bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salbutamol, a β2-adrenoceptor agonist, increases skeletal muscle strength in young men
Authors: Martineau Lucie , Horan Michael A. , Rothwell Nancy J. , Little Roderick A. 
Published: August 2015

1. β2-Adrenoceptor agonists have been shown to increase rapidly lean body mass and reverse muscle wasting in several animal models of human illness. However, no published information is available for humans. In the present study, we investigated the effects of a slow-release preparation of salbutamol or a placebo on skeletal muscle functional capacity in 12 healthy men. The strength of different muscle groups was measured on two occasions before and after 14 and 21 days of treatment.
2. No significant changes in muscle strength were observed with placebo during the trial. In contrast, the strength of both quadriceps muscles increased significantly (12 ± 3%) after 14 days on salbutamol, and remained elevated at 21 days. Whereas the strength of the hamstring muscles of the dominant leg significantly increased after 21 days on salbutamol (22 ± 6%), the strength of the non-dominant hamstring muscles returned to baseline values.
3. There was no significant change in the grip strength of either hand in these subjects during the trial. The maximal static inspiratory mouth pressure increased significantly (7 ± 2%) after 14 days on salbutamol, and increased further after 21 days (15 ± 4%); the expiratory mouth pressure remained constant. No significant changes in body weight, skinfold thickness, lean body mass or limb circumferences were measured in either group.
4. These data demonstrate that short-term administration of salbutamol increases voluntary muscle strength in man. However, the magnitude and duration of this effect vary between muscle groups. This study implies that the β2-adrenoceptor agonists may be of therapeutic potential in altering skeletal muscle function in humans.
Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis
Authors: Raouf A. H. , Tsai H. H. , Parker N. , Hoffman J. , Walker R. J. , Rhodes Jonathan M. 
Published: August 2015

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis.
2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetyl-glucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetyIglucosamine incorporated into pure mucin was assessed.
3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305–0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959–1.111, P&lt;0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378–0.829) did not quite reach statistical significance (P=0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetyl-glucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26).
4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618–1.022) than in their paired proximal colonic biopsies (0.602, 0.421–0.861; P&lt;0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262–0.773; right colon: 0.470, 0.321–0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260–0.815; right colon: 0.492, 0.260–0.929, P = 0.8).
5. There was no significant difference in N-[3H]acetylglucosamine incorporation among the three groups (control subjects: 21195, 16611–32695 d.p.m./mg of biopsy protein content; ulcerative colitis: 12108, 7663-21 548 d.p.m./mg of biopsy protein content; Crohn's disease: 14 891, 8620-34 419 d.p.m./mg of biopsy protein content, P = 0.17), suggesting that there is a selective reduction of incorporation of sulphate per mucin side chain.
6. This study demonstrates a reduced ability of the rectal mucosa to sulphate mucin in patients with inflammatory bowel disease.
Inhibition of neutral endopeptidase stimulates renal sodium excretion in patients with chronic renal failure
Authors: Dussaule J. C. , Michel C. , Peraldi M. N. , Lecomte J. M. , Gros C. , Mignon F. , Ardaillou R. 
Published: August 2015

1. The acute effects of a single oral dose of sinorphan (100 mg), an inhibitor of neutral endopeptidase, on the plasma atrial natriuretic factor level and the fractional excretion of sodium were examined in 12 patients with severe chronic renal failure who were not on maintenance haemodialysis and who ingested a normal sodium diet. The drug was administered against placebo by a double-blind cross-over protocol.
2. Basal plasma atrial natriuretic factor level and fractional excretion of sodium were high (23.2 ± 3.7 pmol/l and 2.64 ± 0.38%, respectively). Sinorphan inhibited plasma neutral endopeptidase activity by 68–75% 30 min after ingestion. This effect persisted for at least 4 h. There were simultaneously increases in plasma atrial natriuretic factor and cyclic GMP levels to 1.9 and 1.4 times the basal values, respectively. Fractional excretion of sodium increased during the second and third hour periods after ingestion of the drug with a peak of 1.9 times the basal value in the second period. Changes in fractional excretion of sodium were significantly correlated with those in plasma atrial natriuretic factor and cyclic GMP levels. Plasma aldosterone level, creatinine clearance and mean blood pressure were unchanged, whereas plasma renin activity increased slightly. An increase in urinary cyclic GMP excretion was observed in parallel with the increase in plasma cyclic GMP level.
3. The results of the present study indicate that (i) high basal values of plasma atrial natriuretic factor level and fractional excretion of sodium, as observed in patients with chronic renal failure, are associated with marked effects of neutral endopeptidase inhibition; (ii) fractional sodium excretion increases after protection of endogenous atrial natriuretic factor from degradation independently of any initial change in extracellular fluid volume or sodium intake, which suggests that this hormone may play a role in the control of sodium excretion in chronic renal failure.
Regulation of β myosin heavy chain, c-myc and c-fos proto-oncogenes in thyroid hormone-induced hypertrophy of the rat myocardium
Authors: Green N. K. , Gammage M. D. , Franklyn J. A. , Heagerty A. M. , Sheppard M. C. 
Published: August 2015

1. In order to investigate the molecular mechanisms determining the hypertrophic response of the ventricular myocardium to thyroid hormone administration, changes in left and right ventricular expression of the c-myc, c-fos and H-ras proto-oncogenes in response to treatment with 3,3′,5-tri-iodothyronine were defined.
2. Adult female Wistar rats were treated with daily subcutaneous injections of 3,3′,5-tri-iodothyronine (50 μg) for 1, 3, 7 or 14 days (n = 6 in each treatment group) and the results from 3,3′,5-tri-iodothyronine-treated animals were compared with those obtained from untreated controls (n = 6). Changes in the weight of the left and right ventricles in response to 3,3′,5-tri-iodothyronine treatment were measured; changes in expression of the c-myc, c-fos and H-ras proto-oncogenes were determined in parallel by measurement of specific messenger RNAs by Northern and dot hybridization, as well as changes in expression of β myosin heavy chain messenger RNA.
3. Treatment with 3,3′,5-tri-iodothyronine resulted in increases in both left and right ventricular weights after 3 days, an effect maintained up to 14 days. Despite an increase in left ventricular weight, levels of β myosin heavy chain, c-myc, c-fos and H-ras mRNAs in the left ventricle were unchanged; in contrast, an increase in right ventricular weight was associated with increased expression of β myosin heavy chain, c-myc and c-fos messenger RNAs.
4. These specific ventricular changes in gene expression, in the face of a hypertrophic response of both ventricles to 3,3′,5-tri-iodothyronine, suggest that the cardiac growth response to thyroid hormones reflects the well-documented secondary haemodynamic influences rather than direct gene regulatory actions of 3,3′,5-tri-iodothyronine at the transcriptional level on the genes studied. Changes in right ventricular proto-oncogene and β myosin heavy chain expression may in turn reflect an increase in right ventricular pressure load.
Coagulation and fibrinolytic systems in type I diabetes: effects of venous occlusion and insulin-induced hypoglycaemia
Authors: Wieczorek Iwona , Pell Alistair C. H. , McIver Brian , MacGregor Ian R. , Ludlam Christopher A. , Frier Brian M. 
Published: August 2015

1. The effects of venous occlusion on the coagulation and fibrinolytic systems were investigated in six patients with type 1 (insulin-dependent) diabetes and 11 age- and sex-matched non-diabetic control subjects. The coagulation parameters (fibrinogen, prothrombin time, partial thromboplastin time with kaolin, von Willebrand factor antigen) did not differ between patients and control subjects either before or after 20 min of venous occlusion. No rise was observed in von Willebrand factor antigen after venous occlusion in either group.
2. In the diabetic patients, chronic activation of the fibrinolytic system was found at baseline, which was indicated by a shortened euglobulin lysis time (P &lt; 0.01), increased tissue plasminogen activator activity (P &lt; 0.05) and decreased plasminogen activator inhibitor type 1 antigen level (P &lt; 0.05), when compared with control subjects. In both groups venous occlusion resulted in significant increments in all measurements, except plasminogen activator inhibitor type 1 antigen level. The post-occlusion values did not differ between the two groups, except the plasminogen activator inhibitor type 1 antigen level, which remained significantly lower in the diabetic patients. The mean increments in each parameter did not differ between the two groups.
3. Coagulation and fibrinolysis were assessed in response to acute insulin-induced hypoglycaemia. Von Willebrand factor antigen levels increased significantly in both groups, with no difference in maximal increments. Significant activation of the fibrinolytic system occurred in response to hypoglycaemia, demonstrated by shortened euglobulin lysis time and increased fibrin plate lysis, tissue plasminogen activator antigen level and tissue plasminogen activator activity. The absolute increments were significantly lower in the diabetic group, with an attenuated response of euglobulin lysis time (P &lt; 0.05), tissue plasminogen activator antigen level (P &lt; 0.01) and tissue plasminogen activator activity.
4. Although fibrinolysis was higher in the basal state in the diabetic patients, the attenuated response to hypoglycaemia may indicate the presence of an underlying acquired dysfunction of the vascular endothelium in diabetes. This may be of relevance to the pathogenesis of microvascular disease in type 1 diabetes.
Molecular studies on an ancient gene encoding for carbamoyl-phosphate synthetase
Authors: Schofield J. P. 
Published: August 2015

1. Carbamoyl-phosphate synthetase (EC 6.3.5.5.) catalyses the synthesis of carbamoyl phosphate, the immediate precursor of arginine and pyrimidine biosynthesis, and is highly conserved throughout evolution. The large subunit of all carbamoyl-phosphate synthetases sequenced to date comprises two highly homologous halves, the product of a proposed ancestral gene duplication. The sequences of the enzymes of Escherichia coli, Drosophila melanogaster, Saccharomyces cerevisiae, rat and Syrian hamster all have duplications, suggesting that this event occurred in the progenote predating the separation of the major phylae. Until now, only limited data on carbamoyl-phosphate synthetase were available for the primitive eukaryote Dictyostelium discoideum and for the Archaea Methanosarcina barkeri MS. The DNA sequence of the D. discoideum carbamoylphosphate gene and additional sequence for the carbamoyl-phosphate synthetase gene of M. barkeri MS have been determined, and a duplicated structure for both is clearly demonstrated.
2. Genes with ancient duplications provide unique information on their evolution. A study of the intron/exon organization of the rat carbamoylphosphate synthetase I gene and the carbamoylphosphate synthetase hamster II gene in the CAD multi-gene complex shows that at least some of their introns are very old. Evidence is provided that some introns must have been present in the ancestral precursor before its duplication.
3. The human carbamoyl-phosphate synthetase I gene has been isolated and characterized. A human liver cDNA library was constructed and probed for carbamoyl-phosphate synthetase I. A human genomic DNA cosmid library was also probed for the carbamoyl-phosphate synthetase I gene. The cDNA sequence of the human carbamoyl-phosphate synthetase I gene has been determined, and work has been initiated to confirm that at least part of this gene is contained within two cosmids spanning 46 kb. This will enable future studies to be made on mutations in this gene in the rare autosomal recessive deficiency of carbamoyl-phosphate synthetase I.
Effect of residence at altitude on the perception of breathlessness on return to sea level in normal subjects
Authors: Wilson Rachel C. , Oldfield W. L. G. , Jones P. W. 
Published: August 2015

1. The effect of residence at altitude on the perception of breathlessness after return to sea level was examined in normal subjects. Breathlessness (Borg scale), minute ventilation, respiratory frequency, tidal volume, ‘oxygen pulse’ (oxygen consumption/heart rate) and the ventilatory equivalent for oxygen (minute ventilation/oxygen consumption) were measured at exercise (cycle-ergometer) during 5 months of training before 4 weeks at 4000 m and during the 6 month period after return to sea level.
2. There was no change in the subjects' pattern of breathing (respiratory frequency and tidal volume) or ‘oxygen pulse’ after the period at altitude (P = 0.0001). The ventilatory equivalent for oxygen was increased at all work rates after the period at altitude (P = 0.02). This ratio was slightly lower after 6 weeks and had returned to normal by 6 months (P = 0.4).
3. During training there was no change in breathlessness score (P = 0.6). On return to sea level, breathlessness score relative to ventilation was reduced (P = 0.0001). This was maintained for at least 6 weeks, but not as long as 6 months.
4. This study has demonstrated that, in normal subjects, the otherwise stable and reproducible relationship between breathlessness and ventilation may be disrupted for several weeks by factors other than lung disease.
5. The mechanism responsible for this is not clear, but the observations are consistent with the hypothesis that prior experience of breathlessness may condition subsequent estimates of breathlessness.
Evidence against a putative role for glucagon as a physiological splanchnic vasodilator in man
Authors: Braatvedt G. D. , Stanners A. , Newrick P. G. , Halliwell M. , Corrall R. J. M. 
Published: August 2015

1. Previous studies have suggested that glucagon in supraphysiological doses may mediate postprandial and hypoglycaemia-induced splanchnic vasodilatation in man and experimental animals. There are no reported studies investigating the role of glucagon in doses producing circulating concentrations within the physiological range.
2. Two separate studies were performed. In study 1, superior mesenteric artery blood flow was measured by Doppler ultrasound in six normal subjects during either saline or glucagon infusion at 1, 3 and 6 ng min−1 kg−1, which resulted in circulating glucagon levels within the physiological range. Mean superior mesenteric artery blood flow fell during the 3 and 6 ng min−1kg−1 glucagon infusions (3 ng min−1kg−1: −31.8%, range −20 to −56% of baseline; 6 ng min−1 kg−1: −20.7%, range −8 to −53% of baseline; P &lt; 0.05).
3. In study 2, superior mesenteric artery blood flow was measured during hypoglycaemia induced by an insulin infusion in 12 normal subjects. In six of these subjects the effect of suppression of glucagon release during hypoglycaemia was assessed by preteatment with the somatostatin analogue octreotide (0.8 μg/kg subcutaneously) given 30 min before the insulin infusion.
4. The nadir in blood glucose concentration at the hypoglycaemic reaction was similar in both groups and glucose recovery was complete by 60 min after the hypoglycaemic reaction. Plasma catecholamine concentrations rose in both groups after the hypoglycaemic reaction.
5. Superior mesenteric artery blood flow rose at the hypoglycaemic reaction in both groups despite suppression of glucagon release with octreotide.
6. These data suggest that at physiological concentrations glucagon does not mediate splanchnic vasodilatation in man.
Nocturnal desaturation and serum erythropoietin: A study in patients with chronic obstructive pulmonary disease and in normal subjects
Authors: Fitzpatrick Michael F. , MacKay Tom , Whyte Kenneth F. , Allen Martin , Tam Robert C. , Dore Caroline J. , Henley Michael , Cotes P. Mary , Douglas Neil J. 
Published: August 2015

1. To clarify the relationship between nocturnal oxygen desaturation and erythropoietin production in patients with chronic obstructive pulmonary disease, we determined arterial oxygen saturation and serum immunoreactive erythropoietin levels over 24 h in eight patients with chronic obstructive pulmonary disease and in nine normal subjects.
2. In the normal subjects, there was a significant circadian variation in serum erythropoietin levels with the highest mean deviation from the geometric mean at 22.00 hours and the nadir at 05.00 hours.
3. The three patients with chronic obstructive pulmonary disease with the most marked nocturnal desaturation (lowest arterial oxygen saturation &lt;57%) and most marked daytime hypoxaemia (daytime arterial partial pressure of oxygen &lt; 6 kPa) had raised nocturnal serum erythropoietin levels. In two of these patients, the serum erythropoietin level was raised throughout the 24 h and erythrocyte mass was also raised. In the other patient, the serum erythropoietin level was not raised in five daytime samples and erythrocyte mass was normal.
4. The other five patients with chronic obstructive pulmonary disease with less severe nocturnal hypoxaemia (lowest arterial oxygen saturation range 78–86%) had serum erythropoietin levels (range 14–36 m-i.u./ml) which were indistinguishable from normal (range 12–44 m-i.u./ml) and showed circadian changes which were not significantly different (P = 0.35) from those in the normal subjects.
5. Thus, mild nocturnal oxygen desaturation is not associated with elevation of serum erythropoietin levels, whereas daytime hypoxaemia with associated severe nocturnal desaturation is associated with increased serum erythropoietin levels both by day and by night.
Electron paramagnetic resonance spectroscopy of stable free radicals in the liver compared with ultrastructural and functional damage in a rat model of alcohol- and iron-overload
Authors: Butcher Graham P. , Deighton Nigel , Batt Roger M. , Ding Boliang , Haywood Susan , Hoffman John , Jackson Malcolm J. , Symons Martyn C. R. , Rhodes Jonathan M. 
Published: August 2015

1. Electron paramagnetic resonance spectroscopy was used to study free-radical signals in freeze-clamped frozen liver tissue from rats after a 1 year period of dietary supplementation with alcohol, iron, or alcohol and iron. In alcohol-fed, iron-fed and alcohol- and iron-fed animals, mild histological damage was seen on light microscopy and evidence of mitochondrial and nuclear injury was identified by electron microscopy.
2. Subcellular fractionation studies showed an increase in the activity of the peroxisomal marker catalase (P &lt;0.01) in alcohol-fed rats compared with controls, but a fall of 82% (P &lt;0.001) in alcohol- and iron-fed animals. The activity of the mitochondrial marker succinate dehydrogenase rose by 7% (not significant) in alcohol-fed animals and by 17% (not significant) in iron-fed animals, but fell by 94% (P &lt;0.001) in alcohol- and iron-fed animals, suggesting serious impairment of mitochondrial function.
3. Iron overload was substantial in the iron-fed animals and there was an excellent correlation between liver iron concentration and iron-derived signals by electron paramagnetic resonance spectroscopy (P &lt;0.001). A clear free-radical signal of g = 2.003–2.005 was detected in all liver samples, but there was no significant difference in the magnitude of this signal in any study group.
4. The absence of any increase in the stable free-radical signal, even in the presence of considerable hepatic damage, does not support the hypothesis that free radicals mediate alcoholic liver disease in this animal model, although the results cannot be taken as proof against this hypothesis.
Noradrenaline Kinetics and Coronary Haemodynamics during Acute β1-Adrenoceptor Blockade in Man
Authors: McCance Alastair J. , Forfar J. Colin 
Published: August 2015

1. To investigate the effects of acute β1-adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 μg min−1 kg−1) in 10 patients undergoing diagnostic cardiac catheterization, in whom β-adrenoceptor antagonists had been discontinued for 7 days.
2. Coronary haemodynamics were measured in these 10 patients plus two others. Compared with saline placebo, metoprolol administration was associated with decreases in heart rate (68 ± 2 to 59 ± 3 beats/min, P &lt; 0.001) and coronary sinus blood flow (86 ± 8 to 68 ± 6 ml/min, P &lt; 0.001) and an increase in calculated coronary vascular resistance (1.42 ± 0.19 to 1.75 ± 0.22 mmHg min ml−1, P &lt; 0.001). Arterial and femoral venous noradrenaline concentrations, whole-body noradrenaline clearance and whole-body noradrenaline spillover to arterial plasma did not change. In contrast, cardiac noradrenaline spillover (33.7 ± 5.1 to 20.2 ± 4.3 pmol/min, P &lt; 0.05) and cardiac noradrenaline clearance (31 ± 3 to 23 ± 3 ml/min, P &lt; 0.001) were significantly decreased during metoprolol administration.
3. These results may be explained by inhibition of pre-junctional facilitatory β-adrenoceptors, which we hypothesize may be predominantly of the β1-subtype in the heart and of the β2-subtype in the periphery.