Das Mammakarzinom gehört zu den häufigsten Krebserkrankungen der Frau. Die Prognose einer Brustkrebserkrankung richtet sich nach den Stadien der TNM-Klassifikation, dabei ist die Wahrscheinlichkeit eines fortgeschrittenen Stadiums bei später Diagnosestellung erhöht. Daher ist insbesondere die Früherkennung der Erkrankung Gegenstand klinischer Forschung. Das Risiko, an Brustkrebs zu erkranken, liegt in der Normalbevölkerung bei 7-10%. Eine individuelle Erhöhung des Risikos findet sich bei familiärer Belastung bezüglich Brustkrebs, sowie einer früheren Erkrankung an einer Präkanzerose wie des Carcinoma ductale in situ (DCIS), des Carcinoma lobulare in situ (CLIS) und der atypischen ductalen Hyperplasie (ADH). Besonderes Augenmerk in der Krebsforschung liegt zur Zeit auf dem Zusammenhang zwischen Tumorwachstum und der Bildung neuer Gefäße, der Angiogenese. Diese Neubildung von Kapillaren ist in hohem Maße von der Ausschüttung bestimmter Wachstumsfaktoren abhängig, von denen der vaskuläre endotheliale Wachstumsfaktor (VEGF) aufgrund seiner Endothelspezifität der mitogenen Wirkung große Bedeutung besitzt. Aber auch der in fast allen Geweben vorkommende und für viele physiologische Prozesse entscheidende Insulin-like growth factor-1 (IGF-1) und seine Bindungs-proteine (IGFBP-1 bis IGFBP-7) scheinen bei der Tumorentwicklung eine wichtige Rolle zu spielen. Zahlreiche klinische Studien beschäftigen sich daher mit dem Vergleich von Serum-oder Plasmakonzentrationen an VEGF, IGF-1 und seiner Bindungsproteine zwischen Krebspatienten und Kontrollgruppen. Dabei sind für Brustkrebspatientinnen erhöhte VEGF- und IGF-1-Konzentrationen und erniedrigte IGFBP-3-Konzentrationen beschrie-ben. Auch für Patientinnen mit einer DCIS-Erkrankung sind erhöhte VEGF-Konzentrationen gefunden worden. Diese Untersuchung beschäftigt sich mit der Wertigkeit einer Messung der genannten Wachstumsfaktoren zur regelmäßigen Untersuchung von Brustkrebsrisikopatientinnen in der Klinik. Dafür wurde ein Kollektiv von 106 Frauen untersucht, die entweder aufgrund einer familiären Belastung oder der Erkrankung an einer Präkanzerose in der Spezial-sprechstunde der Frauenklinik der Charité behandelt bzw. beraten wurden. Für einen Vergleich innerhalb der Hauptgruppen "familiäre Belastung" und "Präkanzerose" wurde eine Einteilung in Subgruppen nach Menopausenstatus, in der Gruppe der familiär belasteten Frauen zusätzlich nach Höhe des berechneten Risikos und in der Gruppe der Patientinnen mit Präkanzerose zusätzlich nach Antiöstrogenbehandlung und Familienanamnese bezüglich Brustkrebs vorgenommen. Als Kontrollgruppen dienten ein Kollektiv von Mammakarzinompatientinnen sowie ein Normalkollektiv aus 234 gesunden Frauen ohne ersichtliche Risiken. Die VEGF, IGF-1 und IGFBP-3-Konzentrationen wurden mittels eines Enzyme-linked Immunoassays (ELISA) im Serum gemessen und verglichen. Dabei fanden sich für VEGF und IGFBP-3 keine signifikanten Unterschiede zwischen den einzelnen Haupt- und Subgruppen (p>0,05). Für IGF-1 konnte eine signifikante Abhängigkeit der Serumkonzentration vom Menopausenstatus bestätigt werden (p0,05). Auch der Vergleich zwischen den VEGF-Konzentrationen von Risikopatientinnen und dem Normalkollektiv wies keinen signifikanten Unterschied aus (p>0,05). Um die intraindividuelle Konstanz der Werte über einen längeren Zeitraum zu prüfen, wurden 34 Frauen, von denen mehr als ein Serum-Wert vorlag, untersucht. Dabei konnte eine intraindividuelle Streubreite der VEGF-Werte im Mittel von 115 pg/ml (Median 118,5 pg/ml, Range 2-310 pg/ml), der IGF-1-Werte im Mittel von 36 ng/ml (Median 27,5 ng/ml, Range 0-134 ng/ml) und der IGFBP-3-Werte im Mittel von 1792 ng/ml (Median 1587 ng/ml, Range 1-4074 ng/ml) festgestellt werden. Zusammenfassend lässt sich sagen, dass aufgrund der starken interindividuellen Streuung der VEGF-, IGF-1- und IGFBP-3-Werte eine Kontrolle der Serum-konzentration nur nach Bestimmung eines individuellen Referenzwertes von klinischem Nutzen sein kann. Zur Zeit scheint die Messung von VEGF, IGF-1 und IGFBP-3 zur Kontrolle von Risikopatientinnen wenig aussagekräftig zu sein. / Breast Cancer is among the most common female malignancies. The prognosis in the case of breast cancer is made according to the status of the TNM-classification, in which the possibility of an advanced stage is higher in the case of a late diagnosis. This is the reason why the early recognition of the illness receives special attention in clinical research. The average risk among the normal population lies at 7-10%. Individually increased risk is given in the case of family history for breast cancer, having earlier suffered from precancer, a carcinomca ductale in situ (DCIS), a carcinoma lobulare in situ (CLIS) and the atypical ductal hyperplasie (ADH). In cancer research special attention is currently given to the connection between tumour growth and the creation of new blood vessels, called angiogenesis. This new creation of capillaries is highly dependent on the setting free of certain growth factors of which the vascular endothelial growth factor (VEDF) is especially important due to ist endothelspecificity. However the insulin-like growth factor-1 (IGF-1) which occurs in nearly all tissues and is decisive for many physiological processes, and its binding proteins (IGFBP-1 to IGFBP-7) appear to play an important role in tumour development. Many clinical studies therefore occupy themselves with a comparison between the serum or plasma-concentrations at VEGF, IGF-1 and its binding proteins among cancer patients and control groups. These comparisons find higher VEGF and IFG-1 concentrations and lower IGFBP-3-concentrations among breast cancer patients. For patients with a DCIS illness higher VEGF concentrations have also been found. This study looks at the possible clinical use of the measurement of the mentioned growth factors during the regular check up of breast cancer risk patients. For this purpose a collective of 106 women were examined that were being treated or advised during the consultancy of the Charité's women's clinic due to a family cancer risk or having been diagnosed with a precancer. In order to compare among the main groups "family risk" and "precancer" a separation into subgroups according to menopausal status was undertaken, within the group "family risk" an additional separation according to the calculated risk was done and the group "precancer" was further split according to anti-estrogen treament and family anamnesis with regards to breastcancer. A collective of breast cancer patients as well as a collective of 234 healthy women without distinct risks functioned as control groups. The concentrations of VEGF, IGF-1 and IGFBP-3 in the serum were measured with an enzyme linked immunoassays (ELISA) and compared. No significant differences between the separate maingroups and subgroups could be found (p>0,05). In the case of IGF-1 a significant dependency of the concentration in the serum and the menopausal status could be confirmed (p0,05). The comparison between the concentrations of VEGF of risk patients and the healthy collective also did not show any significant differences (p>0,05). In order to check the intraindividual consistency of the values over a longer period of time 34 women, for which there existed more than one serum-value, were examined. Here, intraindividual differences of the VEGF-values of 115 pg/ml (Median 118,5 pg/ml, Range 2-310 pg/ml), the IGF-value of 36 ng/ml (Median 27,5 ng/ml, Range 0-134 ng/ml) and the IGFBP-3-value of 1792 ng/ml (Median 1587 ng/ml, Range 1-4074 ng/ml) was found. In summary it can be said that, due to the high interindividual differences of the values of VEGF, IGF-1 and IGFBP-3, a control of the serum concentration can only be of clinical use if a individual reference value is measured.

GH and IGF-1 play an important role in the regulation of metabolism and body composition. In patients with uncontrolled acromegaly, cardiovascular morbidity and mortality are increased but are supposed to be normalised after biochemical control is achieved. We aimed at comparing body composition and the cardiovascular risk profile in patients with controlled acromegaly and controls. A cross-sectional study. We evaluated anthropometric parameters (height, weight, body mass index (BMI), waist and hip circumference, waist to height ratio) and, additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c, triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81 acromegalic patients (58% cured) compared to 320 age- and gender-matched controls (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group of 81 acromegalic patients presented with significantly higher anthropometric parameters, such as weight, BMI, waist and hip circumference, but with more favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total cholesterol, triglycerides and HDL levels, in comparison to their respective controls. Biochemically controlled acromegalic patients again showed significantly higher measurements of obesity, mainly visceral adiposity, than age- and gender-matched control patients (BMI 29.5 ± 5.9 vs. 27.3 ± 5.8 kg/m2; P = 0.020; waist circumference 100.9 ± 16.8 vs. 94.8 ± 15.5 cm; P = 0.031; hip circumference 110.7 ± 9.9 vs. 105.0 ± 11.7 cm; P = 0.001). No differences in the classical cardiovascular biomarkers were detected except for fasting plasma glucose and triglycerides. This effect could not be attributed to a higher prevalence of type 2 diabetes mellitus in the acromegalic patient group, since stratified analyses between the subgroup of patients with acromegaly and controls, both with type 2 diabetes mellitus, revealed that there were no significant differences in the anthropometric measurements. Biochemically cured acromegalic patients pertain an adverse anthropometric risk profile, mainly because of elevated adiposity measurements, such as BMI, waist and hip circumference, compared to an age- and gender-matched primary care population.

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Made available in DSpace on 2015-07-22T20:49:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-06-25. Added 1 bitstream(s) on 2015-08-11T03:25:48Z : No. of bitstreams: 1 Publico-10869.pdf: 639507 bytes, checksum: 4b13227940debf1c6d9d1683aa25bd22 (MD5) / Objetivo: Observar o comportamento metabólico e os ajustes fisiológicos promovidos por um protocolo de atividades físicas em meio aquático com o uso de cargas complementares, variando entre 3-5% do peso corporal. Métodos: Para a realização do experimento, foram utilizados 30 ratos machos, adultos da linhagem Wistar. Os 30 animais empregados no estudo foram divididos aleatoriamente, em dois grupos sendo um o Grupo Treinado (GT) e outro o Grupo Controle (GC). Os animais (15) submetidos ao treinamento físico (GT) foram divididos em três subgrupos: GT1; GT2 e GT3, todos foram submetidos a cinco sessões semanais de natação com duração de 60 minutos, totalizando três, seis e doze semanas respectivamente de treinamento. Dosagens das concentrações de insulina, IGF, glicose e lactato em diferentes momentos e fases do protocolo, foram adotadas como ferramentas para a interpretação de possíveis adaptações. O tratamento estatístico empregado para a análise da glicose, insulina e IGF, foi ANOVA ONEWAY para dados não pareados. Para o lactato plasmático empregou-se ANOVA TWO-WAY empregando o pacote estatístico SAS para PC versão 6.08, (SAS Institute, Cary, NC). Resultados: não houve alterações significativas das concentrações plasmáticas analisadas. Conclusão: O presente estudo demonstrou que o modelo experimental empregado não induz ajustes fisiológicos ou tampouco adaptações hormonais quando estas são analisadas pelos métodos e pelas variáveis bioquímicas acima citadas. Contudo, novos estudos devem ser realizados com experimentos de longo prazo, associando técnicas e abordagens distintas. / Objective: Observe metabolic behavior and physiological adjustments promoted by a protocol of physical activities in aquatic way with the use of additional loads varying between 3 and 5% of body weight. Methods: Thirty adult male Wistar rats were randomly divided into two groups: the Trained Group (TG) and Control Group (CG). The 15 animals of the TG, which underwent physical training, were subdivided into three subgroups: GT1, GT2 and GT3. They underwent 5 weekly swimming sessions during 60 minutes, respectively totaling 3, 6 and 12 weeks of training. Insulin concentration doses, IGF, glucose and lactate at different periods and stages of protocol were used as tools to interpret possible adaptations. ANOVA ONE-WAY for unpaired data was the statistical method for glucose, insulin and IGF analysis. ANOVA TWO-WAY, statistic SAS for PC 6.08 (SAS Institute, Cary, NC) was used for plasmatic lactate. Results: No significant changes in plasmatic concentrations occurred. Conclusion: Current analysis showed that experimental model used does not induce physiological adjustments and hormone adaptations when these are analyzed by the above-mentioned methods and biochemical variables. Other researches should be undertaken involving long-term experiments coupling distinct techniques and approaches. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2016-01-26T18:55:27Z (GMT). No. of bitstreams: 1 dissertacao Bianca.pdf: 325135 bytes, checksum: 8bbf94808bc25e72a05aba3d84bca76a (MD5) Previous issue date: 2008-11-14 / The aim of the study was to evaluate the effect of bovine somatotropin in follicular deviation of sixteen Tabapuã cows. The animals received an ear implant of progesterone and 1 mg of estradiol benzoate, IM (day 0). On day 5, the females were divided into 2 groups: GI (control, n=8) and GII (treated with 500 mg bST, n=8). On day 10, the implants were removed and injected 500 µg of PGF2α in all cows. Only cows with follicles bigger 9 mm received 300 µg of GnRH. Ultrasound examinations were performed each 12 hours. There was no statistical difference between the follicular deviation in GI (2.4 days) and GII (2,1 days). At the divergence moment, FD and FS of GI were 6.28±0.42 and 6.26±0.41 mm, respectively, and FD and FS of GII were 6.08±0.72 and 6.12±0.39 mm. The mean maximum diameter of FD after ovulation was at 110.0±8.43 hours in GI and 115.2±8.98 hours in GII. FS reached the maximum diameter at 55.0±20.0 hours in GI and 76.8±10.46 hours in GII. The mean maximum diameter reached by FD and FS in GI was 8.85±0.41 and 6.5±0.42 mm, respectively, and GII 9.83±0.63 and 6.87±0.35 mm. There was no significant difference (p> 0.05) in diameter of FD and FS, neither in growth rates (mm/12 hours) of the FD before and after the deviation, neither in the moment of follicle deviation / O objetivo do presente estudo foi avaliar o efeito da somatotrofina bovina na divergência folicular em vacas da raça Tabapuã. Foram utilizadas 16 vacas da raça Tabapuã, inicialmente receberam implante de progestágeno auricular concomitante à aplicação IM de 1mg de benzoato de estradiol (dia 0). No dia 5, dividiram-se as fêmeas em 2 grupos: G-I (controle, n=8) e as vacas do G-II foram tratadas com 500 mg bST (n=8). No dia 10 foi feita a retirada do crestar concomitante a aplicação de 500 g de PGF2 e apenas nas vacas com folículos> 9 mm aplicação de 300 g de GnRH. Foram realizados exames ultrassonográficos a cada 12 horas por 5 dias. Não houve diferença estatística entre os momentos de divergência folicular, no G-I foi de 2,4 dias e no G-II 2,1 dias. Nesse momento o FD e FS mediram 6,28  0,42 e 6,26  0,41 mm no G-I e 6,08  0,72 e 6,12  0,39 mm no G-II. O FD atingiu diâmetro máximo após a ovulação em média 110,00 ± 8,43 horas no GI e 115,20 ± 8,98 horas no GII. Já o FS atingiu o diâmetro máximo às 55,00 ± 20,00 e 76,80 ± 10,46 horas, respectivamente. A média do diâmetro máximo atingido pelo FD e FS no GI foi respectivamente 8,85 ± 0,41 e 6,50 ± 0,42 mm e no GII foi 9,83 ± 0,63 e 6,87 ± 0,35 mm. Não houve diferença significativa (p>0,05) no diâmetro do FD e FS e nem nas taxas de crescimento (mm/12h) do FD antes e após a divergência folicular. Concluímos que a aplicação de bST não afetou o diâmetro folicular, a taxa de crescimento do FD e FS antes e após a divergência, nem tampouco, o momento da divergência folicular

Made available in DSpace on 2016-07-18T17:53:05Z (GMT). No. of bitstreams: 1 dissertacao Bianca.pdf: 325135 bytes, checksum: 8bbf94808bc25e72a05aba3d84bca76a (MD5) Previous issue date: 2008-11-14 / The aim of the study was to evaluate the effect of bovine somatotropin in follicular deviation of sixteen Tabapuã cows. The animals received an ear implant of progesterone and 1 mg of estradiol benzoate, IM (day 0). On day 5, the females were divided into 2 groups: GI (control, n=8) and GII (treated with 500 mg bST, n=8). On day 10, the implants were removed and injected 500 µg of PGF2α in all cows. Only cows with follicles bigger 9 mm received 300 µg of GnRH. Ultrasound examinations were performed each 12 hours. There was no statistical difference between the follicular deviation in GI (2.4 days) and GII (2,1 days). At the divergence moment, FD and FS of GI were 6.28±0.42 and 6.26±0.41 mm, respectively, and FD and FS of GII were 6.08±0.72 and 6.12±0.39 mm. The mean maximum diameter of FD after ovulation was at 110.0±8.43 hours in GI and 115.2±8.98 hours in GII. FS reached the maximum diameter at 55.0±20.0 hours in GI and 76.8±10.46 hours in GII. The mean maximum diameter reached by FD and FS in GI was 8.85±0.41 and 6.5±0.42 mm, respectively, and GII 9.83±0.63 and 6.87±0.35 mm. There was no significant difference (p> 0.05) in diameter of FD and FS, neither in growth rates (mm/12 hours) of the FD before and after the deviation, neither in the moment of follicle deviation / O objetivo do presente estudo foi avaliar o efeito da somatotrofina bovina na divergência folicular em vacas da raça Tabapuã. Foram utilizadas 16 vacas da raça Tabapuã, inicialmente receberam implante de progestágeno auricular concomitante à aplicação IM de 1mg de benzoato de estradiol (dia 0). No dia 5, dividiram-se as fêmeas em 2 grupos: G-I (controle, n=8) e as vacas do G-II foram tratadas com 500 mg bST (n=8). No dia 10 foi feita a retirada do crestar concomitante a aplicação de 500 g de PGF2 e apenas nas vacas com folículos> 9 mm aplicação de 300 g de GnRH. Foram realizados exames ultrassonográficos a cada 12 horas por 5 dias. Não houve diferença estatística entre os momentos de divergência folicular, no G-I foi de 2,4 dias e no G-II 2,1 dias. Nesse momento o FD e FS mediram 6,28  0,42 e 6,26  0,41 mm no G-I e 6,08  0,72 e 6,12  0,39 mm no G-II. O FD atingiu diâmetro máximo após a ovulação em média 110,00 ± 8,43 horas no GI e 115,20 ± 8,98 horas no GII. Já o FS atingiu o diâmetro máximo às 55,00 ± 20,00 e 76,80 ± 10,46 horas, respectivamente. A média do diâmetro máximo atingido pelo FD e FS no GI foi respectivamente 8,85 ± 0,41 e 6,50 ± 0,42 mm e no GII foi 9,83 ± 0,63 e 6,87 ± 0,35 mm. Não houve diferença significativa (p>0,05) no diâmetro do FD e FS e nem nas taxas de crescimento (mm/12h) do FD antes e após a divergência folicular. Concluímos que a aplicação de bST não afetou o diâmetro folicular, a taxa de crescimento do FD e FS antes e após a divergência, nem tampouco, o momento da divergência folicular

In der Nutztierhaltung besitzt die Erkennung und Vermeidung von Geburtsstörungen beim Rind insbesondere aus ökonomischer Sicht einen hohen Stellenwert. Bei Hochleistungskühen können Schwergeburten eine erhöhte metabolische Belastung im peripartalen Zeitraum reflektieren. Besonders betroffen sind Färsen und Milchkühe mit einer negativen Energiebilanz. Hormon- und Stoffwechselfaktoren sind von zentraler Bedeutung für die Anpassung der Tiere an Veränderungen ihrer Körpermasse und -konstitution. Zur differenzierten Beurteilung metabolischer Belastungen bei Hochleistungskühen im peripartalen Zeitraum wurden mögliche Zusammenhänge zwischen Geburtsverlauf und den stoffwechselrelevanten Parametern Leptin, Insulin-like growth factor-1 (IGF-1) und freien Fettsäuren (FFS) untersucht. Die vorliegende Studie umfasste 28 adulte, hochträchtige (13 primipare, 15 pluripare) Kühe mit Normal- bzw. Schwergeburt. Die Kälber wurden analog zu ihren Müttern ebenfalls 4  Gruppen (Kuhkalb/Normalgeburt; Kuhkalb/Schwergeburt; Färsenkalb/Normalgeburt; Färsenkalb/Schwergeburt) zugeordnet. Die Analyse von Leptin, IGF-1 und FFS im Blutserum erfolgte zwischen dem 16./14. Tag ante partum (a. p.) und dem 14. Tag post partum (p. p.). Leptin und IGF-1 wurden zusätzlich bei den neugeborenen Kälbern ab der Geburt bis 14 Tage p. p. gemessen. Die Hormonkonzentrationen wurden mittels eines Enzymimmunoassays bestimmt. Die FFS-Analysen erfolgten im Labor der Medizinischen Tierklinik mit dem Labor-Automaten HITACHI 912 i (Roche Diagnostics GmbH, Mannheim). Unabhängig vom Geburtsverlauf konnten während des gesamten Untersuchungszeitraums bezüglich der Leptinkonzentrationen keine signifikanten Unterschiede zwischen Färsen und Milchkühen festgestellt werden. Vor allem zur Geburt besteht für alle Erstkalbinnen eine erhöhte metabolische Belastung, da deren IGF-1-Konzentrationen zu diesem Zeitpunkt niedriger (114 ±  40 vs. 158 ±  108 ng/ml) und deren FFS-Konzentrationen signifikant höher lagen (896 ±  273 vs. 705 ±  225 µmol/l, p = 0,05) als bei den Milchkühen. Im Vergleich zu den Kälbern von Milchkühen wiesen Kälber von Färsen 12 Stunden nach der Geburt signifikant höhere IGF-1-Werte (p = 0,05) auf. In Abhängigkeit vom Geburtsverlauf lagen die Leptinwerte bei allen Kühen mit Schwergeburt von Beginn der Untersuchungen bis einen Tag vor der Geburt niedriger als bei den Tiere mit Normalgeburt mit signifikanten Unterschieden am 13. bis 11. Tag a. p. (p = 0,009) und am 7. bis 5. Tag a. p. (p = 0,05). Während des gesamten Untersuchungszeitraums waren keine signifikanten Unterschiede in den Konzentrationen an IGF-1 und FFS zwischen allen Muttertieren mit einem normalen und einem erschwerten Geburtsverlauf festzustellen. Bei pluriparen Kühen mit Schwergeburt wurden im gesamten Untersuchungszeitraum niedrigere Leptinspiegel nachgewiesen als bei Tieren mit Normalgeburt, mit signifikanten Unterschieden a. p. und ab 3. Tag p. p. (p < 0,05 bzw. p < 0,01). Darüber hinaus fanden sich bei pluriparen Kühen mit Dystokie ab der Geburt höhere FFS-Konzentrationen mit signifikanten Unterschieden zur Kalbung (p = 0,05). Die Leptinkonzentrationen der Kälber lagen analog zu den dazugehörigen Muttertieren ab der Geburt bis 14. Tag p. p. bei allen Kälbern von pluriparen Kühen mit Schwergeburt niedriger als bei den normal geborenen Kälbern mit signifikanten Unterschieden am 7. Tag p. p. (p = 0,04). Im Vergleich zu den Färsen mit Normalgeburt hatten diejenigen mit Schwergeburt signifikant höhere Leptinwerte vom 3. bis 14. Tag p. p. (p = 0,004), signifikant niedrigere IGF-1-Konzentrationen am 10. bis 8. Tag a. p., zur Geburt und vom 3. Tag bis 14. Tag p. p. (jeweils p < 0,01) sowie postpartal niedrigere FFS-Konzentrationen mit signifikanten Unterschieden 12 Stunden p. p. (p = 0,008). Kälber von Färsen mit gestörtem Geburtsverlauf wiesen im Vergleich zu den Normalgeburtskälbern 12 Stunden nach der Geburt signifikant niedrigere IGF-1-Werte (p = 0,005) auf. Die vorliegende Studie verdeutlicht den Zusammenhang zwischen einem gestörten Geburtsablauf und veränderten Serumkonzentrationen an Leptin, IGF-1 und FFS. Damit konnte gezeigt werden, dass diese Parameter zur Interpretation von Stoffwechselstörungen bei Hochleistungskühen im peripartalen Zeitraum geeignet sind. / For livestock management, the identification and prevention of dystocia in cattle is of high significance, especially from an economic point of view. Dystocia in the high-yield cows may reflect an increased metabolic disorder during the peripartal period. Heifers and dairy cows with a negative energy balance are particularly affected. For the adaptation of animals to changes in their body mass and constitution, endocrine and metabolic factors are of central importance. To perform a differentiated assessment of metabolic disorders in high-yield cows during the peripartal period, possible relationships between calving and relevant parameters (leptin, insulin-like growth factor1 [IGF-1] and non-esterified fatty acids [NEFA]) were examined. The present study involved 28 adult high-pregnant (13 primiparous, 15 pluriparous) cows with normal birth and dystocia, respectively. Analogous to their mothers, the calves were likewise categorized into four groups (cow calve/ normal birth; cow calve/ dystocia; heifer calve/ normal birth; heifer calve/ dystocia). The analyses of leptin, IGF-1 and NEFA in blood serum were performed from 16/14 day ante-partum (a. p.) to day 14 post-partum (p. p.). Leptin and IGF-1 were additionally determined in all newborn calves from birth to 14 days p. p. Hormone concentrations were measured by enzyme immunoassay (EIA). Analyses of NEFA in dairy cows and heifers were carried out using HITACHI 912i device (Roche Diagnostics GmbH, Mannheim) at the laboratory of Large Animal Clinic for Internal Medicine. Independent of course of parturition, no significant differences between heifers and dairy cows were noticed concerning serum leptin during the entire examination period. Especially around calving time, all heifers were more intensively affected with metabolic disorders based on their lower IGF-1 values (114 ±  40 vs. 158 ±  108 ng/ml) as well as significantly higher NEFA (896 ±  273 vs. 705 ±  225 µmol/l, p = 0.05) compared to dairy cows. Calves of heifers had significantly higher IGF-1 values 12 hours after birth (p = 0.005) than calves of dairy cows. Dependent of course of parturition, all cows with dystocia displayed lower leptin concentrations from the beginning of the examination period to 1 day a. p compared to animals with normal calving with significant differences from day 13 to day 11 a. p. (p = 0.009) and from day 7 to day 5 a. p. (p = 0.05). During the entire examination period, no significant differences in the concentrations of IGF-1 and NEFA were found between all cows with a normal and difficult parturition. In pluriparous cows with difficult parturition lower leptin levels were detected during the entire examination period than in animals with normal calving with significant differences a. p. and from day 3 to day 14 p. p. (p < 0.05 and p < 0.01, respectively). Furthermore, higher NEFA concentrations were found from birth until 14 days p. p. in pluriparous cows with dystocia and significant differences at calving (p = 0.05). Calves of pluriparous cows with dystocia had p. p. lower leptin concentrations in comparison to those with normal births with significant differences on day 7 p. p. (p = 0.04). In comparison to heifers with normal birth, those with dystocia displayed significantly higher leptin levels in the period from day 3 to day 14 p. p. (p = 0.004), significantly lower IGF-1 concentrations (from day 10 to day 8 a. p., at birth and from day 3 to day 14 p. p.; each p < 0.01), as well as lower NEFA levels after birth with significant differences 12 hours p. p. (p = 0.008). Heifer calves with difficult parturition presented significantly lower IGF-1 values 12 hours p. p. (p = 0.005) in comparison to those with normal births. The present study underlines the relationship between dystocia and changed serum concentrations of leptin, IGF-1 and NEFA. In summary, it can be concluded that these parameters are suitable for interpretation of metabolic disorders in high-yielding cattle during peripartal period.

In der Nutztierhaltung besitzt die Erkennung und Vermeidung von Geburtsstörungen beim Rind insbesondere aus ökonomischer Sicht einen hohen Stellenwert. Bei Hochleistungskühen können Schwergeburten eine erhöhte metabolische Belastung im peripartalen Zeitraum reflektieren. Besonders betroffen sind Färsen und Milchkühe mit einer negativen Energiebilanz. Hormon- und Stoffwechselfaktoren sind von zentraler Bedeutung für die Anpassung der Tiere an Veränderungen ihrer Körpermasse und -konstitution. Zur differenzierten Beurteilung metabolischer Belastungen bei Hochleistungskühen im peripartalen Zeitraum wurden mögliche Zusammenhänge zwischen Geburtsverlauf und den stoffwechselrelevanten Parametern Leptin, Insulin-like growth factor-1 (IGF-1) und freien Fettsäuren (FFS) untersucht. Die vorliegende Studie umfasste 28 adulte, hochträchtige (13 primipare, 15 pluripare) Kühe mit Normal- bzw. Schwergeburt. Die Kälber wurden analog zu ihren Müttern ebenfalls 4  Gruppen (Kuhkalb/Normalgeburt; Kuhkalb/Schwergeburt; Färsenkalb/Normalgeburt; Färsenkalb/Schwergeburt) zugeordnet. Die Analyse von Leptin, IGF-1 und FFS im Blutserum erfolgte zwischen dem 16./14. Tag ante partum (a. p.) und dem 14. Tag post partum (p. p.). Leptin und IGF-1 wurden zusätzlich bei den neugeborenen Kälbern ab der Geburt bis 14 Tage p. p. gemessen. Die Hormonkonzentrationen wurden mittels eines Enzymimmunoassays bestimmt. Die FFS-Analysen erfolgten im Labor der Medizinischen Tierklinik mit dem Labor-Automaten HITACHI 912 i (Roche Diagnostics GmbH, Mannheim). Unabhängig vom Geburtsverlauf konnten während des gesamten Untersuchungszeitraums bezüglich der Leptinkonzentrationen keine signifikanten Unterschiede zwischen Färsen und Milchkühen festgestellt werden. Vor allem zur Geburt besteht für alle Erstkalbinnen eine erhöhte metabolische Belastung, da deren IGF-1-Konzentrationen zu diesem Zeitpunkt niedriger (114 ±  40 vs. 158 ± 108 ng/ml) und deren FFS-Konzentrationen signifikant höher lagen (896 ±  273 vs. 705 ±  225 µmol/l, p = 0,05) als bei den Milchkühen. Im Vergleich zu den Kälbern von Milchkühen wiesen Kälber von Färsen 12 Stunden nach der Geburt signifikant höhere IGF-1-Werte (p = 0,05) auf. In Abhängigkeit vom Geburtsverlauf lagen die Leptinwerte bei allen Kühen mit Schwergeburt von Beginn der Untersuchungen bis einen Tag vor der Geburt niedriger als bei den Tiere mit Normalgeburt mit signifikanten Unterschieden am 13. bis 11. Tag a. p. (p = 0,009) und am 7. bis 5. Tag a. p. (p = 0,05). Während des gesamten Untersuchungszeitraums waren keine signifikanten Unterschiede in den Konzentrationen an IGF-1 und FFS zwischen allen Muttertieren mit einem normalen und einem erschwerten Geburtsverlauf festzustellen. Bei pluriparen Kühen mit Schwergeburt wurden im gesamten Untersuchungszeitraum niedrigere Leptinspiegel nachgewiesen als bei Tieren mit Normalgeburt, mit signifikanten Unterschieden a. p. und ab 3. Tag p. p. (p < 0,05 bzw. p < 0,01). Darüber hinaus fanden sich bei pluriparen Kühen mit Dystokie ab der Geburt höhere FFS-Konzentrationen mit signifikanten Unterschieden zur Kalbung (p = 0,05). Die Leptinkonzentrationen der Kälber lagen analog zu den dazugehörigen Muttertieren ab der Geburt bis 14. Tag p. p. bei allen Kälbern von pluriparen Kühen mit Schwergeburt niedriger als bei den normal geborenen Kälbern mit signifikanten Unterschieden am 7. Tag p. p. (p = 0,04). Im Vergleich zu den Färsen mit Normalgeburt hatten diejenigen mit Schwergeburt signifikant höhere Leptinwerte vom 3. bis 14. Tag p. p. (p = 0,004), signifikant niedrigere IGF-1-Konzentrationen am 10. bis 8. Tag a. p., zur Geburt und vom 3. Tag bis 14. Tag p. p. (jeweils p < 0,01) sowie postpartal niedrigere FFS-Konzentrationen mit signifikanten Unterschieden 12 Stunden p. p. (p = 0,008). Kälber von Färsen mit gestörtem Geburtsverlauf wiesen im Vergleich zu den Normalgeburts-kälbern 12 Stunden nach der Geburt signifikant niedrigere IGF-1-Werte (p = 0,005) auf. Die vorliegende Studie verdeutlicht den Zusammenhang zwischen einem gestörten Geburtsablauf und veränderten Serumkonzentrationen an Leptin, IGF-1 und FFS. Damit konnte gezeigt werden, dass diese Parameter zur Interpretation von Stoff-wechselstörungen bei Hochleistungskühen im peripartalen Zeitraum geeignet sind. / For livestock management, the identification and prevention of dystocia in cattle is of high significance, especially from an economic point of view. Dystocia in the high-yield cows may reflect an increased metabolic disorder during the peripartal period. Heifers and dairy cows with a negative energy balance are particularly affected. For the adaptation of animals to changes in their body mass and constitution, endocrine and metabolic factors are of central importance. To perform a differentiated assessment of metabolic disorders in high-yield cows during the peripartal period, possible relationships between calving and relevant parameters (leptin, insulin-like growth factor1 [IGF-1] and non-esterified fatty acids [NEFA]) were examined. The present study involved 28 adult high-pregnant (13 primiparous, 15 pluriparous) cows with normal birth and dystocia, respectively. Analogous to their mothers, the calves were likewise categorized into four groups (cow calve/ normal birth; cow calve/ dystocia; heifer calve/ normal birth; heifer calve/ dystocia). The analyses of leptin, IGF-1 and NEFA in blood serum were performed from 16/14 day ante-partum (a. p.) to day 14 post-partum (p. p.). Leptin and IGF-1 were additionally determined in all newborn calves from birth to 14 days p. p. Hormone concentrations were measured by enzyme immunoassay (EIA). Analyses of NEFA in dairy cows and heifers were carried out using HITACHI 912i device (Roche Diagnostics GmbH, Mannheim) at the laboratory of Large Animal Clinic for Internal Medicine. Independent of course of parturition, no significant differences between heifers and dairy cows were noticed concerning serum leptin during the entire examination period. Especially around calving time, all heifers were more intensively affected with metabolic disorders based on their lower IGF-1 values (114 ± 40 vs. 158 ± 108 ng/ml) as well as significantly higher NEFA (896 ± 273 vs. 705 ± 225 µmol/l, p = 0.05) compared to dairy cows. Calves of heifers had significantly higher IGF-1 values 12 hours after birth (p = 0.005) than calves of dairy cows. Dependent of course of parturition, all cows with dystocia displayed lower leptin concentrations from the beginning of the examination period to 1 day a. p compared to animals with normal calving with significant differences from day 13 to day 11 a. p. (p = 0.009) and from day 7 to day 5 a. p. (p = 0.05). During the entire examination period, no significant differences in the concentrations of IGF-1 and NEFA were found between all cows with a normal and difficult parturition. In pluriparous cows with difficult parturition lower leptin levels were detected during the entire examination period than in animals with normal calving with significant differences a. p. and from day 3 to day 14 p. p. (p < 0.05 and p < 0.01, respectively). Furthermore, higher NEFA concentrations were found from birth until 14 days p. p. in pluriparous cows with dystocia and significant differences at calving (p = 0.05). Calves of pluriparous cows with dystocia had p. p. lower leptin concentrations in comparison to those with normal births with significant differences on day 7 p. p. (p = 0.04). In comparison to heifers with normal birth, those with dystocia displayed significantly higher leptin levels in the period from day 3 to day 14 p. p. (p = 0.004), significantly lower IGF-1 concentrations (from day 10 to day 8 a. p., at birth and from day 3 to day 14 p. p.; each p < 0.01), as well as lower NEFA levels after birth with significant differences 12 hours p. p. (p = 0.008). Heifer calves with difficult parturition presented significantly lower IGF-1 values 12 hours p. p. (p = 0.005) in comparison to those with normal births. The present study underlines the relationship between dystocia and changed serum concentrations of leptin, IGF-1 and NEFA. In summary, it can be concluded that these parameters are suitable for interpretation of metabolic disorders in high-yielding cattle during peripartal period.

GH and IGF-1 play an important role in the regulation of metabolism and body composition. In patients with uncontrolled acromegaly, cardiovascular morbidity and mortality are increased but are supposed to be normalised after biochemical control is achieved. We aimed at comparing body composition and the cardiovascular risk profile in patients with controlled acromegaly and controls. A cross-sectional study. We evaluated anthropometric parameters (height, weight, body mass index (BMI), waist and hip circumference, waist to height ratio) and, additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c, triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81 acromegalic patients (58% cured) compared to 320 age- and gender-matched controls (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group of 81 acromegalic patients presented with significantly higher anthropometric parameters, such as weight, BMI, waist and hip circumference, but with more favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total cholesterol, triglycerides and HDL levels, in comparison to their respective controls. Biochemically controlled acromegalic patients again showed significantly higher measurements of obesity, mainly visceral adiposity, than age- and gender-matched control patients (BMI 29.5 ± 5.9 vs. 27.3 ± 5.8 kg/m2; P = 0.020; waist circumference 100.9 ± 16.8 vs. 94.8 ± 15.5 cm; P = 0.031; hip circumference 110.7 ± 9.9 vs. 105.0 ± 11.7 cm; P = 0.001). No differences in the classical cardiovascular biomarkers were detected except for fasting plasma glucose and triglycerides. This effect could not be attributed to a higher prevalence of type 2 diabetes mellitus in the acromegalic patient group, since stratified analyses between the subgroup of patients with acromegaly and controls, both with type 2 diabetes mellitus, revealed that there were no significant differences in the anthropometric measurements. Biochemically cured acromegalic patients pertain an adverse anthropometric risk profile, mainly because of elevated adiposity measurements, such as BMI, waist and hip circumference, compared to an age- and gender-matched primary care population.