Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 80-97).

Thesis (Ph.D. (Psychiatry))--University of Pretoria, 2003. / Summary in English and Afrikaans. Includes bibliographical references.

H ιδιοπαθής θρομβοπενική πορφύρα είναι ένα αυτοάνοσο νόσημα που χαρακτηρίζεται από χαμηλό αριθμό αιμοπεταλίων και αιμορραγίες. Επιπλέον αυτή η ασθένεια κατηγοριοποιείται σε οξεία (όταν διαρκεί λιγότερο από έξι μήνες) και χρόνια μορφή. Η λεπτίνη είναι μια ορμόνη/κυτταροκίνη που παράγεται από τα αδιποκύτταρα και ρυθμίζει την όρεξη και τον μεταβολισμό. Ως κυτταροκίνη η λεπτίνη προάγει την Th1 απόκριση και παίζει πολύ σημαντικό ρόλο στα αυτοάνοσα νοσήματα όπως έχει παρατηρηθεί σε πολλά μοντέλα ζώων. Στην εργασία αυτή μελετήσαμε τον ρόλο της λεπτίνης στην παιδική ιδιοπαθή θρομβοπενική πορφύρα (ΙΘΠ). Από τα πειράματά μας διαπιστώσαμε ότι τα επίπεδα της λεπτίνης συσχετίζονται αρνητικά με τον αριθμό των αιμοπεταλίων των ασθενών. Επιπλέον αποδείξαμε ότι στην ασθένεια που μελετήσαμε η λεπτίνη έχει αντί-φλεγμονώδη ρόλο αφού επάγει την έκφραση της IL-10 από το μονοκύτταρα Το μόριο της εκλυτικής ορμόνης της κορτικοτροπίνης (CRH) εκφράζεται κυρίως στον υποθάλαμο και ενεργοποιεί μέσω του άξονα υποθάλαμος-υπόφυση-επινεφρίδια τα γλυκοκορτικοειδή τα οποία έχουν ανοσοκατασταλτική δράση. Η CRH που εντοπίζεται στην περιφέρεια έχει αντιθέτως προ-φλεγμονώδη δράση. Εμείς μετρήσαμε τα επίπεδα της CRH στο πλάσμα υγιώς και ασθενών δοτών και παρατηρήσαμε ότι στους υγιείς δότες η CRH έχει την ικανότητα να ρυθμίζει αρνητικά την έκφραση της λεπτίνης. Ο έλεγχος όμως αυτός χάνεται στους ασθενείς με αποτέλεσμα τα επίπεδα τα λεπτίνης αυξάνονται στον ορό τους / Ιdiopathic thrombocytopenic purpura is an autoimmune disease characterized by a low platelet count and bleeding. Moreover this disorder is classified as acute (of six month or less duration) or chronic. Leptin is an adipocyte-derived hormone/cytokine that regulates food intake and basal metabolism. As a cytokine leptin promotes T helper 1 (TH1)-cell differentiation and can modulate the onset and progression of autoimmune responses in several animal models of disease. Here, we review the role of leptin in childhood idiopathic thrombopenic purpura (ITP). We found that leptin levels negatively correlated with platelet numbersand also that it plays an active anti-inflammatory role by promoting IL-10 secretion by monocytes. Corticotropin-Releasing Hormone (CRH) CRH, the hypothalamic component of the hypothalamic-pituitary,adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. We measured CRH levels in the plasma of children suffering from ITP and in the plasma of the paediatric controls, and we found that in controls CRH down-regulates leptin’s expression but not in patients.

Please read the abstract in the section 00front of this document / Thesis (DPhil (Psychiatry))--University of Pretoria, 2003. / Psychiatry / unrestricted

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No / Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction of cAMP with up-regulation of pro-opiomelanocortin gene expression and subsequent production of adrenocorticotropin hormone. However, the role of CRH/CRH-R in melanocyte biology is complicated by the significant heterogeneity of cutaneous melanocyte subpopulations, from continuously active and UV-responsive melanocytes in epidermis to UV nonresponsive, hair growth cycle-coupled melanogenesis in hair follicles. In the present study we report that normal human scalp hair follicle melanocytes express CRH at the mRNA level. Furthermore, CRH, urocortin and CRH-R 1 and 2 were differentially expressed in follicular melanocytes, fibroblasts, and keratinocytes depending on anatomic location and differentiation status in situ and in vitro. Stimulation of follicular melanocytes with CRH and CRH peptides, modified for selectivity for CRH-R1 and/or CRH-R2, variably induced cell melanogenesis, dendricity, and proliferation. CRH-peptides also stimulated the expression and activity of Tyrosinase, and expression of Tyrosinase-related protein-1 and-2. However, a modified urocortin peptide highly selective for CRH-R2 down-regulated melanocyte differentiation phenotype. This study indicates that CRH peptides can differentially influence hair follicle melanocyte behavior not only via CRH-R1 signaling but also by complex cross-talk between CRH-R1 and CRH-R2.¿Kauser, S., Slominski, A., Wei, E. T., Tobin, D. J. Modulation of the human hair follicle pigmentary unit by corticotropin-releasing hormone and urocortin peptides.

Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder.

Play fighting is common in juvenile mammals as a peri-pubertal form of agonistic behavior preceding adult aggressive behavior. In golden hamsters, play fighting peaks in early puberty around postnatal day 35 (P-35), and gradually matures into adult aggression in late puberty. Though extensively studied, the neural mechanisms underlying play fighting remains poorly understood. My dissertation focuses on identifying the neural circuitry and neural transmitter systems that mediate this behavior in juvenile golden hamsters. Based on behavioral similarities between the offensive components of play fighting and adult aggression, I predicted that the neural circuitries mediating both behaviors shared common components. This possibility was tested by quantifying the immunolabeling of c-Fos expression in juvenile hamsters after the consummation of play fighting. In support of my hypothesis, I found that areas previously associated with offensive aggression in adult hamsters, including the ventrolateral hypothalamus (VLH), the posterior dorsal part of the medial amygdala (MePD), and the bed nucleus of the stria terminalis (BST), also showed enhanced c-Fos expression after play fighting, which supported my hypothesis. Vasopressin (AVP) facilitates aggression in adult hamsters. Therefore, I hypothesized that AVP also activates play fighting. To test my hypothesis, juvenile male golden hamsters were tested for play fighting after they received central microinjections of an AVP V1A-receptor antagonist into the anterior hypothalamus (AH). Also, immunocytochemistry was performed to identify possible AVP neurons associated with this behavior. I found that the AVP antagonist selectively inhibited the attack components of play fighting in experimental animals. In addition, AVP cells in the nucleus circularis (NC) and the medial division of the supraoptic nucleus (mSON), which were associated with offensive aggression, also showed increased c-Fos activity after play fighting. Together, these results show that AVP facilitates offensive behaviors throughout hamster development, from play fighting in juveniles to aggression in adults. A recent study shows that oral administration of a CRH receptor antagonist inhibits aggression in adult hamsters. Therefore, I predicted that CRH plays a similar role in play fighting. To test my prediction, juvenile hamsters were tested for play fighting after central microinjections of a CRH receptor antagonist. I found that microinjections of the CRH receptor antagonist within the lateral septum (LS) resulted in an inhibition of several aspects of play fighting. The possible source of CRH affecting the behavior was tested through combined immunocytochemistry to CRH and c-Fos. I found CRH neurons in the diagonal band of Broca (DBB), an area with extensive connections with the LS, were particularly activated in association with play fighting. In conclusion, I find that shared neural elements participating in the “vertebrate social behavior neural network” are associated with both aggression and play fighting in hamsters. This circuitry is activated before the onset of puberty and is affected by rising levels of steroid hormones during the developmental period leading to adult behaviors. Within the circuitry, vasopressin release in the AH appears to control the activation of play fighting attacks. In contrast, CRH release in the LS affects a broader range of aspects of play fighting, including not just consummatory aspects of the behavior, but apparently also appetitive components in the form of contact duration. / text

Made available in DSpace on 2016-03-22T17:27:35Z (GMT). No. of bitstreams: 1 xenia1.pdf: 708937 bytes, checksum: cc885d49bb2a8c9ada32a3218f9e37f3 (MD5) Previous issue date: 2014-01-24 / Objective: To investigate the relationship between peripheral levels of corticotropin releasing hormone (CRH) and interleukin-1 (IL-1) in BD individuals with and without suicide risk (SR) and controls. Methods: 120 young adults (40 controls, 40 BD subjects without SR and 40 BD subjects with SR) were enrolled from a population-based study carried out in the city of Pelotas, (Brazil). BD and SR were assessed with MINI 5.0 and peripheral markers were evaluated by ELISA. Results: Levels of CRH were significantly lower both in BD subjects without SR (p = 0.04) or with SR (p = 0.02) when compared to control. However, levels of IL-1 were increased in BD subjects with SR (p = 0.05) when compared to control. Socio-demographic and clinical variables, current mood episode and use of psychiatry medication were not associated with changes in these markers. No correlation was found between peripheral levels of CRH and IL-1 (p = 0.60) in the population or in BD with SR group (p = 0.88) Conclusions: These results suggest that peripheral mechanisms linking stress hormones and the immune system might be critical patterns involved in suicidal behavior associated with BD / Avaliar se existem alterações nos níveis periféricos do hormônio liberador de corticotropina (CRH) e na interleucina-1 (IL-1) em pacientes com transtorno bipolar, com ou sem risco de suicídio comparando com indivíduos sem transtornos de humor. 2.3.2. Objetivos específicos 1. Avaliar os níveis séricos de CRH e IL-1 em pacientes com diagnóstico de transtorno bipolar comparando com controles sem transtornos de humor; 2. Comparar os níveis séricos de CRH e IL-1 em pacientes com diagnóstico de transtorno bipolar com e sem risco de suicídio, e controles sem transtornos de humor; 3. Investigar se existe algum efeito da diferença de gênero, idade, atividade física, índice de massa corporal e fatores sócio- demográficos com os níveis de CRH e IL-1 em pacientes bipolares com e sem risco de suicídio e controles. 4. Verificar se existem alterações nos níveis periféricos de CRH e IL-1 durante os episódios atuais de humor dentro do transtorno bipolar. 5. Verificar se existem uma correlação entre os níveis periféricos de CRH e IL-1