bluuebunny/crossref_metadata_2025 huggingface dataset:
Substrate induction of bilirubin conjugation and biliary excretion in the rat
Authors: Muñoz Maria E. , Esteller Alejandro , González Javier
Published: August 2015

1. The effect of high bilirubin loads (60 μmol/kg twice daily for 2 days) on glucuronosyltransferase activity and biliary excretion of bilirubin was studied in Wistar rats.

2. The concentration of bilirubin in serum increased from 1.1 μmol/l in controls to 5.5 μmol/l after bilirubin pretreatment.

3. Bilirubin pretreatment led to a 25% increase in hepatic UDP-glucuronosyltransferase activity. Bilirubin Tm, was increased by 22% and correlated positively with glucuronosyltransferase activity.

4. The output of conjugated bilirubin in bile was enhanced but no changes in the proportion of monoconjugates to diconjugates were observed.

5. Our data suggest that prolonged treatment with bilirubin can increase biliary bilirubin excretion by inducing glucuronosyltransferase activity.
Metabolic and ventilatory responses during very low level exercise
Authors: Goldstein Susan A. , Weissman Charles , Askanazi Jeffrey , Rothkopf Michael , Milic-Emili J. , Kinney John M.
Published: August 2015

1. Nine male and six female healthy subjects were studied during supine bicycle exercise at workloads of 12 and 37 W; pedalling rates varied between 30 and 50 cycles/min at each workload. Measurements were made of oxygen consumption (Vo2), carbon dioxide production (Vco2), minute ventilation (VE), tidal volume (VT), respiratory frequency (fR), inspiratory and expiratory time (TI, TE) and mean inspiratory flow (VT/TI) using a non-invasive canopy–computer–spirometer system.

2. At rest, males had greater values of VE, VT, TI, inspiratory duty cycle (TI/TTOT), Vco2 and Vo2, and a lower fR, than females.

3. At the lower workload, Vo2, Vco2, VE, VT and VT/TI increased linearly with increasing pedalling rate, whereas at the higher workload there was a decrease in Vo2 and little or no change in ventilatory parameters from 30 to 50 cycles/min except for an increase in fR in females.

4. While performing supine exercise, there was an effect of pedalling rate on ventilatory and metabolic parameters at the low workload (12 W) which diminished at the higher workload (37 W). An increase in pedalling rate appears to enhance efficiency at these low workloads.

5. Differences between the sexes during exercise generally include: (a) a higher breathing frequency, (b) a greater mechanical efficiency, and (c) lower ventilatory equivalents of O2 and CO2 (VE/Vo2 and VE/Vco2) during the higher workload in females than males.
Human atrial natriuretic polypeptide during escape from mineralocorticoid excess in man
Authors: Miyamori Isamu , Ikeda Masatoshi , Matsubara Takao , Okamoto Shinya , Koshida Hideo , Morise Toshio , Takeda Ryoyu
Published: August 2015

1. Plasma concentrations of human α-atrial natriuretic polypeptide (h-αANP) during escape from the effects of mineralocorticoid excess were determined in six healthy volunteers.

2. Escape, as indicated by an abrupt increase in sodium excretion on the third to sixth day of 9α-fludrocortisone acetate administration (0.6 mg/day), was observed in all subjects.

3. The mean plasma h-αANP level was 30.9 ± sem 8.8 pmol/l on the control day; it increased exponentially in response to 9α-fludrocortisone acetate administration, reached a significant level (114.0 ± 22.4 pmol/l, P < 0.05) on the day before escape and remained elevated during escape.

4. The 24 h creatinine clearance and blood pressure did not change significantly before the escape. Plasma h-αANP increased markedly when the cumulative sodium balance exceeded 220 mmol.

5. These results suggest that h-αANP may play a contributory role in natriuresis and diuresis after mineralocorticoid excess.
Whole body leucine turnover and nutritional status in continuous ambulatory peritoneal dialysis
Authors: Goodship T. H. J. , Lloyd S. , Clague M. B. , Bartlett K. , Ward M. K. , Wilkinson R.
Published: August 2015

1. Nutritional status and leucine turnover has been measured in ten patients with chronic renal failure before the onset of continuous ambulatory peritoneal dialysis (CAPD) and after 3 months treatment, and in five normal subjects.

2. Somatic muscle protein reserves, as judged by anthropometry and measurement of total body potassium, showed no significant changes after 3 months treatment and were not significantly different from normal.

3. Visceral protein reserves, as judged by serum albumin and plasma amino acids, showed a significant fall after 3 months CAPD and were also lower than in normal subjects.

4. Protein turnover was lower in uraemic than in normal subjects, but the balance between synthesis and breakdown was significantly higher and was maintained after 3 months on CAPD.
Short-term studies on the use of amino acids as an osmotic agent in continuous ambulatory peritoneal dialysis
Authors: Goodship T. H. J. , Lloyd S. , McKenzie P. W. , Earnshaw M. , Smeaton I. , Bartlett K. , Ward M. K. , Wilkinson R.
Published: August 2015

1. A 1% amino acid dialysis solution with a high concentration of the branched-chain amino acids has been compared with 1.36% glucose in short-term studies.

2. The 1% amino acid solution was as effective an agent as 1.36% glucose with respect to ultrafiltration and clearance of creatinine, urea and potassium.

3. Levels of branched-chain amino acids rose to the upper end of the normal range within 1 h and remained at this level over the entire period of the study. Total and non-essential amino acids had returned to baseline by the end of the cycle.

4. Blood glucose rose to significantly greater levels during the 1.36% glucose exchange than during the 1% amino acid exchange. There was an increase in serum insulin levels during both cycles; this was significantly greater with the 1% amino acid solution than the 1.36% glucose.

5. There was no evidence of short-term metabolic complications with the 1% amino acid solution.
Diurnal change in plasma atrial natriuretic peptide concentrations
Authors: Richards A. M. , Tonolo G. , Fraser R. , Morton J. J. , Leckie B. J. , Ball S. G. , Robertson J. I. S.
Published: August 2015

1. Diurnal changes in plasma concentrations of atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were investigated in seven normal volunteers studied under standardized conditions of dietary sodium, posture and physical activity. After completion of the diurnal study serial measurements of these variables were continued during, and on recovery from, a 2 day period of severe sodium depletion.

2. Clear diurnal variations in plasma concentrations of renin, angiotensin II, aldosterone, Cortisol and antidiuretic hormone were observed.

3. Plasma ANP concentrations also varied significantly over 24 h. Values peaked about mid-day and a distinct trough in peptide concentrations occurred in the early evening. However, variations in plasma ANP values were of relatively small amplitude and not clearly independent of modest parallel shifts in sodium balance.

4. Changes in plasma ANP concentrations both within the diurnal study period and during sodium deprivation were closely and positively correlated with concomitant changes in cumulative sodium balance.

5. No simple parallel or reciprocal relationships between plasma concentrations of ANP, on the one hand, and concurrent plasma concentrations of other hormones or in the rate of urinary sodium excretion, on the other, were observed during the 25 h of the diurnal study.
Vitamin B12 homoeostasis after haemorrhage in the rat: the importance of skeletal muscle
Authors: Bhatt H. R. , Linnell J. C.
Published: August 2015

1. The effects of haemorrhage on vitamin B12 (cobalamin) homoeostasis have been studied in rats with and without prior administration of 57Co-labelled cyanocobalamin.

2. Arteriovenous differences in radioactivity and endogenous B12 were measured across the thigh extensor muscles. Radioactivity and endogenous B12 were also measured in skeletal muscle, liver and kidney.

3. Haemorrhage induced a marked rise in circulating B12 with a concomitant loss of the vitamin from skeletal muscle and liver, but in kidney there was a net gain. Restoration of the blood volume with autologous plasma did not prevent release of B12 from tissues.

4. The results suggest that vitamin B12 reserves may be seriously depleted by the wasting of skeletal muscle.
Glucocorticosteroid status in chronic alcoholics with and without skeletal muscle myopathy
Authors: Duane P. , Peters T. J.
Published: August 2015

1. Chronic alcoholism is associated with a selective atrophy of type II skeletal muscle fibres. We studied the glucocorticoid status of chronic alcoholics with and without myopathy to determine if hypercortisolism is responsible for the myopathy.

2. Twenty-four hour urinary Cortisol excretion and diurnal serum Cortisol measurements were not significantly different in chronic alcoholics, with and without atrophy of type II skeletal muscle fibres.

3. Diurnal serum Cortisol variation was normal for both groups of alcoholics studied. None of the patients with myopathy had raised serum Cortisol levels.

4. We conclude that chronic alcoholic myopathy is not due to alcohol-related pseudo-Cushing's syndrome.
Effect of verapamil on polycythaemia secondary to hypoxia in rats
Authors: Douglas A. R. , Moore-Gillon J. C. , Sheldon J. W. S. , Cameron I. R.
Published: August 2015

1. Polycythaemia occurs in man secondary to chronic hypoxaemia, and may lead to morbidity from hyperviscosity of the blood. Hypoxaemic rats develop similar changes. We have investigated the effect of the calcium antagonist verapamil upon the polycythaemic response to hypoxia in rats.

2. Control groups of 10 male rats breathed air in an environmental chamber for 28 days. Hypoxic groups breathed a normobaric atmosphere of 10% oxygen for 6 h each day, and air for the remaining 18 h. Control and hypoxic groups were treated with intraperitoneal or subcutaneous water, or with intraperitoneal or subcutaneous water plus verapamil.

3. On day 28, packed cell volume (PCV) was measured by a microhaematocrit technique and red cell mass (RCM) by dilution of injected 51Cr-labelled rat erythrocytes.

4. PCV and RCM were significantly higher in all the hypoxic groups compared with the control groups (P < 0.01 in each case).

5. PCV and RCM were significantly lower in the hypoxic groups treated with intraperitoneal or subcutaneous verapamil than in the hypoxic groups treated with intraperitoneal or subcutaneous water (P < 0.01). There were no significant differences between PCV and RCM in verapamil- and water-treated normoxic control groups. Verapamil had no effect on the shift of the oxygen/haemoglobin dissociation curve produced by hypoxia.

6. Verapamil reduces the polycythaemic response to repeated intermittent hypoxia in rats. Venesection is usually performed for excessive secondary polycythaemia in man. Our results suggest a possible therapeutic role for verapamil in such individuals.
Muscle strength in the triceps surae and objectively measured customary walking activity in men and women over 65 years of age
Authors: Bassey E. J. , Bendall M. J. , Pearson M.
Published: August 2015

1. Objective measurements of the maximal voluntary strength of triceps surae and the amount and speed of customary walking have been made in 56 men and 66 women aged over 65 years, who were living independently.

2. Strength was measured using a dynamometer based upon a hydraulic system (Bourdon tube). Walking was assessed, for amount using a mechanical accelerometer (pedometer) over a week, and for speed using a self-paced test for normal walking over 100 m on the level. The reliability and validity of these methods has been described.

3. The men were significantly stronger (1128 ± 206 vs 873 ± 177 N) even after adjustment for body weight; their amount of walking was similar to that of women, but they walked significantly faster (4.8 ±0.6 vs 4.2 ±0.6 km/h). Men were significantly more active in leisure pursuits (as assessed by questionnaire).

4. Significant associations between strength and chosen normal walking speed were found for both sexes (r = 0.41, P < 0.001 for men and r = 0.36, P < 0.01 for women). The amount of walking (daily stepscore as a mean from 7 consecutive days recorded) was significantly but less strongly correlated with strength (r = 0.30, P < 0.05) in the men only.

5. Multiple regression analysis showed that in men neither age nor amount of walking had any further effect in addition to speed, but in women age had an additional effect (multiple R = 0.48).

6. An association has been demonstrated which raises the possibility of reversing loss of muscle strength through increased daily activity.
Plasma [3H]noradrenaline kinetics in man: is separation of alumina extracts by high performance liquid chromatography necessary?
Authors: McCance Alastair J. , Forfar J. Colin
Published: August 2015

1. After an 80 min intravenous infusion of 1-[3H]noradrenaline ([3H]NA) in 19 subjects, the proportion of alumina-extractable 3H due to [3H]NA was 86 ± 2% in arterial and 78 ± 2% in venous plasma. [3H]Dihydroxy-phenylethyleneglycol ([3H]DHPG) accounted for 8 ± 1% in arterial and 13 ± 1% in venous plasma. [3H]Dihydroxymandelic acid ([3H]DOMA) was not detected.

2. No time-dependent change in the proportion of alumina-extractable 3H due to [3H]NA was seen in either arterial or venous plasma over this period. In venous plasma the proportion of alumina-extractable 3H due to [3H]DHPG increased slightly between 30 and 80 min, from 10 ± 1% to 13 ± 1%.

3. The results were unchanged with chronic β-blockade and with either 1-[2,5,6-3H]NA or 1-[7,8-3H]NA.

4. After [3H]NA infusion in man the radioactivity recovered after alumina extraction is predominantly [3H]NA and thus can be used directly to determine [3H]NA kinetics without the need for metabolite separation.
Abnormal diurnal variation in salt and water excretion in patients with obstructive sleep apnoea
Authors: Warley A. R. H. , Stradling J. R.
Published: August 2015

1. In healthy individuals, sleep is associated with a fall in urine and sodium output.

2. Seven male patients with obstructive sleep apnoea exhibited a paradoxical rise in both urine and sodium output during the hours of sleep.

3. Continuous positive airway pressure applied via the nose abolished both the apnoea and the nocturnal rise in urine and sodium output, thereby restoring the diurnal pattern towards normal.
Decreased density of binding sites for atrial natriuretic peptide on platelets of patients with severe congestive heart failure
Authors: Schiffrin Ernesto L.
Published: August 2015

1. Binding sites for atrial natriuretic peptide (ANP) with a specificity similar to that of vascular ANP receptors have been demonstrated previously in human platelets. The density of these binding sites for ANP on platelets is decreased after increased dietary sodium intake, when plasma ANP levels increase. ANP-binding sites were investigated in patients with severe congestive heart failure (CHF), a condition in which there is an increase in the concentration of ANP in plasma.

2. In 24 patients with a clinical diagnosis of functional class III–IV CHF, plasma ANP (90.3 ± 13.4 fmol/ml, mean ± sem) was significantly higher (P < 0.001) than in 16 age-matched patients without cardiac disease (15.4 ± 2.0 fmol/ml). The density of ANP-binding sites on platelets was significantly lower (P < 0.01) in the 24 CHF patients (6.3 ± 0.8 fmol/109 cells) than in the non-cardiac patients (11.8 ± 1.4 fmol/109 cells). There was no significant difference in affinity of the ANP-binding sites between both groups. There was a significiant non-linear inverse correlation of the density of ANP-binding sites on platelets with plasma ANP concentration. These results could not be explained by prior receptor occupancy secondary to the elevated concentration of circulating ANP.

3. In conclusion, ANP-binding sites on platelets are decreased in patients with severe CHF and with significantly elevated concentration of ANP in plasma.
Inherited glomerular properties and their role in the expression of various forms of experimental glomerular injury
Authors: Chandrachud Lata , Jones J. M. Boulton
Published: August 2015

1. Glomeruli possess properties which vary between Lewis and DA strains of rat.

2. These properties may account for differences in the expression of various forms of experimental glomerular injury.

3. The difference in susceptibility to Heymann nephritis in the Lewis strain was confirmed.

4. Chronic serum sickness induced by cationic human serum albumin led to capillary loop deposits in Lewis rats, whereas DA rats had mesangial deposits of rat immunoglobulin G even in control kidneys.

5. Lewis rats developed proteinuria after infusion of the polycation hexadimethrine whereas DA rats did not.

6. DA rats developed greater proteinuria after injection of puromycin aminonucleoside.

7. These results support the hypothesis that an individual's susceptibility to different forms of glomerulonephritis may result from their glomerular properties and not necessarily from their immune responses.
Ventilation and breathlessness on maximal exercise in patients with interstitial lung disease after local anaesthetic aerosol inhalation
Authors: Winning A. J. , Hamilton R. D. , Guz A.
Published: August 2015

1. The ventilatory response to maximal incremental exercise and the accompanying sensation of breathlessness were studied after the inhalation of 0.9% sodium chloride (saline) and 5% bupivacaine aerosols in six patients with interstitial lung disease.

2. The adequacy of airway anaesthesia induced by bupivacaine aerosol was confirmed by the absence of the cough reflex to 5% citric acid aerosol on completion of exercise.

3. All subjects first performed a trial exercise test to familiarize them with the procedure and to assess the degree of arterial oxygen desaturation on exercise. In subsequent tests, supplementary oxygen was given to maintain the saturation at 95% or above.

4. Airway anaesthesia had no effect on the ability to perform exercise as assessed by maximum workload, CO2 production or heart rate. No significant changes were seen on the pattern of breathing, minute ventilation or endtidal Pco2 on exercise. There was, however, a small but statistically significant increase in ventilation related to CO2 production (VE/Vco2) at the end of exercise.

5. There was a tendency for breathlessness to be increased by airway anaesthesia but this did not reach statistical significance.

6. These results provide no evidence that vagal afferent activity is responsible for the abnormal ventilatory response to exercise in patients with interstitial lung disease. The perception of breathlessness in these patients was not diminished by anaesthesia of the airway.
A DNA polymorphism of the apolipoprotein C-III gene in extracoronary atherosclerosis
Authors: O'Connor G. , Stocks J. , Lumley J. , Galton D. J.
Published: August 2015

1. A genetic polymorphism of apolipoprotein (apo) C-III was studied in 49 Caucasian patients with extra-coronary atherosclerosis demonstrated by angiography.

2. Twelve patients (24%) possessed an uncommon allelic variant of the apo A-I/C-III gene cluster compared with two (4%) in 50 healthy controls (P < 0.01).

3. Of 27 patients with carotid atherosclerosis, 22% had the uncommon genotype (P < 0.02), and in aortofemoral atherosclerosis (n = 22) 27% possessed the uncommon variant (P < 0.01).

4. When normotriglyceridaemic subgroups (n = 32) with arterial disease were studied the difference in genotype frequencies persisted, 22% having the uncommon allele (P < 0.01), suggesting that such genetic variants have effects independent of circulating levels of plasma lipids.
Effect of high protein intake on sodium, potassium-dependent adenosine triphosphatase activity in the thick ascending limb of Henle's loop in the rat
Authors: Bouby Nadine , Bankir Lise
Published: August 2015

1. We have previously shown that the hypertrophy of the kidney induced by a high protein diet consists of a preferential hypertrophy of the thick ascending limb (TAL) of Henle's loop. This might be related to an increase in the active salt transport by this segment. Sodium, potassium-dependent adenosine triphosphatase (Na+,K+-ATPase) activity was measured in TAL from kidneys of rats fed either a low (LP) or a high (HP) protein diet for several weeks.

2. Enzymatic activity was measured by microdensitometry, after appropriate cytochemical reaction, for an adenosine 5′-triphosphate (ATP) concentration of 0–66 mmol/l. Both activity per unit tubular length and mean activity per unit tissue volume were recorded. A calibration was designed to convert usual microdensitometry units (extinction) into conventional biochemical units (mol of product formed).

3. For non-limiting substrate concentrations, the Na+,K+-ATPase activity, expressed per unit length of tubule on the sections, was 50% higher in HP than in LP rats, an increase proportional to that of the simultaneously measured tubule diameter. When expressed per unit tubular volume, Na+,K+-ATPase activity was similar in both groups of rats. The dissociation constant for ATP was also similar in both groups.

4. Results show that a high protein diet induces an increase in Na+,K+-ATPase activity in TAL, thus enabling an enhanced NaCl transport in this segment. This increase in transport capacity is not due to an increase in the density of enzymatic units but to an increase in their number, in relation to the hypertrophy of the TAL.
Renal transplantation: HLA-linked, non-cytotoxic antibodies develop after blood transfusion
Authors: MacLeod Alison M. , Stewart Keith N. , Urbaniak Stanislaw , Catto Graeme R. D.
Published: August 2015

1. A previously untransfused dialysis patient was given blood from a single donor on three occasions and sera were obtained from the recipient before and after transfusion.

2. The sera were tested against B-lymphocytes from the blood donor and his family in the erythrocyte–antibody rosette inhibition assay to determine whether any Fc-receptor-blocking activity which developed was HLA linked.

3. Antibody activity was noted after the second transfusion and was directed toward B-lymphocytes from the blood donor and his family members sharing the haplotype HLA A11, B12 with him.

4. These antibodies were removed by the absorption of active sera with lymphocytes from the blood donor but not from (a) his sibling who shared no HLA antigens with him or (b) the transfusion recipient. Absorption of the active sera with platelets from the blood donor did not remove activity.

5. These results indicate that Fc-receptor-blocking antibodies developing after blood transfusion are directed to HLA-linked antigens on donor lymphocytes.
Hepatic cholesterol synthesis and esterification in rats after chronic ethanol feeding
Authors: Venkatesan S. , Simpson K. J. , Peters T. J.
Published: August 2015

1. Chronic (5 weeks) alcohol-fed and isocaloric glucose pair-fed control rats had similar body weights, liver weights and liver protein contents.

2. Hepatic esterified cholesterol and triacylglycerol levels were two- to three-fold higher in alcohol-fed rats than in controls.

3. Hepatic cholesterol synthesis rates measured in vivo with 3H2O were significantly reduced in alcohol-fed rats.

4. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (NADPH) (EC 1.1.1.34) activity was increased and the apparent Km for 3-hydroxymethyl-3-glutaryl-CoA was decreased in alcohol-fed rats.

5. Hepatic acyl-CoA:cholesterol acyltransferase (cholesterol acyltransferase; EC 2.3.1.26) activity was significantly increased in alcohol-fed rats.

6. These results indicate that there is no direct relationship between 3-hydroxy-3-methylglutaryl-CoA reductase activity and sterol synthesis in liver of alcohol-fed rats.
Acute effects of ethanol on protein synthesis in different muscles and muscle protein fractions of the rat
Authors: Preedy Victor R. , Peters Timothy J.
Published: August 2015

1. The effects of a single dose of ethanol (75 mmol/kg body weight) on rates of muscle protein synthesis were examined in young rats. Fractional rates of protein synthesis were measured in the soleus, plantaris, gastrocnemius, diaphragm and stomach by the large ‘flooding-dose’ technique.

2. After 150 min, the fractional synthesis rates of all muscles were reduced by 15–35%. Skeletal muscles containing a predominance of anaerobic (fast-twitch, type II) fibres showed greater changes when compared with skeletal muscles with a predominance of aerobic (slow-twitch, type I) fibres.

3. Gastrocnemius muscles were separated into sarcoplasmic, stromal and myofibrillar protein fractions. Protein synthesis was reduced similarly in all fractions by ethanol treatment, by approximately 30%.

4. As skeletal muscle mass comprises 40% of body weight, the responses have important physiological implications and may also be responsible for the muscle atrophy observed in alcoholic patients.
31P nuclear magnetic resonance measurement of free erythrocyte magnesium concentration in man and its relation to blood pressure
Authors: Woods K. L. , Walmsley D. , Heagerty A. M. , Turner D. L. , Lian Lu-Yun
Published: August 2015

1. 31P n.m.r. spectroscopy was used to measure the dissociation constant of MgATP under simulated intracellular conditions and to measure erythrocyte free magnesium concentration.

2. In a group of 40 subjects, the relationship between erythrocyte free magnesium and blood pressure, age and sex was examined by univariate and multivariate regression analysis.

3. A weak positive association was found between erythrocyte free magnesium and mean blood pressure. This association was lost in a multivariate regression analysis including both age and sex.

4. No significant relationship was found between erythrocyte free magnesium and age, sex, family history of hypertension or use of the combined oral contraceptive pill in the sample studied.
Biochemical studies of N-methyltransferase in human and guinea-pig lung: no apparent role in the pathogenesis of asthma
Authors: Henderson G. D. , Ruffin R. E. , Alpers J. H. , Crockett A. J. , Schembri D. A. , Latimer K. M.
Published: August 2015

1. N-Methyltransferase activity was measured in surgical specimens of human lung using phenylethanolamine as substrate. Thirty-three male and seven female patients, age range 19–78 (median 62.5) years were studied. The activity in lung homogenates was 0.59 × 10−6 units/mg of protein (sem 0.03, n = 40), with a range of 0.16–1.16 × 10−6 units/mg of protein. There was no difference (P = 0.97) in activity between males and females.

2. Non-specific N-methyltransferase activity was estimated in 17 of the surgical specimens using β-phenylethylamine as substrate. This activity was 38.9% (sem 5.3) of that with phenylethanolamine. Comparative studies with rabbit lung, which has a well-characterized non-specific N-methyltransferase, showed significant differences in substrate specificity between the two species.

3. The apparent Km and Vmax for phenylethanolamine in seven human lung homogenates was 22.0 (sem 4.6). mmol/l and 1.82 × 10−6 units/mg of protein (sem 0.36). The noradrenaline N-methyltransferase (NMT; EC 2.1.1.28) inhibitors SKF 64139-A and LY 134046 did not inhibit this activity up to a concentration of 100 μmol/l. This activity was inhibited 51.4% (sem 8.6, n = 6) by 100 μmol/l S-adenosyl-l-homocysteine. Immunohistochemistry did not reveal immunoreactive NMT in human lung sections.

4. Comparative studies with guinea-pig lung homogenates demonstrated non-specific N-methyltransferase activity in this species which is similar to the human lung. Using an ovalbumin-sensitized guinea-pig model of allergic bronchoconstriction, there was no difference (P = 0.24) between control (2.74 × 10−6 units/mg of protein, sem 0.25, n = 5) and sensitized (2.24 × 10−6 units/mg of protein, sem 0.27, n = 9) guinea pigs.

5. These results show that human lung has significant N-methylating activity. This is not NMT but a nonspecific N-methyltransferase. There was no difference (P = 0.34) in activity between asthmatic and non-asthmatic lung. The animal model did not reveal a relationship between this activity and the development of allergic bronchoconstriction.
Pathogenesis of abnormal acid–base balance in the young spontaneously hypertensive rat
Authors: Lucas Philip A. , Lacour Bernard , Comte Lydie , Drüeke Tilman
Published: August 2015

1. We have previously reported reduced blood pH and plasma bicarbonate in young Okamoto–Aoki spontaneously hypertensive rats (SHR) compared with normotensive Wistar–Kyoto rats (WKY). Acid loading with 1.5% (w/v) NH4Cl as the sole drinking fluid produced identical falls in blood pH, the difference remaining significant.

2. The ability of SHR to excrete acid and alkaline loads was compared with that of WKY under metabolic cage conditions. The effects of such manipulations on urinary sodium, potassium, calcium and phosphate excretion were also determined.

3. No difference was found in the ability to excrete an acid load or to reduce urine pH. Neither total urinary ammonium ion nor titratable acid differed significantly between the strains under either baseline or acid-loading conditions.

4. Baseline urinary bicarbonate excretion was not significantly different between strains but intraperitoneal administration of NaHCO3 at 2.0 mmol/kg body weight resulted in enhanced excretion in the SHR (SHR vs WKY: 625.2±71.5 vs 381.8±40.6 μmol 24h−1 kg−1 body weight, P < 0.01, mean±sem).

5. No difference in urinary sodium or potassium excretion was observed between SHR and WKY, but basal calcium and phosphate excretion were reduced in SHR (P < 0.05).

6. Increased urinary bicarbonate excretion in the presence of significantly reduced plasma bicarbonate suggests reduced tubular reabsorption of bicarbonate, which may contribute to the mild metabolic acidosis in young SHR.
Atrial natriuretic peptide inhibits osmolality-induced arginine vasopressin release in man
Authors: Allen M. J. , Ang V. T. Y. , Bennett E. D. , Jenkins J. S.
Published: August 2015

1. Eight normal volunteers were infused with 5% saline (5 g of NaCl/100 ml) at a rate of 0.06 ml min−1 kg−1 for 120 min to increase plasma osmolality and plasma arginine vasopressin. Human atrial natriuretic peptide (α-hANP; 100 μg) or placebo was given in random order in a double-bind cross-over design for the last 20 min of the saline infusion.

2. Compared with the placebo infusion, atrial natriuretic peptide (ANP) produced a 43% greater sodium excretion and a 34% greater urinary volume in the subsequent hour.

3. Mean plasma immunoreactive ANP did not increase in response to changes in osmolality and rose to a peak of 118 pg/ml during the α-hANP infusion. α-hANP produced significant suppression of mean plasma arginine vasopressin over the 60 min after the infusions.

4. We conclude that ANP is not released in response to increased osmolality in vivo, and that it inhibits osmolality-induced arginine vasopressin release in man.
Fluid homoeostasis during prolonged low-intensity walking on consecutive days
Authors: Leiper J. B. , McCormick K. , Robertson J. D. , Whiting P. H. , Maughan R. J.
Published: August 2015

1. The effect on fluid homoeostasis of walking 37 km on each of 4 consecutive relatively cool days was studied in six male subjects. The daily exercise intensity was consistent and was equivalent to 17(1)% [mean (se)] of maximum oxygen uptake for these subjects.

2. The diet during the study consisted of a mainly carbohydrate breakfast, consumed immediately before each day‘s exercise, and unrestricted access to a normal mixed diet after completion of each day's exercise. Water was allowed ad libitum during the walk. Food and fluid intake were recorded.

3. Body weight remained constant over the 4-day walk. The difference between total daily fluid intake and the corresponding 24 h urine output was 1684 (250) ml, 1621 (522) ml, 1107 (252) ml and 1406 (208) ml, respectively, on each of the 4 exercise days.

4. There was a calculated increase of 21.3(6.6)% in plasma volume over the 4-day walk; the largest daily change [11.3(2.9)%] occurred during the walk on day 1. The increase in plasma volume was maintained for at least 4 days after completion of the walk.

5. From day 2, serum sodium concentration tended to increase during the exercise period and fell to the pre-exercise concentration during the overnight rest periods. The concentration of the other measured serum constituents remained relatively constant, and serum osmolality did not alter over the study period.
Effects of hyperinsulinaemia on the cardiovascular responses to graded hypovolaemia in normal and diabetic subjects
Authors: Scott A. R. , Bennett T. , MacDonald I. A.
Published: August 2015

1. Two experiments were carried out. The first with five normal male subjects was placebo controlled and single blind, each subject being studied on two occasions. Lower body subatmospheric pressure (LBSP) was used to assess the cardiovascular effects of graded hypovolaemia before and during either a hyperinsulinaemic, euglycaemic clamp or a placebo clamp using 0.9% (w/v) NaCl only.

2. During hyperinsulinaemia, resting systolic blood pressure rose and was accompanied by forearm vasodilatation. Forearm blood flow (FABF) and heart rate (HR) were higher at each level of LBSP during than before hyperinsulinaemia. In addition, hyperinsulinaemia was accompanied by a small increase in noradrenaline, but packed cell volume did not change.

3. In the second experiment, the effects of a hyperinsulinaemic euglycaemic clamp on the cardiovascular responses to LBSP were assessed in seven diabetic subjects with peripheral and autonomic neuropathy.

4. In contrast to the normal subjects, there was a slight fall in systolic blood pressure during the clamp but no effect was noted on HR or FABF. Mean arterial blood pressure was lower at each level of LBSP during hyperinsulinaemia compared with the pre-elamp period. Packed cell volume fell during the clamp and plasma noradrenaline rose. In one of the diabetic subjects, a precipitous fall in blood pressure occurred during hyperinsulinaemia when LBSP of 10 mmHg (1.3 kPa) was applied, this manoeuvre having been well tolerated before the clamp.

5. The mode of action of hyperinsulinaemia is not clear, but there was, however, no evidence that a fall in plasma volume had occurred.
Effect of a meal containing protein on lithium clearance and plasma immunoreactive atrial natriuretic peptide in man
Authors: Solomon L. R. , Atherton J. C. , Bobinski H. , Cottam S. L. , Gray C. , Green R. , Watts H. J.
Published: August 2015

1. The effect of meals with a high and low protein content and of the fasting state on renal function and plasma atrial natriuretic peptide was studied in water-loaded normal volunteers.

2. Creatinine clearance increased after the high protein meal, but did not change after the low protein meal or while fasting. Observations of similar increases in urine sodium and potassium excretion and a transient decrease in urine flow after both meals suggest that the protein content of the meal is not an important contributory factor in these responses to feeding.

3. Absolute delivery of sodium and water out of the proximal tubules (assessed by the lithium clearance method) was higher after both meals than while fasting; fractional lithium clearance was higher after the low protein meal than the high protein meal and while fasting. Absolute reabsorption from proximal tubules was increased after only the high protein meal.

4. A transient decrease in the fraction of water delivered to distal nephron segments that appeared in the urine (fractional distal water excretion) was observed after both meals. Fractional distal sodium excretion and absolute distal sodium and water reabsorption increased after both meals.

5. Since plasma atrial natriuretic peptide either decreased (high protein meal) or remained unchanged (low protein meal and fasting), it is unlikely that this hormone is involved in the hyperfiltration after the high protein meal and the natriuresis after both high and low protein meals.
Age-related changes in factor VII activation in healthy women
Authors: Scarabin P. Y. , Van Dreden P. , Bonithon-Kop C. , Orssaud G. , Bara L. , Conard J. , Samama M.
Published: August 2015

1. To investigate the age-related changes in factor VII activation in healthy women, a regular factor VII clotting assay (factor VIIc) was carried out simultaneously with a new enzyme immunoassay for the quantification of antigen factor VII (factor VIIag).

2. Both factor VIIc and factor VIIag levels were positively correlated with age (r = 0.79 and r = 0.62, respectively, n = 25, P < 0.001). The rise with age in factor VIIc was steeper than in factor VIlag and the ratio of factor VIIc to factor VIlag (an indicator of the activity state of factor VII) increased with age (r = 0.42, P < 0.05).

3. The results show that an increased conversion of native single-chain factor VII to the fully active double-chain form is associated with advancing age in women.

4. This finding is consistent with a possible role of activated factor VII in the pathogenesis of thromboocclusive vascular disease in women.
Acute effect of smoking on rebreathing carbon monoxide, breath-hold carbon monoxide and alveolar oxygen
Authors: Kirkham Andrew J. T. , Guyatt Andrew R. , Cumming Gordon
Published: August 2015

1. The rise (‘boost’) in carboxyhaemoglobin (HbCO) on smoking has been studied with alveolar carbon monoxide measurements before and after smoking a cigarette. We re-examined this in 28 subjects with HbCO values compared with rebreathing carbon monoxide [FAco(Rb)] and breath-hold alveolar carbon monoxide and oxygen concentrations, obtained after a 20 s breath-hold [FAco(Bh)] and FAo2(Bh), respectively]. Tests were done in the order FAco(Bh) and FAo2(Bh), FAco(Rb), FAco(Bh) and FAo2(Bh) before and after smoking a single cigarette, with HbCO being measured 1 min before and after smoking.

2. The changes were expressed as the relative boost:

For HbCO the average value was 23.7%, but the FAco(Rb) boost was only 9.8%. The first post-smoking FAco(Bh) boost was 3.9% (5.0 min after smoking), rising to 8.5% 9.4 min later.

3. The FAo2(Bh) values fell from a mean of 15.4% before smoking to 14.3% (5.0 min after smoking) then recovered to 15.4% 9.4 min later, suggesting a transient effect on pulmonary gas exchange. Correction of the first post-smoke FAco(Bh) data for this effect increased the relative boost to 11.5%. Routine FAo2(Bh) measurements may be useful in further smoking studies.

4. We conclude that none of the alveolar sampling techniques gives a reliable measurement of the acute HbCO changes associated with smoking.
Effect of intravenous infusion of adrenaline on the cardiovascular responses to distal body subatmospheric pressure in man
Authors: Fellows I. W. , MacDonald I. A. , Bennett T. , O'Donoghue D. P.
Published: August 2015

1. On two separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline [0.27 nmol (50 ng) min−1 kg−1] or saline (154 mmol/l NaCl), plus ascorbic acid (5.68 mmol/l), over 30 min.

2. On each occasion, the subjects were exposed to distal body subatmospheric pressure (DBSP), 0 to 50 mmHg (0 to 6.65 kPa) in 10 mmHg (1.33 kPa) steps, before infusion, during the final 15 min of the infusion, and at 15 min and 30 min after the cessation of the infusion.

3. Venous adrenaline concentrations of 2.85 ±0.22 nmol/l were achieved during the adrenaline infusion, compared with 0.49 ± 0.07 nmol/l during the saline infusion (P < 0.001). At 15 min and at 30 min after cessation of the adrenaline infusion, venous adrenaline concentrations had fallen to levels similar to those achieved after the cessation of the saline infusion.

4. Heart rate rose significantly from 58 ±4 beats/min to 67 ±4 beats/min during the adrenaline infusion (P < 0.05), but there was no further significant change in response to 50 mmHg (6.65 kPa) DBSP. At 30 min after the cessation of the adrenaline infusion, heart rate rose from 60 ± 4 beats/min to 78 ± 7 beats/min in response to 50 mmHg DBSP. This increase was significantly greater than that observed before the adrenaline infusion [58 ± 4 beats/min to 69 ±7 beats/min during 50 mmHg (6.65 kPa) DBSP; P < 0.01].

5. During the infusion of adrenaline, systolic arterial blood pressure rose and diastolic arterial blood pressure fell, but the blood pressure responses to DBSP were unaffected.

6. Forearm blood flow increased significantly during adrenaline infusion but there was no significant difference in the fall in forearm blood flow during DBSP compared with the values before infusion. At 15 min after the cessation of the adrenaline infusion, forearm vascular resistance rose proportionately more in response to DBSP than it had before the adrenaline infusion (P < 0.05).

7. These results are consistent with adrenaline-mediated facilitation of sympathetic neuronal release of noradrenaline in the heart and in the forearm vascular bed.
Effect of low dose infusion of atrial natriuretic peptide on renal function in man
Authors: Solomon L. R. , Atherton J. C. , Bobinski H. , Hillier V. , Green R.
Published: August 2015

1. The effects of the infusion of a low dose (2 pmol min−1 kg−1 for 3 h) of human atrial natriuretic peptide (hANP) were studied in seven healthy volunteers undergoing a water diuresis. Lithium clearance was used to monitor proximal tubular function.

2. hANP increased urine flow rate, sodium, calcium and magnesium excretion without significant changes in potassium and phosphate excretion, heart rate or blood pressure.

3. hANP caused a small change in fractional lithium clearance, and larger changes in distal nephron handling of sodium and water.

4. Plasma renin activity tended to decrease during the infusion of hANP, while plasma aldosterone concentration decreased during and increased after stopping the infusion of hANP.

5. The data suggest that hANP inhibits the reabsorption of sodium and water by an action on distal segments of the nephron and perhaps the proximal tubule. Inhibition of renin and aldosterone secretion may contribute to the natriuresis.
Urinary guanosine 3′: 5′-cyclic monophosphate but not tissue kallikrein follows the plasma atrial natriuretic factor response to acute volume expansion with saline
Authors: Lewis Helen M. , Wilkins M. R. , Selwyn Brenda M. , Yelland Ursula J. , Griffith Megan E. , Bhoola K. D.
Published: August 2015

1. The relationship between plasma immunoreactive atrial natriuretic factor (Ir-ANF) and the urinary excretion of sodium, guanosine 3′:5′-cyclic monophosphate (cyclic GMP) and of tissue kallikrein was examined in seven healthy female volunteers.

2. Each volunteer attended on two occasions, a control and a saline infusion day. On the infusion day saline (2 litres, 0.9% NaCl) was administered over 60 min. Measurements of plasma Ir-ANF and urinary excretion of sodium, cyclic GMP and of tissue kallikrein were made at 30 min intervals during the infusion and for 3 h after the infusion.

3. Mean (± sem) urinary sodium excretion increased from a basal value (time 0) of 102 ±15 μmol/min to 222 ± 47 μmol/min 60–90 min from the start of the infusion and thereafter remained significantly elevated (P < 0.01) above sodium excretion on the control day.

4. In response to saline infusion there was a transient rise in mean (± sem) plasma Ir-ANF from 6.7 ± 0.8 pmol/l to a peak of 22.5 ±3.7 pmol/l at 75 min, falling to 12.7 ± 1.9 pmol/l at 135 min. The peak plasma Ir-ANF level on the infusion day was significantly elevated (P < 0.05) above the time-matched measurement on the control day.

5. Similarly, there was a transient rise in mean (± sem) urinary cyclic GMP excretion on the infusion day from 30.9 ±4.4 fmol/min to 64.6 ± 11.4 fmol/min during the 60–90 min collection period, returning to 43.7 ± 14.5 fmol/min at 210–240 min. Cyclic GMP excretion on the infusion day was significantly elevated (P < 0.05) above the time-matched measurement on the control day during the period 60–180 min.

6. Serum and urinary tissue kallikrein on the infusion day did not differ significantly from time-matched measurements on the control day.

7. Thus urinary cycle GMP but not tissue kallikrein follows the plasma Ir-ANF response to acute volume expansion with saline, and may be a useful marker of the activity of this peptide.
Effect of potassium supplementation on blood pressure and vasodilator mechanisms in spontaneously hypertensive rats
Authors: Barden Anne , Beilin Lawrence J. , Vandongen Robert
Published: August 2015

1. Supplementation with 1% (w/v) KCl solution significantly attenuated the blood pressure rise with age normally observed in spontaneously hypertensive rats, resulting in a difference in blood pressure of 18 mmHg after 5 weeks.

2. Urinary 6-keto-prostaglandin F1α (the stable hydrolysis product of prostacyclin) and kallikrein excretion were significantly elevated in rats receiving potassium.

3. No difference was observed in sodium excretion during the initial days of potassium supplementation; however, the potassium-supplemented animals excreted relatively more sodium over the 5 week period.

4. Plasma renin activity was significantly reduced in those animals receiving potassium after 5 weeks.

5. It is proposed that a combination of increased systemic and/or renal prostacyclin and kallikrein synthesis may, in combination with reduced renin activity, contribute to the attenuation of blood pressure in potassium-supplemented spontaneously hypertensive rats.
Changes in calcium metabolic indices during long-term treatment of patients with essential hypertension
Authors: Hvarfner Andreas , Bergström Reinhold , Lithell Hans , Mörlin Claes , Wide Leif , Ljunghall Sverker
Published: August 2015

1. Disturbances of calcium metabolism, mimicking mild, compensated secondary hyperparathyroidism, accompany essential hypertension, but it is not known whether these alterations are primary or only secondary to the elevated blood pressure.

2. Indices of systemic calcium metabolism were followed prospectively during 6 months' treatment with either propranolol, bendroflumethiazide or verapamil in 35 patients with essential hypertension. Multivariate statistical methods were employed to study the effects of blood pressure reduction upon the metabolic indices with adjustment for the effects of the different antihypertensive agents.

3. Propranolol treatment increased the plasma ionized calcium and serum phosphate concentrations, and reduced the serum levels of parathyroid hormone, free fatty acids and glycerol. Neither the total nor the total albumin-modified serum calcium concentration was significantly affected. Thus, presumably the decrease in free fatty acids reduced the calcium complex and the calcium binding to albumin, and consequently increased the plasma ionized calcium, thereby suppressing the secretion of parathyroid hormone.

4. Bendroflumethiazide caused a reduction of the fasting renal calcium excretion to half the pretreatment level, but produced no other significant changes in the various indices of calcium metabolism.

5. During verapamil treatment, the fasting renal excretion of calcium and magnesium increased, whereas the free fatty acids and glycerol concentrations in serum were reduced. These two changes presumably balanced each other, as the plasma ionized calcium and serum parathyroid hormone concentrations were not significantly altered.

6. There were no consistent relationships between the decrease in blood pressure and the changes in the metabolic indices, either in the total sample or within any subgroup. These findings indicate that disturbances of calcium metabolism in essential hypertension are primary to, and not induced by, the elevated blood pressure per se.