bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and rapid method for the determination of the concentrations of magnesium, sodium, potassium and sodium, potassium pumps in human skeletal muscle
Authors: Dørup Inge , Skajaa Kristjar , Clausen Torben
Published: August 2015

1. For the diagnosis of electrolyte disorders, data on skeletal muscle composition are often valuable, but rarely available. We have therefore developed a simple and rapid needle biopsy procedure for the determination of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in muscle.

2. Using a Bergström needle, biopsies weighing around 25 mg were taken from the vastus lateralis muscle of 18 normal subjects (aged 44–86 years) and extracted with trichloroacetic acid (TCA). The concentrations of K+, Na+ and Mg2+ were 90.7 ± 1.8, 31.9 ± 1.6 and 9.5 ± 0.2 μmol/g wet wt., respectively (means ± se).

3. The TCA extraction gave the same values as digestion with 65% HNO3 or 35% H2O2, could be used over the weight range 10–55 mg and showed a Mg2+ recovery of 101.7%.

4. The concentration of Na+, K+-pumps was quantified as the total capacity for [3H]ouabain binding. In vastus lateralis biopsies obtained from six normal subjects the mean value was 258 ± 16 pmol/g wet wt.

5. Comparison of the concentrations of K+, Mg2+ and [3H]ouabain-binding sites in samples obtained post mortem showed modest variation among different muscles with varying fibre composition.

6. Measurements of the concentrations of K+, Na+, Mg2+ and Na+, K+-pumps in duplicate biopsies of the vastus lateralis yield values which seem representative for the total pool of skeletal muscle fibres and can be performed within a few hours.

7. Measurements on patients receiving chronic diuretic treatment demonstrated that these procedures allow the detection of reduced levels of K+, Mg2+ and Na+, K+-pumps in skeletal muscle, as well as a partial recovery after oral Mg2+ supplementation.
Effect of single respiratory manoeuvres on specific airway conductance in heart–lung transplant recipients
Authors: Glanville Allan R. , Yeend Richard A. , Theodore James , Robin Eugene D.
Published: August 2015

1. The time course and magnitude of the effect of single slow and rapid respiratory manoeuvres on specific airway conductance (sGaw) was assessed in seven normal control subjects and in seven heart–lung transplant (HLT) recipients before and after experimentally induced bronchoconstriction.

2. Neither full inspiration, full exhalation nor vital capacity manoeuvres significantly altered sGaw in normal controls or HLT recipients under baseline conditions despite the presence of hyper-responsiveness to methacholine (MC) in the latter group.

3. After induced bronchoconstriction, single slow and rapid inspirations to total lung capacity transiently abolished or attenuated the bronchoconstriction in normal controls. This effect was absent in the HLT recipients.

4. In HLT recipients, the combination of hyper-responsiveness to MC, the absence of bronchoconstriction with respiratory manoeuvres and the absence of significant bronchodilatation after deep inspiration suggest lack of normal pulmonary innervation.
Regulation of lactate uptake and lactate production in liver from 48-h-starved rats: Effects of pH, flow and glucose concentration
Authors: Sestoft Leif , Marshall Michael O.
Published: August 2015

1. The effects of medium glucose concentration (0–20 mmol/l) and flow (100–33% of normal) on lactate uptake at low lactate concentration were studied in perfused livers from 48-h-starved rats with perfusate pH values of 7.4 and 6.8.

2. Lactate uptake was independent of glucose concentration in the range 5–10 mmol/l, but was slightly inhibited with time at 20 mmol/l glucose. This pattern was independent of perfusate pH.

3. At both pH values lactate uptake decreased proportionally with flow, and at low flow lactate was produced by the livers. The effect of flow was greatest at pH 7.4 where a net lactate production was found at 48% of normal flow, whereas at pH 6.8 lactate production was not seen until the flow was reduced to 33% of normal.

4. When glucose was omitted from the perfusate lactate production ceased at both pH values.

5. The effect of low pH on lactate uptake and production in liver probably reflects inhibition of glycolysis by low pH.
Decline of atrial natriuretic peptide release in dogs during sustained rapid cardiac pacing
Authors: Walsh K. P. , Williams T. D. M. , Wilder R. , Pitts E. , Lightman S. L. , Sutton R.
Published: August 2015

1. To assess the ability of the atria to maintain elevated plasma concentrations of atrial natriuretic peptide (ANP), the temporal changes in plasma ANP concentrations were studied in seven chloralose-anaesthetized dogs during 4 h of sustained rapid cardiac pacing.
Atrial natriuretic peptide released by rapid ventricular pacing in dogs does not cause a natriuresis
Authors: Walsh K. P. , Williams T. D. M. , Canepa-Anson R. , Roe P. , Pitts E. , Lightman S. L. , Sutton R.
Published: August 2015

1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min.

2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P < 0.05), and decreased cardiac output and mean arterial pressure (P < 0.05).

3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P < 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change signficantly.

4. Urine flow and free water clearance increased during the latter 30 min of pacing (P < 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP.

5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.
Reciprocal change, exercise-induced ST segment depression and coronary anatomy: Are they related in the post-infarct patient?
Authors: Murray Donal P. , Tan Lip Bun , Salih Mahmood , Weissberg Peter , Murray R. Gordon , Littler William A.
Published: August 2015

1. The relationship of reciprocal change on the electrocardiogram, at the time of acute myocardial infarction, to exercise-induced ST segment depression and coronary anatomy was studied in 125 post-infarct patients.

2. Eighty-three patients had reciprocal changes, 90 had exercise-induced ST depression and 72 had both of these findings.

3. Patients with reciprocal changes had larger myocardial infarctions, as assessed by peak enzyme release and ejection fraction, than patients without this finding.

4. Multi-vessel disease was significantly more common among patients with reciprocal changes and those with exercise-induced ST depression compared with patients without these findings.

5. The exercise test was more sensitive and had a higher predictive accuracy than reciprocal change when electrocardiographic changes were compared with findings at coronary angiography.

6. With both tests the antero-lateral leads were significantly more sensitive, but less specific, than the inferior leads in classifying patients.

7. Thus while both tests yielded information with regard to coronary anatomy in post-infarct patients, the exercise test was a better predictor of coronary anatomy than reciprocal change.

8. Therefore, reliance should not be placed on the presence or absence of reciprocal change alone when assessing patients for further investigation after myocardial infarction.
Neutrophil chemotaxis in bronchiectasis: A study of peripheral cells and lung secretions
Authors: Stockley R. A. , Shaw J. , Hill S. L. , Burnett D.
Published: August 2015

1. Some bronchiectatic patients persistently expectorate purulent secretions containing many polymorphonuclear leucocytes (PMN) and bacteria, suggesting ineffective microbial clearing from the lung. We have therefore studied several aspects of PMN recruitment to the lung by chemotaxis.

2. Circulating PMN from patients with bronchiectasis show a variable chemotactic response to the synthetic peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine. This is similar to the response of PMN from healthy controls and suggests that failure to clear microbial organisms is not due to defective chemotaxis as measured here.

3. Purulent sputum solphase demonstrates chemotactic activity against control PMN. This activity is greater (P < 0.001) than that found with mucoid sputum solphase, which is consistent with the neutrophil content of the secretions in vivo.

4. Successful antibiotic therapy reduces the chemotactic activity of purulent sputum solphase from a median value of 183 (range 28–201) cells/high power field to 33.5 (range 0.7–64) cells/high power field (P < 0.0025). This indicates that the chemotactic activity is largely associated with bacterial load.
Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor
Authors: Afzal Mir M. , Morgan Kevin , Chappell Stephen , Lewis Mark , Spurlock Gillian , Collins Peter , Collins Philip , Lewis Malcolm , Scanlon Maurice
Published: August 2015

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c, and its effects on de-endothelialized rabbit aortic strips were investigated.

2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips.

3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l.

4. Both ASTI and ouabain caused a significantly greater (P < 0.01) calcium retention than control medium in aortic strips.

5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective.

6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.
Further studies on the activity and subcellular distribution of alanine: Glyoxylate aminotransferase in the livers of patients with primary hyperoxaluria type 1
Authors: Danpure Christopher J. , Jennings Patricia R.
Published: August 2015

1. The activity of alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44) has been measured in the unfractionated livers of 20 patients with primary hyperoxaluria type 1 (PH1), three patients with other forms of primary hyperoxaluria and one PH1 heterozygote. The subcellular distribution of AGT activity was examined in four of the PH1 livers and in the liver of the PH1 heterozygote.

2. The mean AGT activity in the unfractionated PH1 livers was 12.6% of the mean control value. The activities of other aminotransferases and the peroxisomal marker enzymes were normal. When corrected for cross-over from glutamate:glyoxylate aminotransferase (GGT; EC 2.6.1.4), the mean AGT activity in the PH1 livers was reduced to 3.3% of the control values.

3. The livers from a patient with primary hyperoxaluria type 2 (d-glycerate dehydrogenase deficiency) and one with an undefined form of primary hyperoxaluria (possibly oxalate hyperabsorption) had normal AGT levels. The livers of a very mild PH1-type variant and a PH1 heterozygote had intermediate levels of AGT activity.

4. Subcellular fractionation of four PH1 livers by sucrose gradient isopycnic centrifugation demonstrated a complete absence of peroxisomal AGT activity. The subcellular distribution of the residual AGT activity was very similar to that of GGT activity (i.e. mainly cytosolic with a small amount mitochondrial). There were no alterations in the subcellular distributions of any of the peroxisomal marker enzymes. The subcellular distribution of AGT activity in the PH1 heterozygote liver was similar to that of the control (i.e. mainly peroxisomal).

5. The residual AGT activity in two of the PH1 livers, which could be accounted for largely by cross-over from GGT, was only slightly dependent on substrate (glyoxylate and alanine) concentration and virtually independent of cofactor (pyridoxal phosphate) concentration.

6. These data confirm our previous findings (C. J. Danpure & P. R. Jennings, FEBS Letters, 1986, 201, 20–24), but on a much larger number of patients, that AGT deficiency is pathognomic for PH1, and is not found in other forms of hyperoxaluria.
Ultrafiltration of renin in the mouse kidney studied by inhibition of tubular protein reabsorption with lysine
Authors: Mazanti Ingrid , Hermann Kirstine Lintrup , Nielsen Arne Høj , Poulsen Knud
Published: August 2015

1. In order to study the role of the kidney in the elimination of endogenous plasma renin, renin was measured in the plasma and urine of female mice.

2. The renin concentration was two orders of magnitude lower in urine than in plasma, but it increased after intraperitoneal injection of submandibular mouse renin. No correlation between the plasma renin concentration and the urinary renin concentration and renin excretion rate could be demonstrated.

3. Blockade of the tubular reabsorption of proteins by intraperitoneal injection of the basic amino acid lysine increased the urinary renin concentration, renin excretion rate and renin clearance two to three orders of magnitude, without affecting the plasma renin concentration.

4. This finding demonstrates that ultrafiltered renin is reabsorbed almost completely in the renal tubules and that the mechanism most likely is the same as for other filtered proteins.

5. The large renal renin clearance obtained after intraperitoneal lysine is in accordance with a major role of the kidneys in the elimination of renin from the circulation, by a glomerular ultrafiltration and tubular reabsorption and metabolization of renin.
Quantity of anti-leucoprotease relative to α1-proteinase inhibitor in peripheral airspaces of the human lung
Authors: Kramps Johannes A. , Franken Claus , Dijkman Joop H.
Published: August 2015

1. Peripheral airspaces were selectively lavaged using balloon-tipped catheters of 2 mm diameter.

2. Molar anti-leucoprotease/α1-proteinase inhibitor ratios as determined in these lavage fluids by enzyme immunoassays ranged from 0.02 to 0.14 (mean 0.08).

3. These data indicate that peripheral airspaces contain minor amounts of anti-leucoprotease relative to α1-proteinase inhibitor. This observation does not necessarily mean that anti-leucoprotease is of minor importance in protecting the lung interstitium.
Effect of gut-derived acetate on oral glucose tolerance in man
Authors: Scheppach W. , Cummings J. H. , Branch W. J. , Schrezenmeir J.
Published: August 2015

1. Dietary fibre has a moderating impact on glucose metabolism. To test the hypothesis that this effect of fibre may be mediated by its breakdown product acetate, oral glucose tolerance tests were carried out in healthy volunteers with and without acetate.

2. Five subjects received 50 g of glucose orally while taking either acetate (15 mmol every 15 min) by mouth or chloride as control. Oral acetate made no detectable difference to glucose tolerance or to levels of free fatty acids, 3-hydroxybutyrate, lactate, insulin, glucagon and gastric inhibitory polypeptide.

3. The 50 g dose of glucose temporarily depressed acetate levels in blood. This was probably due to an interaction between glucose and acetate in the gastrointestinal lumen as the same effect was seen with 50 g of xylose in three subjects.

4. Plasma acetate concentrations were unaffected by 50 g of oral glucose in one subject when acetate was instilled into the sigmoid colon.

5. It is unlikely that the improvement of glucose tolerance by dietary fibre is mediated by acetate.
Contrasting plasma atrial natriuretic factor concentrations during comparable natriuresis with infusions of atrial natriuretic factor and saline in normal man
Authors: Richards A. Mark , Tonolo Giancarlo , Polonia Jorge , Montorsi Piero
Published: August 2015

1. To explore the role of atrial natriuretic factor (ANF) in the response to an acute saline load, we compared plasma hormone and urinary electrolyte interrelationships during administration of ANF and saline. Plasma concentrations of ANF, renin, angiotensin II and aldosterone, together with urine volume and electrolytes, were measured during infusions of placebo, ANF [α-human ANF (99–126)] and 0.9% (w/v) NaCl solution in normal subjects under standardized conditions of diet and posture.

2. Saline loading and ANF infusions initially induced similar natriuresis and suppression of renin–angiotensin– aldosterone system activity in association with markedly disparate values of plasma ANF. Plasma ANF levels rose to two- and eight-fold placebo values with saline and ANF, respectively (P < 0.001). Conversely, in the period after infusion plasma ANF values were similar while natriuresis differed significantly. Peak natriuresis lagged behind peak plasma ANF values with both stimuli.

3. ANF, but not saline, enhanced urinary excretion of calcium and magnesium. Saline, but not ANF, caused increased kaliuresis.

4. The data suggest that ANF makes only a minor contribution to natriuresis induced by saline challenge, although full confirmation of this point requires quantification of end-organ responses to endogenous ANF in the face of changing arterial pressure and circulating volume.
Haemodynamic effects of physiological concentrations of circulating noradrenaline in man
Authors: Chang Peter C. , Kriek Eugene , Van Der Krogt Jacques A. , Blauw Gerard-Jan , Van Brummelen Peter
Published: August 2015

1. To define the role of circulating noradrenaline in cardiovascular regulation, threshold concentrations for haemodynamic effects were determined in arterial and venous plasma of eight healthy volunteers.

2. Five doses of noradrenaline, 0–54 ng min−1 kg−1, were infused intravenously in random order and single-blind for 15 min per dose. Changes in intra-arterial blood pressure, heart rate, forearm blood flow and forearm vascular resistance were determined, and plasma noradrenaline was measured in arterial and venous blood samples.

3. Significant increases in systolic and diastolic blood pressure were found at arterial and venous plasma noradrenaline concentrations (means ±sem) of 3.00 ± 0.23 and 1.35 ±0.12 nmol/l, respectively. A significant decrease in heart rate was found at arterial and venous plasma noradrenaline concentrations of 8.99 ± 0.69 and 3.09 ± 0.60 nmol/l, respectively. The lower doses of noradrenaline tended to increase forearm blood flow and to decrease forearm vascular resistance, whereas the higher doses had no consistent effect on forearm haemodynamics.

4. During the noradrenaline infusions 73 ± 5% of the increase in arterial plasma noradrenaline concentration was extracted in the forearm.

5. The venous plasma noradrenaline threshold concentration was found to be much lower than previously reported. It is concluded that arterial and venous plasma noradrenaline concentrations which are readily encountered in physiological circumstances elicit haemodynamic effects.
Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid
Authors: Johnson A. W. , Berrington J. M. , Walker I. , Manning A. , Losowsky M. S.
Published: August 2015

1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood.

2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast.

3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography–mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid.

4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment.

5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.
Cyclosporin-induced hypomagnesaemia and renal magnesium wasting in rats
Authors: Wong Norman L. M. , Dirks John H.
Published: August 2015

1. Twenty-four hour clearance studies were performed on three groups of rats to determine the hypomagnesaemic effect of cyclosporin. Group I rats served as controls, whereas group II rats received 10 mg of cyclosporin/kg and group III rats received 20 mg of cyclosporin/kg daily.

2. After 7 days of cyclosporin treatment, plasma magnesium concentration was 1.04 ±0.01 mmol/l in control rats compared with 0.85 ±0.01 mmol/l in group II and 0.81 ±0.02 mmol/l in group III. After 14 days of cyclosporin administration, group III rats developed severe hypomagnesaemia (0.67 ± 0.01 mmol/l). This reduction in plasma magnesium was associated with an increase in the urinary excretion of magnesium.

3. This reduction in plasma magnesium and increment in magnesium excretion returned to normal 7 days after cessation of treatment.

4. Additional three-phase acute clearance experiments were performed on eight normal and 12 cyclosporin-treated rats (20 mg/kg). These animals were subjected to acute magnesium chloride infusion. After graded magnesium chloride infusion, despite a similar rise in plasma magnesium, the fractional magnesium excretion was significantly higher in the cyclosporin-treated animals.

5. Analysis of the fractional intestinal absorption of magnesium suggested that the development of hypomagnesaemia after cyclosporin treatment is due to magnesium loss by the kidney. Furthermore, this effect of cyclosporin on magnesium transport is only present during cyclosporin treatment and is reversible when treatment with cyclosporin is withdrawn.
Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension
Authors: Bruun Niels Eske , Ibsen Hans , Skøtt Peter , Toftdahl Dorthe , Giese Jørn , Holstein-Rathlou Niels Henrik
Published: August 2015

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption.

2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) ± 11/4 (1.5/0.5) to 139/88 (18.5/11.7) ± 16/9 (2.1/1.2) mmHg (kPa) (means ± sd; P < 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight.

3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged.

4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.
Alanylglutamine reduces muscle loss of alanine and glutamine in post-operative anaesthetized dogs
Authors: Roth Erich , Karner Josef , Ollenschläger Günter , Karner Judith , Simmel Annette , Fürst Peter , Funovics Josef
Published: August 2015

1. The present study examined the effect of an infusion of the dipeptide alanylglutamine or of the corresponding amino acids alanine and glutamine in equimolar amounts (10 μmol min−1 kg−1) on the canine hindlimb exchange of alanine and glutamine in the post-operative anaesthetized dog. In contrast to glutamine, the dipeptide alanylglutamine is stable in aqueous solution and therefore would be a suitable substrate for parenteral nutrition.

2. The infusion of alanylglutamine increased (a) the arterial concentration of alanylglutamine to a plateau level (120 ± 9.5 μmol/l, mean ± sem) 20 min after start of the infusion, (b) the mean arterial alanine concentration from 761 ± 42 to a plateau of 1500–1700 μmol/l (P > 0.01) and (c) the arterial glutamine concentration from 407 ± 51 to a plateau of 1050–1500 μmol/l (P > 0.01). Alanine and glutamine levels were slightly higher (14% and 26%, respectively, NS) in the group receiving the equimolar amount of alanine and glutamine.

3. Infusion of alanylglutamine for 1 h abolished the net efflux of glutamine (from −0.80 ± 0.1 to −0.03 ± 0.2 μmol min−1 kg−1; P >0.05) and invoked a net influx of alanine (from −0.50 ± 0.19 to + 0.27 ± 0.14 μmol min−1 kg−1; P > 0.01). These changes were similar to those achieved when the two amino acids were infused.

4. This study demonstrates that during short-term administration of alanylglutamine or of the corresponding amino acids the nitrogen release from the hindlimb of the anaesthetized post-operative dog via alanine and glutamine is reduced.
Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism
Authors: Lalor B. C. , Mawer E. B. , Davies M. , Lumb G. A. , Hunt L. , Adams P. H.
Published: August 2015

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism.

2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency.

3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P < 0.001) and parathyroid hormone (P < 0.003), and with the glomerular filtration rate (P < 0.03), and negatively correlated with the serum concentrations of calcium (P < 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P < 0.002).

4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D.

5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.
Paradoxical effect of respiration on ventricular rate in atrial fibrillation
Authors: Rawles John M. , Pai G. R. , Reid Susan R.
Published: August 2015

1. In 50 subjects with atrial fibrillation we have attempted to demonstrate variation of ventricular rate with respiration, as evidence of cardioregulatory reflex activity.

2. The electrocardiogram was recorded for 3 min during spontaneous respiration. The presence of respiratory variation of R-R intervals was analysed by multiple regression against a cosine function (cosinor analysis), making it possible to determine the phase of respiration when the intervals were longest.

3. Variation in ventricular rate with respect to respiration was demonstrated (P < 0.05) in seven (14%) cases. On average, R-R intervals were longest at the end of inspiration; this contrasts with sinus rhythm where P-P, P-R and R-R intervals are longest around the time of end-expiration.

4. These results suggest that in atrial fibrillation the beat-to-beat ventricular rate may be under the influence of cardioregulatory reflexes, but the effect of respiration is weak and paradoxical.
Human whole-blood granulocyte aggregation in vitro
Authors: Fisher T. C. , Belch J. J. F. , Barbenel J. C. , Fisher A. C.
Published: August 2015

1. Aggregation assays are a commonly used technique for the study of granulocyte activation. These studies are usually performed using a pure cell suspension in buffer. This necessitates a separation procedure which is time-consuming and may modify the function of the cells. Interaction between different cell types is precluded.

2. To avoid these disadvantages a method was developed which quantifies granulocyte aggregation in whole blood. Samples drawn from an incubated vessel before and after the addition of a chemotactic stimulus were fixed with formaldehyde to prevent disaggregation. Erythrocytes were then removed by chemical lysis and using an electronic cell-sizing device the number of single cells and aggregates could then be easily measured.

3. Results from a group of volunteers showed a rapid and reversible response to a chemotactic tripeptide, with a fall in single granulocyte count and the appearance of doublets and triplets. Lymphocytes were unaffected. Intra-assay reproducibility was better than ± 5%.

4. Using this assay, a significant elevation in aggregability was observed in blood from patients after acute myocardial infarction.

5. This novel technique, by avoiding the separation step, is faster, simpler and more physiological than previous methods, and as such is useful for both assays of drug action in vitro and the study of cell activation in disease states.
Effects of hypoxia and hypercapnia on atrial natriuretic factor and plasma renin activity in conscious dogs
Authors: Clozel Jean-Paul , Saunier Claude , Hartemann Denise , Allam Mustapha , Fischli Walter
Published: August 2015

1. The aim of the present study was to assess the effects of hypercapnia or hypoxia on plasma concentrations of atrial natriuretic factor (ANF) in conscious unrestrained dogs.

2. For this purpose, chronically instrumented dogs were exposed in a random order to either room air, or to an atmosphere containing 21% O2/10% CO2/69% N2 to produce hypercapnia, or 10% O2/3% CO2/87% N2 to produce hypoxia without respiratory alkalosis.

3. Plasma concentrations of ANF did not change significantly during hypoxia.

4. In contrast, during hypercapnia, plasma concentrations of ANF increased by more than 100% and returned to baseline at the end of hypercapnia.

5. Hypercapnia, but not hypoxia, induced an increase in left atrial and central venous pressures.

6. We conclude that hypercapnia increases plasma ANF concentration, and that this increase may be secondary to an increase of the left and right atrial pressures. These phenomena may explain the increase in diuresis and natriuresis which has been described during hypercapnia.
Multi-organ damage resulting from experimental faecal peritonitis
Authors: Tighe D. , Moss R. , Boghossian S. , Heath M. F. , Chessum B. , Bennett E. D.
Published: August 2015

1. Using specific-pathogen-free New Zealand White rabbits, we have compared the effects of faecal peritonitis over a period of 5 h in eight test animals with eight controls in which a sham operation was performed.

2. There was morphological damage to lungs, liver and spleen of test animals. Lung capillaries and sinusoids of the liver showed occlusion by cell debris and leucocytes, with endothelial damage. The lungs also showed alveolar epithelial disruption, basement membrane exposure and type II pneumocytes lacking lamellar bodies. In the liver there was fibrin deposition and swollen Kupffer cells. The spleen showed degranulating neutrophils, fibrin deposits, platelet aggregates and activated macrophages, with no damage to the endothelium.

3. There was no morphological damage to the kidney or heart of test animals or to any organs of sham-operated animals.

4. There were mixed anaerobes and aerobes in faecal material used to induce peritonitis. Cultures of liver, spleen and kidney isolated four different types of micro-organisms. Blood cultures showed two types of micro-organisms. Cultures of lung and heart showed one type of micro-organism.

5. The presence of micro-organisms in an organ could not be correlated with the degree of histological damage to that organ.

6. In test animals an early significant reduction in circulating leucocytes and platelets was sustained for the duration of the experiment with significant diffuse intravascular coagulation.

7. There was no change in test animal neutrophil adhesiveness until 120 min, when significant reduction was observed.

8. Serum phospholipase A2 (EC 3.1.1.4) activity in the test group showed a threefold increase at 300 min.
Factors contributing to the accelerated clearance of theophylline and antipyrine in adults with exocrine pancreatic disease
Authors: Acheson David W. K. , Hunt Linda P. , Rose Patricia , Houston J. Brian , Braganza Joan M.
Published: August 2015

1. Oxidative drug metabolizing capacity has been assessed by oral antipyrine and/or theophylline tests in consecutive patients with chronic pancreatitis (CP; alcoholic 24, idiopathic 47), acute pancreatitis (AP; 28) and pancreatic cancer (CA; 11). Most of the patients had drastically reduced their alcohol consumption and dietary fat intake for variable periods before the tests. Excellent bioavailability of theophylline was confirmed from paired oral and intravenous tests in seven subjects, including two with exocrine pancreatic failure.

2. The clearance of theophylline in the patients was faster than in 15 controls with a ‘healthy lifestyle’ [median 104 (range 18–320) ml h−1 kg−1 vs median 68 (range 50–97) ml h−1 kg−1, P < 0.01]. The difference was especially apparent in the groups with alcoholic CP (P < 0.001 and idiopathic CP (P < 0.01), but not in the AP and CA group as a whole, although drug clearance in some 50% of those cases exceeded the reference range.

3. There was good correlation between theophylline and antipyrine clearance in a subset of 91 subjects who had both tests (15 controls, 76 patients), but antipyrine was much less sensitive as a marker of enzyme induction. This suggests that enzyme induction in pancreatic disease preferentially involves the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450.

4. The lack of correlation between pancreatic secretory capacity in 56 cases, judged by a secretin-pancreozymin test, and theophylline clearance suggests that enzyme induction is not secondary to pancreatic dysfunction.

5. Multivariate regression analysis identified approximately 50% of variability in clearance of each probe. For theophylline, smoking and dietary protein were identified as inducers, whilst certain drugs, alcohol and methylxanthines emerged as inhibitors: the highest theophylline clearance values were shared equally between smokers and non-smokers. For antipyrine, smoking and protein had a positive influence.

6. We cannot tell from the study whether enzyme induction is an epiphenomenon or contributes to the pathogenesis of CP, AP and CA. If future studies prove the latter, the corollary may be that xenobiotics which are inducers of and/or processed by the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450 are aetiological factors in exocrine pancreatic disease.
Increased lysine transport capacity in erythrocytes from patients with chronic renal failure
Authors: Fervenza F. C. , Harvey C. M. , Hendry B. M. , Ellory J. C.
Published: August 2015

1. The initial rate of l-lysine influx into erythrocytes from 13 patients with chronic renal failure has been measured using 14C-labelled lysine. Ten patients were on maintenance haemodialysis and three had never been dialysed. The results are compared with data obtained from 12 normal individuals.

2. The rate of lysine influx into washed cells from buffered saline containing 0.02–0.5 mmol of l-lysine/l has been calculated. The results can be fitted with a model in which influx has a single saturable component obeying Michaelis–Menten kinetics, and a linear non-saturable component.

3. In uraemic erythrocytes the saturable component had a mean Vmax. of 0.762 mmol h−1 litre−1 of cells (n = 13, sem 0.072) and a mean Km of 68.2 μmol/l (sem 5.7). These values in normal erythrocytes were 0.566 mmol h−1 litre−1 of cells (n = 12, sem 0.033) and 70.5 μmol/l (sem 4.1), respectively. The mean apparent diffusion constant (KD) for the linear component of influx was 0.224 h−1 (sem 0.039) in uraemic cells and 0.178 h−1 (sem 0.028) in normals.

4. The 35% increase in mean Vmax. seen in uraemic erythrocytes was statistically significant (P = 0.02). A similar increase in Vmax. in uraemic cells compared with controls was seen in erythrocytes which were studied in zero-trans conditions after depletion of intracellular amino acids. The mean values of Km and KD were not significantly different in uraemia. The origins of this increased membrane transport capacity for lysine in uraemia are discussed.
Inactive plasma renin exhibits sex difference in mice
Authors: Nielsen Arne Høj , Johannessen Arne , Poulsen Knud
Published: August 2015

1. The plasma concentration of inactive renin was two-to three-fold higher in male than in female mice independently of whether mice of strains with low (BALB/c) or high (Theiller) content of active renin in the submandibular salivary glands were studied.

2. Removal of the submandibular glands did not affect the high plasma concentration of inactive renin in male mice.

3. Inactive plasma renin decreased over several days after castration of normal and sialoadenectomized male mice to the same levels as those found in normal female mice.

4. Treatment of these castrated male mice with testosterone increased and normalized inactive plasma renin independently of whether the submandibular glands had been previously removed or not.

5. Testosterone treatment of sialoadenectomized female mice increased inactive renin to the same levels as those found in normal male mice.

6. Our findings suggest that the sex difference in inactive plasma renin in mice may be explained by an increased secretion of inactive renin in male mice stimulated by androgens.

7. Since we have recently found that inactive plasma renin in male mice is mainly of renal origin, this increased secretion is most likely located to the kidneys.
Stimulation by uraemic plasma of frusemide-sensitive sodium efflux in erythrocytes from normal women
Authors: Corry Dalila B. , Tuck Michael L. , Lee David B. N.
Published: August 2015

1. Reduced Na+, K+ pump activity has been reported in uraemic erythrocytes, and this has been attributed to the presence of a circulating ouabain-like inhibitor. Since we have previously reported marked suppression of Na+, K+ co-transport activity in erythrocytes from dialysis patients, we have now examined the effect of incubation with uraemic plasma on Na+ efflux through the Na+, K+ pump and the co-transport pathway in normal erythrocytes from both men and women.

2. The results show that Na+ efflux via the Na+, K+ pump is not different between men and women (3.14 ± 0.14 vs 3.68 ± 0.18 mmol h−1 litre−1 of cells) and is not inhibited by incubation with uraemic plasma.

3. In contrast, co-transport-mediated Na+ efflux is lower in erythrocytes from normal women when compared with normal men (0.17 ± 0.02 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells, P < 0.001).

4. Moreover, incubation with uraemic plasma causes stimulation of Na+ efflux through the co-transport pathway in erythrocytes of healthy women (0.17 ± 0.02 vs 0.27 ± 0.03 mmol h−1 litre−1 of cells, P < 0.005), but not in erythrocytes of healthy men (0.27 ± 0.03 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells).

5. Our data do not support the presence of either a Na+, K+ pump or a co-transport inhibitor in plasma from dialysed uraemic patients. Thus, the suppressed co-transport activity demonstrated in uraemic erythrocytes cannot be attributed to a circulating inhibitor, and may reflect an acquired membrane or transport defect.

6. The stimulation of co-transport by uraemic plasma from women provides a further example of sex-determined characteristics in human erythrocytes, the mechanism of which remains to be elucidated.
Correlation of blood pressure in normotensive and hypertensive individuals with platelet but not lymphocyte intracellular free calcium concentrations
Authors: Pritchard K. , Raine A. E. G. , Ashley C. C. , Castell L. M. , Somers V. , Osborn C. , Ledingham J. G. G. , Conway J.
Published: August 2015

1. Fifty-two normotensive and essential hypertensive subjects were studied. Intracellular free calcium concentration ([Ca2+]i) was measured in lymphocytes (37 subjects) and platelets (18 subjects) by means of the fluorescent indicators, quin 2 and fura-2. In 31 subjects, plasma ionized calcium concentration was also measured.

2. There was a positive correlation between platelet [Ca2+]i and systolic blood pressure (r = 0.485, P < 0.05), diastolic blood pressure (r = 0.542, P < 0.02) and mean blood pressure (r = 0.534, P < 0.02).

3. No statistically significant relationship was observed between plasma ionized calcium and blood pressure.

4. No relationship was found between lymphocyte [Ca2+]i and blood pressure, or between lymphocyte [Ca2+]i and plasma ionized calcium.

5. There was no relationship between [Ca2+]i of lymphocytes and platelets measured simultaneously from the same subject.

6. These findings reconcile previous conflicting reports and show a relationship between platelet but not lymphocyte [Ca2+]i and blood pressure in man.
Naloxone-Reversible Inhibition of Gall-Bladder Mucosal Fluid Secretion in Experimental Cholecystitis in the Cat by Acetorphan, an Enkephalinase Inhibitor
Authors: Jivegård L. , Pollard H. , Moreau J. , Schwartz J. C. , Thune A. , Svanvik J.
Published: August 2015

1. Enkephalin immunoreactive nerve fibres have been demonstrated in the gall bladder of various mammals including man. In various tissues, enkephalins are partly degraded by a membrane metallo-endopeptidase, enkephalinase (EC 3.4.24.11).

2. Using 3H-labelled [d-Ala2,Leu5]enkephalin as a substrate, enkephalinase activity, immunoprecipitated by a monoclonal antibody directed against the rabbit kidney enzyme, was demonstrated in the feline gall bladder. Using the same antibody in 125I-labelled form, the peptidase was immunolocalized by autoradiography, mainly in the epithelium.

3. In experimental cholecystitis, elicited by implantation of human gall-stones into the cat gall bladder, the continuous fluid secretion into the lumen was inhibited by exogenous enkephalins.

4. Acetorphan, an enkephalinase inhibitor, was found to block fluid secretion by the inflamed gall bladder via a naloxone-sensitive mechanism, but not to affect fluid transport in the normal gall bladder. The drug also transiently contracted the gall bladder and increased bile outflow from the liver.

5. It is suggested that acetorphan, by reducing the degradation of endogenous enkephalins in the inflamed gall bladder, decreases fluid secretion by the epithelium and that enkephalinase inhibitors may find clinical applications in acute cholecystitis.
Differential Blood Pressure and Hormonal Effects after Glucose and Xylose Ingestion in Chronic Autonomic Failure
Authors: Mathias C. J. , da Costa D. F. , McIntosh C. M. , Fosbraey P. , Bannister R. , Wood S. M. , Bloom S. R. , Christensen N. J.
Published: August 2015

1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects.

2. In the patients oral glucose lowered blood pressure substantially (−34 ± 7% at 60 min, area under curve −24.9 ± 3.5%, P < 0.001) and for a prolonged period (− 25 ± 4% at 120 min). Plasma noradrenaline levels did not change. In the normal subjects blood pressure was unchanged and plasma noradrenaline rose, suggesting a compensatory increase in sympathetic nervous activity.

3. In the patients xylose caused a smaller and more transient fall in blood pressure (−15 ± 6% at 90 min, area under curve −8.9 ± 4%, P < 0.05) with a non-significant elevation in packed cell volume (36.7 ± 1.8 to 38.2 ± 1.8). It was therefore unclear if xylose was exerting osmotic effects within the bowel which contributed to the small blood pressure fall. Packed cell volume did not change in either the patients or normal subjects after glucose.

4. In the patients and normal subjects plasma insulin rose after glucose. Insulin levels were unchanged after xylose. Levels of pancreatic polypeptide and neurotensin, a potential vasodilator, rose in the patients only. The latter rose to a similar extent after both glucose and xylose, making it unlikely that neurotensin alone accounted for the hypotension.

5. These studies indicate that the carbohydrate components of a meal, and in particular those causing insulin release, contribute to postprandial hypotension in patients with autonomic failure.
Intestinal Infection with Nematospiroides Dubius Selectively Increases Lactase Expression by Mouse Jejunal Enterocytes
Authors: Smith M. W. , Lloyd S.
Published: August 2015

1. Intestinal structure, lactase (β-galactosidase; EC 3.2.1.23) activity and alkaline phosphatase activity have been determined in mouse jejunal and ileal tissues before and during infection with the intestinal parasite Nematospiroides dubius.

2. Oral infection with small numbers of N. dubius larvae caused villus height, crypt depth and enterocyte migration rate to increase in the mouse jejunum. None of these effects occurred in ileal tissue.

3. Lactase activity also increased in jejunal, but not ileal, tissue of infected mice. This increase was associated with a doubling of the rate at which activity appeared in the brush-border membrane of enterocytes during migration over the basal regions of jejunal villi. Alkaline phosphatase activity in jejunal tissue remained unchanged in infected mice.

4. Attention is drawn to the fact that this is the first occasion when crypt cell hyperplasia has been found to be positively correlated with an increase in lactase activity and a decrease in cytotoxic/suppressor T-cells. Further work is needed to establish the primary cause of these effects.