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2.
Free Radic Biol Med ; 41(11): 1719-25, 2006 Dec 01.
Article in English | MEDLINE | ID: mdl-17145560

ABSTRACT

Increased amounts of reactive oxygen species (ROS) are generated by skeletal muscle during contractile activity, but their intracellular source is unclear. The oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) was examined as an intracellular probe for reactive oxygen species in skeletal muscle myotubes derived from muscles of wild-type mice and mice that were heterozygous knockout for manganese superoxide dismutase (Sod2(+/-)), homozygous knockout for glutathione peroxidase 1 (GPx1(-/-)), or MnSOD transgenic overexpressors (Sod2-Tg). Myoblasts were stimulated to fuse and loaded with DCFH 5-7 days later. Intracellular DCF epifluorescence was measured and myotubes were electrically stimulated to contract for 15 min. Quiescent myotubes with decreased MnSOD or GPx1 showed a significant increase in the rate of DCFH oxidation whereas those with increased MnSOD did not differ from wild type. Following contractions, myotubes from all groups showed an equivalent increase in DCF fluorescence. Thus the oxidation of DCFH in quiescent skeletal muscle myotubes is influenced by the content of enzymes that regulate mitochondrial superoxide and hydrogen peroxide content. In contrast, the increase in DCFH oxidation following contractions was unaffected by reduced or enhanced MnSOD or absent GPx1, indicating that reactive oxygen species produced by contractions were predominantly generated by nonmitochondrial sources.


Subject(s)
Glutathione Peroxidase/physiology , Muscle Contraction , Muscle, Skeletal/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Superoxide Dismutase/physiology , Animals , Cells, Cultured , Fluoresceins/chemistry , Glutathione Peroxidase/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Fluorescence , Muscle, Skeletal/cytology , Oxidation-Reduction , Oxidative Stress , Superoxide Dismutase/genetics , Glutathione Peroxidase GPX1
3.
Mech Ageing Dev ; 127(11): 830-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16996110

ABSTRACT

This study has characterised the time course of two major transcriptional adaptive responses to exercise (changes in antioxidant defence enzyme activity and heat shock protein (HSP) content) in muscles of adult and old male mice following isometric contractions and has examined the mechanisms involved in the age-related reduction in transcription factor activation. Muscles of B6XSJL mice were subjected to isometric contractions and analysed for antioxidant defence enzyme activities, heat shock protein content and transcription factor DNA binding activity. Data demonstrated a significant increase in superoxide dismutase (SOD) and catalase activity and HSP content of muscles of adult mice following contractile activity which was associated with increased activation of the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and heat shock factor (HSF) following contractions. Significant increases in SOD and catalase activity and heat shock cognate (HSC70) content were seen in quiescent muscles of old mice. The increase in antioxidant defence enzyme activity following contractile activity seen in muscles of adult mice was not seen in muscles of old mice and this was associated with a failure to fully activate NF-kappaB and AP-1 following contractions. In contrast, although the production of HSPs was also reduced in muscles of old mice following contractile activity compared with muscles of adult mice following contractions, this was not due to a gross reduction in the DNA binding activity of HSF.


Subject(s)
Adaptation, Biological/physiology , Aging/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Animals , Catalase/metabolism , Creatine Kinase/metabolism , Enzyme Activation , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , I-kappa B Kinase/metabolism , Male , Mice , Muscle, Skeletal/enzymology , Muscle, Skeletal/metabolism , NF-kappa B/metabolism , Protein Binding , RNA, Messenger/genetics , Superoxide Dismutase/metabolism , Transcription Factor AP-1/metabolism
4.
J Hosp Infect ; 62(3): 304-10, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16406198

ABSTRACT

There are few data measuring rates of contact by healthcare workers (HCWs) with intensive care unit (ICU) patients (direct contacts) and their immediate environment (indirect contacts), or estimates of the time needed for 100% hand hygiene compliance. We measured this using a prospective trained observer study in a 12-bedded UK adult general ICU admitting > 600 mixed medical/surgical patients annually. HCWs were observed in ICU bed spaces for 1-h periods by a single researcher using a pre-determined plan, such that all 12 beds were observed for similar times and throughout the day. Mean daily rates of direct and indirect contact between HCWs and ICU patients were calculated. Observed post-contact hand hygiene compliance was also measured. Numbers of contacts/day that were or were not followed by hand hygiene, and estimates of the time needed daily for 100% compliance were calculated. On average, each patient was contacted directly 159 [95% confidence intervals (CI) 144-178] times and contacted indirectly 191 (95% CI 174-210) times/day. Observed post-contact hand hygiene rates were 43% for direct contacts and 12% for indirect contacts. Staff contacting more than one patient during routine care, who carry the highest risk of transmitting infection between patients, made, on average, 22 direct and 107 indirect contacts without adequate hand hygiene/patient/day. One hundred percent hand hygiene compliance by all healthcare workers would require about 230 min/patient/day (100 min for direct and 130 min for indirect contacts).


Subject(s)
Hand Disinfection , Intensive Care Units , Cross Infection/prevention & control , Hospitals, Teaching , Humans , Intensive Care Units/statistics & numerical data , Personnel, Hospital , Prospective Studies , Time and Motion Studies , United Kingdom
5.
Br J Sports Med ; 39(12): 948-53, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16306505

ABSTRACT

BACKGROUND: Delayed onset muscle soreness (DOMS) occurs after unaccustomed exercise and has been suggested to be attributable to reactive oxygen species (ROS). Previous studies have shown increased ROS after lengthening contractions, attributable to invading phagocytes. Plasma glucose is a vital fuel for phagocytes, therefore carbohydrate (CHO) status before exercise may influence ROS production and DOMS. OBJECTIVE: To examine the effect of pre-exercise CHO status on DOMS, ROS production, and muscle function after contraction induced muscle damage. METHOD: Twelve subjects performed two downhill runs, one after a high CHO diet and one after a low CHO diet. Blood samples were drawn for analysis of malondialdehyde, total glutathione, creatine kinase, non-esterified fatty acids, lactate, glucose, and leucocytes. DOMS and muscle function were assessed daily. RESULTS: The high CHO diet resulted in higher respiratory exchange ratio and lactate concentrations than the low CHO diet before exercise. The low CHO diet resulted in higher non-esterified fatty acid concentrations before exercise. DOMS developed after exercise and remained for up to 96 hours, after both diets. A biphasic response in creatine kinase occurred after both diets at 24 and 96 hours after exercise. Malondialdehyde had increased 72 hours after exercise after both diets, and muscle function was attenuated up to this time. CONCLUSIONS: Downhill running resulted in increased ROS production and ratings of DOMS and secondary increases in muscle damage. CHO status before exercise had no effect.


Subject(s)
Dietary Carbohydrates/administration & dosage , Muscle Contraction/physiology , Muscle, Skeletal/pathology , Reactive Oxygen Species/metabolism , Running/physiology , Adult , Carbohydrate Metabolism/physiology , Creatine Kinase/analysis , Exercise Test/methods , Humans , Leukocyte Count , Male , Muscle, Skeletal/physiopathology , Oxygen Consumption/physiology , Pain/etiology
6.
Br J Anaesth ; 94(4): 445-52, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15708870

ABSTRACT

BACKGROUND: Restrictive transfusion triggers are safe for most critically ill patients, but doubts exist for patients with ischaemic heart disease (IHD). We investigated the prevalence of reported IHD at admission to the intensive care unit (ICU) and investigated how this influenced red cell transfusion triggers. We also compared observed practice with the clinicians' responses to clinical scenarios. METHODS: We studied 1023 sequential ICU admissions over 100 days to 10 Scottish ICUs. Daily haemoglobin, red cell transfusion, and haemorrhage data were available for 99.4% of 5638 ICU patient days. We recorded if IHD was recorded in clinical records at ICU admission. We grouped admissions as having a non-cardiac primary ICU diagnosis and no documentary evidence of IHD (Group 1, n=697), a non-cardiac primary ICU diagnosis with evidence of IHD (Group 2, n=213), or a cardiac primary ICU admission diagnosis (Group 3, n=113). We examined pre-transfusion haemoglobin concentration (Hb) for transfusion episodes not associated with haemorrhage. Clinical transfusion scenarios were sent to intensivists in the ICUs after data collection, which were designed to explore the clinicians' attitude to transfusion triggers in patients with IHD. RESULTS: Previous myocardial infarction was documented in 159 (16%), cardiac failure in 142 (14%), and angina in 167 (16%). Overall, 28.8% of admissions had >/=1 of these documented. The adjusted mean (se) pre-transfusion Hb concentrations varied across the groups. These were 74 (2.2) g litre(-1) in Group 1, 77 (2.3) g litre(-1) in Group 2, and 79 (3.1) g litre(-1) in Group 3 (P=0.003 across the groups). There was concordance between observed practice and responses to the scenario similar to Group 1, but discordance for patients with IHD (Groups 2 and 3). In scenario responses, intensivists stated these patients should have significantly higher transfusion triggers than were actually observed (median [IQR] response for both groups: 90 [80-100] g litre(-1)). CONCLUSIONS: About 29% of patients admitted to Scottish ICUs had documented IHD, which was associated with small adjustments to Hb transfusion triggers. In response to scenarios, clinicians believe that patients with IHD require higher transfusion triggers than are observed in practice.


Subject(s)
Critical Care/statistics & numerical data , Erythrocyte Transfusion/methods , Myocardial Ischemia/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Attitude of Health Personnel , Child , Critical Illness/therapy , Erythrocyte Transfusion/statistics & numerical data , Female , Hemoglobins/analysis , Humans , Male , Medical Audit , Middle Aged , Myocardial Ischemia/blood , Myocardial Ischemia/complications , Patient Admission , Patient Selection , Prevalence , Professional Practice/statistics & numerical data , Scotland/epidemiology , Surveys and Questionnaires
7.
J Physiol ; 561(Pt 1): 233-44, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15331678

ABSTRACT

Adaptations of skeletal muscle following exercise are accompanied by changes in gene expression, which can result in protection against subsequent potentially damaging exercise. One cellular signal activating these adaptations may be an increased production of reactive oxygen and nitrogen species (ROS). The aim of this study was to examine the effect of a short period of non-damaging contractions on the subsequent susceptibility of muscle to contraction-induced damage and to examine the changes in gene expression that occur following the initial contraction protocol. Comparisons with changes in gene expression in cultured myotubes following treatment with a non-damaging concentration of hydrogen peroxide (H(2)O(2)) were used to identify redox-sensitive genes whose expression may be modified by the increased ROS production during contractions. Hindlimb muscles of mice were subjected to a preconditioning, non-damaging isometric contraction protocol in vivo. After 4 or 12 h, extensor digitorum longus (EDL) and soleus muscles were removed and subjected to a (normally) damaging contraction protocol in vitro. Muscles were also analysed for changes in gene expression induced by the preconditioning protocol using cDNA expression techniques. In a parallel study, C(2)C(12) myotubes were treated with a non-damaging concentration (100 microM) of H(2)O(2) and, at 4 and 12 h following treatment, myotubes were treated with a damaging concentration of H(2)O(2) (2 mM). Myotubes were analysed for changes in gene expression at 4 h following treatment with 100 microM H(2)O(2) alone. Data demonstrate that a prior period of non-damaging contractile activity resulted in significant protection of EDL and soleus muscles against a normally damaging contraction protocol 4 h later. This protection was associated with significant changes in gene expression. Prior treatment of myotubes with a non-damaging concentration of H(2)O(2) also resulted in significant protection against a damaging treatment, 4 and 12 h later. Comparison of changes in gene expression in both studies identified haem oxygenase-1 as the sole gene showing increased expression during adaptation in both instances suggesting that activation of this gene results from the increased ROS production during contractile activity and that it may play a role in protection of muscle cells against subsequent exposure to damaging activity.


Subject(s)
Adaptation, Physiological/physiology , Hydrogen Peroxide/pharmacology , Ischemic Preconditioning , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Oxidants/pharmacology , Adaptation, Physiological/drug effects , Age Factors , Animals , Cell Survival/drug effects , Cell Survival/physiology , Creatine Kinase/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/physiology , Heme Oxygenase (Decyclizing)/genetics , Heme Oxygenase-1 , Hyperthermia, Induced , Membrane Proteins , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/cytology , Reactive Oxygen Species/metabolism
8.
Br J Anaesth ; 92(6): 793-9, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15121724

ABSTRACT

BACKGROUND: There is increasing evidence that weaning protocols improve outcome from mechanical ventilation, but it is unclear how best to implement such protocols in large intensive care units. We evaluated a checklist of simple bedside criteria to determine whether it could be used reliably to predict successful discontinuation of mechanical ventilation. METHODS: We carried out a prospective observational cohort study in a 12-bedded general intensive care unit (ICU). We developed a checklist of metabolic, cardiorespiratory and neurological criteria that suggested that patients should start the weaning process. We performed daily assessments throughout ICU stay and recorded whether the criteria were met. Ultimate ventilator independence was used as the reference standard. RESULTS: We studied 325 sequential admissions to the ICU. Data were available for 98% of patients; 97% of admissions were mechanically ventilated on admission to ICU. Overall, 205 of the 308 ventilated patients (67%) achieved ventilator independence during ICU admission; the other patients died or were transferred ventilated to other ICUs. Eighty-three per cent of the patients who achieved ventilator independence met the set criteria. Fulfilling the criteria was a moderately strong predictor of ultimate ventilator independence: specificity 89%, positive predictive value 94%, positive likelihood ratio (LR) 7.6. When we analysed data by the day from admission on which patients were examined, the test was a strong predictor of subsequent ventilator independence when criteria were met by day 1 (LR 11.1) or day 2 (LR 6.9), but weaker when met by more than/equal to 4 days (LR <3). Patients who met criteria after more than/equal to 4 days often had prolonged weaning and a high incidence of re-intubation. Patients who achieved ventilator independence without fulfilling the criteria (n=35) had a short duration of mechanical ventilation (median 2 days, interquartile range 1-3 days). The most frequent reason for failing criteria before ventilator independence was a Pa(O(2))/FI(O(2)) ratio less than 24 kPa (49% of cases). CONCLUSIONS: A simple checklist can assist nurse assessment of suitability for weaning and could be used as a trigger to commence a weaning protocol. The day on which criteria are met is a useful way of stratifying patients for likely patterns of weaning.


Subject(s)
Critical Care/methods , Nursing Assessment/methods , Ventilator Weaning/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Clinical Protocols , Humans , Middle Aged , Monitoring, Physiologic/methods , Patient Selection , Point-of-Care Systems , Predictive Value of Tests , Prospective Studies , Respiration, Artificial , Scotland , Time Factors , Treatment Outcome
9.
Ann N Y Acad Sci ; 1031: 158-68, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15753142

ABSTRACT

There is clear evidence that contracting skeletal muscle generates a complex set of reactive oxygen and nitrogen species and that the pattern and magnitude of this generation is influenced by the type and frequency of the muscle contraction protocol. The functions of these species in exercising organisms are still unclear although data have been presented indicating that they play a role in contraction-induced muscle damage and/or in signaling adaptive responses to contractions. Vitamin E has been claimed to exert a regulatory effect on the actions of contraction-induced oxidants for a considerable time, although evidence for any specific role in this area is lacking. A review of studies in this area suggests that vitamin E supplements are unlikely to reliably reduce the severity of contraction-induced muscle damage but, in contrast, appear capable of modulating redox-regulated adaptive responses to contractions. Full evaluation of the roles of oxidants and antioxidants such as vitamin E in responses of muscle to contractions should enable the manipulation of these processes with potential beneficial effects on maintenance of optimal muscle function.


Subject(s)
Exercise , Oxidative Stress , Vitamin E , Animals , Antioxidants , Gene Expression , Humans , Muscle Contraction/physiology , Muscle, Skeletal/injuries , Muscle, Skeletal/metabolism , Reactive Oxygen Species/metabolism
10.
Carcinogenesis ; 24(5): 919-25, 2003 May.
Article in English | MEDLINE | ID: mdl-12771037

ABSTRACT

Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although omega-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status. In a double-blind randomized study, 42 healthy subjects took 4 g daily of purified omega-3 PUFA, eicosapentaenoic acid (EPA), or monounsaturated, oleic acid (OA), for 3 months. EPA was bioavailable; the skin content at 3 months showing an 8-fold rise from baseline, P < 0.01. No consistent pattern of alteration in basal and UVR-exposed skin content of the antioxidants glutathione, vitamins E and C or lipid peroxidation, was seen on supplementation. Sunburn sensitivity was reduced on EPA, the UVR-induced erythemal threshold rising from a mean of 36 (SD 10) mJ/cm(2) at baseline to 49 (16) mJ/cm(2) after supplementation, P < 0.01. Moreover, UVR-induced skin p53 expression, assessed immunohistochemically at 24 h post-UVR exposure, fell from a mean of 16 (SD 5) positive cells/100 epidermal cells at baseline to 8 (4) after EPA supplementation, P < 0.01. Peripheral blood lymphocytes (PBL) sampled on 3 successive days both pre- and post-supplementation, showed no change with respect to basal DNA single-strand breaks or oxidative base modification (8-oxo-dG). However, when susceptibility of PBL to ex vivo UVR was examined using the comet assay, this revealed a reduction in tail moment from 84.4 (SD 3.4) at baseline to 69.4 (3.1) after EPA, P = 0.03. No significant changes were seen in any of the above parameters following OA supplementation. Reduction in this range of early markers, i.e. sunburn, UVR-induced p53 in skin and strand breaks in PBL, indicate protection by dietary EPA against acute UVR-induced genotoxicity; longer-term supplementation might reduce skin cancer in humans.


Subject(s)
Eicosapentaenoic Acid/pharmacology , Neoplasms, Radiation-Induced/prevention & control , Skin Neoplasms/prevention & control , Skin/radiation effects , Adult , Aged , Ascorbic Acid/metabolism , Biological Availability , DNA/radiation effects , DNA Damage , DNA Repair , Dietary Supplements , Double-Blind Method , Eicosapentaenoic Acid/pharmacokinetics , Female , Genetic Markers , Glutathione/metabolism , Humans , Lipid Peroxidation , Lymphocytes/radiation effects , Male , Middle Aged , Neoplasms, Radiation-Induced/genetics , Oleic Acid/pharmacokinetics , Oleic Acid/pharmacology , Skin/metabolism , Skin Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ultraviolet Rays , Vitamin E/metabolism
11.
Eur J Appl Physiol ; 89(3-4): 393-400, 2003 May.
Article in English | MEDLINE | ID: mdl-12682838

ABSTRACT

The aim of this study was to investigate whether post-exercise vitamin C supplementation influences recovery from an unaccustomed bout of exercise. Sixteen male subjects were allocated to either a placebo (P; n=8) or vitamin C (VC) group ( n=8). Subjects performed a prolonged (90-min) intermittent shuttle-running test, and supplementation began after the cessation of exercise. Immediately after exercise the VC group consumed 200 mg of VC dissolved in a 500 ml drink, whereas the subjects in the P group consumed the drink alone. Later on the same day and then in the morning and evening of the following 2 days, subjects consumed additional identical drinks. Plasma VC concentrations in the VC group increased above those in the P group 1 h after exercise and remained above P values for the 3 days after exercise. Nevertheless, post-exercise VC supplementation was not associated with improved recovery. Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation. Muscle soreness and the recovery of muscle function in the leg flexors and extensors were not different in VC and P groups. Furthermore, although plasma concentrations of interleukin-6 and malondialdehyde increased following exercise, there was no difference between VC and P groups. These results suggest that either free radicals are not involved in delaying the recovery process following a bout of unaccustomed exercise, or that the consumption of VC wholly after exercise is unable to deliver this antioxidant to the appropriate sites with sufficient expediency to improve recovery.


Subject(s)
Ascorbic Acid/administration & dosage , Muscle Fatigue/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Physical Exertion/drug effects , Recovery of Function/drug effects , Running/physiology , Adaptation, Physiological/drug effects , Administration, Oral , Adult , Antioxidants/administration & dosage , Antioxidants/analysis , Ascorbic Acid/blood , Dietary Supplements , Double-Blind Method , Humans , Interleukin-6/blood , Leg/physiopathology , Male , Malondialdehyde/blood , Muscle Contraction/physiology , Muscle, Skeletal/injuries , Pain/physiopathology , Pain/prevention & control
12.
J Physiol ; 549(Pt 2): 645-52, 2003 Jun 01.
Article in English | MEDLINE | ID: mdl-12692182

ABSTRACT

Oxidative stress induces adaptations in the expression of protective enzymes and heat shock proteins (HSPs) in a variety of tissues. We have examined the possibility that supplementation of subjects with the nutritional antioxidant, vitamin C, influences the ability of lymphocytes to express protective enzymes and HSPs following exposure to an exogenous oxidant and the response of skeletal muscle to the physiological oxidative stress that occurs during exercise in vivo. Our hypothesis was that an elevation of tissue vitamin C content would reduce oxidant-induced expression of protective enzymes and HSP content. Lymphocytes from non-supplemented subjects responded to hydrogen peroxide with increased activity of superoxide dismutase (SOD) and catalase, and HSP60 and HSP70 content over 48 h. Vitamin C supplementation at a dose of 500 mg day-1 for 8 weeks was found to increase the serum vitamin C concentration by ~50 %. Lymphocytes from vitamin C-supplemented subjects had increased baseline SOD and catalase activities and an elevated HSP60 content. The SOD and catalase activities and the HSP60 and HSP70 content of lymphocytes from supplemented subjects did not increase significantly in response to hydrogen peroxide. In non-supplemented subjects, a single period of cycle ergometry was found to significantly increase the HSP70 content of the vastus lateralis. Following vitamin C supplementation, the HSP70 content of the muscle was increased at baseline with no further increase following exercise. We conclude that, in vitamin C-supplemented subjects, adaptive responses to oxidants are attenuated, but that this may reflect an increased baseline expression of potential protective systems against oxidative stress (SOD, catalase and HSPs).


Subject(s)
Ascorbic Acid/pharmacology , Catalase/metabolism , Heat-Shock Proteins/metabolism , Lymphocytes/metabolism , Muscle, Skeletal/metabolism , Superoxide Dismutase/metabolism , Adult , Bicycling , Chaperonin 60/metabolism , Dietary Supplements , Exercise/physiology , HSP70 Heat-Shock Proteins/metabolism , Humans , Leg , Male
13.
Vox Sang ; 84(3): 211-8, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12670370

ABSTRACT

BACKGROUND AND OBJECTIVES: The Transfusion Requirements In Critical Care (TRICC) study found that critically ill patients tolerate a restrictive haemoglobin transfusion threshold. We investigated red-cell transfusion practice since publication of the TRICC study in a large Scottish teaching hospital intensive care unit (ICU). MATERIALS AND METHODS: We prospectively collected daily data for a 6-month period on haemoglobin concentrations, red-cell transfusions and indications for transfusions, throughout ICU stay for all patients who stayed for longer than 24 h in the ICU. RESULTS: A total of 176 patients were studied, who utilized 1237 ICU days. Of these 176 patients, 52% received red-cell transfusions. A haemoglobin concentration of < or = 9 g/dl was measured in 55% of patients; this occurred by day 1 and day 2 in 52% and 77% of these cases, respectively. Overall the haemoglobin concentration was < or = 9 g/dl for 45% of all patient days. Total red-cell use was 3.1 units per admission (0.47 units per patient day). Only 18% of transfusion episodes were required as a result of haemorrhage. For 'non-haemorrhage' transfusion episodes, the median pretransfusion haemoglobin concentration was 7.8 g/dl (interquartile range: 7.4-8.4 g/dl), and 64% of transfusion episodes were for 2 units. CONCLUSIONS: Clinicians in our centre were conservative, in keeping with recent transfusion guidelines, but deviated from the TRICC protocol by transfusing at haemoglobin concentrations of between 7 and 9 g/dl, rather than below 7 g/dl, and by prescribing 2 unit transfusions. Significant numbers of red-cell units are still used in the critically ill.


Subject(s)
Erythrocyte Transfusion/statistics & numerical data , Intensive Care Units , Adolescent , Adult , Aged , Aged, 80 and over , Anemia/epidemiology , Anemia/therapy , Cohort Studies , Critical Illness/therapy , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Practice Guidelines as Topic , Prevalence , Prospective Studies , United Kingdom
14.
Biochem Soc Trans ; 31(2): 455-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12653661

ABSTRACT

Skeletal muscle adapts rapidly following exercise by the increased production of heat-shock proteins (HSPs). The aim of this study was to examine the ability of muscle from adult and aged mice to produce HSPs following non-damaging exercise. Adult and aged B6XSJL mice were anaesthetized and their hind limbs were subjected to isometric contractions. At different time points, muscles were analysed for HSP production by Western and Northern blotting and by electrophoretic mobility-shift assay. HSP protein and mRNA levels in muscles from adult mice increased significantly following exercise. This was not evident in muscles of aged mice. In contrast, binding of the transcription factor heat-shock factor 1 (HSF1) was not grossly altered in muscles of aged mice compared with adult mice. The data suggest that the inability of muscles of aged mice to produce HSPs appears to be due to alterations during gene transcription.


Subject(s)
Adaptation, Physiological , Aging , Muscle, Skeletal/physiology , Physical Conditioning, Animal/physiology , Animals , DNA-Binding Proteins/metabolism , Heat Shock Transcription Factors , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Male , Mice , Mice, Inbred Strains , Muscle Contraction , Muscle, Skeletal/chemistry , RNA, Messenger/analysis , Transcription Factors
15.
Free Radic Biol Med ; 33(10): 1355-62, 2002 Nov 15.
Article in English | MEDLINE | ID: mdl-12419467

ABSTRACT

Previous studies of cultured skin cells and murine skin in vivo have indicated that UVR-induced damage involves the generation of reactive oxygen species and depletion of endogenous antioxidant systems. In order to explore the relevance of this to UVR-induced damage to human skin, we have undertaken a detailed examination of the time-course of changes in markers of oxidative stress in human skin following exposure to physiological amounts of UVR in vivo. In addition, we have examined the skin bioavailability of a common nutritional antioxidant, vitamin C, and have assessed the effects of supplementation on markers of oxidative stress. Our hypothesis was that acute exposure of human skin to UVR in vivo would lead to oxidation of cellular biomolecules that could be prevented by prior vitamin C treatment. A UVR-challenge of 120 mJ/cm2 of broadband UVB (peak 310 nm, range 270-400 nm) was applied to buttock skin of 8 healthy volunteers. This caused a rapid and significant rise in activity of skin catalase at 1 h and an increase in the oxidized/total glutathione ratio at 6 h post-UVR. AP-1 DNA binding also peaked at 1-6 h post-UVR, then declined rapidly to baseline levels. No significant changes were seen in skin malonaldehyde content. Oral vitamin C supplements (500 mg/day) were taken by 12 volunteers for 8 weeks resulting in significant rises in plasma and skin vitamin C content. Supplementation had no effect on the UVR-induced erythemal response. The skin malonaldehyde content was reduced by vitamin C supplementation, but surprisingly, reductions in the skin content of total glutathione and protein thiols were also seen. We speculate that this apparently paradoxical effect could be due to regulation of total reductant capacity by skin cells, such that vitamin C may have been replacing other reductants in these cells. No evidence was obtained for an effect of the supplementary vitamin C on the mild oxidative stress seen in human skin following UVR exposure.


Subject(s)
Ascorbic Acid/pharmacology , Dietary Supplements , Oxidative Stress , Skin/metabolism , Ultraviolet Rays , Adult , Ascorbic Acid/metabolism , Biopsy , Catalase/metabolism , DNA/metabolism , Erythema/drug therapy , Fatty Acids/metabolism , Female , Free Radicals , Glutathione/metabolism , Humans , Male , Malondialdehyde/metabolism , Protein Binding , Reactive Oxygen Species , Sulfhydryl Compounds/metabolism , Time Factors , Transcription Factor AP-1/metabolism , Transcription Factors/metabolism , Vitamin E/metabolism
16.
Proc Nutr Soc ; 61(2): 187-9, 2002 May.
Article in English | MEDLINE | ID: mdl-12133200

ABSTRACT

Development of an orally-administered systemic agent that could reduce the effects of u.v. exposure on skin could potentially have a major effect on the incidence of skin cancers and photo-ageing. A number of micronutrients have been suggested to have metabolic properties that could induce this protection, and our data indicate that n-3 polyunsaturated fatty acids are particularly effective in this role. The mechanisms of action of n-3 polyunsaturated fatty acids appear to depend on their anti-inflammatory properties, acting to reduce the u.v.-induced release of cytokines and other mediators from a variety of skin cell types.


Subject(s)
Antioxidants/therapeutic use , Fatty Acids, Omega-3/therapeutic use , Micronutrients/administration & dosage , Skin Neoplasms/prevention & control , Skin/drug effects , Ultraviolet Rays/adverse effects , Aging/radiation effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antioxidants/administration & dosage , Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Humans , Micronutrients/therapeutic use , Skin/radiation effects , Skin Neoplasms/drug therapy , Skin Neoplasms/immunology
17.
Stud Health Technol Inform ; 91: 199-203, 2002.
Article in English | MEDLINE | ID: mdl-15457723

ABSTRACT

Records of Quantec measurements of tlie kypliotic curvature of the back were reviewed for all patients attending the children's orthopaedic clinic who were referred for back shape measurements. Of these, 57 children had five or more preoperative visits allowing trends to be calculated. Linear trends were found in 30 of the patients, with gradients ranging from 1.1 degree/yr to 7.2(0)1/yr. On average, the scatter of measurements about the trend line, or about the mean value in the other 27 cases, compared well with that expected from repeatability studies but the amount of scatter varied from one patient to another. This may well be due to sampling. Where such measurements are monitored for evidence of change in an individual patient, the possibility of larger than average scatter about any emerging trend should be considered.


Subject(s)
Image Processing, Computer-Assisted , Kyphosis/diagnosis , Photogrammetry , Scoliosis/diagnosis , Analysis of Variance , Child , Disease Progression , Female , Follow-Up Studies , Humans , Kyphosis/classification , Kyphosis/surgery , Linear Models , Lumbar Vertebrae/pathology , Lumbar Vertebrae/surgery , Male , Scoliosis/classification , Scoliosis/surgery , Sensitivity and Specificity , Thoracic Vertebrae/pathology , Thoracic Vertebrae/surgery
18.
Acta Paediatr ; 90(8): 950-2, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11529549

ABSTRACT

UNLABELLED: Selenium deficiency is associated with congestive heart failure (CHF) in geographic areas where dietary selenium intake is low and in individuals receiving total parenteral nutrition. Among 66 children with kwashiorkor (including marasmic-kwashiorkor), those who developed CHF had lower serum selenium concentrations than those who did not (32.9 +/- 8.3 vs 41.1 +/- 11.9 microg/L, mean +/- SD, p = 0.03). This association was independent of serum albumin and selenium status was not associated with severity of symptoms, anthropometric indices or HIV infection. CONCLUSION: This association raises the possibility that selenium may contribute to CHF in washiorkor.


Subject(s)
Heart Failure/blood , Kwashiorkor/blood , Selenium/blood , Child , Child, Preschool , Heart Failure/complications , Humans , Kwashiorkor/complications , Selenium/deficiency
19.
Int J Sports Med ; 22(1): 68-75, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11258644

ABSTRACT

Exercise-induced free-radical production may be partly responsible for muscle soreness and damage following demanding exercise. A number of studies have investigated the effect of antioxidant supplementation although there is a paucity of information regarding vitamin C. Therefore the aim of the present study was to investigate the effect of vitamin C supplementation on exercise-induced muscle soreness and damage. Nine habitually active males consumed a 1 g dose of vitamin C 2 h before exercise, and on another occasion consumed an identical placebo. The exercise comprised a 90 min intermittent shuttle-running test, which was designed to simulate the multiple-sprint sports. Vitamin C supplementation increased plasma concentrations of vitamin C before exercise, and plasma concentrations continued to increase during the shuttle-run to reach a peak of approximately 200 micromol x l(-1) immediately after exercise. However, muscle soreness, and markers of both muscle damage (creatine kinase and aspartate aminotransferase) and lipid peroxidation (malondialdehyde) were elevated to an equal extent after exercise in placebo and supplemented trials. Therefore acute supplementation with vitamin C had no beneficial effects although it is possible that such short-term vitamin C supplementation was ineffective because it occurred at an inappropriate time.


Subject(s)
Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Muscle Fatigue/drug effects , Muscle, Skeletal/pathology , Pain/prevention & control , Running/physiology , Administration, Oral , Adult , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Ascorbic Acid/administration & dosage , Ascorbic Acid/pharmacokinetics , Dietary Supplements , Free Radicals , Humans , Male , Muscle Fatigue/physiology , Muscle, Skeletal/drug effects
20.
Int J Sport Nutr Exerc Metab ; 11(4): 466-81, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11915781

ABSTRACT

The aim of the present study was to investigate whether 2 weeks of vitamin C supplementation affects recovery from an unaccustomed bout of exercise. Sixteen male subjects were allocated to either a placebo (P; n = 8) or vitamin C group (VC; n = 8). The VC group consumed 200 mg of ascorbic acid twice a day, whereas the P group consumed identical capsules containing 200 mg of lactose. Subjects performed a prolonged (90-min) intermittent shuttle-running test 14 days after supplementation began. Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation. However, vitamin C supplementation had modest beneficial effects on muscle soreness, muscle function, and plasma concentrations of malondialdehyde. Furthermore, although plasma interleukin-6 increased immediately after exercise in both groups, values in the VC group were lower than in the P group 2 hours after exercise (p < .05). These results suggest that prolonged vitamin C supplementation has some modest beneficial effects on recovery from unaccustomed exercise.


Subject(s)
Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Creatine Kinase/metabolism , Muscle Fatigue/drug effects , Muscle, Skeletal/drug effects , Running/physiology , Administration, Oral , Adult , Antioxidants/pharmacokinetics , Ascorbic Acid/pharmacokinetics , Dietary Supplements , Double-Blind Method , Free Radicals , Humans , Hydrocortisone/blood , Interleukin-6/blood , Male , Malondialdehyde/blood , Muscle Fatigue/physiology , Muscle, Skeletal/injuries , Muscle, Skeletal/physiology , Myoglobin/metabolism , Pain/prevention & control
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