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1.
Exp Physiol ; 105(4): 622-631, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31977105

RESUMO

What is the central question of this study? Fibroblast growth factor 21 (FGF21) plays important therapeutic roles in metabolic diseases but is associated with bone loss, through insulin-like growth factor binding protein 1 (IGFBP1), in animals. However, the effect of the FGF21-IGFBP1 axis on age-related bone loss has not been explored in humans. What is the main finding and its importance? Using 'genetically linked' parent and child family pairs, we show that the FGF21 concentration, but not the IGFBP1 concentration, is higher in older than in younger adults. Our results suggest that age-associated decline in bone mineral density is associated with FGF21 and increased bone turnover but not likely to involve IGFBP1 in healthy humans. ABSTRACT: Bone fragility increases with age. The fibroblast growth factor 21 (FGF21)-insulin-like growth factor binding protein 1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age-associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21-regulatory axis in bone turnover and the age-related decline in bone mineral density (BMD). Twenty 'genetically linked' family (parent and child) pairs were recruited. Younger adults were 22-39 years old and older adults 60-71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor-κB ligand (RANKL), tartrate-resistant acid phosphatase 5b (TRAP5b) and bone-specific alkaline phosphatase (BAP) were measured. Older adults had 10-18% lower BMD at the hip and spine (P < 0.008) and a twofold higher FGF21 concentration (P < 0.001). The IGFBP1 concentration was similar in younger and older adults (P = 0.961). The RANKL concentration was 44% lower (P = 0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P = 0.01 and P = 0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r = -0.460, P = 0.003), but not with the IGFBP1 concentration (r = -0.144, P = 0.374). The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P > 0.05). In humans, FGF21 might be involved in the age-associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age-associated decline in BMD and in RANKL-associated osteoclast differentiation.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Osteoporose/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligante RANK/metabolismo , Adulto Jovem
2.
Eur J Appl Physiol ; 114(1): 93-103, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24150782

RESUMO

PURPOSE: This study aimed to investigate the effects of multi-strain probiotics supplementation on gastrointestinal permeability, systemic markers of inflammation and running performance when exercising in the heat. METHODS: Ten male runners were randomized to 4 weeks of daily supplementation with a probiotics capsule (45 billion CFU of Lactobacillus, Bifidobacterium and Streptococcus strains) or placebo, separated by a washout period (double-blind, cross-over trial). After each treatment, the runners exercised to fatigue at 80% of their ventilatory threshold at 35 °C and 40% humidity. To assess gastrointestinal permeability, runners ingested lactulose and rhamnose before exercise and post-exercise urine was collected to measure sugar concentrations. Venous blood samples were collected before, immediately after and 1 h after exercise, and core temperature was monitored during exercise. RESULTS: Probiotics supplementation significantly increased run time to fatigue (min:s 37:44 ± 2:42 versus 33:00 ± 2:27; P = 0.03, d = 0.54). Average core temperature during exercise was similar between trials (probiotic 38.1 ± 0.2 °C, placebo 38.1 ± 0.1 °C; P = 0.77, d = 0.13). Serum lipopolysaccharide concentration increased post-exercise (P < 0.001), while there was a moderate to large reduction in pre-exercise (d = 0.70) and post-exercise (d = 1.24) concentration following probiotics supplementation. Plasma concentrations of IL-6, IL-10 and IL-1ra increased after exercise (P < 0.01), but there was no significant difference between trials (P > 0.05). There was a small to moderate reduction (d = 0.35) in urine lactulose:rhamnose and a small reduction (d = 0.25) in symptoms of gastrointestinal discomfort following probiotics supplementation (both P = 0.25). CONCLUSION: Four weeks of supplementation with a multi-strain probiotic increased running time to fatigue in the heat. Further studies are required to elucidate the exact mechanisms for this performance benefit.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Temperatura Alta , Absorção Intestinal/efeitos dos fármacos , Probióticos/farmacologia , Corrida , Adulto , Estudos Cross-Over , Citocinas/sangue , Método Duplo-Cego , Humanos , Inflamação/sangue , Inflamação/prevenção & controle , Masculino , Probióticos/uso terapêutico
3.
Eur J Appl Physiol ; 113(6): 1575-83, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23314685

RESUMO

This study investigated plasma lipopolysaccharides (LPS) concentration and intestinal permeability after 60-min run at 70 % maximum oxygen uptake (VO2max) in hot [33 °C, 50 % relative humidity (rH)] and cool (22 °C, 62 % rH) conditions. Fifteen volunteers gave their informed consent to participate in this study. Their venous blood samples were taken before, after, 2 and 5 h after exercise in each of the conditions. The order of the two environmental conditions in which they exercised in was randomised and counterbalanced. Plasma LPS concentration increased by an average of 54.0 % (95 % confidence interval: 30.7, 75.1 %) after exercising in the hot trial but no significant changes were observed in cool trial, where mean plasma LPS concentration was 12.0 ± 6.4 pg mL(-1) (before), 10.9 ± 5.4 pg mL(-1) (after), 10.7 ± 6.0 pg mL(-1) (2 h after) and 10.6 ± 5.7 pg mL(-1) (5 h after). Median (range) plasma claudin-3 (CLDN3) concentration was significantly higher after exercise (hot: 8.2 [1.0-13.0] ng mL(-1) and cool: 7.6 [0.6-13.4] ng mL(-1)) as compared to before exercise (hot: 6.6 [0.7-11.8] ng mL(-1) and cool: 6.7 [0.8-12.6] ng mL(-1)) (p < 0.05), but there is no significant difference observed between trials (p > 0.05). Changes in intestinal permeability are only affected by exercise while exercise-induced endotoxemia is affected by environmental conditions. This study, thus, highlights that an increase in intestinal permeability is not sufficient to trigger exercise-induced endotoxemia, suggesting that post-LPS translocation events may have a greater impact in its occurrence.


Assuntos
Temperatura Baixa , Endotoxemia/sangue , Exercício Físico , Temperatura Alta , Mucosa Intestinal/metabolismo , Adulto , Estudos de Casos e Controles , Claudina-3/sangue , Feminino , Humanos , Lipopolissacarídeos/sangue , Lipopolissacarídeos/metabolismo , Masculino , Permeabilidade
4.
Front Physiol ; 14: 1227502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492640

RESUMO

The effects of different muscle loading exercise (MLEX) modes and volume on musculoskeletal health is not well-studied in older populations. Aim: Therefore, this study aimed to compare the effects of community-based MLEX modalities and volume on musculoskeletal health in elderly people. Methods: Elderly men (n = 86) and women (n = 170), age 50-82 years old, were assigned to the sedentary (SE, n = 60), muscle strengthening exercise (MSE, n = 71), aerobic exercise (AE, n = 62) and Tai Chi exercise (TCE, n = 63) groups, based on > 2 years of exercise history. Exercise volume was compared between "Minimum" ("Min" < 60 min/week), "Low" (60-120 min/week). "Moderate" (121-239 min/week) and "High" (240-720 min/week) volumes. Results: All three modes of MLEX were associated with lower percentage of body fat (BF%) and higher percentage of lean body mass (LBM%, p = 0.003 main effect of group, and p = 0.002 main effect of volume for both BF% and LBM%), but not with higher bone mineral density (BMD, total body, lumbar spine, total hip and neck of femur), than SE. TCE had a distinct advantage in trunk flexibility (p = 0.007 with MSE, p = 0.02 with AE, and p = 0.01 with SE), and both TCE (p = 0.03) and AE (p = 0.03) performed better than SE in the one-leg stand balance test. Isometric strength and throwing speed and peak power with a 2 kg power ball were higher in the MLEX than SE groups (p = 0.01), in the ranking order of MSE, AE and TCE. However, there was no difference in handgrip strength performance between the MLEX groups, which performed better than the SE participants. Accumulating >120 min/week of MLEX can promote body composition health and muscle functions, but 60 min/week of MSE alone may have equal or better outcomes in these parameters. Conclusion: Community-based MLEX classes may be used to mitigate age-related chronic disease that are associated with body composition and muscular functions.

5.
Appetite ; 59(1): 17-20, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22446724

RESUMO

Body fat fluctuation during varying competing academic demand was examined among female adolescents with high (n=24) or low (n=24) restrained eating behaviours. Body fat, perceived stress, energy intake, and exercise behaviour were measured three times with 10 weeks between consecutive sessions. High restrained eaters' body fat increased during a period when academic demands were high. Significant results were found for exercise behaviours but not for food consumption. Post hoc analyses did not reveal significant results for low restrained eaters. The results lend support to Muraven and Baumeister's limited strength model of self-regulation.


Assuntos
Tecido Adiposo/metabolismo , Comportamento Alimentar , Estresse Psicológico , Povo Asiático , Índice de Massa Corporal , Ingestão de Energia , Metabolismo Energético , Feminino , Humanos , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
6.
Artigo em Inglês | MEDLINE | ID: mdl-35270595

RESUMO

Lactate is a metabolite produced during anaerobic glycolysis for ATP resynthesis, which accumulates during hypoxia and muscle contraction. Tobacco smoking significantly increases blood lactate. Here we conducted a counter-balanced crossover study to examine whether this effect is associated with inhaling nicotine or burned carbon particles. Fifteen male smokers (aged 23 to 26 years) were randomized into 3 inhalation conditions: tobacco smoking, nicotine vaping, and nicotine-free vaping, conducted two days apart. An electronic thermal evaporator (e-cigarette) was used for vaping. We have observed an increased blood lactate (+62%, main effect: p < 0.01) and a decreased blood glucose (−12%, main effect: p < 0.05) during thermal air inhalations regardless of the content delivered. Exercise-induced lactate accumulation and shuttle run performance were similar for the 3 inhalation conditions. Tobacco smoking slightly increased the resting heart rate above the two vaping conditions (p < 0.05), implicating the role of burned carbon particles on sympathetic stimulation, independent of nicotine and thermal air. The exercise response in the heart rate was similar for the 3 conditions. The results of the study suggest that acute hypoxia was induced by breathing thermal air. This may explain the reciprocal increases in lactate and decreases in glucose. The impaired lung function in oxygen delivery of tobacco smoking is unrelated to nicotine.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adulto , Carbono/efeitos adversos , Estudos Cross-Over , Humanos , Hipóxia , Ácido Láctico/sangue , Masculino , Nicotina/efeitos adversos , Nicotiana , Fumar Tabaco/efeitos adversos , Fumar Tabaco/sangue , Vaping/efeitos adversos , Adulto Jovem
7.
Front Neurol ; 12: 789784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966354

RESUMO

We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

8.
J Diabetes Complications ; 35(7): 107930, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33902998

RESUMO

AIM: We studied the association between extracellular volume status and chronic kidney disease (CKD) progression; and the role of extracellular volume excess as a potential mediator in the relationship between matrix metalloproteinases (MMP)-2 and CKD progression in Type 2 diabetes mellitus (T2DM). METHODS: We conducted a prospective cohort study of 1079 T2DM patients. Bioelectrical impedance analysis (BIA) was performed to assess body fluid status. RESULTS: After up to 8.6 years of follow-up, 471 (43.7%) patients experienced CKD progression. In the fully adjusted model, extracellular water (ECW)/ total body water (TBW)ratios 0.39-0.40 and > 0.40 were associated with 45% and 78% higher risk of CKD progression respectively. Patients with an increase in ECW/TBW ratio had 40% higher risk of CKD progression compared to those with no change or reduction of ECW/TBW ratio. Higher ECW/TBW ratio accounted for 17.4% of the relationship between MMP-2 and CKD progression in T2DM (p = 0.026). CONCLUSIONS: Extracellular volume excess was independently associated with CKD progression in T2DM. Higher ECW/TBW ratio mediated the positive association between MMP-2 and CKD progression. Further studies are needed to elucidate the role of extracellular volume excess in deterioration of renal function.


Assuntos
Água Corporal , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Composição Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Impedância Elétrica , Humanos , Metaloproteinase 2 da Matriz , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia
9.
Diabetes Res Clin Pract ; 174: 108777, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33745995

RESUMO

AIMS: We examined the longitudinal relationship between baseline skeletal muscle mass and its change over time with eGFR decline and albuminuria progression among Asians with type 2 diabetes(T2D). METHODS: This was a prospective cohort study of 1272 T2D patients. Skeletal muscle mass was estimated using tetra-polar multi-frequency bio-impedance analysis and Skeletal Muscle Mass Index(SMI) was defined as skeletal muscle mass/weight * 100. RESULTS: After up to 8 years of follow-up, 33.3% of participants had CKD progression and 28.3% albuminuria progression. Every 1-SD above baseline SMI was associated with 18% lower risk of CKD progression[Hazards Ratio(HR)0.82; 95%CI 0.70-0.97; p = 0.018] and 17% lower risk of albuminuria progression [HR 0.83 (95%CI 0.71-0.97; p = 0.017)]. The largest decrease in SMI over time was associated with 67% higher risk of CKD progression, compared to those with the smallest change from baseline SMI tertile 2[HR 1.67 (95%CI 1.10-2.55); p = 0.016]. Pigment epithelium-derived factor(PEDF) and plasma leucine-rich α-2-glycoprotein (LRG1) accounted for 40.1% of the association between SMI and CKD progression. CONCLUSIONS: Low baseline skeletal muscle mass and its reduction over time is associated with increased risk of progression of CKD among Asians with T2D. PEDF and LRG1 mediated the inverse relationship between SMI and CKD progression.


Assuntos
Albuminúria/patologia , Povo Asiático/estatística & dados numéricos , Diabetes Mellitus Tipo 2/complicações , Músculo Esquelético/patologia , Insuficiência Renal Crônica/patologia , Sarcopenia/patologia , Adulto , Albuminúria/etiologia , Albuminúria/metabolismo , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Sarcopenia/etiologia , Sarcopenia/metabolismo
10.
J Nephrol ; 34(5): 1429-1444, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33492590

RESUMO

BACKGROUND AND AIMS: Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. METHODS: This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15 ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90 ml/min/1.73 m2; stage 2, 60-89 ml/min/1.73 m2; stage 3a, 45-59 ml/min/1.73 m2; stage 3b, 30-44 ml/min/1.73 m2; stage 4; 15-29 ml/min/1.73 m2; and stage 5, < 15 ml/min/1.73 m2) with ≥ 25% decrease in eGFR from baseline. RESULTS: After follow-up of up to 6 years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression. CONCLUSIONS: Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Rigidez Vascular , Pressão Sanguínea , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Estudos Prospectivos , Análise de Onda de Pulso , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia
11.
J Diabetes ; 13(3): 222-231, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32786001

RESUMO

BACKGROUND: Fluid imbalance is associated with various clinical conditions, but the association between elevated extracellular-water to total-body-water (ECW/TBW) ratio, an indicator of fluid balance, and cognitive impairment is unknown. We aimed to investigate relationship between ECW/TBW ratio and cognitive function in type 2 diabetes mellitus. METHODS: This study was a cross-sectional design, comparing 1233 patients aged 61.4 ± 8.0 years from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) cohort. ECW/TBW was measured using bioelectrical impedance method. Cognitive function was assessed with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine association between ECW/TBW and RBANS scores, adjusting for demographics, education, clinical covariates, and apolipoprotein E allele. RESULTS: In unadjusted analyses, there was an inverse dose-dependent association between ECW/TBW and RBANS total score. The associations persisted in fully adjusted model with ß = -1.18 (95% confidence interval [CI] -2.19 to -0.17; P = 0.022) for slight edema and -2.33 (-3.99 to -0.67; P = 0.006) for edema. Slight edema and edema were significantly associated with reduced cognitive function in delayed memory and attention. There was significant association between edema but not slight edema, with reduced cognitive function in language. Pulse pressure accounted for 16.8% of association between ECW/TBW and RBANS total score. CONCLUSIONS: Our novel finding of an independent association between higher ECW/TBW and poorer cognitive function highlights the potential importance of maintaining body fluid balance in the management of cognitive impairment.


Assuntos
Água Corporal/metabolismo , Cognição/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Espaço Extracelular/metabolismo , Água/metabolismo , Idoso , Pressão Sanguínea , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
12.
Eur J Appl Physiol ; 109(5): 887-98, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20237797

RESUMO

Deep body temperature (T(c)), pacing strategy and fluid balance were investigated during a 21-km road race in a warm and humid environment. Thirty-one males (age 25.3 +/- 3.2 years; maximal oxygen uptake 59.1 +/- 4.2 ml kg(-1) min(-1)) volunteered for this study. Continuous T(c) responses were obtained in 25 runners. Research stations at approximately 3-km intervals permitted accurate assessment of split times and fluid intake. Environmental conditions averaged 26.4 degrees C dry bulb temperature and 81% relative humidity. Peak T(c) was 39.8 +/- 0.5 (38.5-40.7) degrees C with 24 runners achieving T(c) > 39.0 degrees C, 17 runners > or = 39.5 degrees C, and 10 runners > or = 40.0 degrees C. In 12 runners attaining peak T(c) > or = 39.8 degrees C, running speed did not differ significantly when T(c) was below or above this threshold (208 +/- 15 cf. 205 +/- 24 m min(-1); P = 0.532). Running velocity was the main significant predictor variable of T(c) at 21 km (R(2) = 0.42, P < 0.001) and was the main discriminating variable between hyperthermic (T(c) > or = 39.8 degrees C) and normothermic runners (T(c) < 39.8 degrees C) up to 11.8 km. A reverse J-shaped pacing profile characterised by a marked reduction in running speed after 6.9 km and evidence of an end-spurt in 16 runners was observed. Variables relating to fluid balance were not associated with any T(c) parameters or pacing. We conclude that hyperthermia, defined by a deep body temperature greater than 39.5 degrees C, is common in trained individuals undertaking outdoor distance running in environmental heat, without evidence of fatigue or heat illness.


Assuntos
Regulação da Temperatura Corporal/fisiologia , Temperatura Alta , Umidade , Corrida/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Adulto , Metabolismo Basal/fisiologia , Temperatura Corporal/fisiologia , Fadiga/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Fatores de Tempo
13.
Biopharm Drug Dispos ; 31(5-6): 316-30, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20578210

RESUMO

The objective was to develop a population pharmacokinetic-pharmacodynamic model of caffeine's psychomotor effects in healthy, non-habitual users of caffeine. Twenty Chinese males each received a single dose of 250 mg of caffeine orally. Plasma concentrations of caffeine were determined at various times within 24 h after dosing. The subjects' psychomotor performance was evaluated before and at various times after dosing by a test battery consisting of oculomotor assessment (saccadic velocity) as well as the computerised Swedish Performance Evaluation System. Nonlinear mixed-effects modelling to analyse the pharmacokinetic-pharmacodynamic relationships was performed using NONMEM. Model robustness was assessed by a nonparametric bootstrap. The results showed that caffeine caused significant improvements in psychomotor functioning. The time course of these effects was best described by pharmacokinetic/pharmacodynamic models involving an effect compartment. The transfer half-lives between plasma and effect site for different domains of psychomotor functioning were in the range 24.8-49.5 min. Evaluation of the final models showed close agreement between pairs of bootstrapped and final model parameter estimates (all differences<10%). These results provided the first suggestive evidence that caffeine effects on psychomotor performance occur after some time delay relative to changes in plasma caffeine concentration. The models for the neurobehavioural tests provided similar transfer half-lives between plasma and effect site.


Assuntos
Cafeína/sangue , Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Adulto , Povo Asiático/psicologia , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Humanos , Masculino , Dinâmica não Linear , Fatores de Tempo
14.
Artigo em Inglês | MEDLINE | ID: mdl-33114437

RESUMO

The international community has recognized global warming as an impending catastrophe that poses significant threat to life on earth. In response, the signatories of the Paris Agreement (2015) have committed to limit the increase in global mean temperature to < 1.5 °C from pre-industry period, which is defined as 1950-1890. Considering that the protection of human life is a central focus in the Paris Agreement, the naturally endowed properties of the human body to protect itself from environmental extremes should form the core of an integrated and multifaceted solution against global warming. Scholars believe that heat and thermoregulation played important roles in the evolution of life and continue to be a central mechanism that allows humans to explore, labor and live in extreme conditions. However, the international effort against global warming has focused primarily on protecting the environment and on the reduction of greenhouse gases by changing human behavior, industrial practices and government policies, with limited consideration given to the nature and design of the human thermoregulatory system. Global warming is projected to challenge the limits of human thermoregulation, which can be enhanced by complementing innate human thermo-plasticity with the appropriate behavioral changes and technological innovations. Therefore, the primary aim of this review is to discuss the fundamental concepts and physiology of human thermoregulation as the underlying bases for human adaptation to global warming. Potential strategies to extend human tolerance against environmental heat through behavioral adaptations and technological innovations will also be discussed. An important behavioral adaptation postulated by this review is that sleep/wake cycles would gravitate towards a sub-nocturnal pattern, especially for outdoor activities, to avoid the heat in the day. Technologically, the current concept of air conditioning the space in the room would likely steer towards the concept of targeted body surface cooling. The current review was conducted using materials that were derived from PubMed search engine and the personal library of the author. The PubMed search was conducted using combinations of keywords that are related to the theme and topics in the respective sections of the review. The final set of articles selected were considered "state of the art," based on their contributions to the strength of scientific evidence and novelty in the domain knowledge on human thermoregulation and global warming.


Assuntos
Aquecimento Global , Temperatura Alta , Adaptação Fisiológica , Regulação da Temperatura Corporal , Humanos , Paris
15.
Antioxidants (Basel) ; 9(3)2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156043

RESUMO

Fibroblast growth factor 21 (FGF21) and adiponectin increase the expression of genes involved in antioxidant pathways, but their roles in mediating oxidative stress and arterial stiffness with ageing and habitual exercise remain unknown. We explored the role of the FGF21-adiponectin axis in mediating oxidative stress and arterial stiffness with ageing and habitual exercise. Eighty age- and sex-matched healthy individuals were assigned to younger sedentary or active (18-36 years old, n = 20 each) and older sedentary or active (45-80 years old, n = 20 each) groups. Arterial stiffness was measured indirectly using pulse wave velocity (PWV). Fasted plasma concentrations of FGF21, adiponectin and oxidized low-density lipoprotein (oxLDL) were measured. PWV was 0.2-fold higher and oxLDL concentration was 25.6% higher (both p < 0.001) in older than younger adults, despite no difference in FGF21 concentration (p = 0.097) between age groups. PWV (p = 0.09) and oxLDL concentration (p = 0.275) did not differ between activity groups but FGF21 concentration was 9% lower in active than sedentary individuals (p = 0.011). Adiponectin concentration did not differ by age (p = 0.642) or exercise habits (p = 0.821). In conclusion, age, but not habitual exercise, was associated with higher oxidative stress and arterial stiffness. FGF21 and adiponectin did not differ between younger and older adults, meaning that it is unlikely that they mediate oxidative stress and arterial stiffness in healthy adults.

16.
Med Sci Sports Exerc ; 52(2): 370-380, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490857

RESUMO

INTRODUCTION: Aging increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 (FGF21)-adiponectin axis helps regulate glucose metabolism. However, the role of FGF21 in mediating glucose metabolism with aging and exercise remains unknown. PURPOSE: This study examined whether FGF21 responses to a glucose challenge are associated with habitual exercise, aging and glucose regulation. METHODS: Eighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 yr, n = 20 each group) and older sedentary and active (≥45 yr, n = 20 each group) groups. Fasted and postprandial blood glucose concentration and plasma concentration of insulin, FGF21, and adiponectin were determined during an oral glucose tolerance test (OGTT). RESULTS: During the OGTT, glucose concentrations were 9% higher (P = 0.008) and FGF21 concentrations were 58% higher (P = 0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower FGF21 concentration than sedentary participants, independent of age (all P < 0.001). Adiponectin concentration during the OGTT did not differ by age (P = 0.448) or activity status (P = 0.611). Within the younger group, postprandial glucose, insulin and FGF21 concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only postprandial insulin and FGF21 concentrations were lower in active participants. CONCLUSIONS: FGF21, but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.


Assuntos
Envelhecimento/metabolismo , Glicemia/metabolismo , Exercício Físico/fisiologia , Fatores de Crescimento de Fibroblastos/sangue , Adiponectina/sangue , Adulto , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
J Diabetes Complications ; 34(12): 107724, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32900592

RESUMO

AIM: To examine correlation between vascular measures and cognitive performance in type 2 diabetes (T2D). METHODS: This was a cross-sectional study on patients (N = 1167) aged ≥45 years attending Diabetes Centre in a tertiary hospital and primary care polyclinic. The following vascular measures were measured: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), pulse wave velocity (PWV) and augmentation index (AI). Cognition was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine relationships between vascular measures and cognition, adjusting for demographics, education, depression, clinical covariates and presence of APOE Ɛ4 allele. RESULTS: In unadjusted analyses, all the vascular measures, except for MAP, were associated with RBANS total score. In fully adjusted analyses, the association with RBANS total score persisted for peripheral PP, aortic PP and aortic DBP with ßs -0.05 (95%CI -0.07 to -0.02; p = 0.001), -0.04 (95%CI -0.06 to -0.01; p = 0.002) and 0.05 (95%CI 0.00 to 0.09; p = 0.033). Association between peripheral and aortic PP and RBANS total score was unaffected by age-stratification (age <60 and ≥60 years). In contrast, significant association between aortic DBP and RBANS total score was only observed for those ≥60 years. Peripheral and aortic PP (which estimate pulsatility) are negatively associated with attention, visuospatial/constructional and language ability. CONCLUSIONS: Peripheral and aortic PP, and aortic DBP were independently correlated with cognitive performance globally and in multiple domains. Further research should be conducted to establish the clinical relevance and importance.


Assuntos
Pressão Sanguínea , Cognição , Diabetes Mellitus Tipo 2 , Análise de Onda de Pulso , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Humanos , Pessoa de Meia-Idade
18.
Sci Rep ; 10(1): 2956, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076075

RESUMO

Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted a cross-sectional study on 1,235 people (mean age 61.4 ± 8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b = -2.62 (-3.92 to -1.32)) and tertile 2 LESM (b = -1.73 (-2.73 to -0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b = -3.75 (-5.98 to -1.52)) and tertile 2 (b = -1.98 (-3.69 to -0.27)) with immediate memory, and for tertile 1 (b = -3.05 (-4.86 to -1.24)) and tertile 2 (b = -1.87 (-3.25 to -0.48)) with delayed memory, and for tertile 1 (b = -2.99 (-5.30 to -0.68)) with visuospatial/constructional ability. Tertile 1 SMI (b = -1.94 (-3.79 to -0.08) and tertile 2 SMI (b = -1.75 (-3.14 to -0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction.


Assuntos
Disfunção Cognitiva/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Extremidade Inferior/fisiologia , Músculo Esquelético/fisiopatologia , Sarcopenia/epidemiologia , Idoso , Composição Corporal/fisiologia , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/fisiopatologia , Singapura/epidemiologia
19.
Proteome Sci ; 7: 1, 2009 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-19126242

RESUMO

BACKGROUND: Heat stress (HS) and related illnesses are a major concern in military, sports, and fire brigadiers. HS results in physiologic responses of increased temperature, heart rate and sweating. In heat stroke, inflammatory response plays an important role and it is evidenced that turpentine (T) induced circulating inflammatory cytokines reduced survival rate and duration at 42 degrees C. Here we report the alteration in the protein expression in liver cells upon HS with and without T treatment using two dimensional gel electrophoresis (2-DE), tryptic in-gel digestion and MALDI-TOF-MS/MS approaches. RESULTS: The effects of HS and T treatments alone and a combined treatments (T+HS) was performed in Wistar rat models. Proteomic analysis of liver in the HS and T+HS groups were analyzed compared to liver profiles of resting control and T treated groups. The study revealed a total of 25 and 29 differentially expressed proteins in the HS and T+HS groups respectively compared to resting control group. Fourteen proteins showed altered expression upon T treatment compared to resting control group. Proteins that are involved in metabolic and signal transduction pathways, defense, redox regulation, and cytoskeletal restructuring functions were identified. The altered expression of proteins reflected in 2D gels were corroborated by quantitative real time RT-PCR analysis of 8 protein coding genes representing metabolic and regulatory pathways for their expression and normalized with the house keeping gene beta-actin. CONCLUSION: The present study has identified a number of differentially expressed proteins in the liver cells of rats subjected to T, HS and T+HS treatments. Most of these proteins are implicated in cell metabolism, as well as adaptive response to incurred oxidative stress and tissue damage due to T+HS and HS effects.

20.
PLoS One ; 14(11): e0225636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31770392

RESUMO

OBJECTIVE: To investigate age-associated changes in airway microbiome composition and their relationships with lung function and arterial stiffness among genetically matched young and elderly pairs. METHODS: Twenty-four genetically linked family pairs comprised of younger (≤40 years) and older (≥60 years) healthy participants were recruited (Total n = 48). Lung function and arterial stiffness (carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx)) were assessed. Sputum samples were collected for targeted 16S rRNA gene amplicon sequencing and correlations between microbiome composition, lung function and arterial stiffness were investigated. RESULTS: Elderly participants exhibited reductions in lung function (FEV1 (p<0.001), FVC (p<0.001) and percentage FEV1/FVC (p = 0.003)) and a 1.3-3.9-fold increase in arterial stiffness (p<0.001) relative to genetically related younger adults. Elderly adults had a higher relative abundance of Firmicutes (p = 0.035) and lower relative abundance of Proteobacteria (p = 0.014), including specific genera Haemophilus (p = 0.024) and Lautropia (p = 0.020) which were enriched in the younger adults. Alpha diversity was comparable between young and elderly pairs (p>0.05) but was inversely associated with lung function (FEV1%Predicted and FVC %Predicted) in the young (p = 0.006 and p = 0.003) though not the elderly (p = 0.481 and p = 0.696). Conversely, alpha diversity was negatively associated with PWV in the elderly (p = 0.01) but not the young (p = 0.569). Specifically, phylum Firmicutes including the genus Gemella were correlated with lung function (FVC %Predicted) in the young group (p = 0.047 and p = 0.040), while Fusobacteria and Leptotrichia were associated with arterial stiffness (PWV) in the elderly (both p = 0.004). CONCLUSION: Ageing is associated with increased Firmicutes and decreased Proteobacteria representation in the airway microbiome among a healthy Asian cohort. The diversity and composition of the airway microbiome is independently associated with lung function and arterial stiffness in the young and elderly groups respectively. This suggests differential microbial associations with these phenotypes at specific stages of life with potential prognostic implications.


Assuntos
Pulmão/fisiologia , Microbiota , Rigidez Vascular/fisiologia , Adulto , Fatores Etários , Idoso , Família , Firmicutes/genética , Firmicutes/isolamento & purificação , Haemophilus/genética , Haemophilus/isolamento & purificação , Voluntários Saudáveis , Humanos , Leptotrichia/genética , Leptotrichia/isolamento & purificação , Pessoa de Meia-Idade , Análise de Onda de Pulso , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Testes de Função Respiratória , Escarro/microbiologia , Adulto Jovem
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