bluuebunny/crossref_metadata_2025 huggingface dataset:
The Renal Nerves in Dogs: Noradrenergic and Dopaminergic?
Authors: Ball S. G. , Gunn I. G. , Macarthur K. J. D. , Douglas I. H. S. , Inglis G. C.
Published: August 2015

1. Plasma levels of dopa, dopamine, noradrenaline and adrenaline were measured in blood sampled from the renal vein and from the aorta at the origin of the renal artery in six anaesthetized greyhound dogs.

2. Plasma levels of dopa and adrenaline were lower in the renal vein than in the artery, indicating net extraction by the kidney, whereas both noradrenaline and dopamine were secreted into the circulation.

3. Similar measurements of noradrenaline and dopamine in arterial and venous blood were made in a separate group of seven dogs before and during stimulation of the renal nerves and after renal denervation.

4. Stimulation of the renal nerves caused secretion of noradrenaline and of dopamine into the renal vein. After denervation there was no evidence of secretion of noradrenaline into the circulation, whereas dopamine secretion continued, but at a reduced rate, suggesting an extraneuronal source of dopamine.

5. An imbalance of activity between noradrenergic sodium-retaining nerves and an opposing dopamine-secreting natriuretic system could raise blood pressure.
Serotonergic Mechanisms in the Nucleus Tractus Solitarius May Regulate Blood Pressure and Behaviour in the Rat
Authors: Laguzzi R. , Talman W. T. , Reis D. J.
Published: August 2015

1. Highly localized microinjections of serotonin into the nucleus tractus solitarius in rats produced dose-dependent hypotension and bradycardia and electroencephalogram (EEG) changes consistent with an alerting response.

2. Microinjection of the serotinin antagonist metergoline blocked the cardiovascular and EEG effects of serotonin but did not affect the same responses elicited by the microinjection of l-glutamate.

3. Microinjections of l-glutamate produced similar effects; acetylcholine, which lowered arterial pressure and heart rate, did not affect the EEG.

4. Bilateral injections of metergoline into the nucleus tractus solitarius occasionally produced a rise in arterial pressure but did not affect the baroreceptor reflex.

5. Serotonin may integrate cardiovascular and behavioural responses mediated by the nucleus tractus solitarius.

6. Neuronal populations within the nucleus tractus solitarius may be neurochemically and functionally differentiated.
Increased Noradrenaline Content of Hypothalamic Nuclei in Association with Worsening of Hypertension after High Sodium Intake in the Young Spontaneously Hypertensive Rat
Authors: Winternitz S. R. , Wyss J. M. , Meadows J. R. , Oparil S.
Published: August 2015

1. High sodium intake results in an exacerbation of hypertension accompanied by evidence of increased peripheral sympathetic activity in the young spontaneously hypertensive rat (SHR) of the Okamoto strain.

2. To examine the hypothesis that high sodium intake increases peripheral sympathetic activity via an influence on central noradrenergic pathways involved in cardiovascular regulation, the effect of dietary sodium intake on noradrenaline stores of individual hypothalamic nuclei was examined in young SHR.

3. After 2 weeks of high sodium intake, the noradrenaline content of the anterior and dorsomedial hypothalamic nuclei of SHR was increased when compared with SHR receiving normal sodium intake. Increases in the noradrenaline content of anterior hypothalamic nucleus persisted at 4 weeks. No changes were seen in other regions examined.

4. These observations lend support to the hypothesis that sodium and the sympathetic nervous system have synergistic effects in the pathogenesis of hypertension in the SHR.
‘Structural Autoregulation’ of the Preglomerular/Postglomerular Resistance Ratio and Hence of Glomerular Filtration Rate in the Clipped (Low Pressure) Kidney in Two-Kidney, One-Clip Renal Hypertension
Authors: Göthberg Gunnar , Folkow Björn
Published: August 2015

1. The chronically clipped left kidneys of two-kidney, one-clip renal hypertensive rats (duration >4 weeks) showed a 45% decrease in organ weight compared with left kidneys from age-matched normotensive Wistar rats (0.59 ± 0.09 vs 1.12 ± 0.05 g).

2. These ‘low-pressure’ kidneys exhibited at maximal vasodilatation a 40% decrease in total renal vascular resistance per unit kidney weight, a reduction in the preglomerular/postglomerular resistance ratio (filtration curve displaced markedly to the left of the control), though combined with some decrease in maximal glomerular filtration capacity.

3. Thus the vascular bed of chronically clipped low-pressure kidneys displays a ‘downward’ structural autoregulation, which by lowering of the total renal vascular resistance and the preglomerular/postglomerular resistance ratio serves to maintain blood flow and to increase filtration pressure thereby raising the filtration fraction.
Antihypertensive Effect of Calcium Antagonists in Rats Differs from That of Vasodilators
Authors: Kazda S. , Garthoff B. , Thomas G.
Published: August 2015

1. Calcium antagonists of the dihydropyridine type such as nifedipine and nitrendipine are potent antihypertensive drugs in various forms of hypertension in rats. Long term treatment with calcium antagonists lowers high blood pressure and reduces cardiac hypertrophy in spontaneously hypertensive rats and additionally prevents mortality in renal (two-kidney, one-clip) and salt-induced (Dahl salt-sensitive) hypertensive rats.

2. Vasodilators of the hydralazine type only lower blood pressure in spontaneous hypertensive rats but do not influence cardiac hypertrophy. Minoxidil lowers blood pressure in spontaneous and slightly in renal hypertensive rats but does not reduce heart hypertrophy in renal hypertension and may even aggravate hypertrophy in spontaneous and salt-induced hypertension.

3. The antihypertensive effect of calcium antagonists is not only due to peripheral vasodilatation. Calcium antagonists may also improve renal function by lowering renovascular resistance. Reduced volume load may contribute to the reversal of heart hypertrophy seen after calcium antagonists compared with vasodilators.
Pressor Effect of Coffee and Cigarette Smoking in Hypertensive Patients
Authors: Freestone S. , Ramsay L. E.
Published: August 2015

1. Patients with mild hypertension who habitually smoked cigarettes and consumed caffeine were examined after abstaining from caffeine and cigarettes overnight. Their mean blood pressure (147/89 mmHg) was substantially lower than values recorded in the clinic (164/102 mmHg) and remained so when they continued to abstain (149/94 mmHg at 2 h).

2. Smoking two cigarettes (3.4 mg of nicotine) elevated blood pressure by 10/8 mmHg but for only 15 min.

3. Drinking coffee (200 mg of caffeine) elevated blood pressure by up to 10/7 mmHg between 1 and 2 h.

4. Combined coffee and cigarette smoking caused a sustained rise in blood pressure from 5 to 120 min to levels similar to those measured in the clinic (162/102 mmHg at 2 h). The interaction of coffee and cigarettes on blood pressure, but not on pulse rate, was significant.

5. Caffeine ingestion with or without smoking may be important in the genesis of mild hypertension.
The Effect of Potassium and Bicarbonate Ions on the Rise in Blood Pressure Caused by Sodium Chloride
Authors: Morgan T. O.
Published: August 2015

1. A group of eight patients with mild hypertension, sensitive to sodium intake, were studied.

2. Sodium chloride (70 mmol daily) caused their blood pressure to rise by 19/14 mmHg.

3. Sodium bicarbonate (70 mmol daily) caused their blood pressure to rise by 12/5 mmHg.

4. Sodium chloride given together with potassium chloride (70 mmol of each daily) caused their blood pressure to rise by 9.6 mmHg.

5. These results suggest that sodium bicarbonate causes a smaller rise in blood pressure than sodium chloride does and that potassium chloride reduces the blood pressure raising effect of sodium chloride.

6. A low sodium, high potassium and an alkaline diet may therefore be a more effective dietary method to reduce blood pressure than a diet low in sodium alone.
Kidney Size and Body Size in the Context of Salt and Blood Pressure
Authors: Simpson F. O. , Doesburg R. , Dempster A. G. , Kihara M. , Yamori Y. , Koshinaga J.
Published: August 2015

1. Kidney weight was analysed for Japanese and New Zealanders of European origin who had died sudden deaths.

2. Kidney weight was relatively greater in Japanese than in New Zealanders.

3. Kidney weight was closely related to body surface area and weight and less closely to height and body mass index.

4. As kidney function is related to kidney size and thus in turn to body size it is advisable to take account of body size in analyses of sodium intake and excretion in relation to blood pressure.
Haemodynamic Effects of Ketanserin, a Selective 5-Hydroxytryptamine (Serotonin) Receptor Antagonist, in Essential Hypertension
Authors: Wenting G. J. , Veld A. J. Man In 'T , Woittiez A. J. , Boomsma F. , Schalekamp M. A. D. H.
Published: August 2015

1. The new peripherally acting selective 5-hydroxytryptamine receptor blocking agent ketanserin was given (10 mg intravenously) to 17 patients with essential hypertension.

2. Systemic mean systolic arterial pressure fell from 192 ± 6 to 146 ± sem 10 mmHg and mean diastolic arterial pressure fell from 90 ± 4 to 68 ± 5 mmHg. Right atrial pressure, pulmonary arterial pressure and pulmonary capillary ‘wedge’ pressure, measured in 12 patients, were also significantly lowered. Heart rate, cardiac output and plasma noradrenaline rose after ketanserin, probably due to baroreflex-mediated sympathetic stimulation, but the changes were small compared with the fall in systemic arterial pressure.

3. Phenylephrine (50, 100 and 200 μg intravenously) was given to five patients before ketanserin and during continuous infusion of ketanserin (2 mg/h after a loading dose of 10 mg) and dose-response curves for mean systemic arterial pressure were constructed. The pressor response to phenylephrine was not shifted by ketanserin. Thus ketanserin, in a dose capable of lowering systemic arterial pressure, does not act as an α-adrenoceptor antagonist.

4. 5-Hydroxytryptamine receptor blockade appears to cause dilatation of resistance vessels and possibly also of capacitance vessels. The data suggest a hitherto unknown role for 5-hydroxytryptamine in the maintenance of high blood pressure.
Effects of Nifedipine during Low, Normal and High Intakes of Sodium in Patients with Essential Hypertension
Authors: Valdés Gloria , Soto M. Eugenia , Croxatto Hector R. , Bellolio Teresa , Corbalán Ramón , Casanegra Pablo
Published: August 2015

1. Nifedipine (20 mg) was given by mouth to seven patients with moderate essential hypertension receiving a low, normal or high sodium intake. The drug produced an important hypotensive effect. Normal sodium intake enhanced the hypotensive action of the drug compared with that during the low and high sodium regimens. Blood pressure remained significantly lower 3 h after drug ingestion.

2. Increases in heart rate and plasma renin activity under all conditions reflected enhanced adrenergic activity.

3. A short-term natriuresis followed nifedipine ingestion in spite of increased aldosterone excretion during the low sodium diet and a decrease in urinary kallikrein during the low and high sodium diets.

4. Nifedipine increased urinary volume only during the high sodium intake.

5. Apart from vasodilatation, nifedipine induces important changes in neurogenic, renal and adrenal mechanisms that regulate blood pressure homoeostasis. Different conditions of sodium balance modulate most of these effects.
Preferential Desensitization to Cardiovascular β2-Adrenoceptor Stimulation in Patients with Peripheral Autonomic Neuropathy after Treatment with Pindolol
Authors: Veld A. J. Man In 'T , Vincent H. H. , Schalekamp M. A. D. H.
Published: August 2015

1. Three patients with orthostatic hypotension due to peripheral autonomic neuropathy were studied. The diagnosis was based on severe hypotension during 60° head-up tilting and absence of the systolic pressure overshoot in phase IV of the Valsalva response. There was no clinical evidence for central nervous system involvement. Plasma noradrenaline levels were 50 and 90 pg/ml in two patients and below 25 pg/ml in one. Noradrenaline was unresponsive to head-up tilting. Heart rate did not change after atropine (2 mg intravenously) in two patients and it increased from 62 to 118 beats/min in the remaining patient after 1 mg. Thus the three patients had a peripheral sympathetic lesion which was accompanied with an efferent para-sympathetic lesion in two.

2. Infusion of isoprenaline in these patients showed supersensitivity for the chronotropic and vascular effects of this drug. Similar cardiac and vascular supersensitivity was observed for salbutamol. Cardiac chronotropic supersensitivity to prenalterol was less pronounced as compared with isoprenaline and salbutamol. The patients were treated with pindolol, 15 mg daily, divided in three doses. After 4 weeks' treatment pindolol was stopped and the infusions of isoprenaline and salbutamol were repeated 72 h after the last dose of pindolol (5 mg). The isoprenaline dose-heart rate response curve was shifted to the right by a factor of 10. The salbutamol dose-heart rate response curve was shifted by a factor of 45, whereas the prenalterol dose-heart rate response curve was shifted by a factor of only 3.

3. The observed chronotropic effects of salbutamol provide evidence for the existence of cardiac β2-adrenoceptors in man. Comparison of the cardiovascular responses after the non-selective β-adrenoceptor agonist isoprenaline, the β2-selective agonist salbutamol and the β1-selective agonist prenalterol suggests preferential β2-adrenoceptor sensitization in chronic autonomic failure, which can be reversed by treatment with the non-selective partial β-adrenoceptor agonist pindolol.
Myocardial Exchanges of Glutamate, Alanine and Citrate in Controls and Patients with Coronary Artery Disease
Authors: Thomassen A. R. , Nielsen T. T. , Bagger J. P. , Henningsen P.
Published: August 2015

1. Myocardial exchanges of plasma alanine, glutamate, citrate, lactate, glucose and free fatty acids were determined in 17 patients with coronary artery disease and in seven control subjects during rest, atrial pacing and recovery.

2. Myocardial release of alanine was demonstrated in all subjects. The amount released was higher in patients with coronary artery disease than in controls. In the patients alanine release was related to severity of coronary artery stenosis.

3. All subjects showed myocardial uptake of glutamate, higher in patients than in controls at rest and during recovery. During atrial pacing myocardial glutamate extraction remained unchanged in controls but decreased in patients.

4. Citrate was released by the heart in all controls and patients. During recovery citrate output was higher in patients than in controls.

5. Myocardial alanine and citrate release during recovery were positively correlated. Both were positively related to myocardial uptake of glutamate during recovery and to the decrease in glutamate extraction during pacing.

6. The results indicate changed myocardial citrate and amino acid metabolism in coronary artery disease. Measurement of myocardial exchanges of glutamate, alanine and citrate in addition to lactate is suggested as a sensitive biochemical test in assessing myocardial ischaemia in man.
Glucose Turnover and Indices of Recycling in Thyrotoxicosis and Primary Thyroid Failure
Authors: McCulloch A. J. , Nosadini R. , Pernet A. , Piniewska M. , Cook D. B. , Clark F. , Johnston D. G. , Alberti K. G. M. M.
Published: August 2015

1. Glucose turnover was examined by using simultaneous bolus intravenous tracer administration of both [3-3H]glucose and [1-14C]glucose in hyperthyroid and hypothyroid subjects before and during appropriate therapy and in matched controls.

2. In hyperthyroid subjects, total glucose turnover (as indicated by analysis of decay of [3-3H]glucose specific radioactivity) was increased (18.1 ± 1.0 vs 12.4 ± 0.9 μnol kg−1 min−1, P < 0.01), as was the metabolic clearance rate for glucose (3.5 ± 0.3 vs 2.4 ± 0.2 ml kg−1 min−1, P < 0.01).

3. Glucose turnover rates determined with [1-14C]glucose as tracer were lower than total glucose turnover rates in all subjects. This difference represents an index of recycling of the 14C label between glucose and glucose-derived C3 intermediates.

4. The recycling index was increased in hyperthyroidism both in amount (4.7 ± 0.6 vs 1.3 ± 0.3 μmol kg−1 min−1, P < 0.001) and when expressed as a percentage of total glucose turnover (27 ± 3 vs 10 ± 2%, P < 0.001).

5. Turnover rates determined by [1-14C]glucose represent irreversible glucose disposal and were similar in hyperthyroid and control subjects (hyperthyroid 13.4 ± 1.1 vs control 11.2 ± 0.9 μmol kg−1 min−1). The major fraction of the increase in total glucose turnover could thus be accounted for by increased cycling of glucose.

6. Total glucose turnover, metabolic clearance and indices of recycling returned to normal with treatment of hyperthyroidism.

7. In hypothyroidism, total glucose turnover (hypothyroid 8.2 ± 0.3 vs control 11.7 ± 1.2 μmol kg−1 min−1, P < 0.01) and metabolic clearance (hypothyroid 1.6 ± 0.1 vs control 2.3 ± 0.2 ml kg−1 min−1, P < 0.001) were decreased and returned to normal with thyroxine therapy. Indices of glucose recycling were normal.
Effect of Aldosterone on the Human Erythrocyte Sodium-Potassium Pump in vitro
Authors: Stern N. , Beck F. , Sowers J.
Published: August 2015

1. The effects of aldosterone in vitro on the Na+,K+-dependent ATPase activity of isolated human erythrocyte membranes and on rubidium (86Rb) uptake and [3H]ouabain binding of intact erythrocytes were studied.

2. ATPase activity was nearly doubled (0.061 ± 0.006 to 0.110 ± 0.01 μmol of Pl h−1 mg−1 of protein) by the addition of a physiological concentration of aldosterone (2.7 × 10-10 mol/l). Higher concentrations had no greater effect.

3. Aldosterone had no significant effect on 86Rb uptake or [3H]ouabain binding.

4. Erythrocytes contain aldosterone at concentrations similar to that in plasma. The effect of aldosterone on ATPase is probably maximal.
Platelet α2-Adrenergic Receptors in Treated and Untreated Essential Hypertension
Authors: Motulsky Harvey J. , O'Connor Daniel T. , Insel Paul A.
Published: August 2015

1. One hypothesis to account for altered adrenergic response in hypertensive patients is alteration in adrenergic receptors on responsive cells. We therefore used radioligand binding methods to examine the α2-adrenergic receptors on platelets isolated from 17 normal men and from 19 men with essential hypertension. in these studies we used the α2-selective radioligand [3H]yohimbine to determine receptor number and affinity on intact platelets.

2. The median number of receptors per platelet was 265 for the hypertensive patients versus 246 for the platelets of controls. Likewise there was no difference between hypertensives and controls in the dissociation constant of the receptors for [3H]yohimbine or adrenaline.

3. Anti-hypertensive treatment with the α2-agonist guanabenz or the β-antagonist propranolol did not change the number or affinity of platelet α2-receptors.

4. in untreated hypertensives the receptor number did not correlate with age, blood pressure, or 24 h urinary excretion of catecholamines or Na+.

5. We conclude that neither hypertension nor anti-hypertensive treatment alters the number of α2-adrenergic receptors on human platelets. Furthermore, because therapy with an α2-agonist does not alter the receptor number and because the receptor number did not correlate with urinary excretion of catecholamines (an index of sympathetic-nervous-system activity), we conclude that ‘down-regulation’ of human platelet α2-adrenergic receptors may not readily occur in vivo.
Elevated Arterial Cyclic AMP Levels during the Onset of Renal Hypertension in Rats
Authors: Chatelain Ricardo Exequiel
Published: August 2015

1. To determine the possible role of arterial cyclic AMP in the pathogenesis of hypertensive vascular hypertrophy and hyperplasia, the changes in the level of this nucleotide were studied during the development of renal hypertension in rats with aortic ligation between the renal arteries.

2. A twofold increase in the cyclic AMP level of the thoracic aorta was observed in 9-day hypertensive rats when compared with sham-operated controls. At this time the total amounts of DNA and collagen were unchanged, although a marked increase in arterial fibrous protein was already present.

3. Arterial cyclic AMP remained significantly elevated in the thoracic aorta of 30-day hypertensive animals. At this time the hypertensive vascular alterations had reached completion as shown by the abnormal accumulation of collagen, DNA and non-fibrous protein.

4. Contrary to the events taking place in the thoracic aorta, a marked decrease in cyclic AMP was present in the abdominal portion, which was protected from high blood pressure by the aortic ligature. in this segment decreased cyclic AMP coexisted with an unchanged collagen content and a diminution in the contents of DNA and non-fibrous protein.

5. Thus a marked increase in arterial cyclic AMP precedes the initiation of DNA replication and collagen accumulation in vascular territories subjected to high blood pressure. These studies suggest the participation of this nucleotide in the vascular growth induced by hypertension.
Trans-Mucosal Passage of Intact Peptides in the Guinea-Pig Small Intestine in Vivo: A Re-Appraisal
Authors: Gardner Michael L. G. , Lindblad Bo S. , Burston David , Matthews David M.
Published: August 2015

1. Re-examination of data for the chemical analysis of peptide-bound amino acids in the mesenteric venous blood of anaesthetized guinea-pigs suggests that there are small, but significant, amounts of small peptides in the blood of fasted animals.

2. Furthermore, there is a significant increase in the peptide content of the mesenteric venous blood during intraduodenal infusion of a partial digest of casein.

3. The data are consistent with the view that some 10% of the amino nitrogen entering the mesenteric blood during absorption of a casein digest in vivo may be in the form of small peptides, although it is not possible to define confidence limits for this estimate.
Effect of pH, Viscosity and Ionic-Strength Changes on Ciliary Beating Frequency of Human Bronchial Explants
Authors: Luk Chun Ka , Dulfano Mauricio J.
Published: August 2015

1. Ciliary activity is significantly influenced by chemical and physical properties of the liquid medium in which the cilia beat.

2. We studied the effect of changes in pH, ionic strength and viscosity on the ciliary beat frequency (CBF) of explants of human respiratory mucosa.

3. Optimal CBF was elicited at pH 7.0-9.0, with a marked reduction of CBF outside these limits. The CBF was well preserved at NaCl concentrations between 5 g/l (80 mmol/l) and 12 g/l (200 mmol/l), but there was rapid loss at concentrations below 0.5 gA (10 mmol/l). The cilia beat best at viscosities below 1.0 centipoises (1 mN s m−2). Increase of the viscosity gradually decreases CBF with a significant drop at viscosities above 87 millipoises.

4. It is concluded that the above limits may fairly accurately indicate the actual physical characteristics of the periciliary environment (‘sol layer’) in vivo.
The Effect of Phenylephrine upon Arterial Pressure, Carotid Sinus Radius and Baroreflex Sensitivity in the Conscious Greyhound
Authors: Peveler R. C. , Bergel D. H. , Robinson J. L. , Sleight P.
Published: August 2015

1. A method for recording carotid sinus diameter in conscious dogs has been developed, using an ultrasound transit time technique. We have used this method to measure the distensibility of the carotid sinus in resting animals, and we have investigated the effect of injecting the vasoactive drug phenylephrine on the mechanical behaviour of the sinus wall.

2. Baroreflex sensitivity was measured in the dogs by the usual method of relating the slowing of the heart to the transient pressure rise induced by the injections of phenylephrine.

3. We have shown that phenylephrine directly reduces the radius of the carotid sinus during the measurements of baroreflex sensitivity. At a dose of 2–4 μg/kg, phenylephrine has an enhancing effect on the baroreflex response, possibly resulting from a modification of baroreceptor output.
Role of Impaired Inspiratory Muscle Function in Limiting the Ventilatory Response to Carbon Dioxide in Chronic Airflow Obstruction
Authors: Gribbin H. R. , Gardiner I. T. , Heinz G. J. , Gibson G. J. , Pride N. B.
Published: August 2015

1. Twenty patients with severe chronic airflow obstruction (CAFO), four of whom were hypercapnic, had greatly reduced ventilatory responses to rebreathing CO2 under hyperoxic conditions, compared with the responses in normal subjects.

2. Mouth occlusion pressure (P0.1) responses to CO2 were also reduced in the patients compared with those of normal subjects but the reduction was less severe than in the ventilatory response.

3. in ten patients with CAFO minimum pleural pressure during tidal breathing [Ppl min. (dynamic)] at a Pco2 of 8.0 kPa was only slightly less negative than in the normal subjects (−16.2 cm water vs −23.4 cm water).

4. During rebreathing end-expiratory volume (EEV) fell progressively in the normal subjects (mean fall = 800 ml); in the patients there was a progressive rise in EEV (mean rise = 390 ml).

5. When Ppl min. (dynamic) was compared with minimum static pleural pressures at the same lung volume the patients were generating a much higher proportion of their available static pressure (47.0%) than the normal subjects (26.4%) at a Pco2 of 8.0 kPa, suggesting that despite the slightly less negative Ppl min. (dynamic), inspiratory muscle activation was greater in the patients than in normal subjects. Similar conclusions were reached from an analysis of the inspiratory work of breathing.

6. We conclude that hyperinflation, by impairing the capacity of the inspiratory muscles to lower pleural pressure, reduces the ventilatory response to CO2 and adds to the effects of abnormalities in pulmonary mechanics so that measurements of absolute pleural pressure or work of breathing underestimate inspiratory muscle activation in patients with severe CAFO.

7. Hyperinflation and severe airflow obstruction also reduce the change in P0.1 for a given degree of inspiratory muscle activation.

8. Our results suggest that, despite the impaired pressure and ventilatory response to rebreathing CO2 in the patients, their central respiratory drive was greater than that of the normal subjects.
Testing for Autonomic Neuropathy: Heart Rate Changes after Orthostatic Manoeuvres and Static Muscle Contractions
Authors: Wieling W. , Borst C. , Van Brederode J. F. M. , Van Dongen Torman M. A. , Van Montfrans G. A. , Dunning A. J.
Published: August 2015

1. The initial heart rate (HR) response evoked by standing, 70° head-up tilt, handgrip and contraction of abdominal and leg muscles was analysed in diabetic patients with autonomic neuropathy and in matched controls.

2. in healthy subjects standing induced an immediate, large, HR increase lasting 20 s that far exceeded the small HR rise induced by tilt. The HR response with handgrip and to contraction of abdominal and leg muscles was strikingly similar for the first 5 s to the HR increase after standing.

3. in diabetic patients handgrip and standing induced a small HR increase starting after 2–3 s. Contraction of abdominal and leg muscles evoked little or no HR changes. The HR rise after tilt up was delayed by 10 s compared with healthy controls.

4. It is concluded that the circulatory response to active and passive changes of posture differs fundamentally. Standing and handgrip are superior to head-up tilt as a test for vagal HR control. An abrupt and large HR increase after standing excludes cardiac parasympathetic neuropathy. A modified response, however, may be due to afferent as well as to efferent lesions, e.g. in muscle afferents or in vagal afferents from cardiopulmonary receptors.
Influence of Muscle Wasting on Oral Glucose Tolerance Testing
Authors: Moxley Richard T. , Griggs Robert C. , Forbes Gilbert B. , Goldblatt David , Donohoe Katherine
Published: August 2015

1. The effect of muscle wasting on glucose tolerance was studied. Oral glucose tolerance testing was performed in three groups of wasted patients: myotonic dystrophy (11); amyotrophic lateral sclerosis (10); other lower motor neuron disease (four). Normal subjects (11) and non-wasted neurological disease (five) controls were studied for comparison. An average decrease of 29–36% in lean body mass was present in the wasted individuals.

2. A slightly higher plasma glucose occurred at 120 min after glucose ingestion in wasted compared with non-wasted individuals (119.2 ± 5 vs 99.9 ± 4 mg/100 ml, P < 0.05).

3. Normal insulin release was seen in all patient groups except those with myotonic dystrophy, who displayed marked hyperinsulinaemia from 30 to 240 min after glucose. This excessive insulin output was not due to a greater absolute decrease in lean body mass in the myotonic dystrophy patients than in the other wasted subjects. No significant correlation between the cumulative insulin release or peak insulin values and the absolute or height adjusted lean body mass was noted within any of the wasted or non-wasted groups.

4. in contrast to the findings of many studies, only clinically insignificant glucose intolerance was detected in ambulatory wasted patients and only patients with myotonic dystrophy had abnormal insulin release. Muscle loss appeared to exert only a slight influence on glucose regulation in these wasted patients and no typical effect of muscular atrophy on pancreatic insulin release was noted.
The Effects of Human Milk and Low-Protein Formulae on the Rates of Total Body Protein Turnover and Urinary 3-Methyl-Histidine Excretion of Preterm Infants
Authors: Pencharz P. B. , Farri L. , Papageorgiou A.
Published: August 2015

1. The effects of human milk and two low-protein formulae on the protein metabolism of 30 preterm appropriate for gestational age infants, birth weight 1.5-2.0 kg, were studied. The compositions of the two formulae were identical except for the protein source, with either casein or whey predominant.

2. The three diet groups all received similar nitrogen (390 mg of N day−1 kg−1) and energy intakes (500 kJ day−1 kg−1).

3. Growth rates for length and weight were comparable and approximated to intrauterine growth. Nitrogen absorption and net nitrogen utilization were enhanced in the human-milk-fed group. However, there were no differences in nitrogen retention, which averaged 274 mg day−1 kg−1 and approximated to intrauterine accretion rates.

4. Rates of whole-body nitrogen flux, protein synthesis and breakdown in the human-milk group were increased by 43–54% over the values seen in either of the two formula-fed groups (P < 0.01). No differences were seen between the two formula groups.

5. No differences were seen in urine 3-methylhistidine excretion between the three study groups.

6. Our results suggest significant differences in the whole-body protein metabolism of formula-fed infants compared with human-milk-fed infants.
Growth Characteristics of α-Foetoprotein-Secreting Human Hepatocellular Carcinoma in Athymic (Nude) Mice
Authors: Bassendine M. F. , Wright N. A. , Thomas H. C. , Sherlock S.
Published: August 2015

1. The growth characteristics of a human hepatocellular carcinoma, derived from the PLC/PRF/5 cell-line (‘Alexander’), transplanted into sub-lethally irradiated athymic (nu/nu) mice have been examined. The xenograft re-expresses α-foetoprotein production although this tumour marker was not detected during cell culture in vitro.

2. There is a positive correlation between serum α-foetoprotein concentration and tumour mass (r = 0.978), validating the use of this tumour marker to assess growth.

3. in mice with progressively growing xenografts there is a linear correlation between log serum α-foetoprotein concentration and time, compatible with exponential tumour growth. Growth of the human hepatocellular carcinoma xenograft is rapid, with an α-foetoprotein doubling time of 6.1 ± 2.1 days (±standard deviation) and a mass doubling time of 3.6 ± 1.2 days (±standard deviation).

4. The tumour cell birth or production rate, determined by a stathmokinetic (metaphase arrest) technique using vincristine, is 15.7 ± 3.8 (95% confidence limits) cells per 1000 cells per hour. The tumour cell loss factor (49%) is low and may contribute to the rapid growth of this human hepatocellular carcinoma xenograft.
A Radioimmunoassay for α-and β-Gliadins
Authors: Ciclitira P. J. , Lennox E. S.
Published: August 2015

1. A rapid, sensitive specific radioimmunoassay for α- and β-gliadin has been developed using an antiserum raised in rabbits to A-gliadin, a component of α-gliadin.

2. The antigen used in the assay was α-gliadin labelled with 125I; antigen-antibody complexes were collected after adsorption to Staphylococcus aureus in suspension.

3. The sensitivity of the assay, as judged by competitive binding with unlabelled antigen, was 1 ng of α- or β-gliadin, which show complete cross-reaction with this antiserum.

4. Cross-reactivity to other wheat proteins was < 1% and no cross-reactivity to extracts of rye, barley or oats was observed.

5. This radioimmunoassay for α- and β-gliadin has been used to measure their amount in different varieties of wheat flour, several foods prepared from flour, e.g. bread, biscuits and products prepared as ‘gluten free’. The possibility of assaying for α-gliadin in prepared foods is of special value since α-, β-, γ- and ω-gliadin have been shown to exacerbate coeliac disease.
Effects of Haemorrhage in Rats Lacking Vasopressin (Brattleboro Strain): Influence of Naloxone
Authors: Gardiner S. M. , Bennett T.
Published: August 2015

1. The effects of naloxone on blood pressure recovery after either rapid arterial haemorrhage or prolonged venous haemorrhage were studied in rats lacking vasopressin (Brattleboro strain) and in control (Long Evans) rats.

2. To produce similar reductions in blood pressure, less blood had to be taken from the Brattleboro rats than from the Long Evans rats.

3. After rapid arterial haemorrhage in the absence of naloxone, blood pressure recovery was slower in Brattleboro rats than in Long Evans rats. Naloxone did not affect the response to rapid arterial haemorrhage in Long Evans rats, but improved blood pressure recovery in Brattleboro rats; despite this improvement, the Brattleboro rats remained hypotensive at a time when the Long Evans rats were normotensive. These findings suggest that both the absence of vasopressin and a depressor action of β-endorphins may contribute to the poor ability of Brattleboro rats to cope with rapid haemorrhage.

4. After prolonged venous haemorrhage in the absence of naloxone, there was no difference between the recovery of blood pressure in Brattleboro rats and Long Evans rats. Naloxone improved blood pressure recovery to a similar extent in both strains of rat. These findings suggest that the absence of vasopressin does not impair blood pressure recovery after prolonged haemorrhage.
Surgical Reversal of Renovascular Hypertension in Rats: Changes in Blood Pressure, Plasma and Aortic Renin
Authors: Brice Joan M. , Russell G. I. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Blood pressure, plasma and aortic renin concentrations were measured in Goldblatt two-kidney one-clip hypertensive rats before and after surgical correction by removing the renal artery clip.

2. Blood pressure fell rapidly in the first hour and then more slowly over 24 h.

3. Plasma renin concentration fell into the normal range by 3 h after unclipping.

4. Aortic renin concentration was markedly raised in hypertensive rats and declined slowly after unclipping, being virtually unchanged at 3 h and reaching normal levels at 24 h.

5. The fall in blood pressure produced by removal of the renal artery clip in Goldblatt two-kidney one-clip hypertensive rats does not depend upon the renin-angiotensin system in plasma and vascular tissue and indicates that a renal vasodepressor system may be involved.
T-Lymphocyte Subsets in Adult Coeliac Disease
Authors: Corazza G. R. , Tabacchi P. , Frisoni M. , Londei M. , Bastia D. , Gasbarrini G.
Published: August 2015

1. As a defect of suppressor function has been hypothesized in the pathogenesis of coeliac disease, we measured, by monoclonal antibodies, the inducer/suppressor T-cell ratio in adult coeliac disease.

2. No statistical difference was observed between coeliac patients and healthy controls, irrespective of treatment and HLA status.

3. These results do not show an imbalance in the inducer/suppressor T-cell ratio in coeliac disease.
Calcium Transport in Synaptosomes and Subcellular Membrane Fractions of Brain Tissue in Spontaneously Hypertensive Rats
Authors: Kravtsov G. M. , Orlov S. N. , Pokudin N. I. , Postnov Yu. V.
Published: August 2015

1. The uptake of Na+ and Ca2+ by synaptosomes and uptake of Ca2+ by the mitochondria and microsomes of brain tissue of rats with spontaneous hypertension (SH rats) and normotensive Kyoto-Wistar rats (WKY rats) were studied with an isotope-exchange method.

2. By means of inhibitor analysis it has been shown that calcium influx into the synaptosomes during depolarization of their plasma membrane takes place only through the potential-dependent channels in both groups of animals.

3. Basal Ca2+ uptake by the synaptosomes of hypertensive rats was increased, apparently by partial depolarization of the synaptosome membrane caused by the increased membrane permeability to Na+ (basal Na+ uptake by synaptosomes was found to be increased in hypertensive rats).

4. Ca2+ uptake by mitochondria of hypertensive rats was increased, and the Ca2+ uptake by microsomes was decreased in these rats compared with controls.

5. The increment of the maximal Ca2+ transport rate in microsomes after the addition of calmodulin was decreased in spontaneously hypertensive rats compared with normotensive animals. Thus alterations in the interaction of calmodulin with the Ca2+-transporting systems of the plasma membrane are an important part of the widespread membrane defect observed in spontaneous hypertension.

6. The changes in the Ca2+-transporting and Ca2+-regulating systems of the synaptosomes of brain tissue in spontaneously hypertensive rats may be the basis for the increase of the intrasynaptosomal Ca2+ concentration and, in turn, for the alteration in the rate of neurotransmitter release.
Assessment of Gall-Bladder Storage Function in Man
Authors: Jazrawi R. P. , Kupfer R. M. , Bridges C. , Joseph A. , Northfield T. C.
Published: August 2015

1. We have validated a scintiscanning method for measuring fasting-state gall-bladder (GB) filling in man. 99mTc-labelled diethyl phenylcarbamoylmethyliminodiacetate (Tc-HIDA) was given intravenously, and 90 min later GB and gut activity were measured by using two isosensitive rectilinear scanning heads (anterior and posterior). Studies with a phantom GB in vitro, and studies in man in vivo, showed that the maximum error due to differences in isotope depth was 8%, compared with 300% when only one head was used.

2. By combining this technique with measurement of biliary lipid concentrations of fasting-state GB bile obtained by nasoduodenal intubation and intravenous cholecystokinin infusion, we were able to measure for the first time the total mass of all three biliary lipids in the GB. GB bile samples obtained in this way were divided into three consecutive portions of equal size in order to assess GB mixing. Bile acid pool size was also measured by isotope dilution.

3. We studied 12 healthy non-obese men. Fasting-state GB filling over 90 min (mean ± sem) was 54 ±8%. Biliary lipid mass in GB was 4.9 ±0.5 mmol for bile acids (67 ± 5% of the total bile acid pool), 1.6 ±0.2 mmol for phospholipid and 0.5 ± 0.1 mmol for cholesterol. The three consecutive portions of fasting GB bile gave values of 1.05 ± 0.07, 1.05 ± 0.06 and 1.03 ±0.10 for cholesterol saturation index (SI) and 6.6 ±1.1, 7.4 ± 1.6 and 6.5 ± 1.0 for Tc-HIDA c.p.m. × 1000 per mmol of bile acids.

4. The SI of fasting-state GB bile was significantly correlated with fasting-state GB filling (r = 0.63; P < 0.05). It was also correlated with cholesterol mass in GB (r = 0.64; P < 0.05), but not with bile acid and phospholipid mass.

5. We conclude that: (a) valid measurements of GB filling can be made in man by a simple scintiscanning technique employing 99mTc-HIDA as a biliary marker; (b) biliary lipid mass can also be measured if GB bile is obtained; (c) SI in health is in part determined by the degree of fasting-state GB filling, and in part by cholesterol mass in GB; (d) fasting-state GB content is well mixed in health.
The Effects of Captopril on the Acute Vascular Responses to Frusemide in Man
Authors: Johnston G. D. , Nicholls D. P. , Leahey W. J. , Finch M. B.
Published: August 2015

1. To examine the importance of angiotensin II formation in the production of frusemide's acute peripheral venous and arterial responses, the effect of pretreatment with captopril was studied.

2. Captopril abolished the acute increases in venous capacitance and blood pressure and attenuated the increases in forearm vascular resistance produced by intravenous frusemide.

3. The study provides evidence that angiotensin II formation performs an essential role in the production of the acute vascular effects of frusemide in man.
Control of Skeletal Muscle Blood Flow during Postural Changes in Acute Myocardial Infarction
Authors: Skagen K. , Henriksen O.
Published: August 2015

1. Central and local regulation of skeletal muscle blood flow in the leg was studied in the acute phase of myocardial infarction.

2. Blood flow was measured by the local 133Xe washout technique in the anterior tibial muscle.

3. The vasoconstrictor response to increase in venous transmural pressure was not present on day 1 after coronary occlusion but gradually returned during days 2, 3 and 7.

4. A normal response to decrease in arterial perfusion pressure was observed, suggesting that intrinsic vascular reactions responsible for autoregulation of blood flow were not affected in the acute phase of myocardial infarction.

5. Passive head-up tilt (30°) induced vasoconstriction in skeletal muscle tissue. There were no differences in this response at any time during the course of acute myocardial infarction.

6. The abolition of the vasoconstrictor response to increase in venous transmural pressure on day 1 is most likely due to centrally elicited increase in sympathetic activity as a normal vasoconstrictor response was obtained the following days. Decrease in baroreceptor activity induced by head-up tilt enabled a marked neurogenically mediated vasoconstriction in skeletal muscle tissue which was almost unaffected during the course of myocardial infarction.
The Rising Ventilatory Cost of Bicycle Exercise in the Seventh Decade: A Longitudinal Study of Nine Healthy Men
Authors: Patrick J. M. , Bassey E. J. , Fentem P. H.
Published: August 2015

1. Submaximal bicycle exercise tests have been performed in nine healthy men on seven annual occasions between the ages of 64 and 70 years. Ten younger men (average age 33 years) have also been studied once for comparison.

2. The ventilatory cost of submaximal work at V̇o2 = 1 litre/min rises significantly from 24.3 ±0.8 litres/min at age 64 years to 31.8 ± 1.8 litres/min at age 70 years; the latter value differs significantly from that of the young men (25.6 ± 0.9 litres/min). Similar changes are seen in the ventilation at 75 W and at V̇co2 = 1 litre/min. The rate of change, between 3% and 5% per year, is considerably greater than that found for the change with age in cross-sectional studies of younger men. There is also a rise in the respiratory quotient, consistent with the hyperventilation found.

3. The cardiac frequency at 1 litre/min also rose with age in the older men, and rough estimates of the decline in their aerobic capacity suggest that progressive anaerobiosis could account for at least some of this increase in ventilation seen during submaximal work.
Role of Prostacyclin in Blood Pressure Regulation and Aldosterone Production in Conscious Rabbits
Authors: Miyamori Isamu , Morise Toshio , Ikeda Masatoshi , Koshida Hideo , Takeda Yoshiyu , Yasuhara Shuichiro , Takimoto Hiroaki , Takeda Ryoyu
Published: August 2015

1. The effects of subdepressor infusion of prostacyclin (PGI2, 5.3 pmol min−1 kg−1) on arterial pressure and aldosterone production induced by angiotensin II (ANG II) were studied in conscious rabbits.

2. Indomethacin pretreatment caused an augmented blood pressure response after ANG II infusion, which returned to near control level after concomitant infusion of a subdepressor dose of PGI2.

3. Aldosterone production after ANG II was significantly attenuated after pretreatment with indomethacin. PGI2 infusion restored this reduced response to near control level.

4. These results may suggest that PGI2 in the circulation could also serve to modulate the pressor and hormonal action(s) of ANG II.
Glomerular Ultrafiltration and Tubular Reabsorption of Bovine Serum Albumin and Derivatives with Increased Negative Charge in the Normal Female Wistar Rat
Authors: Lawrence Gillian M. , Brewer Douglas B.
Published: August 2015

1. Urinary clearances of bovine albumin derivatives rose with their increasing negative charge.

2. A mathematical model has been developed to assess the relative contributions of glomerular ultrafiltration and tubular reabsorption to overall urinary protein clearance.

3. This model indicates that the increased urinary clearance seen with negatively charged bovine albumin derivatives was due to a large reduction in the amount of protein absorbed by the proximal tubular epithelium, which swamped the effects of a small decrease in glomerular ultrafiltration.

4. Derivatives of bovine albumin with increasing negative charge were also cleared with correspondingly greater rapidity from the blood stream.
Glycine Pools and Turnover Rates in Leukaemia Patients Measured with [15N]Glycine
Authors: Lapidot Aviva , Nissim Itzhak , Shaklai Matityahu , Samuel Ruth , Liberman Uri A.
Published: August 2015

1. Turnover parameters for plasma glycine were measured by administration of a single dose of [15N]glycine to overnight fasted healthy volunteers, nine patients with chronic leukaemia, one patient with acute monocytic leukaemia and one patient with chronic myeloid leukaemia before and after chemotherapy.

2. Gas chromatography-mass spectrometry was used to determine plasma [15N]glycine enrichment. Pool sizes and turnover rate constants were estimated from time-decay curves for isotope enrichment.

3. Turnover rate constants and metabolic clearance rates of plasma glycine in leukaemia patients were elevated in comparison with data for healthy volunteers. The increased rates of glycine disappearance from the circulation were not accompanied by a depletion in glycine pool size. Turnover rate constants fell during chemotherapy and were within the normal range during remission.

4. There was a significant positive correlation between glycine turnover rate constants and leucocyte counts.

5. The increase in glycine turnover rate constants may be related to proliferation of the neoplastic cells.