bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man
Authors: Mavichak Viroon , Coppin Christopher M. L. , Wong Norman L. M. , Dirks John H. , Walker Valerie , Sutton Roger A. L.
Published: August 2015

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours.

2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P < 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P < 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria.

3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients.

4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.
Exercise and platelet intracellular free calcium concentration
Authors: Barr Susan M. , Lees Kennedy R. , McBryan Daniel D. , Reid James , Farish Elizabeth , Rubin Peter C.
Published: August 2015

1. A positive correlation between blood pressure and platelet intracellular free calcium concentration ([Ca2+]i) has been reported. We examined the effect of acute changes in blood pressure associated with exercise on platelet [Ca2+]i.

2. Twenty-one subjects had blood pressure and heart rate readings taken after 60 min rest, and subjects were then exercised on a bicycle ergometer at 120 W for 30 min. Blood pressure and heart rate readings were repeated immediately after exercise, 30 min after exercise, and then after a further hour. Blood samples were taken after each set of blood pressure and heart rate readings for catecholamine, lactate and platelet [Ca2+]i estimations.

3. There were significant increases in systolic and diastolic blood pressure, heart rate, and plasma lactate and catecholamine levels during the course of the study. There were no significant changes in platelet [Ca2+]i.

4. These results suggest that the acute blood pressure changes related to exercise are not associated with a change in platelet [Ca2+]i.
Influence of amino acid administration on whole-body leucine kinetics and resting metabolic rate in postabsorptive normal subjects
Authors: Pacy P. J. , Garrow J. S. , Ford G. C. , Merritt H. , Halliday D.
Published: August 2015

1. We have investigated the effect of an amino acid mixture (Varnin 14; 57.4 ±10.2 μmol h−1 kg−1) on whole-body leucine kinetics, calculated by a steady-state reciprocal pool model, and resting metabolic rate in eight postabsorptive normal subjects.

2. Vamin 14 infusion increased whole-body leucine flux (P < 0.001), leucine employed for protein synthesis (P < 0.001), leucine oxidation (P < 0.001), metabolic clearance rate of α-ketoisocaproic acid (P < 0.05) and levels of all three branched-chain amino acids (P < 0.001) compared with the basal situation. In contrast, whole-body proteolysis was reduced (P < 0.05).

3. Resting metabolic rate was increased during Vamin 14 infusion (P < 0.05) and was positively correlated with whole-body protein synthesis (n = 16, r = 0.6342, P < 0.01; y = 0.605x + 173.7), as was the change in metabolic rate with the change in protein synthesis (n = 8, r = 0.772, P < 0.05; y = 0.493x − 10.85).

4. Overall, Vamin 14 infusion was associated with increased blood glucose (P < 0.001), although the observed increase in plasma glucagon (t = 2.012) and plasma insulin (t = 1.683) failed to reach statistical significance.

5. These data lend a measure of support to the hypothesis that the apparent increase in whole-body protein synthesis in insulin-dependent diabetic (type I) subjects during insulin withdrawal may be substrate related.
Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit
Authors: Weinberg J. R. , Wright D. J. M. , Guz A.
Published: August 2015

1. The cardiovascular effects of intravenous injections of interleukin-1 (IL-1) and tumour necrosis factor (TNF) have been investigated in the conscious rabbit. They have been compared with the effects of bacterial lipopolysaccharide (LPS) because both IL-1 and TNF are released from macrophages by LPS.

2. IL-1, TNF and Escherichia coli J5-LPS all caused hypotension when given intravenously in a dose with low mortality. The time course of the hypotension caused by IL-1 and LPS was similar, although the maximal fall in mean blood pressure occurred earlier after IL-1. TNF produced a more sustained fall in blood pressure. Hypotension was not accompanied by a compensatory tachycardia after any of the test substances. Hypotension was associated with a fever after TNF, hypothermia after LPS and no significant change in temperature after IL-1.

3. The packed cell volume did not change during hypotension in any of the study groups, implying that the hypotension was not due to fluid loss resulting from increased capillary permeability.

4. IL-1 and TNF are candidates for the role of effectors of LPS-induced hypotension.
Absence of a late-phase response or increase in histamine responsiveness after bronchial provocation with adenosine 5′-monophosphate in atopic and non-atopic asthma
Authors: Phillips G. D. , Holgate S. T.
Published: August 2015

1. Adenosine 5′-monophosphate (AMP) causes bronchoconstriction in atopic and non-atopic asthma by a mechanism believed to involve histamine release from airway mast cells. To determine whether preformed mast cell mediators, principally histamine, can initiate a late-phase bronchoconstriction we have investigated the effect on the airways over a 24 h period of a single bronchial challenge with AMP.

2. Six atopic asthmatic subjects (all late responders to inhaled allergen) and six non-atopic asthmatic subjects were studied on two occasions for a 24 h period after inhalation of the provocation concentration of AMP required to produce a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (PC20) and 0.9% (w/v) sodium chloride placebo, respectively. The atopic asthmatic subjects were studied on a further occasion after challenge with the PC20 allergen.

3. Inhalation of the PC20 AMP resulted in an immediate fall in FEV1 to a mean maximum 25.5% below baseline without resulting in any late decrease in airway calibre. No significant increase in non-specific bronchial responsiveness as determined by measuring the PC20 histamine before, and at 3, 9 and 24 h after, AMP challenge, occurred. Inhalation of the PC20 allergen caused a reproducible late-phase bronchoconstriction and increase in non-specific bronchial responsiveness in all the atopic asthmatic subjects studied.

4. These results suggest that preformed mast cell mediators, principally histamine, play no role in the initiation of the late-phase reaction in allergen-provoked asthma, although they may contribute to the inflammatory changes involved.
Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: Kinetic evaluation of l-alanyl-l-glutamine and glycyl-l-tyrosine
Authors: Albers S. , Wernerman J. , Stehle P. , Vinnars E. , Fürst P.
Published: August 2015

1. For the first time utilization of intravenously administered l-alanyl-l-glutamine and glycyl-l-tyrosine was investigated by means of their kinetic behaviour after bolus injection in 10 and 11 apparently healthy male subjects (age 26.6 ± 5.7 years), respectively.

2. The injection of the synthetic dipeptides was not accompanied by any side effects or complaints.

3. The synthetic dipeptides l-alanyl-l-glutamine and glycyl-l-tyrosine were rapidly cleared from plasma. By applying a monoexponential model the elimination half-lives were found to have very similar values (3.8 ± 0.5 and 3.4 ± 0.3 min) whether alanine or glycine was occupying the N-terminal position. The estimated volume of distribution was approximately that of the extracellular space.

4. Peptide disappearance was accompanied by a prompt equimolar increase in the concentrations of the constituent amino acids alanine and glutamine as well as glycine and tyrosine.

5. The study provides firm evidence that l-alanyl-l-glutamine and glycyl-l-tyrosine are rapidly (quantitatively) hydrolysed. The results of this study may indicate a safe and efficient parenteral use of the investigated peptides as sources of free glutamine and free tyrosine.
Derivation of urinary dopamine from plasma dopa
Authors: Zimlichman Reuven , Levinson Paul D. , Kelly Gerald , Stull Robin , Keiser Harry R. , Goldstein David S.
Published: August 2015

1. We estimated the extent to which circulating dopa (3,4-dihydroxyphenylalanine) is the source of urinary dopamine (DA; 3,4-dihydroxyphenethylamine). Tritiated dopa ([3H]dopa) was infused for 90 min into the left renal artery of seven anaesthetized foxhounds, and levels of labelled and unlabelled dopa and DA were measured in the ureteral urine and in the femoral arterial and left renal venous plasma.

2. Only a small percentage of [3H]dopa delivered to the kidneys was excreted as [3H]DA (0.59% from the left kidney, 0.68% from the right); however, the arterial concentration of endogenous dopa (1220 pg/ml) and the renal plasma flows (144 and 141 ml/min by p-aminohippurate clearances) were such that all of the urinary excretion of endogenous DA (about 1 ng/min from each kidney) could be accounted for by uptake and decarboxylation of circulating endogenous dopa.

3. Plasma dopa is the main source of urinary DA.
Increased spontaneous production of interleukin-1 together with inhibitory activity in systemic sclerosis
Authors: Westacott C. I. , Whicher J. T. , Hutton C. W. , Dieppe P. A.
Published: August 2015

1. Increased spontaneous production of interleukin-1, measured as lymphocyte-activating factor activity, was seen in unstimulated monocytes from systemic sclerosis patients.

2. Inhibitory activity to interleukin-1 was seen in both normal and patient monocyte supernatants.

3. Inhibitory activity was significantly higher in unstimulated and stimulated monocyte supernatants from systemic sclerosis patients.

4. The net effect was an apparent decrease in lymphocyte-activating factor activity in the monocyte supernatants from systemic sclerosis patients.

5. These findings suggest a possible mechanism by which collagen deposition could be enhanced, thereby giving rise to the extensive fibrosis characteristic of systemic sclerosis.
A comparison of endogenous digoxin-like immunoreactivity and sodium transport inhibitory activity in umbilical arterial and venous serum
Authors: Morris J. F. , Poston L. , Wolfe C. D. , Hilton P. J.
Published: August 2015

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured by radioimmunoassay for digoxin in 13 paired samples of arterial and venous umbilical cord serum. EDLI was present in vein and artery, but was higher in the venous samples (P < 0.025).

2. The venous cord serum inhibited the ouabain-sensitive sodium efflux rate constant of a normal mixed leucocyte population when compared with the effect of arterial cord serum (P < 0.005).

3. It is suggested that the placenta may be involved in the production or metabolism of neonatal EDLI and of the inhibitor of sodium transport.
Increased urinary excretion of prostaglandin E in patients with idiopathic hypercalciuria
Authors: Henríquez-La Roche Carlos , Rodríguez-Iturbe Bernardo , Herrera José , Parra Gustavo
Published: August 2015

1. Because urinary prostaglandin excretion could play a role in idiopathic hypercalciuria (IH), we studied the excretion of prostaglandin E (PGE), calcium and sodium at various urine flows in 21 patients (14 males) with urolithiasis and IH, seven stone formers (five males) with normal calciuria and 20 controls (11 males). Dietary composition was comparable and sodium intake was restricted to 100–120 mmol/day.

2. Analyses were performed on 30 min urine collections obtained after overnight water deprivation and during water diuresis. Male IH patients had increased levels of urinary PGE at all ranges of urine flow. PGE excretion correlated directly with urine flow in patients and controls, but the slope of this relationship in individual IH male patients was steeper than in controls (P < 0.01). Calciuria correlated directly with urine output in patients with IH but not in controls. Calcium and sodium excretion were directly correlated (P < 0.0001) in patients and controls. There were no significant differences between absorptive IH (seven patients) and renal IH (eight patients). There were no significant differences between stone formers with normocalciuria and control subjects.

3. The findings suggest that increased urinary PGE could play a role in the hypercalciuria syndrome, possibly by promoting natriuresis.
Renal handling of pepsinogens A and C in man
Authors: ten Kate Reinier W. , Pals Gerard , Pronk Jan C. , Bank Ruud A. , Eriksson Aldur W. , Donker Ab J. M. , Meuwissen Stephan G. M.
Published: August 2015

1. Fractional excretions of pepsinogens A and C in the urine were investigated in 21 healthy subjects and in 38 patients with chronic renal insufficiency. In eight of the healthy subjects fractional excretions were measured again after oral administration of omeprazole for 9 days.

2. The mean fractional excretion of pepsinogen A was 27.6% (range 4.4–73.9%) in healthy subjects and remained unchanged after omeprazole administration. In patients with renal failure the mean fractional excretion of pepsinogen A was 37.9% (range 7.0–81.9%). The mean fractional excretion of pepsinogen C was 1.0% (range 0.04–6.8%) in healthy subjects and decreased after omeprazole. In patients with chronic renal diseases a sharp rise in fractional excretion of pepsinogen C was observed once glomerular filtration rate was less than 40 ml/min.

3. Fractional excretion of pepsinogen A was unexpectedly high for a negatively charged protein with a molecule mass of 40 000 daltons. This might be explained by the presence of the positively charged activation peptide. Furthermore, pepsinogen C seemed to be almost entirely reabsorbed from the glomerular filtrate and a tubular reabsorption maximum appeared to be present. Pepsinogen C may, therefore, be a new marker of tubular function. The cause of the remarkable difference in tubular handling of two quite similar low-molecular-mass proteins remains to be elucidated.
Urinary excretion of guanosine 3′:5′-cyclic monophosphate during sleep in obstructive sleep apnoea patients with and without nasal continuous positive airway pressure treatment
Authors: Krieger Jean , Schmidt Mariette , Sforza Emilia , Lehr Lydia , IMBS Jean-Louis , Coumaros Geneviève , Kurtz Daniel
Published: August 2015

1. It has recently been shown that obstructive sleep apnoea (OSA) patients have increased urinary water and salt excretion during sleep which tends to normalize with nasal continuous positive airway pressure (CPAP) treatment.

2. To investigate the mechanisms of these changes in renal function, nocturnal urinary excretion of catecholamines and guanosine 3′:5′-cyclic monophosphate (cyclic GMP), which reflects atrial natriuretic factor (ANF) release, and next-morning plasma active renin concentrations were studied in 21 OSA patients on 2 consecutive nights, either untreated or treated with nasal CPAP.

3. In keeping with previous results, fractional urine flow and fractional Na+ and Cl− excretions were higher during untreated than during CPAP-treated nights.

4. No difference in plasma active renin concentration or in urinary excretion of noradrenaline, adrenaline, free dopamine and total dopamine could be demonstrated, but cyclic GMP excretion was significantly higher during untreated than during CPAP-treated nights.

5. The data are consistent with the hypothesis that the increased water and salt excretion in OSA patients is due to increased ANF release.

6. The proposed mechanism is an atrial distension due to increased (more negative) intrathoracic pressures during ineffective inspiratory efforts against the occluded upper airways which have been found in OSA.
Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats
Authors: Winter R. J. D. , Meleagros L. , Pervez S. , Jamal H. , Krausz T. , Polak J. M. , Bloom S. R.
Published: August 2015

1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h.

2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension.

3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment.

4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found.

5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.
Ascorbic acid: a factor concentrated in human gastric juice
Authors: Rathbone B. J. , Johnson A. W. , Wyatt Judith I. , Kelleher J. , Heatley R. V. , Losowsky M. S.
Published: August 2015

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A+D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology.

2. A significant reduction in gastric juice ascorbic acid (A+D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis.

3. Concentrations of ascorbic acid (A+D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach.

4. These data demonstrate that considerable quantities of ascorbic acid (A+D) are normally ‘secreted’ into the stomach.

5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.
A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise
Authors: Wilson Rachel C. , Jones P. W.
Published: August 2015

1. The intensity of breathlessness during exercise was measured in ten normal subjects using a visual analogue scale (VAS) and a Borg scale to compare the use of the scales and their repeatability, both within the duration of a period of exercise and between tests. For each scale, subjects performed two exercise tests separated by a period of 2–6 weeks. Each exercise test consisted of two cycles of progressively increasing and decreasing workload.

2. All subjects felt confidently able to use both scales to quantify their feelings of breathlessness exclusively of other sensation. Equal preference was expressed for use of a particular scale.

3. With both scales there was a large intersubject variation in the relationship between dyspnoea score and minute ventilation (VE) (P < 0.01), and in the range of the scale used.

4. There was a good correlation between the VAS and Borg scores at each level of VE (r2 = 0.71), but the VAS score was used over a wider range than the Borg score.

5. The relationship between VE and the dyspnoea score measured by the two techniques was predominantly linear. The mean r2 for VAS score/VE was 0.68 (sd 0.19) and for Borg score/VE the mean r2 was 0.75 (sd 0.13).

6. The relationships VAS score/VE and Borg score/VE were unaffected by the direction in which the workload was varied (P > 0.05).

7. VE, measured at each work rate, did not differ between the two cycles (P > 0.05) or between the 2 days (P > 0.05).

8. With both scales, the slope of the VE-breathlessness relationship was slightly higher during the second half of the exercise compared with the first (0.05 < P > 0.01).

9. The scores with both scales were lower in the second test compared with the first (P < 0.01): Borg 16% lower, VAS 27% lower.

10. Measurements of dyspnoea made with the Borg scale appeared to have greater stability than VAS measurements and to correlate with VE a little better.
Hypertension and renal dysfunction in primary hyperparathyroidism: effect of parathyroidectomy
Authors: Salahudeen A. K. , Thomas T. H. , Sellars L. , Tapster S. , Keavey P. , Farndon J. R. , Johnston I. D. A. , Wilkinson R.
Published: August 2015

1. Twenty-four patients with primary hyperparathyroidism were studied before and 18 restudied 6.5 months (mean) after parathyroidectomy, to investigate the pathogenesis of the hypertension which may accompany this condition. Comparison was made with age-matched patients with essential hypertension and with normotensive control subjects.

2. There was a significant inverse relationship between mean arterial pressure and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) clearance in patients with hyperparathyroidism both before and after parathyroidectomy, but not in patients with essential hypertension.

3. Creatinine clearance appeared to overestimate glomerular filtration rate in some patients with hyperparathyroidism, falling significantly after surgery while 51Cr-EDTA clearance was unchanged. This observation may explain the failure of some previous studies to relate hypertension to impairment of renal function.

4. Plasma renin activity, plasma aldosterone and whole-body exchangeable sodium did not differ between normotensive and hypertensive patients with primary hyperparathyroidism and were unchanged after surgery.

5. Parathyroidectomy did not result in any change in blood pressure or in glomerular filtration rate measured by 51Cr-EDTA clearance.
Pharmacological modification of oxygen affinity improves deformability of deoxygenated sickle erythrocytes: a possible therapeutic approach to sickle cell disease
Authors: Keidan A. J. , Sowter M. C. , Johnson C. S. , Marwah S. S. , Stuart J.
Published: August 2015

1. The formation of polymerized haemoglobin S in sickle cells is critically dependent on the concentration of deoxygenated haemoglobin so that compounds which increase the oxygen affinity of haemoglobin S are potential anti-sickling agents.

2. BW12C [5-(2-formyl-3-hydroxyphenoxy)pentanoic acid] and BWA589C [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid] are aromatic benzaldehydes that cause a dose-dependent left-shift of the oxygen saturation curve of haemoglobin S by stabilization of its oxy-(R)-conformation.

3. A 5 μm pore filtration method, which is highly sensitive to polymerization of haemoglobin S, was used to demonstrate a significant improvement in the deformability of deoxygenated sickle erythrocytes at concentrations (0.75–1.5 mmol/l) of BW12C and BWA589C that are achievable in vivo. Both compounds may therefore be of value for the treatment of sickle cell disease.

4. Filtration of sickle cells through pores of 5μm diameter is a sensitive technique for evaluating the rheological effects of potential anti-sickling compounds.
Altered platelet function during mental stress and adrenaline infusion in humans: evidence for an increased aggregability in vivo as measured by filtragometry
Authors: Larsson P. T. , Hjemdahl P. , Olsson G. , Egberg N. , Hornstra G.
Published: August 2015

1. The effects of mental stress induced by a colour word conflict test (CWT; n = 9) or 3 h infusions of placebo or adrenaline (0.4 nmol min−1 kg−1; n = 9) on platelet function in vivo were studied in 16 healthy male volunteers.

2. Platelet function was assessed by a filtragometry technique, which reflects aggregability in vivo, and by measurements of the plasma levels of β-thromboglobulin (β-TG) and platelet factor 4 (PF4).

3. Adrenaline and CWT induced marked cardiovascular responses as expected. Venous plasma adrenaline increased from 0.1–0.2 nmol/l at rest to 4.87 ± 0.42 nmol/l during adrenaline infusion and to 0.46 ± 0.10 nmol/l during CWT.

4. Filtragometry measurements were reproducible within individuals with coefficients of variation of 7.9% during placebo infusion and 5.4% for resting measurements between days.

5. Platelet aggregability, as measured by filtragometry, was similarly increased during both adrenaline infusion (P < 0.05) and CWT (P < 0.01).

6. The coefficients of variation for β-TG and PF4 levels were 17.3% for log β-TG and 27.9% for log PF4 between days, but could not be calculated for within-day variability. Both β-TG (P < 0.05) and PF4 (P < 0.01) levels decreased time-dependently during placebo infusion, indicating that long resting periods (hours) are needed to attain basal levels. Artefactual results could not be identified by evaluating βTG/PF4 ratios.

7. β-TG and PF4 levels did not decrease time-dependently during adrenaline infusion. There were no significant changes of β-TG or PF4 during CWT.

8. Our results suggest that platelet aggregability in vivo is enhanced by mental stress and high physiological levels of circulating adrenaline. The more pronounced effect of adrenaline and CWT on filtragometry readings than β-TG and PF4 levels in plasma suggests that platelet aggregability in vivo is not necessarily paralleled by increased platelet release.
Brainstem auditory evoked responses in rats with experimental chronic renal failure
Authors: Shvili Y. , Gafter U. , Zohar Y. , Talmi Y. P. , Levi J.
Published: August 2015

1. Chronic renal failure was induced in rats by five-sixths nephrectomy. Brainstem auditory evoked response (BAER) was recorded after 3 months.

2. In the uraemic rats latency of the first wave was delayed, while the interpeak I-V latency was similar to that of the controls.

3. These results suggest a delayed neural conduction along the acoustic nerve or cochlear changes in uraemic rats.
Regulation of α- and β-myosin heavy chain messenger RNAs in the rat myocardium by amiodarone and by thyroid status
Authors: Franklyn J. A. , Green N. K. , Gammage M. D. , Ahlquist J. A. O. , Sheppard M. C.
Published: August 2015

1. A number of the cardiovascular effects of amiodarone resemble those of hypothyroidism, prompting examination of the relationship between the actions of the drug and thyroid hormones. Amiodarone treatment of the rat was used as a model to determine the influence of the drug on thyroid hormone-regulated gene expression in the myocardium and liver; interactions between amiodarone and thyroid status were examined in hypothyroid and tri-iodothyronine (T3)-treated animals.

2. Myocardial levels of α- and β-myosin heavy chain (MHC) messenger RNAs (mRNAs) were measured by dot hybridization to specific oligonucleotide probes; myocardial actin mRNA was measured in parallel by hybridization to a complementary DNA (cDNA) probe. Hepatic levels of Spot 14 and thyroxine-binding prealbumin mRNA were similarly determined by dot hybridization to radiolabelled cDNAs.

3. Amiodarone treatment of the rat resulted in specific increases in both α- and β-MHC mRNAs in the myocardium, as well as hepatic Spot 14 mRNA, changes reversed by T3 administration.

4. Hypothyroidism resulted in a reduction in myocardial α-MHC and hepatic Spot 14 mRNAs, in contrast to amiodarone, whilst hypothyroidism and amiodarone both exerted stimulatory influences on β-MHC mRNA. Treatment of hypothyroid rats with amiodarone had no significant effect on β-MHC or Spot 14 mRNAs, but a further reduction in α-MHC mRNA, compared with the untreated hypothyroid state, was evident.

5. The demonstrated influence of amiodarone on both α- and β-MHC mRNAs and interactions between amiodarone and thyroid status in regulating MHC gene expression may be relevant to its therapeutic effect in man.
Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man
Authors: Boer W. H. , Koomans H. A. , Mees E. J. Dorhout
Published: August 2015

1. The acute effects of chlorothiazide and bendroflumethiazide on renal Li+ clearance (CLi) were studied in Na+-restricted healthy humans during maximum water diuresis.

2. Chlorothiazide, which has marked carbonic anhydrase inhibiting activity, increased CLi by about 25%. The concomitant rise in uric acid clearance, maximum urine flow and bicarbonate excretion suggests that this drug suppressed proximal reabsorption through carbonic anhydrase inhibition, which would also explain the observed fall in glomerular filtration rate (increased glomerulotubular feedback activity).

3. Bendroflumethiazide, which lacks carbonic anhydrase inhibiting activity, did not affect CLi or any of the other above-mentioned variables.

4. It is concluded from the lack of an effect of bendroflumethiazide on CLi that Li+ is not reabsorbed in thiazide-sensitive segments of the human distal nephron. The rise in CLi after chlorothiazide is most likely due to suppressed Li+ reabsorption in the proximal tubules resulting from carbonic anhydrase inhibition.

5. The results of this study are compatible with the concept that CLi is an index of Na+ and water delivery from the proximal tubules in humans.
Cardiac autonomic dysfunction in obese subjects
Authors: ROSSI Marco , Marti Giuliano , Ricordi Luigi , Fornasari Gabriele , Finardi Giorgio , Fratino Pietro , Bernardi Luciano
Published: August 2015

1. The prevalence of cardiac autonomic alterations was evaluated in 23 obese subjects with body mass index 37.2 ± 3.03 kg/m2 (mean ± sd), compared with 78 controls with body mass index 22.5 ± 2.6 kg/m2 (P < 0.001).

2. Cardiac autonomic function was assessed by four standard tests (heart rate response to deep breathing and to the Valsalva manoeuvre, systolic blood pressure fall after standing and diastolic pressure rise during handgrip) and by the cross-correlation test, a new method of computerized analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signals.

3. Considering tests indicative of parasympathetic function, only the heart rate response to the deep breathing and the cross-correlation test were significantly lower in the obese than in the control group [deep breathing = 13.95 ± 8.65 beats/min (mean ± sd) vs 24.5 ± 7.65, P < 0.001; cross-correlation 4.28 ± 0.74 units vs 5.14 ± 0.63, P < 0.001]. Deep breathing and/or cross-correlation were abnormal in 10 (43.5%) obese subjects (deep breathing: seven subjects, cross-correlation: eight subjects). No significant difference between groups was found for the response to the Valsalva manoeuvre: the Valsalva ratio was 1.69 ± 0.45 in obese subjects and 1.88 ± 0.33 in controls (P = NS). The Valsalva ratio was abnormal in three obese subjects.

4. No significant differences were found between groups for tests indicative of sympathetic function. The rise in diastolic blood pressure after handgrip was 12.6 ± 6.2 mmHg (1.67 ± 0.82 kPa) in obese subjects and 18.2 ± 4.9 mmHg (2.42 ± 0.65 kPa) in controls (P = NS), and the fall in systolic blood pressure after standing was −6.8 ± 8.6 mmHg (−0.90 ± 1.14 kPa) in obese subjects and −6.9 ± 10.4 mmHg (−0.91 ± 1.38 kPa) in controls (P = NS). The handgrip test was abnormal in four obese subjects, while no obese subject had an abnormal blood pressure response to standing.

5. Our findings suggest a high incidence of cardiac autonomic dysfunction in obese subjects. Since cardiac autonomic alterations have been shown to be involved in the mechanisms of cardiac sudden death, our data suggest a possible role of autonomic dysfunction in the increased risk for sudden death in obesity.
Effect of replacing glucose with lipid on the energy metabolism of newborn infants
Authors: van Aerde J. E. E. , Sauer P. J. J. , Pencharz P. B. , Smith J. M. , Swyer P. R.
Published: August 2015

1. Indirect calorimetry and primed constant infusion of [U-13C]glucose were combined in 28 appropriate-for-gestational age newborn, parenterally fed infants, in order to measure glucose utilization and glucose oxidation and to estimate lipogenesis from glucose.

2. The infants were randomly allocated to either a group receiving glucose as the non-protein energy source or a group having one-quarter of the glucose energy replaced by intravenous fat. The energy intake (370 kJ day−1 kg−1) and protein intake (3.4 g day−1 kg−1) were similar in both groups.

3. Energy expenditure (P < 0.005), non-protein carbon dioxide production (P < 0.005) and non-protein oxygen consumption (P < 0.05) were lower in the lipid-supple-mented group.

4. The significant excess of glucose utilization over oxidation (P < 0.001) can be accounted for by lipid synthesis from glucose.

5. Fat synthesis from glucose was higher in the glucose/amino acid group (P < 0.02), but total fat storage was higher in the lipid-supplemented group (P < 0.02). Nitrogen balance was similar in both groups.

6. As lipogenesis from glucose is an energy- and oxygen-consuming and a carbon dioxide-producing process, the data suggest that the differences between the glucose-only group and the lipid-supplemented group are due to different rates of lipogenesis from glucose.
Somatostatin Analogue Improves Survival in Conscious Cirrhotic Rats Subjected to Gastrointestinal Bleeding
Authors: Cerini Raimondo , Braillon Alain , Hadengue Antoine , Koshy Abraham , Lee Samuel S. , Lebrec Didier
Published: August 2015

1. The continuing doubt concerning the value of vasoconstrictive therapy for gastrointestinal bleeding may be related to the complexity of clinical trials in such a situation.

2. The effect of SM 201–995, a somatostatin analogue, was investigated in conscious cirrhotic rats before, during and after experimental bleeding from the portal territory.

3. Before haemorrhage, somatostatin analogue (8 μg h−1 kg−1 body weight, intravenously) produced a significant decrease in portal pressure (17%), whereas a placebo (saline) lacked significant effect.

4. The rats were then subjected to spontaneous bleeding, by disconnection of the portal catheter from the pressure gauge, for a 5 min period. At the end of the haemorrhage, haemodynamic parameters did not significantly differ between the group receiving somatostatin analogue and that receiving placebo.

5. Fifteen minutes after the end of the bleeding period, portal pressure was significantly lower in rats receiving somatostatin analogue [8.5 ± 0.5 mmHg (1.13 ± 0.07 kPa), mean ± sem] than in rats receiving placebo [11.0 ± 1.1 mmHg (1.50 ± 0.15 kPa)].

6. The volume of blood lost and mortality were significantly lower in the group treated with somatostatin analogue (2.3 ± 0.1 ml/100 g body weight and 8%, respectively) than in the group receiving placebo (3.0 ± 0.1 ml/100 g body weight and 50%, respectively).

7. These results demonstrate, in an experimental model, the beneficial effect of somatostatin analogue for the treatment of gastrointestinal bleeding due to portal hypertension. They suggest that administration of this substance should be started as soon as possible after the beginning of haemorrhage and continued after the cessation of bleeding.
Chronobiological Study of the Relationship between Dyspnoea and Airway Obstruction in Symptomatic Asthmatic Subjects
Authors: Peiffer C. , Marsac J. , Lockhart A.
Published: August 2015

1. We performed a chronobiological study of the relationship between peak expiratory flow rate (PEFR) and magnitude of dyspnoea in 35 symptomatic asthmatic patients to determine how accurately asthmatic subjects assess spontaneous airway obstruction and whether this accuracy varies throughout the 24 h period and depends on characteristics of the subjects or asthma.

2. At 07.00,11.00, 15.00, 19.00 and 23.00 hours on 8 consecutive days in their ordinary environment and under their usual drug regimen, the subjects first rated their dyspnoea with a visual analogue scale and immediately after recorded their PEFR.

3. The linear regression coefficients between dyspnoea score and PEFR for the 35 subjects were continuously distributed between −0.93 and +0.21, with most r values ranging from −0.9 to −0.5. The group median r values calculated at each time point showed that strongest correlation between dyspnoea score and PEFR occurred at 7 h, which coincided with the lowest PEFR values.

4. We chose r = −0.7 (r2 = 0.5) as a limit to distinguish good perceivers (−1 < r ≤ −0.7) from bad perceivers of airway obstruction. These two populations differed only by a higher variability of both PEFR and dyspnoea score in good than in bad perceivers, but not for severity, duration or treatment of asthma, absolute value of dyspnoea score, age or sex.

5. Our study quantified an important intra- and between-subject variability in the accuracy of perception of spontaneous airway obstruction in asthmatic subjects which seems to be unrelated to most characteristics of asthma.
Effects of Meal Composition on the Postprandial Blood Pressure, Catecholamine and Insulin Changes in Elderly Subjects
Authors: Potter J. F. , Heseltine D. , Hartley G. , Matthews J. , Macdonald I. A. , James O. F. W.
Published: August 2015

1. The effects of four meals of similar energy, but different nutritional, composition on postprandial blood pressure, heart rate, autonomic function, catecholamines, insulin and packed cell volume levels were studied in seven fit elderly subjects.

2. The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal (i.e. mixed) and high fat meals. Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure. No significant postural blood pressure fall occurred after any of the meals. Supine heart rate was unaffected by meal type or by time, and although erect heart rate showed a small increase during the study there was no between-meal difference.

3. Parasympathetic function was unaffected by meal type. Plasma noradrenaline rose after the high carbohydrate and mixed meals only, remaining elevated for 120 min after meal consumption. This increase was not related to the changes in blood pressure or plasma insulin levels.

4. Plasma insulin and glucose rose after the high carbohydrate and mixed meals, but were unchanged after the high protein and high fat meals. Packed cell volume showed a small decrease towards the end of the study, although there was no between-meal variation.

5. The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function, insulin release or fall in plasma volume. We propose that the postprandial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load.
Measurement of the Rate of Protein Synthesis in Muscle of Postabsorptive Young Men by Injection of a ‘Flooding Dose’ of [1-13C]leucine
Authors: Garlick Peter J. , Wernerman Jan , McNurlan Margaret A. , Essen Pia , Lobley Gerald E. , Milne Eric , Calder Graham A. , Vinnars Eric
Published: August 2015

1. The ‘flooding dose’ technique for measuring the rate of protein synthesis in tissues in vivo involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize differences in isotopic enrichment of the free amino acid in plasma and tissue compartments. This approach has been investigated in human muscle by taking biopsies from postabsorptive male volunteers given [1-13C]leucine.

2. Intravenous injection of 4 g of unlabelled leucine resulted in a rapid rise in free leucine concentration of seven- to eleven-fold in plasma and five-fold in muscle. Values were still elevated by two-fold after 2 h.

3. Five minutes after injection of [1-13C]leucine (0.05 g/kg) the isotopic enrichment of plasma leucine was 82% that of the injected material, falling to 44% at 120 min. The enrichment of free leucine in sequential muscle biopsies was close to that in plasma and almost identical to that for plasma α-ketoisocaproate.

4. The rate of protein synthesis was determined from the increase in leucine enrichment in protein of muscle biopsies taken before and 90 min after injection of [1-13C]leucine (0.05 g/kg; 19 or 39 atom% excess) and the average plasma α-ketoisocaproate enrichment over this period (taken to represent muscle free leucine). The mean rate of muscle protein synthesis in 10 subjects was 1.95 (sem 0.12)%/day. Rates of protein synthesis calculated from plasma leucine as precursor enrichment were only 5% lower than those calculated from plasma α-ketoisocaproate.

5. It is concluded that a ‘flooding dose’ of 13C-labelled amino acid is a useful and convenient technique for determining the rate of protein synthesis in tissues of human volunteers and patients.
The E1 α and β Subunits of the Pyruvate Dehydrogenase Complex are M2‘d’ and M2‘e’ Autoantigens in Primary Biliary Cirrhosis
Authors: Fussey Shelley P. M. , Bassendine Margaret F. , Fittes Dorothy , Turner Ian B. , James Oliver F. W. , Yeaman Stephen J.
Published: August 2015

1. Sera from 76 patients with primary biliary cirrhosis (PBC) and 66 control subjects (53 with chronic liver disease and 13 healthy normal women) were immunoblotted against purified E1 component of bovine pyruvate dehydrogenase complex (PDC) and bacterial PDC.

2. Thirty-one out of seventy-six (41%) sera from PBC patients showed a positive response to bovine E1α, and five of these 31 (7% of total) reacted with bovine E1β. None of the control sera reacted with bovine E1 α or β.

3. None of the PBC sera that recognized bovine E1 subunits reacted with bacterial PDC E1.

4. In the PBC patients there was no correlation between presence of antibodies to E1α and β subunits and histological stage of the disease.

5. Our data demonstrate that the E1α and β components of mammalian PDC are the M2‘d’ and ‘e’ mitochondrial autoantigens, respectively.
Small-Intestinal Function during Enteral Feeding and Starvation in Man
Authors: Maxton D. G. , Menzies I. S. , Slavin B. , Thompson R. P. H.
Published: August 2015

1. Small-intestinal absorption and permeability were measured in nine patients with malnutrition who were receiving liquid enteral nutrition after different periods of starvation, in five patients receiving enteral nutrition without starvation, in six healthy subjects after starvation for 36 h and in two obese subjects starved for 11 days.

2. Absorption, expressed by the plasma 60 min d-xylose level and the plasma 60 min d-xylose/3-O-methyl-d-glucose ratio, was greatly decreased (P < 0.001) in the nine patients receiving enteral feeding after starvation, whereas permeability, denoted by the 5 h urinary lactulose/rhamnose ratio, was increased (P < 0.05).

3. The five patients receiving enteral feeds without prior starvation had normal intestinal absorption and permeability.

4. Starvation of the healthy subjects reduced absorption (P < 0.05) and this was detectable at 36 h. Permeability, however, was not increased by 36 h starvation. Starvation of the obese subjects also progressively reduced absorption, and this was reversed with refeeding.

5. Changes in intestinal function during enteral feeding are similar to those seen in intestinal diseases. They develop rapidly and are not caused or reversed by liquid enteral feeds. Starvation, before beginning feeding, may explain some of the changes found.
Atrial Natriuretic Peptide Release during Sleep in Patients with Obstructive Sleep Apnoea before and during Treatment with Nasal Continuous Positive Airway Pressure
Authors: Krieger J. , Laks L. , Wilcox I. , Grunstein R. R. , Costas L. J. V. , McDougall J. G. , Sullivan C. E.
Published: August 2015

1. Plasma levels of atrial natriuretic peptide (ANP) were measured in seven patients with obstructive sleep apnoea (OSA) while they were awake, during repetitive apnoea and during treatment with nasal continuous positive airway pressure (CPAP).

2. ANP levels in both pulmonary artery and peripheral venous samples were elevated during apnoeic sleep and reduced when apnoea was prevented by nasal CPAP. Mean values of pulmonary artery ANP were 116.3 ± 17.9 pg/ml during apnoea and 64.8 ± 15.2 pg/ml (P < 0.05) on nasal CPAP.

3. It is concluded that there is increased ANP release during sleep in patients with OSA and that CPAP treatment normalizes ANP secretion. These findings may explain previously identified urinary abnormalities in OSA.
Evidence against a Role for Platelet-Activating Factor in Hypoxic Pulmonary Vasoconstriction in the Rat
Authors: McCormack D. G. , Barnes P. J. , Evans T. W.
Published: August 2015

1. The effect of two structurally different platelet-activating factor (PAF) receptor antagonists, WEB 2086({3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]-treazolo-[4,3-a][1,4]-diazepine-2-yl]-1-(morpholinyl)-1-propanone}) and BN 52021, on hypoxic pulmonary vasoconstriction (HPV) was studied using an isolated rat lung preparation perfused with blood.

2. In lungs treated with WEB 2086 there was a dose-dependent attenuation of HPV, with complete abolition of HPV at the maximum dose.

3. Low doses of WEB 2086 caused only slight diminution of the pressor response to angiotensin II, although higher doses caused increasing attenuation of the angiotensin pressor response.

4. BN 52021 did not affect HPV.

5. Injection of PAF caused an increase in pulmonary artery pressure of 145%, a response abolished by pre-treatment of the lungs with either WEB 2086 or BN 52021.

6. These results suggest that PAF does not mediate HPV in the rat.
Trophic Effect of Efamol on the Rat Small-Intestinal Mucosa
Authors: Jenkins A. P. , Thompson R. P. H.
Published: August 2015

1. The hypothesis that triacylglycerols are trophic to the small-intestinal mucosa of the rat was tested by comparing the action of the essential fatty acid-rich oil Efamol with that of glucose.

2. Two groups of nine female Wistar rats were pair-fed Vivonex HN with 50% calorie substitution by glucose or Efamol for 21 days.

3. Body weight gain was greater with glucose than with Efamol, but, despite this, whole gut weight, mucosal weight and mucosal protein were increased by Efamol in all small-intestinal segments. Total mucosal DNA was also increased with a significant change in the middle small-intestinal segment. These changes were associated with an increased crypt cell production rate.

4. Fasting plasma levels of peptidyltyrosyltyrosine (‘peptide YY’), but not of enteroglucagon, were significantly elevated in the Efamol-fed group.

5. The data show a trophic effect of Efamol on the rat small-intestinal mucosa. Possible mechanisms are discussed.