bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Adrenaline upon Cardiovascular and Metabolic Functions in Man
Authors: Fellows I. W. , Bennett T. , Macdonald I. A.
Published: August 2015

1. On three separate occasions, at least 1 week apart, seven young healthy male subjects received intravenous infusions of either adrenaline, 50 ng min−1 kg−1 (high A), adrenaline, 10 ng min−1 kg−1 (low A) or sodium chloride solution (saline :154 mmol of NaCl/1) plus ascorbic acid, 1 mg/ml (control), over 30 min.

2. Venous adrenaline concentrations of 2.19 ± 0.15 nmol/l, 0.73 ± 0.08 nmol/l and 0.15 ± 0.03 nmol/l were achieved during the high A, low A and control infusions respectively.

3. Heart rate rose significantly by 19 ± 3 beats/min (high A) and by 6 ± 1 beats/min (low A). Heart rate remained significantly elevated 30 min after cessation of the high A infusion, despite venous plasma adrenaline concentration having fallen to control levels.

4. The diastolic blood pressure fell during the high A and low A infusions, but the systolic blood pressure rose only during the high A infusion.

5. Vasodilatation occurred in the calf vascular bed during both high A and low A infusions. The changes in hand blood flow and hand vascular resistance were not statistically significant, although there was a tendency to vasoconstriction during the infusion of adrenaline.

6. Metabolic rate rose significantly by 23.5 ± 1.8% (high A) and by 11.8 ± 1.6% (low A). Metabolic rate remained elevated between 15 and 30 min after termination of the high A infusion. There was an initial transient increase in respiratory exchange ratio (RER) during the adrenaline infusions. During the later stages of the adrenaline infusions and after their cessation, RER fell, probably reflecting increased fat oxidation.

7. Blood glucose, glycerol and lactate concentrations all rose significantly during the high A infusion, but only the blood glycerol concentration rose during the low A infusion. Plasma potassium concentration fell during and after the high A infusion but only after cessation of the low A infusion.

8. When adrenaline was infused intravenously at rates that elevated the plasma adrenaline concentration within the physiological range, peripheral circulatory effects were observed similar to those previously described for larger doses of adrenaline. The persistent tachycardia noted after stopping the high A infusion may, at least in part, have been a consequence of the concomitantly elevated metabolic rate.
The effect of Arginine Vasopressin on Ureagenesis in Isolated rat Hepatocytes
Authors: Drew P. J. T. , Monson J. P. , Metcalfe H. K. , Evans S. J. W. , Iles R. A. , Cohen R. D.
Published: August 2015

1. The effect of arginine vasopressin (AVP) on ureagenesis was measured in isolated rat hepatocytes with ammonium chloride and l(+)-lactate as substrates.

2. AVP was found to stimulate urea synthesis and the dose-response curve suggests that such an effect is present at concentrations of the hormone as low as 25-50 pmol/l.

3. Both the dose-response curve and the concentrations of NH4+ employed suggest that the effect observed could be of physiological significance.
Human pancreatic and biliary responses to physiological concentrations of cholecystokinin octapeptide
Authors: Anagnostides A. A. , Chadwick V. S. , Selden A. C. , Barr J. , Maton P. N.
Published: August 2015

1. To determine the functional significance of physiological plasma concentrations of cholecystokinin, five volunteers each received graded doses of intravenous infusions of cholecystokinin octapeptide (CCK-8). At each dose plasma concentrations of CCK-8 were determined and pancreatic and biliary outputs were measured.

2. Threshold plasma concentrations of CCK-8 for augmenting pancreatic trypsin secretion were undetectable (< 3 pmol/l), and maximal trypsin output of 21.9 ± 1.95 k-i.u./30 min was produced by 17.1 ± 6.4 pmol of CCK-8/1. Calculated half-maximal output was produced by 4.7 pmol of CCK-8/1.

3. Maximal trypsin output during infusions of CCK-8 was significantly less than that after a combination of the CCK-like peptide, caerulein, and secretin (32.95 ± 2.16 k-i.u./30 min, P < 0.001).

4. Biliary bile acid and bilirubin outputs were significantly augmented only when plasma concentrations of CCK-8 were > 5 pmol/l.

5. Plasma concentrations of CCK-8 in the low picomolar range exert significant effects on pancreatic and biliary secretion. CCK-8 fulfills the criteria for a circulating hormone.
Intra-individual variability in postural blood pressure in the elderly
Authors: Lipsitz Lewis A. , Storch Helene A. , Minaker Kenneth L. , Rowe John W.
Published: August 2015

1. Orthostatic hypotension, an age-related phenomenon, has been associated with hypertension and body weight variability. To evaluate the relative contributions of blood pressure elevation and abnormalities in extracellular volume regulation to orthostatic hypotension, elderly institutionalized subjects (mean age = 87 ± 7 years), taking no cardiovascular medications, underwent measurement of body weight (n = 15) and first morning supine and standing blood pressures (n = 19), 12–13 times per subject over a 2–4 week period.

2. There was a wide day-to-day variability in postural systolic blood pressure change (coefficient of variation = 533%) and a strong negative correlation between each day's postural change in systolic blood pressure and basal supine blood pressure (r = −0.55, P < 0.0001).

3. There was no association between postural blood pressure change and heart rate response or body weight changes, which were very small over the duration of the study (coefficient of variation = 0.6%).

4. Elderly individuals have intact homoeostatic mechanisms for the control of standing pressure when basal blood pressure is normal. Postural hypotension in the elderly is a variable phenomenon related to elevations in basal blood pressure.
The characterization and energetic potential of brown adipose tissue in man
Authors: Cunningham S. , Leslie P. , Hopwood D. , Illingworth P. , Jung R. T. , Nicholls D. G. , Peden N. , Rafael J. , Rial E.
Published: August 2015

1. In adult man, brown fat can be detected in perinephric fat depots by visual inspection, electron microscopy and nucleotide binding to the tissue-specific uncoupling protein.

2. The 32 kDa uncoupling protein is functionally active, showing a nucleotide-sensitive conductance to protons and an uncoupling response to fatty acids.

3. The amount of uncoupling protein in human mitochondria is equivalent to that in a partially cold-adapted guinea pig, indicating some potential for thermogenesis.

4. Respiratory capacity measurements indicate that the total perinephric fat in adult man can only account for one-fivehundredth of the whole-body response to infused noradrenaline. Thus, although brown fat has been found to be quantitatively important in animal studies, considerable caution must be exercised in extrapolating its significance to adult man.
Partial isolation and function of the prostacyclin regulating plasma factor
Authors: Deckmyn H. , Zoja C. , Arnout J. , Todisco A. , Bulcke F. VANDEN , D'hondt L. , Hendrickx N. , Gresele P. , Vermylen J.
Published: August 2015

1. Rat aortic rings stop producing prostacyclin upon prolonged washing in buffer. This ‘exhaustion’ is caused by inhibition of cyclo-oxygenase, since these rings still convert cyclic endoperoxides but not arachidonic acid into prostacyclin, and most probably is due to high concentrations of peroxides: it can be accelerated by H2O2 or by interrupting the glutathione cycle, while it is delayed by reduced glutathione.

2. Incubation of exhausted rings in human plasma or in a plasma filtrate restores to some extent prostacyclin formation. This filtrate, in particular from uraemic subjects, also inhibits the H2O2 initiated oxidation of guaiacol by ram seminal vesicle microsomes or horseradish peroxidase.

3. The prostacyclin regulating plasma factor has been partially purified and identified as a stable and very polar molecule of mol. wt. 300–400, able to reactivate prostacyclin generation by exhausted rings. We suggest that one or more low mol. wt. plasma components prolong vascular prostacyclin formation by acting as reducing cofactor for cyclo-oxygenase peroxidase.

4. The main physiological role of this plasma activity is probably to protect the vascular prostacyclin forming system from exhaustion during persistent irritation.
Effect of bisphosphonates on prostaglandin synthesis by rat bone cells and mouse calvaria in culture
Authors: Ohya Keiichi , Yamada Shoji , Felix Rolf , Fleisch Herbert
Published: August 2015

1. Bisphosphonates are potent inhibitors of bone resorption and also inhibit prostaglandin (PG) E2 synthesis in bone cells. Therefore we have investigated whether a correlation exists between inhibition of bone resorption and inhibition of PGE2 formation.

2. Initially, bisphosphonates were tested for their effect on the release of [14C]PGE2 from rat calvaria cells labelled with [14C]arachidonic acid and stimulated by bradykinin, thrombin and mechanical manipulation. The effect on [14C]-PGE2 synthesis was not correlated with the known inhibitory activity of bisphosphonates on bone resorption.

3. Mouse calvaria were then treated with epidermal growth factor (EGF) to induce PGE2 synthesis and bone resorption, with or without bisphosphonates. The bisphosphonates either decreased, had no effect or increased PGE2 production, but all inhibited the release of calcium.

4. Finally, the bisphosphonates were given in vivo to mice before explantation of the calvaria. Some of the bisphosphonates decreased the production of PGE2, suggesting that these compounds may have such an effect in vivo. But again no relationship between the effect on PGE2 synthesis and bone resorption was found.

5. Thus, these experiments show the inhibitory effect of bisphosphonates on bone resorption is unlikely to be explained only by their effect on PGE2 synthesis.
Enhanced distal absorption of potassium by magnesium-deficient rats
Authors: Wong Norman L. M. , Sutton Roger A. L. , Mavichak Viroon , Quamme Gary A. , Dirks John H.
Published: August 2015

1. The effect of acute potassium infusion on renal tubular reabsorption of potassium by magnesium-deficient and pair-fed control rats has been studied by the recollection micropuncture method.

2. During potassium chloride infusion, the amount of potassium remaining in the distal tubule is lower in magnesium-deficient than in pair-fed rats. This could be due to a reduction in potassium secretion or to an enhancement of potassium reabsorption.

3. The present study demonstrates enhanced renal potassium retention in the magnesium-deficient rat, and is in contrast to previous reports of renal potassium wasting in this circumstance.
The effect of indomethacin on the renal response to arginine vasopressin in man
Authors: Dixey J. J. , Williams T. D. M. , Lightman S. L. , Lant A. F. , Brewerton D. A.
Published: August 2015

1. The renal response to graded intravenous infusions of arginine vasopressin (AVP) was investigated in a two part study in six volunteers. First, under maximal water diuresis, seven control incremental infusions of AVP were given from zero to 12 fmol min−1 kg−1. Second, the AVP infusions were repeated after pretreatment with indomethacin, 150 mg daily for 36 h.

2. After the AVP infusions, plasma AVP concentrations did not change significantly and remained within the physiological range; in contrast, urinary AVP excretion rate increased steadily. Indomethacin did not alter the plasma or urinary concentrations of AVP.

3. AVP caused a fall in urine flow rate from a state of maximal diuresis to one of maximal anti-diuresis. After indomethacin, fractional free water clearance was reduced by an average of 26% at the zero, 2 and 4 fmol min−1 kg−1 infusion rates of AVP.

4. A significant increase in fractional sodium clearance of approximately 50% occurred during the AVP infusions, which was abolished after pretreatment with indomethacin.

5. After indomethacin, urinary prostaglandin E2 (PGE2) excretion rate was reduced by an average of 40%) at the zero and 2 fmol min−1 kg−1 infusion rates of AVP. At higher AVP infusion rates, no significant inhibition of PGE2 was observed.

6. Urinary kallikrein excretion rate decreased steadily to one-third of its original value after AVP and this change remained unaltered by indomethacin.

7. The findings show that infusions of AVP, resulting in plasma concentrations in the physiological range, evoke a maximal antidiuretic response, which is accompanied by natriuresis. Significant inhibition of urinary prostaglandin excretion by indomethacin is accompanied by both enhancement of the antidiuretic effect of an abolition of the natriuretic response to AVP.
Calculation of the VD/VT ratio by the helium washout technique
Authors: Jordanoglou J. , Tatsis G. , Bissiouli Z.
Published: August 2015

1. In four normal subjects and 51 patients with chronic bronchitis-emphysema, bronchial asthma and pulmonary fibrosis, the VD/VT ratio was measured by a helium washout technique (w VD/VT) and by the conventional Bohr's method using the arterial CO2 tension (VD/VT).

2. In 16 patients the w VD/VT ratio was compared with that calculated from Bohr's equation with the alveolar CO2 tension measured by the rebreathing technique (A VD/VT).

3. It was found that the values for the VD/VT ratio obtained by the helium washout technique were very close to those obtained by the conventional method using the Paco2 or P¯Aco2 values.
Assessment of the effect of nifedipine on myocardial ischaemia by using the ST segment/heart rate slope
Authors: Bishop N. , Hart G. , Elamin M. S. , Silverton N. P. , Boyle R. , Stoker J. B. , Smith D. R. , Mary D. A. S. G. , Linden R. J.
Published: August 2015

1. Nifedipine is used in patients with stable angina of effort and any resulting change in symptoms is attributed to several effects of nifedipine. However, there have been indications in such patients that one effect of nifedipine could be an increase in the severity of myocardial ischaemia, and the present report involves a trial the results of which could explain this effect.

2. In the present trial, the effect of nifedipine on myocardial ischaemia was assessed by using the maximal ST/heart rate slope. This slope was used as an index of myocardial ischaemia because, in our hands in patients with angina, an increase or a decrease in the value of the slope respectively indicated an increase or a decrease in the severity of myocardial ischaemia as assessed by coronary arteriography.

3. The maximal ST/heart rate slope was obtained at least twice in each of 23 patients with stable angina, with and without nifedipine; two patients were examined twice and three other patients were examined after an increased dose. Nifedipine resulted in an increase in the slope in 24 of the 28 comparisons, no change in three and a decrease in one comparison; there was a statistically significant (P < 0.005; n = 28; paired t-test) increase in the maximal ST/heart rate slope. A further increase in the slope was obtained by increasing the dose of nifedipine in two out of three patients.

4. The increase in the maximal ST/heart rate slope occurred in the absence of any effect of nifedipine on the initial level of the ST segment.

5. It is concluded that nifedipine therapy in the patients with stable angina caused increases in the maximal ST/heart rate slope, suggesting an increase in the severity of myocardial ischaemia.
Effect of peptide chain length on amino acid and nitrogen absorption from two lactalbumin hydrolysates in the normal human jejunum
Authors: Grimble G. K. , Keohane P. P. , Higgins B. E. , Kaminski M. V. , Silk D. B. A.
Published: August 2015

1. A double lumen jejunal perfusion technique has been used in man to study the effect of peptide chain length on absorption of amino acid nitrogen from two partial enzymic hydrolysates of lactalbumin.

2. Copper-chelation chromatography showed that one lactalbumin hydrolysate (LH2) contained 98% peptides with a chain length > 4, whilst the other (LH1) contained a more even spread of chain lengths with 55% <4.

3. Absorption of total nitrogen and of 14 amino acid residues occurred to a significantly greater extent from the low molecular weight LH1 than from the higher molecular weight LH2.

4. The results suggest that the pattern of nitrogen and amino acid absorption from partial enzymic hydrolysates of whole protein is markedly influenced by peptide chain length and that brush border peptide hydrolysis has an important rate limiting effect on absorption rates.
Reappraisal of the ‘lectin hypothesis' in the aetiopathogenesis of coeliac disease
Authors: Colyer J. , Farthing M. J. G. , Kumar P. J. , Clark M. L. , Ohannesian A. D. , Waldron N. M.
Published: August 2015

1. The agglutinating properties of a crude gluten digest, purified gliadin fractions and established plant lectins were investigated using mammalian erythrocytes, rat enterocytes and normal and coeliac human enterocytes as the target systems.

2. Gliadin preparations failed to cause agglutination of any of the cells tested, whereas established pure plant lectins were active cell agglutinins.

3. These studies indicate that gliadin peptides do not interact with intestinal cells in a polyvalent, lectin-like manner and as such cannot be regarded as true lectins.

4. Mucosal damage in coeliac disease is unlikely therefore to be related to lectin-like activity of gliadin.
Effect of simple short term dietary control on urine electrolyte excretion in normal men
Authors: McInnes Gordon T. , Flores Josue G. , Shelton John R. , Harrison Ian R. , Perkins Richard M. , Clarke Joan M.
Published: August 2015

1. Normal diet and a simple short term prescribed diet were compared with respect to mean excretion of urine electrolytes and the variability in these responses in 12 healthy male subjects. Urine was collected from 7 to 15 h (overnight) and 15 to 25 h (daytime) after the start of dietary control.

2. Differences in mean responses were slight. For sodium and potassium excretion, however, there were tendencies for responses in subjects with high excretion on normal diet to decrease and for responses in those with low excretion on normal diet to increase towards the overall mean during the prescribed diet.

3. The prescribed diet reduced markedly the variability in electrolyte responses and for log transformed data reductions in variability were statistically significant in the daytime urine collections.

4. The results of this study have confirmed quantitatively the benefit of a short period of simple dietary control. The marked reduction in the variability of sodium and potassium excretion improves considerably the precision and sensitivity of studies of urine electrolyte composition.
Change in plasma immunoreactive atrial natriuretic peptide during sequential ultrafiltration and haemodialysis
Authors: Wilkins M. R. , Wood J. A. , Adu D. , Lote C. J. , Kendall M. J. , Michael J.
Published: August 2015

1. Plasma immunoreactive human atrial natriuretic peptide (Ir-ANP) levels were measured in eight patients with chronic renal failure who were volume-expanded and during treatment by sequential ultrafiltration and haemodialysis. One patient was studied at two separate treatment sessions.

2. Plasma Ir-ANP levels were raised in all patients (mean ± SE 184 ± 44 pmol/l, n = 9) compared with healthy controls (11 ± 1.4 pmol/l), but showed considerable inter-patient variability.

3. Plasma Ir-ANP levels fell with fluid removal during ultrafiltration (123 ± 30 pmol/l, n = 9, P < 0.02) and again as fluid was removed during haemodialysis (76 ± 20 pmol/l, n = 9, P < 0.02).

4. Seven patients studied 48 h later, before their next dialysis treatment, had regained weight and showed a coincident rise in circulating plasma Ir-ANP (130 ± 33 pmol/l, n = 7).

5. Our data would support the hypothesis that the secretion of ANP is determined by volume or by a stimulus related to volume. However, it does not exclude the possibility that a factor other than extracellular fluid volume expansion contributes to the raised plasma Ir-ANP levels in chronic renal failure.
Kidney protection by pretreatment with free radical scavengers and allopurinol: Renal function at recirculation after warm ischaemia in rabbits
Authors: Hansson R. , Johansson S. , Jonsson O. , Pettersson S. , Scherstén T. , Waldenström J.
Published: August 2015

1. Renal function and morphology were studied before and after 60 min of renal ischaemia and contralateral nephrectomy in five groups of rabbits. The animals were pretreated with superoxide dismutase, catalase, allopurinol or mannitol. One group was not pretreated and served as a control.

2. A moderate transient increase in serum creatinine concentration was observed in the control rabbits, while a significantly less pronounced increase was noted after pretreatment with superoxide dismutase, catalase and mannitol.

3. Pretreatment with allopurinol did not significantly reduce the postoperative increase in serum creatinine and sodium excretion, but the urine osmolality returned to normal more rapidly than in the control group.

4. The appearance under the light microscope of kidney tissue taken from surviving rabbits was found to be normal irrespective of pretreatment. Severe tubular necrosis was observed in the kidneys from rabbits that died during the observation period.
Renal response to atrial natriuretic factor in rats without intact papillae
Authors: Torikai Shozo
Published: August 2015

1. In order to examine the contribution of renal papilla to atrial natriuretic factor (ANF)-induced diuresis, clearance studies were done in rats with intact papillae and bromoethylamine hydrobromide (BEA)-induced papillary necrosis.

2. Papillary necrosis did not attenuate the diuretic and natriuretic response to ANF. In a moderately hydropenic state, urine flow and fractional water excretion were rather more increased in papillary necrosis rats than in papilla-intact ones. In a volume-expanded state, both groups had a similar diuretic response to ANF.

3. Present data indicate that the existence of intact renal papilla is not essential for ANF-induced diuresis. Furthermore, it is suggested that absolute magnitude of ANF-induced diuresis may be dependent on its extrapapillary action(s).
A simple method for definition of incomplete suppression of aldosterone and its association with hypertension and hypokalaemia in man
Authors: Adam William R.
Published: August 2015

1. By defining a model for control of potassium homoeostasis, patients with unexplained hypokalaemia may then be described as fitting or not fitting the model. Fitting the model implies an abnormality of known control mechanisms (e.g. aldosterone); by contrast, not fitting the model suggests other unknown factors responsible for the hypokalaemia and, possibly, hypertension.

2. In the presence of normal acid-base status, potassium excretion (Uκ+. V) is regulated by plasma potassium (Pκ+), delivery of sodium to the distal tubule and aldosterone secretion. A linear relationship (correlation coefficient of 0.72) was defined by:

U κ+ V/P κ+ = 5.1 × log(UAldoV) × log(Uκ+V) + 1.4

based on a 24 h urine collection and plasma sample, in 16 normal subjects, 50 hypertensive normokalaemic subjects and 11 patients with hyperaldosteronism.

3. The relationship was robust and held true for variations in dietary sodium and potassium intake (5–300 and 20–100 mmol/day respectively) and variations in aldosterone excretion produced by enalapril. Patients with abnormal renal potassium wasting due to known extraneous factors (n = 11) all fell outside the 95% confidence limits.

4. Twelve patients with hypertension and hypokalaemia and renal potassium wasting all fitted within the confidence limits, being no different from 22 controls selected on the basis of age and urinary potassium excretion (30–50 mmol/day). This suggests that in these 12 patients the hypokalaemia (but not necessarily the hypertension) was not due to ‘unknown’ steroids but rather lack of regulation of the controlling variable, aldosterone.
Vascular sensitivity to prostaglandin I2 and urinary excretion of 6-keto-prostaglandin F1α in conscious dogs
Authors: Jones Robert L. , Watson Michael L.
Published: August 2015

1. A method is described for measuring the urinary excretion of 6-keto-prostaglandin F1α, the stable hydrolysis product of prostaglandin I2, by stable isotope dilution gas chromatography–mass spectrometry.

2. Three different doses of prostaglandin I2 were infused intravenously into conscious dogs and the effects on systemic and renal haemodynamics and urinary sodium excretion were observed.

3. The two highest infusion rates of prostaglandin I2 (15 and 30 ng min−1 kg−1 body weight) induced significant decreases in systematic blood pressure and dose-related increases in sodium excretion, but no change in renal haemodynamics.

4. There was a linear relationship between urinary excretion of 6-keto-prostaglandin F1α and the rate of infusion of prostaglandin I2.

5. The calculated basal rate of entry of prostaglandin I2 into the systematic circulation in conscious dogs is 4 ng min−1 kg−1 body weight, which is substantially higher than that previously reported in man.
Blood pressure in the puerperium
Authors: Walters B. N. J. , Thompson M. E. , Lee A. , De Swiet M.
Published: August 2015

1. Blood pressure was measured by random zero sphygmomanometer in the morning and afternoon for 5 days after normal delivery in a group of 136 previously normotensive women. The number of women studied each day varied from 32 to 125.

2. The afternoon blood pressure was higher than the morning blood pressure (differences: 1.7 mmHg systolic, 2.6 mmHg diastolic; P < 0.05).

3. Both systolic and diastolic blood pressures rose for the first 4 days after delivery. The average rise over the whole period was about 6 mmHg systolic and 4 mmHg diastolic (P < 0.05).

4. A considerable number of previously normotensive women displayed elevations of blood pressure in the puerperium. Twelve per cent of all patients exceeded a diastolic blood pressure of 100 mmHg.
Smoking behaviour and personality patterns of smokers with low and high CO absorption
Authors: Nil Rico , Woodson Phillip P. , Bättig Karl
Published: August 2015

1. The present experiment describes an attempt to select differentially nicotine dependent smokers by means of an objective and non-invasive measure of cigarette smoke CO absorption. Toward this goal the differences in expiratory tidal air CO concentration before and after smoking a single cigarette (tidal CO boost) were measured in three experimental sessions. The selection criteria were tidal CO boosts greater than 3.5 p.p.m. and less than 1 p.p.m. According to these criteria 19 out of 171 subjects were consistently found to be high CO absorbers and 20 were found to be low CO absorbers.

2. Puffing behaviour was measured throughout all three test sessions by the flowmeter method and respiratory inhalation by thorax impedance plethysmography. In addition, heart rate was continuously measured during smoking. These data were used to assess for specific differences between the two extremes of inhalation behaviour.

3. High CO absorbers differed from low CO absorbers by more intensive patterns of puffing and respiratory inhalation, by higher daily cigarette and coffee consumption, by lower alcohol consumption, by shorter latencies to the first cigarette in the morning, by greater subjective need for smoking and by lower scores for healthy eating habits. No intergroup differences were observed for smoking induced heart rate acceleration. The high CO absorbers were significantly older than the low CO absorbers; however, no evidence was found that any of the differences in smoking style between the two extremes might be related to their difference in age. No differences were seen in cigarette strengths, in personality or in coronary prone behaviour as assessed by means of standardized questionnaires in all subjects.

4. It is concluded that nicotine plays a more important role in smoking motivation among the high than among the low CO absorbing smokers. The role of nicotine and the individual dosage absorbed by the smokers, however, remain to be analysed further and are discussed in the light of nicotine tolerance effects.
A test of the validity of the lithium-marker technique for monitoring dietary sources of salt in man
Authors: Sanchez-Castillo C. P. , Branch W. J. , James W. P. T.
Published: August 2015

1. A lithium-tagged salt for assessing the sources of salt in the human diet was prepared by fusing lithium carbonate and sodium chloride at 900°C followed by grinding and sieving the fused salts to a defined grain size; magnesium carbonate was added as a hygroscopic agent.

2. To validate the use of this tagged salt, which replaced alternately table salt and cooking salt in daily use, a 44 day metabolic study was conducted on five volunteers. Measurements of sodium and lithium balance throughout the study showed that 93% of both dietary sodium and dietary lithium were excreted in the urine and 1.7% of dietary lithium and 2% of dietary sodium in the faeces. Collections of sweat for 48 h at intervals throughout the study showed that only 1.7% of dietary lithium and 1.4% of dietary sodium were recovered in sweat. Thus both elements were excreted equivalently by the three main routes. The apparent mean sodium retention over the whole period of dietary control was 7.4 ± 4.4 mmol/day or 3.4% of the total intake.

3. The excretory patterns of lithium after a period of lithium ingestion were exponential, thus allowing a method to be developed for the prediction of total lithium output from a shorter period of urine collection.

4. This study suggests that the lithium method is suitable for epidemiological use to measure the sources of dietary salt.
Effect of acute ethanol administration on the baroreceptor reflex control of heart rate in normotensive human volunteers
Authors: Abdel-Rahman A.-R. A. , Merrill R. H. , Wooles W. R.
Published: August 2015

1. The effects of acute ethanol administration on blood pressure, heart rate and the baroreceptor reflex control of heart rate were studied in normotensive subjects who served as their own control. Baroreceptor reflex control of heart rate was measured by two methods: the ramp method and the steady state method.

2. None of the doses of ethanol had any effect on blood pressure during the observation period, except for the highest dose where a slight elevation was evident for a short period of time. On the other hand, the heart rate showed a slight but consistent dose-related increase.

3. In general, ethanol attenuated the baroreceptor mediated bradycardia but this effect was dependent on the way in which blood presure was elevated. A dose-related impairment of baroreceptors was evident when the ramp method was used, i.e. ethanol significantly depressed baroreflex sensitivity, expressed as Δheart period (HP)/Δmean arterial pressure (MAP). In contrast, ΔHP/ΔMAP was not influenced by ethanol when the steady state method was used. However, the steady state baroreflex curves were reset about a higher median blood pressure (MAP50), suggesting that the baroreceptors will be operative at higher blood pressure levels after ethanol.

4. The pressor responsiveness was also influenced differently by ethanol depending on the method of injecting phenylephrine. An increase in pressor responsiveness was evident, though not dose-related, after ethanol only when blood pressure was elevated by the ramp method, suggesting that the inverse relationship between baroreflex sensitivity and pressor responsiveness is more prominent with the ramp method and/or when impairment rather than resetting of baroreceptors occurs.

5. That the decrease in baroreflex sensitivity and the increase in MAP50 were related to peak ethanol levels in blood and that the blood pressure was not influenced by ethanol strongly suggest these effects were ethanol mediated. The weakened buffering action of the baroreflexes would be expected to favour the development of higher blood pressure.
Aldosterone responsiveness to metoclopramide in hyperprolactinaemia
Authors: O'Malley B. P. , Mercey D. , Clarke E. , Maguire M. , Jackson J. , Rosenthal F. D.
Published: August 2015

1. Basal serum aldosterone levels in 13 hyperprolactinaemic females did not differ significantly from those of nine control individuals.

2. There was increased responsiveness of circulating aldosterone levels to the long acting dopamine antagonist metoclopramide (10 mg intravenously) in the hyperprolactinaemic patients as compared with the controls.

3. Prolactin responsiveness to metoclopramide was reduced in the patients as compared with the controls, such being considered characteristic of a prolactinoma.

4. Basal serum thyrotrophin (TSH) levels, although within the euthyroid range, were increased in the patients as compared with the controls. There was no significant difference in the TSH responsiveness to metoclopramide between the study groups. However, in the five patients with exaggerated responses of TSH to metoclopramide, basal TSH levels were significantly higher than in the other patients.

5. One explanation for these results is that prolactin can directly or indirectly modulate the aldosterone response to metoclopramide.
Na+, K+ and water balance in young spontaneously hypertensive rats: relationship to blood pressure after high K+ treatment
Authors: Sugden A. Louise , Bean Barbara L. , Straw James A.
Published: August 2015

1. These studies were designed to investigate the effects of high dietary K+ on electrolyte and water balance in young spontaneously hypertensive rats (SHR) and to relate these effects to changes in blood pressure.

2. The high K+ diet reduced blood pressure by approximately 10 mmHg during the development of hypertension. Blood pressure, however, plateaued at the same maximum level as control by age 13 weeks.

3. Rats fed the high K+ diet showed a significant increase in water intake and urine volume throughout the treatment period but no change in plasma volume or extracellular fluid volume occurred.

4. A slight natriuresis was also observed in rats on the high K+ diet, but this was not of sufficient magnitude to decrease total body Na+.

5. These results confirm previous findings that K+ causes a diuresis and a natriuresis, but demonstrate that the diuretic action of K+ cannot explain its antihypertensive properties in young SHR.
Carnitine acyltransferases and acyl-CoA hydrolases in human and rat liver
Authors: Agius L. , Wright P. D. , Alberti K. G. M. M.
Published: August 2015

1. The activities of carnitine acyltransferases and acyl-CoA hydrolases were determined in human and rat liver to establish the validity of extrapolating from studies on rats to human metabolism.

2. In human liver, carnitine acetyltransferase activity was 10–14 times higher and carnitine octanoyltransferase 1.7–2.4 times higher than in rat liver, while carnitine palmitoyltransferase activity was similar in human and rat.

3. Acetyl-CoA hydrolase and octanoyl-CoA hydrolase activities were lower in human (42–57%) than in rat liver, but palmitoyl-CoA hydrolase activity was similar in both species.

4. The activity of citrate synthase was lower (44%) in human than in rat liver. The low citrate synthase activity and the high carnitine acetyltransferase in human liver suggest that in man acetylcarnitine might be more important as a vehicle for export of acetyl units from mitochondria than citrate.

5. The high activity of carnitine acetyltransferase in human liver is consistent with the observation that acetylcarnitine is the predominant acylcarnitine excreted in diabetic ketosis in man.

6. It is concluded that the rat may not be a valid model for carnitine metabolism in man, and that in human liver carnitine may have an important role in transfer of acetyl groups out of mitochondria and possibly also to extrahepatic tissues.
Effects of sodium replacement on uptake of the dipeptide glycylsarcosine by hamster jejunum in vitro
Authors: Burston D. , Matthews D. M.
Published: August 2015

1. We report observations on transport of the hydrolysis-resistant dipeptide glycylsarcosine by rings of everted hamster jejunum in vitro in the presence and absence of Na+, using several substituents for Na+: Li+, K+, Cs+, Tris, choline and mannitol.

2. At most concentrations, mediated influx of glycylsarcosine was depressed by Li+, K+, Cs+ and Tris, though not abolished. At high concentrations, it was moderately increased by choline and mannitol. Under conditions in which the tissue could concentrate the peptide in the presence of Na+, uptake was greatly depressed by all the substituents and the ability to concentrate was abolished.

3. The Kt of mediated influx was affected in different ways according to the substituent used. Kt was reduced by Li+ replacement of Na+ and increased by choline replacement. Vmax. was greatly reduced by all metallic substituents but not by non-metallic substituents.

4. Though the results cannot yet be satisfactorily interpreted, they suggest possible reasons for previous conflicting results and show that it is impossible to make the unqualified statement that transport of glycylsarcosine is ‘Na+-dependent’. It is now doubtful whether transport of this peptide into the intestinal cells is by co-transport with Na+, and the whole matter of Na+-dependence of intestinal peptide transport is in question.
Free d-amino acids in human plasma in relation to senescence and renal diseases
Authors: Nagata Yoko , Akino Toyoaki , Ohno Kimiyoshi , Kataoka Yoshimitsu , Ueda Takahiro , Sakurai Tetsuo , Shiroshita Koh-Ichi , Yasuda Takuji
Published: August 2015

1. Minute but appreciable amounts of d-amino acids were detected in normal human plasma.

2. The content was significantly higher in an elderly population (age 76 ± 6 years, mean ± sd, n = 41) than in a younger group (age 42 ± 4 years, n = 26), i.e. 6.9 ± 4.8 nmol/ml (mean ± sd, range 0–18.8 nmol/ml) and 2.5 ± 1.8 nmol/ml (range 0–6.3 nmol/ml) for the elderly and the younger groups, respectively.

3. Elevation of plasma d-amino acid level was observed in a group of patients with renal disease (3.6–52.6 nmol/ml), in proportion to the serum level of creatinine (n = 50, r = 0.726, P < 0.001), β2-microglobulin (n = 34, r = 0.551, P < 0.005), and to glomerular filtration rate (n = 39, r = 0.556, P < 0.001).
Multifactorial evaluation of blood pressure fall upon hospitalization in essential hypertensive patients
Authors: Nishimura Hikaru , Nishioka Akinori , Kubo Shinichiro , Suwa Michihiro , Kino Masaya , Kawamura Keishiro
Published: August 2015

1. Studies were prospectively performed on 72 hospitalized patients with essential hypertension. Blood pressure was normalized within 1 week of admission in 33 patients (group I), but did not decrease in 39 patients (group II). To determine the factors that differentiate group I from group II, cardio-renal haemodynamic and endocrinological indices were evaluated using multivariate analysis.

2. Systolic, diastolic and mean blood pressures on admission were higher in group II (P < 0.001), whose optic fundi showed more severe changes (P < 0.001). Although group II had greater left ventricular posterior wall thickness (P < 0.02), left ventricular mass index (P < 0.05) and systemic vascular resistance (P < 0.01) on echocardiography, their cardiac index and ejection fraction were comparable with those of group I.

3. Renal blood flow (P < 0.05) and glomerular filtration rate (P < 0.01) were lower in group II than in group I. Renal vascular resistance was more elevated (P < 0.01) in group II than in group I.

4. After severe sodium depletion and ambulation, group I showed a greater increase in plasma noradrenaline and adrenaline (P < 0.05). On multivariate analysis, those with lower systolic blood pressure, better renal function and more reactive sympathetic nervous system were discriminated as group I.

5. These data suggest that group I patients have lower systolic blood pressure on admission, greater sympathetic reactivity and better renal function, all of which contribute to their spontaneous blood pressure fall after admission.
Deferoxamine-induced bone changes in haemodialysis patients: A histomorphometric study
Authors: Charhon Sam A. , Chavassieux Pascale , Boivin Georges , Parisien May , Chapuy Marie-Claire , Traeger Jules , Meunier Pierre J.
Published: August 2015

1. The histological effects of deferoxamine therapy were assessed on transiliac bone biopsies taken after double tetracycline labelling from 16 uraemic patients undergoing chronic haemodialysis, all having aluminium deposits in bone. Eight patients had osteomalacia, five had an ‘aplastic’ bone lesion and three a high bone turnover with a marked increase in osteoid volume.

2. Deferoxamine was administered intravenously once a week at doses ranging from 1 to 6 g for a mean duration of 7.6 ± 3.3 (sd) months.

3. Deferoxamine therapy was associated with significant reductions in stainable aluminium deposits, osteoid volume, osteoid surfaces and thickness index of osteoid seams. The osteoblastic osteoid surfaces as well as the bone formation rates also increased significantly.

4. A rise in resorption parameters and in serum parathyroid hormone levels was observed in patients with osteomalacia. The percentage reductions in stainable aluminium and in osteoid volume were correlated with the degree of hyperparathyroidism.

5. These data show that deferoxamine therapy reduces stainable bone aluminium and improves bone mineralization in low turnover osteomalacia and that the presence of hyperparathyroidism is associated with an increased response to deferoxamine therapy.
Influence of fasting on leucine and muscle protein metabolism across the human forearm determined using l-[1-13C,15N]leucine as the tracer
Authors: Cheng K. N. , Pacy P. J. , Dworzak F. , Ford G. C. , Halliday D.
Published: August 2015

1. We have used l-[1-13C,15N]leucine as the substrate tracer to study leucine and muscle protein metabolism across the forearm of eight normal fasting adults.

2. The rates of protein synthesis and breakdown, de- and re-amination of leucine, and the oxidative de-carboxylation of its keto acid were calculated directly from the arteriovenous metabolite balances and isotope dilutions as described by the metabolic model.

3. The results were compared with those obtained previously when subjects were fed. The effects of fasting on protein and leucine metabolism were a significant decrease in protein synthesis from 127 (sem 11; n = 6) to 70 (sem 6; n = 12) nmol of leucine min−-1 100 ml−-1 of forearm tissue (P < 0.001) and a marked decrease in leucine catabolism in the forearm muscle.

4. This model has demonstrated that each subject was in negative protein balance across the forearm during fasting while positive during feeding, the mean values being −29(sem 5; n = 12) and + 39(sem 9; n = 6) nmol of leucine min−-1 100 ml−-1 of forearm tissue respectively.

5. These results are sufficiently encouraging to suggest a role for this model in future studies on muscle protein metabolism.
Influence of the sympathetic nervous system and vasopressin on the blood pressure lowering effect of nifedipine in deoxycorticosterone acetate–salt hypertensive rats
Authors: Takata Yutaka , Yamashita Yoshiaki , Takishita Shuichi , Fujishima Masatoshi
Published: August 2015

1. The role of the sympathetic nervous system and the effect of vasopressin (AVP) on the hypotensive action of nifedipine (Nf) were evaluated in conscious, unrestrained normotensive and DOCA–salt hypertensive rats.

2. The hypotensive response to Nf was much greater in DOCA rats than in the controls.

3. Solitary blockade of the sympathetic nervous system or AVP, did not alter the Nf effect in either DOCA or control rats. However, a combination clearly diminished the effect of Nf in the DOCA group, but enhanced it in the controls. The inhibition of angiotensin II (ANG II) augmented the hypotensive effect of Nf in control animals, but not in the DOCA rats. The percentage fall in blood pressure with Nf was much the same in both groups after the combined inhibition of the sympathetic nervous system and AVP.

4. The enhanced hypotensive action of Nf in DOCA rats may be dependent on the hyperactivity of the sympathetic nervous system and AVP, which facilitates calcium influx, and in the normotensive animals the depressor response to Nf may relate to blockade of the calcium influx, independent of the sympathetic nervous system, AVP and ANG II.
Time course of end-expired carbon monoxide concentration is important in studies of cigarette smoking
Authors: Woodman G. , Wintoniuk D. M. , Taylor R. G. , Clarke S. W.
Published: August 2015

1. Fifteen asymptomatic habitual smokers each smoked one of their usual cigarettes, not having smoked for 2 h. End-expired carbon monoxide concentration (EECO) was measured with an Ecolyzer 2000 series analyser before smoking (pre-S value), 1 min after finishing smoking (post-S value) and then at intervals up to 1 h.

2. The mean EECO boost (increase) over all subjects declined biphasically after smoking, with an initial fast phase from 1 to 5 min, and then a slow phase from 5 to 60 min. EECO fell by as much in the first 5 min as in the next hour.

3. Post-S EECO was related to pre-S EECO (r = 0.89, P < 0.001), but EECO boost was not related to pre-S (r = 0.00). EECO boost was unaffected by the sampling manoeuvre.

4. EECO measurements in epidemiological and smoking studies should not be made for at least 5 min after a cigarette is finished
Circulating opioid peptides during water immersion in normal man
Authors: Coruzzi P. , Ravanetti C. , Musiari L. , Biggi A. , Vescovi P. P. , Novarini A.
Published: August 2015

1. This study was designed to evaluate variations in plasma β-endorphin, methionine-enkephalin, adrenocorticotropic hormone and serum prolactin in healthy volunteers during head-out water immersion.

2. Water immersion induced an increase in methionine-enkephalin plasma levels, which was associated with a significant fall in mean arterial pressure and heart rate.

3. Conversely, a suppression of plasma β-endorphin, adrenocorticotropic hormone and serum prolactin was detected during water immersion.

4. We suggest that a dopaminergic inhibitory control mechanism may be involved in regulating circulating levels of β-endorphin, adrenocorticotropic hormone and prolactin in normal subjects undergoing extracellular fluid volume expansion produced by water immersion.
Trimethylaminuria (‘fish-odour syndrome’): A study of an affected family
Authors: Al-Waiz Makram , Ayesh Riad , Mitchell Stephen C. , Idle Jeffrey R. , Smith Robert L.
Published: August 2015

1. Beginning with a single propositus, who had been previously diagnosed at the age of 10 as suffering from trimethylaminuria (fish-odour syndrome), both her parents and two sisters were investigated biochemically with respect to their ability to N-oxidize trimethylamine (TMA), both when derived from the diet and when administered exogenously.

2. Both the propositus and a second sister were markedly deficient in their ability to N-oxidize TMA, both when derived from the diet and when given as such; furthermore, both siblings readily developed the symptoms of fish-odour syndrome as characterized by a strong objectionable breath and body odour shortly after the oral administration of TMA (300 mg).

3. At this dose level of TMA, neither of the parents nor the third sister showed any evidence of impaired N-oxidation ability nor did they experience any ‘fish-odour’ symptoms.

4. With an oral challenge of 600 mg of TMA, both the parents showed a clear impairment of N-oxidation capacity which was not seen in six healthy unrelated volunteers. Both parents experienced a fish-odour syndrome at this level of TMA challenge.

5. The family data support the hypothesis that trimethylaminuria is an inborn error in the ability to N-oxidize TMA which is inherited as an autosomal recessive trait. Furthermore, experience with this family suggests that an oral challenge dose with 600 mg of TMA may be used to identify carriers of the condition.