Circulating Pro-Neurotensin in gestational diabetes mellitus.

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.

The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus.

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.

Serum Levels of Copeptin are Decreased in Gestational Diabetes Mellitus.

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.

Association of metabolic parameters and rs726344 in FNDC5 with serum irisin concentrations.

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.

Cardiovascular magnetic resonance feature-tracking assessment of myocardial mechanics: Intervendor agreement and considerations regarding reproducibility.

AIM: To assess intervendor agreement of cardiovascular magnetic resonance feature tracking (CMR-FT) and to study the impact of repeated measures on reproducibility. MATERIALS AND METHODS: Ten healthy volunteers underwent cine imaging in short-axis orientation at rest and with dobutamine stimulation (10 and 20 µg/kg/min). All images were analysed three times using two types of software (TomTec, Unterschleissheim, Germany and Circle, cvi(42), Calgary, Canada) to assess global left ventricular circumferential (Ecc) and radial (Err) strains and torsion. Differences in intra- and interobserver variability within and between software types were assessed based on single and averaged measurements (two and three repetitions with subsequent averaging of results, respectively) as determined by Bland-Altman analysis, intraclass correlation coefficients (ICC), and coefficient of variation (CoV). RESULTS: Myocardial strains and torsion significantly increased on dobutamine stimulation with both types of software (p<0.05). Resting Ecc and torsion as well as Ecc values during dobutamine stimulation were lower measured with Circle (p<0.05). Intra- and interobserver variability between software types was lowest for Ecc (ICC 0.81 [0.63-0.91], 0.87 [0.72-0.94] and CoV 12.47% and 14.3%, respectively) irrespective of the number of analysis repetitions. Err and torsion showed higher variability that markedly improved for torsion with repeated analyses and to a lesser extent for Err. On an intravendor level TomTec showed better reproducibility for Ecc and torsion and Circle for Err. CONCLUSIONS: CMR-FT strain and torsion measurements are subject to considerable intervendor variability, which can be reduced using three analysis repetitions. For both vendors, Ecc qualifies as the most robust parameter with the best agreement, albeit lower Ecc values obtained using Circle, and warrants further investigation of incremental clinical merit.

Circulating angiopoietin-like protein 8 is independently associated with fasting plasma glucose and type 2 diabetes mellitus.

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.

Relationship between serum levels of angiopoietin-related growth factor and metabolic risk factors.

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.

Real-time phase-contrast flow MRI of the ascending aorta and superior vena cava as a function of intrathoracic pressure (Valsalva manoeuvre).

OBJECTIVE: Real-time phase-contrast flow MRI at high spatiotemporal resolution was applied to simultaneously evaluate haemodynamic functions in the ascending aorta (AA) and superior vena cava (SVC) during elevated intrathoracic pressure (Valsalva manoeuvre). METHODS: Real-time phase-contrast flow MRI at 3 T was based on highly undersampled radial gradient-echo acquisitions and phase-sensitive image reconstructions by regularized non-linear inversion. Dynamic alterations of flow parameters were obtained for 19 subjects at 40-ms temporal resolution, 1.33-mm in-plane resolution and 6-mm section thickness. Real-time measurements were performed during normal breathing (10 s), increased intrathoracic pressure (10 s) and recovery (20 s). RESULTS: Real-time measurements were technically successful in all volunteers. During the Valsalva manoeuvre (late strain) and relative to values during normal breathing, the mean peak flow velocity and flow volume decreased significantly in both vessels (p < 0.001) followed by a return to normal parameters within the first 10 s of recovery in the AA. By contrast, flow in the SVC presented with a brief (1-2 heartbeats) but strong overshoot of both the peak velocity and blood volume immediately after pressure release followed by rapid normalization. CONCLUSION: Real-time phase-contrast flow MRI may assess cardiac haemodynamics non-invasively, in multiple vessels, across the entire luminal area and at high temporal and spatial resolution. ADVANCES IN KNOWLEDGE: Future clinical applications of this technique promise new insights into haemodynamic alterations associated with pre-clinical congestive heart failure or diastolic dysfunction, especially in cases where echocardiography is technically compromised.

Serum adiponectin and progranulin levels are associated with gallstone disease.

BACKGROUND/AIM: Aberrant adipokine serum concentrations are associated with a variety of obesity-related diseases. This study was designed to investigate the putative role of the adipokines adiponectin, chemerin, progranulin, vaspin, fibroblast growth factor 21 (FGF21) and adipocyte fatty acid binding protein (AFABP) in gallstone disease. METHODS: Serum levels of adiponectin, chemerin, progranulin, vaspin, FGF21 and AFABP of 189 gallstone patients and 833 healthy controls were measured by enzyme-linked immunosorbent assays. RESULTS: Increased adiponectin levels were nominally associated with lower gallstone risk in women (p=0.036, odds ratio (OR) 0.47, 95% confidence interval (CI) [0.23; 0.95]). Furthermore progranulin serum concentrations in men were significantly elevated in gallstone carriers in comparison to controls (p=0.012, OR 6.1, 95% CI [1.5; 24.9]). Serum levels of chemerin, vaspin, FGF21 and AFABP did not differ between controls and subjects with gallstones. CONCLUSION: Our data further support a protective effect of adiponectin on gallstone risk and suggest a role of progranulin in the pathophysiology of cholelithiasis. Nevertheless, longitudinal data and functional analyses would be required to assess the pathogenetic link between gallstone formation and adipokine serum levels.

Real-time phase-contrast flow MRI of haemodynamic changes in the ascending aorta and superior vena cava during Mueller manoeuvre.

AIM: To evaluate the potential of real-time phase-contrast flow magnetic resonance imaging (MRI) at 40 ms resolution for the simultaneous determination of blood flow in the ascending aorta (AA) and superior vena cava (SVC) in response to reduced intrathoracic pressure (Mueller manoeuvre). MATERIALS AND METHODS: Through-plane flow was assessed in 20 healthy young subjects using real-time phase-contrast MRI based on highly undersampled radial fast low-angle shot (FLASH) with image reconstruction by regularized non-linear inversion. Haemodynamic alterations (three repetitions per subject = 60 events) were evaluated during normal breathing (10 s), inhalation with nearly closed epiglottis (10 s), and recovery (20 s). RESULTS: Relative to normal breathing and despite interindividual differences, reduced intrathoracic pressure by at least 30 mmHg significantly decreased the initial peak mean velocity (averaged across the lumen) in the AA by -24 ± 9% and increased the velocity in the SVC by +28 ± 25% (p < 0.0001, n = 23 successful events). Respective changes in flow volume per heartbeat were -25 ± 9% in the AA and +49 ± 44% in the SVC (p < 0.0001, n = 23). Flow parameters returned to baseline during sustained pressure reduction, while the heart rate was elevated by 10% (p < 0.0001) after the start (n = 24) and end (n = 17) of the manoeuvre. CONCLUSIONS: Real-time flow MRI during low intrathoracic pressure non-invasively revealed quantitative haemodynamic adjustments in both the AA and SVC.

Circulating adipocyte fatty acid binding protein is increased in chronic and acute renal dysfunction.

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.

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes.

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.

Current role of cardiac and extra-cardiac pathologies in clinically indicated cardiac computed tomography with emphasis on status before pulmonary vein isolation.

PURPOSE: The aim of this study was to assess the incidence of cardiac and significant extra-cardiac findings in clinical computed tomography of the heart in patients with atrial fibrillation before pulmonary vein isolation (PVI). MATERIALS AND METHODS: 224 patients (64 ±â€Š10 years; male 63 %) with atrial fibrillation were examined by cardiac 64-slice multidetector CT before PVI. Extra-cardiac findings were classified as "significant" if they were recommended to additional diagnostics or therapy, and otherwise as "non-significant". Additionally, cardiac findings were documented in detail. RESULTS: A total of 724 cardiac findings were identified in 203 patients (91 % of patients). Additionally, a total of 619 extra-cardiac findings were identified in 179 patients (80 % of patients). Among these extra-cardiac findings 196 (32 %) were "significant", and 423 (68 %) were "non-significant". In 2 patients (1 %) a previously unknown malignancy was detected (esophageal cancer and lung cancer, local stage, no metastasis). 203 additional imaging diagnostics followed to clarify the "significant" findings (124 additional CT, costs 38 314.69 US dollars). Overall, there were 3.2 cardiac and 2.8 extra-cardiac findings per patient. Extra-cardiac findings appear significantly more frequently in patients over 60 years old, in smokers and in patients with a history of cardiac findings (p <0.05). CONCLUSION: Cardiac CT scans before PVI should be screened for extracardiac incidental findings that could have important clinical implications for each patient.

Adipocyte fatty acid-binding protein is released from adipocytes by a non-conventional mechanism.

Adipocyte fatty acid-binding protein (AFABP) is an adipokine, which induces insulin resistance. However, AFABP does not possess any secretion-directed signals and the mechanisms for AFABP release have not been thoroughly assessed so far. In the current study, mechanisms for AFABP secretion were elucidated in 3T3-L1 adipocytes in vitro in the presence or absence of hormonal stimulation, calcium ionophore and secretion inhibitors by cell fractionation experiments, immunoblotting and ELISAs. We demonstrate that AFABP secretion is upregulated during adipocyte differentiation. AFABP secretion is not influenced by treatment with protein secretion inhibitors that block vesicular traffic at the endoplasmic reticulum and the Golgi apparatus. AFABP is secreted partially by adipocyte-derived microvesicles (ADMs), an established mechanism for unconventional secretion from adipocytes. Both total and ADM-secreted AFABP are downregulated by insulin and upregulated by the calcium ionophore ionomycin. Furthermore, murine RAW 264.7 macrophages secrete AFABP and AFABP release from these cells is upregulated by lipopolysaccharide treatment. Taken together, these results suggest that AFABP is actively released by unconventional mechanisms and by ADMs from 3T3-L1 adipocytes. Furthermore, AFABP secretion from fat cells is regulated by insulin and intracellular calcium.

Different associations of adipokines in lean and healthy adults.

Regulation of adipokines in lean adults without metabolic disease and without eating disorders has not been comprehensively elucidated. We hypothesized that some of the established associations of these adipocyte-secreted proteins with anthropometric and biochemical measures of glucose homeostasis, lipid metabolism, renal function, as well as inflammation, differ in healthy and low weight adults as compared to overweight/obese patients. Eighty-one subjects with a body mass-index below 22.0 kg/m2 and without malnutrition or eating disorders, as well as fifty overweight/obese patients, were recruited for the study. Serum concentrations of seven adipokines (adiponectin, leptin, adipocyte fatty acid-binding protein [AFABP], chemerin, fibroblast growth factor [FGF]-21, resistin, retinol-binding protein [RBP]-4) were measured by enzyme-linked immunosorbent assays. Lean probands had significantly higher levels of adiponectin and resistin, as well as lower levels of leptin, AFABP, and RBP-4, as compared to overweight/obese subjects. Serum concentrations of adiponectin, leptin, AFABP, chemerin, and resistin were significantly higher in lean women as compared to men (p<0.05). In lean subjects, fasting insulin independently predicted leptin and resistin concentrations. Furthermore, C-reactive protein was independently associated with circulating AFABP and chemerin. Moreover, lean body mass was an independent predictor of leptin, fat mass predicted AFABP levels, whereas RBP-4 was independently correlated to age and triglycerides. In addition, high density lipoprotein cholesterol predicted AFABP. Our results support the notion that several of these adipokines are regulated in a different manner in lean adults as compared to overweight/obese subjects and patients with eating disorders.

Adipocyte fatty acid binding protein: a novel adipokine involved in the pathogenesis of metabolic and vascular disease?

Adipocyte fatty acid binding protein (AFABP, also known as aP2 and FABP4) has recently been introduced as a novel fat-derived circulating protein. AFABP serum concentrations are positively correlated with markers of the metabolic syndrome and vascular disease in various cross-sectional and interventional studies. Furthermore, a small set of prospective studies indicates that high AFABP serum levels at baseline predict the risk for metabolic and vascular morbidity and mortality. Studies in Afabp (also known as Fabp4) knockout mice and AFABP inhibitor-treated animals suggest that total AFABP promotes insulin resistance, hypertriacylglycerolaemia and atherosclerosis by ligand/ligand delivery, as well as ligand-independent mechanisms. In contrast, the pathophysiological significance of circulating AFABP and the mechanisms leading to its release remain to be established. The current review summarises recent findings on the regulation and potential role of AFABP in metabolic and vascular disease.

Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies.

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.

[Immunoglobulins in PID, SID and neurological autoimmune disease]. / Anwendung von Immunglobulinen bei primären und sekundären Immundefekten und neurologischen Autoimmunerkrankungen.

Human immunoglobulins (IG, mostly IgG) are used as replacement therapy in patients with inherited primary immunodeficiencies, and in patients with secondary immuno-deficiencies often observed in multiple myeloma or chronic lymphocytic leukemia. Ig are also approved as immunomodulatory therapy in neurological autoimmune diseases (NAID) such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). 16 different Ig preparations for intravenous and subcutaneous use are at the moment available in Germany. The SIGNS study (Assessment of immunoglobulins in a long-term non-interventional study) investigates the clinical use of these drugs under clinical practice conditions. In this non-interventional prospective open-label cohort study, 550 patients with new or maintenance Ig therapy are observed with respect to drug utilization, effectiveness, (i. e. number of infections in PID and SID, functionality in NAID), tolerability, quality of life and costs in approximately 50 sites throughout Germany (neurologists, pediatricians, oncologists, other) for at least two years. This largest study of its kind is expected to contribute to optimization of Ig therapy in the postmarketing setting.

Serum levels of the adipokine zinc-α2-glycoprotein are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is associated with facets of the metabolic syndrome and an increased future metabolic and cardiovascular risk for mother and newborn. Recently, zinc-α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in the pathogenesis of obesity. AIM: In the current study, we investigated ZAG serum levels in PE patients as compared to healthy gestational age-matched controls. SUBJECTS AND METHODS: We quantified serum concentrations of ZAG in patients with PE (no.=37) as compared to healthy gestational age-matched controls (no.=37) by enzyme-linked immunosorbent assay. Furthermore, association of this adipokine with renal function, glucose and lipid metabolism, as well as inflammation was studied. RESULTS: Median serum ZAG levels were 1.4-fold higher in PE patients (58.8 mg/l) as compared to controls (41.9 mg/l) (p<0.01). Furthermore, circulating ZAG was positively correlated to systolic and diastolic blood pressure, creatinine, triglycerides, and leptin in univariate analyses. In multiple regression analysis, creatinine remained independently associated with ZAG. CONCLUSIONS: We demonstrate that maternal ZAG serum concentrations are significantly increased in PE. Furthermore, renal function is an independent predictor of circulating ZAG.