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Weight-associated stigmatization and discrimination may induce chronic stress in individuals with obesity. As a consequence, this stressor may cause an imbalance of HPA stress axis leading to increased eating behavior, and ultimately, weight gain. However, the direct link between internalized weight bias and stress response to acute stressors via cortisol secretion has not been investigated so far. Therefore, the purpose of this study was to investigate the interaction between internalized weight stigma as a stressor and cortisol reactivity in an acute psychosocial stress situation induced by the Trier Socials Stress Test for groups (TSST-G). Participants with BMI >30 kg/m2 (n = 79) were included in the study. Results reveal that while individuals with low internalized stigma reacted as predicted with an increase in cortisol secretion to acute psychosocial stress, individuals with medium or high internalized stigma did not show a typical cortisol response. However, these findings depend on the several factors, for instance on gender. In sum, acute stress in individuals with internalized weight bias seems to blunt HPA axis reactions to acute psychosocial stress. The study contributes to the understanding of the psychological and endocrinological consequences of internalized weight bias and underlines the importance of interventions to reduce stigmatization.

Background: Elderly patients are under-represented in hepatitis B and C screening approaches, but may be at increased risk for advanced liver disease. We therefore screened a hospitalized elderly population. Materials and methods: 6011 admissions to the department of internal medicine and neurology within one year were screened for HBsAg and anti-HCV (Elecsys ® -HBsAg and -anti-HCV). Positive anti-HCV results were confirmed with the INNO-LIA™ assay. HCV-RNA was analyzed by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in the confirmed HBsAg positive individuals. Results: Patient´s mean age (62.4 years) was 19 years above that of the average German population. The confirmed HBsAg prevalence was 0.6 %. 34 % (n = 12/35) of HBsAg positive cases were newly diagnosed, three of them presented with HBV-DNA levels > 2000 IU/mL. The confirmed anti-HCV prevalence was 0.9 %. 14 % (n = 8/56) of anti-HCV positive patients were previously undiagnosed. HCV-RNA was positive in three of them. In newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8 of the anti-HCV positive individuals. Compared to non-infected controls, the following risk factors were significantly more frequent in infected patients: (i) HBsAg: sexual exposure (20 % vs. 2 %), blood transfusion before 1992 (13 % vs. 6 %), referrals from nursing homes (10 % vs. 1 %). (ii) Anti-HCV: blood transfusion before 1992 (41 % vs. 6 %), IVDU (25 % vs. 0.5 %), organ transplantation (20 % vs. 5 %), hemodialysis (11 % vs. 3 %). Conclusions: HBsAg and anti-HCV were underdiagnosed in a senescent population, however, only few cases presented with advanced liver disease. Referrals from nursing homes were at increased risk for HBV infection.

Die Bestimmungen von 17-α-Hydroxyprogesteron (17-OHP) im morgens stressfrei gewonnenen Speichel dienen dem Therapiemonitoring bei klassischem angeborenem adrenogenitalem Syndrom (AGS). Von 47 erfolgreich behandelten Patienten und von 5 mit Verdacht auf Therapieversagen wurden retrospektiv die vierteljahrlich bei den ambulanten Konsultationen erhobenen Werte altersabhangig erfasst. Das Alter der 47 Patienten betrug bei Beginn der Beobachtung 10,5±5,3 Jahre, am Ende 20,5±5,8 Jahre, die Dauer der Beobachtung damit 10,0±2,8 Jahre mit 30,3±10,0 Werten pro Patient (Gesamtanzahl n=1424). Uber den Beobachtungszeitraum vermittelt der Medianwert der 17-OHP-Konzentrationen den besten Eindruck uber die therapeutische Einstellung bzw. die Therapietreue. Angestrebt werden Medianwerte bis 0,6 nmol/l, die bei 21 von 47 Patienten erreicht wurden. Ursachen hoherer Werte in allen Altersstufen waren Complianceprobleme, nichtoptimale Kortikoiddosierungen oder Therapieversagen. In 24,5% der notwendigen Dosisanderungen war der Speichelwert zusatzlich zu den klinischen Befunden hilfreich. Fur das Monitoring genugen die Werte im morgens zu Hause stressfrei gewonnenen Speichel. Werte im Normbereich sind erzielbar. Bei konstant unregelmasig hohen Werten ist eine Unterscheidung zwischen schlechter Compliance und Therapieversagen kaum moglich.

In 41 men with idiopathic infertility, the effect of pure follicle-stimulating hormone (pFSH) therapy on semen parameters was evaluated in relation to the results of the gonadotrophin-releasing hormone (GnRH) stimulation test in an open study. The patients showed a mean (+/-standard error) sperm concentration of 15.84 (+/-2.87) Mill. ml-1, 41.02 (+/-4.19)% of the spermatozoa were motile and 46.16 (+/-2.36)% normomorph before treatment. All patients were administered 150 IU pFSH subcutaneously three times weekly for 10 weeks. After therapy with pFSH, no significant differences compared with the pre-treatment sperm characteristics were observed (P0.05) except for the velocity average path, VAP (P = 0.029). However, the stimulation factors of FSH in the GnRH test showed a significantly negative correlation with the pFSH mediated improvement of sperm concentration (r = -0.662, P = 0.000002), of percentage of normomorph spermatozoa (r = -0.480, P = 0.0015) and total count of motile spermatozoa per ejaculate (r = -0.567, P = 0.00014). In consequence, the patients were divided into two groups depending on the stimulation factor of hypophyseal FSH secretion, FSH-SF. The cut-off point of the FSH-SF was set at 1.7 because the correlation analyses detected a 1.5-fold improvement of sperm parameters at this hypophyseal response on average. Pure FSH treatment increased the concentration of spermatozoa (P = 0.0007), the total count of motile spermatozoa in the ejaculate (P = 0.015) as well as the computer-aided sperm motion parameters VAP (P = 0.029) and velocity curve linear, VCL (P = 0.049) in patients with FSH-SF1.7, whereas in the patient group with FSH-SF1.7 no improvement of semen parameters was found. Insufficient stimulation of hypophyseal FSH secretion may be a prerequisite but not a guarantee for responsiveness to pFSH treatment. The results of the present investigation suggest that FSH stimulation in the GnRH test should be taken into account in idiopathic infertile men before pFSH therapy.

BACKGROUND To study the levels of transforming growth factor-1beta (TGF-beta1) and of alpha2-macroglobulin (alpha2-M), a high affinity binding protein of TGF-beta1, in comparison to prostate-specific antigen (PSA) in prostate cancer (PCa) patients before and up to 12 months after prostatectomy, and to correlate the results with clinicopathological parameters. METHODS Eighty-one patients who underwent radical prostatectomy for PCa were included in this study. Pre- and postoperatively, plasma levels of TGF-beta1, alpha2-M and PSA were measured in the same samples by ELISA, and were correlated with pathological parameters and clinical outcomes. RESULTS The preoperative TGF-beta1 levels were significantly elevated as compared to the controls; they showed a positive correlation with the Gleason score. Patients with initial androgen-deprivation therapy had lower TGF-beta1 levels than untreated patients. Elevated concentrations of TGF-beta1 levelled off 12 months after prostatectomy approaching values of healthy individuals. Decreased plasma levels of total and transformed alpha2-M (proteinase-complexed form) were observed in PCa. Preoperative levels of TGF-beta1 but not of alpha2-M seem to be influenced by the body mass index (BMI). CONCLUSIONS Elevated TGF-beta1 and decreased alpha2-M were consistently found in patients with PCa, and may be considered as risk factors for tumor development and progression. In comparison to PSA, the TGF-beta1 levels displayed a slow decline after radical prostatectomy; this indicates that TGF-beta1 is mainly produced outside the prostatic tissue. Since TGF-beta1 levels are influenced by the BMI, this indicates that PCa might be sensitive to diet.

To date, the precise etiology of molar-incisor hypomineralization (MIH) is uncertain. Vitamin D plays a key role in hard tissue formation. Therefore, this study aimed to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) status and dental health data obtained from 1,048 children in a 10-year follow-up of the Munich GINIplus and LISAplus birth cohorts. The dental examination included the diagnosis of MIH and recording of (non-)cavitated caries lesions in primary and permanent teeth. Serum 25(OH)D concentrations were taken from blood samples of the 10-year investigation and measured with a fully automated, modular system. Different logistic regression and Poisson hurdle models were calculated. MIH was diagnosed in 13.6% of the study population. Approximately 16.4% of the children demonstrated caries-related defects (D3-4MFS > 0). The mean season-adjusted concentration of 25(OH)D was 75.8 nmol/l (standard deviation 22.0 nmol/l). After adjusting for sex, age, body mass index, parental education, equivalent income, and television/personal computer (TV/PC) viewing hours, a 10 nmol/l increase in serum 25(OH)D concentrations was significantly associated with a lower odds ratio of having MIH (OR = 0.89; P = 0.006). Furthermore, higher 25(OH)D values were associated with a lower number of caries-affected permanent teeth. It is concluded that elevated serum 25(OH)D concentrations were associated with better dental health parameters.

Thyroid dysfunction may impair fertility, course of pregnancy and fetal development. Physiological alterations of thyroid function parameters, that occur during pregnancy need to be distinguished from pathophysiological states of hypo- and hyperthyroidism. We performed a literature search (PubMed 1990-2013) and review relevant publications as well as consensus and practice guidelines of international thyroid/endocrine societies. Interpretation of thyroid function values in pregnancy must be based on trimester-specific TSH and T4 ranges. Alterations in thyroid function are present in up to 15% of pregnancies (0.4% overt hypothyroidism, 0.1-0.4% hyperthyroidism) and may lead to preventable complications in the pregnant woman and the fetus. Hypothyroidism is associated with an increased risk for abortion, premature delivery and stillbirth, besides impairment of neurocognitive development. The latter has also been shown in situations of grave iodine deficiency. In addition to new-born screening directed at early recognition of congenital hypothyroidism (incidence 0.03%), universal screening of all pregnant women should be implemented in health care guidelines. Newly diagnosed overt hypothyroidism in a pregnant woman requires immediate levothyroxine substitution at adequate doses. In subclinical hypothyroidism thyroid hormone replacement should be considered. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Pregnancy causes a number of, that need to be of thyroid dysfunction. Both hypothyroidism and thyrotoxicosis may impair the course of pregnancy and may negatively affect the fetus. In particular, maternal hypothyroidism may lead to irreparable and detrimental deficits in the neurocognitive development of the fetus. Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto's thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the increased thyroid hormone requirement. Graves' disease often shows a characteristic course in pregnancy with amelioration of thyrotoxicosis in the second half of pregnancy and exacerbation after delivery. In addition transplacental passage of maternal TSH receptor antibodies may lead to thyrotoxicosis in the fetus and/or newborn.

OBJECTIVE: To identify binding proteins of leptin in human plasma. METHODS: Binding was evaluated by electrophoresis, size exclusion chromatography (SEC), Western blotting, and radioisotope labeling. Quantification of leptin and the different forms of alpha2-macroglobulin (alpha2-M) was performed by ELISA. RESULTS: Leptin interacts with the proteinase inhibitor, alpha2-M. 125I-labeled leptin specifically binds to the transformed inhibitor, which arises by reaction with proteinases or with reactive primary amines. No leptin binding was observed to the native alpha2-M, which abundantly occurs in plasma. The complex formation between leptin and alpha2-M was found to proceed within minutes and was stable, as it resisted separation by SEC and electrophoresis. The Kd of the complex was 2.14 +/- 0.78 micromol/l. Complex formation with transformed alpha2-M did not interfere with the immunological determination of leptin in plasma. The leptin-alpha2-M complex was found to be recognized by the alpha2-M receptor/low density lipoprotein receptor-related protein. By computer analysis, a simple model is presented showing that the degree of transformation of alpha2-M may significantly influence the leptin concentration in blood. CONCLUSIONS: The proteinase inhibitor, alpha2-M, may act as a leptin-binding protein in human plasma. Binding of leptin to transformed alpha2-M and its rapid clearance by the alpha2-M receptor may significantly influence the bioavailability of leptin in human plasma.

Schilddrusenfunktionsstorungen konnen Fertilitat, Schwangerschaftsverlauf und die kindliche Entwicklung ungunstig beeinflussen. Physiologische Veranderungen in der Schwangerschaft mussen von pathologischen Veranderungen der Schilddrusenfunktion abgegrenzt werden. Es handelt sich um eine Literaturrecherche (1990–2013) aus PubMed sowie um eine Auswertung der aktuellen Empfehlungen von Fachgesellschaften. Es bestehen Trimenon-spezifische Unterschiede der Referenzwerte von TSH und T4 in der Schwangerschaft. Veranderungen der Schilddrusenfunktion liegen in bis zu 15 % aller Schwangerschaften vor (0,4 % manifeste Hypothyreose, 0,1–0,4 % Hyperthyreose) und konnen zu vermeidbaren Komplikationen der Schwangerschaft und der Entwicklung des Kindes fuhren. Eine Hypothyreose erhoht das Risiko fur Spontanabort, Fruh- und Totgeburt, ferner fur neurokognitive Defekte des Kindes, die auch bei einem gravierenden Jodmangel belegt sind. In Erganzung des Neugeborenenscreenings zur Fruherkennung der angeborenen Hypothyreose (Inzidenz 0.03 %) sollte die Screening-Untersuchung auf Schilddrusenfunktionsstorungen in der Schwangerschaft, insbesondere der Hypothyreose, fest in die Vorsorge nach den Mutterschaftsrichtlinien aufgenommen werden. Bei Nachweis einer manifesten Hypothyreose ist unverzuglich eine Schilddrusenhormon-Substitution einzuleiten. Bei latenter Hypothyreose sollte eine Schilddrusenhormon-Therapie ebenfalls in Erwagung gezogen werden. Eine Jodid-Supplementation ist bei allen Schwangeren und Stillenden zur Vermeidung einer fetalen bzw. neonatalen Hypothyreose und Struma zu empfehlen.

Adipokines in breast milk have been associated with infant growth trajectories.We aimed to explore the relationship of leptin and adiponectin in breast milk with infant weight gain and body composition up to the age of 2 years.Breast milk samples were collected from exclusively or partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post-partum. Leptin and adiponectin were determined in skim breast milk and related to infant growth and fat mass assessed by skin-fold thickness measurements. A total of 118 infants were examined at 2 years.The levels of both milk adipokines were slightly lower at 4 months compared with 6 weeks post-partum. Breast milk leptin was largely unrelated to infant anthropometric measures up to 2 years. Milk adiponectin tended to be inversely related to early infant anthropometry up to 4 months, but beyond was positively associated with weight gain and the sum of skin-folds up to 2 years.Our results suggest that higher adiponectin levels in breast milk might be associated with greater weight gain and higher fat mass in the offspring up to 2 years.

OBJECTIVE Derangements in the GH/IGF axis are common in patients with diabetes mellitus. In insulin-dependent diabetes mellitus (IDDM), these disturbances seem to be due to a partial defect in GH action on its own receptor or via a post-receptor defect. In non-insulin-dependent diabetes mellitus (NIDDM), data are limited, and the regulation of the GH receptor (GHR) remains unclear. However, animal studies with diabetic rats demonstrated that the GHR density may be influenced by insulin disposal at the hepatocyte. With respect to this hypothesis we studied the relation between peripheral insulin status and the serum GH-binding protein (GHBP), which reflects indirectly the GHR density in the tissues. Patients with IDDM were compared to a NIDDM group as well as to a group of healthy subjects. DESIGN AND PATIENTS Basal blood samples for the determination of serum GHBP, GH, and IGF-I were obtained from patients with IDDM (n = 27), subjects with NIDDM (n = 112) and healthy controls (n = 42). Insulin, proinsulin, C-peptide and IGF-binding protein 1 (IGFBP-1) serum levels were used to estimate the insulin status in diabetic patients. RESULTS GHBP serum levels were significantly lower in patients with IDDM than in either NIDDM or controls (P

Growth parameters during infancy and early childhood might predict adipokine levels later in life. This study investigates the association between peak growth velocities, body mass index (BMI) and age at adiposity rebound (AR), with leptin and adiponectin levels at age 10 years. Peak height (PHV) and weight (PWV) velocities were calculated from height and weight measurements obtained between birth and age 2 years from 2880 children participating in the GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISAplus (Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics) birth cohorts. BMI and age at AR were calculated using BMI measurements between age 1.5 and 12 years. Blood samples were collected during a physical examination at age 10. Adiponectin and leptin levels were measured by radioimmunoassay. Linear regression models were fitted after adjustment for potential confounding factors and results are presented per interquartile range increase in the exposure. Age at AR was negatively associated with leptin in males and females (percent difference β*: −41.71%; 95% confidence interval: (−44.34;−38.96) and β*: −43.22%; (−45.59; −40.75), respectively). For both males and females PWV (β*: 14.23%; (7.60; 21.26) and β*: 18.54%; (10.76; 26.87), respectively) and BMI at AR (β*: 63.08%; (55.04; 71.53) and β*: 67.02%; (59.30; 75.10), respectively) were positively associated with leptin levels. PHV showed a positive effect on leptin in females only (β*: 10.75%; (3.73; 18.25)). Growth parameters were not significantly associated with adiponectin except for age at AR among females (β: 0.75 ng/ml; (0.42; 1.09)) and PWV among males (β: 0.45 ng/ml; (0.11; 0.79)). Growth patterns in early life may be associated with leptin levels at age 10 years.

Preeclampsia (PE) is associated with facets of the metabolic syndrome and an increased future metabolic and cardiovascular risk for mother and newborn. Recently, zinc-α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in the pathogenesis of obesity.In the current study, we investigated ZAG serum levels in PE patients as compared to healthy gestational age-matched controls.We quantified serum concentrations of ZAG in patients with PE (no.=37) as compared to healthy gestational age-matched controls (no.=37) by enzyme-linked immunosorbent assay. Furthermore, association of this adipokine with renal function, glucose and lipid metabolism, as well as inflammation was studied.Median serum ZAG levels were 1.4-fold higher in PE patients (58.8 mg/l) as compared to controls (41.9 mg/l) (p0.01). Furthermore, circulating ZAG was positively correlated to systolic and diastolic blood pressure, creatinine, triglycerides, and leptin in univariate analyses. In multiple regression analysis, creatinine remained independently associated with ZAG.We demonstrate that maternal ZAG serum concentrations are significantly increased in PE. Furthermore, renal function is an independent predictor of circulating ZAG.

In the clinical routine, the diagnosis of preeclampsia is often challenging. Not all pregnant women with signs and symptoms of preeclampsia develop the disease. Recently, the assessment of the sFlt-1/PlGF ratio in the serum of pregnant women has been proposed as an aid in the diagnosis of preeclampsia.In a retrospective, monocentric case-control study, we reviewed 30 cases of patients who presented with the clinical symptoms of hypertensive disorders of pregnancy in the delivery ward. Next to the standard diagnostic algorithm for preeclampsia, the sFlt-1/PlGF ratio was determined using the automated Elecsys® platform.In 12/30 cases (40%), the diagnosis of a hypertensive pregnancy disorder was confirmed with an sFlt1/PlGF ratio of85. In 18/30 (60%) cases, a ratio85 excluded the diagnosis of preeclampsia at the time of presentation and allowed an adaptation of the patient's surveillance programme.In the clinical setting of "suspected preeclampsia", determination of the sFlt-1/PlGF ratio can serve as an aid in the diagnosis of hypertensive disorders in pregnancy. The reliable exclusion of the diagnosis "preeclampsia" can help in an appropriate and cost-effective management of patients with signs and symptoms of the disease.

For medical, ethical, socioeconomic and humanitarian reasons, it seems mandatory to foster research into the causes and consequences of intrauterine growth retardation in the human. About 5% of newbo

Established reports about endocrine follow-ups in children and adolescents with cancer were rare.53 children were included in the clinical trial. The mean age was 9.6 years (0.5; 17.2 years), 10 patients died within the study period. The mean body length was normal with -0.14 SDS (-2.3; 2.5 SDS), as well as the body weight with 0.01 SDS and BMI with a mean of -0.03 SDS. Children and adolescents with different types of malignant tumors were included. According to the therapy protocol or tumor entity we divided this population in 5 subgroups (group 1 leukemia with 17 patients, group 2 lymphoma with 11 patients, group 3 tumor of CNS with 10 patients, group 4 bone and soft tissue tumors with 8 patients, group 5 different tumors with 7 patients).Anthropometrical and laboratory parameters were analyzed in intervals of 6 months over 2 years from the time point of diagnosis.We found differences in body height in children affected by cerebral tumors at the time of diagnosis and therefore before any therapy was started. These patients were significantly shorter (-0.6 SDS) than the other children. The body weight increased within the first year of therapy and was still higher than normal in the second year (comparison at the time point; from start to the first year+0.5 SDS, to second year+0.4 SDS) independently from the cortisone administration. Moreover, significant differences in the growth factor concentrations between the groups and time points were identified. Interestingly, children who survived their malignant disease tended to have higher levels of IGF-I and IGFBP-3 concentration than the patients who died within the study period. Additionally, the thyroid function was affected, shown as an increase of TSH with a concomitant decrease of the free thyroxin in 91% of all patients independent from the diagnosis (start TSH 1.8, fT4 15.6, after first year TSH 2.8, fT4 15.0). Thyroid function was monitored in 12 children, in 5 patients a short- or long-term substitution with thyroid hormone was indicated. Endocrine testing was initiated in 4 children, in 2 patients affection of the adrenal gland could be excluded, a suspected pituitary dysfunction after radiation was confirmed in 2 patients.We could represent that children and adolescents with malignant diseases showed affection of the endocrine system due to the tumour and the intensive therapy. The dysregulations in the endocrine system can be diagnosed through closely spaced monitoring and interdisciplinary cooperation.

Objectives. Resistin, a peptide hormone produced by adipocytes, has been associated with diabetes mellitus type 2 (DM-2) in some rodent models. In humans the exact function of resistin remains unknown. Some, but not all studies have found associations between polymorphisms in the resistin gene with DM-2. Recently a 3′-untranslated region +62GA polymorphism of the resistin gene has been associated with decreased risk for DM-2 and for hypertension in diabetics in a Chinese population. Purpose of the present study was to examine for the first time in a German Caucasian population the possible association between this polymorphism and DM-2, hypertension, lipoprotein levels, resistin levels as well as atherosclerosis. Design, setting and subjects. A total of 818 subjects participated in the study. The presence of the +62GA polymorphism of the resistin gene was investigated using polymerase chain reaction-restriction fragment length polymorphism in 384 subjects with DM-2 [224 men, 160 women, age 63.4 ± 10.6 years, body mass index (BMI) 28.7 ± 5.1 kg m−2] and in 434 nondiabetic age- and sex-matched control subjects (248 men, 186 women, age 64.4 ± 6.5 years, BMI 26.5 ± 3.7 kg m−2). Results. Thirty-four subjects were found to be carrying the +62GA polymorphism in the control and 24 in the diabetic group (allelic frequencies 4% and 3.2% respectively). Subjects with DM-2 were not found to have a different frequency of the genotypes (93.75% and 6.258%, for GG:GA/AA respectively) than the control subjects (92.2% and 7.8% for GG:GA/AA respectively) (OR 0.75, 95% CI 0.44–1.3, P = 0.31). In the total cohort, carriers of the A allele had a higher prevalence of hypertension (OR 1.82, 95% CI 1.03–3.21, P = 0.039). When analysed separately, the control group showed a strong association between the presence of the A allele and hypertension (OR 2.92, 95% CI 1.38–6.15, P = 0.005), whilst no such association could be established in the diabetic group (OR 1.05, 95% CI 0.43–2.54, P = 0.92). Multiple regression analysis confirmed that the presence of the A variant is associated with hypertension in control but not in diabetic subjects, independent of age and BMI. The polymorphism had no significant influence on the presence of atherosclerotic disease, BMI, and on triglyceride, HDL and LDL cholesterol levels, both, in the control and the diabetic groups. There was no difference in the serum resistin levels between the 62GA variant carriers and noncarriers. Conclusions. In conclusion, the present data suggest that in a German Caucasian population the +62GA polymorphism of the resistin gene is associated with hypertension but not with DM-2.

Benign (n=33) and malignant metastasizing (n=1) granulosa cell tumours (GCTs) from 34 mares aged 3-21 years, and normal (control) ovaries from nine mares aged 3-10 years, were examined histologically and immunohistochemically (for inhibin alpha, glutathione S-transferase alpha [GSTalpha], c-erbB-2 oncoprotein [cerb], cytokeratin, vimentin, desmin and alpha-actin), the results being related where appropriate to clinical signs and endocrinological data. Availability permitting, serum samples from GCT-affected mares before and several weeks after ovariectomy were examined for the following hormones: oestradiol, progesterone and testosterone (by radioimmunoassay); and inhibin B (by a cross-reactive ELISA). Histological examination revealed that the GCTs were predominantly well differentiated neoplasms. The metastasizing GCT differed immunohistochemically from the benign GCTs in respect of the expression patterns of vimentin, cerb and GSTalpha in the granulosa cells. A notable feature was the presence of Leydig-like cells in mares with stallion-like behaviour or elevated serum testosterone, or both. GSTalpha immunolabelling indicated that the Leydig-like cells were potential producers of steroid hormone. From the immunohistochemical and endocrinological findings it was concluded that GCTs produce abnormally high concentrations of inhibin, which reduce the release of follicle-stimulating hormone, leading to atrophy of the contralateral ovary-a finding in 27 of the mares.

To study the levels of transforming growth factor-1beta (TGF-beta1) and of alpha2-macroglobulin (alpha2-M), a high affinity binding protein of TGF-beta1, in comparison to prostate-specific antigen (PSA) in prostate cancer (PCa) patients before and up to 12 months after prostatectomy, and to correlate the results with clinicopathological parameters.Eighty-one patients who underwent radical prostatectomy for PCa were included in this study. Pre- and postoperatively, plasma levels of TGF-beta1, alpha2-M and PSA were measured in the same samples by ELISA, and were correlated with pathological parameters and clinical outcomes.The preoperative TGF-beta1 levels were significantly elevated as compared to the controls; they showed a positive correlation with the Gleason score. Patients with initial androgen-deprivation therapy had lower TGF-beta1 levels than untreated patients. Elevated concentrations of TGF-beta1 levelled off 12 months after prostatectomy approaching values of healthy individuals. Decreased plasma levels of total and transformed alpha2-M (proteinase-complexed form) were observed in PCa. Preoperative levels of TGF-beta1 but not of alpha2-M seem to be influenced by the body mass index (BMI).Elevated TGF-beta1 and decreased alpha2-M were consistently found in patients with PCa, and may be considered as risk factors for tumor development and progression. In comparison to PSA, the TGF-beta1 levels displayed a slow decline after radical prostatectomy; this indicates that TGF-beta1 is mainly produced outside the prostatic tissue. Since TGF-beta1 levels are influenced by the BMI, this indicates that PCa might be sensitive to diet.

Osteopathy is a common clinical feature of chronic inflammatory bowel disease (IBD) in children and young adults at the time of primary diagnosis. The aim of the following study was to address the question of prevalance of a decreased bone density or increased bone metabolism in children with IBD.We examined 63 patients (mean age 13 years; 5 - 18 years): 36 Crohn's disease (MC) patients, 16 colitis ulcerosa (CU) patient and one patient with colitis indeterminata (CID). 10 children who had been referred to the gastroenterological outpatient department due to suspected IBD symptoms were later found not to suffer from IBD. These 10 patients therefore were included in the study as controls.8 of 10 CU patients and 18 of 28 MC patients showed a pathological bone density and abnormalities in bone metabolism. Repetitive bone density measurement was performed in 18 patients. In MC patients a - 0.39 SDS decrease of bone mineral density was found, without a simultaneous deterioration of clinical stage and inspite of a decreased cumulative prednisolon dosage. However in CU patients a + 0.06 SDS increase of bone mineral density was detected. These patients had a lower cumulative prednisolon dosage and a stable clinical course.In conclusion, pediatric IBD patients often show abnormalities in bone metabolism and decreased bone density. There is a need for multicentre, prospective randomised control trials to further identify therapeutic tools on the basis of the multifactorial etiology of bone disease in pediatric IBD patients.

Leptin, a 167 amino acid peptide, is known to influence the gonads via direct and indirect effects. Recent studies provide contradictory proposition about the peripheral impact of leptin in the male gonads. Thus, we examined leptin and its receptors in human seminal plasma and in human ejaculated spermatozoa by Western blot technique and fluorescence microscopy. In seminal plasma we found a free leptin band (16 kDa) by an anti-leptin polyclonal antibody. Incubation of seminal plasma with recombinant leptin caused a statistically significant increase in the amount of free leptin (p0.01) and supports this finding. Furthermore, a soluble leptin receptor (145 kDa) was found in human seminal plasma in the same specimen. We also detected a 145-kDa leptin receptor isoform in ejaculated spermatozoa as a possible target of leptin action in the male genital tract, which was localized at the tail of spermatozoa by immunofluorescence microscopy only. This receptor was significantly associated with the intactness of sperm plasma membranes. Spermatozoa with deteriorated membranes contained 49.2 +/- 6.9% leptin receptor signal intensity compared with spermatozoa having intact membranes (p0.01). This finding is difficult to interpret and may be caused by a leakage of OB-R due to loss of membrane integrity. In conclusion, these data provide further hints for a peripheral role of leptin in the male genital tract, possibly, by an interaction between leptin and spermatozoa via sperm leptin receptors.

The aim of our hGH application study with non-competitive athletes was the investigation of selected serum parameters from different processes affected by hGH. Fifteen athletes (age 21-33, mean 24) were treated with 0.06 IU hGH/kg BW per day or placebo (10 hGH, 5 placebo) respectively for 14 days. Blood samples were taken prior to, during and until 10 weeks after treatment. The concentrations of the following markers were determined in relevant serum samples: IGF-I, IGFBP-3, ALS, PIIINP, PINP, osteocalcin, and leptin. The IGF-I concentration increased rapidly within the hGH treatment group and showed significantly higher levels compared to baseline even 3 days after application. The response of the IGFBP-3 to the hGH applications was lower in comparison to IGF-I. The hGH group showed an increasing IGFBP-3 compared to baseline from day 4 till day 15. The response of PIIINP to hGH is clearly delayed compared to the IGF-I axis, but the PIIINP concentration remains on an increased level for a longer period (from day 4 until day 21). The time course and the extent of response varied strongly interindividually. PINP and osteocalcin showed only a small response to hGH applications. These parameters are characterised by a strong scattering of base values compared with the small response. In the hGH treatment group very different leptin concentrations were found at the beginning of the study, but after treatment decreasing leptin levels were observed in all cases. The determination of only one parameter will not be sufficient for detection of hGH abuse. A combination of markers by mathematical methods can be helpful to distinguish between placebo and hGH-treated athletes. By using the suggested discriminant function the data sets of hGH and placebo-treated athletes could be separated without false positive results.

The laboratory analyses of 404 participants of the health study GUNDULA, 201 men and 203 women between 30 and 80 years old, were performed to evaluate the variables for the determination of biological age. From the more than 70 laboratory variables resulting from clinical-chemical and hematologic tests and from urinalysis, less than 40 are significantly age-dependent. About half of these variables were examined by regression analysis to evaluate whether they are useful for the estimation of biological age by a laboratory index. Considerable sex differences were observed. The laboratory indexes for the participants altogether (resulting from 13 parameters) and separated for women (10 parameters) and men (8 parameters) show more variations than the biological age estimated by non-invasive parameters. In men only, there exists a significant but inverse correlation between laboratory index and relative aging rate, the difference between biological and chronological age. The results of some striking variables (e.g. dehydroepiandrosterone sulfate and others) and the results of an explorative factor analysis with regard to possible interconnections between variables and chronological age will be discussed.

The industrialized countries around the world are experiencing an epidemic of childhood obesity. The level of fatness of a child at which morbidity increases acutely and/or later in life is determined on an individual basis. Overall, however, childhood obesity substantially increases the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge of the role of neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte-concentrating hormone receptors. Environmental and exogenous factors are the main contributors to the development of a high degree of body fatness early in life. Studies involving twins suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders, including a number of endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that can present with obesity. A simple diagnostic algorithm allows for differentiation between primary and secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. It is somewhat ironic that the definition of obesity in childhood is not an easy one. Direct measurements of body fat content, such as hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful tools in scientific studies. Body mass index (BMI) is, however, now generally accepted to be a good clinical measure for the definition of obesity in children and adolescents. In preadolescent boys, BMI also relates to muscle mass and should be used for the definition of fat mass with great caution. An increased risk of death from cardiovascular disease in adults has been found in patients whose BMI had been greater than the 75th percentile as adolescents. Therapeutic strategies include psychological and family therapy, modification of lifestyle and behavior, and nutritional education. The role of regular exercise and exercise programs is emphasized, while surgical procedures and drugs used in adult obesity are still not generally recommended for obese children. Obesity is the most common chronic disorder in industrialized countries, and its impact on individual lives as well as on health economics must be recognized by physicians and the public alike. This review aims to increase awareness of the health burden and economic dimension of the epidemic of childhood obesity that is occurring around the globe.

P637 HBsAg AND ANTI-HCV SCREENING IN SENESCENT HOSPITALIZED PATIENTS OF A GERMAN TERTIARY REFERRAL CENTRE J. Kant, J. Kratzsch, M. Maier, U.G. Liebert, J. Thiery, S. Bohm, T. Berg, J. Wiegand. Department of Gastroenterology and Rheumatology, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Institute of Virology, University of Leipzig, Leipzig, Germany E-mail: juliane.kant@medizin.uni-leipzig.de

The degree of probability to retrieve spermatozoa from testicular tissue for intracytoplasmic sperm injection into oocytes is of interest for counselling of infertility patients. We investigated the relation of sperm retrieval to clinical data and histological pattern in testicular biopsies from azoospermic patients.In 264 testicular biopsies from 142 azoospermic patients, the testicular tissue was shredded to separate the spermatozoa, histological semi-thin sections of which were then evaluated using Johnsen score.The retrieval of spermatozoa correlated significantly ( P0.001) with the testicular volume ( r = 0.49), the FSH concentration ( r = -0.66), the maximum score (r = 0.85) and the mean Johnsen score (r = 0.81). In the multivariate regression analysis the successful testicular sperm extraction showed the closest relationship to the maximum score. The testicular volume correlated significantly with the mean Johnsen score ( r = 0. 64, P0. 001), and the basal serum FSH concentration mainly with the maximum score ( r = - 0.77; P0.001). Patients with a history cryptorchidism showed a significantly lower Johnsen score compared to the patients who did not have any testicular disease in the past (3.7 +/- 2.4 vs. 5.9 +/- 2.5; P0. 01).In a limited range, the testicular volume and the FSH concentration in serum were related to the Johnsen score which correlated significantly with the sperm retrieval. The successful sperm retrieval can be expected in all azoospermic patients irrespective of the results of clinical examination. However, the probability of retrieval of spermatozoa decreased significantly in patients with a FSH level18 U/L, testicular volume5 mL, mean Johnsen score5, and maximum Johnsen score7.

In this study we tested the performance of easy-to-use and rapid, commercially available immunoassays to measure free testosterone (fT) and sex hormone-binding globulin (SHBG). We asked whether fT and SHBG serum levels are age-dependent and whether or not there is a gender dependence of fT and SHBG in this age group. Finally, by measuring fT and SHBG in sera of a cohort of healthy children and adolescents using commercially available immunoassays, we established normative data for fT and SHBG in this age group: in boys fT levels increased significantly (r=0.83, p0.0001) from 0.63 pmol/l (median) in the age group below 5 years to 56.9 pmol/l in the age group 16-20 years. In girls fT levels also increased with age (r=0.66, p0.0001): from 0.72 pmol/l (median) in the age group below 5 years to 3.34 pmol/l in the age group 16-20 years. In contrast, SHBG serum concentrations significantly decreased with age in boys (r=-0.62, p0.0001) but remained constant in girls (r=0.04, n.s.). Importantly, fT values were independent of SHBG levels as determined by our methods. In conclusion, fT can be measured in an acceptable quality using the DSL analog tracer-based immunoassay and normative data are now available. In addition, SHBG levels in healthy children and adolescents are also given and may permit for studies of pathophysiologic states in this age group.

Recently, two isoforms of the growth hormone-binding protein (GHBP), which is identical with the extracellular domain of the growth hormone receptor (GHR), have been described. One isoform contains the exon 3 (E3+GHBP) and one excludes the exon 3 (E3-GHBP). The distribution of both isoforms in peripheral blood and their functional relevance is so far unknown. To study the molecular distribution of both species we have analysed sera of 141 subjects with average weight, overweight and obesity by newly developed immunoassays. The relationship between the different molecular forms of GHBP and specific parameters of body composition as well as risk factors of metabolic disturbances, were then examined. The extracellular domain of the exon 3-retaining and -deleted isoforms of the GHR are released as E3+GHBP and E3-GHBP into the peripheral circulation. Furthermore, both molecular species do not show any correlation to each other (r = 0.67) and their relative proportion in blood is gender-dependent with a higher E3-GHBP proportion in females (P0.01). E3+GHBP appears to have a considerably stronger correlation to indicators (BMI, fat mass, waist circumference) and metabolic risk factors (fasting insulin, uric acid, triglycerides, apolipoprotein B, diastolic blood pressure) of adiposity than E3-GHBP, indicating differences in their functional significance. The availability of assays for the determination of GHBP isoforms may be very important for the study of the GH receptor and its soluble extracellular domain, GHBP.

Experimental rodent studies demonstrate that insulin-like growth factor II (IGF-II) promotes fetal growth, whereas the nonsignaling IGF-II receptor (IGF2R) is inhibitory; in humans their influence is as yet unclear. A soluble, circulating form of IGF2R inhibits IGF-II mediated DNA synthesis and may therefore restrain fetal growth. We measured cord blood levels of IGF-II, soluble IGF2R, insulin, IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and examined their relationships to weight, length, head circumference, ponderal index, and placental weight at birth in 199 normal term singletons. IGF-II levels correlated with levels of IGF-I (r = 0.29; P0.0005), IGFBP-3 (r = 0.45; P0.0005), and soluble IGF2R (r = 0.20; P0.005). Insulin and IGF-I were positively related to all parameters of size at birth. IGF-II was weakly related to ponderal index (r = 0.18; P0.05) and placental weight (r = 0.18; P0.05), and the molar ratio of IGF-II to IGF2R was also related to birth weight (r = 0.15; P0.05). Correlations between the IGFs and size at birth were stronger in nonprimiparous pregnancies; in these, IGF-I (r = 0.52; P0.0005), IGFBP-3 (r = 0.41; P0.0005), and the IGF-II to IGF2R ratio (r = 0.40; P0.0005) were most closely related to placental weight, together accounting for 39% of its variance. We demonstrate for the first time relationships between circulating IGF-II and soluble IGF2R levels and size at birth, supporting their putative opposing roles in human fetal growth.

The measurement of cortisol and 17-hydroxyprogesterone (17-OHP) in saliva has become a reliable tool for both the scientist and the clinician for studying adrenal cortical function in the adult and the older child. We have now established in parallel normative data for salivary cortisol and 17-OHP levels in healthy neonates. We have asked whether or not there is a circadian rhythm of cortisol and 17-OHP saliva levels in neonates. Furthermore, we have asked whether salivary hormone levels correlated with auxologic and clinical data and time of sampling. Cortisol and 17-OHP levels in saliva samples from 119 healthy neonates (55 girls, 64 boys) were measured using in-house time-resolved fluorescent immunoassays. Saliva samples were obtained using a saliva collecting tube three times a day on the first or second day of life. Gender and gestational age did not influence salivary cortisol and 17-OHP levels. No significant circadian rhythm of salivary hormone levels was detected in this group of newborns. However, body mass index, arterial cord blood pH and time of saliva sampling significantly influenced salivary hormone levels. In conclusion, measurement of cortisol and 17-OHP in saliva is feasible in healthy neonates. The existence of normative data forms the basis for future studies on pathophysiologic states in the newborn period.

Progression through the cell cycle and redirection of cells towards programmed cell death (apoptosis) are tightly inter-related processes. However the requirement for tissue and cell type specificity suggests that a wide variety of mechanisms are used to achieve the same purpose. To examine this issue, we investigated cell cycle (c-myc, p53, p21/WAF) and apoptosis related (bcl-2, bcl-X(L), bax-alpha) gene expression in two cell lines of very different origin under proliferating and apoptosis-inducing conditions. Transformed human osteosarcoma cells (MG63) and non-transformed human kidney embryonal fibroblasts (293-0) were kept in culture in medium containing 10% FCS and growth arrest was induced by the addition of 50 ng/ml colcemid. Colcemid treatment caused growth arrest and elevated expression of cyclin B1 protein in both cell lines. Apoptosis was significantly elevated in both cell lines after colcemid exposure for at least one cell cycle. However the pattern of expression of cell cycle and apoptosis related genes, determined by RT-PCR, was quite different between the two cell lines during exponential growth and cell cycle arrest. Colcemid treatment did not markedly influence c-myc, p53 and p21/WAF expression in MG63 cells but did suppress c-myc and increase p21/WAF in 293-0 cells. Furthermore colcemid treated MG63 cells exhibited elevated bcl-2 and bax-alpha expression while similar treatment of 293-0 cells resulted in decreased bcl-X(L) and slightly increased bax-alpha expression. While growth arrest and apoptosis were induced in both MG63 and 293 cells following colcemid treatment, the differences in gene expression suggest that the mechanism by which these cells determine cell fate is quite different and may determine the sensitivity of different cell populations to anti-neoplastic drug therapy. The distinct patterns of gene expression should be carefully defined before mechanisms of apoptotic cell death are studied.

Die phoniatrische Betreuung der kindlichen Singstimme während des Stimmwechsels erscheint gerade bei Sängern in Knabenchören mit hoher stimmlicher Belastung wichtig. Die vorliegende Studie sucht nach Methoden, den Eintrittszeitpunkt der Mutation vorherzusagen und das Vorliegen einer Mutation differentialdiagnostisch von hyperfunktionellen Stimmstörungen oder entzündlichen Erkrankungen des Stimmorganes zu trennen. Dazu wurden 36 Knaben des Leipziger Thomanerchores im Sinne einer Longitudinalstudie alle 3 Monate über 3,5 Jahre bis zum hörbaren Einsetzen der Mutation untersucht. Es erfolgte die Bestimmung von zehn stimmlichen und acht stimmunabhängigen Parametern, die erstmals in solch umfassender Form auf ihre prädiktive Aussagekraft geprüft wurden. Die statistische Auswertung wies besonders den Serumtestosteronspiegel und die Wachstumsrate als Grössen aus, die mit dem Prämutationsverlauf korrelieren und eine konkrete Vorhersage ermöglichen. Das Vorliegen einer Mutation kann ausserdem durch den Verlauf der mittleren ungespannten Sprechstimmlage und unter Hinzuziehung des Genitalstatus bestätigt werden. Durch die exakte und prädiktive Bestimmung des Mutationsbeginnes können Erkrankungen des Stimmapparates vermieden werden, die aus dem intensiven Singen in der Mutation resultieren. Weiterhin geben die Ergebnisse dem Chorleiter wertvolle Informationen für die Planung der Besetzung seiner Knabenstimmen.

Leptin, the ob gene product, plays a key role in the regulation of body fat mass and weight in adult life. The mechanisms by which maternal and fetal/neonatal weight are regulated during human pregnancy and in early postnatal life are poorly understood. High leptin levels are observed in women during gestation and in cord blood at term. We have hypothesized that high leptin levels at term could represent an important feed-back indicator of nutrient supply. Subsequently, leptin could signal adipose tissue status during late gestation and during early neonatal life.51 healthy newborns were studied. Clinical and auxological data (birth length, weight, and iliac, subscapular, biceps and triceps skinfold thickness) were recorded using a standardized data sheet. Venous cord blood was obtained immediately after birth in all neonates. Subsequently, capillary blood was obtained from the heel from some of the newborns when blood had to be obtained because of signs or symptoms of particular problems such as hypoglycaemia or hyperbilirubinaemia, at the following time points: two to four hours after birth in 51 infants, 56-79 h after birth in 47 infants and 99-128 h after birth in 23 of the newborns. The ratio between the sexes (girls/boys) was similar at all time points. The infants that were included in the study were subsequently found to be normal and healthy after analysis of the clinical and biochemical data. A specific ultrasensitive radioimmunoassay was used to measure leptin, while growth hormone and insulin were measured using commercially available immunoassays.Gestational age was 38-42 weeks, maternal age was 21-42 years. Birth weights ranged from 2480 to 4400 g. All newborns and mothers were subsequently found to be healthy. Leptin levels in venous cord blood was 0.16-6.80 microg/l, median 3. 47 microg/l and in capillary blood shortly after birth 0.26-7.03 microg/l, median 3.89 microg/l. 56-79 h after birth leptin levels had fallen dramatically, range 0.02-1.69 microg/l, median 0.26 microg/l, while 99-128 h after birth, leptin concentrations in capillary blood (0.05-2.61 microg/l, median 0.59 microg/l) had significantly increased when compared to the levels at 56-79 h (P0.001). There was a significant correlation between leptin levels in umbilical vein and birth weight of the neonates (r = 0.57, P0.03). Multistep regression analysis revealed that weight and skinfold thickness accounted for approximately 35-70% of the variation of leptin levels. Insulin and growth hormone, and glucose and bilirubin however, had no major impact on leptin levels.High leptin levels are present in cord blood at birth and in capillary blood shortly after birth. Since leptin levels in cord blood correlate with birth weight it is tempting to speculate that in the fetus as in later life leptin is signalling expansion of fat stores. Most importantly, we now report that leptin levels are high in the fetus but decline rapidly and dramatically after birth in healthy neonates. This may be important for the stimulation of feeding behaviour and the acquisition of energy homeostasis in the neonate.