HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124240",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124200",
"results": [
{
"text": "\n156796\nTime to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.\n\nFung, P\n\nBedogni, G\n\nBedogni, A\n\nPetrie, A\n\nPorter, S\n\nCampisi, G\n\nBagan, J\n\nFusco, V\n\nSaia, G\n\nAcham, S\n\nMusto, P\n\nPetrucci, MT\n\nDiz, P\n\nColella, G\n\nMignogna, MD\n\nPentenero, M\n\nArduino, P\n\nLodi, G\n\nMaiorana, C\n\nManfredi, M\n\nHallberg, P\n\nWadelius, M\n\nTakaoka, K\n\nLeung, YY\n\nBonacina, R\n\nSchiødt, M\n\nLakatos, P\n\nTaylor, T\n\nDe Riu, G\n\nFavini, G\n\nRogers, SN\n\nPirmohamed, M\n\nNicoletti, P\n\nGENVABO Consortium\n\nFedele, S\n\nBeiträge in Fachzeitschriften\nISI:000399897700012\n28039941.0\n10.1111/odi.12632\nNone\nOsteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients.\n Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012.\n The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate.\n The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.\n © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nKirnbauer, Barbara\n\n\n"
},
{
"text": "\n161070\nCopeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.\n\nKrane, V\n\nGenser, B\n\nKleber, ME\n\nDrechsler, C\n\nMärz, W\n\nDelgado, G\n\nAllolio, B\n\nWanner, C\n\nFenske, W\n\n4D and LURIC study investigators\n\nBeiträge in Fachzeitschriften\nISI:000401951900013\n28280053.0\n10.1373/clinchem.2016.266254\nNone\nIn chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function.\n Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m(2), 60-89 mL/min/1.73 m(2), <60 mL/min/1.73 m(2), and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study).\n Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m(2)), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m(2)), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m(2)), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m(2). Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function.\n Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.\n © 2017 American Association for Clinical Chemistry.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n3944\nObservations concerning different patterns of bone healing using the Point Contact Fixator (PC-Fix) as a new technique for fracture fixation.\n\nHofer, HP\n\nWildburger, R\n\nSzyszkowitz, R\n\nBeiträge in Fachzeitschriften\nISI:000171873800004\n11718735.0\nNone\nNone\nThe recent trend in all surgical disciplines has been the development of techniques in minimally invasive surgery and the optimal maintenance of the blood supply to the bone fragments during osteosynthesis. Currently, the Point Contact Fixator (PC-Fix) has been introduced as a new implant for the stabilization of forearm bones. This plate-like splint and screw fixation system, which actually acts as an internal fixator, is characterized by minimized isolated contacts to the bone and proven angular stability of the monocortically locked screws. By using the PC-Fix, a further reduction of damage to the blood supply to the bone is achieved. Since 1994, 38 patients have been treated with this new device; we have reviewed the radiographs of 52 consolidated forearm fractures/osteotomies in accordance with the patterns of bone healing associated with the different methods of implant application according to the fracture type. In the groups in which traditionally precise reduction, interfragmentary compression and stable fixation was achieved (N=31), we found in 71% an absence of periosteal callus (direct bone healing). In the groups in which compression and adaptation were combined, or even main fragments adapted without compression, with wedges remaining unreduced in soft tissue connection (N=21), we found a visible external callus in 81% (indirect healing) (P = 0.002). Indirect healing after internal fixation is no longer regarded as a disturbance to healing, but is a goal in itself. The appearance of callus is a welcome sign indicating a prompt and positive reaction in the course of bone union which will lead to progressive fracture immobilization. When using the PC-Fix in a "biological way", callus formation and solid union take place earlier than in conventional plating. The new internal fixator offers substantial technical and mechanical advantages in fracture treatment. Therefore, it is an ideal implant to satisfy the requirements of modern biological osteosynthesis without compromising the restoration of axial alignment, rotation, length and postoperative functional treatment.\n\nHofer, Herwig\n\n\n"
},
{
"text": "\n63996\nFine specificity of anti-Ro(SSA) autoantibodies and clinical manifestations in patients with systemic lupus erythematosus.\n\nZimmermann, C\n\nSmolen, JS\n\nGraninger, W\n\nPetera, P\n\nFabini, G\n\nHassfeld, W\n\nHöfler, E\n\nSteiner, G\n\nBeiträge in Fachzeitschriften\nISI:A1996VR07500015\n8923363.0\nNone\nNone\nOBJECTIVE: To determine the fine specificity of the anti-Ro(SSA) autoimmune response in patients with systemic lupus erythematosus (SLE), and to correlate it with clinical and serological manifestations. METHODS: The frequency of anti-Ro and anti-La autoantibodies was determined by double immunodiffusion (DID), ELISA, and immunoblotting (IB) in 69 patients with SLE and 39 controls. Protein and RNA immunoprecipitation were used to further characterize anti-Ro positive sera. RESULTS: Anti-Ro antibodies were detected in 37 (54%) patients: 33 (48%) were positive by DID, 35 (51%) by ELISA, and 25 (35%) by IB; 32 sera were reactive in at least 2 of these 3 assay systems. By IB, 12 patients had antibodies to both the 60 kDa Ro (Ro60) and the 52 kDa Ro (Ro52), 11 patients were anti-Ro60 positive, 2 patients were anti-Ro52 positive, and 12 patients were not reactive with blotted Ro antigens. However, in immunoprecipitation assays all but one anti-Ro positive sera precipitated both Ro proteins. Anti-La reactivities were found in 15 anti-Ro positive patients: 13 sera were positive by IB, 11 by ELISA, and 9 by DID. Significant associations of anti-Ro antibodies with clinical symptoms were found for sicca syndrome, which was increased in anti-Ro positive patients (p < 0.05 vs anti-Ro negative patients), and for nephritis, for which an inverse correlation was found, since it was less frequently diagnosed in anti-Ro positive patients (p < 0.01). However, this association was seen only for those anti-Ro positive patients who were not reactive with Ro52 by IB. No difference was observed between anti-Ro/La and anti-Ro positive patients. CONCLUSION: DID and ELISA were of comparable sensitivity for detection of anti-Ro, IB was the most sensitive method for detection of anti-La. Moreover, our data indicate that IB may help to characterize clinically distinct subgroups of anti-Ro positive patients with SLE. Thus, determination of anti-Ro by IB may increase the prognostic value of this autoantibody.\n\nGraninger, Winfried\n\n\n"
},
{
"text": "\n66565\nAngiogenic growth factor levels in maternal and fetal blood: correlation with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction.\n\nSchlembach, D\n\nWallner, W\n\nSengenberger, R\n\nStiegler, E\n\nMörtl, M\n\nBeckmann, MW\n\nLang, U\n\nBeiträge in Fachzeitschriften\nISI:000245903400008\n17330322.0\n10.1002/uog.3930\nNone\nObjectives To correlate levels of angiogenic growth factors with Doppler ultrasound parameters in pregnancies complicated by pre-eclampsia and intrauterine growth restriction (IUGR). Methods In 16 women with pre-eclampsia and 15 women with isolated IUGR, pulsatility indices (PI) in the umbilical and uterine arteries were measured by Doppler ultrasonography. At delivery, maternal and fetal blood (umbilical vein and artery separately) was sampled and angiogenic growth factors measured by means of enzyme linked immunosorbent assay (ELISA). Results Umbilical artery PI was significantly higher in women with IUGR than in those with pre-eclampsia, whereas uterine artery PI was not statistically significantly different. Maternal soluble fms-like tyrosine kinase-1 (sFlt-1) levels were higher in women with pre-eclampsia than in those with IUGR (P < 0.0001). Umbilical vein basic fibroblast growth factor (bFGF) levels were lower in women with pre-eclampsia than in those with IUGR (P < 0.05). Placental growth factor (PIGF) levels in the umbilical vein were below the detection limit in nearly all samples of IUGR fetuses and lower than in those with pre-eclampsia (P < 0.001). Maternal PlGF levels were inversely correlated with PI values o f both vessels. In the umbilical vein sFlt-1 was positively and soluble kinase insert domain receptor (sKDR) negatively correlated with umbilical artery PI. No correlation could be found in the serum of the umbilical artery for all growth factors and for vascular endothelial growth factor (VEGF) in all compartments. Conclusions The correlations between maternal and fetal angiogenic growth factor serum levels and Doppler ultrasound indices of uterine and umbilical arteries in pre-eclampsia and IUGR reflect the severity of the disorders especially for the fetus. A combination of both measurements may be useful in future screening for early prediction of pregnancy complications. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.\n\nMörtl, Manfred Georg\n\n\n"
},
{
"text": "\n75068\nThe effect of comorbidities and socioeconomic status on sexual and urinary function in men undergoing prostate cancer screening.\n\nBhojani, N\n\nPerrotte, P\n\nJeldres, C\n\nSuardi, N\n\nHutterer, G\n\nShariat, SF\n\nKarakiewicz, PI\n\nBeiträge in Fachzeitschriften\nISI:000253630700029\n18221289.0\n10.1111/j.1743-6109.2007.00722.x\nNone\nINTRODUCTION: Comorbidities and socioeconomic status (SES) represent known confounders of baseline health-related quality of life. AIM: To assess the effect of comorbidities and of SES variables on urinary function (UF) and sexual function (SF) and on associated bother items. METHODS: A cohort of 1, 62 men without an established diagnosis of prostate cancer (PCa) completed questionnaires addressing SES characteristics, the lifetime prevalence of 12 comorbid conditions, SF and UF as well as their associated bother. MAIN OUTCOME MEASURES: Crude and adjusted logistic regression models tested the association between the predictors, SES and comorbidity, and four separate outcomes, namely SF and UF and their associated bother. RESULTS: Of all men, aged 40-79 years, 172 (14.8%) reported poor or very poor ability to have an erection, and for 165 (14.2%), erectile function (EF) was a big or moderate problem. Daily or weekly urinary incontinence was reported by 98 (8.4%) men, and for 94 (8.1%) men, UF was a big or moderate problem. One or more comorbidities were present in 437 (37.6%) men. In age- and SES-adjusted analyses, major depression and diabetes had the most detrimental effect on EF (5.8 [P < 0.001] and 4.8 [P < 0.001], respectively) and on sexual bother (4.3 [P < 0.001] and 7.2 [P < 0.001], respectively). Stroke (4.7 [P = 0.004]) and drug problems (4.8 [P = 0.002]) had the most detrimental effect on urinary incontinence. Alcoholism and alcohol-related problems (3.1 [P = 0.004]) had the most detrimental effect on the urinary bother scale. Finally, SES only affected urinary incontinence, which was poorer in men who lived with a spouse or partner (2.1 [P = 0.03]). CONCLUSION: Select comorbidities have very strong effects on UF and EF. Conversely, for most SES variables, the effect was weak and insignificant. In consequence, when patients are assessed for definitive PCa therapy, comorbidities require an adjustment, whereas SES assessment may potentially be omitted, especially if questionnaire brevity is a consideration.\n\nHutterer, Georg\n\n\n"
},
{
"text": "\n96732\nPredictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity.\n\nRueff, F\n\nPrzybilla, B\n\nBilo, MB\n\nMuller, U\n\nScheipl, F\n\nAberer, W\n\nBirnbaum, J\n\nBodzenta-Lukaszyk, A\n\nBonifazi, F\n\nBucher, C\n\nCampi, P\n\nDarsow, U\n\nEgger, C\n\nHaeberli, G\n\nHawranek, T\n\nKorner, M\n\nKucharewicz, I\n\nKuchenhoff, H\n\nLang, R\n\nQuercia, O\n\nReider, N\n\nSeverino, M\n\nSticherling, M\n\nSturm, GJ\n\nWuthrich, B\n\nBeiträge in Fachzeitschriften\nISI:000272108000027\n19895993.0\n10.1016/j.jaci.2009.08.027\nNone\nBackground: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. Objective: Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. Methods: In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. Results: Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. Conclusion: In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors. (J Allergy Clin Immunol 2009;124:1047-54.)\n\nAberer, Werner\n\nSturm, Gunter\n\n\n"
},
{
"text": "\n103579\nImpact of IL28B Genotype on the Early and Sustained Virologic Response in Treatment-Naïve Patients With Chronic Hepatitis C.\n\nStättermayer, AF\n\nStauber, R\n\nHofer, H\n\nRutter, K\n\nBeinhardt, S\n\nScherzer, TM\n\nZinober, K\n\nDatz, C\n\nMaieron, A\n\nDulic-Lakovic, E\n\nKessler, HH\n\nSteindl-Munda, P\n\nStrasser, M\n\nKrall, C\n\nFerenci, P\n\nBeiträge in Fachzeitschriften\nISI:000289147400020\n20728570.0\n10.1016/j.cgh.2010.07.019\nNone\nBACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) in the gene that encodes interleukin (IL)-28B predict response of patients with chronic hepatitis C to antiviral therapy. We investigated the roles of polymorphisms rs12979860 and rs8099917 on the early virologic response of treatment-naive patients. METHODS: SNPs were identified by real-time polymerase chain reaction analysis of samples from 682 patients (genotype [GT]1 = 372, GT2/3 = 208, GT4 = 102) who were treated with 180 mu g pegylated interferon-alpha 2a and 400 or 800 mg (GT2/3, depending on the protocol) or 1000-1200 mg (GT1/4) ribavirin/day. The duration of treatment was 24 (GT2/3) or 24-72 weeks (GT1/4). RESULTS: Patients with C/C also had higher rates of rapid virologic response (RVR) (GT1, 38.3% vs 11.6%; GT4, 76.5% vs 23.5%; both P < .001) and sustained virologic responses (SVRs) (GT1, 79.1% vs 43.2%; GT4, 85.3% vs 44.1%; both P < .001). In patients with GT2/3, the RVR was more frequent in carriers of C/C (75.3% vs 52.6%, P < .01), but SVR rates were similar between those with C/C and T (80.5% vs 74.4%, P = .31). Results for rs8099917 were comparable. The positive predictive value of rs12979860 C/C for SVR was higher than that of rs8099917 T/T (80.5% vs 71.6%). Overall, RVR was the best predictor of SVR. In patients who did not have GT1, IL28B polymorphisms did not affect the SVR if RVR data were included in the multivariate analysis. CONCLUSIONS: An early virologic response to pegylated interferon and ribavirin is more likely among carriers of rs12979860 C/C and rs8099917 T/T, which might underlie their high rates of SVR. Determination of the IL28B genotype and whether patients have an RVR might be used in future studies of patients with hepatitis C virus genotype 1 or 4.\n\nKessler, Harald\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n127263\nNeutrophil-to-lymphocyte ratio and its association with critical limb ischemia in PAOD patients.\n\nGary, T\n\nPichler, M\n\nBelaj, K\n\nHafner, F\n\nGerger, A\n\nFroehlich, H\n\nEller, P\n\nPilger, E\n\nBrodmann, M\n\nBeiträge in Fachzeitschriften\nISI:000315603700077\n23457609.0\n10.1371/journal.pone.0056745\nPMC3574103\nBackground: The Neutrophil-to-Lymphocyte ratio (NLR) is an easy to perform test from the white blood cell count. An increase in NLR has been associated with vascular endpoints reflecting inflammation in atherosclerotic lesions. Atherosclerosis is a global threat and vascular endpoints, like myocardial infarction or critical limb ischemia (CLI), are a leading cause of death in industrialized countries. We therefore investigated NLR and its association with CLI and other vascular endpoints in peripheral arterial occlusive disease (PAOD) patients. Methods and Findings: We evaluated 2121 PAOD patients treated at our institution from 2005 to 2010. NLR was calculated and the cohort was divided into tertiles according to the NLR. An optimal cut-off value for the continuous NLR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI. In our cohort occurrence of CLI significantly increased with an increase in NLR. As an optimal cut-off a NLR of 3.95 was identified. Two groups were categorized, one containing 1441 patients (NLR>3.95) and a second group with 680 patients (NLR. 3.95). CLI was more frequent in NLR. 3.95 patients (330(48.5%)) compared to NLR<3.95 patients (350(24.3%)) (p<0.001), as were prior myocardial infarction (48(7.0%) vs. 47(3.3%), p<0.001) and stroke (73(10.7) vs. 98(6.8%), p<0.001). Regarding other inflammatory parameters, C-reactive protein (median 5.6 mg/l (2.3-19.1) vs. median 3 mg/l (1.5-5.5)) and fibrinogen (median 412 mg/dl (345.5-507.5) vs. 344 mg/dl (308-403.5)) also significantly differed in the two patient groups (both p<0.001). A NLR>3.95 was associated with an OR of 2.5 (95% CI 2.3-2.7) for CLI even after adjustment for other vascular risk factors. Conclusions: An increased NLR is significantly associated with patients at high risk for CLI and other vascular endpoints. The NLR is an easy to perform test, which could be used to highlight patients at high risk for vascular endpoints.\n\nBrodmann, Marianne\n\nEller, Philipp\n\nGary, Thomas\n\nGerger, Armin\n\nHafner, Franz\n\nPichler, Martin\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n136246\nEndothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis.\n\nHafner, F\n\nKieninger, A\n\nMeinitzer, A\n\nGary, T\n\nFroehlich, H\n\nHaas, E\n\nHackl, G\n\nEller, P\n\nBrodmann, M\n\nSeinost, G\n\nBeiträge in Fachzeitschriften\nISI:000336863900018\n24740106.0\n10.1371/journal.pone.0093357\nPMC3989175\nEndothelial dysfunction plays a key role in the development, progression, and clinical manifestation of atherosclerosis, and in symptomatic peripheral arterial disease, endothelial dysfunction and enlarged intima-media thickness might be associated with increased cardiovascular risk. Flow-mediated dilatation and serologic parameters are used to evaluate individual endothelial function. Brachial intima-media thickness, a less recognized parameter of cardiovascular risk, is independently associated with coronary artery disease. The aim of this study was to evaluate the prognostic value of ultrasound and serologic parameters of endothelial function in relation to cardiovascular mortality in peripheral arterial disease.\n monocentric, prospective cohort study.\n Flow mediated dilatation and brachial intima-media thickness were assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford stages 2-3). Serologic parameters of endothelial function included asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine. Cardiovascular events were recorded during a follow-up of 99.1±11.1 months. Subjects who died of noncardiovascular causes were excluded from further analysis.\n Eighty-two patients (44.6%) died during follow-up after a mean duration of 49.7±28.3 months. There were 49 cardiovascular deaths (59.8%) and 33 other deaths (40.2%). Flow mediated dilatation was associated with cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001]. Brachial intima-media thickness above 0.345 mm was most predictive of cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657, respectively (p<0.001). Furthermore, ADMA levels above 0.745 µmol/l and SDMA levels above 0.825 µmol/l were significantly associated with cardiovascular death (p<0.001 and 0.030).\n In symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of ADMA and SDMA were associated with increased cardiovascular risk.\n\nBrodmann, Marianne\n\nEller, Philipp\n\nGary, Thomas\n\nHackl, Gerald\n\nHafner, Franz\n\nMeinitzer, Andreas\n\nSeinost, Gerald\n\n\n"
},
{
"text": "\n138329\nTreatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.\n\nGerber, NU\n\nvon Hoff, K\n\nResch, A\n\nOttensmeier, H\n\nKwiecien, R\n\nFaldum, A\n\nMatuschek, C\n\nHornung, D\n\nBremer, M\n\nBenesch, M\n\nPietsch, T\n\nWarmuth-Metz, M\n\nKuehl, J\n\nRutkowski, S\n\nKortmann, RD\n\nBeiträge in Fachzeitschriften\nISI:000338707700021\n24969797.0\n10.1016/j.ijrobp.2014.04.017\nNone\nThe prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.\n After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine).\n Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively).\n Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.\n Copyright © 2014 Elsevier Inc. All rights reserved.\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n148111\nPlasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.\n\nDelgado, GE\n\nSiekmeier, R\n\nKrämer, BK\n\nMärz, W\n\nKleber, ME\n\nBeiträge in Fachzeitschriften\nISI:000361817400009\n25786403.0\n10.1007/5584_2015_127\nNone\nCardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. Parameters of coagulation and fibrinolysis are risk factors of CVD and might be affected by cigarette smoking. Aim of our study was to analyze the effect of cigarette smoking on parameters of fibrinolysis in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the use of these parameters for risk prediction. We determined plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (t-PA), protein C activity, and D-dimers in 3, 16 LURIC patients. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. Cox regression was used to assess the effect of parameters on mortality. We found that of the 3, 16 LURIC patients 777 were AS and 1, 78 NS. Within the observation period of 10 years (median) 221 AS and 302 NS died. In male AS vs. NS, PAI-1 (19.0 (10.0-35.0) vs. 15.0 (9.0-29.0) U/ml; p=0.026) and t-PA antigen (12.7 (9.6-16.3) vs. 11.6 (8.9-14.6) μg/l; p=0.020) were slightly increased, while t-PA activity was slightly decreased (0.63 (0.30-1.05) vs. 0.68 (0.42-1.10) U/l; p=0.005). In female AS vs. NS, t-PA antigen (10.5 (8.3-13.9) vs. 11.5 (8.8-15.0) μg/l; p=0.025) and protein C (108.0±24.1% vs. 118.0±25.7%; p=0.004) were decreased. All parameters except for protein C were predictive for mortality in AS. Fully adjusted hazard ratios (95% CI) were 1.14 (1.04-1.25), 1.19 (1.06-1.34), and 1.29 (1.11-1.49) per 1SD increase for D-dimer, t-PA, and PAI-1, respectively. Including fibrinolysis parameters in risk prediction models for mortality improved the area-under-the-curve (AUC) significantly compared with the conventional risk factors. In conclusion, we found alterations in the fibrinolytic system in smokers, which were more pronounced in male AS. PAI-1, t-PA and D-dimers were significant predictors of mortality in AS in LURIC and should be included into the assessment of cardiovascular risk particularly in patients at risk.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n149363\nTNF-α alters the inflammatory secretion profile of human first trimester placenta.\n\nSiwetz, M\n\nBlaschitz, A\n\nEl-Heliebi, A\n\nHiden, U\n\nDesoye, G\n\nHuppertz, B\n\nGauster, M\n\nBeiträge in Fachzeitschriften\nISI:000372769600005\n26752743.0\n10.1038/labinvest.2015.159\nNone\nImplantation and subsequent placental development depend on a well-orchestrated interaction between fetal and maternal tissues, involving a fine balanced synergistic cross-talk of inflammatory and immune-modulating factors. Tumor necrosis factor (TNF)-α has been increasingly recognized as pivotal factor for successful pregnancy, although high maternal TNF-α levels are associated with a number of adverse pregnancy conditions including gestational hypertension and gestational diabetes mellitus. This study describes effects of exogenously applied TNF-α, mimicking increased maternal TNF-α levels, on the secretion profile of inflammation associated factors in human first trimester villous placenta. Conditioned culture media from first trimester villous placental explants were analyzed by inflammation antibody arrays and ELISA after 48 h culture in the presence or absence of TNF-α. Inflammation antibody arrays identified interleukin (IL)-6, IL-8, chemokine (C-C motif) ligand 2 (CCL2), CCL4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as the most abundantly secreted inflammation-associated factors under basal culture conditions. In the presence of TNF-α, secretion of GM-CSF, CCL5, and IL-10 increased, whereas IL-4 and macrophage CSF levels decreased compared with controls. ELISA analysis verified antibody arrays by showing significantly increased synthesis and release of GM-CSF and CCL5 by placental explants in response to TNF-α. Immunohistochemistry localized GM-CSF in the villous trophoblast compartment, whereas CCL5 was detected in maternal platelets adhering to perivillous fibrin deposits on the villous surface. mRNA-based in situ padlock probe approach localized GM-CSF and CCL5 transcripts in the villous trophoblast layer and the villous stroma. Results from this study suggest that the inflammatory secretion profile of human first trimester placenta shifts towards increased levels of GM-CSF, CCL5, and IL10 in response to elevated maternal TNF-α levels, whereas IL-6 and IL-8 remain unaffected. This shift may represent a protective mechanism by human first trimester villous placenta to sustain trophoblast function and dampen inflammatory processes in the intervillous space.\n\nDesoye, Gernot\n\nEl-Heliebi, Amin\n\nGauster, Martin\n\nHiden, Ursula\n\nHuppertz, Berthold\n\nSiwetz, Monika\n\n\n"
},
{
"text": "\n153968\nSystemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure.\n\nClària, J\n\nStauber, RE\n\nCoenraad, MJ\n\nMoreau, R\n\nJalan, R\n\nPavesi, M\n\nAmorós, À\n\nTitos, E\n\nAlcaraz-Quiles, J\n\nOettl, K\n\nMorales-Ruiz, M\n\nAngeli, P\n\nDomenicali, M\n\nAlessandria, C\n\nGerbes, A\n\nWendon, J\n\nNevens, F\n\nTrebicka, J\n\nLaleman, W\n\nSaliba, F\n\nWelzel, TM\n\nAlbillos, A\n\nGustot, T\n\nBenten, D\n\nDurand, F\n\nGinès, P\n\nBernardi, M\n\nArroyo, V\n\nCANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF)\n\nBeiträge in Fachzeitschriften\nISI:000384552300022\n27483394.0\n10.1002/hep.28740\nNone\nAcute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short-term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short-term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD.\n These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).\n © 2016 by the American Association for the Study of Liver Diseases.\n\nÖttl, Karl\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n161623\nAllergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews.\n\nNurmatov, U\n\nDhami, S\n\nArasi, S\n\nRoberts, G\n\nPfaar, O\n\nMuraro, A\n\nAnsotegui, IJ\n\nCalderon, M\n\nCingi, C\n\nDurham, S\n\nvan Wijk, RG\n\nHalken, S\n\nHamelmann, E\n\nHellings, P\n\nJacobsen, L\n\nKnol, E\n\nLarenas-Linnemann, D\n\nLin, SY\n\nMaggina, V\n\nOude-Elberink, H\n\nPajno, G\n\nPanwankar, R\n\nPastorello, E\n\nPitsios, C\n\nRotiroti, G\n\nTimmermans, F\n\nTsilochristou, O\n\nVarga, EM\n\nWilkinson, J\n\nWilliams, A\n\nWorm, M\n\nZhang, L\n\nSheikh, A\n\nBeiträge in Fachzeitschriften\nISI:000407018600001\n28794855.0\n10.1186/s13601-017-0159-6\nPMC5547534\nThe European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC.\n We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized.\n Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT.\n We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews.\n\nVarga, Eva-Maria\n\n\n"
},
{
"text": "\n164862\nAn open, multicentre, randomized clinical study in patients with bullous pemphigoid comparing methylprednisolone and azathioprine with methylprednisolone and dapsone.\n\nSticherling, M\n\nFranke, A\n\nAberer, E\n\nGläser, R\n\nHertl, M\n\nPfeiffer, C\n\nRzany, B\n\nSchneider, S\n\nShimanovich, I\n\nWerfel, T\n\nWilczek, A\n\nZillikens, D\n\nSchmidt, E\n\nBeiträge in Fachzeitschriften\nISI:000416537700214\n28494097.0\n10.1111/bjd.15649\nNone\nCurrent treatment of bullous pemphigoid (BP) is based on the long-term use of topical and/or systemic corticosteroids, which are associated with a high rate of adverse events and increased mortality.\n To study the corticosteroid-sparing potential of azathioprine and dapsone.\n This was a prospective, multicentre, randomized, nonblinded clinical trial that compared the efficacy and safety of two parallel groups of patients with BP treated with oral methylprednisolone 0·5 mg kg-1 per day in combination with either azathioprine 1·5-2·5 mg kg-1 per day or dapsone 1·5 mg kg-1 per day. Nine German and Austrian departments of dermatology included 54 patients based on clinical lesions, positive direct immunofluorescence (IF) microscopy and detection of serum autoantibodies by indirect IF microscopy, immunoblotting or enzyme-linked immunosorbent assay. The primary end point was the time until complete tapering of methylprednisolone, and the most important secondary end point was the cumulative corticosteroid dose.\n In eight patients (five azathioprine, three dapsone), methylprednisolone could be discontinued after a median time of 251 days in the azathioprine group and 81 days in the dapsone group. The median cumulative corticosteroid dose was 2·65 g for azathioprine compared with 1·92 g for dapsone (P = 0·06). The median numbers of days when corticosteroids were applied were 148 and 51, respectively (P = 0·24). No significant difference in the number of adverse events was seen between the treatment arms. Four patients (8%) died within the observation period of 12 months.\n Due to the lower than intended number of patients, the results of the primary and secondary end points were not or only barely significant. Dapsone appeared to have a moderately higher corticosteroid-sparing potential than azathioprine. The combination regimen of either drug with oral methylprednisolone is associated with a relatively low 1-year mortality in this vulnerable patient population.\n © 2017 British Association of Dermatologists.\n\n\n"
},
{
"text": "\n166296\nThe co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes.\n\nHaluzík, M\n\nFulcher, G\n\nPieber, TR\n\nBardtrum, L\n\nTutkunkardas, D\n\nRodbard, HW\n\nBeiträge in Fachzeitschriften\nISI:000435082500004\n29451706.0\n10.1111/dom.13261\nPMC6033009\nTo investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes.\n This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories.\n We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups.\n IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics.\n © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n167024\nMyristic acid induces proteomic and secretomic changes associated with steatosis, cytoskeleton remodeling, endoplasmic reticulum stress, protein turnover and exosome release in HepG2 cells.\n\nSpeziali, G\n\nLiesinger, L\n\nGindlhuber, J\n\nLeopold, C\n\nPucher, B\n\nBrandi, J\n\nCastagna, A\n\nTomin, T\n\nKrenn, P\n\nThallinger, GG\n\nOlivieri, O\n\nMartinelli, N\n\nKratky, D\n\nSchittmayer, M\n\nBirner-Gruenberger, R\n\nCecconi, D\n\nBeiträge in Fachzeitschriften\nISI:000434750900011\n29654920.0\n10.1016/j.jprot.2018.04.008\nNone\nMyristic acid, the 14-carbon saturated fatty acid (C14:0), is associated to an increased cardiovascular disease risk. Since it is found in low concentration in cells, its specific properties have not been fully analyzed. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. The human liver HepG2 cell line was used to investigate the hepatic response to C14:0 in a combined proteomic and secretomic approach. A total of 47 intracellular and 32 secreted proteins were deregulated after treatments with different concentrations of C14:0. Data are available via ProteomeXchange (PXD007902). In addition, C14:0 treatment of primary murine hepatocytes confirmed that C14:0 induces lipid droplet accumulation and elevates perilipin-2 levels. Functional enrichment analysis revealed that C14:0 modulates lipid droplet formation and cytoskeleton organization, induce ER stress, changes in exosome and extracellular miRNA sorting in HepG2cells. Our data provide for the first time a proteomic profiling of the effects of C14:0 in human hepatoma cells and contribute to the elucidation of molecular mechanisms through which this fatty acid may cause adverse health effects.\n Myristic acid is correlated with an increase in plasma cholesterol and mortality due to cardiovascular diseases. This study is the first example of an integration of proteomic and secretomic analysis of HepG2 cells to investigate the specific properties and functional roles of myristic acid on hepatic cells. Our analyses will lead to a better understanding of the myristic acid induced effects and can elicit new diagnostic and treatment strategies based on altered proteins.\n Copyright © 2018. Published by Elsevier B.V.\n\nBirner-Grünberger, Ruth\n\nGindlhuber, Jürgen\n\nKratky, Dagmar\n\nLiesinger, Laura\n\nSchittmayer-Schantl, Matthias\n\nTomin, Tamara\n\n\n"
},
{
"text": "\n167826\nAnatomy of the Le Fort I segment: Are arterial variations a potential risk factor for avascular bone necrosis in Le Fort I osteotomies?\n\nBruneder, S\n\nWallner, J\n\nWeiglein, A\n\nKmečová, Ĺ\n\nEgger, J\n\nPilsl, U\n\nZemann, W\n\nBeiträge in Fachzeitschriften\nISI:000439559600019\n29805066.0\n10.1016/j.jcms.2018.04.023\nNone\nOsteotomies of the Le Fort I segment are routine operations with low complication rates. Ischemic complications are rare, but can have severe consequences that may lead to avascular bone necrosis of the Le Fort I segment. Therefore the aim of this study was to investigate the blood supply and special arterial variants of the Le Fort I segment responsible for arterial hypoperfusion or ischemic avascular necrosis after surgery.\n The arterial anatomy of the Le Fort I segment's blood supply using 30 halved human cadaver head specimens was analyzed after complete dissection until the submicroscopic level. In all specimens the arterial variants of the Le Fort I segment and also the arterial diameters measured at two points were evaluated.\n The typical known vascularization pattern was apparent in 90% of all specimens, in which the ascending palatine (D1: 1, mm ± 0, 4 mm; D2: 0, mm ± 0, 4 mm) and ascending pharyngeal artery (D1: 1, mm ± 0, 8 mm; D2: <0, mm) were both supplying the Le Fort I segment. However in 10% of all specimens, the Le Fort I segment was dependent on the ascending pharyngeal artery alone and the missing ascending palatine artery was replaced with the anterior branch of the ascending pharyngeal artery (D1: 1, mm ± 0, 2; D2: 1, mm ± 0, mm).\n This study is the first description of a special type of arterial variation of the Le Fort I segment. The type of this arterial variation, its clinical relevance and potential consequences are explained. Individuals with this special arterial anatomy may clinically be at a high risk for hypoperfusion and avascular segment necrosis after surgery. An individualized operation plan may prevent ischemic complications in at-risk patients.\n Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.\n\nBruneder, Simon\n\nEgger, Jan\n\nPilsl, Ulrike\n\nWallner, Jürgen\n\nZemann, Wolfgang\n\n\n"
},
{
"text": "\n171976\nBile acids increase steroidogenesis in cholemic mice and induce cortisol secretion in adrenocortical H295R cells via S1PR2, ERK and SF-1.\n\nLiu, L\n\nPanzitt, K\n\nRacedo, S\n\nWagner, M\n\nPlatzer, W\n\nZaufel, A\n\nTheiler-Schwetz, V\n\nObermayer-Pietsch, B\n\nMüller, H\n\nHöfler, G\n\nHeinemann, A\n\nZollner, G\n\nFickert, P\n\nBeiträge in Fachzeitschriften\nISI:000493736000014\n30664326.0\n10.1111/liv.14052\nPMC6899711\nBile acids are now accepted as central signalling molecules for the regulation of glucose, amino acid and lipid metabolism. Adrenal gland cortex cells express the bile acid receptors farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5) and the sphingosine-1-phosphate receptor 2 (S1PR2). We aimed to determine the effects of cholestasis and more specifically of bile acids on cortisol production.\n FXR and TGR5 knockout mice and controls were subjected to common bile duct ligation (CBDL) or chenodeoxycholic acid (CDCA) feeding to model cholestasis. Human adrenocortical H295R cells were challenged with bile acids for mechanistic studies.\n We found that CBDL and CDCA feeding increased the levels of corticosterone, the rodent equivalent to human cortisol and mRNA and protein levels of steroidogenesis-related enzymes in adrenals independent of FXR and TGR5. Taurine-conjugated CDCA (TCDCA) significantly stimulated cortisol secretion, phosphorylation of extracellular signal-regulated kinase (ERK) and expression of steroidogenesis-related genes in human adrenocortical H295R cells. FXR and TGR5 agonists failed to induce cortisol secretion in H295R cells. S1PR2 inhibition significantly abolished TCDCA-induced cortisol secretion, lowered phosphorylation of ERK and abrogated enhanced transcription of steroidogenesis-related genes in H295R cells. Likewise, siRNA S1PR2 treatment reduced the phosphorylation of ERK and cortisol secretion. Steroidogenic factor-1 (SF-1) transactivation activity was increased upon TCDCA treatment suggesting that bile acid signalling is linked to SF-1. Treatment with SF-1 inverse agonist AC45594 also reduced TCDCA-induced steroidogenesis.\n Our findings indicate that supraphysiological bile acid levels as observed in cholestasis stimulate steroidogenesis via an S1PR2-ERK-SF-1 signalling pathway.\n © 2019 The Authors. Liver International published by John Wiley & Sons Ltd.\n\nFickert, Peter\n\nHeinemann, Akos\n\nHöfler, Gerald\n\nMüller, Helmut\n\nObermayer-Pietsch, Barbara\n\nPanzitt, Katrin\n\nPlatzer, Wolfgang\n\nRacedo, Silvia Maria\n\nTheiler-Schwetz, Verena\n\nWagner, Martin\n\nZaufel, Alex\n\nZollner, Gernot\n\n\n"
}
]
}