As células Y-1 pertencem a uma linhagem clonal de células funcionais de córtex adrenal de camundongo, que respondem a ACTH. Em células Y-1, ACTH promove a esteroidogênese (função) e tem efeitos regulatórios complexos na transição G0→G1→S do ciclo celular. ACTH promove a transição G0→G1, mas inibe a transição G1→S. É possível que a regulação do ciclo celular por ACTH seja mediada pelo controle da expressão dos proto-oncogenes das famílias fos, jun e myc. Nosso laboratório mostrou, anteriormente, que ACTH induz a expressão dos genes fos e jun, mas inibe c-myc. O objetivo deste trabalho foi identificar pontos de controle na expressão dos genes fos, jun e myc e na atividade dos fatores de transcrição AP-1 (dímeros da proteínas Fos e Jun) por ACTH, derivados de cAMP (ativadores de PKA), PMA (ativador de PKC) e FCS (soro fetal bovino). ACTH, PMA e dcAMP aumentam a atividade de ligação de AP-1 a DNA, independentemente de síntese protéica. Ensaios de elongação de cadeia nascente de RNA (run off transcription) mostram que ACTH, PMA e FCS são fortes indutores de c-fos, c-jun e junB, enquanto dcAMP induz apenas c-fos e junB. Hibridizações Northern permitiram estimar a meia-vida dos mRNAs de c-fos e c-jun em 30 min, independentemente do tratamento com ACTH ou PMA. Diferentemente de c-fos, o mRNA de fosB é superinduzido por ActinomicinaD em células Y-1 tratadas com ACTH e PMA. / The Y-1 cells belong to a clonal lineage of functional mouse adrenocortical cells, which are responsive to ACTH. In Y-1 cells, ACTH promotes esteroidogenesis (function) and has complex effects on the G0→G1→S transition of the Y-1 cell cycle. ACTH induces the G0→G1 transition but inhibits the G1+S transition. Probably, the cell cycle regulation by ACTH is mediated by the expression control of the proto-oncogenes from the fos, jun and myc families. Our laboratory has previously shown that ACTH induces the fos and jun genes expression, but inhibits c-myc expression. The target of this work was to identify control points in the fos, jun and myc genes expression and in the AP-1 transcription factors (Fos and Jun proteins dimers) by ACTH, cAMP derivatives (PKA activators), PMA (PKC activator) and FCS (Fetal Calf Serum). ACTH, PMA and dcAMP raise the AP-1 DNA binding activity, independently of protein synthesis. Run off transcription assays show that ACTH, PMA and FCS are strong c-fos, c-jun and junB inducers, while dcAMP induces only c-fos and junB. Northern hybridisations allowed us to estimate the half life of the fos and jun mRNAs in about 30 min, independently of ACTH or PMA treatment. Differently of c-fos, fosB mRNA is superinduced by ActinomicinD treatment in Y-1 cells treated with ACTH or PMA.

The incidence of thyroid diseases in pregnancy in the Czech Republic reaches 10- 15%. Emphasis on early diagnosis and treatment is laid not only during pregnancy but also in the time preceding conception due to the impact of thyroid diseases on fertility, the course of pregnancy, birth and fetal development. The aim of the dissertation was to assess the effectiveness and economical aspects of screening for thyroid disease in pregnancy and in women with fertility disorders in the conditions of the Czech Republic. The dissertation consists of four published studies. The first study is a prospective cross-sectional study of 200 positively screened pregnant women. In the study we come to conclusion that pregnant women who are at high- and low-risk for thyroid disease have similar clinical and laboratory characteristics and screening, currently focused only on risk groups, is ineffective. The second study of 5 223 pregnant women is a case-control study. We find that the age of women over 30 cannot be regarded as a risk factor for thyroid disease in pregnancy, although addition this age criterion to the case-finding screening strategy improve its efficiency and ATA (American Thyroid Association) include it in their guideline 2011. The third publication is a retrospective cross-sectional study of 188...

The incidence of thyroid diseases in pregnancy in the Czech Republic reaches 10- 15%. Emphasis on early diagnosis and treatment is laid not only during pregnancy but also in the time preceding conception due to the impact of thyroid diseases on fertility, the course of pregnancy, birth and fetal development. The aim of the dissertation was to assess the effectiveness and economical aspects of screening for thyroid disease in pregnancy and in women with fertility disorders in the conditions of the Czech Republic. The dissertation consists of four published studies. The first study is a prospective cross-sectional study of 200 positively screened pregnant women. In the study we come to conclusion that pregnant women who are at high- and low-risk for thyroid disease have similar clinical and laboratory characteristics and screening, currently focused only on risk groups, is ineffective. The second study of 5 223 pregnant women is a case-control study. We find that the age of women over 30 cannot be regarded as a risk factor for thyroid disease in pregnancy, although addition this age criterion to the case-finding screening strategy improve its efficiency and ATA (American Thyroid Association) include it in their guideline 2011. The third publication is a retrospective cross-sectional study of 188...

Genetic and Hormonal Regulation of Children's Growth MUDr. Jan Vosáhlo Abstract Growth in childhood is a complex process of changing the body, which can be disrupted by various illnesses including endocrine disorders, particularly growth hormone deficiency. Tumors or other processes affecting hypothalamic-pituitary area can be a postnatal cause of GHD; prenatal causes include 1) developmental disorders of the pituitary as part of complex syndromes, 2) developmental disorders of the pituitary due to defects in regulatory genes and 3) defects in genes involved in the synthesis and secretion of GH. The first topic of the thesis was septo-optic dysplasia - a complex syndrome involving optic nerve hypoplasia, structural brain abnormalities and pituitary dysfunctions. We extensively described phenotype in 11 Czech patients; we observed both complete SOD and incomplete forms variously combining two of the three main components of the syndrome. The cohort then became a part of an international study of 68 patients, in which we studied the phenotype in dependence on the brain morphology. We found correlation between the severity of clinical symptoms and the degree of septum pellucidum abnormities and also a correlation between hippocampus and falx abnormities and neurological symptoms. As the second topic we studied...

Researchers agree that young transgender individuals are at higher risk of mental illness and suicide problems compared to the general population. Through a literature review, the purpose of this study has been to investigate how young transgender people's mental illness can be affected by the National Board of Health and Welfare's new recommendations to limit hormone treatments for transgender people under the age of eighteen.  Since the National Board of Health and Welfare first started to recommend hormone treatment the access to the medication has now been severely limited. The literature review has been conducted through an analysis of 26 scientific articles and the results has been analyzed on the basis of Goffman's theory of stigma and Meyer, minority stress model. The results of this analysis shows that young transgender people pay a high price of stigma and mental illness for living outside of societal norms. As a transgender person, it is important to be seen for who you are and to be able to freely express your gender identity. Being addressed with the right name and pronoun is part of this. The possibility to undergo hormone treatment is thus of great importance for many individuals. At the same time there are risks linked to this treatment. Good relations with and access to health care is therefore crucial. Nevertheless, according to the results in this study young transgender people’s relationship to health care is in fact both complicated and limited.  Based on the identified themes, the conclusion of this study is that the National Board of Health and Welfare's new recommendations increase the risk mental illness for young transgender people, which consequently also may risk costing the lives of these young people.

In einem Fütterungsversuch mit 15 weiblichen, genetisch identischen Zwillingspaaren wurde der anhaltende Effekt energetisch unterschiedlich konzentrierter Futterrationen auf Körper- und Blutmerkmale zwischen dem vierten und 21. Lebensmonat erfasst. Die gleichen Merkmale wurden an den Tieren auch während der Laktation erhoben, als die Tiere einheitlich gefüttert wurden. Zusätzlich wurde die Milchleistung untersucht. Während der Aufzucht wurden Körpergewicht, tägliche Gewichtszunahme, Rückenfettdicke und Widerristhöhe von der Fütterungsintensität signifikant beeinflusst. Körpergewicht und Rückenfettdicke zeigten vom siebenten bis 15. Lebensmonat die größten Unterschiede zwischen den Fütterungsgruppen. Im Gegensatz zum Körpergewicht, wurde der Fettansatz bis zum 21. Lebensmonat kaum gebremst. Für die Serumkonzentrationen von Insulin, Glukose und beta-Hydroybuttersäure und die Erythrozytenindizes MCV und MCH konnte ein signifikanter Fütterungseinfluss während der gesamten Aufzuchtphase nachgewiesen werden. Kortisol, Kreatinin, ASAT, GGT, GLDH, MCHC, Leukozytenzahl, Thrombozytenzahl reagierten auf den Fütterungsstimulus nur innerhalb bestimmter Altersabschnitte. Bis zum neunten Monat differierte der Insulinspiegel zwischen den Fütterungsgruppen kaum, ab dem 10. Lebensmonat aber sehr deutlich. Es kann daher ausgeschlossen werden, dass der Insulinspiegel im präpubertären Abschnitt die Entwicklung der späteren Milchleistung beeinflusste. Nach dem Abkalben war die intensiv gefütterte Gruppe stärkeren metabolischen Belastungen ausgesetzt und hatte eine geringere Milchleistung als die moderat gefütterte Gruppe. Offensichtlich wurde der Stoffwechsel durch die vorangegangene Fütterung geprägt, da der Fettansatz in der Intensivgruppe bei gleicher Fütterung früher einsetzte und auch intensiver erfolgte. Einige Kennwerte beim Jungtier korrelierten signifikant mit der späteren Milchleistung. Altersabhängige Veränderungen der Korrelationskoeffizienten weisen auf unterschiedlich sensible Phasen für die Prägung der späteren Milchleistung hin. / In a feeding trial with 15 pairs of genetically identical female twins, the effect of feeding intensity on body condition and blood parameters were investigated between the fourth and 21st month. The same traits were analysed on the cows during the first lactation when the animals were uniformly fed. In addition to these traits, the milk yield was investigated. During the rearing period; body weight, daily weight gain, back fat thickness, and withers height were significantly influenced by feeding. The largest differences between the feeding groups in body weight and back fat thickness were seen between the ages of seventh to 15th months. In contrast to body weight, back fat thickness hardly exceeded the 21st month between the groups. The serum concentrations of insulin, glucose, beta-Hydroxybutyric acid, and the erythrocyte indices MCV and MCH showed a significant feeding effect throughout the growing period. Cortisol, creatinine, Aspartate transaminase (AST), y-glutamyltransferase (GGT), Glutamate dehydrogenase (GDH), mean corpuscular hemoglobin concentration (MCHC), white blood cells (WBC) and platelet responded to the feeding stimulus only within certain ages. At age nine months, insulin levels were barely differed between the feeding groups but were distinct as from the 10th month. It can therefore be concluded that insulin levels at the pre-pubertal development affects the subsequent milk yield. After calving, the intensively fed group had more metabolic stress and had a lower milk yield than the moderately fed group. Obviously, the metabolism was programmed in the previous feeding period. There was an early onset and a more intensive fat deposition in the intensive group though; they had the same feeding level. Some traits in young animals were significantly correlated with subsequent milk yield. Age-dependent changes in the correlation coefficients suggest the fact that differences in sensible juvenile phases in traits could contribute to milk yield later.

No description available.

No description available.

No description available.

Background: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients’ subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. Methods: Twelve to 28 months (mean 18.6 ± 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). Results: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. Conclusion: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.