The Composition of Hyperacute Serum and Platelet-Rich Plasma Is Markedly Different despite the Similar Production Method

Autologous blood derived products, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are widely applied in regenerative therapies, in contrast to the drawbacks in their application, mainly deriving from the preparation methods used. Eliminating the disadvantages of both PRP and PRF, hyperacute serum (HAS) opens a new path in autologous serum therapy showing similar or even improved regenerative potential at the same time. Despite the frequent experimental and clinical use of PRP and HAS, their protein composition has not been examined thoroughly yet. Thus, we investigated and compared the composition of HAS, serum, PRP and plasma products using citrate and EDTA by simple laboratory tests, and we compared the composition of HAS, serum, EDTA PRP and plasma by Proteome Profiler and ELISA assays. According to our results the natural ionic balance was upset in both EDTA and citrate PRP as well as in plasma. EDTA PRP contained significantly higher level of growth factors and cytokines, especially platelet derived angiogenic and inflammatory proteins, that can be explained by the significantly higher number of platelets in EDTA PRP. The composition analysis of blood derivatives revealed that although the preparation method of PRP and HAS were similar, the ionic and protein composition of HAS could be advantageous for cell function

Autonomic dysregulation in multiple sclerosis

Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literatureon the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. © 2015 by the authors; licensee MDPI, Basel, Switzerland

The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche

Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as "proliferative agents" for the topical MSC pool. Hyperacute serum (HAS), a new serum derivative, has been designed to approximate the natural coagulation cascade with a single-step, additive-free preparation method. We investigated the effects of HAS on monolayer MSC cultures and in their natural niche, in 3D subchondral bone and marrow explants. Viability measurements, RT-qPCR evaluation for gene expression and flow cytometry for cell surface marker analysis were performed to compare the effects of FCS-, PRP-, or HAS-supplemented culture media. Monolayer MSCs showed significantly higher metabolic activity following 5 days' incubation in HAS, and osteoblast-specific mRNA expression was markedly increased, while cells also retained their MSC-specific cell surface markers. A similar effect was observed on bone and marrow explants, which was further confirmed with confocal microscopy analysis. Moreover, markedly higher bone marrow preservation was observed with histology in case of HAS supplementation compared to FCS. These findings indicate possible application of HAS in regenerative solutions of skeletal diseases like OA or osteonecrosis

Recognition of complex mental states in patients with alcoholism after long-term abstinence

AIMS: We used an associative learning task in order to investigate cognitive dysfunctions in alcohol dependence. This test is suitable for the assessment of stimulus-response learning and memory generalization (acquired equivalence), which is related to medial temporal lobe functioning. METHODS: Twenty patients with alcohol dependence (abstinence: >6 months) and 20 matched healthy controls participated in the study. In the task, antecedent stimuli were cartoon faces (girl, boy, man and woman) and consequent stimuli were color cartoon fishes. The task was to learn face-fish associations using feedback. In the transfer phase, the fish-face pairs were generalized to new associations. RESULTS: There was no significant difference between patients and controls during the acquisition phase of fish-face associations. In the transfer phase, patients were impaired relative to controls. We found no association between task performance and intelligence quotient. CONCLUSION: These results suggest that abstinent patients with alcohol dependence show marked dysfunctions in the generalization of associations, which may indicate the dysfunction of the medial temporal lobe

Autonomic Dysregulation in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment

Autonomic Dysregulation in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease

Objectives: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.Materials and methods: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.Results: Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.541.20 vs. 4.48 +/- 1.43ms/10(-3)). FMD was higher in patients (9.81 +/- 3.77 vs. 5.59 +/- 1.36%). FMD and neural BRS were directly related in controls (r=0.62), but inversely related in patients (r=-0.49).Conclusions: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation

The Effects of Hyperacute Serum on the Elements of the Human Subchondral Bone Marrow Niche

Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as “proliferative agents” for the topical MSC pool. Hyperacute serum (HAS), a new serum derivative, has been designed to approximate the natural coagulation cascade with a single-step, additive-free preparation method. We investigated the effects of HAS on monolayer MSC cultures and in their natural niche, in 3D subchondral bone and marrow explants. Viability measurements, RT-qPCR evaluation for gene expression and flow cytometry for cell surface marker analysis were performed to compare the effects of FCS-, PRP-, or HAS-supplemented culture media. Monolayer MSCs showed significantly higher metabolic activity following 5 days’ incubation in HAS, and osteoblast-specific mRNA expression was markedly increased, while cells also retained their MSC-specific cell surface markers. A similar effect was observed on bone and marrow explants, which was further confirmed with confocal microscopy analysis. Moreover, markedly higher bone marrow preservation was observed with histology in case of HAS supplementation compared to FCS. These findings indicate possible application of HAS in regenerative solutions of skeletal diseases like OA or osteonecrosis