Potential for using simulated altitude as a means of prehabilitation: a physiology study.

The current pandemic of surgical complications necessitates urgent and pragmatic innovation to reduce postoperative morbidity and mortality, which are associated with poor pre-operative fitness and anaemia. Exercise prehabilitation is a compelling strategy, but it has proven difficult to establish that it improves outcomes either in isolation or as part of a multimodal approach. Simulated altitude exposure improves performance in athletes and offers a novel potential means of improving cardiorespiratory and metabolic fitness and alleviating anaemia within the prehabilitation window. We aimed to provide an initial physiological foundation for 'altitude prehabilitation' by determining the physiological effects of one week of simulated altitude (FI O2 15%, equivalent to approximately 2438 m (8000 ft)) in older sedentary volunteers. The study used a randomised, double-blind, sham-controlled crossover design. Eight participants spent counterbalanced normoxic and hypoxic weeks in a residential hypoxia facility and underwent repeated cardiopulmonary exercise tests. Mean (SD) age of participants was 64 (7) y and they were unfit, with mean (SD) baseline anaerobic threshold 12 (2) ml.kg-1 .min-1 and mean (SD) peak V̇O2 15 (3) ml.kg-1 .min-1 . Hypoxia was mild (mean (SD) Sp O2 93 (2) %, p < 0.001) and well-tolerated. Despite some indication of greater peak exercise capacity following hypoxia, overall there was no effect of simulated altitude on anaerobic threshold or peak V̇O2 . However, hypoxia induced a substantial increase in mean (SD) haemoglobin of 1.5 (2.7) g.dl-1 (13% increase, p = 0.028). This study has established the concept and feasibility of 'altitude prehabilitation' and demonstrated specific potential for improving haematological fitness. Physiologically, there is value in exploring a possible role for simulated altitude in pre-operative optimisation.

The body composition phenotype of Irish adults aged 18-81 years.

BACKGROUND: Regional distribution of adiposity and lean tissue mass are predictors of health risk that cannot be defined by body mass index but can be attained by dual-energy X-ray absorptiometry (DXA). Age and sex-related adult ranges of whole-body and regional adiposity and lean tissue are not available for Irish men and women. AIMS: The aim of this study was to construct a DXA-based body composition profile of Irish adults, focusing on age- and sex-related difference in total and regional adiposity and lean tissue mass. METHODS: The study population comprised a convenience sample of 1606 participants, aged 18-81 years participating in the University of Limerick Body Composition study. Data were analysed to construct stature-normalised indices of body fat mass (BFMI), site-specific visceral adiposity, lean tissue mass (LTMI) and appendicular lean tissue mass (ALTMI). RESULTS: Compared to the young adult (18-29 years), BFMI was higher in women (p < 0.001) but plateaued in men aged >50 years. For men, age-related difference in LTMI was not evident but ALTMI was significantly lower in those >50 years. For women, there was evidence of significantly lower LTMI with advancing age and, similar to men, significantly lower ALTMI in those >50 years. CONCLUSIONS: These data provide an insight into the age-related anthropometric phenotype of Irish adults. Centile data have been constructed that provide informative data of the age and sex-specific range of adiposity and lean tissue mass. These data may assist in identification of those at risk of aberrant, body composition-related disease.

In vitro bioactive properties of intact and enzymatically hydrolysed whey protein: targeting the enteroinsular axis.

Enzymatically hydrolysed milk proteins have a variety of biofunctional effects some of which may be beneficial in the management of type 2 diabetes mellitus. The purpose of this study was to evaluate the effect of commercially available intact and hydrolysed whey protein ingredients (DH 32, DH 45) on markers of the enteroinsular axis (glucagon like peptide-1 secretion, dipeptidyl peptidase IV inhibition, insulin secretion and antioxidant activity) before and after simulated gastrointestinal digestion (SGID). A whey protein hydrolysate, DH32, significantly enhanced (P < 0.05) insulin secretion from BRIN BD11 ß-cells compared to the positive control (16.7 mM glucose and 10 mM Ala). The whey protein hydrolysates inhibited dipeptidyl peptidase IV activity, yielding half maximal inhibitory concentration values (IC50) of 1.5 ± 0.1 and 1.1 ± 0.1 mg mL(-1) for the DH 32 and DH 45, samples respectively, and were significantly more potent than the intact whey (P < 0.05). Enzymatic hydrolysis of whey protein significantly enhanced (P < 0.05) its antioxidant activity compared to intact whey, as measured by the oxygen radical absorbance capacity assay (ORAC). This antioxidant activity was maintained (DH 32, P > 0.05) or enhanced (DH 45, P < 0.05) following SGID. Intact whey stimulated GLP-1 secretion from enteroendocrine cells compared to vehicle control (P < 0.05). This data confirm that whey proteins and peptides can act through multiple targets within the enteroinsular axis and as such may have glucoregulatory potential.

Predictors of the physical impact of Multiple Sclerosis following community-based, exercise trial.

BACKGROUND: Studies evaluating exercise interventions in people with multiple sclerosis (PwMS) demonstrate small to medium positive effects and large variability on a number of outcome measures. No study to date has tried to explain this variability. OBJECTIVE: This paper presents a novel exploration of data examining the predictors of outcome for PwMS with minimal gait impairment following a randomised, controlled trial evaluating community-based exercise interventions (N = 242). METHODS: The primary variable was the physical component of the Multiple Sclerosis Impact Scale-29, version 2 (MSIS-29, v2) after a 10-week, controlled intervention period. Predictors were identified a priori and were measured at baseline. Multiple linear regression was conducted. RESULTS: Four models are presented lower MSIS-29, v2 scores after the intervention period were best predicted by a lower baseline MSIS-29,v2, a lower baseline Modified Fatigue Impact Score (physical subscale), randomisation to an exercise intervention, a longer baseline walking distance measured by the Six Minute Walk Test and female gender. This model explained 57.4% of the variance (F (5, 211) = 59.24, p < 0.01). CONCLUSION: These results suggest that fatigue and walking distance at baseline contribute significantly to predicting MSIS-29, v29 (physical component) after intervention, and thus should be the focus of intervention and assessment. Exercise is an important contributor to minimising the physical impact of MS, and gender-specific interventions may be warranted.

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing and it is estimated that by 2030 approximately 366 million people will be diagnosed with this condition. The use of dipeptidyl peptidase IV (DPP-IV) inhibitors is an emerging strategy for the treatment of T2DM. DPP-IV is a ubiquitous aminodipeptidase that cleaves incretins such as glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in a loss in their insulinotropic activity. Synthetic DPP-IV drug inhibitors are being used to increase the half-life of the active GLP-1 and GIP. Dietary intervention is accepted as a key component in the prevention and management of T2DM. Therefore, identification of natural food protein-derived DPP-IV inhibitors is desirable. Peptides with DPP-IV inhibitory activity have been identified in a variety of food proteins. This review aims to provide an overview of food protein hydrolysates as a source of the DPP-IV inhibitory peptides with particular focus on milk proteins. In addition, the proposed modes of inhibition and structure-activity relationship of peptide inhibitors are discussed. Milk proteins and associated peptides also display insulinotropic activity and help regulate blood glucose in healthy and diabetic subjects. Therefore, milk protein derived peptide inhibitors may be a unique multifunctional peptide approach for the management of T2DM.

Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides.

The beneficial effects of food-derived antioxidants in health promotion and disease prevention are being increasingly recognized. Recently, there has been a particular focus on milk-derived peptides; as a source of antioxidants, these peptides are inactive within the sequence of the parent protein but can be released during enzyme hydrolysis. Once released, the peptides have been shown to possess radical scavenging, metal ion chelation properties and the ability to inhibit lipid peroxidation. A variety of methods have been used to evaluate in vitro antioxidant activity, however, there is no standardised methodology, which hinders comparison of data. This review provides an overview on the generation of antioxidative peptides from milk proteins, the proposed mechanisms of protein/peptide induced antioxidant activity, in vitro measurement of antioxidant activity, in vivo evaluation of plasma antioxidant capacity and the bioavailability of antioxidative peptides. The understanding gained from other food proteins is referred to where specific data on milk-derived peptides are limited. The potential applications and health benefits of antioxidant peptides are discussed with a particular focus on the aging population. The regulatory requirements for peptide-based antioxidant functional foods are also considered.

The effect of behavioural risk factors on osteoporosis in Irish women.

BACKGROUND: Osteoporosis constitutes a major public health concern and its underlying pathogenesis is complex and multifactorial. Although hereditary factors strongly contribute to bone health, behavioural factors can modulate the genetically determined pattern of skeletal modelling and remodelling. AIM: The aim of this study was to investigate the effect(s) of behavioural risk factors on osteoporosis in Irish women. METHODS: Pre- and post-menopausal adult women (n = 189; 44 ± 15 years) participated in this cross-sectional study. Demographic, anthropometric and lifestyle data were collected during a single clinic visit. Dietary calcium intake and lifetime physical activity (PA) were assessed for each subject. Lumbar and femoral bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA). Multivariate analysis was used to determine the independent predictors of low BMD. RESULTS: Low BMD was present in 59% of subjects (42% pre- and 77% post-menopausal). Smoking was the strongest behavioural predictor of lumbar and femoral BMD. Age, height, family history, smoking, metabolic (MET) and mechanical (MECH) PA (lifetime) and weight (body mass) accounted for 39% of the variance in lumbar BMD. Age, height, family history, alcohol consumption, MET and MECH PA (lifetime) and weight accounted for 41% of the variance in femoral BMD. CONCLUSIONS: Prevalence of osteopenia and osteoporosis is high in Irish women and is associated with modifiable risk factors. A clearer focus should be paid to educate Irish women on preventative health behaviours for osteoporosis to curb the prevalence of this disease and the human and fiscal costs associated with it.

Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial.

BACKGROUND: While there is an increasing body of evidence supporting the efficacy of exercise in people with multiple sclerosis (MS), additional information on the effectiveness of combining aerobic and resistance training, and yoga is required. OBJECTIVES: This study evaluated the effectiveness of community exercise interventions for people with MS having minimal gait impairment. METHODS: A multi-centred, block-randomised, assessor-blinded, controlled trial was conducted. Participants were randomised in groups of eight to physiotherapist (PT)-led exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86) and they took part in weekly community-based group exercise sessions. Those in the control group were asked not to change of their exercise habits (n = 71). The primary outcome was the Multiple Sclerosis Impact Scale (MSIS) 29v2 physical component, measured before and after the 10-week intervention. Secondary outcomes were the MSIS 29v2 psychological component, the Modified Fatigue Impact Scale (MFIS) and the 6-Minute Walk Test (6MWT). RESULTS: The group x time interaction approached significance for the MSIS-29v2 physical component (f = 2.48, p = 0.061) and MFIS total (f = 2.50, p = 0.06), and it was significant for the MFIS physical subscale (f = 4.23, p = 0.006). All three exercise interventions led to a statistically significant improvement on the MSIS-29 psychological component and both the MFIS total and physical subscales, which were greater than the control (p < 0.05). Only the PT-led and FI-led interventions significantly improved the MSIS-29 physical and 6MWT to levels greater than the control (p < 0.05). CONCLUSIONS: This study provides evidence for the positive effect of exercise on the physical impact of MS and fatigue. The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS.

Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study.

OBJECTIVE: It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS. METHODS: High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space. RESULTS: Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe. CONCLUSION: These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.

Human insulinotropic response to oral ingestion of native and hydrolysed whey protein.

The insulinotropic response to the ingestion of whey protein and whey protein hydrolysate, independent of carbohydrate, is not known. This study examined the effect of protein hydrolysis on the insulinotropic response to the ingestion of whey protein. Sixteen healthy males ingested a 500 mL solution containing either 45 g of whey protein (WPI) or whey protein hydrolysate (WPH). The estimated rate of gastric emptying was not altered by hydrolysis of the protein [18 (3) vs. 23 (3) min, n = 16; P = 0.15]. Maximum plasma insulin concentration (Cmax) occurred later (40 vs. 60 min) and was 28% [234 (26) vs. 299 (31) mM, P = 0.018] greater following ingestion of the WPH compared to the WPI leading to a 43% increase [7.6 (0.9) vs. 10.8 (2.6) nM, P = 0.21] in the AUC of insulin for the WPH. Of the amino acids with known insulinotropic properties only Phe demonstrated a significantly greater maximal concentration [C (max); 65 (2) vs. 72 (3) microM, n = 16; P = 0.01] and increase (+22%) in AUC following ingestion of the WPH. In conclusion, ingestion of whey protein is an effective insulin secretagogue. Hydrolysis of whey protein prior to ingestion augments the maximal insulin concentration by a mechanism that is unrelated to gastric emptying of the peptide solution.

Raman spectroscopy of the human nail: a potential tool for evaluating bone health?

Dual X-ray absorptiometry (DEXA) is the current gold standard for the diagnosis of osteoporosis. However, patients can suffer osteoporotic fractures despite normal bone mineral density, partly because of unmeasured influences of both the protein and mineral phases of bone that are affected in osteoporosis. There is currently no clinically applicable method of evaluating the health of the protein phase. The proteins in human nail (keratin) and bone (collagen) require sulphation and disulphide bond (S-S) formation for structural integrity and disorders of either sulphur metabolism or cystathione beta-synthase can lead to structural abnormalities in these tissues. Raman protein spectra provide a method of non-invasive measurement of the degree of sulphation of structurally related proteins that may be indicative of bone health. Raman spectroscopy was used to evaluate the disulphide (S-S) content of fingernails. The nail samples came from from 169 women (84 pre- and 85 post-menopausal), of which 39 had a history of osteoporotic fracture. BMD was measured by DXA at the spine. Analyses included parametric and non-parametric tests, dependent on the distribution of the test variable. Mean disulphide content of the nail reduced with age and was slightly higher in pre-, compared to post-menopausal women (P = 0.187). Significantly lower disulphide content was observed in nails obtained from subjects with a history of fracture (P = 0.025). When either disulphide content or BMD was used as a predictor, the odds ratio of these two measures were found to be comparable predictors for fracture status. This suggests that measurements of change in the protein phase of structural proteins such as keratin in the human nail may be correlated with clinically relevant changes in bone proteins that are important in fracture risk.

Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique.

IGF-I plays a direct role in whole body glucose homeostasis primarily by stimulating skeletal muscle glucose uptake. IGF-I is also involved in exercise induced muscle hypertrophy. Knowledge regarding local changes in muscle IGF-I bioavailability and its regulation by IGFBPs at rest and during exercise is limited. We have therefore explored changes in total IGF-I levels as well as circulating IGFBP levels and their post-translational modifications over an exercising leg. For the first time we have determined IGF-I levels in exercising skeletal muscle microdialysate in an attempt to assess local IGF-I bioavailability. Eighteen healthy young men performed one legged knee-extension exercise during 45min. Blood samples were taken from the femoral artery and vein of the exercising leg. No significant differences between arterial and venous concentrations of total IGF-I or IGFBP-1 were detected over the leg at any time. IGF-I concentrations increased significantly during exercise in the artery but not in the vein. Total IGFBP-1 increased after exercise in both artery and vein. The increase in non-plus less phosphorylated forms of IGFBP-1 was less pronounced and did not reach statistical significance. The proportion of fragmented IGFBP-3 (IGFBP-3 proteolysis) assessed by Western immunoblotting did not change significantly during or after exercise. Although optimization and validation of IGF-I determinations in muscle microdialysate (md) will be required, our first results using this technique demonstrate a significant 2-fold increase in mdIGF-I collected during and after exercise. We conclude that determination of A-V-differences appears to be of limited value in the assessments of local muscle change in the IGF-system. A substantial release of IGF-I during short time is required to detect significant change in the large circulating store of IGF-I. We suggest that an optimized and validated microdialysis technique for determination of local IGF-I may be advantageous in future studies.

Amino acid metabolism, branched-chain amino acid feeding and brain monoamine function.

Although fatigue during prolonged exercise has traditionally been associated with peripheral factors relating to muscle metabolism, such as the depletion of muscle glycogen, more recent research has generated a renewed interest in amino acid metabolism per se and in the role of amino acids as precursors of brain neurotransmitter function. The concept of a 'central fatigue hypothesis' has done much to stimulate scientists to explore the functional role of the brain and CNS in the aetiology of the fatigue process. The concept has also generated a number of testable hypotheses by which it is possible to examine how the 'central' component of fatigue may act. The present review has attempted to bring together the current research in this area. There is good reason to believe that nutritional intervention may play an important role in relation to fatigue residing within the brain and CNS. Although an exciting possibility exists that nutritional manipulation may affect brain neurochemistry and ultimately sports performance, the experimental evidence to support this claim is, as yet, equivocal. A greater understanding of amino acid metabolism and, in particular, amino acid transport, will greatly improve future experimental designs used to test the efficacy of nutritional manipulation of amino acids and their effect on the central component of the fatigue process.

Is human skeletal muscle capillary supply modelled according to fibre size or fibre type?

Analysis of muscle supply usually relies on estimating either the numerical capillary to fibre ratio or capillary density. Both indices are scale dependent, i.e. they vary with fibre size. We have examined the use of an alternative approach based on the anatomical supply area of individual capillaries, which allows the calculation of a local capillary to fibre ration or density based on area, rather than number of fibres. The results suggest that, in human skeletal muscle, capillary supply is primarily scaled according to fibre size, and is relatively independent of fibre type.

Prevention of disability and rehabilitation--results from a collaborative project in China.

Eight different geographical districts in China varying in urban and rural characteristics from 6 provinces and 2 municipalities were selected as pilot areas of the project. The interventions included early detection and treatment of neuritis, self-care training, adapted footwear, surgery, comprehensive treatment of complicated ulcers, and prostheses. Main changes in eye, hand and foot impairments between baseline assessment and assessment at 2 years have been presented in this paper.

The effect of oral creatine supplementation on the 1000-m performance of competitive rowers.

This study investigated the change in 1000-m simulated rowing performance in two matched groups of 19 competitive rowers following a 5-day period of supplementation with placebo (CON group) or creatine at a dose equivalent to 0.25 g creatine monohydrate per kilogram of body mass (BM) (EXP group). Creatine uptake was calculated from the difference between the amount fed and the amount recovered in urine during each 24-h period of supplementation. Total creatine uptake for the EXP group over the 5-day period of supplementation averaged 34.9 +/- 10.9 g (range 20.1-54.9 g), which equated to 3.54 +/- 0.93 mmol kg BM-1. The estimated creatine uptake into muscle was 38.1 +/- 10.0 (range 22.6-56.6) mmol kg dry weight-1 for these subjects. After supplementation with placebo, the CON group showed no change in 1000-m rowing performance (214.0 +/- 30.9 vs 214.1 +/- 31.5 s; P = 0.88). Of these subjects, 7 decreased and 10 increased their performance times (range - 3.1 to 2.7%). By contrast, 16 of the 19 subjects in the EXP group improved their performance times. The mean improvement in rowing performance for the EXP group was 2.3 s (211.0 +/- 21.5 vs 208.7 +/- 21.8 s; P < 0.001), an overall improvement of just over 1% (range - 0.4 to 3.4%). We conclude that in competitive rowers, a 5-day period of creatine supplementation was effective in raising whole-body creatine stores, the magnitude of which provided a positive, though statistically non-significant (r = 0.426, P = 0.088), relationship with 1000-m rowing performance.

Cellular immune activity in response to increased training of elite oarsmen prior to Olympic competition.

This study investigated the changes in urinary neopterin, a biochemical marker of cellular immune activity, in elite male rowers undertaking a progressive increase in training prior to Olympic competition. Twenty-seven male rowers of the 1992 Great Britain team provided daily urine samples for a 4-week period of training that included 17 days of altitude training and 10 days of heat acclimatization. The mean (+/- S.D.) ratio of neopterin/creatinine in urine increased from pre-training values of 135 +/- 32 to a peak of 219 +/- 121 mumol neopterin per mol creatinine on day 19 of training (P < 0.05). Changes in the ratio of neopterin/creatinine with training were found to be transient and highly variable between subjects, ranging from no change to peak values five-fold greater than baseline. On the basis of the in vivo measurement of cell-mediated immunity employed in this study, we conclude that elite athletes engaged in high-intensity training prior to competition show either no change or a moderate increase in cellular immune activation.

Trends in leprosy in the Kingdom of Bhutan, 1982-1992.

An evaluation programme was undertaken 11 years after the introduction of multidrug therapy (MDT) into Bhutan, by examining the case notes of 3239 leprosy patients who had been under treatment at any time during the period. The registered prevalence was found to have fallen markedly, as expected, and this had been accompanied by a clear fall in the case detection rate as well. The lepromatous rate among new patients rose considerably, giving epidemiological hope that the disease may be coming under control. However, no concomitant fall in the proportion of child cases was seen. The disability rate at detection rose slightly, although numbers were small. New cases were increasingly likely to have more highly positive skin smears, and to be self-reported. Programme planners should give thought to the implications of these findings.

Skeletal muscle buffer value, fibre type distribution and high intensity exercise performance in man.

Interrelationships between quadriceps femoris muscle buffer value (beta), fibre type distribution, and lactate concentration and pH following short-term high intensity exercise were examined in eighteen young healthy human volunteers. Muscle biopsy samples were taken from the lateral portion of the quadriceps femoris muscle at rest and after fatiguing dynamic or isometric exercise. Isometric exercise required the maintenance of 60% quadriceps maximum voluntary contraction, and dynamic exercise, the performance of a modified Wingate Test. The muscle buffer value displayed a positive, but non-significant correlation with the relative area of the muscle occupied by type II fibres (r = 0.42, P = 0.09). An elevated beta was associated with a lesser decrement in muscle pH during intensive exercise but did not permit the accumulation of a higher muscle lactate concentration or allow for an enhanced dynamic or isometric exercise performance. A superior performance during dynamic exercise was associated with a high concentration of muscle lactate and a low muscle pH post-exercise; in turn, each of these factors was positively dependent on the relative area of the muscle occupied by type II fibres. The converse was found for isometric exercise, where there was a tendency for an enhanced performance to be associated with a low muscle lactate and high muscle pH post-exercise. No significant relationship between the relative type II fibre area and isometric performance capacity could be established. It was concluded that the muscle buffer value is not a major limiting factor to the performance of high intensity exercise, suggesting that the involvement of intramuscular acidosis in the development of fatigue may be indirect. The most important determinant of high intensity exercise capacity appears to be the proportional area of the muscle occupied by type II fibres, where a high value provides for a superior dynamic but inferior isometric exercise performance.