Análisis pre-clínico comparativo de la eficacia, mecanismo de acción y mecanismos de resistencia de dos fármacos inmunomoduladores (IMIDS), lenalidomida y pomalidomida, en mieloma múltiple

[ES] Esta tesis pretende estudiar de forma comparativa la eficacia y el mecanismo de acción de dos fármacos inmunomoduladores, Lenalidomida y Pomalidomida, tanto solos como en combinación con dexametasona en líneas celulares y células procedentes de pacientes con mieloma múltiple. Además analizar la posible potenciación de dichos fármacos inmunomoduladores con otros fármacos, tanto clásicos como nuevos, empleados en el mieloma múltiple. También pretende desarrollar un modelo “in vivo” de resistencia adquirida a fármacos inmunomoduladores con un doble fin: investigar las características de la resistencia adquirida a fármacos inmunomoduladores, y estudiar algunos de los principales mecanismos implicados en la generación de resistencia adquirida a fármacos inmunomoduladores.[EN] This thesis aims to study comparatively the efficacy and mechanism of action of two immunomodulatory drugs, lenalidomide and pomalidomide, either alone or in combination with dexamethasone in cell lines and cells from patients with multiple myeloma. In addition to analyzing the possible potentiation of these immunomodulatory drugs with other drugs, both classic and new employees in multiple myeloma. It also aims to develop a model "in vivo" immunomodulatory drug resistance acquired with a dual purpose: to investigate the characteristics of acquired resistance to immunomodulatory drugs, and study some of the major mechanisms involved in the generation of acquired resistance to immunomodulatory drugs

Nutrition and muscle recovery

Producción CientíficaExercise-induced muscle damage (EIMD) is characterized by histopathological muscle tissue changes that originate skeletal muscle damage. The destruction of skeletal muscle fibers causes an inflammatory response that decreases the athlete’s physical work capacity and sports performance. Thus, muscle recovery becomes essential and has become a priority for elite athletes in different sports modalities. To achieve optimal muscle recovery, athletes often combine additional recovery strategies (biological, pharmacological, mechanical, and nutritional) in the hope of improving physiological responses and competitive performance. This extra preparation could contribute sensibly and legally to athletes to adequately complement their training to obtain better performance or try “shortcuts” to reach the sport’s elite in less time, with treatments and/or prohibited artificial methods that improve their ability to achieve more extraordinary physical performance. Among the strategies employed, the nutritional plan has a decisive influence on the stimulation of muscle recovery. However, it is necessary to optimize the consumption of adequate amounts of energy, nutrients, and liquids, establishing the correct frequency and associated with the temporality of training and competition. [Texto extraído del artículo de Diego Fernández Lázaro]

Sarcopenia, exercise and quality of life

Producción CientíficaThe loss of strength, power, and muscle mass caused by the progressive deterioration from aging is known as “sarcopenia.” This age-related disease is closely related to the progressive loss of physical and cognitive abilities. The etiology of sarcopenia is multifactorial: hormonal, neurological, muscular, immunological, nutritional, or related to a sedentary lifestyle. These factors cause pathophysiological changes at the neuromuscular and tendon level, increased risk of chronic diseases (diabetes and osteoporosis), suppression of ketogenesis and changes in body temperature. Muscle mass gradually decreases by 3% to 8% every decade from the age of 30 onwards, and is particularly accentuated from 60 ahead. This results in a progressive decline in strength that contributes significantly to disability and loss of independence in the elderly. Therefore, to treat and delay sarcopenia, decisions regarding lifestyle habits must be taken into account. In addition, with the physiological and systemic changes in the body as age advances and accelerates the progression of this syndrome, lifestyle factors are much more controllable, and the inclusion of exercise (both endurance and strength) in a healthy lifestyle is of paramount importance. Therefore, in this Special Issue, “Sarcopenia, Exercise and Quality of Life” we focus on the current state of knowledge on the links between sarcopenia, exercise, and quality of life. [Texto extraído del artículo de Diego Fernández Lázaro]

New trends in biological aids to recovery after exercise: Immunomodulators

The professional sport increases the physical and biochemical demands of muscle that is accompanied by important metabolic changes, such as the accumulation of toxic compounds, increased consumption of nutrients, and alterations in the physical, thermal and mechanical conditions of the cells. Neuroendocrine adaptations to the demands of elite athletic activity also modify local and systemic immune function, which contributes to the development and continuation of the inflammatory response. During intensive training and competition days, the recovery needs are also impressive. In such circumstances, athletes need to ingest often supplements as protein, micronutrients, minerals or substances to improve the muscular recovery In our experience, many specific products as the immunomodulators are directly linked to benefits, such as improved performance and concentration, reduced fatigue, better recovery and improved health or resistance against minor infections, which seem to occur more often when athletes are undergoing very intensive training. The purpose of this review is to provide an update on published research focusing primarily on the efficacy of immunomodulation substances in the recovery of athletes with respect to physical performance

Effect of Iron Supplementation on the Modulation of Iron Metabolism, Muscle Damage Biomarkers and Cortisol in Professional Cyclists

Background: The intense efforts made during 3-week stage races may reduce iron metabolism and hematological parameters. These efforts may increase the levels of circulating muscle damage markers and some hormones. All of these physiological changes may have negative consequences not only for the performance of athletes but also for their health. The main aim of this study was to evaluate the effects of supplementation with 80 mg/day of iron on haematological parameters, serum cortisol and biochemical muscle indicators on elite male cyclists during the 3-week stage race the Vuelta a España. Our secondary aim was to examine whether the hematological profile is associated with muscular damage parameters and cortisol. Methods: Eighteen elite male cyclists from two teams were randomly assigned to one of two groups: (1) control group (CG, n = 9; age: 26.1 ± 4.6 years; maximum oxygen uptake per kg: 78.0 ± 5.4 mL/kg/min) or (2) group treated with 80 mg/day iron (800 mg of iron protein succinylate, ITG, n = 9; age: 25.7 ± 6.4 years; maximum oxygen uptake per kg: 77.6 ± 6.5 mL/kg/min). The cyclists were subjected to blood tests one week before the start of the race (T1) and after 4 weeks of treatment, coinciding with the end of the competition (T2). Iron metabolism parameters, muscle damage indicators and serum cortisol were assessed. Repeated-measures ANOVA with group as a factor (GC and ITG) were used to examine the differences between groups throughout the study (time × group) after iron supplementation treatment. Results: Significant differences were observed between groups throughout the study in the group-by-time interaction and changes in serum iron (GC: -8.93 ± 10.35% vs. ITG: 0.60 ± 8.64%; p = 0.018), ferritin (GC: -13.88 ± 23.53% vs. ITG: 91.08 ± 118.30%; p = 0.004), haemoglobin (GC: 10.00 ± 3.32% vs. ITG: 13.04 ± 5.64%; p < 0.001), haematocrit (GC: -1.17 ± 3.78% vs. ITG: 7.32 ± 3.92%; p < 0.001) and cortisol (GC: 24.74 ± 25.84% vs. ITG: ⁻13.54 ± 13.61%; p = 0.005). However, no significant group-by-time interaction was observed for the circulating muscle biomarkers. Additionally, significant negative correlations of serum iron, haemoglobin and haematocrit with muscle circulating biomarkers and cortisol (p < 0.05) were observed. Conclusions: Oral iron supplementation with 80 mg/day iron (800 mg of iron protein succinylate) effectively prevented a decline in haematological parameters (serum iron, ferritin, haemoglobin and haematocrit) and maintained optimal levels of recovery in elite cyclists during the Vuelta a España. Moreover, the hematological values were shown to have relationship with muscular recovery parameters

Iron and physical activity: Bioavailability enhancers, properties of black pepper (Bioperine®) and potential applications

Producción CientíficaBlack pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia. Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals

The role of selenium mineral trace element in exercise: antioxidant defense system, muscle performance, hormone response, and athletic performance. A systematic review

Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body’s antioxidant capacity to neutralize them. The ROS produce damaging effects on the cell membrane and contribute to skeletal muscle damage. Selenium (Se), a natural mineral trace element, is an essential component of selenoproteins that plays an important role in antioxidant defense. The activity of the enzyme glutathione peroxidase (GPx), a highly-efficient antioxidant enzyme, is closely dependent on the presence of Se. These properties of Se may be potentially applicable to improve athletic performance and training recovery. We systematically searched for published studies to evaluate the effectiveness of Se supplementation on antioxidant defense system, muscle performance, hormone response, and athletic performance among physically active individuals. We used the Preferred Reporting Elements for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched in SCOPUS, Web of Science (WOS), and PubMed databases to identify published studies until March 2020. The systematic review incorporated original studies with randomized controlled crossover or parallel design in which intake of Se administered once a day was compared with the same placebo conditions. No exclusions were applied for the type of physical exercise performed, the sex, nor the age of the participants. Among 150 articles identified in the search, 6 met the criteria and were included in the systematic review. The methodological quality of the studies was evaluated using the McMaster Critical Review Form. Oral Se supplementation with 180 µg/day or 240 µg/day (selenomethionine) and 200 µg/day (Sodium Selenite), significantly decreased lipid hydroperoxide levels and increased GPx in plasma, erythrocyte, and muscle. No significant effects were observed on athletic performance, testosterone hormone levels, creatine kinase activity, and exercise training-induced adaptations on oxidative enzyme activities or on muscle fiber type myosin heavy chain expression. In addition, Se supplementation showed to have a dampening effect on the mitochondria changes in chronic and acute exercise. In summary, the use of Se supplementation has no benefits on aerobic or anaerobic athletic performance but it may prevent Se deficiencies among athletes with high-intensity and high-volume training. Optimal Se plasma levels may be important to minimize chronic exercise-induced oxidative effects and modulate the exercise effect on mitochondrial changes

Impact of oats on appetite hormones and body weight management: A Review

Producción CientíficaPurpose of Review: This study aims to review the hunger hormones in obesity management and the impact of oats in regulating these hormones for hunger suppression and body weight management. In this review, the impact of various edible forms of oats like whole, naked, sprouted, or supplemented has been investigated for their appetite hormones regulation and weight management. Recent Findings: The onset of obesity has been greatly associated with the appetite-regulating hormones that control, regulate, and suppress hunger, satiety, or energy expenditure. Many observational and clinical studies prove that oats have a positive effect on anthropometric measures like BMI, waist circumference, waist-to-hip ratio, lipid profile, total cholesterol, weight, appetite, and blood pressure. Many studies support the concept that oats are rich in protein, fiber, healthy fats, Fe, Zn, Mg, Mn, free phenolics, ß-glucan, ferulic acid, avenanthramides, and many more. Beta-glucan is the most important bioactive component that lowers cholesterol levels and supports the defense system of the body to prevent infections. Hence, several clinical studies supported oats utilization against obesity, appetite hormones, and energy regulation but still, some studies have shown no or little significance on appetite. Summary: Results of various studies revealed the therapeutic potentials of oats for body weight management, appetite con- trol, strengthening the immune system, lowering serum cholesterol, and gut microbiota promotion by increased production of short-chain fatty acids.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Electromyography: a simple and accessible tool to assess physical performance and health during hypoxia training. A systematic review

Hypoxia causes reduced partial pressure of oxygen in arterial blood and induces adaptations in skeletal muscle that may affect individuals’ physical performance and muscular health. These muscular changes are detectable and quantifiable by electromyography (EMG), an instrument that assesses electrical activity during active contraction at rest. EMG is a relatively simple and accessible technique for all patients, one that can show the degree of the sensory and motor functions because it provides information about the status of the peripheral nerves and muscles. The main goal of this review is to evaluate the scientific evidence of EMG as an instrument for monitoring different responses of skeletal muscles subjected to external stimuli such as hypoxia and physical activity. A structured search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in Medline/PubMed, Scielo, Google Scholar, Web of Science, and Cochrane Library Plus. The search included articles published in the last 25 years until May 2020 and was restricted to English- and Spanish-language publications. As such, investigators identified nine articles that met the search criteria. The results determined that EMG was able to detect muscle fatigue from changes in the frequency spectrum. When a muscle was fatigued, high frequency components decreased and low frequency components increased. In other studies, EMG determined muscle activation increased during exercise by recruiting motor units and by increasing the intensity of muscle contractions. Finally, it was also possible to calculate the mean quadriceps quadratic activity used to obtain an image of muscle activation. In conclusion, EMG offers a suitable tool for monitoring the different skeletal muscle responses and has sufficient sensitivity to detect hypoxia-induced muscle changes produced by hypoxic stimuli. Moreover, EMG enhances an extension of physical examination and tests motor-system integrity

Effects of Citrulline Supplementation on Different Aerobic Exercise Performance Outcomes: A Systematic Review and Meta-Analysis

Supplementation with Citrulline (Cit) has been shown to have a positive impact on aerobic exercise performance and related outcomes such as lactate, oxygen uptake (VO2) kinetics, and the rate of perceived exertion (RPE), probably due to its relationship to endogenous nitric oxide production. However, current research has shown this to be controversial. The main objective of this systematic review and meta-analysis was to analyze and assess the effects of Cit supplementation on aerobic exercise performance and related outcomes, as well as to show the most suitable doses and timing of ingestion. A structured literature search was carried out by the PRISMA® (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and PICOS guidelines in the following databases: Pubmed/Medline, Scopus, and Web of Science (WOS). A total of 10 studies were included in the analysis, all of which exclusively compared the effects of Cit supplementation with those of a placebo group on aerobic performance, lactate, VO2, and the RPE. Those articles that used other supplements and measured other outcomes were excluded. The meta-analysis was carried out using Hedges’ g random effects model and pooled standardized mean differences (SMD). The results showed no positive effects of Cit supplementation on aerobic performance (pooled SMD = 0.15; 95% CI (−0.02 to 0.32); I2, 0%; p = 0.08), the RPE (pooled SMD = −0.03; 95% CI (−0.43 to 0.38); I2, 49%; p = 0.9), VO2 kinetics (pooled SMD = 0.01; 95% CI (−0.16 to 0.17); I2, 0%; p = 0.94), and lactate (pooled SMD = 0.25; 95% CI (−0.10 to 0.59); I2, 0%; p = 0.16). In conclusion, Cit supplementation did not prove to have any benefits for aerobic exercise performance and related outcomes. Where chronic protocols seemed to show a positive tendency, more studies in the field are needed to better understand the effects