bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate of protein synthesis in skeletal muscle of normal man and patients with muscular dystrophy: A reassessment
Authors: Halliday D. , Pacy P. J. , Cheng K. N. , Dworzak F. , Gibson J. N. A. , Rennie M. J.
Published: August 2015

1. Quadriceps muscle protein synthetic rate has been determined in healthy subjects in the post-absorptive (n = 18) and fed (n = 10) states and in patients with a variety of myopathies, by analysis of the enrichment of serial muscle biopsies taken during primed continuous infusion of l[1-13C]leucine.

2. Quadriceps protein synthetic rates in normal subjects were (mean ± sd) 0.046 ± 0.012 and 0.075 ± 0.014%/h in the post-absorptive and fed states respectively. These results are significantly lower than we previously reported (M. J. Rennie et al., Clinical Science, 1982, 63, 519–523 [1]) but show the same relative differences of direction and magnitude, confirming the effects of feeding previously reported. In patients with muscular dystrophy, muscle protein synthetic rate was, as previously reported [1], much lower in the fed state than in normal subjects. A new finding is that for patients with myotonic dystrophy the rate is also depressed in the postabortive state.

3. We suggest that the present estimates in post-absorptive and fed normal subjects be used as reference values for quadriceps mixed muscle protein synthetic rate.
Endocrine effects of examination stress
Authors: Semple C. G. , Gray C. E. , Borland W. , Espie C. A. , Beastall G. H.
Published: August 2015

1. We have studied endocrine function in nine healthy young men 16 weeks before and immediately after Final degree examinations. Factors other than psychological stress which might have affected hormone levels were excluded.

2. The presence of psychological stress at the time of examinations was confirmed by finding increased values for two self-rating anxiety scales.

3. Urine metadrenaline excretion was increased in all subjects at the time of examination. Serum and early morning urine Cortisol as well as pituitary–testicular and pituitary–thyroid function and prolactin levels were unaffected by examination stress.

4. This study questions the popular belief that psychological stress stimulates prolactin secretion and suppresses pituitary–testicular function.
Unilateral renal ischaemia in the rat: Effect of contralateral nephrectomy and intrarenal flush with phosphate-buffered sucrose
Authors: Ferwana O. S. , Pirie S. C. , Potts D. J.
Published: August 2015

1. This study examined whether the severity of acute renal failure seen within 4 h of a 45 min period of unilateral occlusion of the renal pedicle could be reduced by removal of the contralateral healthy kidney and/or intrarenal flush with a phosphate-buffered sucrose (PBS50) solution.

2. After ischaemia, unflushed kidneys became oliguric and isosthenuric, with a fall in inulin clearance (Cin) to 0.1% of the pre-ischaemic value. Removal of the healthy contralateral kidney upon release of the occlusion caused no improvement in immediate post-ischaemic function.

3. Intrarenal flush with 1.5 ml of PBS50 resulted in a significantly improved post-ischaemic Cin, with increased urine flow rate and solute excretion; urine was also concentrated.

4. Protection of renal function against ischaemic damage was seen only when kidney tissue remained blood-free and exposed to PBS50 throughout the period of ischaemia, and when the speed of flush was similar to the expected renal blood flow (6 ml/min). Protection did not depend upon the presence or absence of the contralateral kidney.

5. The study also showed that functional removal of one kidney, either by pedicle occlusion or nephrectomy, caused an immediate rise in solution excretion from the contralateral kidney, but Cin remained unchanged. Unflushed severely damaged kidneys showed no compensatory response to unilateral nephrectomy, whereas kidneys flushed with PBS50 exhibited increases in solute excretion similar to those seen in healthy non-ischaemic kidneys.
Epithelial cell proliferation and intestinal absorptive function during starvation and refeeding in the rat
Authors: Goodlad R. A. , Plumb J. A. , Wright N. A.
Published: August 2015

1. Intestinal epithelial cell production and intestinal absorption were measured in fed, starved and refed rats.

2. Four days' starvation significantly decreased the crypt cell production rate (CCPR), absorption, small intestinal length and crypt cell population.

3. There was an immediate increase in absorption 1 day after refeeding, which preceded a slower increase in CCPR. The absorption rate then decreased progressively after refeeding, and was significantly lower than control levels 1 week after refeeding. The CCPR, however, increased more gradually, reaching control levels after 2 days and then ‘overshooting’ control values.

4. There was no significant change in the crypt cell population immediately after refeeding; thus we propose that the initial increase in absorption on refeeding is either due to an accelerated maturation rate of the enterocytes or to the migration of enterocytes from the base of the villus to the functional zone.

5. The rapid recruitment of absorptive function appeared to be a ‘one-off’ event, the villus compartment then having to wait for increased cell production in the crypts to repopulate the villi.
Haemodynamic effects of intravenous human calcitonin-gene-related peptide in man
Authors: Howden C. W. , Logue Catherine , Gavin Karen , Collie Lizbeth , Rubin P. C.
Published: August 2015

1. The effects of intravenous bolus doses of human calcitonin-gene-related peptide (hCGRP) were studied in ten healthy male volunteers. 2.5, 10 and 25 μg of hCGRP and placebo were administered to each subject in a randomized double-blind study.

2. hCGRP had no effect on systolic or diastolic blood pressure in the supine or standing position.

3. hCGRP increased supine and standing heart rate. Both the extent and duration of the tachycardia were dose related.

4. Plasma noradrenaline levels were transiently increased after 10 and 25 μg of hCGRP.

5. All subjects displayed marked facial flushing after the two higher doses of hCGRP.

6. We conclude that systemic administration of hCGRP produces tachycardia and stimulation of the sympathetic nervous system in the absence of any change in blood pressure.
Effects of nitroglycerin on forearm haemodynamics in patients with cirrhosis
Authors: Jiron M. Isabel , Lee Samuel S. , Cerini Raimondo , Pugliese Domenico , Hadengue Antoine , Lebrec Didier
Published: August 2015

1. Basal forearm haemodynamics were studied by venous occlusion plethysmography in three groups of subjects: group I, healthy controls, group II, patients with cirrhosis age- and sex-matched with group I, and group III, an older group of patients with cirrhosis. Subsequently, responses to sublingual nitroglycerin were measured in group I and II subjects.

2. Controls responded to nitroglycerin with an increase in venous distensibility; group II patients had higher initial venous distensibility but did not respond to nitroglycerin. No other variables in either group were affected by nitroglycerin.

3. Group II and III patients differed in forearm blood flow and vascular resistance and venous distensibility. A significant inverse correlation was found between age and forearm blood flow (r = −0.57, P < 0.001) in all patients with cirrhosis.

4. We conclude that (a) venous tone is reduced in cirrhosis, possibly as a result of chronic venodilatation; (b) this venodilatation impedes further dilatory response to a small dose of nitroglycerin; (c) cirrhosis is also associated with age-related decreases in peripheral haemodynamics.
Characterization of leukotriene B3: comparison of its biological activities with leukotriene B4 and leukotriene B5 in complement receptor enhancement, lysozyme release and chemotaxis of human neutrophils
Authors: Lee Tak H. , Sethi Tariq , Crea Attilio E. G. , Peters Wilfried , Arm Jonathan P. , Horton Claire E. , Walport Mark J. , Spur Bernd W.
Published: August 2015

1. Leukotriene (LT) B3 was prepared by total chemical synthesis and its identity was confirmed by nuclear magnetic resonance analysis and proton homonuclear plot of connectivities and chemical shift assignments. The effects of LTB3 on complement receptor enhancement, chemotaxis and lysozyme release in human neutrophils (PMN) were compared with those of LTB4 and LTB5.

2. LTB3 and LTB4 elicited a virtually identical dose- and time-dependent enhancement in complement receptors type 1 (CR1) and type 3 (CR3) and release of lysozyme. LTB5 was approximately 100 times less potent than LTB4 in enhancing CR1 and CR3, whereas it was 10000 times less potent than LTB4 in releasing lysozyme from human PMN.

3. LTB3 and LTB5 were respectively 5- and 100-fold less potent than LTB4 in eliciting chemotaxis.

4. These findings indicate that the pro-inflammatory potential of LTB3 and LTB4 are similar, whereas LTB5 is substantially less potent as an inflammatory mediator.

5. The finding that LTB5 is a weak and partial agonist relative to LTB3 and LTB4 could be due to the rigidity of the C-17–C-18 double bond in LTB5. This may interfere with the active site specificity of LTB5 to a substantial extent.

6. One approach to the development of antagonists to the LTB4 receptor may be to establish a rigid structure in the C-17–C-18 region of the LTB4 molecule.
Changes in concentrations of respiratory components and cytochrome oxidase activity in mitochondria obtained from carbon tetrachloride-induced cirrhotic rat liver
Authors: Morimoto Taisuke , Tanaka Akira , Taki Yoshiro , Noguchi Masashi , Yokoo Naoki , Nishihira Tomohiko , Nishikawa Katsuhide , Yamamoto Shunji , Nitta Naoki , Jikkoh Akira , Kamiyama Yasuo , Yamaoka Yoshio , Ozawa Kazue
Published: August 2015

1. Changes in the concentrations of respiratory components, phosphorylative activity, the cytochrome oxidase activity of mitochondria and the hepatic adenylate energy charge level (in situ) were studied in cirrhotic rat liver induced by carbon tetrachloride (CCl4).

2. In the cirrhotic liver mitochondria, concentrations of cytochrome a(+ a3), cytochrome b, coenzyme Q9 and coenzyme Q10 increased significantly to 2.44 ± 0.02 × 10−10 (mean ± se), 1.37 ± 0.05 × 10−10, 25.57 ± 0.47 × 10−10 and 5.39 ± 0.26 × 10−10 mol/mg of mitochondrial protein, respectively, compared with 1.83 ± 0.03 × 10−10, 1.22 ± 0.02 × 10−10, 16.24 ± 0.39 × 10−10 and 1·81 ± 0.07 × 10−10 in normal rats [P < 0.001 for cytochrome a(+ a3), coenzyme Q9 and coenzyme Q10, and P < 0.01 for cytochrome b].

3. Concentrations of flavoprotein and pyridine nucleotides decreased significantly to 13.33 ± 0.14 × 10−10 and 45.68 ± 1.59 × 10−10 mol/mg of mitochondrial protein, respectively, compared with 14.79 ± 0.33 × 10−10 and 86.26 ± 1.83 × 10−10 in normal rats (P < 0.001). There was no significant difference in the concentration of cytochrome c(+ c1).

4. Cytochrome oxidase activity per unit of cytochrome a(+ a3) increased significantly to 67.43 ± 1.71 atoms O s−1 mol−1, compared with 55.77 ± 1.16 in normal rats (P < 0.001). By contrast, phosphorylative activity per unit of cytochrome a(+ a3) decreased significantly in the cirrhotic liver to 10.40 ± 0.36 s−1 compared with 13.43 ± 0.49 in normal rats (P < 0.001). The total adenine nucleotide concentration and the hepatic energy charge level decreased significantly in the cirrhotic liver to 3.420 ± 0.075 μmol/g of wet liver and 0.806 ± 0.003, respectively, compared with 3·854 ± 0.088 and 0.841 ± 0.004 in normal rats (P < 0.001).

5. It is concluded that in mitochondria obtained from CCl4-induced cirrhotic rat liver in which the energy charge level is decreased, cytochrome oxidase activity per unit of cytochrome a(+ a3) is increased in association with an increase in cytochrome a(+ a3) concentration.
Inhibition of platelet aggregation and thromboxane production by low concentrations of aspirin in vitro
Authors: Sils D. , Rodgers S. E. , Lloyd J. V. , Wilson K. M. , Siebert D. M. , Bochner F.
Published: August 2015

1. The aspirin concentrations previously reported to inhibit platelet aggregation in vitro (40–500 μmol/l) are much greater than those required in vivo in man (5 μmol/l).

2. Human platelet-rich plasma was incubated with buffer or various aspirin concentrations at 37°C for up to 4.5 h. Platelet aggregation and thromboxane generation were measured in response to collagen (0.4–6.3 μg/ml) and adenosine 5′-pyrophosphate (0.5–4 μmol/l).

3. The concentration of aspirin needed to inhibit platelet aggregation in response to a critical concentration of aggregating agent (lowest concentration to cause greater than 50% aggregation) was lower than that required for higher concentrations of aggregating agent.

4. With more prolonged incubation times with aspirin, lower concentrations of aspirin inhibited platelet aggregation.

5. Inhibition of platelet aggregation and thromboxane formation by 10 μmol/l aspirin was maximal by 90 min. There was progressive inhibition by 3 μmol/l aspirin during incubation for 270 min. By the end of this time there was also significant inhibition by 1 μmol/l aspirin.

6. The apparent discrepancy between inhibitory aspirin concentrations in vivo and those observed in vitro in previous studies appears to have been resolved by extending the incubation time of platelets with low aspirin concentrations, thus mimicking the conditions in vivo.
Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney
Authors: Baylis Christine , Falconer-Smith James , Ross Brian
Published: August 2015

1. To examine the effect of charge and molecular size on the renal handling of immunoglobulin light chain, three different human light chains were purified, iodinated and characterized with regard to molecular weight and isoelectric point. The molecular weights were similar, whereas the isoelectric points ranged from markedly cationic to markedly anionic.

2. Renal handling of the light chains was determined in vivo in the Munich–Wistar rat and in vitro in the isolated perfused rat kidney.

3. Significant restriction to the transglomerular passage of all three light chains was evident in the intact kidney, with the most anionic light chain being restricted most while the cationic light chain was restricted least. The charge dependence of filtration of these naturally occurring proteins was, however, much less pronounced than has previously been reported for the synthetic dextrans.

4. Tubular reabsorption of the three light chains was quite variable in the intact kidney and did not appear to be related to molecular charge. In the isolated perfused kidney, once account had been taken of the abnormally high rate of filtration of these proteins, the reabsorption of the three light chains was strikingly similar to that seen in vivo.

5. With these three purified human light chains no marked influence of charge (pI) has been demonstrated in vivo or in vitro, for glomerular restriction or renal tubular reabsorption. Some other properties of human myeloma light chains may determine their renal handling and nephrotoxicity.
Atrial natriuretic peptide and total exchangeable body sodium: Relationships in rats with chronic myocardial infarction
Authors: Hodsman G. P. , Harrison R. W. , Sumithran E. , Johnston C. I.
Published: August 2015

1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially.

2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P < 0.01). The decrease was the same in rats with infarction as in controls.

3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P < 0.01).

4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium.

5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.
An assessment of a double-isotope method for the detection of transferrin accumulation in the lungs of patients with widespread pulmonary infiltrates
Authors: Rocker G. M. , Pearson D. , Stephens M. , Shale D. J.
Published: August 2015

1. The accumulation in the lung of the plasma protein transferrin was determined in 44 patients with widespread pulmonary infiltrates of various causes and in 11 healthy volunteers using a double-isotope method based on labelling in vivo of circulating transferrin with indium and erythrocytes with technetium.

2. In 22 patients meeting criteria for the adult respiratory distress syndrome (ARDS) the mean transferrin accumulation rate was threefold greater (P < 0.005) than in 22 patients not meeting these criteria, although most possessed an appropriate risk factor for ARDS, in addition to extensive radiographic changes.

3. The double-isotope method did not completely separate patients with ARDS from those not meeting the criteria or from control subjects and cannot be considered a diagnostic test for the condition. Statistically significant rates of transferrin accumulation, however, occurred more frequently in patients with ARDS (82%) than in controls (64%) or in those without ARDS (59%).
Elevated protein requirements in cirrhosis of the liver investigated by whole body protein turnover studies
Authors: Swart G. R. , van den Berg J. W. O. , Wattimena J. L. D. , Rietveld T. , Van Vuure J. K. , Frenkel M.
Published: August 2015

1. In patients with cirrhosis of the liver and in healthy control subjects, the rates of nitrogen flux, protein synthesis and protein breakdown were studied, using a single oral dose of 200 mg of [15N]glycine as a tracer. The nitrogen flux through the amino acid pool was measured separately with both urinary ammonia and urinary urea as end products; the average value was used for further calculations.

2. Subjects were studied in the fed state, both on an adequate and a protein-restricted diet, and also in the fasting state.

3. The rates of protein synthesis were markedly increased in the patients, not only in the fed but also in the fasting state. Protein breakdown rates were increased in the patients in the fed state.

4. The nitrogen balance in steady-state conditions in the fed state was more positive in the patients, while their nitrogen loss in the fasting state was no higher than that of control subjects.

5. A hypothesis is put forward that the high protein requirements of cirrhotic patients could be caused by small and inadequate liver glycogen stores; due to these small stores, gluconeogenesis from amino acids will take place and lead to an extra amino acid loss even during short-term fasting. This increased amino acid loss could explain the elevated protein requirements in cirrhotic patients.
Does resection enhance the response of the intestine to urogastrone-epidermal growth factor in the rat?
Authors: Goodlad R. A. , Savage A. P. , Lenton W. , Ghatei M. A. , Gregory H. , Bloom S. R. , Wright N. A.
Published: August 2015

1. The objective of this study was to see whether another proliferative stimulus could modify the marked proliferative effect of human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) on the gastrointestinal epithelium.

2. The response of the gastrointestinal tract to URO-EGF was investigated in rats maintained on total parenteral nutrition (TPN) with or without 75% small bowel resection.

3. Continuous infusion of 60 μg of recombinant β-urogastrone/day per rat increased proliferation in the stomach by over four times (P < 0.01), doubled proliferation in the small intestine (P < 0.001) and increased it by four and a half times in the colon (P < 0.001) in the control group. No significant effect of urogastrone was observed in the stomach of the resected groups, but proliferation was also increased in the small intestine by one and a half times (P < 0.001) and by nearly four times in the colon (P < 0.001).

4. Two-way analysis of variance showed that resection had a significant effect (P < 0.01) on proliferation below the anastamosis and in the ileum. However, the response of the ileum was only half that observed in orally fed rats, which confirms the importance of ‘luminal nutrition’ in the response to resection.

5. Intestinal resection in the TPN rat was associated with a small rise in plasma enteroglucagon levels, suggesting that this hormone may be implicated in the adaptive response of the small intestine to resection. However, the proliferative effects of URO-EGF were not associated with increased plasma enteroglucagon and thus the two agents probably exert their proliferative effects via separate mechanisms.

6. There was no evidence for a significant positive interaction between the effects of URO-EGF and resection. Thus loss of intestinal mass had no influence on the susceptibility of the intestine to the effects of URO-EGF. Although URO-EGF significantly increased intestinal epithelial cell proliferation, it could not entirely compensate for the lack of luminal contents.
Intestinal ion transport in rats with spontaneous arterial hypertension
Authors: Lübcke Ralf , Barbezat Gilbert O.
Published: August 2015

1. Ion balance, intestinal ion transport in vivo with luminal Ringer, and direct voltage clamping in vivo with luminal Ringer and sodium-free choline-Ringer were studied in young (40 days old) and adult (120 days old) spontaneously hypertensive rats (SHR) and age-matched normotensive controls (Wistar–Kyoto rats, WKY).

2. Faecal sodium output was significantly higher in SHR compared with WKY in both young (+ 67%) and adult (+ 43%) rats.

3. Small-intestinal sodium absorption was equal in young SHR and WKY, but significantly greater net sodium absorption was found in the ileum of adult SHR. In contrast, net sodium absorption was reduced from the colon of both young and adult SHR.

4. In adult SHR, the colonic transepithelial short-circuit current (Isc) and the transepithelial potential difference (PD) were significantly higher, whereas the transepithelial membrane resistance (Rm) was significantly lower than in WKY. There was an identical drop in Isc in both strains when luminal sodium was replaced by choline. These data cannot be explained by increased electrogenic cation (sodium) absorption in the SHR, but would favour chloride secretion.

5. It is suggested that in SHR membrane electrolyte transport abnormalities may also be present in the epithelial cells of the small and large intestine, as have been demonstrated already in blood cells by several investigators. The SHR may become an interesting experimental animal model for the study of generalized ion transport disorders.
Serum carnosinase activities in patients with alcoholic chronic skeletal muscle myopathy
Authors: Duane P. , Peters T. J.
Published: August 2015

1. Serum carnosinase activity was assayed in a group of alcoholic patients with and without histologically proven atrophy of type II skeletal muscle fibres, and in control subjects. No significant activity was detected in muscle biopsy samples or washed erythrocytes.

2. Serum carnosinase activity was significantly lower in chronic alcoholic patients compared with a group of age-matched controls. Alcoholics with abnormal muscle biopsies had significantly lower enzyme activities than either those patients with normal muscle biopsies or the controls. Serum enzyme activities in patients with normal muscle biopsies were not significantly different from controls.

3. Serum carnosinase activity was inversely correlated with the degree of muscle atrophy as measured by the type II fibre atrophy factor. There was a positive correlation between the enzyme activity and skeletal muscle mass as reflected by the creatinine-height index. Furthermore, the enzyme activity significantly increased, with resolution or improvement in the myopathy, in patients who abstained from alcohol.

4. Kinetic studies showed that the reduced carnosinase activity was due mainly to a decrease in the apparent Vmax. The apparent Km was significantly higher in the myopathic compared with non-myopathic alcoholics. Mixing serum from controls and patients with myopathy gave the expected values, indicating the absence of a serum enzyme inhibitory factor. Acute alcohol loading had no effect on the serum carnosinase activity.

5. The decrease in serum carnosinase activity in alcoholics was not related to the severity of their liver disease. Assays of serum carnosinase in chronic alcoholics can thus be used as a marker of their associated myopathy.
Autonomic control of heart rate during dynamic exercise in human hyperthyroidism
Authors: Maciel Benedito C. , Gallo Lourenco , Marin Neto Jose A. , Maciel Lea M. Z. , Martins Luiz E. B.
Published: August 2015

1. The relative contribution of the sympathetic and parasympathetic components of the autonomic nervous system to the regulation of the chronotropic reponse to dynamic exercise was evaluated indirectly in nine patients with thyrotoxicosis and in seven normal volunteers. All subjects were women, with equivalent ages in both groups. Six of the nine patients with hyperthyroidism were reevaluated after clinical compensation of the disease with propylthiouracil.

2. Heart rate responses were evaluated during discontinuous dynamic effort maintained for 4 min on a bicycle ergometer at levels of 5, 15, 25 and 50 W, and also of 75 W in normal individuals. The study was also performed under conditions of sympathetic pharmacological blockade with propranolol (0.2 mg/kg body weight).

3. Even though the magnitude of the total increase in heart rate evoked by each level of dynamic exercise was equivalent in normal and hyperthyroid patients, the tachycardiac response occurring at the beginning of the exercise, which depends on a predominantly vagal mechanism, was substantially different from that observed after 30 s of effort, when sympathetic contribution becomes more important. The hyperthyroid patients showed considerably lower increases in heart rate than the normal individuals during the initial 30 s of effort, with the opposite occurring from this moment onward.

4. In the hyperthyroid patients, β-adrenergic blockage depressed tachycardia after 30 s of effort at the 15 and 50 W levels, whereas in normal individuals this effect was only manifested at 50 and 75 W.

5. The patients who obtained clinical compensation showed a pattern of chronotropic response which tended to be close to that shown by normal subjects.

6. These data demonstrate depression of the capacity for vagal withdrawal during exercise in hyperthyroid patients, in association with a greater activation of the sympathetic component in relation to normal subjects. These functional modifications seem to be at least partially reversible when the patients are controlled clinically with anti-thyroid drugs.
Utilization for protein synthesis of 2-ketoisocaproate relative to utilization of leucine, as estimated from exhalation of labelled CO2
Authors: Imura Kenji , Shiota Tetsuya , Swain Louis M. , Walser MacKenzie
Published: August 2015

1. We have previously shown that the ratio (RWBP) of incorporation of label from 2-ketoisocaproate (KIC) into the leucine of whole-body protein to the simultaneous incorporation of label from leucine itself into protein is a measure of the nutritional efficiency of KIC as a substitute for leucine.

2. In order to determine whether RWBP can be estimated indirectly from measurement of labelled CO2 excretion, rats were injected orally or intravenously with [4,5-3H]leucine and either [1-14C]leucine or [1-14C]KIC. Expired CO2 was collected for 6 h.

3. The results show that 9–14% of KIC underwent first-pass oxidation after oral administration. When isotopes were given intravenously, the mean rate of excretion of 14CO2 from KIC, after 20 min, remained 1.8 times the mean rate of excretion of 14CO2 from leucine.

4. Mean RWBP, measured in whole-body protein in rats given isotopes orally or intravenously along with small or large doses of carriers, was the same as mean RWBP estimated from mean cumulative CO2 excretion.

5. We conclude (1) that nutritional efficiency of KIC relative to leucine can be estimated from measurement of labelled CO2 excretion, and (2) that the relative inefficiency of KIC as a substitute for leucine in the rat is attributable to first-pass oxidation of 9–14% (when given orally) and 80% greater susceptibility to systemic oxidation than leucine.
Potent and comparable vasodilator actions of A- and B-calcitonin-gene-related peptides on the superficial subcutaneous vasculature of man
Authors: Williams Gareth , Cardoso Helena , Ball Joanna A. , Mulderry Peter K. , Cooke Ernest , Bloom Stephen R.
Published: August 2015

1. Vasoactivity of human A- and B-calcitonin-gene-related peptides was studied in normal subjects, using reflectance plethysmography to measure relative changes in blood flow produced by superficial subcutaneous injections of the peptides.

2. Injection of 10−11 mol of either peptide caused an immediate 200% increase in local blood flow and prolonged hyperaemia lasting up to 3 h. The hyperaemic response to 10−13 mol of each peptide was significantly (P < 0.01) smaller and shorter in duration than that elicited by 10−1 mol of the same peptide, and 10−15 mol of both peptides produced no hyperaemia other than that attributable to needle insertion alone.

3. At all three dosages examined, there were no significant differences between A- and B-calcitonin-gene-related peptides in magnitude or time course of the hyperaemic response.

4. Human A- and B-calcitonin-gene-related peptides are therefore potent vasodilators in man, causing comparable dose-related vasodilatation in the superficial tissues.
Effect of gut-derived acetate on glucose turnover in man
Authors: Scheppach W. , Wiggins H. S. , Halliday D. , Self R. , Howard J. , Branch W. J. , Schrezenmeir J. , Cummings J. H.
Published: August 2015

1. The effect of acetate absorbed from the gut on glucose turnover has been determined in four healthy subjects during both fasting and an intravenous glucose infusion by using [U-13C]glucose.

2. In the first part of the study, after an overnight fast, a tracer dose of [U-13C]glucose was infused at a constant rate along with an infusion of saline for 7 h. In the second part the saline infusion was replaced by glucose at 4.25 mg min−1 kg−1. In both studies 15 mmol of sodium acetate was given by mouth at 15 min intervals from the fourth to the sixth hour. Glucose turnover, respiratory quotient, metabolic rate and blood levels of acetate, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide were measured.

3. Glucose turnover rates (means ±sem) were 1.88 ±0.1 mg min−1 kg−1 during fasting and 4.0 ± 0.08 mg min−1 kg−1 during glucose infusion. Acetate had no effect on glucose turnover, insulin, glucagon and gastric inhibitory polypeptide levels, but temporarily halted the rise in free fatty acids seen during the fasting study. No changes in oxygen consumption or carbon dioxide output occurred, in keeping with previous observations that acetate substitutes for lipid oxidation during metabolism and has no direct effect on glucose turnover.
Comparison between the cellobiose/mannitol and 51Cr-labelled ethylenediaminetetra-acetate absorption tests in the detection of coeliac disease
Authors: Martines D. , Morris A. I. , Gilmore I. T. , Williams A. , Stockdale H. , Critchley M. , Smith G. A. , Billington D.
Published: August 2015

1. The cellobiose/mannitol and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) absorption tests have been compared with respect to their ability to detect altered intestinal permeability in coeliac disease.

2. In patients with clinically proven coeliac disease, 13 out of 14 (93%) had abnormal urinary cellobiose/mannitol ratios, while only five out of 12 (42%) had abnormal urinary recoveries of 51Cr-EDTA. Thus, the cellobiose/mannitol absorption test is more sensitive in recognizing coeliac disease and this difference was significant (P < 0.02).

3. Possible reasons for this difference in the sensitivity of the two absorption tests are discussed.
Increased levels of immunoreactive plasma renin substrate during infectious peritonitis in patients on continuous ambulatory peritoneal dialysis
Authors: Metsärinne Kaj , Fyhrquist Frej , Grönhagen-Riska Carola
Published: August 2015

1. Renin substrate (RS) and certain serine protease inhibitors share structural homology. Previous studies have shown that RS may be an acute-phase protein.

2. This prospective study was carried out to monitor plasma RS and other components of the renin-angiotensin system and acute-phase proteins during infectious peritonitis in patients on continuous ambulatory peritoneal dialysis.

3. RS was measured by both an enzymatic assay and a direct radioimmunoassay. An enzymatic assay measures intact RS only, whereas a direct radioimmunoassay measures both intact RS, capable of releasing angiotensin I and des-(angiotensin I)-RS, the residue of RS after cleavage of angiotensin I.

4. RS determined by direct radioimmunoassay increased (P < 0.001) during acute inflammation (peritonitis), whereas neither RS measured enzymatically nor plasma renin activity changed significantly.

5. Our observation points to RS being an acute-phase protein in man.

6. Serum angiotensin-converting enzyme was measured by both an enzymatic and an inhibitor-binding assay. Both assays showed decreased levels of angiotensin-converting enzyme during acute inflammation.
Muscle wasting in emphysema
Authors: Morrison W. L. , Gibson J. N. A. , Scrimgeour C. , Rennie M. J.
Published: August 2015

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine.

2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered.

3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed.

4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.
Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease
Authors: Smit A. J. , Meijer S. , Wesseling H. , Donker A. J. M. , Reitsma W. D.
Published: August 2015

1. The effects of intravenous metoclopramide on baseline values and dopamine dose–response curves for renal haemodynamics and natriuresis were investigated in healthy volunteers and patients with renal disease.

2. Dopamine infusion alone, in doses ranging from 0.25 to 8 μg min−1 kg−1, resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with a fall in filtration fraction (FF) in eight hydrated healthy volunteers and, to a lesser degree, in 12 patients with renal disease. An increase in natriuresis (urinary excretion of sodium, UNa+V), fractional excretion of sodium (FENa+) and diuresis (urine flow rate, UV) was found in both groups for doses of 2 μg min−1 kg−1 and higher.

3. Metoclopramide infusion did not alter baseline values of GFR, ERPF or FF, but shifted the dopamine dose–response curve for ERPF and FF in the healthy volunteers. Metoclopramide induced a fall in UNa+V and FENa+ in both groups (fall in baseline FENa+ from 1.52 to 0.71 during metoclopramide in healthy volunteers and from 1.23 to 0.56 in patients; P < 0.01) and blunted the natriuretic response to subsequent dopamine infusion. The fall in UNa+V during metoclopramide infusion showed a strong correlation with baseline GFR (r = −0.944). In the patients, the response for the fractional excretions of β2-microglobulin and γ-glutamyltransferase was comparable with that of FENa+.

4. Dopamine infusion induced a fall, and metoclopramide led to rise, in plasma aldosterone concentration.

5. We conclude that metoclopramide acts as a dopamine antagonist at the renal level in man. Endogenous dopamine secretion does not seem to have a role in maintaining ERPF or GFR in hydrated healthy volunteers or in patients with renal disease, but is important for mediating natriuresis. Dopamine-induced changes in natriuresis were not found to depend on changes in renal haemodynamics.
Decreased membrane fluidity of erythrocytes and cultured vascular smooth muscle cells in spontaneously hypertensive rats: An electron spin resonance study
Authors: Tsuda Kazushi , Tsuda Seiko , Minatogawa Yohsuke , Iwahashi Hideo , Kido Ryo , Masuyama Yoshiaki
Published: August 2015

1. Membrane fluidity of erythrocytes and cultured vascular smooth muscle cells was studied in spontaneously hypertensive rats (SHR; Okamoto and Aoki strains) by means of an electron spin resonance (e.s.r.) and a spin-label technique.

2. The values of outer hyperfine splitting (2T) and of the order parameter (S) determined from e.s.r. spectra for a fatty acid spin-label agent (5-nitroxy stearate) were significantly higher in erythrocytes of SHR (4 and 10–13 weeks of age) than in those of age-matched Wistar–Kyoto rats (WKY). This finding suggests that the membrane fluidity of erythrocytes might be decreased in SHR.

3. The fluidity of cultured vascular smooth muscle cells obtained from 10-13-week-old SHR was also reduced compared with that from WKY.

4. These results suggest that the decreased membrane fluidity might be a genetically determined abnormality of the cell membranes in SHR.
Mechanisms of leucocyte sodium influx in essential hypertension
Authors: Ng L. L. , Harker M. , Abel E. D.
Published: August 2015

1. Leucocyte Na+ influx in media containing 10 mmol/l Na+ was studied directly using a triple-isotope method for measuring initial 22Na uptake rates in 20 normal and 18 untreated hypertensive subjects. The effects of 1 mmol/l amiloride (a Na+-H+-antiport inhibitor) and 0.1 mmol/l bumetanide (a Na+, K+, Cl−-symport inhibitor) were also examined.

2. The total, amiloride-sensitive and bumetanide-sensitive influx rates were raised in hypertensive compared with normotensive subjects [median (range): total 0.63 (0.25–1.82) vs 0.40 (0.09–0.65) mmol min−1 l−1, P < 0.002; amiloride-sensitive 0.43 (0.18–1.56) vs 0.26 (0.04–0.48) mmol min−1 l−1, P < 0.002; bumetanide-sensitive 0.12 (−0.03 to 0.83) vs 0.02 (−0.25 to 0.21) mmol min−1 l−1, P < 0.005].

3. We conclude that hypertensive patients have a raised leucocyte total Na+ influx when measured in media containing 10 mmol/l Na+ and that this is contributed mainly by amiloride-sensitive and bumetanide-sensitive Na+ influx mechanisms.
Aerosol deposition in the human lung: Effect of high-frequency oscillation on the deposition characteristics of an inhaled nebulized aerosol
Authors: Thomas Simon H. L. , Langford Jackie A. , George Robert J. D. , Geddes Duncan M.
Published: August 2015

1. Oral high-frequency oscillation (OHFO) may have important effects on aerosol deposition in the lungs. In order to investigate these, a technique was devised to measure regional deposition rates of a nebulized radio-labelled aerosol in the lungs during normal tidal breathing.

2. The effect of three frequencies of OHFO on pulmonary aerosol deposition rate (PADR) in four normal subjects and five patients with chronic airways obstruction (CAO) were assessed using the technique.

3. In separate experiments employing three normal subjects, the effect of OHFO was studied on the deposition rate of aerosol on the oropharynx and delivery apparatus, and on the amount and characteristics of aerosol inhaled by the subjects.

4. Total PADR was significantly reduced by OHFO at 8 Hz and 16 Hz in the normal subjects, and by all three frequencies of OHFO in the CAO patients. In the normal subjects, the regional distribution of aerosol deposition was unchanged, but in the CAO patients a larger proportion of total aerosol deposition occurred in peripheral lung.

5. OHFO reduced the oropharyngeal aerosol deposition rate, increased the loss of aerosol to the atmosphere before inhalation, and increased the deposition of aerosol on the delivery apparatus. The end result was a reduction in the amount of aerosol inhaled, and in the particle sizes measured at the mouthpiece.

6. We conclude that OHFO reduces the amount of aerosol inhaled, but may improve peripheral deposition of inhaled aerosol in patients with CAO. This effect may be of value in the clinical administration of nebulized drugs.
Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat
Authors: Garcia-Marin J. J. , Redondo-Torres J. G. , Perez-Barriocanal F. , Berenson M. M.
Published: August 2015

1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats.

2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min−1 100 g−1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, Pco2, Po2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose.

3. Sodium taurocholate was infused (0.5 μmol min−1 100 g−1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution.

4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min−1 100 g−1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX.

5. These results indicate that in the rat, in vivo, protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.
Reproducibility of haemodynamic and plasma catecholamine responses to isometric exercise and mental arithmetic in normo- and hyper-tensive subjects
Authors: Lenders Jacques , Houben Harry , Van Valderen Rudolf , Willemsen Jacques , Thien Theo
Published: August 2015

1. To determine the reproducibility of a mental arithmetic stress test and a handgrip exercise test, we studied the responses of blood pressure, heart rate, forearm blood flow and plasma catecholamines on two occasions, with an interval of at least 1 week, in 24 normotensive and 22 hypertensive subjects.

2. The se of a single observation of the percentage changes of blood pressure ranged from 3.9 to 9.3% in normotensive subjects and from 3.9 to 7.4% in hypertensive subjects in both tests. For heart rate, these values were 4.9–12.3% in the normotensive subjects and 4.8–5.7% in the hypertensive subjects. However, there was a wide individual scatter of these haemodynamic responses during both tests. The forearm blood flow, only measured during mental arithmetic, had an se of a single observation of 33.7%.

3. In 10 normotensive subjects the se of a single observation of the change in plasma noradrenaline was 0.16 nmol/l during handgrip exercise and 0.09 nmol/l during mental arithmetic. The corresponding values for plasma adrenaline were 0.04 and 0.05 nmol/l.

4. In conclusion, although both tests showed a rather low se of a single observation for the blood pressure and heart rate responses in normo- and hyper-tensive subjects, there was a considerable individual variability. If related to the mean forearm blood flow responses, the se of a single observation of the forearm blood flow response was of similar magnitude. The limited intra-individual reproducibility of both tests should be borne in mind when interpreting pharmacological intervention studies or studies evaluating sympathoadrenal reactivity in cardiovascular disorders.
Effect of potassium depletion on renal tubular function in the rat
Authors: Walter S. J. , Shore A. C. , Shirley D. G.
Published: August 2015

1. In order to investigate the effects of K+ depletion on renal function, micropuncture studies were performed on anaesthetized rats which had been kept on a K+-deficient diet for 2 weeks; results were compared with those from control animals.

2. In the K+-depleted animals, values for total glomerular filtration rate and single-nephron filtration rate were significantly lower than in controls. Urine osmolality was also reduced; this was associated with reductions in the osmolality, Na+ concentration and K+ concentration of papillary interstitial fluid. No significant difference between urine and papillary osmolality was observed.

3. Fractional reabsorption by the proximal convoluted tubule was enhanced in the K+-depleted animals; end-proximal fluid delivery was markedly reduced.

4. Absolute, but not fractional, delivery of K+ to the beginning of the distal tubule was reduced in the K+-depleted animals. In contrast to observations in control rats, no net secretion of K+ into the distal tubule occurred and there was indirect evidence of K+ reabsorption in the collecting duct.

5. K+ depletion was associated with reductions in the delivery of Na+ and water to early and late regions of the distal tubule, whereas excretion rates of Na+ and water were unaffected.

6. It is suggested that the reduction in Na+ delivery to the loop of Henle (arising from the changes in filtration rate and proximal tubular reabsorption) might contribute to the reduced medullary osmotic concentration observed during K+ depletion. Reductions in fractional reabsorption of Na+ and water in the collecting duct might result from lowered plasma aldosterone levels and the reduced medullary osmolality.