scholarly journals Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model

2018 ◽  
Vol 19 (11) ◽  
pp. 3531 ◽  
Author(s):  
Vivien Kauschke ◽  
Maike Schneider ◽  
Annika Jauch ◽  
Matthias Schumacher ◽  
Marian Kampschulte ◽  
...  

The development of new and better implant materials adapted to osteoporotic bone is still urgently required. Therefore, osteoporotic muscarinic acetylcholine receptor M3 (M3 mAChR) knockout (KO) and corresponding wild type (WT) mice underwent osteotomy in the distal femoral metaphysis. Fracture gaps were filled with a pasty α-tricalcium phosphate (α-TCP)-based hydroxyapatite (HA)-forming bone cement containing mesoporous bioactive CaP-SiO2 glass particles (cement/MBG composite) with or without Brain-Derived Neurotrophic Factor (BDNF) and healing analyzed after 35 days. Histologically, bone formation was significantly increased in WT mice that received the BDNF-functionalized cement/MBG composite compared to control WT mice without BDNF. Cement/MBG composite without BDNF increased bone formation in M3 mAChR KO mice compared to equally treated WT mice. Mass spectrometric imaging showed that the BDNF-functionalized cement/MBG composite implanted in M3 mAChR KO mice was infiltrated by newly formed tissue. Leukocyte numbers were significantly lower in M3 mAChR KO mice treated with BDNF-functionalized cement/MBG composite compared to controls without BDNF. C-reactive protein (CRP) concentrations were significantly lower in M3 mAChR KO mice that received the cement/MBG composite without BDNF when compared to WT mice treated the same. Whereas alkaline phosphatase (ALP) concentrations in callus were significantly increased in M3 mAChR KO mice, ALP activity was significantly higher in WT mice. Due to a stronger effect of BDNF in non osteoporotic mice, higher BDNF concentrations might be needed for osteoporotic fracture healing. Nevertheless, the BDNF-functionalized cement/MBG composite promoted fracture healing in non osteoporotic bone.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
M Camilli ◽  
M Russo ◽  
M Del Buono ◽  
F Gurguglione ◽  
...  

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophine that plays a key role in the regulation of both central and peripheral nervous system. Moreover, BDNF is secreted in multiple tissues and exerts systemic, autocrine, and paracrine effects in the cardiovascular system. Of importance, BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries and may be involved in thrombus formation. Thus, BDNF has been suggested as an important link between inflammation and thrombosis, potentially involved in the pathogenesis of acute coronary syndrome (ACS). Purpose In our study we aimed at assessing serum levels of BDNF in patients with ACS, evaluating differences according to clinical presentation [ST-segment elevation myocardial infarction (STEMI) vs. Non-ST-segment elevation ACS (NSTE-ACS)]. Moreover, we assessed the presence of optical coherence (OCT)-defined macrophage infiltrates (MØI) in the culprit vessel of ACS patients and evaluated their relationship with BDNF levels. Methods ACS patients were prospectively selected. Blood samples were collected at admission and serum levels of BDNF were subsequently assessed. Presence of OCT-defined MØI along the culprit vessel was assessed. Results 166 ACS patients were enrolled [mean age 65.3±11.9 years, 125 (75.3%) male, 109 STEMI, 57 NSTE-ACS]. Serum levels of BDNF were higher among STEMI patients compared with NSTE-ACS [median (IQR) 2.48 pg/mL (1.54–3.34) vs. 2.12 pg/mL (1.34–2.47), p=0.007], while C-reactive protein levels did not differ between the two groups. OCT assessment was performed in 53 patients and MØI were detected in 27 patients. Of importance, patients with MØI in the culprit vessel had higher levels of BDNF compared with patients without MØI [median (IQR) 2.23 pg/mL (1.38–2.53) vs. 1.41 pg/mL (0.93–2.07), p=0.023], while C-reactive protein levels did not differ between the two groups. Of note, at multivariate regression analysis BDNF levels were independent predictor of MØI [OR: 2.20; 95% CI (1.02–4.74), p=0.043]. Conclusions Serum levels of BDNF may reliable identify the presence of local macrophage inflammatory infiltrates in patients with ACS. Moreover, BDNF levels are higher in patients with STEMI compared with NSTE-ACS. Taken together, these data suggest that BDNF may represent an interesting link between local inflammatory activation and enhanced thrombosis in ACS. BDNF serum levels Funding Acknowledgement Type of funding source: None


2008 ◽  
Vol 212 (5) ◽  
pp. 697-701 ◽  
Author(s):  
Volker Braunstein ◽  
Christoph M. Sprecher ◽  
Armando Gisep ◽  
Lorin Benneker ◽  
Kathrin Yen ◽  
...  

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 747
Author(s):  
Edwin Utomo ◽  
Farhat . ◽  
Melvin Nova Gunawanto Barus ◽  
Mohd. Rhiza Z. Tala

Background: Overactive bladder (OAB) is a clinical syndrome characterized by a combination of symptoms including urgency, frequency, and nocturia, with or without urinary incontinence. Overactive bladder has a high prevalence especially in those of an older age and women, with diagnosis depending on the patient’s symptoms. This study aims to assess brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and high sensitivity C-reactive protein (HSCRP) in urine as biomarkers in OAB. Methods: Studies were searched from Pubmed, Science Direct, Wiley Online Library, and Google Scholar. All studies assessing BDNF, NGF, and HSCRP in urine in OAB patients were included. The standardized mean difference (SMD) and 95% confidence intervals (CI) were then calculated. Results: A total of 85 studies were included with a total of 11,483 subjects (6,885 OAB patients and 4,598 controls). Based on data analysis results, urinary NGF/Creatinine (NGF/Cr) and NGF level in OAB patients were significantly higher than control (SMD = 1.00, 95%CI = 0.80-1.20, P<0.00001; and SMD = 1.11, 95%CI = 0.79-1.43, P<0.00001). NGF/Cr level was found higher in OAB with incontinence (OAB wet) compared with OAB without incontinence (OAB dry) (SMD = 0.41, 95%CI = 0.23-0.60, P<0.0001), and decreased after treatment (SMD = 0.76, 95%CI = 0.49-1.03, P<0.00001). Urinary BDNF/Cr level was significantly higher in OAB patients compared with controls (SMD = 1.97, 95%CI = 1.14-2.79, P<0.00001), and also decreased significantly after treatment (SMD = 0.75, 95%CI = 0.42-1.08, P<0.00001). The level of HSCRP was significantly higher in OAB patients when compared with controls (SMD = 0.38, 95%CI = 0.12-0.64, P<0.004). Conclusions: The level of BDNF/Cr, NGF/Cr, NGF, and HSCRP in urine were found higher in OAB compared with controls, which means they may be used as a biomarkers for OAB.


2017 ◽  
Vol 29 (6) ◽  
pp. 337-346 ◽  
Author(s):  
Kyoko Hasebe ◽  
Laura Gray ◽  
Chiara Bortolasci ◽  
Bruna Panizzutti ◽  
Mohammadreza Mohebbi ◽  
...  

ObjectiveThis study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression.MethodsWe embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment.ResultsNAC treatment significantly improved depressive symptoms on the Montgomery–Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment.ConclusionOverall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.


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