Evaluating safety risks of whole-body cryotherapy/cryostimulation (WBC): a scoping review from an international consortium.

Over the two last decades, whole-body cryotherapy/cryostimulation (WBC) has emerged as an exciting non-pharmacological treatment influencing inflammatory events at a cellular and physiological level, which can result in improved sleep quality, faster neuromuscular recovery after high-intensity exercise, and chronic pain relief for patients suffering different types of diseases (fibromyalgia, rheumatism, arthritis). Some evidence even suggests that WBC has benefits on mental health (depression, anxiety disorders) and cognitive functions in both adults and older adults, due to increased circulating BDNF levels. Recently, some safety concerns have been expressed by influential public health authorities (e.g., FDA, INSERM) based on reports from patients who developed adverse events upon or following WBC treatment. However, part of the data used to support these claims involved individuals whose entire body (except head) was exposed to extreme cold vaporized liquid nitrogen while standing in a narrow bathtub. Such a procedure is known as partial-body cryotherapy (PBC), and is often erroneously mistaken to be whole-body cryotherapy. Although having similarities in terms of naming and pursued aims, these two approaches are fundamentally different. The present article reviews the available literature on the main safety concerns associated with the use of true whole-body cryotherapy. English- and French-language reports of empirical studies including case reports, case series, and randomized controlled trials (RCTs) were identified through searches of PubMed, Scopus, Cochrane, and Web of Science electronic databases. Five case reports and two RCTs were included for a total of 16 documented adverse events (AEs). A critical in-depth evaluation of these AEs (type, severity, context of onset, participant's medical background, follow-up) is proposed and used to illustrate that WBC-related safety risks are within acceptable limits and can be proactively prevented by adhering to existing recommendations, contraindications, and commonsense guidelines.

Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing-Remitting from Secondary Progressive Multiple Sclerosis. A Review.

Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing-remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.

Unusual Bioactive Compounds with Antioxidant Properties in Adjuvant Therapy Supporting Cognition Impairment in Age-Related Neurodegenerative Disorders.

Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges.

The Molecular Aspects of Disturbed Platelet Activation through ADP/P2Y12 Pathway in Multiple Sclerosis.

Epidemiological studies confirm a high risk of ischemic events in secondary-progressive multiple sclerosis (SP MS) patients, directly associated with an increased level of pro-thrombotic activity of platelets. Our work aimed to verify potential molecular abnormalities of the platelet P2Y12 receptor expression and functionality as a cause of an increased risk of thromboembolism observed in the course of MS. We have demonstrated an enhanced platelet reactivity in response to adenosine diphosphate (ADP) in SP MS relative to controls. We have also shown an increased mRNA expression for the P2RY12 gene in both platelets and megakaryocytes, as well as enhanced density of these receptors on the platelet surface. We postulate that one of the reasons for the elevated risk of ischemic events observed in MS may be a genetically or phenotypically reinforced expression of the platelet P2Y12 receptor. In order to analyze the effect of the PAR1 (protease activated receptor type 1) signaling pathway on the expression level of P2Y12, we also analyzed the correlation parameters between P2Y12 expression and the markers of platelet activation in MS induced by selective PAR1 agonist (thrombin receptor activating peptide-6, TRAP-6). Identifying the molecular base responsible for the enlarged pro-thrombotic activity of platelets in SP MS could contribute to the implementation of prevention and targeted treatment, reducing the development of cardiovascular disorders in the course of the disease.

A Review of Various Antioxidant Compounds and their Potential Utility as Complementary Therapy in Multiple Sclerosis.

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS). The etiology of this multifactorial disease has not been clearly defined. Conventional medical treatment of MS has progressed, but is still based on symptomatic treatment. One of the key factors in the pathogenesis of MS is oxidative stress, enhancing inflammation and neurodegeneration. In MS, both reactive oxygen and nitrogen species are formed in the CNS mainly by activated macrophages and microglia structures, which can lead to demyelination and axon disruption. The course of MS is associated with the secretion of many inflammatory and oxidative stress mediators, including cytokines (IL-1b, IL-6, IL-17, TNF-α, INF-γ) and chemokines (MIP-1a, MCP-1, IP10). The early stage of MS (RRMS) lasts about 10 years, and is dominated by inflammatory processes, whereas the chronic stage is associated with neurodegenerative axon and neuron loss. Since oxidative damage has been known to be involved in inflammatory and autoimmune-mediated processes, antioxidant therapy could contribute to the reduction or even prevention of the progression of MS. Further research is needed in order to establish new aims for novel treatment and provide possible benefits to MS patients. The present review examines the roles of oxidative stress and non-pharmacological anti-oxidative therapies in MS.

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients.

Background: Neuroplasticity ensures the improvement of functional status in patients after stroke. The aim of this study was to evaluate the effect of extremely low-frequency electromagnetic field therapy (ELF-EMF) on brain plasticity in the rehabilitation of patients after stroke. Methods: Forty-eight patients were divided into two groups underwent the same rehabilitation program, but in the study group, the patients additionally were exposed to a standard series of 10 ELF-EMF treatments. To determine the level of neuroplasticity, we measured the plasma level of the brain-derived neurotrophic factor (BDNF), the vascular-endothelial growth factor, as well as BDNF mRNA expression. Additionally, we determined the molecule levels for hepatocyte growth factor, stem cell factor, stromal cell-derived factor 1α, nerve growth factor ß, and leukemia inhibitory factor, using 5plex cytokine panel in plasma. After 4 weeks, during which patients had undergone neurorehabilitation and neurological examinations, we assessed functional recovery using the Barthel Index, Mini-Mental State Examination (MMSE), Geriatric Depression Scale, National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS). Results: We observed that ELF-EMF significantly increased growth factors and cytokine levels involved in neuroplasticity, as well as promoted an enhancement of functional recovery in post-stroke patients. Additionally, we presented evidence that these effects could be related to the increase of gene expression on the mRNA level. Moreover, a change of BDNF plasma level was positively correlated with the Barthel Index, MMSE, and negatively correlated with GDS. Conclusion: Extremely low-frequency electromagnetic field therapy improves the effectiveness of rehabilitation of post-stroke patients by improving neuroplasticity processes.

Potential of redox therapies in neurodegenerative disorders.

Recently significant advances have been made to understand the pathophysiological mechanisms of neurodegenerative disorders to provide real therapeutic benefits. There is evidence that persistent inflammation and oxidative stress are the crucial factors of ongoing cell damage in neurodegenerative complex etiology. The variety of reactive oxygen and nitrogen species are the cause of both axonal and neuronal destruction, which is pathological hallmark of neurodegeneration. Therefore, the reduction of oxidative stress is currently one of the main neuroprotective strategies. The World Health Organization (WHO) estimates that, by 2040, neurodegenerative diseases will be the main cause of death in industrialized countries ahead of the cancers. The redox therapeutic approch can target: degnerative component, inflammatory/autoimmune component and neurodegenerative component. Redox therapy should not be applied uniformly, and must be develop to target specific mechanisms. This review focus on the main antitoxidative therapies that are used in many countries as a supplements or even as a standart treatment. Aditionally, clinical synmptoms of most common neurodegenerative disordes and centralnervous system structures involved in oxidative/nitrosative stress are showed.

Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage.

Multiple sclerosis (MS) is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases) were examined to evaluate the biological activity of blood platelets (adhesion, aggregation), especially their response to the most important physiological agonists (thrombin, ADP, and collagen) and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2 (-∙) in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

[Cryostimulation factor supporting rehabilitation patients with multiple sclerosis and fatigue syndrome]. / Kriostymulacja czynnikiem wspomagajacym rehabilitacje chorych na stwardnienie rozsiane z zespolem zmeczenia.

INTRODUCTION: Fatigue is considered to be one of the most prevalent and disabling symptoms among individuals with multiple sclerosis (MS). According to different studies, fatigue is reported by 75-95% of patients. Fatigue syndrome considerably affects quality of life. Characteristic feature of fatigue syndrome in multiple sclerosis is its relapse caused by warmth. There are only a few researches into fatigue in multiple sclerosis. The most commonly used scale to estimate fatigue is Fatigue Severity Scale (FSS). Cryostimulation has been applied to treat depression. AIM OF THE STUDY: Comparison of the influence of cryostimulation as a supporting factor of kinesytherapy on increasing strength of selected muscle groups of inferior extremities and degree of disability in case of patients with multiple sclerosis and fatigue syndrome and without the latter. MATERIAL AND METHODS: The examination included 60 randomized patients with diagnosed multiple sclerosis (ICD10-G35). To assess the results scales: EDSS, FSS and widespread Lovett scale (punctation with accuracy of measurement 0.5 point) were used. Interpretation of the FSS scale results was made according to Krupp and comp. Fatigue syndrome was diagnosed where results reached 6.5 and higher. Evaluaton of muscle strength concerning chosen muscles groups of inferior extremities: quadriceps femoris, illopsoas, biceps femoris. When the strength of leg muscles was asymmetric, lower values of Lovett scale were used. Patients were divided into 2 groups with regard to positive or negative fatigue syndrome. In the examined group (n = 24) fatigue syndrome was positive (FSS under 6.5) and control (n = 36) negative (FSS under 6.5). All patients were treated with cryostimulation and individual program of exercises adapted to their degree of disability. RESULTS: The use of cryostimulation and kinesytherapy to patients with MS and fatigue syndrome indicates statistically important (p = 0.05) decrease of disability degree in EDSS scale and improvement of muscle strength of quadriceps femoris and illiopsoas compared to MS patients without fatigue syndrome. CONCLUSIONS: Cryostimulation is a factor supporting rehabilitation patients with multiple sclerosis and fatigue syndrome.

[Role of flavonoids as antioxidants in human organism]. / Rola flawonoidów jako przeciwutleniaczy w organizmie czlowieka.

The increasing interest in flavonoids means higher demand for the complex and synthetic knowledge about those substances. The following study is an overview of the contemporary knowledge about the mentioned substances, and hopefully it will magnify this topic. Flavonoids are the ingredients of many nutrition substances and a vital diet element. They are also a group of many medicines with different influence on live organisms. At the moment, there are over hundreds of bio-flavonoids identified. The phenol compounds are used as natural drugs in the cases of various sicknesses of blood, breathing, food, and urinary circuit, and in dermatology as well. The existence of these compounds in the diet, especially maintenance of their proper consumption level, is a very important element in the prevention of many diseases, such as atherosclerosis. The intensity of experimental studies on flavonoids in the last decade (mainly studies on cell cultures) showed varied attributes of these compounds. The results give hope for the use of flavonoids in prevention and neoplasmatic treatment. Phenol compounds as antioxidants may affect in many different aspects: direct reaction with free radicals, scavenging free radicals, growing dismutation of free radicals to the compounds with much lower reactiveness, chelatation of pro-oxidant metals (mainly iron), delaying or strengthening many enzymes. What is more, they can strengthen the functionality of other antioxidants, such as vitamins resolving in fat, and low-molecular substances resolving in water. The wide spectrum of the functions of flavonoids and their synthetic derivatives gives hope for the research of new chemical compounds (drugs) with exploratory characteristics.

[Activity of superoxide dismutase (CuZn-SOD) in erythrocytes of patients after hips alloplasty]. / Aktywnosc dysmutazy ponadtlenkowej (CuZn-SOD) w krwinkach czerwonych chorych po alloplastyce stawu biodrowego.

UNLABELLED: Hip osteoarthritis leads, among others, to abnormally decreased physical activity (hypokinesia). Adverse effect of physical inactivity can cause inhibition of anabolic processes in favour of enhancement of protein, carbohydrate, and lipid catabolitic reactions, as well as inadequate metabolism of polyunsaturated fatty acids. These alterations can induce an increased lipid peroxide synthesis, overproduction of reactive oxygen species (ROS) and acceleration of lipid peroxidation processes. The aim of the study was to determine superoxide dismutase activity (CuZn-SOD) in red blood cells of patients suffering from hip osteoarthritis prior to and following total alloplasty as compared to healthy subjects, and also to evaluate effect of hypokinesia on oxidative stress. MATERIAL AND METHODS; CuZn-SOD activity in red blood cells was determined according to the Misra and Fridovich method in 36 patients with hip osteoarthritis hospitalized at the Traumatic-Orthopaedic Department of the Ministry of Internal Affairs and Administration Hospital in Lódz. RESULTS: In patients with decreased physical activity in ten days after alloplasty, enzyme activity increased (+24.9%), one month since the operation it decreased, but it higher as compared to result activity of CuZn-SOD prior to surgery (+16.8%). CONCLUSIONS: The results activity of superoxide dysmutase leads to ROS generation and their overgeneration in hip osteoarthritis and in first time of treatment.