Roland Büttner

Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells

Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fibrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells (HSCs), the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media (CM) from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-β, tissue inhibitor of metallo-proteinase-1 (TIMP-1), TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor κB-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.

Comparison between a clinical activity index (Harvey–Bradshaw-Index), laboratory inflammation markers and quantitative assessment of bowel wall vascularization by contrast-enhanced ultrasound in Crohn's disease

PURPOSE Due to its character as a remitting inflammatory disease, patients suffering from Crohns disease (CD) often undergo several imaging studies subjecting the mostly young patients to ionizing. Contrast enhanced ultrasound for capillary microvascular assessment might be a new diagnostic tool for identifying the activity of inflammation by ultrasound techniques. MATERIALS AND METHODS We prospectively evaluated 45 patients with proven Crohns disease performing contrast enhanced ultrasound (CEUS) and laboratory assessment including C-reactive protein (CRP), leucocytes and hematocrit as well as calculating the Harvey-Bradshaw Index (HBI). Thereafter, we applied the quantification software Qontrast(®) to obtain contrast-enhanced sonographic perfusion maps. RESULTS Analysis of the 41 finally included patients revealed a correlation of CRP to HBI and TTP[s], respectively. Moreover, an association was found for HBI and TTP[s] and for HBI and TTP[s]/Peak [%]. Analysis of 34 patients with a Peak [%] ≥ 25 showed a close association of HBI and CRP. Besides, in these patients CRP correlated to TTP[s] and to TTP[s]/Peak [%]. We found a strong negative correlation between HBI and TTP[s] (r = -0.645, p<0.01), thus, the higher the clinical activity the shorter the time-to-peak. CONCLUSION Quantitative evaluation with CEUS, particularly the calculation of TTP[s] in patients with a Peak [%] ≥ 25, provides a simple method to assess the inflammatory activity in CD.

Association of increased C-peptide serum levels and testosterone in type 2 diabetes

Background: The purpose of our study was to investigate the association of C-peptide and steroid hormones in males and females with type 2 diabetes compared to controls. Methods: In 562 subjects, matched for age and body mass index (BMI), 126 female type 2 diabetic patients (known diabetes duration: 7.8+/-0.8 years, HbA(1c): 7.6+/-0.14%), 126 healthy female subjects, 155 male type 2 diabetic patients (known diabetes duration: 6.4+/-0.6 years, HbA(1c): 7.7+/-0.11%), and 155 healthy male controls, C-peptide levels and serum levels of steroid hormones (progesterone, cortisol, DHEAS, estradiol, and testosterone) were measured by immunometric assays. Ratios of steroid hormones were calculated to investigate shifts in steroidogenesis. Results: In female patients, testosterone was significantly higher than in controls (1.7+/-0.1 vs. 1.4+/-0.2 pmol/l; P<0.05), something that was also demonstrated for the ratio of testosterone/estradiol (P<0.05). In male patients, lower levels of testosterone (11.8+/-0.5 vs. 14.3+/-0.5 pmol/l; P<0.05) and higher cortisol levels (257.5+/-9.9 vs. 228.2+/-7.9 µmol/l, P<0.01) were found than in controls. The progesterone/DHEAS ratio (P<0.05) and the progesterone/testosterone ratio (P<0.001) were significantly higher and DHEAS/cortisol significantly lower in type 2 diabetic males than in controls. In a multiple linear regression analysis that controlled for age, BMI, C-peptide, HDL-cholesterol, and HbA(1c), testosterone was significantly and positively correlated with C-peptide levels in female (P<0.05) but not in male type 2 diabetic patients. Conclusions: Testosterone levels were higher in female patients than in controls and correlated with C-peptide levels while testosterone levels were lower in male patients than in controls and showed no correlation with C-peptide. A higher ratio of testosterone/estradiol in type 2 diabetic females and of progesterone/DHEAS and progesterone/testosterone in type 2 diabetic males than in controls may indicate gender-dependent shifts in steroidogenesis. Whether the shifts in steroidogenesis contribute to insulin resistance in diabetic patients should be the subject of further studies.

Smoldering myeloma presenting as progressive multifocal leukoencephalopathy: a case report

IntroductionProgressive multifocal leukoencephalopathy is an opportunistic infection occurring in patients with severe cellular immunodeficiency. This case highlights the role of cellular immunodeficiency in the reactivation of John Cunningham virus in a case of an early stage plasmacytoma.Case presentationA 76-year-old Caucasian woman presented with progressive left-sided hemiparesis, accompanied by hypoesthesia, hypoalgesia and neuropsychological symptoms. Magnetic resonance imaging demonstrated new hyperattenuating lesions in the right thalamus and left-sided subcortically. A polymerase chain reaction test revealed 4500 copies of John Cunningham virus-deoxyribonucleic acid/ml in cerebrospinal fluid. Human immunodeficiency virus infection was ruled out. A bone marrow biopsy showed an early stage immunoglobulin G-kappa plasmacytoma. Cidofovir (5mg/kg) weekly for three weeks was started. A significant improvement of her neuropsychological symptoms was achieved, but motor system and sensory symptoms did not change.ConclusionsThis case shows a rapid course of progressive multifocal leukoencephalopathy with severe residual deficits. In the diagnostic workup of all patients with atypical neurologic symptoms or immunodeficiency, progressive multifocal leukoencephalopathy should be included as a differential diagnosis.

Messung des Knöchel-Arm-Index (ankle brachial index; ABI)

Unter praxisrelevanten Gesichtspunkten fur den Diabetes mellitus mit zusatzlich bestehender peripherer arterieller Verschlusskrankheit wird die Messung des Knochel-Arm-Index, auch genannt ABI (ankle brachial index), dargestellt unter ubersichtlicher Zusammenstellung der exakten Vorgehensweise und der Grenzwerte.

Klassifikation des GdB (Grad der Behinderung) bei Endokrinopathien

Unter Fokussierung auf den Diabetes mellitus werden knapp und ubersichtlich die Kriterien zur Klassifikation des GdB (Grad der Behinderung) zusammengefasst.

Perzentilendokumentation bei Kindern und Jugendlichen

Praxisnah wird die bei Kindern und Jugendlichen erforderliche geschlechter-getrennte Dokumentation von Grose, Gewicht und Wachstumsgeschwindigkeit in Perzentilen darstellt und in Bezug gesetzt zu Erkrankungen wie Wachstumshormonmangel, konstitutionelle Entwicklungsverzogerung (KEV) aber auch zum Knochenalter.

Online engines, Apps und database tools in der Endokrinologie

Erlautert werden kurz und pragnant hilfreiche online-Kalkulatoren, Apps, Dienstprogramme und Datenbank-Server fur die Endokrinologie.

Die ambulante Langzeitblutdruckmessung (ABDM)

Erlautert werden die Methodik, Durchfuhrung und Auswertung der ambulanten Langzeitblutdruckmessung mittels Oberarmmanschette sowie die klinische Bedeutung der Methodik und die grafische Art der Aufbereitung inklusive detaillierter Grenzwerte.

Die Analyse der Pulswellengeschwindigkeit

Erlautert werden die Methodik, Durchfuhrung und Auswertung der Pulswellengeschwindigkeit im Rahmen einer Langzeitblutdruckmessung mittels Oberarmmanschette sowie die klinische Bedeutung der Methodik.