Cold therapy is commonly used as a procedure to relieve pain symptoms, particularly in inflammatory diseases, injuries and overuse symptoms. A peculiar form of cold therapy (or stimulation) was ...proposed 30 years ago for the treatment of rheumatic diseases. The therapy, called whole-body cryotherapy (WBC), consists of exposure to very cold air that is maintained at -110 degrees C to -140 degrees C in special temperature-controlled cryochambers, generally for 2 minutes. WBC is used to relieve pain and inflammatory symptoms caused by numerous disorders, particularly those associated with rheumatic conditions, and is recommended for the treatment of arthritis, fibromyalgia and ankylosing spondylitis. In sports medicine, WBC has gained wider acceptance as a method to improve recovery from muscle injury. Unfortunately, there are few papers concerning the application of the treatment on athletes. The study of possible enhancement of recovery from injuries and possible modification of physiological parameters, taking into consideration the limits imposed by antidoping rules, is crucial for athletes and sports physicians for judging the real benefits and/or limits of WBC. According to the available literature, WBC is not harmful or detrimental in healthy subjects. The treatment does not enhance bone marrow production and could reduce the sport-induced haemolysis. WBC induces oxidative stress, but at a low level. Repeated treatments are apparently not able to induce cumulative effects; on the contrary, adaptive changes on antioxidant status are elicited--the adaptation is evident where WBC precedes or accompanies intense training. WBC is not characterized by modifications of immunological markers and leukocytes, and it seems to not be harmful to the immunological system. The WBC effect is probably linked to the modifications of immunological molecules having paracrine effects, and not to systemic immunological functions. In fact, there is an increase in anti-inflammatory cytokine interleukin (IL)-10, and a decrease in proinflammatory cytokine IL-2 and chemokine IL-8. Moreover, the decrease in intercellular adhesion molecule-1 supported the anti-inflammatory response. Lysosomal membranes are stabilized by WBC, reducing potential negative effects on proteins of lysosomal enzymes. The cold stimulation shows positive effects on the muscular enzymes creatine kinase and lactate dehydrogenase, and it should be considered a procedure that facilitates athletes' recovery. Cardiac markers troponin I and high-sensitivity C-reactive protein, parameters linked to damage and necrosis of cardiac muscular tissue, but also to tissue repair, were unchanged, demonstrating that there was no damage, even minimal, in the heart during the treatment. N-Terminal pro B-type natriuretic peptide (NT-proBNP), a parameter linked to heart failure and ventricular power decrease, showed an increase, due to cold stress. However, the NT-proBNP concentrations observed after WBC were lower than those measured after a heavy training session, suggesting that the treatment limits the increase of the parameter that is typical of physical exercise. WBC did not stimulate the pituitary-adrenal cortex axis: the hormonal modifications are linked mainly to the body's adaptation to the stress, shown by an increase of noradrenaline (norepinephrine). We conclude that WBC is not harmful and does not induce general or specific negative effects in athletes. The treatment does not induce modifications of biochemical and haematological parameters, which could be suspected in athletes who may be cheating. The published data are generally not controversial, but further studies are necessary to confirm the present observations.
Saliva represents a low stress, not-invasively collected matrix that allows steroid hormone monitoring in athletes by reflecting type, intensity and duration of exercise. Whole body cryotherapy (WBC) ...consists of short whole-body exposures to extremely cold air (-110° to -140°C) which, despite being initially used to treat inflammatory diseases, is currently acquiring increasing popularity in sports medicine. Cryostimulation practice is now widely accepted as an effective treatment to accelerate muscle recovery in rugby players. The aim of this work was to study the changes of steroid hormones in saliva of rugby players after both 2 and 14 consecutive WBC sessions, in order to investigate the effects of the treatment on their salivary steroid hormonal profile. Twenty-five professional rugby players, belonging to the Italian National Team, underwent a 7-day cryotherapy protocol consisting of 2 daily sessions. Saliva samples were taken in the morning prior to the start of the WBC, in the evening after the end of the second WBC, and in the morning of the day after the last WBC session. The samples were analyzed for cortisol, DHEA, testosterone and estradiol using competitive enzyme-linked immunosorbent assays. Cortisol and DHEA showed a reduction already after the 2 WBC sessions of the first day; after 14 consecutive WBC sessions cortisol, DHEA, and estradiol levels decreased, while testosterone increased as did the testosterone to cortisol ratio. These results were confirmed by the fact that the majority of subjects showed variations exceeding the critical difference (CD). In conclusion, we found that WBC acutely affects the salivary steroid hormone profile, and the results are evident already after only one twice-daily session. Most significantly, after one-week of consecutive twice-daily WBC sessions, all the hormones were modified. This is the first experimental report that links changes in the hormonal asset to WBC.
The present work is aimed at the design and fabrication of microfluidic devices for pharmacological in-vitro tests on cells as a tool for individuating the concentration range in which the drug ...effectiveness is guaranteed, with particular attention to anti-osteoporotic therapies with strontium ranelate.
The microsystem consists of a microchannels network for the delivery and mixing of chemical species, designed to provide a controlled drug concentration to each cell culture 1.
The design and the optimization of the microfluidic network were carried out by means of both analytical and computational approaches. Besides, micromixers and wells modules were modeled, fabricated and tested separately.
A prototype of the complete device has been produced and further experimental tests will be performed.
Osteoarthritis (OA) is the most prevalent joint disease, and to date, no options for effective tissue repair and restoration are available. With the aim of developing new therapies, the impact of ...mesenchymal stem cells (MSCs) has been explored, and the efficacy of MSCs started to be deciphered. A strong paracrine capacity relying on both secreted and vesicle-embedded (EVs) protein or nucleic acid-based factors has been proposed as the principal mechanism that contributes to tissue repair. This work investigated the mechanism of internalization of extracellular vesicles (EVs) released by adipose-derived MSCs (ASCs) and the role of shuttled miRNAs in the restoration of homeostasis in an in vitro model of human fibroblast-like synoviocytes (FLSs) from OA patients.
ASC-EVs were isolated by differential centrifugation and validated by flow cytometry and nanoparticle tracking analysis. ASC-EVs with increased hyaluronan (HA) receptor CD44 levels were obtained culturing ASCs on HA-coated plastic surfaces. OA FLSs with intact or digested HA matrix were co-cultured with fluorescent ASC-EVs, and incorporation scored by flow cytometry and ELISA. ASC-EV complete miRNome was deciphered by high-throughput screening. In inflamed OA FLSs, genes and pathways potentially regulated by ASC-EV miRNA were predicted by bioinformatics. OA FLSs stimulated with IL-1β at physiological levels (25 pg/mL) were treated with ASC-EVs, and expression of inflammation and OA-related genes was measured by qRT-PCR over a 10-day time frame with modulated candidates verified by ELISA.
The data showed that HA is involved in ASC-EV internalization in FLSs. Indeed, both removal of HA matrix presence on FLSs and modulation of CD44 levels on EVs affected their recruitment. Bioinformatics analysis of EV-embedded miRNAs showed their ability to potentially regulate the main pathways strictly associated with synovial inflammation in OA. In this frame, ASC-EVs reduced the expression of pro-inflammatory cytokines and chemokines in a chronic model of FLS inflammation.
Given their ability to affect FLS behavior in a model of chronic inflammation through direct interaction with HA matrix and miRNA release, ASC-EVs confirm their role as a novel therapeutic option for osteoarthritic joints.
The stability of haematological parameters is crucial to guarantee accurate and reliable data for implementing and interpreting the athlete's biological passport (ABP). In this model, the values of ...haemoglobin, reticulocytes and out-of-doping period (OFF)-score (Hb-60√Ret) are used to monitor the possible variations of those parameters, and also to compare the thresholds developed by the statistical model for the single athlete on the basis of its personal values and the variance of parameters in the modal group. Nevertheless, a critical review of the current scientific literature dealing with the stability of the haematological parameters included in the ABP programme, and which are used for evaluating the probability of anomalies in the athlete's profile, is currently lacking. In addition, we collected information from published studies, in order to supply a useful, practical and updated review to sports physicians and haematologists. There are some parameters that are highly stable, such as haemoglobin and erythrocytes (red blood cells RBCs), whereas others, (e.g. reticulocytes, mean RBC volume and haematocrit) appear less stable. Regardless of the methodology, the stability of haematological parameters is improved by sample refrigeration. The stability of all parameters is highly affected from high storage temperatures, whereas the stability of RBCs and haematocrit is affected by initial freezing followed by refrigeration. Transport and rotation of tubes do not substantially influence any haematological parameter except for reticulocytes. In all the studies we reviewed that used Sysmex instrumentation, which is recommended for ABP measurements, stability was shown for 72 hours at 4 ° C for haemoglobin, RBCs and mean curpuscular haemoglobin concentration (MCHC); up to 48 hours for reticulocytes; and up to 24 hours for haematocrit. In one study, Sysmex instrumentation shows stability extended up to 72 hours at 4 ° C for all the parameters. There are significant differences among methods and instruments: Siemens Advia shows lower stability than Sysmex as regards to reticulocytes. However, the limit of 36 hours from blood collection to analysis as recommended by ABP scientists is reasonable to guarantee analytical quality, when samples are transported at 4 ° C and are accompanied by a certified steadiness of this temperature. There are some parameters that are highly stable, such as haemoglobin and RBCs; whereas others, such as reticulocytes, mean cell volume and haematocrit are more unstable. The stability of haematological parameters might be improved independently from the analytical methodology, by refrigeration of the specimens.
Leucemia es la enfermedad neoplásica más común en la infancia representando una tercera parte de todas las malignidades. La incidencia global de leucemia en pacientes menores de 15 años es de ...aproximadamente 40 casos por año por millón. El 75% de las leucemias son leucemias linfoblástica agudas, 20% son leucemias linfoblásticas no agudas y leucemias mieloide crónicas menos el 15%. La incidencia máxima de las leucemias linfoides agudas ocurren entre los 3-6 años de edad. La etiología permanece todavía desconocida ya que no existe una relación, causa, efecto clara para agentes que han sido alguna vez implicados como son infecciones virales, contaminación, radiación, ionizante, compuesto químico, factores genéticos. Este artículo describe lo más relevante acerca del diagnóstico, tratamiento y seguimiento de los pacientes afectados con leucemia linfoblástica aguda.
In recent years, Brazil has experienced several crises of electric energy, and in the face of this situation, there is a concern to apply consumer reduction actions based on the government program ...PROCEL. Public lighting, in particular, is one of the areas where energy efficiency actions can be applied through technological updating of lighting equipment. This study, therefore, aims to evaluate the impact of such a change in the electric sector. For that, pilot projects were considered with complete technological update of this park by LED technology. In this context, it was evaluated the reduction of the electric energy consumption and thus, presented a 10-year projection scenario in order to verify the benefits of the technological update in terms of electric energy consumption and reduction of the energy demand with some economic considerations and, consequently reduction in the energy bill of final consumers. In addition, this projection can be used to discuss the reduction of CO2 emissions, as upgrading of public lighting by LED technology will bring savings in consumption and energy production.
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