scholarly journals Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum

2021 ◽  
Vol 10 (15) ◽  
pp. 3271
Author(s):  
Martin Berghoff ◽  
Alexandra Höpfinger ◽  
Ranjithkumar Rajendran ◽  
Thomas Karrasch ◽  
Andreas Schmid ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pilot Study ◽  
Secreted Protein ◽  
Human Cerebrospinal Fluid ◽  
Csf Levels ◽  
Paired Serum ◽  
Grade 3 ◽  
And Migration ◽  
Serum Ratio ◽  
Present Pilot Study

Data on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quantified by ELISA in paired serum and CSF samples of 260 patients (107 males, 153 females) undergoing neurological evaluation. METRNL was abundant in serum (801.2 ± 378.3 pg/mL) and CSF (1007.2 ± 624.2 pg/mL) with a CSF/serum ratio of 1.4 ± 0.8. Serum METRNL levels were significantly correlated (rho = +0.521) to those in CSF. CSF METRNL concentrations were significantly correlated (rho = +0.480) with albumin CSF/serum ratios. The CSF/serum ratios of METRNL and albumin were positively correlated in Reibergram analysis (rho = 0.498), indicating that raising CSF concentrations of METRNL are mediated by increasing BBB dysfunction. The CSF concentrations of METRNL strongly increased in a stepwise manner along with increasing BBB dysfunction from grade 0 to grade 3 and with rising CSF cell count. CSF/serum ratio of METRNL also increased from grade 0 (1.2 ± 0.7) to grade 3 (3.0 ± 0.2). Furthermore, CSF levels were positively correlated with age. In conclusion, METRNL is a secreted and neurotrophic myokine that crosses over the BBB. CSF concentrations of METRNL increase with BBB dysfunction.

scholarly journals Human Cerebrospinal Fluid Regulates Proliferation and Migration of Stem Cells Through Insulin-Like Growth Factor-1

2015 ◽  
Vol 24 (2) ◽  
pp. 160-171 ◽  
Author(s):  
Mingxin Zhu ◽  
Yun Feng ◽  
Sean Dangelmajer ◽  
Hugo Guerrero-Cázares ◽  
Kaisorn L. Chaichana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Human Cerebrospinal Fluid ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals 750. Isavuconazole Cerebrospinal Fluid Concentration in Refractory Coccidioidal Meningitis - A Three-Patient Case Series

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S422-S422
Author(s):  
Matthew R Davis ◽  
Sandy Chang ◽  
Pryce Gaynor ◽  
Erin K McCreary ◽  
Paul R Allyn
Keyword(s):  
Cerebrospinal Fluid ◽  
External Ventricular Drain ◽  
Treatment Success ◽  
Case Series ◽  
Serum Levels ◽  
Published Data ◽  
Cerebrospinal Fluid Concentration ◽  
Fluid Concentration ◽  
Csf Levels ◽  
Paired Serum

Abstract Background Coccidioidal meningitis (CM) causes life-threatening infection with limited treatment options. Small series have reported variable treatment success with isavuconazole. An absence of published data exists on cerebrospinal fluid (CSF) penetration of this agent. Methods Paired serum and CSF levels were measured on three patients with refractory CM treated on salvage isavuconazole therapy. Results 11 CSF levels were sent on 3 patients; 7 from ventricular sources (Ommaya reservoir or external ventricular drain) and 4 from lumbar punctures at 6-44 days after treatment initiation, 2-24.6 hours after oral or intravenous dose. All levels sent from ventricular sources were undetectable < 25µg/mL despite adequate paired serum levels (mean 2.45 µg/mL, range 1.25-6.38 µg/mL; n = 7 levels). Mean lumbar CSF levels were 1.00 µg/mL (range 0.45-1.72 µg/mL; n = 4 levels) with adequate serum levels (mean 3.57 µg/mL, range 1.78-5.63 µg/mL; n = 4 levels). Table 1. Isavuconazole serum and cerebrospinal fluid concentration measurements Conclusion Isavuconazole was detected in lumbar, but not ventricular CSF in three patients treated for CM. Disclosures All Authors: No reported disclosures

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

2021 ◽  
Author(s):  
Alexandra Höpfinger ◽  
Martin Berghoff ◽  
Thomas Karrasch ◽  
Andreas Schmid ◽  
Andreas Schäffler
Keyword(s):  
Cerebrospinal Fluid ◽  
Pigment Epithelium ◽  
Serum Levels ◽  
Retinol Binding Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Serum Concentrations ◽  
Type 2 Diabetic Patients ◽  
Human Cerebrospinal Fluid ◽  
Csf Levels

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.

scholarly journals Effects of Anesthetic Isoflurane and Desflurane on Human Cerebrospinal Fluid Aβ and τ Level

2013 ◽  
Vol 119 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Bin Zhang ◽  
Ming Tian ◽  
Hui Zheng ◽  
Yu Zhen ◽  
Yun Yue ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Spinal Anesthesia ◽  
Amyloid Protein ◽  
Total Tau ◽  
Human Cerebrospinal Fluid ◽  
Csf Levels ◽  
Β Amyloid ◽  
Spinal Catheter

Abstract Background: Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aβ levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aβ and tau in humans. Methods: The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aβ (Aβ40 and Aβ42) and total tau in the CSF were determined. Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aβ40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in Aβ42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aβ levels.

scholarly journals Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus

2007 ◽  
Vol 92 (3) ◽  
pp. 1129-1136 ◽  
Author(s):  
Katarina Kos ◽  
Alison L. Harte ◽  
Nancy F. da Silva ◽  
Anton Tonchev ◽  
Georgi Chaldakov ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cerebrospinal Fluid ◽  
Energy Homeostasis ◽  
Elective Surgery ◽  
Inverse Correlation ◽  
Energy Regulation ◽  
Adiponectin Receptors ◽  
Human Hypothalamus ◽  
Human Cerebrospinal Fluid ◽  
Csf Levels

Abstract Context: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. Objective: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin. Furthermore, we wished to examine the expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human hypothalamus. Methods: For this purpose, serum and CSF samples were collected from 20 men and 19 women matched for age [men, 69.8 ± 8.6 yr (mean ± sd); women, 69.4 ± 4.3 yr] and BMI (men, 29.4 ± 3.4 kg/m2; women, 27.3 ± 4.8 kg/m2) undergoing elective surgery under spinal anesthesia. Results: Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas resistin and leptin levels were 100-fold less. Unlike their serum levels, adiponectin CSF levels showed no gender difference or correlation with insulin resistance, which is similar to resistin CSF levels. The adiponectin and leptin CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI association with inverse correlation in women (r = −0.61; P = 0.02) and no correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in the paraventricular nucleus, which is involved in energy regulation. Conclusion: In summary, our findings show both the presence of adiponectin and resistin in human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of adiponectin and leptin in women appears to be impaired in obesity.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

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