Platelet concentrates for surgical use are tools of regenerative medicine designed for the local release of platelet growth factors into a surgical or wounded site, in order to stimulate tissue ...healing or regeneration. Leukocyte content and fibrin architecture are 2 key characteristics of all platelet concentrates and allow to classify these technologies in 4 families, but very little is known about the impact of these 2 parameters on the intrinsic biology of these products. In this demonstration, we highlight some outstanding differences in the growth factor and matrix protein release between 2 families of platelet concentrate: Pure Platelet-Rich Plasma (P-PRP, here the Anitua's PRGF - Preparation Rich in Growth Factors - technique) and Leukocyte- and Platelet-Rich Fibrin (L-PRF, here the Choukroun's method). These 2 families are the extreme opposites in terms of fibrin architecture and leukocyte content. The slow release of 3 key growth factors (Transforming Growth Factor β1 (TGFβ1), Platelet-Derived Growth Factor AB (PDGF-AB) and Vascular Endothelial Growth Factor (VEGF)) and matrix proteins (fibronectin, vitronectin and thrombospondin-1) from the L-PRF and P-PRP gel membranes in culture medium is described and discussed. During 7 days, the L-PRF membranes slowly release significantly larger amounts of all these molecules than the P-PRP gel membranes, and the 2 products display different release patterns. In both platelet concentrates, vitronectin is the sole molecule to be released almost completely after only 4 hours, suggesting that this molecule is not trapped in the fibrin matrix and not produced by the leukocytes. Moreover the P-PRP gel membranes completely dissolve in the culture medium after less than 5 days only, while the L-PRF membranes are still intact after 7 days. This simple demonstration shows that the polymerization and final architecture of the fibrin matrix considerably influence the strength and the growth factor trapping/release potential of the membrane. It also suggests that the leukocyte populations have a strong influence on the release of some growth factors, particularly TGFβ1. Finally, the various platelet concentrates present very different biological characteristics, and an accurate definition and characterization of the different families of product is a key issue for a better understanding and comparison of the reported clinical effects of these surgical adjuvants.
Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is ...contradictory and the published data are difficult to sort and interpret. In bone graft, implant and reconstructive surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this second article, we describe and discuss the current published knowledge about the use of PRP and PRF during implant placement (particularly as surface treatment for the stimulation of osseointegration), the treatment of peri-implant bone defects (after peri-implantitis, during implantation in an insufficient bone volume or during immediate post-extraction or post-avulsion implantation), the sinuslift procedures and various complex implant-supported treatments. Other potential applications of the platelet concentrates are also highlighted in maxillofacial reconstructive surgery, for the treatment of patients using bisphosphonates, anticoagulants or with post-tumoral irradiated maxilla. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the use of L-PRF (Leukocyte- and Platelet-Rich Fibrin) clots and membranes during the regeneration of peri-implant bone defects, during the sinus-lift procedure and during complex implant-supported rehabilitations. The use of L-PRF allowed to define a new therapeutic concept called the Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges at the gingival and bone levels. As it is illustrated in this article, the NBR principles allow to push away some technical limits of global implant-supported rehabilitations, particularly when combined with other powerful biotechnological tools: metronidazole solution, adequate bone substitutes and improved implant designs and surfaces (for example here AstraTech Osseospeed or Intra-Lock Ossean implants). As a general conclusion, we are currently living a transition period in the use of PRP and PRF in oral and maxillofacial surgery. PRPs failed to prove strong strategic advantages that could justify their use in daily practice, and the use of most PRP techniques will probably be limited to some very specific applications where satisfactory results have been reached. Only a few simple, inexpensive and efficient techniques such as the L-PRF will continue to develop in oral and maxillofacial surgery in the next years. This natural evolution illustrates that clinical sciences need concrete and practical solutions, and not hypothetical benefits. The history of platelet concentrates in oral and maxillofacial surgery finally demonstrates also how the techniques evolve and sometimes promote the definition of new therapeutical concepts and clinical protocols in the today's era of regenerative medicine.
Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is ...contradictory and the published data are difficult to sort and interpret. In periodontology and dentoalveolar surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this first article, we describe and discuss the current published knowledge about the use of PRP and PRF during tooth avulsion or extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal intrabony defects, and regeneration of alveolar ridges using Guided Bone Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a confusing literature and to highlight the underlying universal mechanisms of these products. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the systematic use of L-PRF (Leukocyte- and Platelet- Rich Fibrin) clots and membranes during tooth avulsion, cyst exeresis or the treatment of gingival recessions by root coverage. The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges. In periodontology, this field of research will soon find his golden age by the development of user-friendly platelet concentrate procedures, and the definition of new efficient concepts and clinical protocols.
Abstract
Platelet derivatives are commonly used in wound healing and tissue regeneration. Different procedures of platelet preparation may differentially affect growth factor release and cell growth. ...Preparation of platelet-rich fibrin (PRF) is accompanied by release of growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGFβ1), and several cytokines. When compared with the standard procedure for platelet-rich plasma (PRP), PRF released 2-fold less PDGF, but >15-fold and >2-fold VEGF and TGFβ1, respectively. Also, the release of several cytokines (IL-4, IL-6, IL-8, IL-10, IFNγ, MIP-1α, MIP-1β and TNFα) was significantly increased in PRF-conditioned medium (CM), compared to PRP-CM. Incubation of both human skin fibroblasts and human umbilical vein endothelial cells (HUVECs) with PRF-derived membrane (mPRF) or with PRF-CM enhanced cell proliferation by >2-fold (p < 0.05). Interestingly, PRP elicited fibroblast growth at a higher extent compared to PRF. At variance, PRF effect on HUVEC growth was significantly greater than that of PRP, consistent with a higher concentration of VEGF in the PRF-CM. Thus, the procedure of PRP preparation leads to a larger release of PDGF, as a possible result of platelet degranulation, while PRF enhances the release of proangiogenic factors.
► In chronic spontaneous urticaria free IL-18 is increased. ► IL-18 binding protein counteracts the inflammatory effects of IL-18. ► IL-33 does not play a role in chronic spontaneous urticaria.
...Overproduction of IL-18 has been described in chronic urticaria. To evaluate free IL-18 and IL-33 in chronic spontaneous urticaria (CSU). IL-18, its inhibitor IL-18BP, IL-33 and its soluble receptor ST2 (sST2) were measured (ELISA) in the sera of 73 CSU patients. Free IL-18 was calculated (law of mass action). Autologous serum skin test (ASST) was performed in all patients. Total IL-18, IL-18BP and free IL-18 serum levels were significantly higher in CSU than in controls. IL-18 and IL-18BP increased significantly in both ASST-positive and negative subgroups. Free IL-18 resulted significantly higher in the ASST-negative, but not in the ASST-positive subgroup. No differences in IL-33/sST2 levels were detected between CSU and controls. Increased levels of free IL-18 and IL-18BP, but not IL-33, was detected in CSU. Whether IL-18 up-regulation is a consequence of inflammation or one of the causes of the pathology needs to be addressed.
To determine the success rate of percutaneous first stage of sacral neuromodulation (SNM) and the efficacy and safety of permanent SNM for incomplete spinal cord lesion (SCL) patients suffering from ...chronic neurogenic non-obstructive urinary retention (N-NOR).
From January 2003 to December 2012, 85 individuals underwent the percutaneous first stage of SNM. Subsequently, only responders who reached a concomitant reduction by at least 50% of volume per catheterization and in the number of catheterizations per day comparing their 7-day voiding diaries at baseline underwent permanent SNM. Final follow-up was conducted by April 2013.
Thirty-six individuals responded to percutaneous first stage of SNM. Post-surgery urodynamics documented all patients experiencing first sensation of bladder filling. A statistically significant increase in Qmax ml per sec and decrease in post-voiding residual urine per ml were documented. (P<0.01). First sensation of bladder filling at baseline represented a statistically significant parameter for the success of the first stage SNM (P<0.05). Eleven out of 34 patients at follow-ups were 'inconstant responders' because they returned to similar baseline voiding symptoms, but responded again with an implant on the controlateral S3 sacral root. Two failed twice and responded once again after an S4 sacral root implant. All but one failure occurred more than 3 years after the previous implant. Other drawbacks were resolved telemetrically.
Research is needed to increase the success rate of the first stage SNM on incomplete SCL patients with N-NOR. Permanent SNM is highly efficacious in the medium follow-up.
The aim of this study is to collect normative data of Transcranial-Magnetic-Stimulation (TMS) in pediatric age. 46 healthy children (2–14 years, ranges: 2–5; 5–8; 8–10; 10–12; 12–14; M:F = 25:21) ...were tested with TMS, with an intensity stimulation of 70–80% of resting motor threshold. All children were free of neurologic, psychiatric and serious medical illness, not taking any neuropsychiatric medications, and did not have any contraindication to TMS. A statistic analysis of results noticed a correlations between the cortico-spinal conduction and the myelination of the peripheral nervous system, related with the age and height of the child. The most affected parameters results to be the Latency of the Motor Evoked Potential (L-MEP) and the Central Motor Conduction Time (CMCT). Both parameters are stable during the childhood growing progressively with the age and height. This study demonstrated how the motor conduction is closely related to the age and height of the child and, consequently, to the degrees of maturation of the nervous fibers, and how the CMCT and L-MEP are affected by the maturation of the peripheral nerves. In addition this work also emphasizes the importance of knowing the normative data of MEP in all ranges of ages to better identify the pathological findings in child’s nervous system injury.
State-of-the-art physics experiments require high-resolution, low-noise, and low-threshold detectors to achieve competitive scientific results. However, experimental environments invariably introduce ...sources of noise, such as electrical interference or microphonics. The sources of this environmental noise can often be monitored by adding specially designed “auxiliary devices” (e.g. microphones, accelerometers, seismometers, magnetometers, and antennae). A model can then be constructed to predict the detector noise based on the auxiliary device information, which can then be subtracted from the true detector signal. Here, we present a multivariate noise cancellation algorithm which can be used in a variety of settings to improve the performance of detectors using multiple auxiliary devices. To validate this approach, we apply it to simulated data to remove noise due to electromagnetic interference and microphonic vibrations. We then employ the algorithm to a cryogenic light detector in the laboratory and show an improvement in the detector performance. Finally, we motivate the use of nonlinear terms to better model vibrational contributions to the noise in thermal detectors. We show a further improvement in the performance of a particular channel of the CUORE detector when using the nonlinear algorithm in combination with optimal filtering techniques.
To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary ...retention (N-NOR).
In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM.
Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months.
A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.
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