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1.
Phys Rev E ; 104(4-2): 045210, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34781535

ABSTRACT

Numerous experiments on laser-driven proton acceleration in the MeV range have been performed with a large variety of laser parameters since its discovery around the year 2000. Both experiments and simulations have revealed that protons are accelerated up to a maximum cut-off energy during this process. Several attempts have been made to find a universal model for laser proton acceleration in the target normal sheath acceleration regime. While these models can qualitatively explain most experimental findings, they can hardly be used as predictive models, for example, for the energy cut-off of accelerated protons, as many of the underlying parameters are often unknown. Here we analyze experiments on laser proton acceleration in which scans of laser and target parameters were performed. We derive empirical scaling laws from these parameter scans and combine them in a scaling law for the proton energy cut-off that incorporates the laser pulse energy, the laser pulse duration, the focal spot radius, and the target thickness. Using these scaling laws, we give examples for predicting the proton energy cut-off and conversion efficiency for state-of-the-art laser systems.

2.
Rev Sci Instrum ; 92(9): 093302, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34598491

ABSTRACT

Laser-based particle accelerators have been an active field of research for over two decades moving from laser systems capable of one shot every hour to systems able to deliver repetition rates in the Hz regime. Based on the advancements in laser technology, the corresponding detection methods need to develop from single to multiple use with high readout speed. Here, we present an online compact tracker of particles using scintillators with nine resolvable energy levels and a spatial resolution of 3.6 × 3.6 mm2 over the whole active area. This paper describes the design and construction of the detector, which is based on pixellated scintillators embedded inside an absorber matrix. The scintillator pixels are fiberoptically coupled to a camera system for online readout and analysis. Calibration with a radioactive source and first experimental data measuring laser accelerated ions at the PHELIX laser at GSI, Darmstadt, Germany, are presented and discussed.

4.
Cell Rep ; 36(3): 109409, 2021 07 20.
Article in English | MEDLINE | ID: mdl-34289357

ABSTRACT

Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.


Subject(s)
Astrocytes/cytology , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cellular Reprogramming , Nerve Tissue Proteins/metabolism , Neurons/cytology , Spinal Cord/cytology , Animals , Astrocytes/metabolism , Biomarkers/metabolism , Electrophysiological Phenomena , Mice, Inbred C57BL , Neurons/metabolism , Organ Specificity , Transcription, Genetic
5.
J Intern Med ; 290(4): 910-921, 2021 10.
Article in English | MEDLINE | ID: mdl-33998741

ABSTRACT

BACKGROUND: Patients with end-stage kidney disease have an extremely high cardiovascular mortality rate, but there is a paradoxical relationship between lipid profile and survival in haemodialysis patients. To investigate whether inflammation/malnutrition confounds the associations between lipids and mortality, we studied a full lipid profile comprising of five clinically well-established lipid parameters and its associations with mortality in a large, multinational European cohort with a median follow-up >3 years. METHODS: The association between quartiles of total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, as well as triglyceride, levels and the end-points of all-cause, cardiovascular and non-cardiovascular mortality was assessed in a cohort of 5,382 incident, adult haemodialysis patients from >250 Fresenius Medical Care dialysis centres out of 14 participating countries using baseline and time-dependent Cox models. Analyses were fully adjusted and stratified for inflammation/malnutrition status and other patient-level variables. RESULTS: Time-dependent quartiles of total, HDL, non-HDL and LDL cholesterol were inversely associated with the hazard for all-cause, cardiovascular and non-cardiovascular mortality. Compared with the lowest quartile of the respective lipid parameter, hazard ratios of other quartiles were <0.86. Similar, albeit weaker, associations were found with baseline lipid profile and mortality. Neither time-dependent nor baseline associations between lipid profile and mortality were affected by inflammation/malnutrition, statin use or geography. CONCLUSIONS: Baseline and time-dependent lipid profile are inversely associated with mortality in a large, multicentre cohort of incident haemodialysis patients. Inflammation/malnutrition is not a confounder nor effect modificator of the associations between lipid profile and mortality in European haemodialysis patients.


Subject(s)
Cardiovascular Diseases , Lipids/blood , Renal Dialysis , Cardiovascular Diseases/mortality , Cholesterol, HDL , Cholesterol, LDL , Humans , Inflammation , Malnutrition , Risk Factors
6.
Phys Rev E ; 104(6-2): 065207, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35030937

ABSTRACT

We present the usage of two-layer targets with laser-illuminated front-side microstructures for x-ray backlighter applications. The targets consisted of a silicon front layer and copper back side layer. The structured layer was irradiated by the 500-fs PHELIX laser with an intensity above 10^{20}Wcm^{-2}. The total emission and one-dimensional extent of the copper Kα x-ray emission as well as a wide spectral range between 7.9 and 9.0 keV were recorded with an array of crystal spectrometers. The measurements show that the front-side modifications of the silicon in the form of conical microstructures maintain the same peak brightness of the Kα emission as flat copper foils while suppressing the thermal emission background significantly. The observed Kα source sizes can be influenced by tilting the conical microstructures with respect to the laser axis. Overall, the recorded copper Kα photon yields were in the range of 10^{11}sr^{-1}, demonstrating the suitability of these targets for probing applications without subjecting the probed material to additional heating from thermal line emission.

7.
Urologe A ; 59(9): 1082-1091, 2020 Sep.
Article in German | MEDLINE | ID: mdl-32274545

ABSTRACT

BACKGROUND: Due to the high incidence and demographic development, there is an urgent need for healthcare research data on lower urinary tract symptoms due to benign prostatic hyperplasia (LTUS/BPH). Since 2005 the Governing Body of German Prostate Centers (DVPZ) has been collecting data from 22 prostate centers in order to determine the quality and type of cross-sectoral care in particular for LUTS/BPH patients. OBJECTIVES: Presentation of the DVPZ database in general, as well as an investigation of treatment patterns for medical and instrumental therapies. MATERIALS AND METHODS: The analysis is based on UroCloud data sets from 30 November 2017. In the UroCloud data on diagnostics, therapy and course of disease are recorded in a web-based manner. RESULTS: A total of 29,555 therapies were documented for 18,299 patients (1.6/patient), divided into 48.5% instrumental, 29.2% medical treatment, and 18.0% "wait and see" (in 4.3% no assignment was possible). Patients treated with an instrumental therapy were oldest (median: 72 years, interquartile range: 66-77), had the largest prostate volumes (50 ml, 35-75 ml), and were mostly bothered by symptoms (International Prostate Symptom Score = 19/4). The majority of patients under medical treatment received alphablockers (56%); phytotherapeutics were used least frequently (3%). Instrumental therapies are dominated by transurethral resection (TUR) of the prostate (60.0%), open prostatectomy (9.4%) and laser therapy (5.0%), with laser therapy having the shortest hospital stay (5 days) and the lowest transfusion and re-intervention rates (1.0% and 4.6%, respectively). CONCLUSIONS: The DVPZ certificate covers the complete spectrum of cross-sectoral care for LUTS/BPH patients and documents the use of the various therapies as well as their application and effectiveness in the daily routine setting.


Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Laser Therapy , Lower Urinary Tract Symptoms/therapy , Prostatic Hyperplasia/complications , Transurethral Resection of Prostate , Aged , Combined Modality Therapy , Germany , Humans , Incidence , Lower Urinary Tract Symptoms/etiology , Male , Prostatectomy , Prostatic Hyperplasia/therapy , Treatment Outcome
8.
J Econ Entomol ; 112(2): 644-652, 2019 03 21.
Article in English | MEDLINE | ID: mdl-30602019

ABSTRACT

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae) is the vector of Candidatus Liberibacter asiaticus (CLas), the presumed cause of Huanglongbing (HLB) in citrus. Management strategies were developed in Florida that used soil-applied neonicotinoids to protect young trees. Despite the implementation of intense management programs, infection spread among the most intensively managed groves. We used electopenetrography to test five imidacloprid doses (0.55, 5.5, 55, 550, and 5,500 ppm) administered in artificial diet to approximate the dosage required to reduce feeding activity and prevent salivation/ingestion activity. We failed to detect a significant effect of 0.55 ppm imidacloprid on probing behavior, pathway, or salivation/ingestion activity when compared with the untreated control. We observed a significant reduction in the number of probes and the number of pathway with both 5.5 and 55 ppm imidacloprid. We detected a significant reduction in the number of salivation/ingestion events at both 5.5 ppm and 55 ppm imidacloprid (57 and 54 percent, respectively) compared with the untreated control, and a reduction in number of sustained (>600 s) salivation/ingestion at 55 ppm. While reductions in feeding activity were apparent at dosages of at least 5.5 ppm, we were unable to prevent salivation/ingestion with dosages as high as 5,500 ppm, which is greater than what is known to occur following application in the field. While soil-applied imidacloprid may slow the spread of CLas, our findings suggest that prevention of CLas inoculation in the field is unlikely. Management strategies must be refined to prevent the spread of HLB in Florida.


Subject(s)
Citrus , Hemiptera , Animals , Diet , Feeding Behavior , Florida , Neonicotinoids , Nitro Compounds
9.
Nutr Metab Cardiovasc Dis ; 29(1): 23-29, 2019 01.
Article in English | MEDLINE | ID: mdl-30527352

ABSTRACT

BACKGROUND AND AIMS: Pro-Neurotensin (NT), a stable surrogate parameter of NT, has recently been introduced as a peptide predicting the development of obesity, diabetes mellitus, cardiovascular diseases, and cardiovascular mortality. However, regulation of Pro-NT in gestational diabetes mellitus (GDM) remains uninvestigated. METHODS AND RESULTS: Pro-NT was quantified in 74 women with GDM, 74 healthy, gestational age-matched, pregnant controls, as well as in a second cohort comprising of 74 healthy, non-pregnant control women, using a chemiluminometric sandwich immunoassay. Pro-NT was correlated to measures of obesity, hypertension, glucose and lipid metabolism, renal function, and inflammation. Mean ± standard deviation of circulating Pro-NT levels were not significantly different in women with GDM (100.2 ± 75.7 pmol/l) as compared to healthy, pregnant controls (103.2 ± 37.4 pmol/l) and healthy, non-pregnant female controls (105.9 ± 38.9 pmol/l) (p = 0.661). Homeostasis model assessment of insulin resistance (HOMA-IR) and creatinine positively correlated with serum Pro-NT in multivariate regression analysis. In contrast, free fatty acids (FFA) were inversely correlated with circulating Pro-NT. Results sustained adjustment for pregnancy status. CONCLUSIONS: Circulating Pro-NT is not independently associated with GDM, but is with HOMA-IR, creatinine, and FFA even after adjustment for pregnancy status.


Subject(s)
Diabetes, Gestational/blood , Neurotensin/blood , Protein Precursors/blood , Biomarkers/blood , Blood Glucose/analysis , Case-Control Studies , Creatinine/blood , Cross-Sectional Studies , Diabetes, Gestational/diagnosis , Fatty Acids, Nonesterified/blood , Female , Humans , Insulin/blood , Insulin Resistance , Pregnancy
10.
Diabetes Metab ; 44(2): 150-154, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28709749

ABSTRACT

AIMS: Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated. METHODS: Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls. Also, neuregulin 4 was quantified during pregnancy and compared with postpartum levels in a follow-up study of 25 women with previous GDM and 25 healthy control women. RESULTS: Women with GDM had lower median serum levels of the novel BAT-secreted adipokine neuregulin 4 (3.0µg/L) compared with healthy (non-GDM) pregnant controls (3.5µg/L; P=0.020), and the area under the glucose curve (AUCGlucose) was an independent and negative predictor of circulating neuregulin 4 (P=0.033). Also, median postpartum serum concentrations of neuregulin 4 (3.2µg/L) were not significantly different from prepartum levels (2.8µg/L; P=0.328). In addition, neuregulin 4 was positively and independently associated with irisin (P=0.009), but not other BAT-secreted adipokines. CONCLUSION/INTERPRETATION: Women with GDM have significantly lower circulating neuregulin 4 levels compared with healthy pregnant controls, and the AUCGlucose is negatively and independently associated with neuregulin 4 during pregnancy. Neuregulin 4 is positively correlated with irisin during pregnancy, as well as in a longitudinal fashion. Future studies are now needed to better elucidate the precise pathomechanisms of the regulation of BAT-secreted adipokines during pregnancy.


Subject(s)
Diabetes, Gestational/blood , Diabetes, Gestational/epidemiology , Neuregulins/blood , Adipose Tissue, Brown/metabolism , Adult , Case-Control Studies , Female , Follow-Up Studies , Humans , Insulin Resistance , Pregnancy , Young Adult
11.
Environ Entomol ; 46(5): 1090-1097, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28961753

ABSTRACT

In the Asian citrus psyllid (Diaphorina citri Kuwayama), learning facilitates host recognition and mate preference; however, it is unclear whether induced female oviposition preference occurs in this species. We investigated the influence of natal host experience on adult oviposition preference when reared on either 'Valencia' orange (Citrus x sinesis) or orange jasmine (Murraya paniculata). Psyllids reared on 'Valencia' orange preferred 'Valencia' orange as an oviposition host compared with orange jasmine, whereas there was no difference in oviposition between the two hosts in orange jasmine reared psyllids. Nymphs transferred from 'Valencia' orange to orange jasmine were smaller in adult size and required more time for development. These findings were reversed in orange jasmine reared psyllids, which increased in size and displayed shorter development times when transferred from orange jasmine to 'Valencia' orange. However, mortality increased in nymphs transferred to the non-natal host species in both treatment groups compared with nymphs transferred to the same host. These results indicate an association between host plant preference and performance in this species. Maternal host experience appeared to influence the oviposition preference in this species. Juvenile psyllid performance appeared negatively affected by orange jasmine plants such that fitness was reduced, suggesting benefits for maternal host fidelity in those insects not acclimated to feeding on orange jasmine. Induced oviposition preference may provide an important mechanism of adaptive plasticity in D. citri reproductive strategies, allowing females to discriminate among potential host species in favor of those to which her offspring are best adapted.


Subject(s)
Genetic Fitness , Hemiptera/physiology , Herbivory , Insect Vectors/physiology , Animals , Body Size , Female , Host Specificity , Male , Nymph/growth & development , Oviposition , Species Specificity
13.
Exp Clin Endocrinol Diabetes ; 124(4): 257-60, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26824282

ABSTRACT

OBJECTIVE: Copeptin, the c-terminal part of pro-Arginine vasopressin, has recently been introduced as a novel risk factor to develop facets of the metabolic syndrome. However, regulation of copeptin in pregnancy-associated metabolic disease, i. e., gestational diabetes mellitus (GDM), has not been fully understood, so far. PATIENTS AND MEASUREMENTS: For this study, 74 GDM patients and 74 healthy, pregnant, age-, body mass index-, and gestational age-matched controls were recruited. Serum levels of copeptin were quantified by an illuminometric assay. Furthermore, copeptin concentrations were correlated to biochemical and anthropometric markers of obesity, glucose and lipid metabolism, renal function, and inflammation. RESULTS: Median [interquartile range] serum copeptin levels were significantly lower in subjects with GDM (3.5 [2.0] pmol/l) as compared to controls (4.4 [3.2] pmol/l) (p<0.05). Furthermore, GDM remained an independent predictor of circulating copeptin in multivariate regression analysis (p<0.05). Moreover, copeptin was independently associated with gestational age at blood sampling (p<0.05). CONCLUSIONS: Copeptin serum levels are significantly lower in GDM as compared to healthy pregnant controls. Further studies are needed to better clarify the pathophysiological role of copeptin in GDM.


Subject(s)
Diabetes, Gestational/blood , Glycopeptides/blood , Adult , Female , Humans , Pregnancy
14.
Int J Obes (Lond) ; 40(2): 260-5, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26285604

ABSTRACT

BACKGROUND/OBJECTIVES: Irisin has been suggested as a novel myokine with beneficial effects in rodents. However, previous data in humans showed conflicting results regarding its association with metabolic phenotypes and regulation of secretion. Furthermore, although an association of rs726344 in FNDC5 (fibronectin type III domain containing 5) coding for irisin with insulin sensitivity was reported, the effects of genetic variation at this locus on irisin serum levels have not been investigated, so far. Therefore, we investigated circulating irisin and the associations with rs726344 in a cohort of >1000 subjects. SUBJECTS/METHODS: Irisin serum concentrations were measured with enzyme-linked immunosorbent assay. Associations with metabolic parameters including renal function, glucose and lipid metabolism, inflammation, as well as adipokine profiles, were assessed in regression models. Dynamic changes of serum irisin were investigated during oral glucose tolerance test (OGTT) in a subset of the cohort (n=136). rs726344 was genotyped in all subjects and analyzed for associations with serum irisin and traits of the metabolic syndrome. RESULTS: Irisin was negatively associated with fat mass, fasting glucose and dyslipidemia but not with other adipokines. Moreover, irisin decreased during an OGTT in a subcohort comprising subjects with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. rs726344 was not associated with serum irisin levels or with other anthropometric and biochemical parameters. CONCLUSIONS: Circulating irisin levels are associated with a beneficial metabolic profile but not with other adipokines and not with rs726344 in our cohort. Our data suggest a potential favorable role of irisin in the regulation of metabolism.


Subject(s)
Blood Glucose/metabolism , Fibronectins/blood , Genetic Predisposition to Disease/epidemiology , Insulin Resistance/genetics , Metabolic Syndrome/blood , Adult , Body Fat Distribution , Enzyme-Linked Immunosorbent Assay , Female , Fibronectins/genetics , Gene Expression Regulation/genetics , Gene Frequency , Germany/epidemiology , Humans , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Middle Aged , Reproducibility of Results
15.
Med Teach ; 38(4): 378-84, 2016.
Article in English | MEDLINE | ID: mdl-26052882

ABSTRACT

BACKGROUND: An increasing demand for proof of professionalism in higher education strives for quality assurance (QA) and improvement in medical education. A wide range of teacher trainings is available to medical staff in Germany. Cross-institutional approval of individual certificates is usually a difficult and time consuming task for institutions. In case of non-acceptance it may hinder medical teachers in their professional mobility. AIM: The faculties of medicine aimed to develop a comprehensive national framework, to promote standards for formal faculty development programmes across institutions and to foster professionalization of medical teaching. METHODS AND RESULTS: Addressing the above challenges in a joint approach, the faculties set up the national MedicalTeacherNetwork (MDN). Great importance is attributed to work out nationally concerted standards for faculty development and an agreed-upon quality control process across Germany. Medical teachers benefit from these advantages due to portability of faculty development credentials from one faculty of medicine to another within the MDN system. CONCLUSION: The report outlines the process of setting up the MDN and the national faculty development programme in Germany. Success factors, strengths and limitations are discussed from an institutional, individual and general perspective. Faculties engaged in similar developments might be encouraged to transfer the MDN concept to their countries.


Subject(s)
Faculty, Medical/education , Inservice Training/standards , Program Development/methods , Germany , Inservice Training/organization & administration , Professionalism/standards
16.
Urologe A ; 54(11): 1546, 1548-54, 2015 Nov.
Article in German | MEDLINE | ID: mdl-26518302

ABSTRACT

BACKGROUND: In prostate centers of the Governing Body of German Prostate Centers (DVPZ, Dachverband der Prostatazentren Deutschlands e.V.) treatment data from 3 university clinics, 21 treatment clinics, 3 private clinics and 330 general practitioners incorporated under 22 certificates are collated, in order to document the quality and type of cross-sectoral and interdisciplinary treatment, in particular of prostate cancer (PCA) patients. METHODS: This analysis is based on the DVPZ UroCloud data sets from 20 July 2015. The UroCloud reflects the web-based chronological disease development and quality parameters. For the descriptive analysis of particular key figures, available complete data sets were selected. RESULTS: Of the centers 22 held a valid certificate and fulfilled all required case numbers and structural prerequisites at the primary certification or recertification. In three cases a reauditing led to requirements before certification. Since 2005 a total of 9650 PCA patients have been pseudonymized and followed up (41,247 follow-up forms, 4.3 forms per patient). In 2014 the median number of newly documented PCA patients was 61 per center (minimum 7 and maximum 295). Radical prostatectomy (RP) dominated with 4491 (56 %) cases followed by primary hormonal therapy (1210 cases, 15 %), irradiation (809, 10 %) and non-interventional therapy, such as active surveillance (AS) or watchful waiting (WW) in 760 cases (10 %). A prostate-specific antigen (PSA) reduction was documented in 50 % of the patients with a preoperative PSA value > 20, in 60 % of pT4 tumors and in 50 % of patients with a tumor Gleason score of 9-10. A positive incision margin (R+) was found in in 15 % of pT2 stages, 41 % of pT3 stages and 85 % of pT4 stages. A secondary intervention was documented in 6.5 % of RP. CONCLUSION: The DVPZ certificate reflects the complete spectrum of treatment of PCA patients. The strength of the certificate lies in the documentation of patient development and a simultaneous collation of quality parameters.


Subject(s)
Oncology Service, Hospital/statistics & numerical data , Oncology Service, Hospital/standards , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/therapy , Quality Assurance, Health Care/statistics & numerical data , Registries , Adult , Aged , Aged, 80 and over , Germany/epidemiology , Guideline Adherence/statistics & numerical data , Humans , Male , Medical Oncology/standards , Middle Aged , Practice Guidelines as Topic , Quality Assurance, Health Care/standards , Treatment Outcome
17.
J Clin Endocrinol Metab ; 99(12): E2510-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25325797

ABSTRACT

OBJECTIVE: Angiopoietin-like protein 8 (Angptl8) has recently been introduced as a novel adipokine/hepatokine that promotes pancreatic ß-cell proliferation and improves glucose tolerance in mouse models of insulin resistance. However, regulation of Angptl8 in human type 2 diabetes mellitus (T2DM) and renal dysfunction has not been determined. RESEARCH DESIGN AND METHODS: Serum Angptl8 levels were quantified by ELISA in 62 patients with T2DM as compared with 58 nondiabetic subjects in vivo. Within both groups, about half of the patients were on chronic hemodialysis or had an estimated glomerular filtration rate above 50 mL/min/1.73 m(2). Furthermore, we investigated the effect of insulin and differentiation on Angptl8 mRNA expression in 3T3-L1 adipocytes in vitro. RESULTS: Median [interquartile range] serum Angptl8 levels were higher in patients with T2DM (1.19 [0.37] µg/L) as compared with nondiabetic subjects (1.03 [0.47] µg/L) (P = .005). Furthermore, the adipokine/hepatokine was significantly higher in women (1.21 [0.47] µg/L) as compared with men (1.05 [0.44] µg/L]) (P = .013). In multivariate analysis, fasting glucose and T2DM but not renal function remained independent and positive predictors of circulating Angptl8 even after adjustment for markers of obesity, lipid status, and inflammation (P < .05). Furthermore, Angptl8 mRNA expression was induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro. CONCLUSIONS: Circulating Angptl8 is positively and independently associated with T2DM and fasting glucose in vivo. Furthermore, Angptl8 mRNA expression is induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Peptide Hormones/blood , 3T3-L1 Cells , Adipocytes/metabolism , Angiopoietin-Like Protein 8 , Angiopoietin-like Proteins , Animals , Cells, Cultured , Chromans/pharmacology , Cross-Sectional Studies , Diabetic Nephropathies/blood , Female , Humans , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Male , Mice , Middle Aged , Peptide Hormones/biosynthesis , Peptide Hormones/genetics , RNA, Messenger/biosynthesis , Renal Dialysis , Thiazolidinediones/pharmacology , Troglitazone
18.
Horm Metab Res ; 46(10): 685-90, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25011017

ABSTRACT

Angiopoietin-related growth factor (AGF, also known as angiopoietin-like protein 6) has been introduced as a novel hepatocyte-derived factor, which antagonizes obesity and insulin resistance in mice. However, human studies show conflicting results and are limited to a small cohort of patients. In the current study, we therefore sought to investigate AGF serum levels in a large metabolically well-characterized cohort. AGF serum concentrations were determined by commercial enzyme-linked immunosorbent assay in 697 patients of a cohort from Eastern Germany (Sorbs). Correlations of AGF serum levels with clinical and biochemical measures of glucose and lipid metabolism, as well as markers of renal function, were investigated. In nondiabetic subjects (n=627), AGF was positively correlated with markers of insulin resistance and negatively correlated with high-density lipoprotein cholesterol in univariate analyses (p<0.05). After adjustment for age, gender, and body mass index, none of these factors remained independently associated with AGF, neither in nondiabetic subjects nor in patients with type 2 diabetes mellitus (T2DM) (n=70). However, we confirmed existing data of significantly higher AGF concentrations in patients with T2DM as compared to controls in this large cohort. Circulating AGF is elevated in subjects with T2DM and related to the type of antidiabetic treatment, but is not independently associated with anthropometric parameters, indices of insulin sensitivity and secretion, or a number of other adipokines.


Subject(s)
Angiopoietins/blood , Diabetes Mellitus, Type 2/blood , Adult , Angiopoietin-Like Protein 6 , Angiopoietin-like Proteins , Animals , Blood Glucose/metabolism , Body Mass Index , Cholesterol, HDL/metabolism , Cohort Studies , Female , Germany , Glycated Hemoglobin/metabolism , Humans , Lipoproteins, HDL/blood , Male , Mice , Middle Aged
19.
Nutr Metab Cardiovasc Dis ; 24(9): 1027-34, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24813306

ABSTRACT

BACKGROUND AND AIMS: The adipokine adipocyte fatty acid binding protein (AFABP) is positively associated with the development of the metabolic syndrome, diabetes mellitus, and cardiovascular disease. We hypothesized that AFABP also increases with deteriorating renal function. METHODS AND RESULTS: Serum AFABP levels were quantified by enzyme linked immunosorbent assay in 532 patients with chronic kidney disease (CKD) covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5 (study population 1). Furthermore, AFABP was measured in 32 patients before and within 30 h after elective unilateral nephrectomy, a model of acute kidney dysfunction (AKD) (study population 2). Moreover, circulating AFABP was investigated in rats undergoing bilateral nephrectomy (BNE) as compared to sham-operated animals. Median serum AFABP levels adjusted for age, gender, and body mass index significantly increased with increasing eGFR category (G1: 22.0 µg/l; G2: 34.6 µg/l; G3: 56.7 µg/l; G4: 95.2 µg/l; and G5: 173.9 µg/l). Furthermore, renal dysfunction remained positively associated with AFABP in multivariate analysis in this cohort. In patients undergoing unilateral nephrectomy, AFABP increased significantly after surgery (42.1 µg/l) as compared to pre-surgical values (29.3 µg/l). Furthermore, relative changes of post-to-pre-surgical AFABP levels were independently associated with relative changes of post-to-pre-surgical creatinine concentrations. After BNE in rats, AFABP increased significantly as compared to sham-operated animals. CONCLUSIONS: We show that AFABP is significantly elevated in CKD and AKD patients. Furthermore, measures of renal function are associated with circulating AFABP. Moreover, animal experiments indicate that AFABP levels strongly depend on renal function.


Subject(s)
Acute Kidney Injury/blood , Adipocytes/metabolism , Fatty Acid-Binding Proteins/blood , Renal Insufficiency, Chronic/blood , Adipokines/blood , Adult , Aged , Aged, 80 and over , Animals , Body Mass Index , Creatinine/blood , Cross-Sectional Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Multivariate Analysis , Nephrectomy , Rats , Young Adult
20.
Diabet Med ; 31(8): 1014-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24673545

ABSTRACT

AIMS: Fractalkine has recently been introduced as an adipokine that improves glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as its association with markers of obesity, glucose and lipid metabolism, inflammation and renal function, has not been elucidated. METHODS: Circulating fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with gestational diabetes and 74 healthy, pregnant control subjects matched for age, BMI, and gestational age. RESULTS: Median (interquartile range) levels of fractalkine were not significantly different between the two groups [gestational diabetes: 2.24 (2.16) µg/l; control: 2.45 (1.38) µg/l] (P = 0.461). In multivariate linear regression analysis, fractalkine remained independently associated with homeostasis model assessment of insulin resistance (ß = -0.253, P = 0.002) and the proinflammatory adipokine progranulin (ß = 0.218, P = 0.007). CONCLUSIONS: Circulating fractalkine is not different between women with gestational diabetes and control subjects, but the adipokine is independently associated with markers of insulin resistance and proinflammatory progranulin in pregnancy.


Subject(s)
Chemokine CX3CL1/blood , Diabetes, Gestational/blood , Insulin Resistance , Intercellular Signaling Peptides and Proteins/blood , Adult , Biomarkers/blood , Cohort Studies , Cross-Sectional Studies , Diabetes, Gestational/metabolism , Female , Germany , Glucose Tolerance Test , Hospitals, University , Humans , Insulin/blood , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/metabolism , Outpatient Clinics, Hospital , Pregnancy , Progranulins , Reproducibility of Results , Young Adult
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