bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide Y in renovascular models of hypertension in the rat
Authors: Allen J. M. , Godfrey N. P. , Yeats J. C. , Bing R. F. , Bloom S. R.
Published: August 2015

1. Neuropeptide Y content of the kidneys, heart, blood vessels, adrenals and brain stem was determined in both two-kidney, one-clip and one-kidney, one-clip Goldblatt hypertension in rats and compared with levels in age- and sex-matched controls.

2. Renal neuropeptide Y content was significantly reduced in the clipped kidney of rats in both Goldblatt two-kidney, one-clip and Goldblatt one-kidney, one-clip models of hypertension. The content of neuropeptide Y was also reduced but to a lesser extent in the contralateral, non-ischaemic kidney in the two-kidney, one-clip model.

3. In both models of hypertension, neuropeptide Y content in the heart was significantly reduced in the left ventricle and septum but unchanged in the atria and right ventricle wall.

4. There was no significant change in the concentration of neuropeptide Y through the vasculature (major arteries and veins), including the renal artery distal to the clip, or in adrenals and brain stem.
Effects of sulindac on renal function and prostaglandin synthesis in patients with moderate chronic renal insufficiency
Authors: Mistry C. D. , Lote C. J. , Gokal R. , Currie W. J. C. , Vandenburg M. , Mallick N. P.
Published: August 2015

1. The renal effects of therapeutic doses of sulindac were studied in nine patients with stable renal insufficiency, mean creatinine clearance 37.0 ± 2.2 ml min−1 1.73 m−2 (range 24.7–54.6 ml min−1 1.73 m−2).

2. Nine days' treatment with sulindac produced a small, but significant, reduction in the mean creatinine clearance (37.0 ± 2.2 to 34.7 ± 2.2 ml min−1 1.73 m−2; P < 0.02) and 99mTc diethylenetriaminepenta-acetate (DTPA) clearance (35.5 ± 3.4 to 31.4 ± 3.6 ml min−1 1.73 m−2; P < 0.02) without altering body weight, effective renal plasma flow [131I]hippuran clearance), plasma renin activity (PRA), 24 h urinary volume or electrolyte excretion.

3. After discontinuation of sulindac, creatinine clearance returned to pretreatment values.

4. In five female patients, pretreatment urinary excretion of the 6-ketoprostaglandin F1α (6-keto-PGF1α), a stable breakdown product of prostacyclin (PGI2), was significantly reduced (P < 0.02) when compared with four healthy controls, whereas prostaglandin E2 (PGE2) was unchanged. Administration of sulindac did not significantly alter the excretion rate of PGE2 or 6-ketoPGF1α in this group of patients.

5. In chronic renal disease with moderate renal impairment, reduced renal prostacyclin synthesis may be an important predisposing factor to the renal toxicity associated with the use of nonsteroidal anti-inflammatory drugs (NSAID). Short term use of sulindac in therapeutic doses does not appear to influence the excretion of prostaglandins and produces only a minor reversible change in renal function; used cautiously it may have advantages over other NSAID in these patients.-
Dopamine blockade and natriuresis during water immersion in normal man
Authors: Coruzzi P. , Biggi A. , Musiari L. , Ravanetti C. , Vescovi P. P. , Novarini A.
Published: August 2015

1. Natriuresis was studied during water immersion in eight normal subjects either in the absence or in the presence of dopamine blockade by domperidone.

2. Creatinine clearance showed no significant changes; urine flow remained significantly above control values during water immersion, implying persistent suppression of antidiuretic hormone.

3. The marked natriuresis seen during water immersion alone was significantly blunted (P < 0.05) but not abolished during water immersion plus domperidone.

4. Suppression of the renin–aldosterone system by water immersion alone was not significantly different from that obtained during water immersion plus dopamine blockade.

5. On the contrary, plasma prolactin levels, previously suppressed during water immersion alone, were significantly stimulated during water immersion plus domperidone, thus indirectly suggesting a role of dopamine in mediating the blunted natriuresis seen during water immersion.
Sensory mechanisms in the upper respiratory tract affect the inhalation of cigarette smoke in man
Authors: Grant S. G. N. , Woodman G. , Newman S. P. , Pavia D. , Clarke S. W.
Published: August 2015

1. Cigarette puffing parameters (puff volume, puff duration, number of puffs, total smoking time) and inhaled smoke volume (by a radiotracer techique) have been measured in a group of 11 asymptomatic smokers, once after topical anaesthesia of the upper airways and once without anaesthesia.

2. Topical anaesthesia significantly reduced the mean inhaled smoke volume per puff for the group from 41.1 ml to 30.6 ml (P < 0.05) and the total inhaled smoke volume from 575 ml to 528 ml (P = 0.05), but cigarette puffing parameters were unchanged.

3. It is concluded that stimulation of upper airway sensory receptors, probably sensitive to nicotine, may be an important mechanism in determining the amount of cigarette smoke inhaled by smokers.
The plasma release of atrial natriuretic peptide in man
Authors: Anderson J. V. , Donckier J. , McKenna W. J. , Bloom S. R.
Published: August 2015

1. We studied plasma atrial natriuretic peptide (ANP) concentrations in seven normal subjects after the acute intravenous infusion of sodium chloride/potassium chloride solution (saline).

2. Three separate infusions of 6, 12 and 18 ml of saline/kg body weight each significantly increased the circulating concentration of ANP without changes of plasma osmolality or electrolyte concentrations.

3. The mean maximal rise of the plasma ANP concentration after the three saline infusions was significantly correlated (r = 0.74, P < 0.001) with, but occurred 10–30 min later than, the maximal atrial pressure rise.

4. These observations are in accord with the hypotheses that: (a) ANP is a circulating natriuretic factor; (b) atrial distension is an important stimulus to ANP release in man.
Palmitic acid oxidation and incorporation into triglyceride by needle liver biopsy specimens from control subjects and patients with alcoholic fatty liver disease
Authors: Leung N. W. Y. , Peters T. J.
Published: August 2015

1. A micro-technique was developed to measure fatty acid oxidation in vitro and to investigate its possible derangement in alcoholic fatty liver disease.

2. Percutaneous liver biopsy specimens were obtained from nine control subjects and 28 alcoholic patients with mild to severe fatty liver. Fresh tissue (10–15 mg) was incubated at 37°C for 90 min in a sealed reaction flask containing 1.92 mmol/l [l-14C]palmitic acid (1–2 μCi) and 1% essentially fatty acid free albumin in Krebs-Henseleit buffer, pH 7.4. Radiolabelled CO2 and perchloric acid-soluble ketone bodies were isolated and counted.

3. CO2 production was markedly reduced in alcoholic patients with mild and severe fatty liver compared with controls. This depression was reversed by the addition of malate to the reaction flask but not by carnitine or coenzyme A.

4. Ketone body production was similar in controls and patients with mild and severe fatty liver.

5. After the incubation in vitro, the tissue was extracted with chloroform/methanol and the triglyceride fraction isolated by thin layer chromatography and counted for radioactivity. The rate of palmitic acid incorporation into triglyceride was higher in alcoholic patients, particularly those with severe fatty infiltration, compared with controls.

6. It is suggested that alcoholic fatty liver is accompanied by a progressive reduction in palmitic acid oxidation with the major defect occurring in the tricarboxylic acid cycle. In contrast, the rate of palmitic acid esterification into ‘triglyceride is enhanced.
Effects of thyroid dysfunction on serum calcium in the rat
Authors: Gammage M. D. , Logan S. D.
Published: August 2015

1. Serum calcium was measured under different circumstances of thyroid dysfunction in male Sprague-Dawley and female Wistar rats.

2. After induction of hypothyroidism with 131I and propylthiouracil, serum calcium fell from a control value of 2.43 ± 0.08 mmol/l to 2.07 ± 0.08 mmol/l (P < 0.01).

3. Thyroid hormone replacement therapy in hypothyroid rats caused a return of serum calcium to control values (2.09 ± 0.04 mmol/l to 2.41 ± 0.02 mmol/l, P < 0.01).

4. Treatment of normal rats with thyroid hormones caused elevation of serum calcium to 2.59 ± 0.04 mmol/l compared with a control value of 2.44 ± 0.02 mmol/l (P < 0.01).

5. Time-course studies demonstrated a slow decline in serum calcium levels over a 10 week period during induction of hypothyroidism with propylthiouracil alone but a very rapid normalization of serum calcium (within 1 h) after replacement therapy with l-tri-iodothyronine.

6. These data illustrate the considerable influence that thyroid hormones exert on calcium metabolism and demonstrate for the first time consistent changes in serum calcium in the rat with hypo- and hyper-thyroidism.
Brown adipose tissue uncoupling protein content in human infants, children and adults
Authors: Lean M. E. J. , James W. P. T. , Jennings G. , Trayhurn P.
Published: August 2015

1. A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity.

2. The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly.

3. The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue.

4. Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects. Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children.
Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man
Authors: Solomon L. R. , Atherton J. C. , Bobinski H. , Green R.
Published: August 2015

1. The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers.

2. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30–60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position.

3. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased.

4. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture.

5. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.
Effect of increasing calcium intake on urinary sodium excretion in normotensive subjects
Authors: Cappuccio Francesco P. , Markandu Nirmala D. , Beynon Gareth W. , Shore Angela C. , MacGregor Graham A.
Published: August 2015

1. Eight normotensive subjects were studied in a randomized crossover trial of a high calcium diet (1800 mg of calcium/day) for a week against a low calcium diet (200 mg of calcium/day) for a further week.

2. The subjects were placed on a diet containing 200 mg of calcium/day throughout the study and the high calcium diet was achieved by supplementing the low calcium diet with calcium glubionate and galactogluconate. Sodium and potassium intake were kept constant throughout the study.

3. Twenty-four hour urinary sodium, potassium, calcium and phosphate were measured daily.

4. In spite of a highly significant increase in calcium excretion from the low to the high calcium diet (P < 0.0001), there was no increase in sodium or change in potassium excretion with the increased calcium intake. A transient but significant fall in urinary sodium excretion was observed up to the fourth day of the high calcium diet (P = 0.021). Twenty-four hour urinary phosphate excretion fell significantly on the high calcium diet (P < 0.0001). Body weight, blood pressure, plasma renin activity, aldosterone, plasma creatinine and serum ionized calcium did not change.

5. These results suggest that a short-term increase in calcium intake in normotensive subjects does not increase urinary sodium and potassium excretion.
Implication of thromboxane in frusemide diuresis in rats
Authors: Melki T. S. , Foegh M. L. , Ramwell P. W.
Published: August 2015

1. Administration of the thromboxane A2 (TXA2) synthase inhibitor OKY 1581 to rats significantly increased the urine output elicited by the loop diuretic frusemide.

2. The administration of the TXA2 receptor antagonist SQ 29548 significantly increased the diuretic effect of frusemide.

3. Another TXA2 receptor antagonist L-640,035 increased significantly the diuretic effect of frusemide.

4. Both the sodium excretion rate and urine osmolar excretion rate were significantly increased in rats treated with the TXA2 synthase inhibitor OKY 1581 and frusemide.

5. The data suggest that TXA2 is released during frusemide-induced diuresis in rats, and the released TXA2 has an opposing antidiuretic effect.
Carrier-mediated efflux of ketone bodies in isolated rat hepatocytes
Authors: Metcalfe H. K. , Monson J. P. , Welch S. G. , Cohen R. D.
Published: August 2015

1. The rate of efflux of ketone bodies has been studied in isolated hepatocytes prepared from starved rats and preloaded with d-3-[14C]hydroxybutyrate.

2. Efflux of ketone bodies was temperature-dependent, saturable and inhibited by α-cyano-3-hydroxycinnamate and phloretin. The rate of efflux was also reduced by 6 mmol/l lactate and pyruvate added to the external medium.

3. Under conditions of simulated metabolic acidosis in the hepatocyte suspension medium, ketone body efflux rate was reduced.

4. The experimental data suggest that hepatic plasma membrane ketone body transit is carrier-mediated.
Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity
Authors: Lenz Tomas , Haller Hermann , Lüudersdorf Mihaela , Thiede Hans Michael , Kribben Andreas , Jendroska Klaus , Distler Armin , Philipp Thomas
Published: August 2015

1. The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h.

2. The free calcium concentration in platelets decreased after the first hour of infusion (P < 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion.

3. Plasma noradrenaline increased during the infusion (P < 0.05), with no change in plasma adrenaline.

4. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.
Measurement of fingertip blood flow using thermal clearance reflects anastomotic rather than nutrient blood flow
Authors: Corcoran J. S. , Owens C. W. I. , Yudkin J. S.
Published: August 2015

1. A thermal clearance probe was used to measure fingertip blood flow. When flow was occluded the baseline value was reproducible (coefficient of variation 2% between subjects), whereas basal and maximum flow were poorly reproducible even within subjects.

2. Synchronous changes in thermal clearance were seen when two probes were used on fingers and toes of different limbs (r = 0.77–0.97), in keeping with a central control mechanism.

3. Fingertip blood flow, as measured by thermal clearance, correlated with Po2 of venous blood draining from the dorsum of the hand (r = 0.72–0.92).

4. Contralateral hand cooling caused a sharp reduction of fingertip thermal clearance by 44.2 ± 3.7%.

5. Thermal clearance traces were damped in fingers with heavy keratinization, and improved when keratin was removed.

6. Comparisons with venous occlusion plethysmography (VOP) and photoelectric plethysmography (PPG) showed that thermal clearance correlates with both methods (r = 0.60–0.92 for VOP and 0.64–0.93 for PPG) but with much integration of the signal and a 10 s lag.

7. It is concluded that the probes used measure predominantly anastomotic flow and not nutrient skin blood flow alone.
Resting and stimulated cytosolic free calcium levels in neutrophils from patients with Bartter's syndrome
Authors: Di Virgilio Francesco , Calò Lorenzo , Cantaro Salvatore , Favaro Silvana , Piccoli Antonio , Borsatti Arturo
Published: August 2015

1. Cytosolic free calcium concentrations ([a2+]i) were measured in resting and chemotactic peptide-activated neutrophils from eight patients with Bartter's syndrome and compared with levels determined in neutrophils isolated from healthy controls.

2. [Ca2+]i was measured with the intracellular trappable fluorescent indicator Quin2. The synthetic tripeptide formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) was used as a stimulant.

3. No difference was found in resting [Ca2+]i between neutrophils from normal controls and those from patients with Bartter's syndrome.

4. On the contrary increases in [Ca2+]i stimulated by fMet-Leu-Phe concentrations higher than 10−8 mol/l were significantly less in neutrophils from patients with Bartter's syndrome.

5. It is suggested that neutrophils from patients affected by Bartter's syndrome exhibit an intrinsic anomaly in the mechanism responsible for intracellular Ca2+ mobilization.
Trace elements during the development of hypertension in the spontaneously hypertensive rat
Authors: Berthelot A. , Luthringer C. , Exinger A.
Published: August 2015

1. Total plasma concentrations of bromine, copper, rubidium, selenium and zinc were measured in spontaneously hypertensive rats (SHR) and Wistar–Kyoto rats (WKY) of 5–20 weeks of age, using an X-ray fluorescence spectrometry technique.

2. Although plasma levels of bromine, rubidium, selenium and zinc varied at different ages when comparing SHR and WKY, their general evolution was similar. Copper levels increased more in SHR than in WKY.

3. These perturbations in trace element levels could perhaps participate in the establishment of hypertension in SHR, but could also be due to genetic differences between the strains, unrelated to the development of hypertension.
The effects of neonatal hypothyroidism on brain catecholamine turnover in adult rats: Assessment by a steady-state method
Authors: Harris P. E. , Lewis B. M. , Dieguez C. , Hall R. , Scanlon M. F.
Published: August 2015

1. The effects of hypothyroidism in utero, and continuing into postnatal life, on the central turnover of catecholamines, noradrenaline and dopamine were studied in rats.

2. Rats were rendered hypothyroid in utero by treating pregnant females with methimazole in the drinking water. In two groups goitrpgen treatment continued for 3 or 10 weeks postnatally.

3. Methimazole treatment in utero did not produce significant changes in noradrenaline, dopamine or tyrosine content in either the hypothalamus or striatum.

4. Three weeks' postnatal treatment reduced tyrosine specific radioactivity in the anterior hypothalamus and dopamine specific radioactivity in the striatum. Ten weeks' treatment increased dopamine content and reduced noradrenaline synthesis in the mediobasal hypothalamus and a reduction in tyrosine content in the anterior hypothalamus.

5. These data suggest that hypothyroidism restricted to intrauterine life does not produce permanent changes in adult catecholamine neuronal function. Long term hypothyroidism produced localized changes, suggesting a specific rather than general effect.
Circadian variation of thyrotrophin, determined by ultrasensitive immunoradiometric assay, and the effect of low dose nocturnal dopamine infusion
Authors: Kerr D. J. , Singh V. K. , McConway M. G. , Beastall G. H. , Connell J. M. C. , Alexander W. D. , Davies D. L.
Published: August 2015

1. The effect of low dose dopamine infusion on the circadian rhythm of thyrotrophin (TSH), prolactin and Cortisol in a group of six healthy male volunteers is reported. Subjects were infused in random order with either saline (154 mmol/l NaCl solution; control) or dopamine (0.1 and 1 μg min−1 kg−1) between 21.00 and 01.00 hours, in random order.

2. The serum TSH profile was characterized by a maximal peak occurring at 23.00 hours and higher nocturnal than diurnal values. Superimposed on this are short term oscillations in serum TSH levels, typical of an ultradian rhythm.

3. The maximal peak in TSH, occurring at 23.00 hours, was abolished by dopamine infused at a rate of 1 μg min−1 kg−1, and was unaffected by the lower rate of dopamine infusion (0.1 μg min−1 kg−1).

4. The serum prolactin profile was characterized by a peak occurring soon after the onset of sleep (23.30–00.30 hours), which fell during the morning, and began to rise in late evening.

5. Low dose dopamine (0.1 μg min−1 kg−1) had a slight but insignificant effect with decreased prolactin levels at the end of the infusion whereas the higher dopamine dose was associated with significantly lower prolactin levels during and throughout the infusion. There was a rebound to levels significantly higher than control on cessation of the infusion. Cortisol levels were unaffected by dopamine.
Unilateral renal ischaemia in the rat: Effect of method of occlusion of the blood supply on function of ipsilateral and contralateral kidneys
Authors: Ferwana O. S. , Pirie S. C.
Published: August 2015

1. The functions of right and left kidneys were measured immediately preceding, during and for 4 h after 45 min occlusion of the blood supply to the left kidney.

2. The blood supply was occluded by placing a clamp around the renal artery near to the aorta (group 1), near to the renal hilus (group 2) or by clamping the renal pedicle after prior separation of the kidney from perirenal tissue (group 3).

3. During ischaemia right kidneys had increased urine flow rates and excretion of sodium and water, but inulin clearances (CIn) remained unchanged.

4. After ischaemia left kidneys were isosthenuric with depressed CIn.

5. Occlusion of the renal artery alone resulted in non-oliguric kidneys in which CIn was reduced to 10% and 1% respectively for groups 1 and 2.

6. The most severe damage to function was seen in the kidneys of group 3 which were oliguric and in which CIn was depressed to 0.1% of the pre-ischaemic value.

7. It is concluded that the pedicle clamp method produced complete renal ischaemia and the most severe damage to function. Occlusion of the renal artery produced incomplete ischaemia and a less severe fall in function which depended upon the site of occlusion.
The influence of pregnancy on drug action: Concentration–effect modelling with propranolol
Authors: Rubin Peter C. , Butters Lucy , McCabe Rosemary , Kelman Andrew
Published: August 2015

1. The physiological changes of pregnancy have been shown to alter the disposition of some drugs. However, there are no data on the possible influence of pregnancy or its complications on drug effect. We have applied drug concentration–effect analysis to determine whether pregnancy influences the action of propranolol.

2. Twelve women with pregnancy induced hypertension were studied during the third trimester and again 2–3 months post partum. On each occasion propranolol (10 mg) was given intravenously and measurements of heart rate, blood pressure and whole blood propranolol concentration were determined over the ensuing 8 h.

3. Pregnancy did not alter propranolol disposition. Clearance was 0.63 ± 0.18 and 0.71 ± 0.24 litre h−1 kg−1, and volume of distribution at steady state was 4.02 ± 2.98 and 3.07 ± 1.58 litres/kg during and after pregnancy respectively.

4. There was no fall in blood pressure over the period of the acute study. The reduction in heart rate (beats/min per ng of propranolol/ml) was greater during compared with after pregnancy: −0.61 ± 0.23 and −0.39 ± 0.19 respectivly (F = 6.64; df 1,9; P<0.03). There was no relationship between blood pressure or pretreatment heart rate and the slope of the concentration–effect relationship.

5. We conclude that pregnancy can significantly alter drug effect in the absence of any pharmacokinetic changes. These findings suggest that therapeutic ranges established in non-pregnant patients may not be applicable during pregnancy.
Platelet sodium kinetics, blood pressure and serum urate: Aberrations in non-obese men at risk for type 2 diabetes mellitus
Authors: Berntorp K. , Lindgäurde F. , Mattiasson I.
Published: August 2015

1. The rate constants for the ouabain- and frusemide-sensitive 22Na+ efflux, the number of [3H]ouabain binding sites and the effect of plasma on [3H]ouabain binding were determined in platelets, as were blood pressure (BP) and serum urate concentrations, in 35 normoglycaemic men with family histories of type 2 diabetes (hereditary group), in 18 subjects with impaired glucose tolerance (IGT) and in 28 normoglycaemic controls. All subjects were non-obese males of comparable age.

2. Earlier findings of increased BP both in normoglycaemic subjects with family histories of type 2 diabetes and in IGT subjects were confirmed.

3. The mean serum urate concentration was significantly higher in the hereditary group than in controls, and intermediate in IGT subjects.

4. The ouabain-sensitive 22Na+ efflux rate constant was significantly decreased in IGT subjects without any concomitant change in the number of [3H]ouabain binding sites. No differences in any of the rate constants for 22Na+ efflux, or in the number of [3H]ouabain binding sites, were noted between the hereditary group and controls.

5. The ability of deproteinized plasma samples to interfere with [3H]ouabain binding to test platelets from one healthy individual was similar in all three groups.

6. The present findings are not consistent with the hypothesis that the BP increase in normoglycaemic subjects with family histories of type 2 diabetes is linked to a disturbance in sodium transport. Our data suggest a decreased Na+/K+-ATPase activity in IGT, which may be of pathophysiological significance in relation to hypertension.
Effect of total starvation and very low calorie diets on intestinal permeability in man
Authors: Elia M. , Goren A. , Behrens R. , Barber R. W. , Neale G.
Published: August 2015

1. The effect of total starvation for 4–5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5 g), [14C]mannitol (0.5 μCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 μCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g), [14C]mannitol (10 μCi), lactulose (0.1 g) and 51Cr-EDTA (5 μCi).

2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P < 0.025), 33% in group 2 obese subjects (P < 0.05) and 41% in group 3 obese subjects P > 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.

3. There was no significant effect of starvation on transit time, whether assessed by the increase in breath hydrogen concentration in expired air or by radionuclide scanning.

4. Starvation produced no significant change in the clearance of the intravenously administered markers from the plasma. Oxidation of intravenous mannitol was estimated to account for about 1% of the clearance both before and during starvation.

5. The data provide evidence of a selective decrease in the absorption and excretion of mannitol during short-term total starvation. The changes in the excretion of mannitol are not due to alterations in renal function or gastrointestinal transit time, or to changes in the oxidation and plasma clearance of mannitol. They are likely to reflect changes in the small intestinal mucosa during early starvation. In contrast, very low calorie diets taken for at least 1 week prevent changes in small intestinal permeability.
The effects of posture on abnormalities of forearm venous tone in women with pregnancy-induced hypertension
Authors: Stainer Karen , Pickles C. , Cowley A. J.
Published: August 2015

1. Forearm venous tone was measured in the left lateral supine position and in response to passive leg elevation in a group of women with pregnancy-induced hypertension and compared with a group of normotensive pregnant women and a group of non-pregnant women.

2. The women with pregnancy-induced hypertension were venoconstricted in the supine position compared with the normal pregnant women (P < 0.002). There was no difference in forearm venous tone between the women with pregnancy-induced hypertension and the non-pregnant women.

3. In response to passive leg elevation the women with pregnancy-induced hypertension venodilated (P < 0.002) whereas there was no change in forearm venous tone in the normotensive pregnant women and the non-pregnant women. There was no change in blood pressure in any of the women after 35 min of leg elevation.

4. These results demonstrate that the abnormal venous vasoconstriction that occurs in women with pregnancy-induced hypertension in the supine position is corrected by passive leg elevation, a manoeuvre which leads to an increase in central blood volume.
Breathlessness and respiratory mechanics during reflex or voluntary hyperventilation in patients with chronic airflow limitation
Authors: Freedman S. , Lane R. , Guz A.
Published: August 2015

1. Six patients with chronic airflow limitation rebreathed CO2. Subsequently they voluntarily copied their stimulated breathing pattern while normocapnia was maintained. On a separate occasion four of these patients performed progressively increasing exercise and later copied these breathing patterns.

2. During all experiments flow, ventilation and pleural pressures were recorded. In addition, breathlessness was measured on a visual analogue scale every 30 s.

3. In these patients voluntary copying of either form of stimulated breathing resulted in diminished breathlessness and in some cases in complete abolition of the sensation, despite similar levels and patterns of ventilation in the two situations.

4. No systematic or consistent differences in the mechanics of breathing between stimulated and voluntarily copied breathing were found.

5. There was no correlation found between breathlessness score and any mechanical variable measured.

6. These results show that despite similarity in mechanics between stimulated and voluntary hyperventilation, the sensation of breathlessness is much diminished during the latter in these patients. This suggests that the sensation of breathlessness is more dependent upon the awareness of central processing than upon input from peripheral mechanoreceptors.
The role of superoxide anion and hydrogen peroxide in glomerular injury induced by puromycin aminonucleoside in rats
Authors: Beaman M. , Birtwistle R. , Howie A. J. , Michael J. , Adu D.
Published: August 2015

1. The nephrotic syndrome was induced in inbred female Wistar rats by the intravenous injection of puromycin aminonucleoside (PA) (5 mg/100 g body weight).

2. One group (n = 12) received superoxide dismutase (SOD) (15 mg/kg body weight), a second group (n = 12) received polyethylene glycol coupled catalase (PEG-catalase) (5000 i.u./kg body weight) and the third (n = 9) saline (150 mmol/l NaCl) via the intraperitoneal route, in addition to the PA.

3. SOD and PEG-catalase reduced the 24 h urine protein on days 8 and 15 compared with unmodified puromycin treated animals and this difference was significant on day 15 for SOD (P < 0.05) and for PEG-catalase (P < 0.01). Glomerular filtration rate, as measured by the creatinine clearance, was lower in the PEG-catalase group but did not differ significantly from the saline treated group.

4. These data suggest that superoxide anion and hydrogen peroxide, or their reaction products, are involved in the glomerular injury of puromycin nephropathy.
Human alveolar gas-mixing efficiency for gases of differing diffusivity in health and airflow limitation
Authors: Harris E. A. , Buchanan P. R. , Whitlock R. M. L.
Published: August 2015

1. Incomplete mixing of alveolar gas may be expressed as an equivalent alveolar dead space serving a remaining alveolar space in which mixing is regarded as complete. Calculation of this dead space during multiple-breath, inert gas wash-in or wash-out leads to an estimate of ‘multiple-breath alveolar mixing efficiency’ (MBME).

2. We measured MBME in 25 healthy subjects and six patients with chronic airflow limitation (CAL), and in three asthmatic patients before and after bronchial provocation with histamine aerosol, from successive breaths during open-circuit, multiple-breath wash-in of a mixture containing helium (He) and sulphur hexafluoride (SF6). The simultaneous use of a light and a heavy gas helps to identify diffusive mechanisms.

3. MBME fell almost linearly with log Z, the proportion of total wash-in remaining uncompleted. For a given Z, MBME was always lower for SF6 than for He in the same subject. In health the lowest MBME (52.2%) was seen for SF6 in a man aged 21 years. The same wash-in yielded a ventilation distribution with an extreme range of specific ventilation of less than 1 decade. MBME of this order is thus consistent with estimates of ventilation distribution in health.

4. Patients with CAL showed a big increase in the volume of the conducting airways or ‘series dead space’ (VDS) for both gases, and VDS was always bigger for SF6 than for He. This very large VDS appears to be the main reason for wash-in delay in these patients, followed by impaired diffusive mixing in the peripheral air spaces. Ventilation maldistribution may play little part in the mixing defect.

5. In asthma, bronchoconstriction by histamine reduced VDS and MBME, but MBME did not differ between He and SF6. This suggests a shortening of diffusion distances beyond the narrowed bronchioles which may help to mitigate the (here predominant) effects of maldistribution on mixing efficiency.
Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease
Authors: Pacheco Sergio , Hillier Keith , Smith Colin
Published: August 2015

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0).

2. Gas–liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 ± 4) and Crohn's disease (20 ± 3) than in controls (13 ± 5 μg/mg of protein) (means ± sd). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations.

3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease.

4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.
Increased bronchial reactivity to histamine in diabetic autonomic neuropathy
Authors: Rhind George B. , Gould Grahame A. , Ewing David J. , Clarke Basil F. , Douglas Neil J.
Published: August 2015

1. Twelve male diabetic patients inhaled nebulized histamine in doubling concentrations from 0.03 mg/ml to 32 mg/ml until they reached the maximum concentration or until their forced expiratory volume in 1 s (FEV1.0) fell by at least 20%. Six had evidence of severe autonomic neuropathy (DAN), while the other six did not.

2. More of the DAN group decreased their FEV1.0 on histamine inhalation by at least 20% (P < 0.02) and more of them decreased their maximal flow at 50% vital capacity by at least 20% than those in the group without DAN (P < 0.05).

3. The fall in FEV1.0 and in maximal flow at 50% of vital capacity was greater (P < 0.05) in the DAN group than in the group without DAN.

4. This suggests that diabetic patients with autonomic neuropathy have increased bronchial reactivity to histamine. This could either be due to differential damage of the respiratory autonomic nerves or, alternatively, to denervation hypersensitivity.
Voluntary isocapnic hyperventilation and breathlessness during exercise in normal subjects
Authors: Lane R. , Cockcroft A. , Guz A.
Published: August 2015

1. Nine normal subjects performed 6 min, constant-workload, exercise tests on a bicycle ergometer at either a ‘high workload’ or at a ‘low workload’. During the first ‘high workload’ test their spontaneous breathing pattern was recorded on to magnetic tape. During one subsequent ‘high workload’ test and one ‘low workload’ test they voluntarily copied their recorded breathing pattern. During a second ‘low workload’ test they breathed spontaneously. Isocapnia was maintained by the operator throughout both the copying tests. During the exercise tests ventilation was recorded and subjects indicated the level of their sensation of breathlessness every 30 s.

2. Subjects felt markedly less breathless when a proportion of their ventilation was produced by voluntary effort than when the same total level of ventilation was produced entirely by the stimulus of exercise. Furthermore, voluntary isocapnic hyperventilation during exercise did not increase breathlessness above that normally associated with that level of exercise.

3. These results suggest that it is reflexly driven ventilation, and not simply the level of ventilation itself, which relates to the level of breathlessness during exercise.
Muscle strength in healthy White and Asian subjects: The relationship of quadriceps maximum voluntary contraction to age, sex, body build and vitamin D
Authors: Shaunak S. , Ang Liza , Colston Kay , Patel Swatee , Bland M. , Maxwell J. D.
Published: August 2015

1. The maximum voluntary isometric contraction (MVC) of the dominant quadriceps muscle was measured in 136 healthy White and 172 healthy Hindu Asian subjects resident in London, using a specially designed chair equipped with a force measuring load cell.

2. Males were stronger than females, and for both sexes MVC declined with age. From age 20 to 60 the annual decline in MVC ranged from 0.56% in White males to 1.5% in female Asians.

3. White subjects were stronger than Asian subjects even after correcting for the effect of age, height, weight and sex in a multi-factorial analysis.

4. Only in males did MVC correlate with height and weight. Asian women were more obese than any other group, and showed an increase in body mass index with age.

5. Twenty-two per cent of Asian subjects had marked vitamin D deficiency (plasma 25-hydroxycholecalciferol < 10 nmol/l). There was no correlation between MVC, and plasma 25-hydroxycholecalciferol.
Lithium clearance in man: Effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide
Authors: Atherton J. C. , Green R. , Hughes S. , McFall V. , Sharples J. A. , Solomon L. R. , Wilson L.
Published: August 2015

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers.

2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3–4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively.

3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high.

4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small.

5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water re-absorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.
The effect of ketone bodies on leucine and alanine metabolism in dogs
Authors: Umpleby A. M. , Chubb D. , Boroujerdi M. A. , Sonksen P. H.
Published: August 2015

1. The effect of an infusion of sodium β-hydroxybutyrate on leucine and alanine metabolism was investigated in dogs starved for 12 h. To determine whether the metabolic changes produced by this infusion were due to the resultant alkalaemia the effect of an equimolar infusion of sodium bicarbonate was also studied.

2. The sodium β-hydroxybutyrate infusion reduced alanine concentration as a result of a decrease in alanine production rate and an increase in alanine metabolic clearance rate. The sodium bicarbonate infusion induced a small decrease in alanine concentration which was due to an increased metabolic clearance rate. Alanine production rate showed no change. This demonstrates that the fall in alanine concentration after a sodium β-hydroxybutyrate infusion is due both to a ketone-specific inhibitory effect on alanine production rate and an increased metabolic clearance rate caused by the alkalaemia.

3. Leucine concentration was increased after the ketone infusion due to a small increase in production rate and there was a small increase in the rate of leucine incorporation into protein. Alkalaemia had no effect on leucine concentration or metabolism.
The strength, contractile properties and radiological density of skeletal muscle before and 1 year after gastroplasty
Authors: Newham D. J. , Harrison R. A. , Tomkins A. M. , Clark C. G.
Published: August 2015

1. Skeletal muscle strength, contractile properties and radiological composition have been studied in seven morbidly obese adults (six female) before and 1 year after gastroplasty operations. The mean body weight fell from 138.3 kg (sd 25.2) to 99.7 kg (sd 23.0) (P < 0.001).

2. The strength and contractile properties (force/frequency, relaxation rate and fatiguability) of both the adductor pollicis and quadriceps muscles were unaffected by the weight loss.

3. Computerized axial tomography scans obtained 1 year after surgery showed that the quadriceps contained an abnormally high proportion of fat. The mean fat content was 10.8% (range 3.0–30.1%) compared with 1.6% (range 0–5%) for normal muscle. Two individuals were scanned before and after surgery and the fat content of their quadriceps fell from 12.6% and 6.9% to 3.1% and 3.0%, respectively.

4. It is concluded that in obese individuals large amounts of weight can be lost, from both subcutaneous and intramuscular fat stores, without compromising either the strength or contractile properties of skeletal muscles. These results do not support the claim that skeletal muscle contractility is a sensitive indicator of changes in nutritional status.
Protein and substrate metabolism during starvation and parenteral refeeding
Authors: Tracey Kevin J. , Legaspi Adrian , Albert James D. , Jeevanandam Malayappa , Matthews Dwight E. , Brennan Murray F. , Lowry Stephen F.
Published: August 2015

1. Healthy male volunteers underwent 10 days of hospitalized protein-calorie starvation and a subsequent 10 day repletion phase with complete intravenous nutritional support (IVF). Non-protein calories were provided as either all d-glucose or as 50% d-glucose/50% lipid.

2. In comparison with starvation, whole-body protein breakdown, as assessed by [15N]glycine, [13C]leucine and urinary excretion of 3-methylhistidine (3-MH), was diminished during IVF. The administration of parenteral nutrition did not specifically suppress peripheral tissue protein breakdown, as measured by extremity 3-MH efflux.

3. Despite the differential insulin response to d-glucose/amino acid (50 ± 6 m-units/ml) as compared with the d-glucose/lipid/amino acid regimen (25 ± 4 m-units/ml), there was no difference in nitrogen retention between the regimens. Indirect calorimetric determinations revealed that oxidation of substrate during IVF was related to the proportion of d-glucose and lipid infusion.
Naloxone increases mucosal fluid secretion in the inflamed and distended feline gall bladder: Evidence for a possible protective mechanism by endogenous opioids
Authors: Jivegård Lennart , Svanvik Joar
Published: August 2015

1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory actions in the small intestine, is also contained in nerves in the gall-bladder wall.

2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin.

3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall-bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high.

4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall.