1. Initial glutathione depletion during short-term bed rest : pinpointing synthesis and degradation checkpoints in the γ-glutamyl cycleFilippo Giorgio Di Girolamo, Filippo Mearelli, Mariella Sturma, Nicola Fiotti, Kaja Teraž, Alja Ivetac, Alessio Nunnari, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young male volunteers before and during a 10-day experimental bed rest. Additionally, we tracked changes in glutathione levels and specific metabolite ratios up to 21 days of bed rest. Using gas chromatography-mass spectrometry and the internal standard technique, we observed a 9 ± 9% decrease in glutathione levels during the first 5 days of bed rest, followed by an 11 ± 9% increase from the 5th to the 10th day, nearly returning to baseline ambulatory levels. The cysteinyl-glycine-to-glutathione ratio, reflecting γ-glutamyl cyclotransferase activity (a key enzyme in glutathione breakdown), rose by 14 ± 22% in the first 5 days and then fell by 10 ± 14% over the subsequent 5 days, again approaching baseline levels. Additionally, the γ-glutamyl cysteine-to-cysteine ratio, indicative of γ-glutamyl cysteine synthetase activity (crucial for glutathione synthesis), increased by 12 ± 30% on day 5 and by 29 ± 41% on day 10 of bed rest. The results observed on day 21 of bed rest confirm those seen on day 10. By calculating the ratio of product concentration to precursor concentration, we assessed the efficiency of these key enzymes in glutathione turnover. These results were corroborated by directly measuring glutathione synthesis and degradation rates in vivo using stable isotope techniques. Our findings reveal significant changes in glutathione kinetics during the initial days of bed rest and identify potential therapeutic targets for maintaining glutathione levels.
Ključne besede: antioxidant, muscle unloading, glutathion turnover, γ-glutamyl cycle, gamma-glutamyl cycle
Objavljeno v DiRROS: 21.11.2024; Ogledov: 115; Prenosov: 1101
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2. The abdominal adiposity index (a body shape index) predicts 10-year all-cause mortality in elderly active non-obese subjectsAlessio Nunnari, Filippo Giorgio Di Girolamo, Kaja Teraž, Nicola Fiotti, Boštjan Šimunič, Filippo Mearelli, Rado Pišot, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Background/Objectives: A Body Shape Index (ABSI), which accounts for waist circumference relative to mass and height, shows a robust association with mortality risk. The present study evaluates the effectiveness of ABSI as a predictor of 10-year all-cause mortality in physically active, non-obese elderly individuals. Methods: This prospective cohort study included 159 volunteers (94 women, aged 60–80 years), recruited in the frame of the “Physical Activity and Nutrition for Great Ageing” (PANGeA) Cross-border Cooperation Program Slovenia–Italy 2007–2013, and followed for 10 years. Baseline characteristics included anthropometric measurements, bioelectrical impedance analysis, and cardiovascular fitness tests (VO2max). Statistical analyses (Cox regression, Kaplan–Meier survival) were conducted to examine the relationship between ABSI and mortality. Results: During the 10-year follow-up, 10 deaths (6.7%) were recorded. ABSI (adjusted for age, smoking, comorbidities, and therapy) was an independent predictor of mortality (hazard ratio = 4.65, p < 0.001). Higher ABSI scores were linked to reduced VO2max (r = −0.190, p = 0.017) and increased systolic blood pressure (r = 0.262, p = 0.001). An ABSI-based predictive model showed strong discriminatory power (AUROC = 0.91). Conclusions: ABSI is a reliable predictor of 10-year mortality in active, non-obese elderly individuals and may improve risk stratification in clinical practice.
Ključne besede: ABSI, a body shape index, body shape, fre fat mass, sarcopenia, prognostic index, elderly, mortality
Objavljeno v DiRROS: 16.10.2024; Ogledov: 173; Prenosov: 296
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3. Metabolic consequences of anabolic steroids, insulin, and growth hormone abuse in recreational bodybuilders : implications for the world anti-doping agency passportFilippo Giorgio Di Girolamo, Chiara Biasinutto, Alessandro Mangogna, Nicola Fiotti, Pierandrea Vinci, Rado Pišot, Filippo Mearelli, Boštjan Šimunič, Chiara Roni, Gianni Biolo, 2024, izvirni znanstveni članek Povzetek: Background Hormonal doping in recreational sports is a public-health concern. The World Anti-Doping Agency (WADA) promoted the creation of the Athlete Biological Passport, aiming to monitor athlete’s biological variables over time to facilitate indirect detection of doping. Detection tests for anabolic androgenic steroids (AAS) and growth hormone (GH) are available while insulin abuse cannot be revealed. We have determined in recreational bodybuilders the metabolic effects associated with different patterns of hormone abuse. All analyses were conducted using Statistical Package for Social Sciences (SPSS) 21.0 software (SPSS Chicago, IL). Results We have assessed plasma concentrations of selected metabolic markers and fatty acid content in erythrocyte membranes of 92 male bodybuilders and in 45 healthy controls. Hormonal abuse was identified by anonymous questionnaires. 43% (%) of recruited bodybuilders regularly abused hormones, i.e., anabolic androgenic steroids (95%) often associated with GH (30%) and/or insulin (38%). HDL-cholesterol was lower in insulin and/or GH abusers. Alanine (ALT) and aspartic (AST) transaminases were greater in hormone abusing bodybuilders than in non-doping bodybuilders and controls. Insulin doping was selectively associated with increased plasma ALT-to-AST ratio. In erythrocyte membranes, elongase activity (i.e., stearic-to-palmitic ratio) was lower in insulin and/or growth hormone doping, whereas increased Δ-9 desaturase activity (i.e., palmitoleic-to-palmitic ratio) was selectively associated with insulin doping. Conclusions In conclusion, our study demonstrates that insulin and GH abuse are characterized by multiple alterations of specific metabolic markers. Although further studies are needed to test whether longitudinal monitoring of selected metabolic marker such as muscle contraction time, HDL levels, ALT-AST ratio as well as the activities of selected enzymes (e.g. Δ-9 desaturase and elongase), could contribute to the detection of insulin and GH abuse in sport.
Ključne besede: bodybuilders, doping, drug abuse, matabolism
Objavljeno v DiRROS: 03.04.2024; Ogledov: 556; Prenosov: 217
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4. The aging muscle in experimental bed rest : ǂa ǂsystematic review and meta-analysisFilippo Giorgio Di Girolamo, Nicola Fiotti, Zoran Milanović, Roberta Situlin, Filippo Mearelli, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, Gianni Biolo, 2021, pregledni znanstveni članek Povzetek: Background: Maintaining skeletal muscle mass and function in aging is crucial for preserving the quality of life and health. An experimental bed rest (BR) protocol is a suitable model to explore muscle decline on aging during inactivity. Objective: The purpose of this systematic review and meta-analysis was, therefore, to carry out an up-to-date evaluation of bed rest, with a specific focus on the magnitude of effects on muscle mass, strength, power, and functional capacity changes as well as the mechanisms, molecules, and pathways involved in muscle decay. Design: This was a systematic review and meta-analysis study. Data sources: We used PubMed, Medline; Web of Science, Google Scholar, and the Cochrane library, all of which were searched prior to April 23, 2020. A manual search was performed to cover bed rest experimental protocols using the following key terms, either singly or in combination: %Elderly Bed rest,% %Older Bed rest,% %Old Bed rest,% %Aging Bed rest,% %Aging Bed rest,% %Bed-rest,% and %Bedrest%. Eligibility criteria for selecting studies: The inclusion criteria were divided into four sections: type of study, participants, interventions, and outcome measures. The primary outcome measures were: body mass index, fat mass, fat-free mass, leg lean mass, cross-sectional area, knee extension power, cytokine pattern, IGF signaling biomarkers, FOXO signaling biomarkers, mitochondrial modulation biomarkers, and muscle protein kinetics biomarkers. Results: A total of 25 studies were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. In total, 118 healthy elderly volunteers underwent 5-, 7-, 10-, or 14-days of BR and provided a brief sketch on the possible mechanisms involved. In the very early phase of BR, important changes occurred in the skeletal muscle, with significant loss of performance associated with a lesser grade reduction of the total body and muscle mass. Meta-analysis of the effect of bed rest on total body mass was determined to be small but statistically significant (ES = %0.45, 95% CI: %0.72 to %0.19, P < 0.001). Moderate, statistically significant effects were observed for total lean body mass (ES = %0.67, 95% CI: %0.95 to %0.40, P < 0.001) after bed rest intervention. Overall, total lean body mass was decreased by 1.5 kg, while there was no relationship between bed rest duration and outcomes (Z = 0.423, p = 672). The meta-analyzed effect showed that bed rest produced large, statistically significant, effects (ES = %1.06, 95% CI: %1.37 to %0.75, P < 0.001) in terms of the knee extension power. Knee extension power was decreased by 14.65 N/s. In contrast, to other measures, meta-regression showed a significant relationship between bed rest duration and knee extension power (Z = 4.219, p < 0.001). Moderate, statistically significant, effects were observed after bed rest intervention for leg muscle mass in both old (ES = %0.68, 95% CI: %0.96 to %0.40, P < 0.001) and young (ES = %0.51, 95% CI: %0.80 to %0.22, P < 0.001) adults. However, the magnitude of change was higher in older (MD = %0.86 kg) compared to younger (MD = %0.24 kg) adults. Conclusion: Experimental BR is a suitable model to explore the detrimental effects of inactivity in young adults, old adults, and hospitalized people. Changes in muscle mass and function are the two most investigated variables, and they allow for a consistent trend in the BR-induced changes. Mechanisms underlying the greater loss of muscle mass and function in aging, following inactivity, need to be thoroughly investigated.
Ključne besede: bed rest, aging, muscles, muscle physiopathology, muscle function
Objavljeno v DiRROS: 26.08.2021; Ogledov: 2039; Prenosov: 1273
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5. Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health : physiological and pathophysiological implications and recommendations for physical and nutritional countermeasuresMarco Vicenzo Narici, Giuseppe De Vito, Martino V. Franchi, Antonio Paoli, Tatiana Moro, Giuseppe Marcolin, Bruno Grassi, Giovanni Baldassarre, Lucrezia Zuccarelli, Gianni Biolo, Filippo Giorgio Di Girolamo, Nicola Fiotti, F. Dela, Paul L. Greenhaff, Constantinos Maganaris, 2020, izvirni znanstveni članek Ključne besede: COVID-19, sedentarism, neuromuscular system, cardiovascular system, glucose homeostasis, body composition, nutrition, exercise
Objavljeno v DiRROS: 18.12.2020; Ogledov: 1817; Prenosov: 427
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