The effects of underfeeding on whole-body carbohydrate partitioning, thermogenesis and uncoupling protein 3 expression in human skeletal muscle

AIM: Underfeeding is known to reduce resting energy expenditure (REE) as an energy-conserving mechanism and may also reduce insulin sensitivity. Uncoupling protein 1 is known to have a significant role in energy expenditure (EE) in small mammals, but the role of UCPs in humans is unclear. UCP3 is primarily expressed in human skeletal muscle, a significant site of whole-body EE in lean individuals and therefore has a potential role in human metabolism. Here, we examine the effects of short-term underfeeding on UCP3 skeletal muscle expression, and on whole-body insulin sensitivity, substrate utilization and thermogenesis. METHODS: Eleven non-obese men [age 22.8 +/- 1.34 years, body mass index 23.4 +/- 0.71 kg/m(2), mean +/- s.e.m.] were fed for two periods of 6 days, an underfeeding diet (UF) (50% predicted requirements for weight maintenance) and an eucaloric diet (EU), with the same macronutrient composition, in random order. Subjects visited the laboratory on four separate occasions, before and after each dietary period. REE, metabolites and muscle biopsies (vastus lateralis) were taken and the thermogenic response to a hyperinsulinaemic euglycaemic clamp was measured over a 2-h period. UCP3 mRNA levels were measured using Taqman. RESULTS: After underfeeding for 6 days, REE fell by 0.43 +/- 0.17 kJ/min (p = 0.032), with weight loss of 2.05 +/- 0.34 kg (p < 0.001). Baseline fasting glucose was significantly lower at 4.26 +/- 0.07 mmol/l (p = 0.005), with a corresponding fall in carbohydrate oxidation (0.08 +/- 0.03 g/min; p = 0.04). Fasting free fatty acids (FFA) increased by 0.13 +/- 0.03 mmol/l (p < 0.001), with an increase in beta-hydroxybutyrate concentrations of 0.41 +/- 0.07 mM (p < 0.001) compared with post-EU. There was no significant change in UCP3 mRNA levels pre- and post-UF [10.4 +/- 6.8 arbitrary units (au); p = 0.16] compared with pre- and post-EU (3.2 +/- 7.3 au; p = 0.67). There was no thermogenic response to the clamp after 6 days of underfeeding and a significant reduction in glucose disposal rates (from 46.35 +/- 2.15 to 39.46 +/- 1.12 micromol/min/kg; p = 0.003). Carbohydrate oxidation rates were lower by 0.08 +/- 0.03 g/min (p = 0.011) compared with pre-UF, with no change in glucose storage rates (28.2 +/- 2.4 micromol/min/kg pre-UF; 27.0 +/- 2.3 micromol/min/kg post-UF; p = 0.7). EU resulted in a mildly underfed state with marginal weight loss (0.55 +/- 0.28 kg; p = 0.08), and fasting FFA increased by 0.13 +/- 0.03 mmol/l (p < 0.001) and beta-hydroxybutyrate concentrations by 0.05 +/- 0.02 mM (p = 0.03) compared with pre-EU. There was no change in glucose disposal or storage rates compared with pre-EU. CONCLUSIONS: Underfeeding for 6 days has no significant effect on UCP3 mRNA expression in skeletal muscle in non-obese men but is associated with changes in carbohydrate fuel partitioning, REE and the thermogenic response to the glucose clamp. Mild underfeeding had no effect on insulin sensitivity, but more severe energy restriction reduced insulin-stimulated glucose oxidation without affecting glucose storage.     

Living in limbo--patients with cystic fibrosis waiting for transplant

Lung transplant for patients with end-stage cystic fibrosis (CF) in the UK is recognized as the only successful treatment for CF patients with advanced lung disease. This study uses an exploratory approach to examine how patients with CF and their carers cope with the rigours of chronic illness and life on a transplant waiting list. Eight patients with CF, four awaiting transplant and four who had been transplanted within the previous 3 years, along with five of their carers, were asked to recount their experiences using a semi-structured interview technique. Four themes emerged from the interview data; displacement, disorder, life in limbo and readjustment to wellness. Support appears to be particularly important to patients and families after false alarms occur, and upon return home after transplant. The small sample size precludes generalization of the results to all patients with CF but gives an in-depth insight into the lived experience of waiting for transplant.     

Male gender influences response to an educational package for delirium prevention among older people: a stratified analysis

BACKGROUND: Increasing evidence is pointing towards the efficacy of intervention programmes in decreasing the incidence of delirium among older people admitted to hospital. We have previously shown that an educational package directed at doctors and nurses significantly decreased the point prevalence of delirium among older people on a general medical ward. It is not yet established whether specific and 'fixed' patients' characteristics influence the rate of response to such an intervention. METHODS: A secondary, exploratory stratified analysis was carried out to determine whether age, sex and presence of dementia might influence the effect of the intervention through a delirium educational package. This information is important in order to increase the effectiveness of preventive measures across various patients' subgroups. RESULTS: Male gender (OR 0.17, 0.05-0.65) significantly (p = 0.030) and positively influence the response to the educational package compared to female gender (OR 1.04, 0.38-2.81). Neither age nor the presence of underlying dementia was associated with a significant influence on the rate of response to the delirium prevention package. CONCLUSION: Staff may be more likely to implement an earlier and more effective intervention for males who are perceived as presenting a higher risk to themselves and others. The results reported highlight the need to increase staff's vigilance to female patients whose prodromal symptoms of delirium may be underemphasised. Understanding different sub-group responses to preventive educational packages for delirium is an important consideration if these are to be applied widely.     

Electromyographic adjustments during continuous and intermittent incremental fatiguing cycling

We studied the sensitivity of electromyographic (EMG) variables to load and muscle fatigue during continuous and intermittent incremental cycling. Fifteen men attended three laboratory sessions. Visit 1: lactate threshold, peak power output, and VO_2max. Visits 2 and 3: Continuous (more fatiguing) and intermittent (less fatiguing) incremental cycling protocols [20%, 40%, 60%, 80% and 100% of peak power output (PPO)]. During both protocols, multichannel EMG signals were recorded from vastus lateralis: muscle fiber conduction velocity (MFCV), instantaneous mean frequency (iMNF), and absolute and normalized root mean square (RMS) were analyzed. MFCV differed between protocols (P < 0.001), and only increased consistently with power output during intermittent cycling. RMS parameters were similar between protocols, and increased linearly with power output. However, only normalized RMS was higher during the more fatiguing 100% PPO stage of the continuous protocol [continuous–intermittent mean difference (95% CI): 45.1 (8.5% to 81.7%)]. On the contrary, iMNF was insensitive to load changes and muscle fatigue (P = 0.14). Despite similar power outputs, continuous and intermittent cycling influenced MFCV and normalized RMS differently. Only normalized RMS was sensitive to both increases in power output (in both protocols) and muscle fatigue, and thus is the most suitable EMG parameter to monitor changes in muscle activation during cycling.     

Reliability of a telephone‐administered cognitive test battery (TACT) between telephone and face‐to‐face administration

We have previously described the development and initial validation of a telephone administered cognitive test battery (TACT). This report investigates the retest reliability of the TACT battery between telephone administration and face‐to‐face administration and measures the concurrent validity of the test components against a standard test of cognitive ability, the WAIS‐R^UK. Data were collected on 27 participants aged 62–63 years. There was a two‐ to 10‐month interval between time 1 (telephone) and time 2 (face‐to‐face) administration. Intra‐class correlation coefficients for telephone versus face‐to‐face administration of the TACT were satisfactory for all component measures except for ‘object rotation’ and WAIS similarities. There was no evidence of systematic cheating on the telephone‐administered test. Tests of concurrent validity showed stronger correlations for the TACT battery components with verbal tests rather than performance tests, as measured by the WAIS‐R^UK. A few administration difficulties are noted and recommendations for change are outlined. The TACT is a convenient assessment tool with potential for measuring cognitive change in epidemiological studies. Copyright © 2001 Whurr Publishers Ltd.     

HEPES inhibits contractile responses of canine basilar artery .

Abstract

N-2-hydroxyethylpiperazine-N’-2-ethanesulphonic acid (HEPES) is a commonly-used buffer. This study determined the effect of HEPES on contractility of the dog basilar artery and tested the hypothesis that HEPES inhibits vasoconstriction ofisolated arterial segments by generating H² O₂ . Rings ofdog basilar artery with or without endothelium were suspended under isometric tension and contracted with Kel, serotonin, or prostaglandin F2α (PGF2α) in bicarbonate or HEPES buffer. Addition of HEPES, 30 mmoll^-1, before or after contraction with Kel, serotonin or PGF2α significantly decreased maximal tension in rings with or without endothelium. Preincubation with HEPES buffer, 10 mmoll^-1, significantly decreased maximal contractions to each agonist in rings with endothelium and to Kel and serotonin in rings without endothelium. HEPES, 30 mmoll^-1 , noncompetitively inhibited concentration-contraction curves to increasing concentrations of each agonist in rings with or without endothelium. Inhibition by HEPES was completely reversible with washing. The inhibitory effects of HEPES on responses to each agonist in rings with endothelium were significantly less in the dark or after coincubation with catalase. Unlike HEPES, effects of H20 2 were endothelium-dependent in that H₂ O₂ caused contractions in rIngs with endothelium and relaxations in rings without endothelium. 5-(N,N’-dimethyO-amiloride and 4,4’diisothiocyanataostilbene- 2,2’-disulfonic acid did not affect contractility in this preparation. These results show that HEPES exerts significant inhibitory effects on arterial smooth muscle contractility. The mechanism does not involve endothelium-dependent relaxation, effects on chloride channels or the sodium-hydrogen exchanger or generation of H₂ O₂ by HEPES in the light. [Neural Res 1997; 19: 527-533]