Reduced cerebral oxygen–carbohydrate index during endotracheal intubation in vascular surgical patients

Brain activation reduces balance between cerebral consumption of oxygen versus carbohydrate as expressed by the so‐called cerebral oxygen‐carbohydrate‐index (OCI). We evaluated whether preparation for surgery, anaesthesia including tracheal intubation and surgery affect OCI. In patients undergoing aortic surgery, arterial to internal jugular venous (a‐v) concentration differences for oxygen versus lactate and glucose were determined from before anaesthesia to when the patient left the recovery room. Intravenous anaesthesia was supplemented with thoracic epidural anaesthesia for open aortic surgery (n = 5) and infiltration with bupivacaine for endovascular procedures (n = 14). The a‐v difference for O₂ decreased throughout anaesthesia and in the recovery room (1·6 ± 1·9 versus 3·2 ± 0·8 mmol l^?1, mean ± SD), and while a‐v glucose decreased during surgery and into the recovery (0·4 ± 0·2 versus 0·7 ± 0·2 mmol l^?1, P<0·05), a‐v lactate did not change significantly (0·03 ± 0·16 versus ?0·03 ± 0·09 mmol l^?1). Thus, OCI decreased from 5·2 ± 1·8 before induction of anaesthesia to 3·2 ± 1·0 following tracheal intubation (P<0·05) because of the decrease in a‐v O₂ with a recovery for OCI to 4·6 ± 1·4 during surgery and to 5·6 ± 1·7 in the recovery room. In conclusion, preparation for surgery and tracheal intubation decrease OCI that recovers during surgery under the influence of sensory blockade.     

Positive effect of exercise training at maximal fat oxidation intensity on body composition and lipid metabolism in overweight middle‐aged women

The purpose of this study was to test the hypothesis that 10 weeks of supervised exercise training at the maximal fat oxidation (FATmax) intensity would improve important variables of body composition and lipid metabolism in overweight middle‐aged women. A longitudinal study design was employed to evaluate the effects of FATmax exercise training. Thirty women (45–59 years old; BMI 28·2 ± 1·8 kg m^?2; body fat 38·9 ± 4·1%) were randomly allocated into the Exercise and Control groups, n = 15 in each group. Body composition, FATmax, predicted VO₂max, lipid profile, plasma lipoprotein lipase activity and serum leptin concentration were measured before and after the experimental period. The Exercise group was trained at the individualized FATmax intensity, 5 days per week and 1 h per day for 10 weeks. No diet control was introduced during the experimental period for all participants. Exercise group obtained significant decreases in body mass, BMI, body fat % and abdominal fat mass, as well as the concentrations of triglycerides, serum leptin and blood glucose. The activity of lipoprotein lipase was increased in trained participants. There were no changes in these variables in the Control group. In addition, there was no significant change in daily energy intake for all participants before and after the experimental period. In conclusion, the 10‐week FATmax exercise training achieved improvements in body composition and lipid metabolism in overweight middle‐aged women. This result suggests FATmax is an effective exercise training intensity for obesity treatment.     

The exercise heart rate profile in master athletes compared to healthy controls

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle‐aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle‐aged athletes and controls. Fifty endurance‐trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom‐limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O₂ uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg^?1 min^?1; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between‐group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle‐aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.     

Effects of short‐term detraining following blood flow restricted low‐intensity training on muscle size and strength

We investigated the effects of 3 weeks of detraining on muscle cross‐sectional area (CSA) and one‐repetition maximum strength (1‐RM) in young men who had previously participated in 6 weeks (3 days week^?1) of bench press training [blood flow restricted low‐intensity (LI‐BFR; n = 10, 20% 1‐RM) or high‐intensity (HI; n = 7, 75% 1‐RM)]. Bench press 1‐RM and muscle CSA of triceps brachii (TB) and pectoralis major (PM) were evaluated before (pre) and after training period (post) as well as after detraining period (detraining). Bench press 1‐RM was higher at both post and detraining than at pre for LI‐BFR (P<0·01) and the HI (P<0·01). TB and PM muscle CSA were higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at post. Relative dynamic strength (1‐RM divided by TB muscle CSA) was higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at detraining. In conclusion, increased muscle strength following 6 weeks of training with LI‐BFR as well as HI was well preserved at 3 weeks of detraining. HI‐induced muscle strength appears to be dependent upon both neural adaptations and muscle hypertrophy with training and detraining. On the other hand, LI‐BFR‐induced muscle strength appears to be related primarily to muscle hypertrophy with training and to neural adaptations with detraining.     

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects

Background To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat‐derived factor retinol‐binding protein‐4 (RBP‐4) in HIV‐infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Materials and methods Fourteen HIV‐positive, HAART‐naïve subjects were compared with 10 HIV‐negative healthy controls and reassessed after a 1‐year treatment with HAART. Plasma visfatin and RBP‐4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X‐ray absorptiometry (DXA). Homeostasis model assessment (HOMA‐IR) was assessed using insulin and glucose levels. Results Visfatin and RBP‐4 levels in HIV‐positive subjects were comparable with those of HIV‐negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6·9‐fold and 7·1‐fold increase of visfatin and RBP‐4 levels (+54·0 ± 9·7 ng mL^?1, P < 0·0001 and +95·3 ± 31·7 ng mL^?1, P < 0·01), respectively. Leptin (?2·7 ± 1·6 ng mL^?1, P = 0·054) was unchanged and adiponectin (?2·8 ± 0·7 µg mL^?1, P < 0·01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP‐4 (r = 0·78, P = 0·001), fat‐free mass (FFM, r = 0·75, P < 0·05) and change of HOMA‐IR (r = 0·64, P < 0·05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Conclusions Treatment with HAART induced a pronounced increase of plasma visfatin and RBP‐4 as well as a decrease of adiponectin in HIV‐infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.     

Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes

Background It has been speculated that oral hypoglycaemic agents that block K‐ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. Design A multicentre, double‐blind, placebo‐controlled, randomized trial was conducted in 109 drug‐naive 30‐ to 75‐year‐old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C‐peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)‐B% (as surrogate of β‐cell activity) and HOMA‐S% (as surrogate of insulin sensitivity). Results At the end of the follow‐up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6·7 ± 0·6 vs. 7·2 ± 0·7%, respectively; P < 0·001), fasting plasma glucose (7·9 ± 2·1 vs. 8·5 ± 2·0 mmol L^?1; P = 0·023) and systolic blood pressure (125·3 ± 15·4 vs. 129·3 ± 18·7 mmHg; P = 0·015), and higher values of HOMA‐B%[75·7 (51·8–99·4) vs. 57·7 (42·2–83·4); P = 0·033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0·355, P = 0·011). Conclusions In drug‐naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.     

Glucose turnover and intima media thickness of internal carotid artery in type 2 diabetes offspring

Background First‐degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a ~40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle‐aged OFF. Materials and methods T2DM‐OFF (n = 18, 14f/4m, 45·6 ± 2·1 years, BMI: 26 ± 1 kg m^?2) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44·5 ± 2·1 years, BMI: 24 ± 1 kg m^?2; each P > 0·30), all with normal glucose tolerance as tested by three‐hour (75 g) oral glucose tolerance tests (OGTT). Two‐hour hyperinsulinaemic (40 mU min^?1·m^?2)isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D‐[6,6‐²H₂]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI). Results Before and during OGTT, both groups were similar in plasma glucose, insulin, C‐peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0·03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was ~38% lower (P < 0·03) in OFF who showed higher plasma FFA (44 ± 9 µmol L^?1) than CON (26 ± 3 µmol L^?1, P < 0·05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0·007) reduced AI. ICA‐IMT was ~18% higher in OFF (P < 0·002), but did not correlate with insulin sensitivity. Conclusion The data obtained show middle‐aged T2DM‐OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin‐dependent suppression of plasma FFA and increased ICA‐IMT.     

Head‐to‐head comparison between Actigraph 7164 and GT1M accelerometers in adolescents

We compared, head‐to‐head, the old generation Actigraph model 7164 with the new generation Actigraph GT1M accelerometer. A total of 15 randomly selected teenagers (eight girls and seven boys) were investigated. They performed a treadmill test wearing the two kinds of accelerometers around the waist simultaneously. The treadmill test consisted of three different levels of speed 4, 6 and 8 km h^?1 for four consecutive minutes. Accelerometer counts per 1 sec epoch for the Actigraph GT1M versus the Actigraph 7164 were at 4 km h^?1 21·6 ± 12·9 versus 26·5 ± 11·5 counts, at 6 km h^?1 56·0 ± 23·2 versus 62·9 ± 25·6 counts and at 8 km h^?1 142·6 ± 37·2 versus 156·4 ± 34·9 counts (P<0·01 for all levels of speed). Data from the old generation Actigraph 7164 and the new generation Actigraph GT1M accelerometers differ, where the Actigraph GT1M generates 10‐23% lower values. Correction equation for Actigraph GT1M was Actigraph 7164 = 5·2484 +  Actigraph GT1M counts × 1·0448. These results need to be taken into consideration when using these devices.     

Arterial stiffening and cardiac hypertrophy in a new rat model of type 2 diabetes

Background We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. Methods Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg⁻¹ of NA, 30 min before an intravenous injection of 50 mg kg⁻¹ STZ, to induce type 2 diabetes. The STZ‐NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age‐matched controls. Pulsatile aortic pressure and flow signals were measured by a high‐fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. Results In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8‐week but not the 4‐week STZ‐NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1·49 ± 0·33 (mean ± SD) to 1·95 ± 0·28 mmHg s mL⁻¹ (P < 0·05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ‐NA diabetic animals after 8 weeks had an increased wave reflection factor (0·46 ± 0·09 vs. 0·61 ± 0·13, P < 0·05) and decreased wave transit time (25·8 ± 3·8 vs. 20·6 ± 2·8 ms, P < 0·05). Ratio of the left ventricular weight to body weight was also enhanced in the 8‐week STZ‐NA diabetic rats. Conclusion The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration.     

Whole body,regional fat accumulation,and appetite‐related hormonal response after hypoxic training

The present study was conducted to determine change in regional fat accumulation and appetite‐related hormonal response following hypoxic training. Twenty sedentary subjects underwent hypoxic (n = 9, HYPO, FiO₂ = 15%) or normoxic training (n = 11, NOR, FiO₂ = 20·9%) during a 4‐week period (3 days per week). They performed a 4‐week training at 55% of maximal oxygen uptake (O_2max) for each condition. Before and after the training period, O_2max, whole body fat mass, abdominal fat area, intramyocellular lipid content (IMCL), fasting and postprandial appetite‐related hormonal responses were determined. Both groups showed a significant increase in O_2max following training (P<0·05). Whole body and segmental fat mass, abdominal fat area, IMCL did not change in either group. Fasting glucose and insulin concentrations significantly reduced in both groups (P<0·05). Although area under the curve for the postprandial blood glucose concentrations significantly decreased in both groups (P<0·05), the change was significantly greater in the HYPO group than in the NOR group (P<0·05). Changes in postprandial plasma ghrelin were similar in both groups. A significant reduction of postprandial leptin response was observed in both groups (P<0·05), while postprandial glucagon‐like peptide‐1 (GLP‐1) concentrations increased significantly in the NOR group only (P<0·05). In conclusion, hypoxic training for 4 weeks resulted in greater improvement in glucose tolerance without loss of whole body fat mass, abdominal fat area or IMCL. However, hypoxic training did not have synergistic effect on the regulation of appetite‐related hormones.     

Reproducibility of peak oxygen consumption and the impact of test variability on classification of individual training responses in young recreationally active adults

This study investigated whether VO₂peak is reproducible across repeated tests before (PRE) and after (POST) training, and whether variability across tests impacts how individual responses are classified following 3 weeks of aerobic exercise training (cycle ergometry). Data from 45 young healthy adults (age: 20·1 ± 0·9 years; VO₂peak, 42·0 ± 6·7 ml·min^?1) from two previously published studies were utilized in the current analysis. Non‐responders were classified as individuals who failed to demonstrate an increase or decrease in VO₂peak that was greater than 2·0 times the typical error of measurement (107 ml·min^?1) away from zero, while responders and adverse responders were above and below this cut‐off, respectively. VO₂peak tests at PRE (three total) and POST (three total) were highly reproducible (PRE and POST average and single measures ICCs: range 0·938–0·992), with low coefficients of variation (PRE:4·9 ± 3·1%, POST: 4·8 ± 2·7%). However, a potential learning effect was observed in the VO₂peak tests prior to training, as the initial pretraining test was significantly lower than the third (p = 0·010, PRE 1: 2 946 ± 924 ml·min^?1, PRE 3: 3 042 ± 919 ml·min^?1). This resulted in fewer individuals classified as adverse responders for Test 3 compared to any combination of tests that included Test 1, suggesting that a single ramp test at baseline may not be sufficient to accurately classify the VO₂peak response in young recreationally active individuals. Thus, it is our recommendation that the initial VO₂peak test be used as a familiarization visit and not included for analysis.     

Effects of walking with blood flow restriction on limb venous compliance in elderly subjects

Venous compliance declines with age and improves with chronic endurance exercise. KAATSU, an exercise combined with blood flow restriction (BFR), is a unique training method for promoting muscle hypertrophy and strength gains by using low‐intensity resistance exercises or walking. This method also induces pooling of venous blood in the legs. Therefore, we hypothesized that slow walking with BFR may affect limb venous compliance and examined the influence of 6 weeks of walking with BFR on venous compliance in older women. Sixteen women aged 59–78 years were partially randomized into either a slow walking with BFR group (n = 9, BFR walk group) or a non‐exercising control group (n = 7, control group). The BFR walk group performed 20‐min treadmill slow walking (67 m min^?1), 5 days per week for 6 weeks. Before (pre) and after (post) those 6 weeks, venous properties were assessed using strain gauge venous occlusion plethysmography. After 6 weeks, leg venous compliance increased significantly in the BFR walk group (pre: 0·0518 ± 0·0084, post: 0·0619 ± 0·0150 ml 100 ml^?1 mmHg^?1, P<0·05), and maximal venous outflow (MVO) at 80 mmHg also increased significantly after the BFR walk group trained for 6 weeks (pre: 55·3 ± 15·6, post: 67·1 ± 18·9 ml 100 ml^?1 min^?1, P<0·01), but no significant differences were observed in venous compliance and MVO in the control group. In addition, there was no significant change in arm compliance in the BFR walk group. In conclusion, this study provides the first evidence that 6 weeks of walking exercise with BFR may improve limb venous compliance in untrained elder female subjects.     

Mannitol clearance for the determination of glomerular filtration rate–a validation against clearance of 51Cr‐EDTA

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of ⁵¹Cr‐EDTA in outpatients with normal to moderately impaired renal function. Forty‐one patients with a serum creatinine <200 μmol l^?1 entered the study. ⁵¹Cr‐EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single‐sample method described by Jacobsson. Mannitol, 0·25 g kg^?1 body weight (150 mg ml^?1), was infused for 4–14 min and blood samples taken at 1‐, 2‐, 3‐ and 4‐h (n = 24) or 2‐, 3‐, 3·5‐ and 4‐h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner‐Mortensen. Mean plasma clearance (±SD) for ⁵¹Cr‐EDTA was 59·7 ± 18·8 ml min^?1. The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min^?1 and Vd was 21·3 ± 6·2% per kg b.w. The between‐method bias ranged between ?0·23 and 2·73 ml min^?1, the percentage error between 26·7 and 39·5% and the limits of agreement between ?14·3/17·2 and ?25·3/19·9 ml min^?1. The best agreement was seen when three‐ or four‐sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88–96% (P30) and 41–63% (P10) and was highest when three‐ or four‐sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and ⁵¹Cr‐EDTA for the assessment of GFR.     

Calculation algorithms alter the breath‐by‐breath gas exchange values when abrupt changes in ventilation occur

The automatic metabolic units calculate breath‐by‐breath gas exchange from the expiratory data only, applying an algorithm (‘expiration‐only’ algorithm) that neglects the changes in the lung gas stores. These last are theoretically taken into account by a recently proposed algorithm, based on an alternative view of the respiratory cycle (‘alternative respiratory cycle’ algorithm). The performance of the two algorithms was investigated where changes in the lung gas stores were induced by abrupt increases in ventilation above the physiological demand. Oxygen, carbon dioxide fractions and ventilatory flow were recorded at the mouth in 15 healthy subjects during quiet breathing and during 20‐s hyperventilation manoeuvres performed at 5‐min intervals in resting conditions. Oxygen uptakes and carbon dioxide exhalations were calculated throughout the acquisition periods by the two algorithms. Average ventilation amounted to 6·1 ± 1·4 l min^?1 during quiet breathing and increased to 41·8 ± 27·2 l min^?1 during the manoeuvres (P<0·01). During quiet breathing, the two algorithms provided overlapping gas exchange data and noise. Conversely, during hyperventilation, the ‘alternative respiratory cycle’ algorithm provided significantly lower gas exchange data as compared to the values yielded by the ‘expiration‐only’ algorithm. For the first breath of hyperventilation, the average values provided by the two algorithms amounted to 0·37 ± 0·34 l min^?1 versus 0·96 ± 0·73 l min^?1 for O₂ uptake and 0·45 ± 0·36 l min^?1 versus 0·80 ± 0·58 l min^?1 for exhaled CO₂ (P<0·001 for both). When abrupt increases in ventilation occurred, such as those arising from a deep breath, the ‘alternative respiratory cycle’ algorithm was able to halve the artefactual gas exchange values as compared to the ‘expiration‐only’ approach.     

Endothelial nitric oxide synthase Glu298Asp gene polymorphism influences body composition and biochemical parameters but not the nitric oxide response to eccentric resistance exercise in elderly obese women

Both endothelial nitric oxide synthase (eNOS) gene polymorphism and nitric oxide (NO) are involved in important cardiovascular, muscular and inflammatory physiological mechanisms during ageing and response to exercise. The aim of this study was to investigate the NO kinetic response following an acute eccentric resistance exercise (ERE) session and the possible effect of the Glu298Asp eNOS gene polymorphism in elderly obese women. Eighty‐seven women (age 69·4 ± 6·1 years, body weight 74·9 ± 12·7 kg, height 151·9 ± 6·0 cm and BMI 32·5 ± 5·7 kg m^?2) completed seven sets of ten eccentric repetitions at 110% of the ten repetitions maximum (10RM). NO concentrations remained elevated up to 48 h following the acute ERE session as compared with baseline, for GG and GT/TT groups (P<0·05), with no differences between genotypes. The GG genotype group had higher body weight, prevalence of obesity (BMI classification – 81% versus 56%), BMI and higher relative muscle strength, while they had significantly lower triglycerides, VLDL and urea concentrations as compared with TT/TG group. In conclusion, NO remains elevated for up to 48 h after an acute ERE session, without genotype interaction. The TT/TG genotype had a negative impact on triglycerides, VLDL and urea concentrations. Thus, T carriers should increase their attention to cardiovascular risk factor and metabolic disorders.     

Abnormal vascular reactivity at rest and exercise in obese boys

Background Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls. Materials and methods Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m^?2)] and thirteen controls (BMI:17·4 ± 1·8 kg m^?2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima‐media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow‐mediated dilation (FMD) and nitrate‐dependent dilation (NDD), lower limb blood flow during local knee‐extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. Results Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min^?1·100 g^?1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. Conclusions Mild‐to‐moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.     

Low intensity strength training for ambulatory stroke patients

Purpose. To investigate feasibility and effectiveness of an individually-directed, group strength-training programme on knee muscle strength after stroke.

Method. Ten volunteers (62 ± 11 years, mean ± SD), 6 – 12 months after first-ever unilateral stroke, walking independently with or without aids were recruited. Using an A1-B-A2 design, 3 sets of baseline measures were taken at 2 weekly intervals; volunteers then attended twice weekly sessions of low intensity progressive strengthening exercises and were assessed after each series of 8 sessions to a maximum of 24 sessions; post training, measures were repeated after 4 – 6 weeks. Measures included isometric and concentric knee extensor muscle strength and 10 m walking velocity.

Results. Strength of knee extensor muscles was improved after training (ANOVA, p < 0.05). On cessation of training, isometric strength increased by 58 ± 19% and concentric strength at 30°/s by 51 ± 14%; walking velocity quickened from 0.47 ± 0.06 m · s^?1 to 0.57 ± 0.08 m · s^?1 (t = ?3.31, p < 0.01). These gains were maintained 4 – 6 weeks after completion of training.

Conclusions. These findings support the use of low intensity strength training after stroke and confirm published evidence. It was feasible for one therapist to deliver the training programmes for 4 – 6 participants at a time; an important feature when resources are limited.     

Anatomical vertebral artery hypoplasia and insufficiency impairs dynamic blood flow regulation

Recent studies have suggested that vertebral artery (VA) hypoplasia is a predisposing factor for posterior cerebral stroke. We examined whether anatomical vertebrobasilar ischemia, i.e., unilateral VA hypoplasia and insufficiency, impairs dynamic blood flow regulation. Twenty‐eight female subjects were divided into three groups by defined criteria: (i) unilateral VA hypoplasia (n = 8), (ii) VA insufficiency (n = 6), and (iii) control (n = 14). Hypoplastic VA criterion was VA blood flow of 40 ml min^?1, whereas VA insufficiency criterion was net (left + right) VA blood flow of 100 ml min^?1 or less. We evaluated left, right, and net VA blood flows by ultrasonography during hypercapnia, normocapnia, and hypocapnia to evaluate VA CO₂ reactivity. The unilateral VA hypoplasia group showed lower CO₂ reactivity at hypoplastic VA than at non‐hypoplastic VA (2·65 ± 0·58 versus 3·00 ± 0·48% per mmHg, P = 0·027) and net VA CO₂ reactivity was preserved (Unilateral VA hypoplasia, 2·95 ± 0·48 versus Control, 2·93 ± 0·42% per mmHg, P = 0·992). However, the VA insufficiency group showed a lower net VA CO₂ reactivity compared to the control (2·29 ± 0·55 versus 2·93 ± 0·42% per mmHg, P = 0·032) and the unilateral VA hypoplasia (P = 0·046). VA hypoplasia reduced CO₂ reactivity, although non‐hypoplastic VA may compensate this regulatory limitation. In subjects with VA insufficiency, lowered CO₂ reactivity at the both VA could not preserve normal net VA CO₂ reactivity. These findings provide a possible physiological mechanism for the increased risk of posterior cerebral stroke in subjects with VA hypoplasia and insufficiency.     

New evidence for the role of TNF-alpha in liver ischaemic/reperfusion injury

Background Tumour necrosis factor‐alpha (TNF‐α) plays a key role in causing ischaemia/reperfusion (I/R) injury. I/R also causes activation of xanthine oxidase and dehydrogenase (XDH + XO) system that, via generated free radicals, causes organ damage. We investigated the effect of ischaemia, reperfusion and non‐ischaemic prolonged perfusion (NIP) on TNF‐α and XDH + XO production in an isolated perfused rat liver model. Materials and methods Rat livers underwent 150 min NIP (control group) or two hours of ischaemia followed by reperfusion (I/R group). TNF‐α (TNF‐α mRNA and protein level), XDH + XO production and bile secretion were determined in tissue and effluent at baseline, at 120 min of ischaemia, after 30 min of reperfusion (I/R group) and after 120 and 150 min of prolonged perfusion (control). Results Unexpectedly, neither ischaemia nor reperfusion had any effect on TNF‐α production. TNF‐α in effluent was 11 ± 4·8 pg mL^?1 at baseline, 7 ± 3·2 pg mL^?1 at the end of ischaemia, and 13 ± 5·3 pg mL^?1 after 30 min of reperfusion. NIP, however, caused a significant increase of TNF‐α synthesis and release. TNF‐α effluent level after 120 and 150 min of perfusion was 392 ± 78·7 pg mL^?1 and 408 ± 64·3 pg mL^?1, respectively. TNF‐α mRNA in tissue was also significantly elevated compared to baseline levels (1·31 ± 0·2 P < 0·001 and 1·38 P < 0·002, respectively). Decrease of liver function (expressed by bile secretion) during I/R and NIP was accompanied by significant XDH + XO elevation. Conclusion This is the first evidence that NIP, and not I/R, is the decisive trigger for TNF‐α production. This study leads to a better understanding of pathogenesis of liver I/R and perfusion damage.     

Glucagon-like peptide-1 reduces the pulsatile component of testosterone secretion in healthy males

Background Glucagon‐like‐peptide‐1 (7–36) amide (GLP‐1), a potent regulator of glucose homeostasis, has been implicated in the control of hypothalamic‐pituitary function. In vivo it is a relevant neuroendocrine modulator of gonadotropin‐releasing hormone release, suggesting its possible role as a metabolic signal to the reproductive system. The present study was undertaken to establish its effect on luteinizing hormone (LH) and testosterone secretion in nine healthy male volunteers. Materials and methods Each subject underwent an oral glucose tolerance test to establish LH, testosterone, and GLP‐1 responses to glucose. Euglycaemic clamp experiments (6 h) were performed on two occasions with saline or with a constant infusion of GLP‐1 (0·4 pmol kg^?1 min ^?1). Blood samples were drawn at 10‐min intervals to measure the pulsatile pattern of LH and testosterone secretion. Results Ingestion of oral glucose resulted in a reduction in plasma testosterone levels at 30 min compared with baseline (P < 0·004) despite unaltered LH levels (P = 0·5). Constant GLP‐1 infusion resulted in no change in LH (P = 0·83), testosterone (P = 0·96), follicle stimulating hormone (FSH) (P = 0·86) and leptin levels (P = 0·3). Pulse analysis revealed no significant difference in the number (P = 0·1) or median absolute amplitude (P = 0·3) of the LH pulses. However, there was a significant decrease in the number (3·0 ± 0·6 vs. 1·3 ± 0·4; P < 0·05) and a tendency for increased duration of testosterone pulses (97·4  16·7 vs. 170  27·1 min; P = 0·06). Conclusion Oral glucose ingestion and intravenous GLP‐1 infusion reduce the pulsatile component of testosterone secretion by a mechanism independent of LH release.