bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splanchnic haemodynamic changes during acute hypoglycaemia in man
Authors: Braatvedt G. D. , Newrick P. G. , Halliwell M. , Wells P. N. T. , Read A. E. , Corrall R. J. M. 
Published: August 2015

1. Splanchnic haemodynamic changes were studied in seven healthy subjects during hypoglycaemia induced by the intravenous infusion of insulin. Superior mesenteric artery blood flow and cardiac output were examined non-invasively by a Doppler ultrasound technique.
2. Blood glucose concentration fell from 4.5 (0.14) mmol/l basally to 1.5 (0.09) mmol/l [mean (sem), P &lt; 0.003] at the hypoglycaemic reaction (‘R’) and recovered to baseline by ‘R’ + 60 min. There was an associated rise in plasma glucagon, adrenaline and noradrenaline levels.
3. Superior mesenteric artery blood flow rose at ‘R’ from a basal value of 532 (38) ml/min to a peak of 803 (73) ml/min at ‘R’+10 min [mean (sem), P &lt; 0.005] and remained significantly elevated until ‘R’ + 40 min. Resistance in this vessel fell by 33% at ‘R’+ 10 min (P &lt; 0.005) and remained significantly low until ‘R’ + 40 min.
4. Cardiac output rose by 33% at ‘R’ (P &lt; 0.004) and returned to normal by ‘R’ + 20 min. This was associated with a 24% rise in pulse rate (P 0.03), but no change in stroke volume or mean arterial pressure. Total peripheral resistance fell by 21% at ‘R’ (P 0.005) and had returned to normal by ‘R’ + 20 min.
5. The sustained rise in splanchnic blood flow during hypoglycaemic recovery may be of homoeostatic importance by providing metabolic fuel to the liver for gluconeogenesis.
Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat
Authors: McKeever M. P. , Weir D. G. , Molloy A. , Scott J. M. 
Published: August 2015

1. Conflicting reports exist as to the organ distribution of betaine-homocysteine methyltransferase (EC 2.1.1.5). It is important to establish its presence or absence in brain, since its substrate, betaine, has recently become established in the treatment of certain diseases involving this organ.
2. It remains unclear whether the reported success of this treatment results from the use of betaine to methylate homocysteine and produce methionine in situ in neural tissue, or whether the effect is secondary to these same reductions happening in other organs, such as the liver. The former would require the presence of betaine-homocysteine methyltransferase in neural tissue.
3. This study demonstrates the complete absence of any activity for this enzyme in the brain of the three species examined. The enzyme was found to be present in both the liver and kidney of man and pig, but only in the liver of the rat.
4. The only source of betaine in cells is via the oxidation of choline. Since the enzymes involved in this conversion have never been shown to exist anywhere other than the mitochondria, it has been assumed that the methyltransferase is also mitochondrial. In this study, it is demonstrated that the enzyme exists only in the cytoplasm of rat liver cells.
Separation of the impairment of haemostasis by aspirin from mucosal injury in the human stomach
Authors: Hawkey C. J. , Hawthorne A. B. , Hudson N. , Cole A. T. , Mahida Y. R. , Daneshmend T. K. 
Published: August 2015

1. An increasing body of data suggests that the anti-haemostatic as well as the ulcerogenic actions of aspirin and other non-steroidal anti-inflammatory drugs may be operative when patients present with haematemesis and melaena.
2. We therefore developed methods to allow separate evaluation of the erosive and anti-haemostatic actions of aspirin in the human gastric mucosa. Volunteer subjects took 300 mg of aspirin daily in the morning or 600 mg of aspirin four times a day for 5 days under blinded randomized conditions. Changes in spontaneous gastric microbleeding, endoscopic signs of injury, spontaneous bleeding per gastric erosion, biopsy-induced bleeding and eicosanoids were studied.
3. Both doses of aspirin significantly inhibited gastric mucosal synthesis of prostaglandin E2 and reduced the serum thromboxane concentration. Erosions developed and regressed rapidly; compared with baseline 300 mg of aspirin daily in the morning caused substantial numbers of gastric erosions to develop (mean 5.3, 95% confidence limits 2.7–10.2) but this was significantly less than that caused by 600 mg of aspirin four times a day (10.9, 7.2–16.5, P &lt; 0.05). The presence of erosions was associated with enhanced spontaneous bleeding, but only during aspirin administration.
4. Aspirin significantly increased bleeding induced by mucosal biopsy and was associated with significant enhancements in the rate of bleeding per gastric erosion. Bleeding rate per erosion but not biopsy-induced bleeding showed a significant dose-related increase with 600 mg of aspirin four times a day. Enteric coating reduced endoscopic signs of injury, but did not affect the impaired haemostasis caused by aspirin.
5. We conclude that aspirin can be shown to have both erosive and anti-haemostatic effects in the human stomach. Each can be evaluated separately in our model system. Both are potential therapeutic targets for the prevention of major upper-gastrointestinal bleeding caused by aspirin and probably other non-steroidal antiinflammatory drugs.
Short-term reproducibility of a mental arithmetic stress test
Authors: Jern Sverker , Pilhall Martin , Jern Christina , Carlsson Sven G. 
Published: August 2015

1. To evaluate the short-term reproducibility of heart rate, oscillometrically determined blood pressure, ante-cubital venous plasma catecholamine concentrations and subjective responses to strictly standardized mental arithmetic, we performed two identical tests 1 h apart in 14 young, healthy and normotensive male subjects (age 22–35 years)
2. Heart rate and blood pressure responses to the two stress tests were highly correlated, when expressed both as correlations between levels attained during stress (rs &gt;0.80 throughout) and as absolute reactivity measures (all rs &gt;0.75). Also, subjective stress responses were highly correlated, when considering both levels during stress and reactivity (r = 0.97 and r = 0.85, respectively). Stress levels of catecholamines were correlated, but the change scores (reactivity) were unrelated.
3. The measurement error sd for heart rate was 2.6 and 3.0 beats/min for reactivity and stress levels, respectively. The corresponding sd for blood pressure ranged between 2.7 and 4.4 mmHg. Subjective stress experience showed an sd of a similar magnitude. The responses of plasma catecholamine concentrations were subject to considerable variability.
4. It is concluded that haemodynamic and subjective stress responses and stress levels during the mental arithmetic stress test show acceptable reproducibility and high test-retest correlations. However, stress-induced changes in venous plasma catecholamine concentrations show low reproducibility.
Abnormal expression of growth regulatory factors in Barrett's oesophagus
Authors: Jankowski J. , McMenemin R. , Hopwood D. , Penston J. , Wormsley K. G. 
Published: August 2015

1. In order to assess potential abnormalities in the control of mucosal proliferation, 30 patients with Barrett's oesophagus were studied in order to evaluate the presence and distribution of epidermal growth factor, transforming growth factor-α and epidermal growth factor receptor to determine the Ki-67 labelling index in the affected oesophageal mucosa. Serial sections were analysed immunohistochemically. Ten of the patients had adenocarcinoma in the Barrett's mucosa and the other 20 had differing histological types of Barrett's mucosa (10, intestinal-type; 10, fundic-or cardiac-type).
2. The expression of transforming growth factor-α, epidermal growth factor and epidermal growth factor receptor was increased and the Ki-67 labelling index was higher in Barrett's mucosa compared with normal gastric mucosa. The ‘intestinal-type’ of Barrett's mucosa had the greatest expression of transforming growth factor-α, epidermal growth factor receptor and the highest Ki-67 labelling index compared with the other types of Barrett's metaplasia. Five cases of ‘intestinal-type’ Barrett's metaplasia had especially high Ki-67 labelling indices and these patients over-expressed both transforming growth factor-α and epidermal growth factor receptor. The patients with adenocarcinomas in the Barrett's mucosa also over-expressed transforming growth factor-α and epidermal growth factor receptor, but not epidermal growth factor, compared with normal gastric mucosa.
3. In conclusion, both normal gastric mucosa and Barrett's mucosa have potential autocrine growth regulatory mechanisms, but Barrett's mucosa has increased expression of both of the measured ligands and of the epidermal growth factor receptor.
Strenuous exercise: analogous to the acute-phase response?
Authors: Weight Lindsay M. , Alexander Donald , Jacobs Peter 
Published: August 2015

1. It has been suggested that the physiological consequences of strenuous exercise are analogous to those of the acute-phase response.
2. In 70 male and 20 female competitive distance runners, a marked, but transient, neutrophil leucocytosis occurred immediately after these athletes completed a standard (42 km) marathon race. Concomitant significant increases were noted in the plasma cortisol levels, creatine kinase activity, C-reactive protein level, total protein level and albumin level (P &lt;0.01).
3. The plasma fibrinogen, C-reactive protein and total protein concentrations were markedly increased both 24 h and 48 h after exercise (P &lt;0.01). The serum haptoglobin level was significantly decreased after exercise (P &lt;0.01), and increased 48 h later (P &lt;0.05). There was no change in the serum iron level, total iron-binding capacity, per cent saturation of transferrin and serum ferritin level.
4. A significant increase in interleukin-1-type activity was demonstrated immediately and 24 h after exercise (P &lt;0.01).
5. It is concluded that the metabolic sequelae of sustained exercise are similar, but not analogous, to the acute-phase response, and interleukin-1 probably plays a significant role in linking the haematological and immunological changes observed after sustained strenuous exercise.
Na+/H+ and HCO3−/Cl− exchange in the control of intracellular pH in vivo in the spontaneously hypertensive rat
Authors: Syme P. D. , Aronson J. K. , Thompson C. H. , Williams E. M. , Green Y. , Radda G. K. 
Published: August 2015

1. We have previously shown that the cytosolic acid concentration changes in skeletal muscle during contraction in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats in vivo. We have now found that this change was unaffected by 20% inhaled CO2 or by 4,4′-di-isothiocyanostilbene-2,2′-disulphonate. This is evidence that HCO3− exchange in vivo is not important in the control of cytosolic acid concentration during skeletal muscle contraction in either spontaneously hypertensive or Wistar-Kyoto rats.
2. We have also previously shown that the difference in cytosolic acid response during contraction between spontaneously hypertensive and Wistar-Kyoto rats is due to increased Na+/H+ antiporter activity in the spontaneously hypertensive rats. Our current findings suggest that this increase in Na+/H+ antiporter activity is more likely to be due to a change in the Km of the antiporter than to a change in the Vmax. We estimate that the Km of the antiporter changes in hypertension from pH 7.16 to 7.33.
3. We did not find any differences between adult spontaneously hypertensive and Wistar-Kyoto rats with regard to resting intracellular and extracellular pH and resting intracellular and extracellular HCO3− concentrations. In addition, we did not find any evidence of a difference in skeletal muscle HCO3−/Cl− exchange between adult spontaneously hypertensive and Wistar-Kyoto rats.
4. At rest, skeletal muscles of the spontaneously hypertensive and Wistar-Kyoto rats have the same lactate production, HCO3−/Cl− exchange and arterial partial pressure of CO2. In addition, we can also calculate that at a resting intracellular pH of 7.05 in the spontaneously hypertensive rats, the antiporter is 66% saturated. The corresponding value in the Wistar-Kyoto rats (resting intracellular pH 7.04) is 57%. This explains the lack of difference in resting intracellular pH between the two strains of rat and suggests that at rest differences in Na+/H+ antiporter activity due to a shift in Km of the antiporter are too small to result in a difference in resting pH.
5. Furthermore, Na+/H+ antiporter activity around pH 7.0 was unable to prevent the acidosis caused by CO2 loading. Thus resting pH in skeletal muscle in vivo is determined largely by the HCO3− system and in this regard skeletal muscle is similar to vascular smooth muscle.
Nocturnal variations in lower-leg subcutaneous blood flow in paraplegic men
Authors: Sindrup J. H. , Wroblewski H. , Kastrup J. , Biering-Sørensen F. 
Published: August 2015

1. Lower-leg subcutaneous adipose tissue blood flow rates were measured over 12-20 h under ambulatory conditions by means of the 133Xe-washout technique in nine paraplegic men, all with complete spinal cord lesions at or below the Th 6 level, and in nine age-matched healthy men. Portable CdTe(Cl) detectors and datastorage units were used.
2. The central and local sympathetic vasoconstrictive activity at the lower leg was measured under laboratory conditions by means of the l33Xe-washout technique and a stationary NaI(TI) detector system.
3. The paraplegic men were found to have intact central and local sympathetic vasoconstrictive activity in their lower legs. Moreover, they all had a nocturnal hyperaemic blood flow phase of the same magnitude and duration as the control subjects.
4. The possibility that the somaesthetic nerves play a role in the hyperaemic response could be excluded, as all the paraplegic men suffered from complete lower-leg somaesthetic denervation.
5. A significant correlation was found between the time of going to bed and the nightly hyperaemic response in the right and left lower legs (P &lt; 0.01).
6. It is concluded that the present data are in accordance with the concept of a central nervous or humoral elicitation of nocturnal hyperaemia, although local metabolic and other factors might participate as well. Paraplegic men have an intact regulation of the postural and nocturnal changes in peripheral blood flow whether of central sympathetic or humoral origin.
Increased energy expenditure in cystic fibrosis is associated with specific mutations
Authors: O'Rawe A. , McIntosh I. , Dodge J. A. , Brock D. J. H. , Redmond A. O. B. , Ward R. , MacPherson A.J. S. 
Published: August 2015

1. Measurements of resting metabolic rate were made by open-circuit indirect calorimetry in 78 unrelated cystic fibrosis patients and 30 healthy control subjects. The aims of this study were: (i) to determine the range of variability in resting metabolic rate in cystic fibrosis, (ii) to relate this to pulmonary function and body size, and (iii) to investigate the hypothesis that, in cystic fibrosis, genotype exerts a significant influence on energy requirements.
2. There was no significant difference in age or body weight between patients with cystic fibrosis and control subjects. Resting metabolic rates for control subjects fell within ± 10% of predicted values. Fifty-nine per cent of patients with cystic fibrosis had elevated resting metabolic rates (i.e. &gt; 111% of predicted). Genotype analysis divided the patients with cystic fibrosis into three groups: AF508 homozygotes, AF508 heterozygotes and others. Patients homozygous for the AF508 allele had a significantly higher resting metabolic rate (121% of predicted, 95% confidence interval 116-126%), compared with other genotypes (P&gt; 0.005).
3. There were significant differences in pulmonary function between the groups (P&gt; 0.005). However, after adjustment of individual resting metabolic rates for differences in pulmonary function by using analysis of co-variance, resting metabolic rates remained significantly higher for ΔF508 homozygotes than for other genotypes (P&lt;0.05).
4. We conclude that there is a significant contribution to resting metabolic rate in cystic fibrosis associated with specific mutations that is not explained by declining pulmonary function. The increase in resting metabolic rate in patients homozygous for mutations involving a nucleotide-binding fold, which may result from a disruptive effect on ATP binding, indicates a practical implication of genotype identification with the need for effective nutritional intervention and support in this patient subgroup.
Metabolic effects of dobutamine in normal man
Authors: Green Ceri J. , Frazer R. S. , Underhill S. , Maycock Paula , Fairhurst Judith A. , Campbell I. T. 
Published: August 2015

1. Dobutamine in 5% (w/v) d-glucose was infused at sequential doses of 2, 5 and 10 μg min−1 kg−1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) d-glucose alone.
2. The energy expenditure increased and was 33% higher than control (P&lt;0.001) at 10 μg of dobutamine min−1 kg−1. The respiratory exchange ratio decreased from 0.85 (sem 0.02) before infusion to 0.80 (sem 0.01) at 10 μg of dobutamine min−1 kg−1, but did not alter during the placebo infusion (P&gt; 0.001).
3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of d-glucose alone (P &lt; 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions.
4. Compared with during the placebo infusion, the blood glucose concentration decreased (P &lt; 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P &lt; 0.001), and the plasma potassium concentration decreased from 3.8 (sem 0.07) to 3.6 (sem 0.04) mmol/l (P&lt;0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 μg of dobutamine min−1 kg−1 (P&lt;0.001) with no further rise at 10 μg of dobutamine min−1 kg−1.
5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P&lt;0.01). At 10 μg of dobutamine min−1 kg−1, the systolic blood pressure was around 160 mmHg (P &lt; 0.001) and the heart rate was around 92 (sem 8) beats/min compared with 59 (sem 4) beats/min during the placebo infusion (P &lt; 0.001).
6. Dobutamine has metabolic effects. It is markedly thermogenic and lipolytic. It depresses the respiratory exchange ratio and endogenous noradrenaline secretion, stimulates insulin secretion and depresses the blood glucose concentration.
Insulin resistance and Na+/K+-ATPase in hypertensive women: a difference in mechanism depending on the level of glucose tolerance
Authors: Mattiasson Ingrid , Berntorp Kerstin , Lindgärde Folke 
Published: August 2015

1. The peripheral glucose disposal rate (assessed with the euglycaemic-hyperinsulinaemic clamp technique), the serum sex hormone-binding globulin concentration and total and ouabain-sensitive 22Na-efflux rate constants in leucocytes were determined in 41 women with impaired glucose tolerance and in 40 women with normal glucose tolerance. The groups were matched for body mass index and diastolic blood pressure (range 55-112 mmHg).
2. Stepwise regression analysis showed that diastolic blood pressure in the group with impaired glucose tolerance was inversely correlated with the glucose disposal rate (model r2 = 21%) and was correlated with the plasma glucose concentration at 120 min after an oral glucose load (model r2 = 31%). In the group with normal glucose tolerance, however, neither of these two variables was correlated with blood pressure, although the ouabain-sensitive 22Na efflux rate constant was (model r2=11%).
3. Among insulin-resistant subjects, those with hypertension had significantly lower serum sex hormone-binding globulin concentrations than the normotensive subjects.
4. We conclude that insulin resistance is correlated with high blood pressure in women with glucose intolerance and increased androgenic activity. In women with normal insulin sensitivity, a low level of the Na+/K+-ATPase-mediated sodium efflux is associated with high blood pressure.
Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy
Authors: Rutherford Peter A. , Thomas Trevor H. , Carr Susan J. , Taylor Roy , Wilkinson Robert 
Published: August 2015

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity.
2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax.) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects.
3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean ± sem, 0.26 + 0.12 mmol of Li+ h−1 (l of cells)−1] was not significantly higher than in the uncomplicated diabetic patients [0.27 ± 0.03 mmol of Li+ h−1 (1 of cells)−1] or in the normal control subjects [0.25 ± 0.02 mmol of Li+ h−1 (l of cells)−1].
4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax.
5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes.
6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes
Authors: Rogers Mark E. , Williams Dean T. , Niththyananthan Ratnam , Rampling Michael W. , Heslop Kirsten E. , Johnston Desmond G. 
Published: August 2015

1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood.
2. Using g.c.–m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01–11.90) versus 18.60 (3.20–32.60) μg/100 μg of protein, P&lt;0.02].
3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (Ls/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean ± sem, 37.6 ± 1.3 versus 33.8 ± 0.6, P&lt;0.02).
4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically(LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P &lt;0.05).
5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes.