Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum

Author(s):  
Alexandra Höpfinger ◽  
Martin Berghoff ◽  
Thomas Karrasch ◽  
Andreas Schmid ◽  
Andreas Schäffler

Abstract Context Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain. Objective This work aimed to quantify RBP4, PEDF, and clusterin in paired serum and CSF samples of patients undergoing neurological evaluation. Methods A total of 268 patients (109 male, 159 female) were included. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay in duplicate. Results RBP4 was abundant in serum (mean, 31.9 ± 24.2 μg/mL). The serum concentrations were approximately 145 times higher than in CSF (CSF to serum RBP4 ratio, 8.2 ± 4.3 × 10–3). PEDF was detectable in serum (mean, 30.2 ± 11.7 μg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to serum PEDF ratio, 42.3 ± 15.6 × 10–3). Clusterin serum concentrations were abundant with mean levels of 346.0 ± 114.6 μg/mL, which were approximately 40 times higher than CSF levels (CSF to serum clusterin ratio, 29.6 ± 23.4 × 10–3). RBP4 and PEDF serum levels correlated positively with CSF levels, which were increased in overweight/obese patients and in type 2 diabetic patients. The CSF concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF correlated positively with inflammatory parameters. In detail, only RBP4 showed the kinetics and associations that are mandatory for a putative mediator of the fat-brain axis. Conclusion RBP4, PEDF, and clusterin are permeable to the BBB and increase with the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis.

2019 ◽  
Vol 19 (6) ◽  
pp. 845-851 ◽  
Author(s):  
Sahar Ahmed ◽  
Rasha Sobh

Background:Osteoprotegerin (OPG) is a tumor necrosis factor receptor super-family member. It specifically acts on bone by increasing bone mineral density and bone volume. Recent studies have evidenced its close relation to the development of atherosclerosis and plaque destabilization. Elevated OPG level has also been associated with the degree of coronary calcification in the general population and it has been considered to be a marker of coronary atherosclerosis.Objective:The aim of this study was to determine the relation between OPG levels and Coronary Artery Calcification score (CACs) in Type 2 diabetic patients in comparison to healthy controls.Methods:Our study included 45 type 2 diabetic patients (mean age 51.7 years; 51.1% male) without evidence of previous CVD and 45 healthy age and sex matched subjects as control. All participants were subjected to full history, full examination and lab investigations. Serum OPG concentration was measured by an enzyme-linked immunosorbent assay (ELISA) and CAC imaging was performed using non contrast Multi detector CT of the heart.Results:Significant CAC (<10 Agatston units) was seen in 23 patients (51.11 %).:OPG was significantly high in diabetic patients in comparison to controls with mean 12.9±5.7 pmol/l in cases, and 8.6±0.5 pmol/l in controls (P value < 0.001).:The Coronary Artery Calcification Score (CACS) was positively correlated with age and duration of diabetes. The OPG was positively correlated with age, fasting blood sugar and duration of diabetes. The CACS showed a significantly positive correlation with OPG.Conclusion:Findings suggested that increasing in serum OPG was consistent with CAC and could be used for the early diagnosis of subclinical atherosclerosis.


2020 ◽  
Author(s):  
Ramin Lotfi ◽  
Mohsen Molaie ◽  
Ehsan Mohammadi Noori ◽  
Khalil Soleiman ◽  
Amir Kiani

Adipose tissue-derived hormones known as adipokines, like leptin, have multiple bioactions. Notwithstanding the key roles of leptin in regulating energy homeostasis and metabolism, its cardiovascular functions are complex and not fully understood. This study aimed to investigate the association between serum concentrations of leptin and lipid profiles in patients with valve calcification. Seventy-two patients with valve calcification and 72 healthy individuals participated in this case-control study. The serum levels of biochemical markers and leptin were measured by the standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA) technique, respectively. Significantly increased serum concentrations of FBS (P=0.001), urea (P<0.0001), creatinine (P=0.018), P (P<0.0001), LDL-C (P=0.011) and lower Ca (P=0.006), and HDL-C (P<0.0001) levels were observed in patients compared to controls. There was no significant difference in the serum level of TG and TC of patients than controls. Systolic and diastolic blood pressures were significantly increased in patients relative to controls (P<0.0001). However, a significantly diminished serum level of leptin was observed in patients than controls (P<0.0001). The correlation analysis demonstrated that the serum leptin concentration is negatively correlated with creatinine, but it is positively correlated with systolic blood pressure (P=0.0302, P=0.0362, respectively). There was no statistically significant association between serum levels of leptin and lipid profiles. Our findings indicated dyslipidemia and reduced serum leptin concentrations in patients with valve calcification, suggesting the role of lipid abnormalities and reduced leptin levels in the development and pathogenesis of valve calcification diseases.


PEDIATRICS ◽  
1981 ◽  
Vol 67 (3) ◽  
pp. 387-388
Author(s):  
Michael E. Speer ◽  
Edward O. Mason ◽  
John T. Scharnberg

Simultaneous serum and CSF samples were obtained following the intramuscular administration of 50,000 units/kg of aqueous procaine penicillin G in 25 neonates. Penicillin activity was detected in the sera and CSF of all patients. Peak serum levels were noted at four hours (mean ± SEM, 17.1 ± 6.3 µg/ml). Peak CSF levels were noted at 12 hours (0.70 ± 0.35 µg/ml). The serum level at 24 hours was 2.1 ± 0.98 µg/ml (range, 0.2 to 5.8 µg/ml); the CSF level at 24 hours was 0.12 ± 0.05 µg/ml (range, 0.03 to 0.27 µg/ml). These results demonstrate that spirocheticidal levels (≥0.03 µg/ml) are achieved for at least 24 hours in the CSF following the intramuscular administration of aqueous procaine penicillin G in neonates.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Polkowska ◽  
Izabela Elżbieta Pasierowska ◽  
Marta Pasławska ◽  
Elżbieta Pawluczuk ◽  
Artur Bossowski

Introduction. The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). Aim of the Study. Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. Materials and Methods. The study consisted of 138 patients aged 5–18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p<0.05. Results. The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. Conclusions. Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.


2018 ◽  
Vol 6 (2) ◽  
pp. 314-319 ◽  
Author(s):  
Doaa Samir Salah El-Din ◽  
Ahmed Ibrahim Amin ◽  
Ahmed Osman Egiza

AIM: This work investigated associations between tissue inhibitor metalloproteinase-1 and diabetic cardiovascular diseases in type 2 diabetic patients; also it investigated the role of osteopontin in the diagnosis of type 2 cardiovascular diabetes complications.SUBJECTS AND METHODS: These were examined on eighty subjects, divided into three groups as follows: twenty volunteer healthy control subjects, thirty type 2 diabetes mellitus (DM) patients, and thirty cardiovascular, diabetic patients. Full clinical measurements were carried out, and the expression level of tissue inhibitor metalloproteinase-1 in blood samples was analysed by real-time PCR, using gene-specific primer pairs. Also osteopontin concentrations had been measured by the enzyme-linked immunosorbent assay. Data were tested statistically by parametric tests.RESULTS: The concentrations of osteopontin and the expression levels of tissue inhibitor metalloproteinase-1 were significantly increased in diabetic and cardiovascular diabetic groups compared to control group also they were significantly increased in the cardiovascular diabetic group compared to the diabetic group.CONCLUSION: Tissue inhibitor metalloproteinase-1 and osteopontin concentrations were significantly increased in diabetic patients with cardiovascular complications than other groups.


2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.


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