bluuebunny/crossref_metadata_2025 huggingface dataset:
Cigarette smoke-induced ‘chronic bronchitis’: A study in situ of laryngo–tracheal hypersecretion in the rat
Authors: Rogers D. F. , Turner N. C. , Marriott C. , Jeffery P. K.
Published: August 2015

1. Mucous secretion and mucosal permeability by the larynx and trachea, isolated in situ, was investigated in normal rats and in those in which ‘chronic bronchitis' was induced by daily exposure to cigarette smoke for 2 weeks. Fucose was used as a specific marker for the secretion of mucus glycoprotein, and hexose and protein were markers both for mucus and plasma-type glycoproteins present in tissue fluid transudate. Albumin was used as an indicator of the contribution of serum to the secretions.

2. After equilibration, the mean basal secretion of fucose (μg/30 min collection) was significantly higher in ‘bronchitic’ rats than in the controls (P < 0.01). Mean values for controls were: fucose 3 (sem 1; n = 9), hexose 41 (sem 9; n = 8), protein 1082 (sem 385; n = 8), albumin <2 (n = 8); for ‘bronchitic’ rats the values were: 24 (sem 6; n = 7), 101 (sem 26; n = 8), 2000 (sem 520; n = 8) and <2 μg (n = 7) respectively.

3. In control and bronchitic animals acute administrations of cigarette smoke, blown directly through the laryngo-tracheal segment after equilibration, caused significant (P < 0.05) transient increases in the secretion of fucose, hexose and protein, but not of albumin.
Time course of changes in hepatic metabolism in response to sepsis in the rat: Impairment of gluconeogenesis and ketogenesis in vitro
Authors: De Vasconcelos Paulo R.L. , Kettlewell Michael G. W. , Williamson Dermot H.
Published: August 2015

1. The time course (12, 24 and 48 h) of changes in blood metabolites, and in gluconeogenesis and ketogenesis, in isolated hepatocytes from rats made septic by caecal ligation and puncture was measured.

2. Blood glucose was not significantly different in septic rats, but lactate was increased at 12, 24 and 48 h; pyruvate and alanine were increased at 48 h. The blood ketone body concentrations were decreased at all times studied after induction of sepsis. These changes were accompanied by increased plasma insulin in the septic rats.

3. The rate of hepatic lipogenesis in vivo was increased at 24 and 48 h.

4. There were appreciable increases in the hepatic concentrations of alanine (200%), lactate (200%) and pyruvate (100%) as well as other intermediates in the gluconeogenic pathway. The hepatic concentrations of acetyl-CoA and ketone bodies were decreased.

5. The rate of gluconeogenesis from added lactate, pyruvate, alanine and glutamine was depressed in isolated hepatocytes from septic rats at 24 and 48 h.

6. The basal rate of ketogenesis or the rate from butyrate in isolated hepatocytes was not significantly altered by sepsis, whereas the rate from oleate was decreased at all time points.

7. It is concluded that there is an impairment of the capacity for gluconeogenesis and ketogenesis in livers of septic rats. The latter may be due to decreased entry of long-chain acyl-CoA into the mitochondria for oxidation. The possibility that these changes are in part brought about by the hyperinsulinaemia associated with the sepsis is discussed.
Absorption of 5-fluorouracil and related pyrimidines in rat small intestine
Authors: Bronk J. R. , Lister Norma , Lynch Susan
Published: August 2015

1. The transport of 5-fluorouracil, uracil and thymine has been studied with isolated jejunal loops of rat small intestine. High performance liquid chromatography was used to identify the pyrimidines and measure their concentrations.

2. When the lumen of the intestine was perfused with 5-fluorouracil or uracil at 0.1 mmol/l or 0.2 mmol/l, the concentration in the serosal secretions was significantly higher than that in the lumen. For thymine the serosal concentration exceeded that in the lumen only at 0.1 mmol/l.

3. Analysis of the mucosal tissue water at the end of the perfusion demonstrated that when the intestinal lumen was perfused with any one of the three pyrimidines at 0.1 mmol/l or 0.2 mmol/l the concentration within the tissue was significantly above that in the lumen.

4. After an initial lag period linear rates of transport from the lumen to the serosal secretions were obtained for all three pyrimidines over a 10-fold concentration range from 0.1 mmol/l to 1 mmol/l.

5. Uracil and thymine inhibited the transmural transport of 5-fluorouracil.

6. The transport of 5-fluorouracil was also studied with a vascularly perfused preparation of rat small intestine. At 0.1 mmol/l the rate of transmural transport of the drug in this preparation was substantially higher than in the jejunal loops. This difference was eliminated by adding 5-fluorouracil to the vascular perfusate, suggesting that the higher transport rate in the vascularly perfused preparation was due to the lower serosal drug concentrations in the mesenteric circulation of the perfused intestine.

7. At a concentration of 5 mmol/l 5-fluorouracil inhibited water transport in the isolated loops and transmural D-galactose transport in the vascular perfusions.
Blood fuel metabolites in asthma during and after progressive submaximal exercise
Authors: Packe G. E. , Wiggins J. , Singh B. M. , Nattrass M. , Wright A. D. , Cayton Ruth M.
Published: August 2015

1. Ten male stable asthmatic subjects and 10 matched control subjects performed a progressive exercise test on a treadmill to 85% of their predicted maximum heart rate.

2. Blood lactate, pyruvate, hydrogen ion, glucose, alanine, glycerol and total ketone body concentrations were measured at frequent intervals during and up to 60 min after exercise. Carbon dioxide production, oxygen consumption, ventilation, respiratory exchange ratio and oxygen saturation were also measured during and up to 10 min after exercise.

3. There were no significant differences between the asthmatic and control subjects in levels of carbon dioxide production, oxygen consumption and ventilation. The respiratory exchange ratio was greater in the asthmatic subjects during recovery from exercise (P < 0.05). No changes in oxygen saturation were observed during exercise in either group.

4. In both asthmatic and control subjects, lactate, pyruvate, hydrogen ion, alanine and glycerol concentrations showed an increase from baseline levels, reaching maximum levels up to 10 min after exercise and returning to baseline within 1 h after exercise. Total ketone body concentrations decreased during exercise.

5. There were no significant differences between the asthmatic and control subjects in the concentration of any metabolite over the study period.

6. These data indicate that fuel metabolism during and after short-term progressive exercise is similar in stable asthmatic and normal subjects.
Relationship between hepatic levels of glutathione and sulphobromophthalein retention in hyperthyroidism
Authors: Sir Teresa , Wolff Carlos , Soto Juan Ramon , Perez Gilberto , Merino Rodolfo Armas
Published: August 2015

1. Sulphobromophthalein (BSP) retention and liver glutathione levels were studied in uncomplicated hyperthyroid patients.

2. BSP retention was increased in 52.5% of the subjects at admission (n = 40) and in 28% of the cases after 3 months of propylthiouracil treatment (300–400 mg/day) (n = 25).

3. Hepatic levels of glutathione were measured in six patients and significant inversed power correlation with BSP retention was observed (r = 0.968, P < 0.001).

4. These data support the contention that the alteration of the BSP retention observed in hyperthyroidism could be due to a decreased availability of hepatic glutathione for conjugation.
Bronchial hyper-responsiveness after human cardiopulmonary transplantation
Authors: Glanville Allan R. , Burke Conor M. , Theodore James , Baldwin John C. , Harvey James , Vankessel Antonius , Robin Eugene D.
Published: August 2015

1. Bronchial responsiveness to inhaled methacholine was studied in ten heart-lung transplant (HLT) recipients a mean 10.6 months (range 1.5–28 months) post-HLT and in ten normal subjects.

2. The mean provocation dose of methacholine producing a 20% fall in FEV1 (PD20 FEV1) was significantly lower in the HLT recipients (1.70 ± 3.96 mg vs 11.55 ± 3.79 mg; P < 0.001), as was the mean provocation dose of methacholine producing a 50% fall in specific airway conductance (PD50 sGAW) (0.08 ± 0.08 mg vs 5.13 ± 5.47 mg; P < 0.005).

3. These results establish the presence of significant bronchial hyper-responsiveness to inhaled cholinergic agonists in the transplanted lung.
Measurement of lung tissue mass, thoracic blood and interstitial volumes by transmission/emission scanning using [99mTc]pertechnetate
Authors: Briggs B. A. , Bradley T. M. , Vernon P. , Cooke N. T. , Drinkwater C. , Gillett M. K. , Snashall P. D.
Published: August 2015

1. We have developed a method for non-invasive measurement of lung tissue mass, thoracic blood and interstitial volumes by a combination of transmission and emission scanning with technetium isotope (99mTc).

2. In a lung model we demonstrated that emission counts could be successfully corrected for attenuation with data obtained by transmission scanning, despite an uneven distribution of radioactivity and attenuation in the model.

3. In dogs we compared regional transthoracic tissue thickness, measured by transmission scanning, and regional ‘thickness’ of blood measured by transmission/emission scanning with direct gravimetric measurements made post mortem. Scanning and direct measurements correlated significantly.

4. In man we used a [99mTc]pertechnetate (99mTcO4) flood source to obtain antero–posterior transmission scans with a gamma-camera. The thickness of attenuating tissue was estimated in each pixel. Scans were obtained of thoracic blood (by labelling erythrocytes with 99mTcO4) and of interstitium (with 99mTc-labelled diethylene-triaminepenta-acetic acid and subtraction of the blood image). We used a computer program to correct the emission scans for attenuation using the transmission scan derived tissue thickness, pixel by pixel. Finally we took a lateral chest radiograph to estimate chest wall thickness.

5. In normal man lung tissue thickness at hilar level was 3.1 ± 0.5 cm (n = 8). Thoracic blood thickness increased from the apex downwards in the upright lung, being 1.2 ± 0.1 cm at the hilar level and 2.0 ± 0.3 cm at the lung base. Interstitial thickness was 0.8 ± 0.3 cm at the hilum and 0.85 ± 0.2 at the base. These values compare well with data in the literature.

6. In emphysema (n = 5) lung tissue and blood thickness were decreased; interstitial thickness was normal. In patients with interstitial pneumonitis (n = 7) lung tissue thickness was approximately doubled, and interstitial thickness similarly increased. In two patients with acute pulmonary sarcoidosis interstitial thickness was not increased despite a marked increase in lung tissue thickness.

7. In conclusion, this technique gives information not readily obtainable by other methods, which may be of clinical utility. Further evaluation and development is warranted.
The effects of atrial fibrillation on coronary blood flow and performance of ischaemic myocardium in dogs with coronary artery stenosis
Authors: Ertl Georg , Meesmann Malte , Krumpiegel Klaus , Kochsiek Kurt
Published: August 2015

1. Atrial fibrillation may impair coronary blood flow by tachycardia and reflex vasoconstriction. It has not been documented, however, whether in the presence of coronary stenosis atrial fibrillation exceeds the effects of rhythmic atrial tachycardia.

2. The effects of experimentally induced atrial fibrillation compared with atrial tachycardia, therefore, were tested in 22 anaesthetized dogs. Stenosis of the left anterior descending coronary artery was induced to reduce coronary blood flow by about 40%.

3. In the presence of coronary stenosis, atrial fibrillation (ventricular rate: 234 ± 21 beats/min) reduced coronary blood flow from 58 ± 7 to 44 ± 8 ml min−1 100 g−1 (P < 0.001, mean ± sem) and subendocardial segment shortening (ultrasonic crystals) from 12 ± 2 to 4 ± 2% (P < 0.0025), and resulted in a lactate production of 30 ± 11% (P < 0.005 vs sinus rhythm).

4. Atrial tachycardia (heart rate: 216 ± 21 beats/min, NS vs atrial fibrillation) did not significantly change coronary blood flow and reduced segment shortening to 7 ± 3% (P < 0.05 vs atrial fibrillation). Significant lactate production did not occur.

5. Since mean arterial pressure fell from 100 ± 4 mmHg at sinus rhythm to 89 ± 3 mmHg (P < 0.01) during atrial fibrillation but not during atrial tachycardia, it was held constant in 13 dogs by a pressurized blood reservoir. Coronary blood flow, however, fell from 43 ± 6 to 36 ± 5 ml min−1 100 gv1 (P < 0.0025).

6. Thus atrial fibrillation may reduce coronary blood flow and induce myocardial ischaemia in the presence of coronary stenosis in excess of atrial tachycardia.
Influence of exercise on ascorbic acid status in man
Authors: Gleeson M. , Robertson J. D. , Maughan R. J.
Published: August 2015

1. The response of circulating leucocytes with regard to changes in number, proportion of granulocytes and lymphocytes, as well as changes in the ascorbic acid (AA) concentration of plasma and isolated lymphocytes, were studied in nine men who ran a 21 km race. A marked leucocytosis was noted 5 min after the race, the predominant increase being in granulocytes (P < 0.001) with smaller relative increases in circulating lymphocytes (P < 0.01) and platelets (P < 0.001). Numbers of leucocytes and platelets returned to pre-exercise levels within 24 h after the race.

2. The concentration of AA in plasma increased from 52.7 ± 4.1 μmol/l before the race to 67.0 ± 5.3 μmol/l within 5 min after the race (P < 0.001). This increase in plasma AA concentration was positively correlated with the rise in plasma Cortisol concentration during the race (r = 0.89; P < 0.01). However, within 24 h after the race the plasma concentration of AA fell 20 ± 4% below pre-exercise values (P < 0.01) and remained low for at least the next 2 days (P < 0.05).

3. Lymphocyte AA concentration increased from 15.6 ± 0.6 to 19.7 ± 0.9 μmol/g of lymphocyte protein during the race (P < 0.01) but returned to normal levels within 2 days after the race.

4. It is suggested that the adrenal gland may be the major source of AA efflux into the circulation during exercise.
Ageing and the α2-adrenergic system of the platelet
Authors: Davis Pamela B. , Silski Catherine
Published: August 2015

1. Platelets taken from healthy unmedicated subjects over 65 years of age display less inhibition of prostaglandin E1 (PGE1)-stimulated adenosine 3′:5′-cyclic monophosphate (cyclic AMP) synthesis by noradrenaline than do platelets taken from young adults aged 18–25 years (P < 0.03). The inhibition of cyclic AMP production by noradrenaline (10−5 mol/l) correlates negatively with age over the range 18–92 years (r = −0.338, n = 108, P < 0.005). The reduced cyclic AMP inhibition by noradrenaline in the elderly is not explained by basal cyclic AMP levels or degree of stimulation of platelets by PGE1, which do not differ between young and elderly subjects. The reduction itself is small, though, and cannot be demonstrated for a more potent agonist, adrenaline.

2. Despite the reduced noradrenaline response in the cyclic AMP system in the aged, platelet aggregation in response to α2-adrenergic agents is normal or even slightly increased. Aggregation responses to adrenergic agents correlate well with aggregation responses to adenosine 5′-diphosphate, suggesting that the effector system is a major determinant of the aggregation response.

3. α2-Adrenoceptor number measured by Scatchard analysis of equilibrium binding of [3H]yohimbine to platelet membranes is comparable in young and old subjects, and does not correlate with age. The KD for [3H]yohimbine does not correlate with age. The IC50 for noradrenaline displacing [3H]yohimbine is comparable in young and elderly subjects. Therefore the reduced inhibition of cyclic AMP production by noradrenaline in platelets from elderly subjects is not explained by changes in α2-adrenoceptor number, or agonist- or antagonist-binding properties, but may reside in the coupling of receptor to cyclase.
Specific binding of atrial natriuretic peptide to rat mesenteric artery: Effect of calcium and 5-guanylylimidodiphosphate
Authors: Lyall Fiona , Morton J. J.
Published: August 2015

1. High-dissociation equilibrium constant (20 pmol/l, receptor number 17 fmol/mg) and low-dissociation equilibrium constant (10 nmol/l, receptor number 5 nmol/mg) affinity binding sites for atrial natriuretic peptide have been identified in membrane preparations from rat mesenteric artery.

2. Tracer degradation was corrected for mathematically and binding data were analysed by a non-linear computer technique.

3. Non-atrial natriuretic peptide vasoactive hormones, angiotensin II, vasopressin and bradykinin, did not compete for the high-affinity site. Related peptides with either C- or N-terminal amino acids missing still competed, while peptides without an intact disulphide bridge did not compete.

4. Neither the addition nor the removal of calcium affected the affinity or density of binding sites. Also the non-hydrolysable guanosine triphosphate analogue 5-guanylylimidodiphosphate had no effect on either affinity or number of sites.

5. These results indicate the presence of a specific high-affinity vascular receptor for atrial natriuretic peptide which could interact with the hormone under physiological conditions. The mechanism of binding is uncertain but is unlikely to involve calcium- or guanosine triphosphate-associated regulatory sites.
Endogenous vasopressin affects postural control of blood pressure in man
Authors: Simpson H. C. R. , Zubillaga J. E. , Collier J. G. , Bennett E. D. , Mehta N. , Ang V. T. Y. , Jenkins J. S.
Published: August 2015

1. Six healthy volunteers received intravenous infusions of isotonic (0.9% NaCl) and hypertonic (3% NaCl) saline on separate days. There were no significant changes in blood pressure or forearm blood flow, despite an increase in plasma arginine vasopressin (AVP) during hypertonic saline.

2. Immediately and 10 min after passive tilting to 50°, mean forearm blood flow fell by 17.1 and 14.3% compared with the values in the supine position during isotonic saline and by 40.3 and 43.3% during hypertonic saline. Forearm vascular resistance rose by 23.6 and 17.8% with isotonic saline and by 80.2 and 88.2% with hypertonic saline for the two readings in the tilted compared with the supine position.

3. Tilting was associated with a 14.9 and 12.1% rise in diastolic blood pressure immediately and 10 min after assuming this position during hypertonic saline, and a rise of 6.4% in mean arterial pressure.

4. The results from this study are similar to those obtained previously, when small amounts of AVP were infused. They provide further evidence that AVP may have a physiological role in the postural regulation of blood pressure.
Is low-level respiratory resistive loading during exercise perceived as breathlessness?
Authors: Lane R. , Adams L. , Guz A.
Published: August 2015

1. The effect of adding low-level (2.7 cmH2O 1−1 s) external respiratory resistive loads on exercise-induced breathlessness has been examined in naive normal subjects; the intensity of this loading was chosen to simulate that confronting an asthmatic subject during exercise.

2. Each of 18 subjects performed two separate tests in which workload was oscillated while the respiratory loading was changed every minute between no loading, inspiratory loading only, and inspiratory plus expiratory loading. Each loading condition was given three times, and both these changes and those in workload were unpredictable as far as the subject was concerned.

3. The purpose was to ‘confuse’ subjects and obtain subjective estimates of their intensity of breathlessness independent of any expectation associated solely with the readily perceptible changes in external resistances to breathing. The study design was balanced for the group as a whole, both in terms of workload and respiratory loading condition.

4. The addition of these respiratory resistive loads during exercise did not result in a significant increase in the intensity of breathlessness.

5. Estimates of the rate of work of breathing revealed that this increased more with respiratory loading than it did as ventilation rose throughout the test; on the other hand, the intensity of breathlessness increased by a greater extent with continued exercise compared with the changes accompanying the addition of respiratory loads.

6. It is concluded that the intensity of the sensation of breathlessness experienced by normal subjects during exercise is not simply a reflection of an increased rate of work of breathing being performed by the respiratory muscles.

7. It is further suggested that similar studies in which internal resistances are increased experimentally are indicated in order to analyse the factors underlying the breathlessness of asthma.
Influence of sodium concentration in cerebrospinal fluid on plasma atrial natriuretic peptide in conscious rats
Authors: Kawano Yuhei , Yoshida Kaoru , Hirata Yukio , Yoshimi Hiroki , Kuramochi Morio , Ito Keiichi , Omae Teruo
Published: August 2015

1. To test the influence of a sodium (Na+) stimulus within the central nervous system on the release of atrial natriuretic peptide (ANP), we examined the effects of intracerebroventricular infusion of high Na+ artificial cerebrospinal fluid (CSF) on blood pressure, urinary Na+ excretion and plasma ANP levels in conscious Wistar rats.

2. Infusion of high Na+ (0.6 mol/1) CSF into the lateral ventricle at a rate of 1 μl/min for 60 min significantly increased mean blood pressure and urinary Na+ excretion, while normal Na+ (0.15 mol/1) CSF had no effects. Plasma ANP levels were higher in the high Na+ CSF group than in the normal Na+ group (154 ±39 vs 52 ±19 pmol/l, P < 0.05).

3. Interruption of the sympathetic nervous system and the vascular action of vasopressin with intravenous hexamethonium and d(CH2)5Tyr(Me)arginine vasopressin attenuated the pressor and natriuretic responses to intracerebroventricular high Na+ CSF. Plasma ANP levels in these rats did not differ significantly from those in rats which were similarly treated but were given normal Na+ CSF.

4. These results indicate that elevation of the CSF Na+ concentration without peripheral volume loading can stimulate ANP release into the circulation. ANP release due to central Na+ stimulus appears to be mediated by the sympathetic nervous system, vasopressin, and/or haemodynamic change caused by these factors.
Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis
Authors: Herbert K. E. , Scott D. L. , Perrett D.
Published: August 2015

1. Nucleosides and bases in physiological fluids result from metabolism of nucleic acids and nucleotides and from dietary sources. As nucleotide catabolism increases during tissue injury, nucleosides and bases could serve as useful biochemical markers in arthritis.

2. We have quantified nucleosides and bases in synovial fluid and plasma by high-performance liquid chromatography in order to examine whether nucleotide metabolism is increased in patients with rheumatoid arthritis and osteoarthritis.

3. At least ten u.v.-absorbing compounds were detected in plasma and synovial fluid; only urate, creatinine, hypoxanthine and uridine were present in identifiable and quantifiable amounts.

4. In synovial fluid from patients with rheumatoid arthritis the concentration of hypoxanthine was increased and that of urate decreased compared with osteoarthritis.

5. These data suggest that there is an increase in purine metabolism in the rheumatoid arthritis joint and that hypoxanthine is a potential marker of synovitis.
Acute effects of surgery on carbohydrate production and utilization in the fed rat
Authors: French Timothy J. , Holness Mark J. , Goode Anthony W. , Sugden Mary C.
Published: August 2015

1. The work utilized a model of uncomplicated abdominal surgery (laparotomy under ether anaesthesia) to delineate the effects of abdominal trauma on glucose homoeostasis in the fed rat.

2. Regulation of glucose production and utilization was investigated by observing the response to the administration of glucose, insulin plus glucose and 5-methylpyrazole 3-carboxylic acid.

3. Glucose administration suppressed hepatic glucose output as assessed by portal–venous concentration differences in control or surgically stressed rats. In contrast, glycaemia was increased and lactaemia decreased in the latter group. Portal–venous concentrations differences for lactate were unaffected.

4. Surgery increased plasma fatty acid concentrations and the antilipolytic response to glucose or glucose plus insulin was diminished. Post-operative increases in fatty acid concentrations were associated with inhibition of hepatic pyruvate dehydrogenase complex which was reversed by insulin, indicating a differential sensitivity of adipose tissue and liver to the hormone.

5. The model of surgical stress utilized, while affecting extrahepatic glucose disposal, did not elicit depletion of liver glycogen or inactivation of l-pyruvate kinase.

6. It is concluded that the initial response to uncomplicated abdominal surgery involves carbohydrate conservation rather than increased glucose production, with effects to decrease extrahepatic glucose uptake and hepatic glucose oxidation.
Evaluation of angiogenesis in chronic inflammation by laser-Doppler flowmetry
Authors: Orlandi C. , Dunn C. J. , Cutshaw L. G.
Published: August 2015

1. A non-invasive method is described for the assessment of angiogenesis in chronic inflammation using laser-Doppler flowmetry.

2. Significant increases in capillary blood flow were seen on days 5 and 7 after induction of subcutaneous granulomatous lesions, as compared with control skin.

3. Changes in blood flow were accompanied by changes in pulsatile flow pattern and by an intense angiogenic response observed by light microscopy.

4. The potential application of laser-Doppler flowmetry to quantitative and qualitative studies of evolving angiogenesis in pathological responses is discussed.
Effect of changes in dietary sodium on active electrolyte transport by erythrocytes at different stages of human pregnancy
Authors: Gallery E. D. M. , Rowe J. , Brown M. A. , Ross M.
Published: August 2015

1. Active electrolyte transport was examined in erythrocytes from women in the second and third trimesters of pregnancy and post partum, and compared with that in ovulating women.

2. There was a significant reduction in intracellular sodium ([Na]i) and increase in intracellular potassium ([K]i) in pregnancy with a return towards normal values in the post-partum period.

3. Maximum specific ouabain binding [number of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) units] was increased by 70% in pregnancy and returned slowly towards normal values post partum.

4. Na+,K+-ATPase activity as determined by ouabain-sensitive 86Rb influx in artificial media was also increased in pregnancy by 13%. It returned towards normal post partum.

5. The increases in Na+,K+-ATPase in pregnancy were not closely related to the concomitant increases in aldosterone or cholesterol nor to reticulocytosis and were not affected by 7 days of high (> 250 mmol/day) or low (< 50 mmol/day) sodium intake.
Influence of hyperinsulinaemia on intracellular amino acid levels and amino acid exchange across splanchnic and leg tissues in uraemia
Authors: Alvestrand Anders , Defronzo Ralph A. , Smith Douglas , Wahren John
Published: August 2015

1. To examine whether insulin resistance in uraemia extends to amino acid metabolism, the effect of physiological hyperinsulinaemia on plasma amino acid concentrations was studied in 17 chronically uraemic and 28 healthy subjects by using the euglycaemic insulin clamp technique.

2. In six uraemic and seven control subjects, splanchnic and leg exchange of amino acids was quantified with hepatic and femoral venous catheterization, and in five uraemic and eight control subjects intracellular free amino acid concentrations were determined in muscle tissue obtained by needle biopsy.

3. In response to hyperinsulinaemia the plasma concentrations of all amino acids except alanine decreased by 10–50% in both uraemic and control subjects. Splanchnic alanine uptake declined by 20% and leg amino acid release tended to decrease in both groups.

4. The intracellular levels of all measured amino acids except alanine fell significantly and to a similar extent in uraemic and control subjects.

5. These results indicate that insulin-mediated alterations in regional amino acid exchange and in plasma and intracellular amino acid concentrations are similar in uraemic and control subjects.

6. It is concluded that tissue insensitivity to insulin in uraemia does not extend to uptake or release of amino acids and that resistance to insulin can be selective in its effect on different metabolic functions.
Effect of inhaled methacholine on gas mixing efficiency
Authors: Langley F. , Horsfield K. , Burton G. , Seed W. A. , Parker S. , Cumming G.
Published: August 2015

1. Pulmonary function tests, including alveolar mixing efficiency by the single-breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance.

2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml (P < 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% (P < 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 > P > 0.05).

3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal.

4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81mKr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well.
Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man
Authors: Morice Alyn , Pepke-Zaba Joanna , Loysen Elena , Lapworth Ruth , Ashby Michael , Higenbottam Tim , Brown Morris
Published: August 2015

1. The effects of low dose infusion of atrial natriuretic peptide (ANP) were observed in a double-blind, placebo-controlled study in six fluid-loaded volunteers. After baseline observations, hourly increments of 0.4, 2 and 10 pmol min−1 kg−1 were infused with continuous observation of heart rate, blood pressure and cardiac output. Plasma ANP, aldosterone, and catecholamines, and urinary volume and sodium excretion, were estimated at half-hourly intervals.

2. ANP infusion resulted in an increase of 35, 98 and 207% in urinary sodium excretion and of 10, 20 and 71% in urinary volume when compared with placebo. Plasma ANP was markedly elevated above placebo levels only during infusion of 10 pmol of ANP min−1 kg−1.

3. No change in heart rate or blood pressure was noted during the study, but a significant fall in stroke volume index was observed during active treatment. Plasma levels of aldosterone and catecholamines were not significantly different on the 2 treatment days.

4. The potent natriuretic and diuretic effects of this peptide at plasma concentrations not significantly elevated from physiological suggest a hormonal role for ANP in the homoeostasis of salt and water balance.
Rapid changes in plasma potassium during a game of squash
Authors: Struthers A. D. , Quigley C. , Brown M. J.
Published: August 2015

1. The game of squash has recently been associated with a high incidence of ventricular arrhythmias and sudden death. To investigate this further, plasma catecholamines and potassium (K+) were monitored during a game of squash in six normal volunteers.

2. No cardiac arrhythmias were seen in this study despite the subjects reaching maximum heart rates of 181 ± 5 beats/min (mean ± sem).

3. During exercise, plasma K+ rose from 3.82 ± 0.16 to 4.29 ± 0.2 mmol/l, but after 90 s rest this fell to 3.68 ± 0.28 mmol/l and after 180 s to 3.44 ± 0.17 mmol/l. This rapid K+ shift could not be accounted for by generalized changes in venous acid-base status or by changes in venous plasma catecholamines. Although pre-treatment with a β2-antagonist caused the overall plasma K+ levels to be higher, it had no significant effect on the fall in plasma K+ after exercise.

4. Such rapid K+ shifts after exercise might contribute to arrhythmogenesis in susceptible individuals. The precise mechanism of the fall in K+ after exercise remains undetermined, but it seems not to involve catecholamines stimulating β2-adrenoceptors and is more likely to be due to increased skeletal muscle blood flow and/or intracellular acidosis.
Effects of angiotensin II and atrial natriuretic peptide alone and in combination on urinary water and electrolyte excretion in man
Authors: McMurray J. , Struthers A. D.
Published: August 2015

1. Atrial natriuretic peptide (ANP) has previously been shown to inhibit the renin–angiotensin–aldosterone system (RAAS) at several different levels. We have now investigated a further non-endocrine, renal interaction between ANP and the RAAS.

2. The effects of ANP and angiotensin II (ANG II) alone, and in combination, on urinary electrolyte and water excretion were studied in eight normal male subjects undergoing maximal water diuresis.

3. ANP caused a significant increase in urine flow and sodium excretion. ANG II alone was antidiuretic, antinatriuretic and antikaliuretic. When ANP was given against a background infusion of ANG II, urinary flow rate and electrolyte excretion increased from a new lower level to reach a value intermediate between that found with ANG II alone and ANP alone.

4. It is concluded that the renal effects of ANP are modified in the presence of simultaneously elevated levels of ANG II and that net water and electrolyte excretion reflect the sum of the opposing influences of each peptide. While this interplay may be non-specific, it is possible that ANP may exert some of its actions by specifically inhibiting the intrarenal effects of ANG II.
Prostaglandins E2 and F2α are not involved in the monocytic-product (interleukin-1)-induced stimulation of hepatic fibrinogen synthesis in rats
Authors: Holtslag J. C. W. M. , Moshage H. J. , van Pelt J. F. , Kleuskens J. A. G. M. , Gribnau F. W. J. , Yap S. H.
Published: August 2015

1. Monocytic products, especially interleukin-1 (IL-1), play an important role in the acute-phase response. Prostaglandins have been shown to act as second messengers in several physiological alterations of the acute-phase response, such as fever, muscle wasting and immunoregulation. The present study was undertaken to determine the role of prostaglandins in the monocytic-product-induced stimulation of the hepatic synthesis of fibrinogen, a well-known acute-phase protein.

2. Prostaglandin (PG) E2, PGF2α and 16,16-dimethyl-PGE2 did not stimulate fibrinogen synthesis and fibrinogen polypeptide mRNA content when administered intraperitoneally to rats or when added to monolayer cultures of rat hepatocytes.

3. Cyclo-oxygenase inhibitors did not abolish the stimulation of fibrinogen synthesis and its mRNA content induced by monocytic products in vivo or in vitro.

4. These findings indicate that the enhanced synthesis of fibrinogen induced by monocytic products (including IL-1) during the acute-phase response is not mediated by prostaglandins or other products of the cyclo-oxygenase pathway of arachidonic acid.
Partial enterectomy decreases somatostatin-binding sites in residual intestine of rabbits
Authors: Colas B. , Bodegas G. , Sanz M. , Prieto J. C. , Arilla E.
Published: August 2015

1. Three weeks after partial enterectomy in the rabbit there was an increased somatostatin concentration and a decreased number of somatostatin-binding sites (without changes in the corresponding affinity values) in the cytosol of the residual intestinal tissue, except in the terminal ileum and the colon.

2. Five weeks after surgery both the somatostatin concentration and the number of somatostatin-binding sites returned towards control values.

3. These results suggest that an increase in bowel somatostatin content could lead to down-regulation of somatostatin-binding sites in the intestinal mucosa.
A renorenal suppression in response to atrial natriuretic peptide in the unilateral ischaemic rat
Authors: Torikai Shozo
Published: August 2015

1. The present study was carried out to investigate the haemodynamic and natriuretic effects of atrial natriuretic peptide (ANP) in normal rats and in rats with unilateral ischaemia.

2. Twenty-four hour unilateral ureter occlusion gave rise to a marked vasoconstriction in the ipsilateral kidney after its release. Intravenous infusion of ANP doubled p-aminohippurate clearance and inulin clearance and elicited massive natriuresis in the hydronephrotic kidney, while in the contralateral kidney these clearance values were decreased and there was a lack of natriuresis. The responses in the latter kidney were also different from those in the normal rat, in which significant natriuresis was elicited by ANP even though a decrease in p-aminohippurate clearance occurred.

3. After the control kidney in the unilateral hydronephrotic rat was denervated either mechanically or by pretreatment with prazosin, ANP induced a natriuresis in both kidneys. Furthermore, the renal denervation prevented the decrease in inulin clearance in the control kidney after ANP administration.

4. These findings suggest that the renal response to ANP may depend on the vascular tone before administration, and that renal nerve activity may modify the effects of ANP on renal haemodynamics and sodium excretion.
2,3-Diphosphoglycerate in normal, anaemic and transfused human fetuses
Authors: Soothill P. W. , Lestas A. N. , Nicolaides K. H. , Rodeck C. H. , Bellingham A. J.
Published: August 2015

1. The effect of anaemia and transfusion with adult blood on fetal 2,3-diphosphoglycerate levels was investigated by studying fetal blood from 45 normal pregnancies at 17–42 weeks of gestation and in 34 pregnancies complicated by erythroblastosis fetalis.

2. In normal fetuses, 2,3-diphosphoglycerate concentration was higher than in adults and did not change significantly with gestational age.

3. In erythroblastotic fetuses, there was a significant negative correlation between 2,3-diphosphoglycerate concentration and haemoglobin concentration.

4. When adult blood was transfused into the fetal circulation, 2,3-diphosphoglycerate concentration reached similar levels to that found in untransfused fetuses after allowing for the severity of anaemia.
Increased hepatic amino nitrogen conversion after elective cholecystectomy in man
Authors: Heindorff Hans , Vilstrup Hendrik , Bucher Ditlev , Billesbølle Per , Thygesen Vibeke
Published: August 2015

1. The effect of elective, uncomplicated cholecystectomy on plasma clearances of amino acids and on amino acid-stimulated urea synthesis was investigated in 10 patients, pre-operatively and on the first post-operative day, and compared with six controls treated identically apart from the surgery.

2. A mixture of amino acids was given as a prime-continuous infusion. Steady-state concentrations 75% higher than basal were attained and were maintained for 90 min. The clearances of amino acids were calculated as the ratios between amino acid infusion rate and the concentration. The urea synthesis rate was calculated as urinary excretion corrected for accumulation and intestinal loss.

3. After surgery the fasting plasma concentrations of alanine, arginine, glutamine plus glutamate, glycine, proline, lysine and threonine decreased by 20–30%, but were unchanged in the control group. The plasma clearance of α-amino nitrogen increased from 5.1 ± 1.2 ml/s before surgery (mean ± sd) to 6.1 ± 1.1 ml/s (P < 0.05, paired t-test) after surgery due to increased clearances of the above-mentioned amino acids. In the control group, the clearance decreased from 6.4 ± 1.6 to 5.9 ± 1.1 (P < 0.05, paired t-test). The amino acid-stimulated urea synthesis rate after surgery was 37 ± 9 μmol of N/s vs 30 ± 6 (P < 0.01, paired t-test) in the controls despite a lower α-amino nitrogen concentration (4.5 ± 0.5 mmol/l vs 5.1 ± 0.5 mmol/l, P < 0.05, paired t-test). The post-operative urea synthesis rate exceeded the amino nitrogen infusion by 20%.

4. Post-operatively, the insulin response to the amino acid infusion more than doubled, and the glucagon response increased by 54 %. Fasting Cortisol doubled but decreased similarly to controls during amino acid infusion.

5. After surgery amino nitrogen was cleared from the plasma pool by the liver more rapidly than it was released into the pool.

6. Our data indicate that the liver is partly responsible for the post-operative catabolism. This is not attributable to increased substrate load on the liver, but results from changed hepatic kinetics of amino nitrogen conversion. The altered hormonal responses may play a role in this condition.
Use of fractional lithium clearance in clinical and epidemiological investigation: A methodological assessment
Authors: Strazzullo P. , Iacoviello L. , Iacone R. , Giorgione N.
Published: August 2015

1. The fractional clearance of lithium (FCLi) has been validated in the rat under controlled experimental conditions as a reliable indicator of sodium and water handling in the proximal tubule. The purpose of the present study was to evaluate some key methodological aspects related to the use of the FCLi in clinical and epidemiological investigation.

2. FCLi was determined in healthy normotensive, or in some cases, in borderline/mild essential hypertensive subjects, by a morning urine collection obtained between 09.00 and 13.00 hours after a 300 mg oral lithium carbonate load (= 8.1 mmol of elemental lithium).

3. The ratio of intra-individual to inter-individual variance of FCLi, measured in free-living subjects on unrestricted diet, was shown to be low enough (0.33) to allow adequate characterization of individuals in a population with a single measurement, or at most with two (compared with at least four measurements needed to characterize the fractional excretion of sodium).

4. The remarkable influence of dietary sodium intake on FCLi, demonstrated under metabolic ward conditions, might explain a major portion of the observed intra-individual variability.

5. At the dosage employed in the present study, oral lithium administration did not affect the renal handling of sodium, potassium or calcium. Likewise, it did not induce any change in a series of 17 metabolic parameters and indicators of renal and liver function.

6. It is concluded that the FCLi may be a safe and useful tool for the clinical and epidemiological investigation of renal sodium and water handling. The possibility of a confounding effect of dietary sodium intake, however, should be kept in mind.
Effect of glucocorticoid treatment on glucose and glutamine metabolism by the small intestine of the rat
Authors: Ardawi M. Salleh M. , Majzoub May F. , Newsholme Eric A.
Published: August 2015

1. The effect of dexamethasone (30 μg day−1 100 g−1 body wt.) on the metabolism of glucose and glutamine was studied in the small intestine of rats after 9 days of treatment.

2. Dexamethasone treatment resulted in negative nitrogen balance (P < 0.001), and produced increases in the concentrations of plasma glucose (22%, P < 0.05), alanine (32%, P < 0.001) and insulin (127%, P < 0.001), but a decrease in the plasma concentration of glutamine (20%, P < 0.05).

3. Portal-drained visceral blood flow increased by approximately 22% (P < 0.001) in dexamethasone-treated rats, and was accompanied by a decrease in the arteriovenous concentration difference of glucose (43%, P < 0.001) and an increase in that of lactate (22%, P < 0.05), glutamine (35%, P < 0.01), glutamate (33%, P < 0.01) and alanine (21%, P < 0.05).

4. Enterocytes isolated from dexamethasone-treated rats showed decreased and increased rates of glucose and glutamine utilization, respectively.

5. The maximal activities of hexokinase, 6-phosphofructokinase, citrate synthase and oxoglutarate dehydrogenase were decreased (30–64%, P < 0.001) in intestinal mucosal scrapings of dexamethasone-treated rats, whereas the activity of glutaminase was increased (35%, P < 0.001).

6. It is concluded that glucocorticoid administration decreases the rate of glucose utilization but increases that of glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells.
Cardiovascular responses to stimulation of carotid baroreceptors in healthy subjects
Authors: Hainsworth R. , Al-Shamma Y. M. H.
Published: August 2015

1. Carotid baroreceptors were stimulated by application of a subatmospheric pressure to a chamber fitted round the anterior and lateral aspects of the subject's neck (neck suction). Pulse interval and heart rate were determined from an electrocardiogram, cardiac output by a single-breath method and arterial blood pressure by an automatic sphygmomanometer.

2. The maximal prolongation of the pulse interval, determined during held expiration, occurred within 2–3 s from the onset of the neck suction. All the measured variables were in steady states between 2 and 3 min from the start of neck suction.

3. Neck suction at − 10 mmHg resulted only in an immediate change in pulse interval. All variables changed approximately linearly with the magnitude of the neck suction between − 10 and − 40 mmHg.

4. The reproducibilities of the responses to neck suction at − 30 mmHg, expressed as two standard deviations of the differences between responses on two occasions, were (mean responses in parentheses): immediate pulse interval, ± 32 (+ 236) ms; steady-state heart rate, ± 2.5 (− 6.5) beats/min; cardiac output ± 0.14 (− 0.59) 1/min; systolic and diastolic blood pressures, ± 10.0 (− 16.9) and ± 5.4 (− 10.1) mmHg, respectively.

5. Control values and responses to neck suction at − 30 mmHg were compared in subjects grouped in four age bands between 19 and 80 years. With increasing age, the control value of cardiac index (cardiac output divided by calculated body surface area) decreased, systolic and diastolic pressures increased, and the responses of all the measured variables to neck suction decreased. These results, obtained from a healthy population, provide reference values for comparison with those of individuals who may have abnormal baroreceptor reflexes.
Zinc status in inflammatory bowel disease
Authors: Ainley C. C. , Cason J. , Carlsson L. K. , Slavin B. M. , Thompson R. P. H.
Published: August 2015

1. The zinc contents of plasma, erythrocytes, polymorphonuclear leucocytes and mononuclear leucocytes from 18 normal control subjects, 31 patients with Crohn's disease and 15 patients with ulcerative colitis were measured.

2. Plasma zinc levels were low in Crohn's disease, particularly in malnourished patients, and related to plasma albumin concentrations, but were normal in ulcerative colitis.

3. Erythrocyte zinc levels were normal in both Crohn's disease and ulcerative colitis.

4. Mean polymorphonuclear leucocyte zinc levels were normal in Crohn‘s disease and ulcerative colitis. Ten per cent of Crohn's disease patients had subnormal levels, which were associated with inactive disease, while 10% had elevated levels, which were associated with active disease. Seven per cent of ulcerative colitis patients had subnormal levels. Mononuclear leucocyte zinc levels were normal in Crohn's disease and in ulcerative colitis.

5. Tissue zinc depletion occurs in only a few patients with Crohn's disease and ulcerative colitis.