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BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).
Assuntos
Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Deficiência de alfa 1-Antitripsina , Humanos , Masculino , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , Estudos Transversais , Genótipo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/epidemiologia , Enfisema Pulmonar/complicações , Sistema de RegistrosRESUMO
PURPOSE: The ergogenic effect of oral caffeine administration on short-term all-out exercise performance is well established. However, the potential mechanisms associated with caffeine's ergogenicity in this type of exercise are poorly understood. The aim of this study was to investigate whether caffeine intake modifies muscle oxygen saturation during the 15-s Wingate Anaerobic Test. METHODS: Fifteen moderately trained individuals (body mass = 67.4 ± 12.3 kg; height 171.3 ± 6.9 cm; age 31 ± 6 years) took part in two identical experimental trials after the ingestion of (a) 3 mg/kg of caffeine or (b) 3 mg/kg of cellulose (placebo). After 60 min for substances absorption, participants performed a 15-s Wingate test on a cycle ergometer against a load representing 7.5% of participant's body mass. Muscle oxygen saturation was continuously measured during exercise with near-infrared spectroscopy and blood lactate concentration was measured 1 min after exercise. RESULTS: In comparison to the placebo, the oral administration of caffeine increased peak power by 2.9 ± 4.5% (from 9.65 ± 1.38 to. 9.92 ± 1.40 W/kg, P = 0.038; effect size (ES), 95% confidence intervals = 0.28, 0.05-0.51), mean power by 3.5 ± 6.2% (from 8.30 ± 1.08 to 8.57 ± 1.12 W/kg, P = 0.044; ES = 0.36, 0.01-0.71) and blood lactate concentration by 20.9 ± 24.7% (from 12.4 ± 2.6 to 14.8 ± 4.0 mmol/L, P = 0.005; ES = 0.59, 0.16-1.02). However, caffeine did not modify the curve of muscle oxygen desaturation during exercise (lowest value was 23.1 ± 14.1 and 23.4 ± 14.1%, P = 0.940). CONCLUSION: Caffeine's ergogenic effect during short-term all-out exercise seems to be associated with an increased glycolytic metabolism with no influence of enhanced muscle oxygen saturation.
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Cafeína , Substâncias para Melhoria do Desempenho , Adulto , Cafeína/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Humanos , Lactatos/farmacologia , Músculo Esquelético , Saturação de Oxigênio , Substâncias para Melhoria do Desempenho/farmacologiaRESUMO
In the last decade, Acinetobacter baumannii has emerged as a pathogen associated with infections in intensive care units worldwide, especially due to its ability to resist an extensive list of antibiotics. In this context, porphyrins have emerged as an important strategy in photodynamic therapy, since they are a group of tetrapyrrolic compounds with important photochemical and photobiological activities. In this study, the antimicrobial photodynamic activity of meso-tetra(4-N-methyl-pyridyl)porphyrin (H2TMePyP+) and meso-tetra(4-sulfonatophenyl)porphyrin (H2TPPSâ) was evaluated against A. baumannii by minimum inhibitory concentration (MIC), anti-biofilm activity, and the interaction with antibiotics after exposure to white-light LED irradiation. The cationic derivative H2TMePyP+ was more potent (MIC = 0.61 µM) than H2TPPSâ, with anti-biofilm activity and increased the antimicrobial activity of ciprofloxacin and amikacin. Given these findings, the tetra-cationic porphyrins can be assumed as prototypes to optimize and develop new agents by promoting oxidative stress and inducing free radical production.
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Acinetobacter baumannii , Porfirinas , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Cátions/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , ÁguaRESUMO
PURPOSE: Caffeine is widely considered an ergogenic aid to increase anaerobic performance although most of this evidence is supported by investigations with only male samples. To date, it is unknown if the ergogenic effect of caffeine on anaerobic performance is of similar magnitude in men and women athletes. The aim of this study was to determine the magnitude of the ergogenic effect of caffeine on the Wingate test in men and women. METHODS: In a double-blind, placebo-controlled, cross-over experimental trial, ten women athletes and ten men athletes performed a 15-s adapted version of the Wingate test after ingesting 3 mg of caffeine per kg of body mass or a placebo (cellulose). RESULTS: In comparison to the performance obtained in the 15-s Wingate test with a placebo, caffeine increased peak power in men (9.9 ± 0.8 vs. 10.1 ± 0.8 W/kg, p < 0.01, d = 0.26) and in women (8.8 ± 0.9 vs. 9.1 ± 0.8 W/kg, p = 0.04, d = 0.30). Caffeine was also effective to increase the mean power in men (8.9 ± 0.7 vs. 9.0 ± 0.7 W/kg, p = 0.01, d = 0.21) and women (8.1 ± 0.7 vs. 8.3 ± 0.7 W/kg, p = 0.01, d = 0.27). The ergogenic effect of caffeine on the 15-s Wingate peak power (2.3 ± 3.2% in men and 3.2 ± 2.8% in women; p = 0.46) and mean power (2.0 ± 1.7% and 2.4 ± 2.3%, respectively; p = 0.93) was of similar magnitude in both sexes. CONCLUSION: Acute ingestion of 3 mg kg-1 of caffeine enhanced peak and mean cycling power during a 15-s adapted version of the Wingate test in men and women and the ergogenic effect was of similar magnitude in both sexes. This information suggests that both men and women athletes might obtain similar benefits from caffeine supplementation during anaerobic exercise.
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Desempenho Atlético , Substâncias para Melhoria do Desempenho , Anaerobiose , Atletas , Cafeína/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
AIMS: In male athletes, caffeine is considered an ergogenic aid to increase anaerobic performance during the Wingate anaerobic test (WANT). However, information about the effect of caffeine on WANT performance in female athletes is contradictory. Furthermore, it is unknown whether the ergogenicity of caffeine is present during all the phases of the menstrual cycle. The aim of this study was to investigate the effects of caffeine intake on WANT performance during 3 phases of the menstrual cycle. METHODS: Thirteen well-trained eumenorrhoeic triathletes participated in a double-blind, placebo-controlled, cross-over experimental trial. On 2 different days in each phase, and in randomized order, participants ingested caffeine (3 mg kg-1 ) or a placebo (cellulose). The menstrual cycle phases were individually characterized as follows: (i) early follicular; (ii) preovulatory; and (iii) midluteal. In each trial, participants performed a 15-s adapted version of the WANT. RESULTS: In comparison to the placebo, caffeine increased peak power during the WANT in the early follicular (8.6 ± 0.8 vs 8.9 ± 0.9 W/kg, P = .04; effect size [d] = 0.45), preovulatory (8.6 ± 0.9 vs 8.9 ± 0.9 W/kg, P = .04; d = 0.23) and mid-luteal phases (8.6 ± 0.8 vs 8.9 ± 0.9 W/kg, P < .01; d = 0.52). CONCLUSION: The ergogenic effect of caffeine on WANT peak cycling power was of a similar magnitude in the follicular, preovulatory, and mid-luteal phases. These results suggest that caffeine increases performance in the 15-s Wingate test in women athletes and it might be considered an ergogenic aid to increase anaerobic performance in eumenorrhoeic women during their menstrual cycle.
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Cafeína , Substâncias para Melhoria do Desempenho , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Ciclo MenstrualRESUMO
AIMS: The main mechanism behind caffeine's ergogenicity lies in its tendency to bind to adenosine receptors, although other mechanisms might be involved. The aim of this investigation was to analyse the effects of caffeine on muscle oxygen saturation during exercise of increasing intensity. METHODS: Thirteen healthy and active individuals volunteered to participate in a randomized, double blind, placebo-controlled crossover trial. During 2 different trials, participants either ingested a placebo (cellulose) or 3 mg/kg of caffeine. After waiting for 60 min to absorb the substances, participants underwent a maximal ramp cycle ergometer test (25 W/min). Near infrared spectrometers were positioned on each leg's vastus lateralis to monitor tissue O2 saturation. Blood lactate concentration was measured 1 min after the end of the exercise test. RESULTS: In comparison to the placebo, the ingestion of caffeine improved the maximal wattage (258 ± 50 vs 271 ± 54 W, respectively, P < .001, effect size [ES] = 0.27; 95% confidence interval [CI] 0.14-0.35) and blood lactate concentration (11.9 ± 3.8 vs 13.7 ± 3.5 mmol/L, P = .029, ES = 0.38; 95% CI 0.14-0.75) at the end of the test. Caffeine increased muscle oxygen saturation at several exercise workloads with a main effect found in respect to the placebo (F = 6.28, P = .029; ES = 0.30 to 0.54; 95% CI 0.01-0.78). Peak pulmonary ventilation (124 ± 29 vs 129 ± 23 L/min, P = 0.035, ES = 0.25; 95% CI 0.07-0.40) and peak oxygen uptake (3.18 ± 0.70 vs 3.33 ± 0.88 L/min, P = 0.032, ES = 0.26; 95% CI 0.08-0.51) were also increased with caffeine. CONCLUSION: Acute ingestion of 3 mg/kg of caffeine improved peak aerobic performance and increased peak pulmonary ventilation. In addition, caffeine induced changes in muscle oxygen saturation during submaximal workloads, suggesting that this mechanism might also contribute to caffeine's ergogenic effect.
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Cafeína , Teste de Esforço , Oxigênio , Adulto , Ciclismo , Cafeína/farmacologia , Método Duplo-Cego , Ingestão de Alimentos , Feminino , Humanos , Músculo Esquelético/fisiologia , Oxigênio/metabolismoRESUMO
PURPOSE: Recent investigations have established that the ingestion of a moderate dose of caffeine (3-6 mg kg-1) can increase exercise and sports performance in women. However, it is unknown whether the ergogenicity of caffeine is similar during all phases of the menstrual cycle. The aim of this investigation was to determine the ergogenic effects of caffeine in three phases of the menstrual cycle. METHODS: Thirteen well-trained eumenorrheic triathletes (age = 31 ± 6 years; body mass = 58.6 ± 7.8 kg) participated in a double-blind, cross-over, randomised experimental trial. In the (1) early follicular (EF); (2) preovulation (PO); (3) and mid luteal (ML) phases, participants either ingested a placebo (cellulose) or 3 mg kg-1 of caffeine in an opaque and unidentifiable capsule. After a 60-min wait for substance absorption, participants performed an incremental maximal cycle ergometer test until volitional fatigue (25 W/min) to assess peak aerobic cycling power (Wmax). RESULTS: In comparison to the placebo, caffeine increased Wmax in the EF (4.13 ± 0.69 vs. 4.24 ± 0.71 W kg-1, Δ = 2.7 ± 3.3%, P = 0.01), in the PO (4.14 ± 0.70 vs. 4.27 ± 0.73 W kg-1, Δ = 3.3 ± 5.0%; P = 0.03) and in the ML (4.15 ± 0.69 vs. 4.29 ± 0.67 W kg-1, Δ = 3.6 ± 5.1%; P = 0.01) phases. The magnitude of the caffeine ergogenic effect was similar during all of the menstrual cycle phases (P = 0.85). CONCLUSION: Caffeine increased peak aerobic cycling power in the early follicular, preovulatory, and mid luteal phases. Thus, the ingestion of 3 mg of caffeine per kg of body mass might be considered an ergogenic aid for eumenorrheic women during all three phases of the menstrual cycle.
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Desempenho Atlético/fisiologia , Cafeína/farmacologia , Exercício Físico/fisiologia , Ciclo Menstrual/fisiologia , Substâncias para Melhoria do Desempenho/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , HumanosRESUMO
PURPOSE: This study aimed to identify and describe the time course of tolerance to the most common caffeine-induced side effects. METHODS: Eleven participants took part in a crossover, double-blind placebo-controlled experimental design. In one phase, participants ingested 3 mg/kg/day of caffeine for 20 days, while in another phase, they ingested a placebo. Resting heart rate and blood pressure were measured three times per week during each 20-day phase and a quantitative survey was used to categorise the magnitude of side effects. RESULTS: In the pairwise comparison with the placebo, the ingestion of caffeine increased systolic (+ 7.8 ± 10.1%, P < 0.05) and diastolic blood pressure (+ 6.4 ± 12.9% P < 0.05) for the first 8 days of ingestion, but then this effect became attenuated for both outcomes (on day 20, - 1.1 ± 4.3% and + 0.9 ± 9.6%, respectively). The ingestion of caffeine did not affect heart rate at any time point. Caffeine increased the feelings of nervousness and vigour and the rating of gastrointestinal complaints, insomnia and diuresis at several time points in the treatment (P < 0.05) and they did not disappear after 20 days of ingestion. CONCLUSIONS: The daily intake of 3 mg/kg of caffeine induced a meaningful elevation in arterial blood pressure that disappeared after 8 days. However, other caffeine-induced effects such as increased nervousness and vigour, irritability, insomnia and diuresis remained after 20 days of consecutive caffeine ingestion. Although there was clear tolerance to the effect of caffeine on blood pressure, the persistence of other side effects suggests the inconvenience of maintaining a chronic caffeine intake, at least at the dose of 3 mg/kg/day.
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Cafeína/administração & dosagem , Cafeína/efeitos adversos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Fatores de TempoRESUMO
Del Coso, J, Salinero, JJ, Lara, B, Gallo-Salazar, C, Areces, F, Herrero, D, and Puente, C. Polygenic profile and exercise-induced muscle damage by a competitive half-ironman. J Strength Cond Res 34(5): 1400-1408, 2020-To date, it is still unknown why some individuals develop higher levels of muscle damage than other individuals, despite participating in exercise with comparable levels of physical intensity. The aim of this investigation was to analyze 7 single-nucleotide polymorphisms (SNPs) that are candidates to explain individual variations in the level of muscle damage attained during a half-ironman competition. Using the model of Williams and Folland (2, 1, and 0 points for optimal, intermediate, and suboptimal genotype), we determined the total genotype score from the accumulated combination of 7 SNPs (ACE = 287bp Ins/Del; ACTN3 = p.R577X; creatine kinase, muscle type = NcoI; insulin-like growth factor 2 = C13790G; interleukin-6 = 174G>C; myosin light chain kinase = C37885A; and tumor necrosis factor-α = 308G>A) in 22 experienced triathletes. Before and after the race, a sample of venous blood was obtained to measure serum markers of muscle damage. Two groups of triathletes were established according to their postcompetition serum CK concentration: low CK responders (n = 10; 377 ± 86 U·L) vs. high CK responders (n = 12; 709 ± 136 U·L). At the end of the race, low CK responders had lower serum myoglobin concentrations (384 ± 243 vs. 597 ± 293 ng·ml, p = 0.04). Although the groups were similar in age, anthropometric characteristics, and training habits, total genotype score was higher in low CK responders than in high CK responders (7.7 ± 1.1 vs. 5.5 ± 1.1 point, p < 0.01). A favorable polygenic profile can contribute to reducing the level of muscle damage developed during endurance exercise.
Assuntos
Creatina Quinase/sangue , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Actinina/sangue , Actinina/genética , Adulto , Biomarcadores , Pesos e Medidas Corporais , Feminino , Genótipo , Humanos , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like II/genética , Interleucina-6/sangue , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Mioglobina/sangue , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto JovemRESUMO
Fungal pathogens produce toxins that are important for their pathogenesis and/or aggressiveness towards their hosts. Picolinic acid (PA), a non-host selective toxin, causes lesions on rice leaves resembling those originated from Pyricularia oryzae infection. Considering that non-host selective toxins can be useful for plant diseases control, this study investigated whether the foliar spray with PA on wheat (Triticum aestivum L.) plants, in a non-phytotoxic concentration, could increase their resistance to blast, stimulate the anti-oxidative metabolism, and minimize alterations in photosynthesis. The PA spray at concentrations greater than 0.1 mg ml-1 caused foliar lesions, compromised the photosynthesis and was linked with greater accumulation of hydrogen peroxide (H2 O2 ) and superoxide anion radical (O2 â¢- ). Fungal mycelial growth, conidia production and germination decreased by PA at 0.3 mg ml-1 . Blast severity was significantly reduced by 59 and 23%, respectively, at 72 and 96 h after inoculation for plants sprayed with PA (0.1 mg ml-1 ) at 24 h before fungal inoculation compared to non-sprayed plants. Reduction on blast symptoms was linked with increases on ascorbate peroxidase (EC 1.11.1.11), catalase (EC 1.11.1.6), glutathione peroxidase (EC 1.11.1.9), glutathione reductase (EC 1.8.1.7), glutathione-S-transferase (EC 2.5.1.18), peroxidase (EC 1.11.1.7), and superoxide dismutase (EC 1.15.1.1) activities, lower H2 O2 and O2 â¢- accumulation, reduced malondialdehyde production as well as less impairments to the photosynthetic apparatus. A more efficient antioxidative metabolism that rapidly scavenges the reactive oxygen species generated during P. oryzae infection, without dramatically decreasing the photosynthetic performance, was a remarkable effect obtained with PA spray.
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Antioxidantes/metabolismo , Ascomicetos/patogenicidade , Fotossíntese , Ácidos Picolínicos/farmacologia , Triticum/efeitos dos fármacos , Estresse Oxidativo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Triticum/microbiologiaRESUMO
OBJECTIVE: Assess the association between social and economic conditions and homicide rates in young people between 10 and 24 years of age in Mexico in 2017. METHODS: This ecological study looked at the social inequalities associated with homicides in the population 10-24-year-old population in 2017 in Mexico, using secondary data sources for deaths by homicide in each Mexican state. Social inequalities in health were studied by measuring absolute and relative inequality gaps. Mortality rates were estimated using Poisson regression models. RESULTS: In 2017, there were 8,094 homicides in the target population, predominantly in men (86.7%). There was high variance in inequality between states. Unemployment in the population over 12 years of age, households composed of people who are not family members, low school attendance rates, and income below the poverty line showed significant association with homicide rates. CONCLUSIONS: There is a strong association between social determinants and homicides in the study population. Policies and intersectoral actions should be implemented to help bridge inequality gaps and achieve better living conditions and higher levels of well-being and health for people and their communities.
OBJETIVO: Descrever a associação entre as condições socioeconômicas e as taxas de homicídios em jovens entre 10 e 24 anos no México em 2017. MÉTODOS: Neste estudo ecológico foram examinadas as desigualdades sociais associadas aos homicídios na população entre 10 e 24 anos no México em 2017 com base em dados obtidos de fontes de informação secundárias relativos a mortes por homicídio por entidade federativa. As desigualdades sociais em saúde foram avaliadas com a mensuração absoluta e relativa das lacunas de desigualdade. As razões de prevalências de mortalidade foram estimadas com modelos de regressão de Poisson. RESULTADOS: Em 2017, houve 8.094 homicídios na população jovem, com predomínio no sexo masculino (86,7%). As lacunas de desigualdade entre os estados foram significativas. Ociosidade juvenil (em maiores de 12 anos), domicílios constituídos por pessoas sem laços de parentesco, baixa frequência escolar e renda abaixo da linha do bem-estar foram fatores que tiveram uma associação significativa com as taxas de homicídios. CONCLUSÕES: Observou-se uma forte associação entre os determinantes sociais e os homicídios na população estudada. Políticas e ações intersetoriais devem ser implementadas para ajudar a reduzir as lacunas de desigualdade e melhorar as condições de vida, o nível de bem-estar e a saúde das pessoas e suas comunidades.
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The standardization and unification of the procedures to analyze and quantify the airborne pollen concentrations are very important topics. In this work, the effectiveness of the two most used adhesives in aerobiological sampling, silicone prepared with cyclohexane solvent (Silicone) and petroleum jelly (Vaseline), was compared under outdoor conditions. This comparison was carried out using the traditional method based on the identification and quantification by optical microscopy (OM) of the airborne pollen and the novel methodology by high-throughput sequencing analysis (HTS). Globally, the results from both methods of analysis (OM and HTS) showed a good agreement between the two adhesives tested regarding the abundance of the main pollen types present in the samples: Cupressaceae, Olea, Poaceae, Platanus, Quercus. We concluded that the results from both adhesives are comparable data. Furthermore, the comparisons between methodologies, OM vs. HTS, showed that both techniques can accurately identify the most abundant pollen types in the atmosphere for the studied periods, with a good agreement of their relative abundances especially when the airborne pollen diversity is low but showing some divergences as the number of pollen types increases.
Assuntos
Adesivos , Sequenciamento de Nucleotídeos em Larga Escala , Monitoramento Ambiental , Microscopia , Pólen , Estações do AnoRESUMO
The aim of this investigation was to perform a systematic review and meta-analysis to determine the efficacy of the acute ingestion of caffeine (from 3 to 6 mg/kg) to increase performance on variables related to team sports. A systematic review was performed in scientific databases from January to April 2018. All studies included had cross-over experimental designs comparing caffeine to an identical placebo condition. A meta-analysis was performed using the random effects model and pooled standardized mean differences (Glass's Δ). Thirty-four studies published between 2001 and 2018 were included in the analysis. The meta-analysis revealed that caffeine increased single (Δ;95% confidence intervals = 0.19;0.14-0.25; p < 0.01) and repeated jump height (0.29;0.16-0.42; p < 0.01), single (0.16;0.02-0.30; p = 0.03) and repeated sprint velocity (0.14;0.03-0.25; p = 0.02), and reduced the time to complete agility tests (0.41;0.04-0.77; p = 0.03). During team sport matches, caffeine increased total running distance (0.41;0.20-0.62; p < 0.01), distance covered at sprint velocity (0.36;0.12-0.59; p < 0.01) and the number of sprints (0.44;0.18-0.69; p < 0.01). The acute ingestion of a moderate dose of caffeine had a small but significant positive effect on several aspects related to physical performance in team sports.
Assuntos
Desempenho Atlético/fisiologia , Cafeína/administração & dosagem , Substâncias para Melhoria do Desempenho/administração & dosagem , Fenômenos Fisiológicos da Nutrição Esportiva/efeitos dos fármacos , Esportes/fisiologia , Humanos , Resistência Física/efeitos dos fármacos , Resistência Física/fisiologiaRESUMO
The SERPINA1 gene is highly polymorphic, with more than 100 variants described in databases. SERPINA1 encodes the alpha-1 antitrypsin (AAT) protein, and severe deficiency of AAT is a major contributor to pulmonary emphysema and liver diseases. In Spanish patients with AAT deficiency, we identified seven new variants of the SERPINA1 gene involving amino acid substitutions in different exons: PiSDonosti (S+Ser14Phe), PiTijarafe (Ile50Asn), PiSevilla (Ala58Asp), PiCadiz (Glu151Lys), PiTarragona (Phe227Cys), PiPuerto Real (Thr249Ala), and PiValencia (Lys328Glu). We examined the characteristics of these variants and the putative association with the disease. Mutant proteins were overexpressed in HEK293T cells, and AAT expression, polymerization, degradation, and secretion, as well as antielastase activity, were analyzed by periodic acid-Schiff staining, Western blotting, pulse-chase, and elastase inhibition assays. When overexpressed, S+S14F, I50N, A58D, F227C, and T249A variants formed intracellular polymers and did not secrete AAT protein. Both the E151K and K328E variants secreted AAT protein and did not form polymers, although K328E showed intracellular retention and reduced antielastase activity. We conclude that deficient variants may be more frequent than previously thought and that their discovery is possible only by the complete sequencing of the gene and subsequent functional characterization. Better knowledge of SERPINA1 variants would improve diagnosis and management of individuals with AAT deficiency.
Assuntos
Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Adulto , Idoso , Feminino , Frequência do Gene , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto , Estabilidade Proteica , Proteólise , alfa 1-Antitripsina/químicaRESUMO
PURPOSE: Alpha-actinin-3, encoded by the ACTN3 gene, is an actin-binding protein with an important role in myofibril contraction and muscle force output. In humans, there is a relatively common deficiency of the α-actinin-3 due to homozygosity in a polymorphism of the ACTN3 gene (R577X, rs1815739), that has been related to decreased resistance to strain during voluntary muscle contractions. The purpose of this study was to investigate the influence of the ACTN3 genotype on the level of exercise-induced muscle damage attained by 23 experienced triathletes during an official half-ironman competition. METHODS: Before and after the race, a sample of venous blood was obtained and jump height was measured during a countermovement jump. The changes in serum creatine kinase (CK-MM isoform) were measured in the blood samples and muscle pain was measured with a visual analogue scale (0-10 cm). Data from RX heterozygotes and XX mutant homozygotes were grouped as X-allele carriers (n = 13) and compared to RR homozygotes (n = 10). RESULTS: Race time was very similar between groups (313 ± 31 vs. 313 ± 25 min; P = 0.45); however, pre-to-post-competition reduction in jump height was greater in X-allele carriers than RR homozygotes (-18.4 ± 11.4 vs. -8.2 ± 6.9%; P = 0.04). At the end of the race, X-allele carriers presented higher serum CK-MM concentrations (682 ± 144 vs. 472 ± 269 U/L; P = 0.03), and there was also a tendency for higher self-reported values of lower limb muscle pain (7.7 ± 1.1 vs. 6.3 ± 2.3 cm; P = 0.06). CONCLUSIONS: X-allele triathletes in the ACTN3 R577X polymorphism presented greater signs of exercise-induced muscle damage during a half-ironman race than RR homozygotes.
Assuntos
Actinina/genética , Exercício Físico , Heterozigoto , Fadiga Muscular/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Exercise-induced muscle damage has been identified as one of the main causes of the progressive decrease in running and muscular performance in marathoners. The aim of this investigation was to determine the influence of the ACTN3 genotype on exercise-induced muscle damage produced during a marathon. METHODS: Seventy-one experienced runners competed in a marathon race. Before and after the race, a sample of venous blood was obtained and maximal voluntary leg muscle power was measured during a countermovement jump. In the blood samples, the ACTN3 genotype (R577X) and the changes in serum creatine kinase and myoglobin concentrations were measured. Data from RX heterozygotes and XX mutant homozygotes were grouped as X allele carriers and compared to RR homozygotes. RESULTS: At the end of the race, X allele carriers presented higher serum myoglobin (774 ± 852 vs 487 ± 367 U L-1; P = 0.02) and creatine kinase concentrations (508 ± 346 vs 359 ± 170 ng mL-1; P = 0.04) than RR homozygotes. Pre-to-post-race maximal voluntary leg muscle power reduction was more pronounced in X allele carriers than RR homozygotes (-34.4 ± 16.1 vs -27.3 ± 15.4%; P = 0.05). X allele carriers self-reported higher levels of lower limb muscle pain (7 ± 2 vs 6 ± 2 cm; P = 0.02) than RR homozygotes at the end of the race. CONCLUSIONS: In comparison to RR homozygotes, X allele carriers for the R577X polymorphism of the ACTN3 gene presented higher values for typical markers of exercise-induced muscle damage during a competitive marathon. Thus, the absence of a functional α-actinin-3 produced by the X allele might induce higher levels of muscle breakdown during prolonged running events.
Assuntos
Actinina/genética , Músculo Esquelético/fisiologia , Mialgia/genética , Polimorfismo de Nucleotídeo Único , Corrida , Adolescente , Adulto , Idoso , Creatina Quinase/sangue , Feminino , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/genética , Músculo Esquelético/metabolismo , Mialgia/sangue , Mioglobina/sangueRESUMO
The aim of this study was to assess different physiological variables before and after a 5-km (women) and 10-km (men) cross-country skiing competition to determine potential mechanisms of fatigue. Fourteen elite-level skiers competed in an official cross-country skiing competition using the classical style (9 men and 5 women). Instantaneous skiing velocity was measured during the race by means of 15-Hz global positioning system devices. Before and after the race, a sample of venous blood was obtained to assess changes in blood lactate and serum electrolyte and myoglobin concentrations. Prerace to postrace changes in blood oxygen saturation, forced vital capacity during a spirometry test, jump height during a countermovement jump, and handgrip force were also measured. Mean race speed was 15.8 ± 2.5 and 15.4 ± 1.5 km·h, whereas mean heart rate was 171 ± 6 and 177 ± 3 b·min for men and women, respectively. There were no significant prerace to postrace changes in jump height, handgrip force, and forced vital capacity in men and women. Blood oxygen saturation was reduced from prerace to postrace in men (95.9 ± 2.1% to 93.1 ± 2.3%, p = 0.02) and women (97.8 ± 1.1% to 92.4 ± 2.1%, p < 0.01), whereas blood lactate concentration increased at the end of the race in men (1.4 ± 0.5 to 4.9 ± 2.1 mmol·L, p < 0.01) and women (1.9 ± 0.1 to 6.9 ± 3.2 mmol·L, p < 0.01). After the race, blood markers of muscle damage were at low concentrations, whereas serum electrolytes remained unchanged. Fatigue in 5- and 10-km cross-country skiing competitions was related to a reduced blood oxygen carrying capacity and presumably increased muscle and blood acidosis, whereas the influence of exercise-induced muscle damage on fatigue was minor.
Assuntos
Atletas , Força Muscular , Esqui/fisiologia , Adolescente , Adulto , Desempenho Atlético , Feminino , Força da Mão , Humanos , Ácido Láctico/sangue , Masculino , Mioglobina/sangue , Oximetria , Troca Gasosa Pulmonar , Equilíbrio Hidroeletrolítico , Adulto JovemRESUMO
PURPOSE: The aim of this investigation was to determine the influence of endurance running on calcaneus bone stiffness in male and female runners. METHODS: A total of 122 marathoners (longer distance runners, men = 101; women = 21) and 81 half-marathon and 10-km runners (shorter distance runners; men = 48; women = 33), competing in an international running event, underwent an ultrasonographic assessment of the right and left calcaneus. Calcaneus bone stiffness was estimated using the measurements of the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Seventy-five age-matched sedentary people served as the control group. RESULTS: Male and female longer distance runners and shorter distance runners presented higher values than sedentary counterparts in SOS (P < 0.05), and calcaneus stiffness (P < 0.05). Although there were no significant differences between longer distance and shorter distance runners in the ultrasonographic variables, longer distance runners presented greater effects size in SOS (1.00 vs. 0.93 males; 1.10 vs. 0.77 females), BUA (0.62 vs. 0.25 males; 0.89 vs. 0.20 females) and calcaneus stiffness (0.88 vs. 0.66 males; 1.20 vs. 0.60 females) than shorter distance endurance runners. CONCLUSION: Calcaneus bone stiffness was higher in all endurance runners compared to a sedentary control population. The volume of ground reaction forces which occur during endurance running might induce the adaptation of the calcaneus bone.