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By P. Brant. Rollins College. 2018.

Boca Raton buy quetiapine 50 mg amex,FL: CRC Press effective 50mg quetiapine, couraged the further development of such agents purchase quetiapine 300mg overnight delivery. Complete amino acid promise for novel therapies for the treatment of these var- sequence of urotensin I,a hypotensive and corticotropin releasing ious neuropsychiatric disorders without severely compro- neuropeptide from Catoftomus. Amino acid composition and mising this highly complex hormonal system. Clearly with sequence analysis of sauvagine,a new active peptide from the the recent advances made within a very short period of time, skin of Phyllomedusa sauvagei. Cloning and sequence increasingly complex neurohormone system. Characteriza- ACKNOWLEDGMENT tion of the genomic corticotropin-releasing factor (CRF) gene from Xenopus laevis: two members of the CRF family exist in Dr. De Souza is a stockholder in Neurocrine Biosciences, amphibians. Urocortin,a mam- malian neuropeptide related to fish urotensin I and to corticotro- 1. Characterization of a 41-residue pin-releasing factor. Physiological and behavioral responses trophin releasing factor receptors. Identification of a tor of anxiety of stress responses? Physiology and pharmacology of corti- factor and sauvagine in mammalian brain. Identification of a second corticotropin-releasing factor and corticotropin in plasma during corticotropin-releasing factor receptor gene and characterization pregnancy,labour and puerperium. Neuropeptides 1987;10: of a cDNA expressed in heart. Heterogeneity between brain and substance for human corticotropin-releasing factor in late gesta- pituitary corticotropin-releasing factor receptors is due to differ- tional maternal plasma which could mask the ACTH-releasing ential glycosylation. Characterization of CRH pin-releasing factor receptor expressed in heart and skeletal mus- binding protein in human plasma by chemical cross-linking and cle. New tion of the cDNAs for human and rat corticotropin-releasing York: The New York Academy of Sciences,1987:48–66. Corticotropin-releasing factor receptors in the rat 49. Corticotropin-releasing central nervous system: characterization and regional distribu- factor-binding protein is a glycoprotein. The central distribution ing factor receptors in the brain-pituitary-immune axis. In: Stress, of a corticotropin-releasing factor (CRF)-binding protein predicts neuropeptides, and systemic disease. San Diego: Academic Press, multiple sites and modes of interaction with CRF. Chemical and biological Handbook of chemical neuroanatomy: neuropeptide receptors in the characterization of corticotropin-releasing factor. Catecholami- regulation of corticotropin-releasing factor receptors in the cen- nergic modulation of corticotropin-releasing factor and adreno- tral nervous,endocrine and immune systems. Age-related decreases chemical study of human corticotropin-releasing factor2 recep- in corticotropin-releasing factor (CRF) receptors in rat brain and tors. Effects of CRF on spontaneous and sensory-evoked for rapid screening of corticotropin-releasing factor receptor lig- activity of locus ceruleus neurons. Electrophysiology of corticotropin-releasing factor in ings of the 25th Annual Meeting of the Neuroscience Society, San nervous tissue.

This reflects easy permeability between the urinary and the venous compartments of the kidney cheap quetiapine 100mg overnight delivery. Imaging W hen indicated order quetiapine 300 mg free shipping, ultrasound imaging generic 200mg quetiapine with visa, tomodensitometry, and scintigraphy provide objective evidence of pyelonephritis. In case of vesicoureteral reflux, urinary tract infection necessarily involves the upper urinary tract. As specified else- where, renal abscess due to enterobacteri- aceae (as opposed to hematogenous renal abscess, often of staphylococcal origin) can be considered a severe form of pyelonephritis with renal tissue liquefaction, ending in a walled-off cavity. Primary versus secondary urinary tract infection FIGURE 7-19 Cystogram of a 65-year-old wom an. A volum inous blad- der tum or (arrows) infiltrates the blad- der floor and the initial segm ent of the urethra. FIGURE 7-18 An episode of urinary tract infection (UTI) should prompt considera- tion of whether it involves a normal urinary tract or, alternatively, if it is a complication of an anatomic malformation. This is especially true of relapsing UTI in both genders, and this hypothesis should be systematically raised in males and in children. Recurrent cystitis in fem ales can be explained by hym eneal scars that pull open the urethral outlet during intercourse. Although rarely, other m alform ations that prom ote recurrent fem ale cystitis are occasionally discovered, such as urethral diverticula (arrows). Finally, it should be recalled that recurrent or chronic cystitis in an older wom an can also reveal an unsuspected bladder tum or. In males, acute prostatitis may reveal urethral stenosis. Urethral stenosis is a good explanation for acute prostatitis. The beaded appearance of the stenosis (arrow) suggests an earlier episode of gonorrheal urethritis. Childhood vesicoureteral reflux is five times more common in girls than in boys. It has a genetic background: several cases occasionally occur in the same family. Unless detected and corrected early, espe- cially the most severe forms of this class and when urine is infected (one episode of pyelonephritis suffices), childhood VUR is a major cause of cortical scarring, renal atrophy, and in bilateral cases chronic renal insufficiency. The International Reflux Study classifies reflux grades as follows: I) ureter only; II) ureter, pelvis, and calyces, no dilation, and normal calyceal fornices; III) mild or moderate dilation or tortuosity of ureter and mild or moderate dilation of renal pelvis but no or slight blunting of fornices; IV) moderate dilation or tortu- I II III IV V osity of ureter and moderate dilation of renal pelvis and calyces, complete obliteration of sharp angle of fornices but maintenance of papillary impressions in majority of calyces; V) gross dilation and FIGURE 7-21 tortuosity of ureter, gross dilation of renal pelvis and calyces. Papillary The severity of vesicoureteral reflux (VUR) as graded in 1981 by impressions are no longer visible in the majority of calyces. W hen children have International Reflux Study Committee; with permission. The calyceal cavities are very close to the quences on the left kidney (B) consist of calyceal distension and a renal capsule, indicating com plete cortical atrophy. This picture is clubbed appearance due to the destruction of the papillae and of typical of chronic pyelonephritis secondary to vesicoureteral reflux. Here, the right kidney is globally the lower pyelocalyceal system crosses the upper ureter and opens atrophic. A typical cortical scar is seen on the outer aspect of the left into the bladder less obliquely than normally, allowing reflux of urine kidney. The lower pole, however, is fairly well-preserved with nearly and explaining repeated attacks of pyelonephritis followed by atrophy normal parenchymal thickness. Retrograde cystography is indicated for repeated episodes of pyelonephritis and when intravenous pyelog- raphy or computed tomography renal examination discovers cortical scars. In adults, retrograde cystography is obtained by direct catheter- ization of the bladder. FIGURE 7-25 FIGURE 7-26 (see Color Plate) In the paraplegic, In children, isotopic and m ore generally cystography allows in patients with a diagnosis of vesi- spinal disease, coureteral reflux neurogenic bladder with m uch less radi- is responsible for ation than if cystog- stasis, bladder raphy were carried distension, and out with iodinated diverticula. Ultrasonography typically discloses a swollen FIGURE 7-28 kidney with loss of corticom edullary differentiation, denoting renal The ultrasound procedure occasionally discloses the cavity of a small inflam m atory edem a. Im ages corresponding to the infected zones renal abscess, a common complication of acute pyelonephritis, even are m ore dense than norm al renal tissue (arrows). Sim ple pyelonephritis does not areas in an edem atous, swollen kidney.

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In all of these revealed the localization of both the CRF1 and CRF2 recep- tissues buy cheap quetiapine 300mg on line,the primary second messenger system involved in tor subtypes quality 100mg quetiapine,demonstrating the utility of this novel radioli- transducing the actions of CRF is stimulation of cAMP Chapter 7: Corticotropin-Releasing Factor 99 production (29 purchase quetiapine 100 mg on line,31–33,40). CRF initiates a cascade of enzy- cDNA and Amino Acid Sequences matic reactions in the pituitary gland beginning with the The CRF-BP was first isolated and purified to near homoge- receptor-mediated stimulation of adenylate cyclase,which neity for sequencing and generation of oligonucleotide ultimately regulates POMC-peptide secretion and possibly probes (47). Screening a human liver cDNA library using synthesis. POMC-derived peptide secretion mediated by the probes generated from the original amino acid sequence activation of adenylate cyclase in the anterior and neuroin- revealed a full-length cDNA containing a 1. Similarly in the brain and putative N-linked glycosylation site was found at amino spleen,the pharmacologic rank order profile of CRF-related acid 203,which agrees with the previous observation of the peptides for stimulation of adenylate cyclase is analogous presence of asparagine-linked sugar moieties on the native to the profile seen in pituitary and in keeping with the protein (49). Subsequent screening of a rat cerebral cortical affinities of these compounds for receptor binding. In addi- cDNA library,revealed the presence of a single clone con- tion,the putative CRF receptor antagonist -hel ovine taining a 1. The transduction mechanisms may be involved in the actions of pharmacology of these proteins appears to be similar with CRF. For example,CRF has been shown to increase protein both the rat and human binding proteins having high affin- carboxyl methylation,and phospholipid methylation in ity for the rat/human CRF (Kd 0. Preliminary evidence suggests that CRF affinity for the ovine form of CRF (Kd 250 nM). Al- may regulate cellular responses through products of arachi- though there may be some similarities in the binding do- donic acid metabolism (42). Furthermore,although the evi- mains of the binding protein and the CRF receptor (as dence in anterior pituitary cells suggests that CRF does not evidenced by the equal affinity of r/hCRF),these are distinct directly regulate phosphatidylinositol turnover or protein proteins,each with unique characteristics and distributions. Thus, the effects of CRF on anterior pituitary cells and possibly Although the human and rat forms of the CRF-BP are ho- in neurons and other cell types expressing CRF receptors mologous (as indicated),there is a somewhat different ana- are likely to involve complex interactions among several in- tomic distribution pattern in the two species. Peripheral expres- sion of the binding protein may have its greatest utility in CRF and Its Binding Protein in Human the modulation and control of the elevated levels of CRF Plasma in circulating plasma induced by various normal physiologic Under normal conditions,the plasma levels of CRF remain conditions (see the preceding). In addition,expression of low; however,CRF levels are markedly elevated in plasma this binding protein in the brain and pituitary offers addi- during the late gestational stages of pregnancy (43–45). The tional mechanisms by which CRF-related neuronal or neu- source of the pregnancy-associated CRF is most likely the roendocrine actions may be modulated. The CRF in brain regions including neocortex,hippocampus (primarily the maternal plasma is bioactive in releasing ACTH from in the dentate gyrus),and olfactory bulb. In spite of the high levels of brain,mRNA is localized to the amygdaloid complex with CRF in the maternal plasma,there is no evidence of mark- a distinct lack of immunostained cells in the medial nucleus. A plausible explanation for this paradoxic the brainstem particularly in the auditory,vestibular,and situation could be the presence of a binding protein in the trigeminal systems,raphe nuclei of the midbrain and pons, plasma of pregnant women that could specifically inhibit and reticular formation (50). In addition,high expression the biological actions of CRF (44,45). This hypothesis was levels of binding protein mRNA are seen in the anterior validated by the isolation of a CRF-binding protein (CRF- pituitary,predominantly restricted to the corticotrope cells. BP) from human plasma and its subsequent cloning and Expression of this protein in the corticotropes strongly sug- expression (see the following). Norepinephrine has been the interactions of CRF with its receptor,which is also reported to have both stimulatory and inhibitory effects on known to reside on corticotropes; however,the detailed role CRF release that may be a consequence of the dose adminis- of the binding protein in regulating pituitary–adrenal func- tered as well as the receptor subtype involved. Similarly,opioids have been re- ported to either inhibit or stimulate CRF release depending Regulation of Pituitary Hormone on the nature of the opioid tested,dose utilized,and recep- Secretion tor specificity ( versus ) involved. Drugs acting at CRF is the major physiologic regulator of the basal and GABA–benzodiazepine–chloride ionophore complex are stress-induced release of ACTH, -endorphin,and other potent inhibitors of CRF secretion. The extent and time course of changes POMC-derived peptides in anterior pituitary cells in culture in CRF in the paraventricular nucleus and median eminence and in vivo; these actions of CRF can be antagonized by of the hypothalamus following application of stress are the CRF receptor antagonist -helical ovine CRF(9-41) or highly dependent on the nature of the stressor as well as by immunoneutralization with an anti-CRF antibody. The effects of stress to increase eral other lines of evidence support a critical role for endoge- the release and synthesis of CRF are mediated by many of nous CRF in regulating ACTH secretion.

Evidence suggests a culture bound syndrome purchase quetiapine 300mg mastercard, as AN is rare in Asia and developing countries - although this pattern is probably changing (Jennings et al order quetiapine 50 mg with amex, 2006) buy cheap quetiapine 50mg line. Earlier reports found that the prevalence of AN was higher in higher socio-economic schools, but the evidence is now equivocal. Recent studies, however, indicate the risk for hospitalization for NA is related to mothers level of education (higher risk is associated with higher maternal education; Ahren et al, 2011). Perhaps such mothers are more demanding of their daughters. Maintaining factors Mentioned under etiology, the relief of anxiety by dieting and dysphoric mood caused by eating, may also serve as a maintaining factor. Starvation is another maintaining factor, inducing complex physiological and psychological reactions involving central and peripheral mechanisms. Such mechanism may have had evolutionary value, allowing animals to survive periods of food shortage, but in the current setting they serve only to perpetuate a vicious cycle of weight loss. Neuropsychological testing Neuropsychological testing reveals cognitive deficits (Weider et al, 2013) which are related to severity of the disorder, and may play a role in cause and outcome (Zakzanis et al, 2009). Executive control is impaired with problems in set-shifting, attention and decision-making (Treasure & Russell, 2011). A link has been demonstrated between amenorrhoea, brain structure and deficits in cognition, including recall, verbal fluency, working memory, visual reproduction, reading, maths and oral language (Chui et al, 2008). Neuroimaging Neuroimaging studies demonstrate structural and functional abnormalities. There is global reduction of grey (GM) and white matter (WM) during the acute stage. GM is reduced by 5-20%, and WM is reduced to a lesser extent. GM loss is found in the anterior cingulate, hippocampi and the temporal, parietal and prefrontal regions. With recovery GM is restored, but most studies find small residual deficits remain. In one study, there was 60% restoration after 15 weeks of successful treatment. A recent diffusion tensor imaging study (DTI; Kazlouski et al, 2011) revealed WM abnormalities in the fornix, fronto-occipital fasciculus and the posterior cingulum. Magnetic resonance spectroscopy (MRS), which gives information on nerve cell damage by assessing brain metabolites, indicates altered cell membrane turnover which is reversible with recovery. Functional magnetic resonance imaging (fMRI) using visual stimuli of food or body image has been reviewed (Garcia-Garcia et al, 2013). Differences between those with eating disorders and healthy controls located differences in two circuits, 1) limbic and paralimbic areas (associated with reward), and 2) prefrontal regions associated with cognitive functions and control. The insula may be of particular importance (Kaye et al, 2009), as it integrates interoceptive information – confirmation is awaited. The hippocampal volume of women with AN who are food restricting and exercising is larger than that of normal controls. Interestingly hippocampal volume of healthy individuals who engage in food restriction and exercise is also enlarged and is considered to have a protective function (Beadle et al, 2014). Neurotransmitters and cells The pathogenic involvement of the serotonergic system in eating disorders is an established finding (Sigurth et al, 2013). Dopamine (DA) dysfunction, particularly in striatal circuits, may contribute to altered reward centre responses (Kontis and Theochari et al, 2012). The clinical picture The clinical picture is embodied in the DSM-5 diagnostic criteria listed above. The patient is usually a teenage female, brought in by her parents. There has been weight loss, cessation of the menses, fine hair growth on the face and limbs, refusal to eat in the manner expected for her age and family circumstances, particular avoidance of carbohydrate and fatty foods, frequent weighing, often vomiting and excessive laxative use, insomnia, irritability, sensitivity to cold, and withdrawal from friends. The hands and feet are cold, the skin is dry, the pulse is slow (50-60/min) and the blood pressure is low (e.

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