Made available in DSpace on 2014-06-12T23:02:21Z (GMT). No. of bitstreams: 2 arquivo9492_1.pdf: 649734 bytes, checksum: 28723ca76fa40f2c9caa3d4d758a7caa (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2012 / Objetivo: Avaliar a função do eixo hipotálamo-hipófise-adrenal, através do cortisol salivar da meia-noite, e sua relação com parâmetros clínicos e laboratoriais em mulheres na pós-menopausa inicial, antes e após seis meses do uso da terapia hormonal (TH). Métodos: Ensaio clínico aberto realizado em mulheres nos primeiros cinco anos de menopausa com indicação para o uso da TH. Foram avaliados os níveis pressóricos, a medida da circunferência abdominal (CA), o índice de massa corpórea (IMC), perfil lipídico, perfil glicêmico e dosagem do cortisol salivar da meia-noite antes e após seis meses de uso diário de 17-β-estradiol 1g e drospirenona 2mg. Resultados: Dezenove pacientes concluíram o estudo. Observamos um declínio dos níveis de cortisol salivar ao longo do tratamento, porém, sem relevância estatística (p=0,488). A medida da CA apresentou redução significativa (90,21 cm vs 88,53 cm) com p=0,011, dado não observado com a média do IMC (27,55 kg/m2 vs 27,26 kg/m2; p=0,152). A média dos níveis de pressão arterial sistólica, colesterol total, glicemia de jejum (GJ) e lipoproteína de baixa densidade (LDL) apresentaram declínio estatisticamente significante após os seis meses de tratamento. Houve uma correlação entre os níveis de cortisol e pressão arterial sistólica, diastólica e GJ, antes do uso da TH, que não se manteve após o período de tratamento. Conclusão: O uso da TH por seis meses não foi capaz de promover alteração nos níveis de cortisol salivar à meia noite, mas foi responsável por uma redução significativa na CA, pressão arterial sistólica, níveis de LDL e GJ

Hintergrund: Anorexia nervosa (AN), allgemein als Magersucht bezeichnet, gehört zu den häufigsten psychischen Erkrankungen im Kindes- und Jugendalter. Dabei kommt es aufgrund einer gestörten Wahrnehmung der eigenen Figur zu einem erheblichen, selbst herbeigeführten Gewichtsverlust. Die Mehrheit der Patientinnen muss aufgrund der Schwere der Erkrankung mindestens einmal stationär behandelt werden. Cortisol ist ein lebenswichtiges Steroidhormon, das dafür sorgt, dass der menschliche Körper länger andauernde Belastungen bewältigen kann. Halten diese Stresssituationen jedoch zu lange an, kann es erhebliche Störungen des Stoffwechsels, des Wachstums, der Reproduktion und der Immunkompetenz verursachen. Cortisol und seine Stoffwechselprodukte werden überwiegend mit dem Urin ausgeschieden. Die Bestimmung der Urincortisolkonzentration (UCC) gehört daher zur klinischen Standarddiagnostik. In der Forschung hat sich die UCC als zuverlässige Methode zur Untersuchung des Stresshormons bei gesunden Probanden und psychischen Erkrankungen bewährt. Auch im Haar kann das Stresshormon nachgewiesen werden. Hauptsächlich gelangt es aus dem Blut in die Zellen des wachsenden Haarschaftes. Haaranalysen werden seit langer Zeit als zuverlässige Methode in der Forensik und Toxikologie angewandt. Mittlerweile hat sich die Analyse von Haarproben zur Bestimmung der Haarcortisolkonzentration (HCC) auch in der Forschung als valide Methode etabliert. Dabei bietet diese nicht-invasive und leicht durchführbare Methode einen retrospektiven Blick auf die Langzeitausschüttung von Cortisol. In zahlreichen Studien wurde bei AN eine Erhöhung des Stresshormons Cortisol nachgewiesen (sog. Hypercortisolismus). Dabei scheinen sich der Hypercortisolismus, die körperlichen Symptome und die psychischen Veränderungen in einer komplexen Krankheitspathologie wechselseitig zu beeinflussen. Mehrere Studien konnten bei AN bereits eine erhöhte Cortisolausscheidung im Urin nachweisen, die mit zunehmender Gewichtsnormalisierung rückläufig ist. Die HCC wurde bei AN bisher nur in einer Querschnittstudie untersucht. Entgegen des bekannten Hypercortisolismus konnte hier eine signifikant niedrige HCC nachgewiesen werden. Fragestellung: Die vorliegende Studie untersucht die HCC bei Patientinnen mit AN zum ersten Mal in einer Längsschnittstudie. Durch Beobachtung von Patientinnen über den Verlauf einer stationären, krankheitsbildspezifischen Therapie und zusätzlicher Erhebung der UCC als Vergleichsvariable sollte die Anwendbarkeit der HCC bei AN untersucht werden. Material und Methoden: Neben der Anwendung psychopathologischer Testverfahren (EDI-2) und regelmäßiger Bestimmung des BMI wurde wöchentlich durch einen 24-h-Sammelurin die UCC bestimmt. Eine Substichprobe gab am Ende des durchschnittlich 13-wöchigen Therapiezeitraumes eine Haarprobe ab, anhand derer eine monatliche HCC bestimmt wurde. Die Analyse der Urinproben erfolgte mittels immunochemischer Verfahren, die Haarproben wurden mittels Hochleistungsflüssigkeitschromatographie mit Tandem-Massenspektrometrie analysiert. Durch individuelle Zuordnung einer medianen UCC zu jeder HCC wurden für jede Patientin schließlich drei HCC-UCC-Wertepaare erzeugt, die den Anfang, die Mitte und das Ende der stationären Therapie abbildeten. Ergebnisse: Insgesamt nahmen 33 Patientinnen des Zentrums für Essstörungen der Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und -psychotherapie teil (Stichprobe 1), wobei 16 Patientinnen der Entnahme einer Haarprobe zustimmten (Stichprobe 1a). Während der stationären Therapie kam es zu einer leitliniengerechten Gewichtsrehabilitation. Die UCC war deutlich erhöht und fiel während des Therapieverlauf signifikant ab. Die HCC zeigte hingegen keine Veränderung. Bei der Korrelation der HCC mit der medianen UCC konnte lediglich ein Trendeffekt nachgewiesen werden. Separate Analysen der einzelnen Zeitabschnitte ergaben eine signifikante Korrelation von HCC und UCC am Ende der stationären Therapie. Bei Analyse des EDI-2 korrelierte die Unzufriedenheit mit dem eigenen Körper zu Beginn und am Ende der Therapie mit der UCC, jedoch nicht mit der HCC. Haareigenschaften und Haarbehandlungen hatten keinen Einfluss auf die HCC. Schlussfolgerungen: Insgesamt konnte die UCC den bekannten Hypercortisolismus abbilden und bildete eine valide Grundlage für die Überprüfung der HCC bei AN. Trotz ihres Absinkens blieb die UCC nach erfolgreicher Gewichtsrehabilitation erhöht. Zudem konnte eine Korrelation der UCC mit einer zentralen psychopathologischen Veränderung bei AN nachvollzogen werden. Dies bestätigt die Hypothese einer komplexen Krankheitspathologie mit somatischen und psychiatrischen Einflussfaktoren auf den Hypercortisolismus. Bei einem Literaturvergleich der HCC mit gesunden Probanden konnte kein Hypercortisolismus nachvollzogen werden. Insgesamt konnte die HCC die UCC insbesondere in der Phase der akuten Erkrankung und beginnenden Gewichtsrehabilitation nicht zuverlässig abbilden. Nach Gewichtsnormalisierung schienen sich HCC und UCC jedoch wieder dem bei gesunden Probanden bestätigten Verhältnis anzunähern. Als Ursache für diese fehlende Korrelation kommen trophische Störungen des Haarwachstums bei AN in Betracht. So ist aufgrund eines verminderten Haarwachstums eine gestörte Einlagerung des Hormons in den Haarschaft möglich. Auch enzymatische Störungen des Cortisolabbaus werden diskutiert. Ein gestörtes Gleichgewicht des Enzyms 11-β-HSD, welches die Umwandlung von Cortisol zu Cortison (und umgekehrt) katalysiert, scheint ebenfalls die Einlagerung in das Haar zu beeinflussen. Insgesamt ergaben sich zahlreiche Hinweise, dass die HCC entgegen den Studienergebnissen bei gesunden Probanden und anderen stressassoziierten Zuständen bzw. Erkrankungen nicht zur Untersuchung des Hypercortisolismus bei AN im akuten Erkrankungszustand und im Verlauf einer stationären Therapie angewendet werden kann. Eine Nutzung dieser Methode zur Untersuchung gewichtsrehabilitierter Patientinnen bleibt offen und bedarf weiterer Forschungen. / Background: Anorexia nervosa (AN) is one of the most common mental disorders in children and adolescents. Disturbances in the way in which one´s body shape is experienced lead to a severe self-inflicted weight loss. Majority of patients need to be treated in hospital at least once in a lifetime. Cortisol is an essential adrenal cortical hormone, which enables human organism to cope with long-lasting stress. However, perseverative stress can cause abnormalities in metabolism, growth, reproduction and the immune system. Cortisol and its metabolites are excreted renal predominantly. Therefore, analyzing urinary cortisol concentration (UCC) is part of good clinical practice and proved of value in research. Recently, the assessment of long-term cortisol concentration via hair samples has been shown to be a sensitive cortisol parameter too. According to the multicompartment model diffusion of cortisol from blood capillaries into the growing hair cells of the follicle represents the main pathway of cortisol incorporation into the hair. Hair cortisol concentrations (HCC) offer a retrospective view that is easily accessible. Numerous studies have used hair cortisol successfully to examine changes in long-term cortisol levels in a number of psychiatric diseases. Underweight patients with AN are known to have increased cortisol levels (hypercortisolism). Cortisol levels were found to correlate with both physical and mental symptoms in a complex interplay. Most studies reported a urinary hypercortisolism in AN and a significant decrease in cortisol levels during weight gain. So far, the only other study that examined HCC in AN found lower HCC compared to healthy controls, which is contradictory to the existing literature. Aim: The aim of this study was to investigate whether HCC in acutely ill AN patients reflects a well-established classic cortisol measure (UCC) using a longitudinal study design over the course of inpatient weight-restoration treatment. Methods: Therefore, after admission every patient provided a weekly 24-h-urine sample. The corresponding body weight was measured on each day of collection. After the last urine collection, a hair sample was taken for analyzing a monthly HCC. Additionally, eating disorder symptoms were measured by EDI-2. Hair samples were analyzed by a LC-MS/MS-based method. The determination of cortisol concentration in urine was performed by using a competitive immuneenzymatic colorimetric method. As urinary cortisol was measured weekly while hair cortisol values were reflecting cortisol levels over one month, we calculated the median urinary cortisol corresponding to each monthly hair cortisol value individually. In sum, we matched three pairs of median UCC and HCC for each patient, representing the beginning, middle and end of the therapy. Results: The cohort in our longitudinal analysis consisted of a total of 33 patients who participated for 13 weeks on average. A subsample of 16 patients provided a hair sample after inpatient treatment. UCC was increased and revealed the expected decrease during weight gain while HCC showed no significant change. Tested for associations between HCC and UCC there was a trend effect for UCC on HCC. Separate correlation analyses per time-period showed a significant correlation between UCC and HCC for the third time period at the end of the therapy. Disaffection with the own body correlated with UCC, but not with HCC at the beginning and end of inpatient therapy. Hair treatment had no effect on HCC. Discussion: In summary UCC proved to be a reliable cortisol measure in our sample. Despite reduction, UCC remained increased after weight-restoration and correlated with eating disorder symptoms. This confirms the supposed complex interplay of hypercortisolism with physical and mental symptoms. Compared to cortisol levels of previously reported healthy females HCC was normal in AN and did not decline significantly during weight-restoration. Overall HCC did not reflect UCC, particularly with regard to the phase of acute starvation and incipient weight gain. However, association of HCC and UCC seemed to approximate healthy conditions after weight restoration. One possible explanation for lack of correlation might be trophic disturbances of hair in AN. Studies reported that scalp hair in AN show a higher percentage of hair in the telogen (resting) phase, which implies no further hair follicle activity, consequently less hair growth, and less storage of hormones like cortisol in hair. Furthermore, disturbances of the activity of 11-β-HSD-enzymes, converting cortisol in cortisone and vice versa, might influence the incorporation of cortisol in hair too. Altogether we suggest that incorporation of cortisol into the hair might be impaired due to factors associated with underweight and undernutrition in AN. Our data demonstrate that HCC does not reflect hypercortisolism in individuals suffering from acute AN, while after some weight gain it may proof to be a useful measurement of long-term cortisol levels.

Reliable observation of ECT-induced hormone release requires that other processes that affect hormone levels remain constant and not obscure it. This article reviews principles and pitfalls in making such observations. Clinical applicability and limitations of measurements of prolactin, cortisol, oxytocin, in vasopressin, and other hormones are described. Applications, include elucidation of ECT physiology and seizure quality, comparison of ECT techniques, and description of illness severity. Accounting for each of these different effects can be needed to characterize any of them. An important but unrealized application of neuroendocrine measurement is prediction of the stability of individual ECT response.

The hypothalamic-pituitary-interrenal (HPI) axis in fishes controls the production of cortisol in response to a stressor. To study HPI axis regulation during chronic stress, pairs of juvenile rainbow trout (Oncorhynchus mykiss) were allowed to form dominance hierarchies. Subordinate trout experience chronic social stress associated with a sustained elevation in circulating cortisol levels. Circulating cortisol levels reflect the balance between negative feedback regulation of the HPI axis and cortisol clearance, both of which lower cortisol levels, and cortisol production via HPI axis activation. The capacity for negative feedback and cortisol clearance appeared to be intact in subordinate fish, based on the rapid decline in cortisol after cortisol injection or during recovery from social stress. In addition, corticosteroid receptor transcript and protein abundances throughout the HPI axis did not differ between dominant and subordinate trout. Elevated transcript abundances of 11β-hydroxysteroid dehydrogenase type 2 (11βhsd2) in the preoptic area (POA) and pituitary of subordinate fish suggested an enhanced role for this cortisol-inactivating enzyme during chronic social stress. Steroidogenesis occurs in the interrenal cells of the head kidney, and appeared to be a primary driver of increased plasma cortisol levels in subordinate trout. Transcript abundances of the HPI axis effectors corticotropin releasing factor (crf) and pro-opiomelanocortin (pomc) were not elevated in the POA or pituitary, respectively, of subordinate trout. However, rate-limiting components of head kidney steroidogenesis were elevated, including steroidogenic acute regulatory protein (star) and P450 side chain cleavage enzyme (p450scc). A novel finding in the head kidney was increased transcript abundance of steroidogenic factor 1, which regulates steroidogenic enzyme transcription in mammals. Accordingly, head kidney preparations from subordinate trout exhibited increased basal cortisol production in vitro. Despite this elevation in basal steroidogenesis, subordinate rainbow trout demonstrated attenuated cortisol production in response to stimulation by exogenous adrenocorticotropic hormone (ACTH) both in vivo and in vitro. A similar attenuation was observed with cAMP, suggesting that impairment of acute cortisol production arises downstream of cAMP in the ACTH signalling pathway. The regulation of crf in the POA during chronic social stress was probed in more detail by measuring the abundance of selected microRNAs (miRNA) predicted to target and reduce crf or 11βhsd2 mRNA, but these were not found to play a role. Methylation of the crf promoter revealed significantly decreased methylation at two loci in dominant trout, but the functional significance of this methylation pattern requires further study. Collectively, the present thesis used an array of experimental approaches to provide a comprehensive picture of HPI axis regulation during chronic social stress in rainbow trout.

No description available.

No description available.

The concept of quantifying animal welfare has received much discussion, in various industries such as agriculture, laboratory, and zoological facilities. Behavioral, physical, and physiological indicators of welfare have previously been used to assess animal welfare; each having advantages and disadvantages, ranging from the practicality of data collection, to the validity of the data and how it is interpreted. Concurrent assessment of multiple measures is a more robust way to examine animal welfare, which utilizes the advantages of each measure, and provides additional information on which to base conclusions and animal care management decisions. This study used measures of behavior and urinary cortisol to examine the potential stress response of a captive gorilla group to short-term space restriction associated with temporary confinement to indoor housing facilities. The study duration was three months; one month of baseline data collection, one month of indoor restriction, and one month of monitoring post-restriction. All-occurrences of selected behaviors were collected, with an emphasis on social and stress-related behaviors, and urine samples were collected daily from a sub-set of the group. A urinary cortisol metabolite enzyme immunoassay was validated and used to monitor adrenal activity in gorillas. Measured cortisol increases in response to a known stressor (medical illness) provided a physical validation of the cortisol EIA and established biological relevance of the assay system. No significant differences in social behaviors (aggression, affiliation) or stereotypic behaviors were observed. Significant (p<0.05) increases in cortisol concentration were measured, suggesting that the gorillas were responding to a stressor during the study period. The observed cortisol increase was not likely to have been caused exclusively by the temporary indoor confinement. Potential additional causes of increased adrenal activity during the study included: presence of the observer and novelty of re-landscaped outdoor enclosure. While the increases in cortisol concentration demonstrate an observed stress response, the magnitude of this stressor, and thus the degree of the stress response, was minor. The stress experienced was not significant enough to alter the normal biological function of the gorillas, and thus, can be considered negligible. The gorillas' ability to effectively deal with this expected stressor may have been enhanced by the additional enrichment provided to the gorillas during their indoor confinement. Gorillas were provided with additional browse, more enrichment items, additional training sessions, and increased keeper interaction while they remained indoors. These animal care and management techniques may have buffered the predicted negative impact on animal welfare due to increases in stress by providing stimulating novelty in the gorillas' indoor environment.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

This study examined effects of carbohydrate (C), carbohydrate-protein (CP), or placebo (P) beverages following eccentric resistance exercise on muscle damage by serum creatine kinase (CK), muscle protein breakdown by urinary 3-methylhistidine (3MH), muscle soreness, isokinetic muscle strength, muscle glycogen resynthesis, and serum hormones. Untrained males (N=26) underwent a 9-day controlled meat-free diet and 24 hr urine collections. To reduce glycogen, subjects cycled for 40 min at 70% of VO_2peakfollowed by 5 cycling sprints on day 4 evening. On day 5, fasted subjects performed 100 eccentric leg flexions at 120% of 1-RM and drank C (n=8, 1.25 g C/kg), CP (n=9, 0.875 g C/kg, 0.375 g protein/kg), or P (n=9) beverages immediate post-exercise (IPE) and 2 hr later. Muscle biopsies were taken IPE on day 5, and days 6 and 8 mornings. Blood was obtained days 4-10 fasted plus IPE, 3 hr, and 6 hr post-exercise on day 5. At 3 hr on day 5, insulin was higher for CP (24.6 ( 15.5 &amp;#181;IU/ml) and C (17.2 +/- 10.9 &amp;#181;IU/ml) than P (5.3 +/- 0.4 &amp;#181;IU/ml, p<.05). Glycogen was low on day 5, partially recovered on day 6, and normal by day 8 (p<.01) with no difference among groups. Isokinetic quadriceps peak torque at 60^o/s decreased 24% on day 6 and remained depressed by 21% on d 8 (p<.01) for all groups. Soreness peaked on day 7 and CK on day 8 (p<.01) with no differences by group. CK increased (p<.01) over day 5 (delta CP 24.6 +/- 19.1, delta P 39.2 +/- 71.6, delta C 70.8 +/- 60.4 U/L) and was highest for C (p<.05). On day 5, CP had lowest 3MH (193.0 +/- 13.8 &amp;#181;mol/d) versus C (251.1 +/- 22.5 &amp;#181;mol/d, p<.05). Testosterone at 3 hr on day 5 was lower for C (4.2 +/- 0.3 ng/ml) and CP (4.3 +/- 0.3 ng/ml) versus P (5.1 +/- 0.2 ng/ml, p<.05). In summary, glycogen, muscle strength and soreness were unaffected by beverage. However, a CP beverage may be beneficial for reducing muscle damage and protein breakdown on the day of eccentric resistance exercise. / Ph. D.

Both animal and human studies suggest that cognitive bias toward negative information, such as that observed in major depression, may arise through the interaction of cortisol (CORT) and norepinephrine (NE) within the amygdala. To date, there is no published account of the relationship between endogenous NE and CORT levels and cognitive bias. The present study examined salivary CORT and salivary alpha-amylase (sAA), an indirect measure of NE, in relation to masked affective priming of words in young female participants. Women with higher salivary CORT showed increased priming to negative word pairs only when sAA was also high; when sAA was low, no effect of CORT on priming was observed. These results are in line with previous research indicating that increased CORT is linked to enhanced processing of negative information. However, our findings extend this literature in providing evidence that CORT predicts enhanced processing of negatively valenced information only in the presence of higher sAA.