bluuebunny/crossref_metadata_2025 huggingface dataset:
The Measurement of Whole Body Protein Turnover in the Preterm Infant with Intragastric Infusion of l-[1-13C]Leucine and Sampling of the Urinary Leucine Pool
Authors: De Benoist B. , Abdulrazzak Y. , Brooke O. G. , Halliday D. , Millward D. J.
Published: August 2015

1. The measurement of whole body protein turnover in the preterm infant has been investigated with an intragastric infusion of L[1-13C]-leucine and with sampling of the urinary leucine pool.

2. Measurements have been made in seven preterm infants with body weights averaging 1733 g, fed with either human breast milk (n = 3) or proprietary formulae (n = 4), giving intakes of 541 (±25)kJ/kg and 465 (±42)mg of N day−1kg−1 and growing satisfactorily (14.7 ± 2.6 g day−1 kg−1).

3. The measurement of the enrichment of urinary leucine was well within the capability of gas chromatography-spectrometry, and similar values for the enrichment of plasma and urinary leucine were observed (plasma/urinary ratio was 0.93 ± 0.04, mean ± 1 sem, n = 13). Isotopic equilibrium, as indicated by a plateau in the urinary leucine and expired CO2 enrichment, was obtained within 8 h and was maintained for at least 48 h.

4. Nitrogen retention, measured by nitrogen balance, was similar to that calculated from the leucine retention (determined as the leucine intake — oxidation), i.e. 310 ± 45 and 301 ± 38 mg of N day−1 kg−1 (means ± 1 sem). Because of this it is suggested that in this specific type of study the direct measurement of nitrogen retention dispenses with the need for measurement of leucine oxidation, thereby simplifying the measurements.

5. From the leucine flux, leucine intake and nitrogen retention, rates of whole body protein synthesis and degradation were shown to be 11.32 (±0.78) and 9.54 (±0.55) g day−1 kg−1.
Ephedrine-Induced Thermogenesis in Man: No Role for Interscapular Brown Adipose Tissue
Authors: Astrup A. , Bülow J. , Christensen N. J. , Madsen J.
Published: August 2015

1. The warmest interscapular skin areas were located by thermography in six healthy subjects during ephedrine-induced thermogenesis.

2. In these interscapular areas, and in lumbar control areas, the skin temperature, subcutaneous temperature and adipose tissue blood flow were measured before and during ephedrine-induced thermogenesis.

3. The skin and subcutaneous temperatures increased in the interscapular area as well as in the lumbar area, by about 0.7-1.2°C. The interscapular skin temperature remained about 1°C higher than the lumbar; the subcutaneous temperatures in the two areas were identical during the experiments.

4. Although the interscapular subcutaneous adipose tissue blood flow increased about sixfold and the lumbar increased twofold, the absolute flows were higher in the lumbar area.

5. The oxygen uptake increased to a maximum of 30% above control level.

6. Plasma glucose and glycerol concentrations remained unchanged, and plasma non-esterified fatty acids, lactate and noradrenaline concentrations increased slightly but significantly.

7. Biopsies taken from the hot interscapular areas did not contain brown adipose tissue.

8. It is concluded that the high interscapular skin temperature may be due to a lower insulating fat thickness and that the increases in skin and subcutaneous temperatures during ephedrine-induced thermogenesis are caused by an increased blood flow. These observations weigh against the hypothesis that the interscapular temperature increase is due to functional, interscapular brown adipose tissue.
Whole Body Nitrogen Kinetics in Man: Determination from Plasma [Guanidino-15N]Arginine
Authors: Yudkoff Marc , Nissim Itzhak , Glassman Mark , Segal Stanton
Published: August 2015

1. Whole body nitrogen turnover and protein synthesis were calculated by the method of D. Picou & T. Taylor-Roberts [Clinical Science and Molecular Medicine (1969) 36, 283–296] except that plateau plasma enrichment of [guanidino-15N]arginine was used in place of the [15N]urea enrichment after a constant infusion of [15N]-glycine. With this approach metabolic pool turnover and protein synthesis were 637.2 ± 73.0 mg of N day−1 kg−1 and 2964.0 ± 409.5 mg of protein day−1 kg−1 respectively.

2. Virtually identical isotopic enrichment in [guanidino-15N]arginine and [15N]urea were observed in a healthy young adult who took repeated oral doses of [15N]glycine for a period of 60 h: 0.47 (arginine) and 0.48 (urea) atom% excess.

3. The turnover of glycine nitrogen and of urea, determined from the constant infusion of [15N]glycine and [13C]urea, was 66.2 ± 3.3 mg of N day−1 kg−1 and 156.2 ± 4.3 mg of urea day−1 kg−1 respectively. The ratio of steady-state enrichment in arginine to that in glycine, reflecting the fraction of arginine derived from glycine, was 10.5%. By using the [guanidino-15N]arginine enrichment as representative of the expected enrichment in [15N]urea at plateau, it was calculated that approximately 25% of glycine N flux is directed toward the synthesis of urea, with the remainder directed to protein and quantitatively minor products like haem and creatinine.

4. Unlike steady-state [15N]urea labelling, which is achieved only after infusion of [15N]-glycine for several days, plateau isotopic abundance in [guanidino-15N]arginine was attained after only 1–2 h of [15N]glycine infusions, thereby allowing estimation of whole body nitrogen kinetics and the rate of transfer of glycine nitrogen to urea in a relatively brief experiment.
Effect of Clofibrate on the Metabolism of Bilirubin, Bromosulphophthalein and Indocyanine Green and on the Biliary Lipid Composition in Gilbert's Syndrome
Authors: Kutz Klaus , Kandler Harald , Gugler Roland , Fevery Johan
Published: August 2015

1. Clofibrate (20 mg day−1 kg−1 body weight) given orally for 2 weeks to 18 subjects with Gilbert's syndrome reduced the total serum bilirubin concentration from 44.4 (22.1–71.7) μmol/l (median, range) to 15.0 (7.9–28.9) μmol/l, mainly by decreasing the ‘indirect’ fraction to 34.5% of pretreatment values.

2. In contrast to treatment with phenobarbitone, clofibrate did not change the ratio of bilirubin mono- to di-conjugates in bile.

3. The initial plasma disappearance rate of indocyanine green and of bromosulphophthalein did not show consistent changes during clofibrate treatment but the ‘apparent’ maximal biliary secretion capacity of bromosulphophthalein (Tm) decreased in most of the patients studied, whereas the relative storage capacity (S) tended to increase.

4. As expected, the cholesterol saturation of bile increased in all subjects.

5. These results suggest that clofibrate increases mainly the glucuronidation of bilirubin, promoting as such the overall hepatic transport in Gilbert's syndrome. However, it decreases the maximal biliary secretion of bromosulphophthalein, possibly by an increased hepatic retention. These phenomena might be linked to the augmented content of Z protein in the liver.
Inhibition of Partially Purified Rat Brain Na+, K+- Dependent Atpase by Bile Acids, Phenolic Acids and Endotoxin
Authors: Seda H. W. M. , Gove C. D. , Hughes R. D. , Williams Roger
Published: August 2015

1. Sera from patients with fulminant hepatic failure (FHF) has previously been shown to contain substance(s) which inhibit leucocyte ouabain-sensitive sodium efflux and rat brain Na+,K+-dependent ATPase in vitro. Similar effects in the patients could be an important mechanism in the development of encephalopathy and cerebral oedema.

2. In previous studies, bilirubin, free fatty acids and mercaptans have been shown to inhibit Na+,K+-ATPase in vitro. The present report is concerned with the effects of a number of other potentially toxic substances present in the serum of patients with FHF.

3. Chenodeoxycholic acid, p-hydroxyphenyllactic acid, p-hydroxyphenylpyruvic acid and endotoxin caused 30–45% inhibition of partially purified rat brain Na+,K+-ATPase at concentrations known to occur in the serum of patients with FHF. At low concentrations the inhibitory effects of these substances were additive, but at higher concentrations a maximum level of inhibition was reached.

4. These further substances are likely, therefore, to be of importance in the disturbances of brain function found in FHF.
The Role of Corticosteroids in the Regulation of Myocardial Na, K-ATPase in Normotensive and Spontaneously Hypertensive Rats
Authors: Stern Naftali , Beck Frances W. J. , Chandler Donald Walt , Mayes Douglas M. , Sowers James R.
Published: August 2015

1. Sodium, potassium-dependent adenosine triphosphatase (ATPase) of the renal tubule is known to be dependent on both gluco- and mineralo-corticoids. Recent evidence suggests that corticosteroids may modulate ATPase activity at extrarenal sites. The myocardium contains glucocorticoid receptors to which mineralocorticoids can also bind. Thus, the possibility that myocardial ATPase is corticosteroid dependent was examined in the Wistar-Kyoto (WKY) normotensive rat and also in the spontaneously hypertensive (SH) rat, a strain previously shown to exhibit reduced myocardial ATPase activity.

2. WKY and SH rats (in groups of 10) were either sham operated or adrenalectomized and placed on 1% NaCl solution as drinking water. Adrenalectomized rats subsequently received daily intraperitoneal injections of either vehicle (1% NaCl, 0.5 ml), aldosterone (30 μg/kg) or dexamethasone (60 μg/kg). Renal cortical and myocardial ATPase activities were determined 21 days later in all groups.

3. Adrenalectomized WKY rats had reduced myocardial ATPase activity (5.15 ± 0.88 vs 8.18 ± 0.93 μmol of phosphate h−1 mg−1 of protein in controls; P < 0.01). This observed decrease in ATPase in adrenalectomized rats could be at least partly prevented by selective aldosterone or dexamethasone replacement. Parallel changes were observed with renal cortical ATPase.

4. SH rat myocardial ATPase was lower than in WKY rats (P<0.05, 5.88 ± 0.99 μmol of phosphate h−1 mg−1 of protein) and was unaffected by adrenalectomy (5.47 ± 0.68 μmol of phosphate h−1 mg−1 of protein) whether accompanied by aldosterone (6.08 ± 0.68 μmol of phosphate h−1 mg−1 of protein) or dexamethasone (6.47 ± 0.84 μmol of phosphate h−1 mg−1 of protein) therapy or not. Renal cortical ATPase, however, exhibited corticosteroid dependency in the SH rats that resembled the pattern observed in WKY rats.

5. It is suggested that the lower ATPase activity observed in SH rats after the evolution of hypertension may result from decreased sensitivity to endogenous corticosteroids.
The Effects of Oral Almitrine on Pattern of Breathing and Gas Exchange in Patients with Chronic Obstructive Pulmonary Disease
Authors: Stradling J. R. , Nicholl C. G. , Cover D. , Davies E. E. , Hughes J. M. B. , Pride N. B.
Published: August 2015

1. Almitrine at a low dose of 100 mg orally significantly raises Pao2 and lowers Paco2 in patients with chronic obstructive pulmonary disease, compared with placebo, when they were breathing air or 28% oxygen.

2. The estimated ideal alveolar — arterial Po2 difference was less after almitrine compared with placebo, when patients were breathing either air or 28% oxygen.

3. After almitrine overall ventilation breathing air increased by 10% but this did not reach statistical significance. During 28% oxygen breathing almitrine hardly altered overall ventilation but the inspiratory duty cycle (Ti/Ttot.) decreased and mean inspiratory flow rate (VT/Ti) increased compared with placebo. These changes were significant on a paired t-test (P<0.05).

4. Changes in both volume and pattern of breathing may explain the improved gas exchange in the lung after almitrine.
The Importance of Conjugation in Biliary Secretion of Ursodeoxycholate and 7-Ketolithocholate in the Rat
Authors: Erlinger S. , Dumont M. , Zouboulis-Vafiadis I. , De Couet G.
Published: August 2015

1. The biliary maximum secretory rate (SRmax.) of glycoursodeoxycholate in the bile fistula anaesthetized rat was about five times that of unconjugated ursodeoxycholate.

2. Likewise, the biliary SRmax. of tauro-7-ketolithocholate was more than three times that of unconjugated 7-ketolithocholate. The SRmax. of 7-ketolithocholate infused with taurine (to avoid depletion of the taurine pool) was still significantly lower than that of exogenous tauro-7-ketolithocholate.

3. These data support the hypothesis that, for bile acids that are poorly water soluble, the maximal biliary secretion rate is dependent on conjugating capacity, which is the limiting step in the overall transport from plasma into bile.
Lipid peroxidation in rheumatoid arthritis: Thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients
Authors: Rowley David , Gutteridge John M. C. , Blake David , Farrs Margaret , Halliwell Barry
Published: August 2015

1. Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo.

2. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo.

3. There appear to be significant correlations between the contents of TBA-reactive material and bleomycindetectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters.
Oophorectomy leads to a selective decrease in 1,25-dihydroxycholecalciferol receptors in rat jejunal villous cells
Authors: Chan S. D. H. , Chiu D. K. H. , Atkins D.
Published: August 2015

1. The distribution of 1,25-dihydroxychole-calciferol [1,25-(OH)2D3] receptors in isolated rat jejunal cells was investigated in normal and oophorectomized female rats and also in vitamin D-deficient animals.

2. Oophorectomy caused a selective reduction in 1,25-(OH)2D3 receptor numbers in villous cells, the reduction being similar (37%) in both normal and vitamin D-deficient animals.

3. The data suggest that this effect of oophorectomy reflects a direct effect of oestrogens in the intestinal synthesis of 1,25-(OH)2D3 receptors, independent of the renal synthesis of 1,25-(OH)2D3.

4. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs after oophorectomy or the menopause.
Vascular Hypersensitivity to Noradrenaline: A Possible Mechanism of Hypertension in Rats with Chronic Uraemia
Authors: Zimlichman R. R. , Chaimovitz C. , Chaichenco Y. , Goligorsky M. , Rapoport J. , Kaplanski J.
Published: August 2015

1. Studies were performed to evaluate the mechanism involved in the hypertension of moderate renal failure in partially (five-sixths) nephrectomized rats. Cardiac index (CI) was studied by means of the microsphere technique, and systemic vascular resistance (SVR) calculated from the mean arterial resistance MAP/CI, in four groups of experimental animals: (A) partially nephrectomized rats; (B) group A rats chronically treated with the calcium channel blocker verapamil; (C) sham-operated rats; (D) sham-operated rats treated with verapamil.

2. The results demonstrate a significant increase in MAP in group A rats, which was due to a 72% increase in SVR as compared with groups C and D. In group B rats, MAP decreased significantly owing to a marked decrease in SVR (40%) as compared with group A. However, MAP remained higher in group B than in group C.

3. The vascular responsiveness to noradrenaline was studied in group A, group C and group A rats after parathyroidectomy (group A1). An increased pressor responsiveness to noradrenaline was indicated by a shift of the noradrenaline dose-response curve to the left in group A rats as compared with group C rats. This change was corrected after partial nephrectomy.

4. We conclude that hypertension in nephrectomized rats is due to an increase in SVR, and that an increased pressor responsiveness to catecholamines may play a role in this phenomenon. Furthermore, verapamil reduced the hypertension, and parathyroidectomy improved the abnormal sensitivity to noradrenaline in group A rats.

5. These results raise the possibility that an abnormality in calcium metabolism, possibly due to secondary hyperparathyroidism, may be implicated in the hypertension of mildly uraemic rats.
Mechanisms of Initial Blood Pressure Response to Postural Change
Authors: Borst C. , Van Brederode J. F. M. , Wieling W. , Van Montfrans G. A. , Dunning A. J.
Published: August 2015

1. The influence of supine rest on the blood pressure response to standing and 70° head-up tilt was studied in detail for the first 30 s after the change of posture.

2. Following 20 min of supine rest, the active transition to standing was accompanied by an immediate increase in systolic pressure of 29 ± 6 mmHg (mean ± sem). This was followed by large fluctuations in systolic pressure: to −28 ± 2 mmHg below control after 7 s and to 22 ± 2 mmHg above control after 22 s (17 mmHg in excess of the systolic pressure level after head-up tilt).

3. Following 1 min of supine rest, there was no difference in the immediate increase in systolic pressure. However, the magnitude of the subsequent changes was significantly diminished.

4. With head-up tilt the immediate increase in blood pressure was absent and afterwards small changes were found that were also significantly influenced by the period of prior rest.

5. Taken in conjunction with earlier studies, the following mechanisms are suggested. The immediate blood pressure increase resulted from compression of arteries by the contracting postural muscles. The subsequent blood pressure fall was caused by at least two mechanisms: (a) the fall was predominantly of reflex origin, because the immediate pressure increase stimulated the systemic baroreceptors; (b) supine rest possibly augmented the translocation of blood from the thorax which contributed, approx. 5 s from standing, to the reflex fall of blood pressure.
Sex Differences in the Metabolism of Ethanol and Acetaldehyde in Normal Subjects
Authors: Arthur M. J. P. , Lee A. , Wright R.
Published: August 2015

1. Blood ethanol and acetaldehyde concentrations were compared in normal young male and female subjects after intravenous infusion of 0.5 g of ethanol/kg body weight.

2. After the infusion was completed, females had significantly higher mean concentrations of blood ethanol than males, but a significantly lower apparent volume of distribution (Vd) of ethanol (0.56 ± 0.06 l/kg vs 0.68 ± 0.17 l/kg, P<0.05). There were no differences in ethanol elimination rate (EER) (females 1.78 ± 0.3 mmol h−1 kg−1; males 1.87 ± 0.41 mmol h−1 kg−1). The mean value of the areas under the acetaldehyde/time curves (AUC) were significantly greater for males (88.5 ± 26.4 μmol/l. h) than for females (58.6 ± 31.5 μmol/l. h, P<0.05).

3. Since the ethanol elimination rate was similar in both sexes, the observed differences in AUC for acetaldehyde may reflect the sex differences in metabolism of this substrate by the liver.
Circadian Rhythms of Serum Thyrotrophin and Body Temperature in Euthyroid Individuals and their Responses to Warming
Authors: O'malley B. P. , Richardson A. , Cook N. , Swart S. , Rosenthal F. D.
Published: August 2015

1. The diurnal rhythms of body temperature and serum thyrotrophin (TSH) levels in euthyroid individuals behaved inversely to one another.

2. An artificially induced rise in the body temperature of these individuals was accompanied by a fall in serum thyrotrophin levels, the amplitudes of their respective rhythms decreasing simultaneously.

3. There was a marked correlation between the degrees of change in body temperature and circulating thyrotrophin levels respectively during warming.

4. In normal subjects manipulation of the diurnal rhythm of body temperature brings about inverse alterations in the thyrotrophin rhythm.
Serum Alkaline Phosphodiesterase I in Experimental Biliary Obstruction in the Rat
Authors: Simpson Stuart R. , Rahman K. , Billington D.
Published: August 2015

1. Alkaline phosphodiesterase I was present in rat liver at approx. 100-fold greater activity than alkaline phosphatase, and in rat bile at approx. 25-fold greater activity.

2. Rat serum alkaline phosphodiesterase I was increased 6-fold whilst serum alkaline phosphatase was increased only 2-fold 96 h after bile duct ligation.

3. In contrast to alkaline phosphatase, hepatic alkaline phosphodiesterase I was not affected by bile duct ligation, suggesting its raised serum activity was due to bile regurgitation rather than overspill of the enzyme from liver into blood.

4. Gel filtration showed that 8 and 96 h after bile duct ligation the serum contained a high molecular weight form of alkaline phosphodiesterase I.

5. It is suggested that alkaline phosphodiesterase I offers a potentially useful indicator of biliary obstruction in the rat.
Possible Therapeutic Applications of Antagonists of Excitatory Amino acid Neurotransmitters
Authors: Meldrum Brian
Published: August 2015

The dicarboxylic amino acids, glutamate and aspartate, are excitatory neurotransmitters in many brain regions. Recent animal experiments with analogues of dicarboxylic amino acids that block their excitatory actions, suggest that such selective antagonists could have important therapeutic uses in neurology and psychiatry. The strongest evidence concerns epilepsy and disorders of the motor system. However, there are theoretical and experimental grounds for studying therapeutic applications in cerebral ischaemia and in chronic degenerative disorders. This review summarizes the experimental background, and proposes some key future studies.
Platelet volume subpopulations in acute myocardial infarction: an investigation of their homogeneity for smoking, infarct size and site
Authors: Kishk Y. T. , Trowbridge E. A. , Martin J. F.
Published: August 2015

1. Mean platelet volume and count were measured in three groups: patients with acute myocardial infarction, a control group with myocardial ischaemia but no infarction and an asymptomatic group of young males.

2. Mean platelet volume was significantly larger in the myocardial infarction group compared with the ischaemic heart disease group or the asymptomatic group.

3. Two subpopulations were present within the myocardial infarction group. One subgroup had a large mean platelet volume and low count. The other subpopulation was indistinguishable, with regard to platelet count and mean volume, from the ischaemic heart disease group.

4. Over 60% of the myocardial infarction group lay in the area of high platelet volume and low count compared with 13% of the ischaemic heart disease control group and 38% of the asymptomatic group. Acute myocardial infarction is likely to be associated with a large mean platelet volume and low count compared with the ischaemic heart disease group. There is no statistical evidence that this condition is related to smoking or size and site of infarct.

5. This evidence suggests that large mean platelet volume and low platelet count could be a major risk factor for myocardial infarction.
Cathepsin B-like cysteine proteinase activity in sputum and bronchoalveolar lavage samples: relationship to inflammatory cells and effects of corticosteroids and antibiotic treatment
Authors: Burnett David , Stockley Robert A.
Published: August 2015

1. Cathepsin B-like activity was measured in lung secretions by using the fluorimetric substrate benzyloxycarbonyl-l-arginine-l-arginine-4-methyl-7-coumarylamide (Z-Arg-Arg-MEC). The enzyme had a pH optimum of approximately 5.5 and had the characteristics of an alkaline-stable cysteine proteinase.

2. Enzyme activity in the sputum from ten subjects with chronic bronchitis was significantly reduced after 5 days’ treatment with prednisolone.

3. Seven patients with bronchiectasis were studied before and after 14 days’ treatment with amoxycillin. Cysteine proteinase activity was significantly reduced after 7 days’ therapy, in parallel with a change in sputum quality from purulent to mucoid. One week after cessation of treatment enzyme levels were again increased but were still significantly lower than pretreatment values.

4. Enzyme activity in 21 bronchoalveolar lavage specimens correlated significantly with neutrophil counts but not with macrophage counts.

5. Cysteine proteinase activity in lung secretions resembles that of cathepsin B but is alkaline-stable, suggesting it is a distinct enzyme. The levels of cysteine proteinase in lung secretions appear to be related to the presence of inflammation or infection.
Effects of glucose and d-3-hydroxybutyrate on human pancreatic islet cell function
Authors: Rhodes C. J. , Campbell I. L. , Szopa T. M. , Biden T. J. , Reynolds P. D. , Fernando O. N. , Taylor K. W.
Published: August 2015

1. β-Cell function in human islets derived from a number of kidney donors was investigated by using various types of islet preparations.

2. With fresh islets, both insulin release and biosynthesis were increased by raising glucose concentrations, although the response was a variable one.

3. In fresh islets, the effects of 5 mmol of glucose/l on release were potentiated by 10 mmol of d-3-hydroxybutyrate/l.

4. Insulin release at 20 mmol of glucose/l was inhibited by adrenaline (0.1 mmol/l), and potentiated by theophylline (10 mmol/l) in the presence of 5 mmol of glucose/l, in islets cultured for 4 days.

5. After culture for 8 days, islets still showed an increase in insulin release and biosynthesis in response to glucose.

6. Pancreas slices derived from fresh human tissue also responded to increasing concentrations of glucose with a sigmoidal curve for insulin release.
Cholesterol gallstone pathogenesis: a study of potential nucleating agents for cholesterol crystal formation in bile
Authors: Whiting M. J. , Watts J. McK.
Published: August 2015

1. Cholesterol monohydrate crystal formation was measured quantitatively in model bile solutions, which were supersaturated with cholesterol, by a radiochemical method and qualitatively in human gallbladder bile by polarizing microscopy.

2. Various agents, which have been postulated to act as nucleating factors for cholesterol crystal and gallstone formation, were added to bile and their effect on the appearance of cholesterol crystals was determined. These agents included calcium salts found in gallstones (calcite, aragonite, apatite, bilirubinate), Escherichia coli bacteria, pigment residues from cholesterol gallstones, bilirubin and several mucin preparations.

3. Human gallbladder bile, which was collected from patients with and without cholesterol gallstones, was also mixed with model bile to examine whether nucleating or anti-nucleating factors were present.

4. None of the agents tested markedly and consistently promoted cholesterol monohydrate crystal formation in model or human bile, except seed crystals of cholesterol monohydrate which were used as a control. Human gallbladder bile from obese patients without gallstones delayed the appearance of cholesterol crystals in model bile solutions, whereas gallbladder bile from gallstone patients did not.

5. These results do not provide experimental support for the hypothesis that calcium salts and pigment material found in gallstones, or gallbladder mucin at concentrations less than 10 mg/ml, act as nucleating agents for cholesterol crystal and stone formation. The difference between gallbladder biles from patients with and without gallstones in their propensity to form cholesterol crystals may be due to the presence of an anti-nucleating factor in normal bile.
Relative agonist potency as a means of differentiating α-adrenoceptors and α-adrenergic mechanisms
Authors: Ruffolo Robert R.
Published: August 2015

1. Relative potencies (ED50), affinities (assessed as dissociation constants) and efficacies (i.e. ability to activate the receptor) of agonists are useful in subclassifying and differentiating α-adrenoceptors.

2. The postsynaptic α-adrenoceptor of rat aorta is of the α1-subtype, but may differ from the α1-adrenoceptor of rabbit and guinea pig aortae, based on comparison of relative potencies of selected agonists.

3. By evaluating the relative potency of agonists, qualitative and quantitative species differences between α1-adrenoceptors in rat and guinea pig are observed in a variety of test systems in vivo and in vitro.

4. By comparing the relative potencies of aromatic hydroxyl-substituted phenethylamines and imidazolines at α1-adrenoceptors in guinea pig aorta, differences in the ability of these two classes of α-adrenoceptor agonists to bind to, and subsequently activate, α1-adrenoceptors have been observed.

5. Evaluating the relative potencies of agonists, when used in conjunction with other techniques, provides a valuable method for classifying α-adrenoceptors and for studying α-adrenergic mechanisms.
Ageing and α-adrenoceptors
Authors: Docherty J. R. , O'Malley K.
Published: August 2015

1. Ageing changes in α-adrenoceptors can be summarized as follows: except in the eye, where there is an apparent increased responsiveness with increasing age in man, peripheral α-adrenoceptor responsiveness has generally been found to be either unchanged or reduced with increasing age in animals and man.

2. Even where changes have been found it remains to be clarified whether these changes are selective changes in α-receptors or whether they are due to alterations in responsiveness beyond the level of the receptor.
The adrenaline -α2-adrenoceptor-mediated vasoconstrictor axis
Authors: Bolli Peter , Erne Paul , Kiowski Wolfgang , Amman Franz W. , Bühler Fritz R.
Published: August 2015

1. In patients with essential hypertension plasma adrenaline concentrations have been found to be higher than in normotensive subjects and this may represent increased adrenergic activity. Adrenaline released into the circulation can be taken up by the sympathetic nerve ending and as it is re-released as a co-transmitter it enhances exocytotic noradrenaline release by stimulating prejunctional β-adrenoceptors and as a consequence it contributes to postjunctional α1-adrenoceptor-induced vasoconstriction. Adrenaline may also induce vasoconstriction via post- and extra-junctional (α2-adrenoceptors, as shown by a decrease in the forearm blood flow during adrenaline infusions in the postjunctional α1- and β-blocked forearm vasculature, an effect that could be antagonized by α2-adrenoceptor blockade with yohimbine.

2. α2-Adrenoceptor stimulation in platelets showed an increased sensitivity to adrenaline, as determined by sensitivity in counteracting the inhibitor effect of PGI2 on intracellular free calcium concentration in untreated patients with essential hypertension, when compared with treated patients or normotensive subjects. As these effects can be normalized by antihypertensive treatment this suggests that the increased hormone sensitivity may be related to the elevated intracellular free calcium concentration.

3. Thus adrenaline, via pre- and post-junctional adrenoceptors, may contribute to enhanced vascular smooth muscle contraction, which most likely is sensitized by the elevated intracellular calcium concentration.
Renal adaptation and gut hormone release during sodium restriction in ileostomized man
Authors: Unwin R. J. , Moss S. , Peart W. S. , Wadsworth Jane
Published: August 2015

1. The renal excretion of water, electrolytes, aldosterone and kallikrein was monitored in 12 ileostomized patients before and during sodium deprivation. Changes in plasma renin activity (PRA), plasma aldosterone and plasma arginine vasopressin (AVP) concentrations were measured, together with aldosterone in ileal fluid. The pattern of gut peptide release in response to a test meal was also examined to assess whether a circulating gut peptide might be involved in the renal adaptation to sodium restriction, and compared with healthy normal subjects who were under no dietary constraint.

2. In each patient renal sodium excretion fell within 8–12 h of sodium deprivation and was associated with a prompt and significant rise in PRA; much later increases in plasma aldosterone concentration and renal aldosterone excretion occurred, and were established by day 2 of sodium restriction. No consistent change in renal kallikrein excretion was found.

3. Ileal sodium loss was little changed by sodium deprivation, but ileal potassium concentration rose steadily and became significantly correlated with PRA, and to a lesser extent with renal aldosterone excretion.

4. Of the gut peptides measured in plasma, only the insulin profile was altered by sodium deprivation, with an increase in the test meal response; insulin has previously been shown to have a significant antinatriuretic action at physiological concentrations. Plasma levels of pancreatic polypeptide and motilin were increased in ileostomized patients when compared with normal subjects, but were unaffected by the change to a low sodium diet.

5. An early increase in urine flow and water diuresis occurred during sodium deprivation, following a cyclical pattern with peaks each evening. There were no corresponding changes in measured plasma AVP concentration or creatinine clearance. This observation remains unexplained.
Serum immunoreactive erythropoietin in hypoxic lung disease with and without polycythaemia
Authors: Wedzicha J. A. , Cotes P. Mary , Empey D. W. , Newland A. C. , Royston J. P. , Tam R. C.
Published: August 2015

1. We studied 20 patients with chronic airflow obstruction, 10 patients without polycythaemia and 10 patients with compensatory polycythaemia having respectively mean red cell mass 24.7 (sd 4.2) and 47.8 (sd 7.5) ml/kg, mean daytime Pao2 7.6 and 6.9 kPa, mean FEV, 0.85 and 0.82 1. Groups were matched for severity of daytime arterial hypoxaemia but nocturnal arterial oxygen desaturation was more severe in the patients with polycythaemia than in those without. We also studied six additional patients with chronic airflow obstruction and polycythaemia and 19 normal controls.

2. Estimates of serum immunoreactive erythropoietin (siEp) in those without polycythaemia were 19 m-i.u./ml (geometric mean) with 95% confidence range 11–35 m-i.u./ml and stable during 3 months. In those with polycythaemia they were similar and consistent in five and, in the other five, higher on at least one occasion. There was no significant difference between siEp in daytime (12.00 hours to 16.00 hours) and morning (07.00 hours) samples but geometric mean estimates of erythropoietin in paired daytime and morning samples were higher and more variable in patients with polycythaemia than in those without. The geometric mean estimate of siEp in all patients with chronic airflow obstruction and polycythaemia was greater than in normal subjects but, despite secondary polycythaemia, siEp could be in the range for normal subjects.

3. In the patients with polycythaemia we were unable to predict the finding of normal or elevated siEp.

4. Changes in siEp after erythrapheresis (10–26% reduction in packed cell volume) were observed in the 10 patients with polycythaemia and in one without. One month after erythrapheresis, packed cell volume remained below and siEp was above initial pretreatment levels, implying an erythropoietin secretory response and that the development of secondary polycythaemia had induced a fall in siEp.
The effect of undernutrition on thermoregulation in the elderly
Authors: Fellows I. W. , Macdonald I. A. , Bennett T. , Allison S. P.
Published: August 2015

1. With use of a liquid-conditioned coverall, the thermoregulatory responses to a lowering of environmental temperature from 35°C to 23°C were assessed in eight normally nourished and six undernourished elderly female patients, during their convalescence after surgical repair of a fracture of the femoral neck.

2. There was no difference in the peripheral vasoconstriction of the two groups in response to a cold environment.

3. On lowering the environmental temperature, the increase in metabolic rate was significantly impaired in the undernourished group compared with the normally nourished group (P < 0.05).

4. There was a small decrease in core temperature in the undernourished group (median change −0.1°C) during the period of exposure to the lowest environmental temperature (23°C). This was significantly different from the lack of change (median change 0°C) in core temperature observed in the normally nourished group (P < 0.05).

5. This defect of thermogenesis may underlie the propensity of undernourished elderly patients to suffer hypothermia and fracture of the femoral neck in the winter months.
Variability of the haemodynamic responses to laboratory tests employed in assessment of neural cardiovascular regulation in man
Authors: Parati Gianfranco , Pomidossi Guido , Ramirez Agustin , Cesana Bruno , Mancia Giuseppe
Published: August 2015

1. In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation. Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses, their reproducibility in any given subject is critical.

2. In 39 subjects with continuous blood pressure (intra-arterial catheter) and heart rate monitoring we measured (i) the blood pressure and heart rate rises during hand-grip and cold-pressor test, (ii) the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine, and (iii) the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber. Each test was carefully standardized and performed at 30 min intervals for a total of six times in each subject.

3. The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied. For the group as a whole the average response variability (coefficient of variation) ranged from 10.2% for the blood pressure response to carotid baroreceptor stimulation to 44.2% for the heart rate response to cold-pressor test. The variability of the responses was not related to basal blood pressure or heart rate, nor to the temporal sequence of the test performance.

4. Thus tests employed for studying neural cardiovascular control in man produce responses whose reproducibility is limited. This phenomenon may make it more difficult to define the response magnitude typical of each subject, as well as its comparison in different conditions and diseases.
Na+ leak in erythrocytes from essential hypertensive patients
Authors: Garay Ricardo P. , Nazaret Corinne
Published: August 2015

1. Ouabain- and bumetanide-resistant (OBR) Na+ efflux from human erythrocytes into a Mg2+-sucrose medium exhibits kinetic properties consistent with a transmembrane Na+ leak.

2. In 52 essential hypertensive patients, the rate constant of Na+ leak (ke) was 15.0 ± 2.9 × 10−3h−1 (mean ±sd). This was significantly higher than the ke in 47 normotensive controls (13.2 ± 1.6 × 10−3h−1; t = 3.81, P < 0.001; Mann-Whitney U rank sum test P = 0.0014). The relatively small number of patients studied was insufficient to decide if the hypertensive population was bi-modally distributed. Nevertheless, if the upper end of the normotensive population is used as a cutoff point, it appears that a subgroup of 12 hypertensive patients had an increased Na+ leak, ke = 19.5 ± 1.9 × 10−3 h−1 (mean±sd). The increased Na+ leak remained constant in repeated determinations over several months.

3. Na+ movements catalysed by the Na+-K+ co-transport and Na+-Li+ countertransport systems were measured in the above 52 hypertensive patients. Seventeen hypertensive patients showed a low apparent affinity of the co-transport system for internal Na+ and 12 exhibited a high maximal rate of Na+-Li+ countertransport. None of these two abnormalities was found in the 12 hypertensive patients with increased ke. We propose to denote them as Leak-(+) hypertensive patients.

4. Passive net Na+ entry was abnormally high in all Leak-(+) hypertensive patients. However, erythrocyte Na+ content was increased in only five of the 12 Leak-(+) hypertensive patients. A normal or even decreased Na+ content was associated with the presence of compensatory increases in the maximal rate of the Na+-K+ pump and the Na+-K+ co-transport system.
Evidence against a role for superoxide ions in the injury of nephrotoxic nephritis in rats
Authors: Webb D. B. , Mackenzie R. , Zoob S. N. , Rees A. J.
Published: August 2015

1. The accelerated model of nephrotoxic serum nephritis (NTSN) was produced in 12 Sprague-Dawley rats. Six of these rats were administered superoxide dismutase (EC 1.15.1.1; SOD) subcutaneously (8 mg/kg) 8-hourly for 4 days. The first dose was given 6 h before the nephrotoxic serum (NTS).

2. The progression of renal disease was monitored by following (i) albumin excretion, (ii) serum creatinine and creatinine clearance and (iii) renal histopathology and immunofluorescence.

3. There was no evidence that SOD influences the course of NTSN.

4. SOD was scarcely excreted by control rats or rats with NTSN.
Hepatic lactate uptake is enhanced by low pH at low lactate concentrations in perfused rat liver
Authors: Sestoft Leif , Marshall Michael O.
Published: August 2015

1. The effect of pH on lactate uptake was studied in perfused liver of rats starved for 48 h.

2. At both low pH (6.8) and normal pH (7.4) lactate uptake was a linear function of lactate concentration in input medium in the range 0.4–1.5 mmol/l.

2. In the lower concentration range (0.4–0.8 mmol/l) the rate of lactate uptake was 30% higher at pH 6.8 than at pH 7.4.

4. At pH 6.8 lactate uptake was independent of whether Pco2 was 2.7 or 5.3 kPa.

5. We suggest the increased rate of lactate uptake at low pH and concentrations lower than 0.8 mmol/l was due to the stimulatory effect of H+ on the lactate carrier.
Biochemical evidence for an increased and progressive deposition of collagen in lungs of patients with pulmonary fibrosis
Authors: Kirk Jacqueline M. E. , Da Costa P. E. , Turner-Warwick Margaret , Littleton R. J. , Laurent G. J.
Published: August 2015

1. To assess the role of changes in lung collagen in pulmonary fibrosis, the content of this protein was measured in biopsy and autopsy lung from patients with cryptogenic fibrosing alveolitis (CFA), a fibrotic lung disorder of unknown cause.

2. The collagen concentration was measured in lung samples from 21 patients with CFA (14 autopsy and seven open-lung biopsy) and 17 normal subjects; total lung collagen was determined in the right lung of 10 patients who died from CFA and the results were compared with those from 10 normal lungs.

3. There was a wide variation in the collagen concentrations but the mean value (±sem) for patients with CFA (217±13mg/g dry weight) was significantly higher (P < 0.02) than that of the controls (155 ± 15mg/g dry weight). The mean collagen concentration of the autopsy samples (243 ± 20 mg/g dry weight) was significantly higher (P < 0.05) than that of the biopsy samples (165 ± 24 mg/g dry weight).

4. The mean total collagen was markedly raised (P < 0.001) in right lungs of patients with CFA (32.5 ± 4.3g) compared with normal lungs (14.0 ± 1.1g). When corrected for the predicted lung volume this difference in total lung collagen remained statistically significant (P < 0.01, mean for patients 4.7 ± 0.7 mg/ml, controls 2.3 ± 0.2 mg/ml).

5. These results demonstrate an increased deposition of lung collagen in this form of pulmonary fibrosis. They also suggest that there is a greater collagen concentration in lungs of patients with later disease, indicating a progressive deposition of collagen during the course of the disease.
A microcalorimetric study of heat production in resting skeletal muscle from human subjects
Authors: Fagher B. , Monti M. , Wadsö I.
Published: August 2015

1. Different microcalorimetric techniques have been compared for the assessment in vitro of the total metabolic activity of resting skeletal muscle. Human fibre bundles were suspended in Krebs-Ringer-phosphate buffer containing glucose and insulin and the heat evolution was continuously monitored for 2–6 h. Palmitate as substrate was also tested.

2. The power signals declined rapidly when a static calorimetric method (A) was used. Two different perfusion methods (B, C) gave higher power values. Long-lasting steady states were observed with method C, where the sample was contained in a cage acting as a stirrer.

3. Significant differences were found for fibre bundles from different human muscles as well as age- and sex-related differences. The heat production in samples from the rectus abdominis muscle (method B), 0.73 mW/g muscle wet wt., was significantly higher than for the obliquus internus muscle, 0.44 mW/g, and the vastus lateralis muscle, 0.55 mW/g, but not different from the heat production value of vastus medialis, 0.66 mW/g.

4. In method C particularly, the fibre bundles are believed to be in adequate contact with the surrounding medium. With the use of a multichannel calorimeter it is possible to perform up to four experiments simultaneously, e.g. involving the calorigenic effects of pharmacological substances. The technique provides a new approach for detailed studies of muscle metabolism in physiological and pathological conditions.
Atrial natriuretic peptide: an endogenous factor enhancing sodium excretion in man
Authors: Anderson John , Struthers Allan , Christofides Nic , Bloom Stephen
Published: August 2015

1. For many years experimental evidence has suggested the existence of a circulating factor able to enhance sodium excretion.

2. Very recently peptides with natriuretic activity in experimental animals have been isolated from mammalian and human cardiac tissue. In order to determine whether this natriuretic activity has relevance to man we have studied the effects of an infusion of α-human atrial natriuretic peptide (α-h-ANP) in normal subjects.

3. Sodium excretion trebled (P = <0.005) during the infusion of a calculated dose of 15 pmol of α-h-ANP min−1 kg−1 and there was an accompanying diuresis; radioimmunoassay of plasma α-h-ANP during the natriuresis indicated a mean peak incremental concentration of 203 ± 78 (sem) pmol/l. The infusion of a calculated dose of 1.5 pmol min−1 kg−1 did not affect sodium excretion.

4. There were no haemodynamic changes and no side effects were noted.
Thermogenesis in human skeletal muscle as measured by direct microcalorimetry and muscle contractile performance during β-adrenoceptor blockade
Authors: Fagher Birger , Liedholm Hans , Monti Mario , Moritz Ulrich
Published: August 2015

1. The influence of β-adrenoceptor-blockade on skeletal muscle was studied in ten healthy males with propranolol, atenolol and pindolol randomly given for 8 days each in a cross-over double blind test. After 7 days on each drug, muscle function was tested by an isokinetic dynamometer. Thermogenesis in biopsy samples taken from vastus lateralis muscle after a low grade exercise was studied after 8 days on each drug by direct calorimetry with a perfusion microcalorimeter.

2. Before drug administration, a median heat production rate of 0.67 mW/g of muscle was measured. This value was significantly reduced by 25% during propranolol, but no significant change was found during atenolol or pindolol administration.

3. Peak torque decline during isokinetic endurance test changed significantly in knee flexor but not in extensor muscles, from 15% to 27% after propranolol and from 15% to 23% after pindolol. Maximum dynamic strength was unaltered.

4. Our data suggest that blockade of sympathetic β2-receptors decreases thermogenesis in human skeletal muscle and impairs isokinetic endurance.