase 400 mg viagra plus with amex. Individ- help the individual improve or stabilize uals as well as family members may feel motor ability buy discount viagra plus 400 mg on-line, prevent contractures buy 400 mg viagra plus otc, or helpless and hopeless. As a result, they adapt the environment to promote safe- may be reluctant to participate in activi- ty and maximum independence. Occupa- ties designed to maintain or improve their tional therapists may help individuals current level of function. Speech therapists ed to behavioral changes may result in may help individuals maximize their unsafe situations for the individual. Those speech capability as well as their ability to who are in denial about their condition swallow. In some instances cognitive and their limitations may also be exposed retraining and memory training may be to situations that could result in unsafe useful. Individuals are usually affected in cult, social interactions also become more middle or later life, with males affected difficult, resulting in increasing social iso- more frequently than women. Personality changes that may pro- duce violent or hostile behaviors further Manifestations of ALS stress support systems. Because Huntington’s disease has a Symptoms of ALS depend on the area of genetic component, family members may the nervous system affected; both upper be under the additional stress of knowing and lower extremities are affected. There that they may themselves be at risk for are two primary forms of ALS: developing Huntington’s disease. Coun- • Spinal form seling, education, and support can help to • Bulbar form reduce the stress that family members may be experiencing. The spinal form of ALS is characterized by muscular weakness, muscle atrophy Vocational Issues in Huntington’s Disease (decrease in size), spasticity, and hyperac- tive reflexes. Individuals may first com- Huntington’s disease is a progressive, plain of tripping, stumbling, or awk- degenerative disease; however, in the ear- wardness when walking or running. In the bulbar condition progresses and individuals have form individuals may first notice difficul- increasing difficulty with memory, com- ty in breathing, slurring of speech or low- munication skills, and physical ability, ered volume when speaking, or difficulty sheltered employment may be the most with swallowing. As the condition progresses, symptoms become worse, spreading to other parts of Amyotrophic Lateral Sclerosis the body so that eventually, whether the (ALS; Lou Gehrig’s Disease) individual first experienced the bulbar or spinal form of ALS, he or she eventually Amyotrophic lateral sclerosis (ALS), also experiences all the symptoms. Individuals sometimes referred to as Lou Gehrig’s dis- become increasingly weak and immobile. They may experience respiratory mus- current medical theory suggests a multi- cle weakness leading to breathing factorial etiology that may include genet- problems, and in later stages of the con- ic, viral, autoimmune, and neurotoxic fac- dition they may require ventilatory assis- Neuromuscular Conditions 101 tance in order to breathe. Cognitive func- Psychosocial Issues in ALS tion, sensation, vision, hearing, and bow- el and bladder function are usually not The social, economic, and psychologi- affected. It is common for individuals with ALS to Diagnosis of ALS experience fear, anxiety, and depression, especially as the condition progresses There is no reliable laboratory test to and the individual recognizes rapid pro- detect the presence of ALS. Diagnosis is gressive deterioration of physical func- usually based on the symptoms the indi- tion. Because of loss of mobility and in- vidual exhibits and their progression and creased dependency, feelings of helpless- the individual’s medical history, and by ness and powerlessness are also common. Some individuals may experience discour- agement and become angry as their phys- Treatment and Management of ALS ical limitations increase. They may ex- perience grief with each subsequent loss of There is no cure for ALS, and no effec- function. There may be loss in social rela- tive treatment is currently available. They may feel vidual with ALS to remain independent as guilty because of their increased depend- long as possible, be comfortable, and ence on others and may express concern avoid complications. Treatment of symp- and frustration over the burden they feel toms is used to maintain muscle function, is being placed on family members. Medications to reduce Since individuals with ALS need sub- spasticity may be used; however, these stantial help with most activities of daily can also increase muscle weakness and living, family members most often find cause sedation. Physical therapy may be themselves in a caregiving role even in helpful to maintain function and to the early stages of the individual’s condi- reduce the painful symptoms brought on tion. If the individ- Occupational therapists can provide sup- ual with ALS is also the major breadwin- port and help individuals to adapt their ner, financial issues may become a major environment in order to maximize func- concern. Individuals with speech difficul- to assume the caregiving role, which fur- ties may utilize speech therapists to help ther contributes to financial distress. Family members may also have feelings of Speech pathologists may be utilized to help powerlessness, anger, or anxiety about the individuals who have difficulty with swal- future.

Circulatory System © The McGraw−Hill Anatomy purchase 400mg viagra plus, Sixth Edition Body Companies cheap 400mg viagra plus otc, 2001 566 Unit 6 Maintenance of the Body going to the esophagus as it passes through the mediastinum; seg- Subclavian a viagra plus 400 mg. Portion of the Aorta The abdominal portion of the aorta is the segment of the aorta between the diaphragm and the level of the fourth lumbar ver- tebra buy 400mg viagra plus mastercard, where it divides into the right and left common iliac ar- teries purchase viagra plus 400mg with mastercard. Small inferior phrenic arteries that serve the diaphragm are the first vessels to arise from the abdominal portion of the aorta. It arises anteriorly from the abdominal portion of the aorta, just below the celiac trunk. The superior mesenteric artery supplies Deep palmar Superficial palmar blood to the small intestine (except for a portion of the duode- arch arch num), the cecum, the appendix, the ascending colon, and the proximal two-thirds of the transverse colon. The next major vessels to arise from the abdominal portion of the aorta are the paired renal arteries that carry blood to the Digital arteries Digital arteries kidneys. Smaller suprarenal arteries, located just above the renal arteries, serve the adrenal (suprarenal) glands. The testicular ar- teries in the male and the ovarian arteries in the female are small FIGURE 16. The inferior mesenteric artery is the last major branch of the abdominal portion of the aorta. It is an unpaired anterior ves- The ulnar artery extends down the medial, or ulnar, side of sel that arises just before the iliac bifurcation. The inferior the forearm and gives off many small branches to the muscles on mesenteric supplies blood to the distal one-third of the transverse that side. It, too, has an initial large branch, the ulnar recurrent colon, the descending colon, the sigmoid colon, and the rectum. At Several lumbar arteries branch posteriorly from the ab- the wrist, the ulnar and radial arteries anastomose to form the su- dominal portion of the aorta throughout its length and serve the perficial and deep palmar arches. The metacarpal arteries of the muscles and the spinal cord in the lumbar region. In addition, an hand (not shown) arise from the deep palmar arch, and the digital unpaired middle sacral artery (fig. Branches of the Thoracic Portion of the Aorta Arteries of the Pelvis and Lower Extremity The thoracic portion of the aorta is a continuation of the aortic arch as it descends through the thoracic cavity to the diaphragm. The abdominal portion of the aorta terminates in the posterior This large vessel gives off branches to the organs and muscles of pelvic area as it bifurcates into the right and left common iliac the thoracic region. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 16 Circulatory System 567 Ribs FIGURE 16. Pericardium of heart cecum, appendix, of aorta ascending colon, and Posterior intercostal aa. Intercostal and thoracic transverse colon muscles, and pleurae Suprarenal aa. Transverse colon, descending colon, sigmoid colon, and rectum Common iliac aa. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 568 Unit 6 Maintenance of the Body FIGURE 16. Two branches arise from the external arterial blood to the gluteal muscles and the organs of the iliac artery, however, before it passes beneath the inguinal liga- pelvic region (fig. An inferior epigastric artery branches from the external the iliolumbar and lateral sacral arteries. The internal vis- iliac artery and passes superiorly to supply the skin and muscles ceral organs of the pelvis are served by the middle rectal and of the abdominal wall. The deep circumflex iliac artery is a the superior, middle, and inferior vesicular arteries to the small branch that extends laterally to supply the muscles at- urinary bladder. The muscles of the buttock are femoral triangle on the upper medial portion of the thigh served by the superior and inferior gluteal arteries. At this point, it is close to the surface the upper medial thigh muscles are supplied with blood from and its pulse can be palpated. The internal pudendal artery of the in- femoral artery to serve the thigh region. The largest of these, ternal iliac artery serves the musculature of the perineum and the deep femoral artery, passes posteriorly to serve the ham- the external genitalia.

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