Expression of corticosteroid-binding globulin CBG in the human heart.

Glucocorticoids are known to be involved in myocardial regeneration and destruction. Cardiomyocytes are mostly devoid of nuclear glucocorticoid receptors (GRs) and it is generally assumed that effects of adrenal steroids in heart are mediated through the mineralocorticoid receptor (MR). Here we used immunocytochemistry to study localization of corticosteroid binding globulin (CBG) in semithin sections of human cardiac tissue samples. With staining of consecutive sections we examined colocalization with GR and MR immunoreactivities. While GR staining was almost undetectable, a portion of myocytes with MR immunostained nuclei was found. Almost all cardiomyocytes exhibited CBG immunostaining in cytoplasm and on the cell membrane. Most pronounced CBG immunoreactivities were found in Purkinje fibers and in smooth muscle cells of arterial walls. With RT-PCR, we found in homogenates of cardiac tissue detectable levels of CBG encoding mRNA. Our findings indicate that CBG is expressed in human heart. Known cardiac effects of adrenal steroids may in part be mediated through the binding globulin and its putative membrane receptor in addition to nuclear steroid receptors and direct genomic action. Highlights of our study: Human cardiomyocytes express mineralocorticoid receptors, but are mostly free of nuclear glucocorticoid receptors. CBG is expressed in myocardium and in Purkinje fibers. CBG in heart is colocalized with mineralocorticoid receptor. Endothelia and smooth muscle cells of arterial walls show colocalization of CBG and MR.

Altered oxytocinergic hypothalamus systems in sepsis.

Sepsis is known to affect neuroendocrine circuits: injections of lipopolysaccaride are potent stimulators of oxytocin secretion from the posterior lobe, acute sepsis leads to uterus contractions and spontaneous abort. Here, we report changes in expression and distribution of hypothalamic oxytocin in rats that had been subjected to caecal ligation and puncture which led to acute sepsis. Septic animals showed loss of oxytocin immunostaining in perikarya of the supraoptic and paraventricular nuclei and an increase of oxytocin positive fibres, suggesting a shift of oxytocin pools into the axonal compartment. Immunostaining of the posterior lobe revealed reduction of oxytocin in septic rats. Magnocellular neurons in supraoptic- and to a lesser extent in paraventricular nuclei showed nuclear immunoreactivity for the protooncogene c-Fos, indicating stimulation of transcriptional activity upon sepsis. Contrary to magnocellular oxytocin immunoreactivity, we observed increased oxytocin immunoreactivity in cell bodies and processes of periventricular nucleus and in perivascular neurons. Oxytocin neurons in other regions of the hypothalamus and the preoptic region did not appear to be affected by acute sepsis. Our findings suggest a differential activation of neurohypophyseal and cerebrospinal fluid contacting oxytocin systems while centrally projecting oxytocin neurons may not be affected. Systemic oxytocin levels may serve as additional diagnostic marker for sepsis.

Altered homeostasis of systemic glucocorticoids as related to obesity, glucose tolerance, and smoking.

The hypothalamic-pituitary-adrenal axis is supposed to be involved in the pathogenesis of the metabolic disorders. Differences in adipose tissues and parameters of insulin resistance are linked to steroid homeostasis. We assessed the correlation of fat tissue distribution, gender, and glucose control with levels of systemic corticosteroid-binding globulin (CBG), free cortisol (FuF), and total cortisol (FuM). Data of 1 114 patients with overweight, lipid disorders, and impaired glucose tolerance were collected. Blood samples were sorted according to gender and anthropometric measures. Variable-association was calculated using the Spearman Rank Correlation coefficient and tested for significance (p<0.05 and p<0.01). CBG and FuF were consistently negatively correlated to each weight parameter. Especially in women, fat mass index (FMI) was significantly negatively correlated with CBG-levels. While CBG levels dropped with increasing age, FuF showed an inverse behavior. Glycohemoglobin levels showed negative correlations with CBG while fasting glucose did not. Both changes were associated with significant increases in FuF. All negative correlations to cortisol and its binding globulin with regards to weigh- and glucose-control parameters were absent in smokers compared to nonsmokers. Our observations suggest that different weight parameters correspond to adrenal steroids and their buffer systems. Especially in women, CBG levels might serve as prognostic marker for the fat mass. In addition, CBG levels may predict long term blood glucose control more reliably than FG. However, the value of CBG as an indirect surrogate-marker for obesity and glucose is limited in smokers.

["Fiction and Truth": Goethe's anatomical research at the University of Jena]. / "Dichtung und Wahrheit": Goethes anatomische Forschung an der Universität Jena.

Johann Wolfgang von Goethe was one of the most renowned German poets of the late Age of Enlightenment. However, his engagement went far beyond literature especially relating to politics and natural science. Goethe, primarily trained as a lawyer, developed his own theory of colors and even challenged the concepts of Isaac Newton. His discovery of the human intermaxilary bone questioned all the dogmas of the religious-minded world of the 18th century. Together with the anatomy professor Justus Christian Loder, Goethe performed comparative anatomy and proved the conceptual uniformity of humans and animals on 27 March 1784. Even though, Félix Vicq d'Azyr described the intermaxilary bone simultaneously in Catholic France, Goethe's findings were politically accepted due to the liberal Protestantism of the Duchy of Weimar. Nevertheless, leading anatomists of the century (Johann Friedrich Blumenbach, Petrus Camper and Samuel Thomas v. Soemmerring) mainly rejected Goethe's postulates which led to a delayed publication in 1820; almost 36 years after writing his original manuscript. Today, Goethe's discovery is known to be a fundamental basis for the development of Charles Darwin's theory of phylogenetic evolution. Nowadays, the Department of Anatomy contains the Museum Anatomicum Jenense which was founded by the Duke of Weimar, Carl August and Goethe and entails Goethe's premaxillary bones as its main attraction. The University values the cultural heritage of Goethe's contribution to Medicine and provides access to the collection to the public and generations of medical students. Still today Goethe's legacy is noticeable in the halls of the Alma Mater Jenensis.

[The contribution of Christian Barnard to the history of transplantation medicine]. / Der Beitrag Christian Barnards zur Geschichte der Transplantationsmedizin.

On December 3 rd, 1967, Christian Barnard conducted the first orthotopic heart transplant at Groote Schuur hospital in Cape Town, South Africa. Barnard competed with the American heart surgeons Norman Shumway, Adam Kantrowitz and Richard Lower, who laid the experimental foundations for the operation in the previous years. The patient, Loius Washkansky, survived 18 days. Today, Barnard is revered as a pioneer in the history of medicine. However, his achievement is discussed controversially due to the unselective choice of patients, the lack of legal provision for the removal of organs in South Africa, and the absence of therapeutic options for prevention of transplant rejection. Barnard's success was supported by a well established interdisciplinary cooperation within different departments at Groote Schuur. The financial stability and the high standard of science in South Africa in the 1960 s contributed to this surgical victory. In 2011, the Department maintains a transplant program and conducts international renowned research in the field of biomechanics and in vivo tissue engineering.

[Local excision with transanal endoscopic microsurgery (TEM) after endoscopic R1/R2-polypectomy of pT1 "low-risk" carcinomas of the rectum]. / Lokale Nachexzision nach endoskopischer R1/R2-Polypektomie von pT1-,,low-risk''- Karzinomen des Rektums durch transanale endoskopische Mikrochirurgie (TEM).

The transanal endoscopic microsurgery (TEM) is an adequate method for the local full-thickness excision of large rectum polyps and pT1 "low-risk" rectal carcinomas. We studied prospectively the relevance of this surgical technique concerning complete tumour excision after R1/R2-polypectomy of malignant rectal polyps. 16 patients with pT1 "low-risk" rectal carcinoma and macroscopic (R2) or microscopic (R1) incomplete endoscopic polypectomy were locally resected by TEM. In 12 patients (75 %) no residual tumour was found. In the remaining four cases (25 %), one adenoma with high-grade atypia, two pT1 "low-risk" carcinomas and one tumour infiltration in the mesorectal fat were diagnosed. The patient with the mesorectal infiltration was immediately operated on with radical resection. No further tumour cells were found in this specimen. The median follow-up was 21 months. One patient with a pT1 "low-risk" carcinoma developed a local recurrence and a single hepatic metastasis in the left liver lobe after TEM. Both were completely resected. Currently, all patients are living without evidence of tumour recurrence. Transanal endoscopic microsurgery is a suitable method for the treatment of pT1 "low-risk" rectal carcinomas after incomplete endoscopic polypectomy. In cases of a "high-risk" tumour or deeper tumour infiltration (pT> 1) after TEM radical resection must be carried out.

Theophylline therapy in sleep apnoea syndrome.

There is evidence that theophylline improves obstructive sleep apnoea, although the existing studies are not comparable because of different patient groups, methods and treatment regimes and therefore may give partly conflicting results. In our opinion, patients with mild or moderate sleep apnoea syndrome, who do not need nasal ventilation therapy urgently, or who are not at a high cardiovascular risk, are the favourite group for theophylline therapy and an attempt in oral treatment in this group of patients is recommendable, since all other drugs have failed. Serum theophylline level should be lower than in anti-obstructive therapy, because of its otherwise deleterious effect in sleep structure. The improvement in apnoea index, when responding is not only a short-term effect, but lasts over a long-term treatment period, although patients should still be monitored, because of the possibility of worsening in some cases. The reason for responding and not responding in different patients remains unclear, and further studies are needed to investigate the precise mechanisms of action of theophylline in sleep apnoea, which include central and peripheral effects, to establish predictors for treatment in different groups of sleep apnoea patients.

[Long-term theophylline therapy in sleep apnea--follow-up over a period of 12 months]. / Theophyllinlangzeittherapie bei Schlafapnoe--Verlaufsbeobachtung über einen Zeitraum von 12 Monaten.

Among all the sleep-related respiratory disorders, sleep apnoea is clinically the most important one because of its high incidence and potential cardiovascular sequelae. Treatment depends upon the risk profile of the individual patient; in severe cases or in risk patients nasal continuous superpressure ventilation is employed, whereas in milder cases theophylline has been successfully used alongside general measures. 103 patients were followed up during treatment on an outpatient basis for 2 to maximum 12 months. Initially a significant reduction of the apnoea index by a 50% average was achieved. This therapeutical effect remained largely constant with a slight average deterioration at the end of the observation period, whereas the subjective feeling tone also improved in most patients. The treatment course was prematurely discontinued in 34 patients. Good to very good success was achieved in a total of 43 patients, whereas 26 patients were non-responders either initially or as the treatment proceeded. Even though theophylline treatment is now well-tried in mild forms of sleep apnoea, predictors for its use in certain groups of patients must be determined before treatment is initiated.