bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Propranolol on Hepatic Blood Flow in Normal and Portal Hypertensive Rats
Authors: Hillon P. , Blanchet L. , Lebrec D.
Published: August 2015

1. The effects of propranolol on heart rate, arterial pressure, portal venous pressure and fractional hepatic blood flow were studied in rats with hepatic artery ligature or with portal vein stenosis, and in sham-operated rats. The effect of propranolol on cardiac output was also studied in normal rats.

2. In rats with hepatic artery ligature or with portal vein stenosis, and in sham-operated rats, propranolol decreased heart rate and portal venous pressure significantly and did not alter arterial pressure. Propranolol decreased fractional hepatic blood flow significantly in rats with hepatic artery ligature, but did not change hepatic blood flow in rats with portal vein stenosis or in sham-operated rats.

3. We conclude therefore that: (a) propranolol decreases portal venous pressure in rats; (b) this decrease in portal venous pressure results in a reduction in portal blood flow which is related, in part, to a reduction in cardiac output; (c) propranolol does not alter hepatic blood flow in normal rats or in rats with portal hypertension.
Clinical Effects and Metabolism of Diazepam in Patients with Chronic Liver Disease
Authors: McConnell J. B. , Curry S. H. , Davis M. , Williams Roger
Published: August 2015

1. After a fixed weight-related dose given intravenously, plasma diazepam concentrations were significantly lower in 11 cirrhotic patients than in controls matched for age and sex, in the 4 h after diazepam administration but not thereafter.

2. When measured at a single fixed time point, a greater proportion of the drug was in the unbound form in the plasma of cirrhotic patients, but non-bound diazepam concentrations were not significantly different in the two groups.

3. Several psychomotor tests showed that cirrhotic patients, although having significantly impaired liver function, did not as a group have increased sensitivity to diazepam compared with their matched controls.

4. Only those cirrhotic patients who at the time of drug administration had impaired cerebral function, as judged by baseline performance of psychomotor tests, showed increased sensitivity to the effects of intravenous diazepam.

5. Psychomotor tests, particularly the Reitan trail test, seem more useful than tests of liver function or drug metabolism for identifying those patients with liver cirrhosis at risk of excessive sedation after diazepam administration.
Low-Frequency Fatigue in Isolated Skeletal Muscles and the Effects of Methylxanthines
Authors: Jones D. A. , Howell S. , Roussos C. , Edwards R. H. T.
Published: August 2015

1. A form of skeletal muscle fatigue was examined with isolated animal and human muscle preparations. The possibility that methylxanthines could overcome this was investigated.

2. Prolonged contractile activity resulted in a long-lasting impairment of force generation at low frequencies of stimulation at times when the force at higher frequencies had substantially recovered. This was seen with both fast-twitch and slow-twitch animal muscles and with samples of isolated human muscle.

3. The decrease in low-frequency force was due to a decrease in twitch amplitude, suggesting damage to the processes involved in excitation-contraction coupling.

4. Caffeine and theophylline at concentrations of 1 mmol/l rapidly and completely reversed the effects of this form of fatigue in both animal and human muscle preparations.

5. Agents that potentiate muscle force production could be an effective means of counteracting the effects of an important form of skeletal muscle fatigue, but a clinically useful compound would need to be more potent than the methylxanthines currently in use.
Metabolic Response in Different Muscle Types to Reduced Blood Flow during Exercise in Perfused Rat Hindlimb
Authors: Walker Paul M. , Idström Jan-Peter , Schersten Tore , Bylund-Fellenius Ann-Christin
Published: August 2015

1. In peripheral arterial insufficiency, leg blood flow during exercise is reduced. The aim of this study was to investigate the metabolic response in different muscle types during exercise at reduced versus normal exercise blood flow.

2. A modified rat hindlimb perfusion model was used. Muscle metabolites and distribution of labelled microspheres were analysed in the soleus and the gastrocnemius muscles during exercise induced by sciatic nerve stimulation.

3. Blood flow distribution between the soleus and the gastrocnemius muscles (per unit weight) was 1·7:1 at rest, and this ratio did not change significantly during exercise at reduced flow.

4. There was a more pronounced decrease in the [phosphocreatine], the [glycogen] and the [ATP]/[ADP] ratio as well as a more pronounced increase in the [lactate] and the [lactate]/[pyruvate] ratio in the gastrocnemius muscle during exercise at reduced blood flow as compared with values obtained at normal exercise flow. In the soleus muscle the difference between the two conditions was confined to an increased [lactate]/[pyruvate] ratio.

5. The results show that a muscle composed mainly of fast-twitch fibres with a high glycolytic and low oxidative capacity is much more susceptible to a reduced exercise flow than a muscle composed of slow-twitch, oxidative fibres. It is suggested that claudicating pain is related to these metabolic changes and it is concluded that pain most probably originates in type II fibres.
Arterial Smooth Muscle Effects of Aldosterone: Action on Ionic Fluxes
Authors: Moura Anne-Marie , Worcel Manuel
Published: August 2015

1. Aldosterone given acutely to male Wistar rats stimulated ouabain-sensitive and ouabain-insensitive 22Na efflux from tail arteries.

2. These effects of aldosterone seem to depend on the activation of specific mineralocorticoid receptors, as they are blocked by antimineralo-corticoid drugs.

3. The results suggest that aldosterone may have a physiological role in the control of vascular tone.
The Effect of Bromocriptine on Circulating Vasopressin
Authors: Robinson Bruce G. , Clifton-Bligh Phillip , Posen Solomon , Morris Brian J.
Published: August 2015

1. The oral administration of 2·5 mg of the dopamine (3,4-dihydroxyphenethylamine) agonist bromoergocriptine enhanced the osmotically stimulated rise in plasma [arginine]vasopressin ([Arg]VP) concentrations in five normal human subjects.

2. This finding lends support to the suggestion that the osmotically induced release of [Arg]VP is under dopaminergic control in man.
Breathing Pattern during and after Smoking Cigarettes
Authors: Tobin Martin J. , Schneider Anne W. , Sackner Marvin A.
Published: August 2015

1. The breathing patterns of ten habitual smokers were monitored in the semi-recumbent position with respiratory inductive plethysmography before and after smoking cigarettes. The subjects smoked a high-tar-content (HTC) and a low-tar-content (LTC) cigarette. The mean (±sd) values and frequency histograms of minute ventilation , tidal volume (VT), frequency (fR), inspiratory time (TI), fractional inspiratory time (TI/TTOT) and mean inspiratory flow (VT/TI) during baseline were compared with the values during and after smoking.

2. On a separate occasion, specific airway conductance (sGaw) and multiple-breath nitrogen washout were measured before and after smoking in six of the subjects.

3. One group of smokers (n = 4) had a greatly increased mean (±sd) baseline VT/TI (390 ± 39 ml/s) compared with normal non-smokers and another group (n = 6) a near normal VT/TI (246 ± 36 ml/s). The first group (‘deep inhalers’) had a significantly higher mean inhalation fraction (volume of inhaled smoke and air/vital capacity; 0·25 ± 0·05). The second group had a lower mean inhalation fraction of 0·14 ± 003 (‘moderate inhalers’).

4. VT/TI decreased to 323 ± 33 ml/s in the post-smoking period in the deep inhalers, whereas it increased to 345 ± 65 ml/s in the moderate inhalers during smoking. No systematic difference in VT/TI was noted between smoking high- and low-tar cigarettes, although the high-tar brand tended to have a greater effect on VT/TI. Deep inhalers showed a fall in VT during and after smoking. Moderate inhalers showed a decrease in TI/TTOT during and after smoking.

5. sGaw, measured in four moderate inhalers and two deep inhalers, fell in all subjects after smoking HTC (19 ± 8·7%; P < 0·01) and LTC (13·9 ± 10%) cigarettes.

6. ‘Sham’ smoking with an unlit cigarette produced no change in breathing pattern.

7. In moderate inhalers, the increase in respiratory output (as reflected by increased VT/TI) combined with a reduction in TI/TTOT appears to reflect the respiratory-centre stimulant effect of nicotine directly or indirectly through broncho-constriction. This contrasts with the reduced neural drive in deep inhalers, which may relate to some overriding satiating effect of the smoking.
Seasonal Changes in Serum 25-Hydroxyvitamin D Concentrations among Asian Immigrants
Authors: Stephens W. P. , Klimiuk P. S. , Warrington S. , Taylor J. L. , Mawer E. B.
Published: August 2015

1. The exposure of Asian immigrants to effective quantities of naturally occurring ultraviolet light was investigated by observing the increase in serum 25-hydroxyvitamin D concentrations during the summer months.

2. The seasonal increase in adult males was greater than in adult females.

3. There was a significant positive correlation between the seasonal increase and the prevailing 25-hydroxyvitamin D concentration, compatible with the view that the accumulation of inadequate stores of 25-hydroxyvitamin D during the summer months results in the low serum concentrations seen in Asian immigrants.
Dissociation between Plasma Prostaglandins E and Fα, Renin and Catecholamines in Hypertensive Patients
Authors: Lijnen P. , Fagard R. , Staessen J. , Amery A.
Published: August 2015

1. Plasma prostaglandins (PGE and PGFα) and catecholamine concentrations, and plasma renin activity were measured during an uninterrupted graded exercise test on the bicycle ergometer in 11 hypertensive patients. Blood was withdrawn from the brachial and pulmonary artery after 30 min recumbent rest, after 15 min rest sitting and at the final work load of the exercise test, which averaged 143 ± 16.5 W.

2. Exercise did not provoke a significant change in these plasma PGE or PGFα concentrations, but a rise (P < 0.001) in arterial plasma renin activity and (nor)adrenaline concentration was observed. It is thus unlikely that prostaglandins E or Fα are an important determinant of release of plasma renin during exercise.
Effects in Healthy Subjects of a New Non-Thiol-Containing Angiotensin-Converting Enzyme Inhibitor, Enalapril Maleate (MK-421)
Authors: Nakashima Mitsuyoshi , Nishijima Kenji
Published: August 2015

1. Single doses of enalapril maleate, ranging from 2.5 to 20 mg, were given orally to 12 normotensive volunteers to determine tolerability, activity on the various components of the renin-angiotensin-aldosterone system and initial pharmacokinetics.

2. Enalapril was rapidly absorbed and maximum plasma concentrations of the diacid, the active metabolite of enalapril, occurred at 3–6 h after dosing.

3. Enalapril significantly decreased systolic blood pressure at 4–6 h after the drug and diastolic blood pressure at 3–6 h after the drug. The maximum decrease of systolic blood pressure was observed at 3–4 h, whereas the maximum decrease of diastolic blood pressure was observed at 6 h.

4. Plasma angiotensin-converting enzyme activity was significantly reduced at all doses. The reduction persisted through 24 h after dosage. Plasma renin activity significantly increased after doses of 5 mg and 20 mg. Aldosterone levels significantly decreased after doses of 10 mg and 20 mg.

5. There were no adverse clinical experiences or abnormal laboratory values noted.
Sodium Balance and Adrenergic Activity in ‘Low-Renin’ Hypertension
Authors: De Leeuw P. W. , Van Leeuwen S. J. , Van Soest G. A. W. , Birkenhäger W. H.
Published: August 2015

1. Fifty patients with uncomplicated essential hypertension were hospitalized and put on a diet containing 55 mmol of sodium daily.

2. Blood pressure was measured at 2 h intervals and averaged for each day. On the first, second, third and seventh days blood samples were drawn for measurement of renin and catecholamines. On the basis of levels on the seventh day patients were divided into a low-renin, normal-renin and a high-renin group.

3. When on balance on their sodium-restricted diet low-renin patients had significantly higher blood pressure, but similar catecholamine levels to the other groups. Cumulative sodium loss on the seventh day was significantly greater in low-renin patients than in the others.

4. It is concluded that low-renin patients exhibit enhanced sensitivity to the effect of sodium. The low-renin state seems to be associated with more severe hypertension, rather than with a disturbance in sympathetic activity.
Effect of Cyclo-Oxygenase Inhibition on Renin, Catecholamine and Blood Pressure Responses to Haemorrhage and Captopril in Conscious Rabbits
Authors: Golub M. S. , Berger M. E. , Vlachakis N. D. , Eggena P. , Sambhi M. P.
Published: August 2015

1. Changes in plasma renin activity, plasma noradrenaline and adrenaline, and blood pressure were evaluated after mild haemorrhage (6 ml/kg) and subsequent intravenous captopril in conscious, restrained rabbits. Two protocols were followed. In the first, control animals (n = 8) were compared with rabbits receiving indomethacin (n = 8) in their drinking water for 5 days and intravenously during the haemorrhage and captopril study. In the second protocol, animals receiving propranolol in the drinking water and intravenously (n = 7) were compared with a group (n = 7) receiving propranolol plus indomethacin.

2. Urinary prostaglandin E excretion was decreased significantly with the oral administration of indomethacin in both protocols. Plasma renin activity levels were not significantly different at baseline, but the animals receiving indomethacin had significantly (P < 005) lower values after haemorrhage in both studies. The large increases in plasma renin activity after captopril were not influenced by indomethacin in either study.

3. The blood pressure response to captopril was significantly blunted in the indomethacin group in the first experiment.

4. Plasma noradrenaline and adrenaline levels were not affected by indomethacin treatment in either protocol.

5. It is concluded that the plasma renin activity response to haemorrhage in conscious rabbits is mediated in part by a cyclo-oxygenase-dependent component separable from the β-adrenoceptor. The renin response to converting enzyme inhibition is not influenced by cyclo-oxygenase inhibition. A component of the blood pressure response to captopril may involve a cyclo-oxygenase product.
Decreased Prostaglandin E2 Renal Synthesis in Women with Phaeochromocytoma
Authors: Ignatowska-Świtalska H. , Wocial B. , Filipecki S. , Januszewicz W.
Published: August 2015

1. Urinary excretion of prostaglandins E2 and F2α were determined in 11 women with phaeochromocytoma and in 23 healthy women.

2. In patients with phaeochromocytoma a significant decrease in urinary excretion of PGE2 and a significant increase in urinary excretion of PGF2α were observed in comparison with controls.

3. Decreased urinary PGE2 and increased urinary PGF2α excretion suggest impaired renal prostaglandin synthesis or metabolism.

4. High PGF2α excretion in association with reduced PGE2 excretion may reflect enhanced activity of 9-ketoreductase, probably caused by excess catecholamines.
Different Haemodynamic Reaction Patterns during Noise Exposure in Normotensive Subjects with and without Heredity for Essential Hypertension
Authors: Andrén L. , Piros S. , Hansson L. , Herlitz H. , Jonsson O.
Published: August 2015

1. Stimulation with noise (100 dBA) for 10 min caused a significant increase in diastolic and mean arterial pressure in normotensive subjects with and without a positive family history of hypertension.

2. The blood pressure response in the group with a positive family history of hypertension was due to a significant increase in total peripheral resistance (9%, P < 0.05); no such change was seen in the group without heredity for hypertension.

3. Systolic blood pressure, heart rate, stroke volume and cardiac output did not change significantly during exposure to noise.

4. There was no difference between the groups in mean intracellular sodium concentration measured in erythrocytes.
Cerebral Blood Flow and Cerebral Metabolism in Normal and Intrauterine Growth Retarded Neonatal Piglets
Authors: Flecknell P. A. , Wootton R. , John Muriel
Published: August 2015

1. Cerebral blood flow and cerebral metabolism were measured in conscious, normally grown neonatal piglets and in littermates which had undergone intrauterine growth retardation.

2. Cerebral blood flow was measured by the Kety-Schmidt technique using [125I]iodoantipyrine as the tracer. The tissue: blood partition coefficient of this tracer was measured in separate groups of growth retarded and normal animals. Cerebral utilization rates of glucose and oxygen were calculated from the arteriovenous concentration differences on the Fick principle.

3. The mean body weight of the growth retarded animals was about half that of their normally grown littermates, and liver weight was reduced in proportion. Brain weight was slightly but significantly lower in the growth retarded animals.

4. Cerebral blood flow was lower in the growth retarded piglets but the rates of cerebral utilization of oxygen and glucose were not significantly different in the two groups. The fractional extraction of arterial oxygen by the brain was significantly higher in the growth retarded animals.

5. The partition coefficient of ipdoantipyrine was significantly lower in the growth retarded animals, being about 75% of the normal value. It is clear that had the partition coefficients been assumed to have been the same in both groups the calculated cerebral blood flows would have been identical.

6. It is concluded that growth retarded neonatal piglets have relatively normal sized brains, with a rate of glucose and oxygen consumption that is not significantly different from normal, despite a reduction in cerebral blood flow of about 35%. Consequently the fractional extraction rate of arterial oxygen by the brain is increased from 50% to 70%.
The Reliability of the Carbon Dioxide-Rebreathing, Indirect Fick Method of Cardiac Output Determination in Patients with Pulmonary Disease
Authors: Stewart R. I. , Lewis C. M.
Published: August 2015

1. The CO2-rebreathing indirect Fick method of cardiac-output measurement was compared with the standard invasive direct Fick method for oxygen during rest and treadmill exercise in 15 patients with pulmonary disease characterized by the common feature of expiratory-airflow limitation.

2. The correlation coefficient for all 37 determinations was 0.94 (P < 0.01); in patients who had a Pa-ETco2 (arterial end-tidal Pco2 gradient) of greater than 5 mmHg, the coefficient was 0.69 (P < 0.05), and in the remainder, with a normal Pa-ETco2, 0.98 (P < 0.01).

3. The difference in correlation between these two latter groups is statistically significant.

4. It is concluded that the indirect method is valid in most patients with pulmonary disease, but that the correlation with the direct Fick method is significantly worse when the Pa-ETco2 exceeds 5 mmHg.
The Cardiovascular and Renal Responses to Short-Term Isolation in Brattleboro Rats
Authors: Gardiner S. M. , Bennett T.
Published: August 2015

1. The effects of isolation on systolic blood pressure, heart rate and fluid and electrolyte balances were studied in rats with a congenital inability to synthesize vasopressin (Brattleboro strain) and in the normal parent strain (Long Evans).

2. There was no significant difference between the systolic blood pressures of Brattleboro rats and Long Evans rats while the animals were housed in groups, although the heart rates of the Brattleboro rats were significantly higher.

3. After S days of isolation in metabolism cages, systolic blood pressure was significantly increased in the Long Evans rats, but not in the Brattleboro rats.

4. Since there were no significant differences between the fluid and electrolyte balances of the two groups after 5 days of isolation, it is unlikely that the hypertension in the Long Evans rats was attributable to a renal action of vasopressin.

5. It is possible that vasopressin was involved in the development of isolation-induced hypertension by virtue of its pressor effects. Alternatively, the failure of Brattleboro rats to develop hypertension may have been due to some abnormality in these animals other than the lack of vasopressin.
A Micro-Method for the Study of Acid Secretory Function in Isolated Human Oxyntic Glands from Gastroscopic Biopsies
Authors: Fellenius E. , Elander B. , Wallmark B. , Haglund U. , Helander H. F. , Olbe L.
Published: August 2015

1. A method has been developed whereby gastric glands can be obtained from biopsies taken from the human gastric mucosa.

2. Minced pieces of the mucosa incubated with collagenase (1 mg/ml) for 2 h yielded a fraction rich in isolated glands. Shorter incubation with collagenase produced larger chunks of tissue, whereas longer incubation resulted in many free cells which were less responsive to dibutyryl-cAMP and histamine; electron microscopy revealed the presence of mucous neck cells, parietal cells, zymogen cells and endocrine cells in the glands. Most of the cells appeared normal, but some of them were vacuolized. Acid secretion in these human glands was determined by the [14C]aminopyrine accumulation technique.

3. Owing to the limited amount of starting material, only a few determinations could be made from each set of biopsies by using the regular macro-method, which normally requires approximately 15 mg dry weight of glands per incubation. To overcome this problem a micro-method was developed which permitted the sample size to be scaled down to approximately 0.1 mg dry weight; in comparison with the previously used macro-method, the glands assayed by the micro-method seemed less sensitive to the method of shaking during incubation. In the micro-method the glands also seemed more responsive to secretagogues, i.e. histamine or dibutyryl-cAMP produced a two- to three-fold increase in [14C]aminopyrine accumulation. The histamine-induced secretion in human glands was effectively inhibited by the histamine H2-receptor antagonist, cimetidine, and that of dibutyryl-cAMP by the substituted benzimidazole, timoprazole. Cholinergic stimulation in the form of carbacholine led to a small and transient response.

4. Thus human gastric glands, as studied by this micro-method, seem to reveal normal secretory properties. The method may be used to study acid secretory function of gastric glands when human gastric material is restricted, as in the case of gastroscopic biopsies.
An Improved Method for the Determination of Potassium in Leucocytes
Authors: Schlebusch H. , Sorger M. , Höck A. , KrüCk F.
Published: August 2015

1. in twenty normal subjects and five patients with disturbances of potassium balance, the potassium concentration in leucocytes was measured by a modified technique.

2. The precision of the method was three to four times greater than that of techniques previously described, with a coefficient of variation for duplicate analyses of 2.3%.

3. A comparison between intraleucocyte potassium concentration and total body potassium in five patients with pathological alterations in their potassium balance showed that intracellular potassium concentration may reflect the clinical state better than total body potassium.
Vertebral Bone Loss: An Unheeded Side Effect of Therapeutic Bed Rest
Authors: Krølner Bjørn , Toft Birte
Published: August 2015

1. The skeletal effects of simple bed rest and re-ambulation were studied in a consecutive series of 34 patients (aged 18–60 years) hospitalized with low backache due to protrusion of a lumbar intervertebral disc. The bone mineral content of the second, third and fourth lumbar vertebrae was determined by dual-photon (153Gd) absorptiometry immediately after admission to the hospital, at the end of the bed-rest period (mean 27 days, range 11–61 days) and approximately 15 weeks later (range 11–24 weeks).

2. During recumbency a mean decrease in lumbar spine bone mineral content of 0.9% per week was observed.

3. Re-ambulation resulted in bone mineral gain, and restoration of lumbar spine bone mineral content was nearly complete after 4 months.

4. The findings suggest that the simple therapeutic bed-rest regimen leads to excessive vertebral bone loss. Recurrent bed-rest periods may predispose to spinal osteoporosis.
Central and Peripheral Nerve Conduction in Thyroid Dysfunction: The Influence of l-Thyroxine Therapy Compared with Warming upon the Conduction Abnormalities of Primary Hypothyroidism
Authors: Abbott R. J. , O'Malley B. P. , Barnett D. B. , Timson L. , Rosenthal F. D.
Published: August 2015

1. The latencies of the visual evoked responses, indices of central nerve conduction, and peripheral nerve conduction were slowed in patients with primary hypothyroidism compared with controls.

2. in thyrotoxic patients, there was no change in the latencies of the visual evoked responses and peripheral nerve conduction compared with the control group.

3. The abnormalities seen in hypothyroidism were reversed by L-thyroxine therapy.

4. Warming untreated hypothyroid patients significantly improved both central and peripheral nerve conduction.

5. The conduction delay found in hypothyroidism is to a large extent dependent upon a subnormal body temperature.
Impairment of Cyclic AMP Response to Bovine Parathyroid Hormone in Patients on Chronic Lithium Therapy with Diminished Renal Urine-Concentrating Ability
Authors: Waller D. G. , Albano J. D. M. , Millar J. G. B. , Polak A.
Published: August 2015

1. Urinary and plasma levels of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of bovine parathyroid hormone (PTH) were measured in 12 patients on long-term lithium treatment and in nine control subjects. The maximum urine osmolality (Umax.) after an intravenous injection of desamino-d-arginine vasopressin (DDAVP) was also measured.

2. in all the control subjects and six of the patients, the Umax. after DDAVP exceeded 700 mosmol/kg. The cyclic AMP responses in these two groups did not differ significantly.

3. in the remaining six patients whose Umax. did not reach 700 mosmol/kg, the cyclic AMP response to PTH was significantly less than that of the controls.

4. A strong correlation was demonstrated in the patients between the urinary cyclic AMP response after PTH and the maximum osmolality after the administration of DDAVP.

5. These observations are consistent with the hypothesis that reduced adenylate cyclase activity contributes to the development of nephrogenic diabetes insipidus in patients on long-term lithium treatment.
Formation of Hydroxyl Radicals from Hydrogen Peroxide and Iron Salts by Superoxide- and Ascorbate-Dependent Mechanisms: Relevance to the Pathology of Rheumatoid Disease
Authors: Rowley D. A. , Halliwell B.
Published: August 2015

1. Superoxide and hydrogen peroxide are formed by activated phagocytes and react together in the presence of iron salts to form the hydroxyl radical, which attacks hyaluronic acid. Ascorbic acid also interacts with hydrogen peroxide and iron salts to form hydroxyl radical in a reaction independent of superoxide. Since iron salts, ascorbate and activated phagocytes are present in the rheumatoid joint, experiments were designed to see whether ascorbate-dependent or superoxide-dependent formation of hydroxyl radicals would be more important in vivo.

2. in the present study, addition of ascorbate to a superoxide-generating system at concentrations of 100 μmol/l provoked a superoxide-independent formation of hydroxyl radicals for a short period. Lower concentrations of ascorbate did not do this. It is therefore suggested that the superoxide-dependent reaction is probably more important.

3. It is further suggested that destruction of ascorbate by oxygen radicals formed by activated phagocytes accounts for the previously reported low concentrations of this compound in the serum and synovial fluid of rheumatoid patients.
Adrenalectomy and Glucocorticoid Administration In Vivo do Not Affect Production of 6-Oxoprostaglandin F1α by Rat Aortae
Authors: Rogers S. P. , Khalid B. A. K. , Funder J. W. , Larkins R. G.
Published: August 2015

1. Rats were bilaterally adrenalectomized and treated for periods of up to 32 days with doses of dexamethasone equivalent to physiological and supraphysiological endogenous glucocorticoid secretion. Aortic production of 6-oxoprostaglandin F1α (6-oxo-PGF1α) was measured by radioimmunoassay of the supernatant fluid from rings of aorta incubated in vitro.

2. Up to 32 days after adrenalectomy, neither adrenalectomy nor dexamethasone (2 μg/day and 20 μg/day) influenced aortic 6-oxo-PGF1α production.

3. High doses of dexamethasone (60 μg/day for 6 days) in the presence or absence of mineralocorticoid (11-deoxycorticosterone, 600 μg/day) had no effect on aortic 6-oxo-PGF1α production.

4. in contrast to the lack of effect of dexamethasone administered in vivo, incubation of aortic discs for 5 h with dexamethasone (1 μmol/l) in vitro caused inhibition of aortic 6-oxo-PGF1α production to 23% of control levels.

5. Alteration in endogenous glucocorticoid secretion is unlikely to be involved in the physiological regulation of aortic 6-oxo-PGF1α, production.
Lack of Correlation between the Maximum Low-Density Lipoprotein (Ldl) Receptor Activity of Blood Lymphocytes and Plasma LDL Concentration in Normal Men
Authors: Cortese C. , Turner P. R. , Marenah C. B. , Sule U. , Price S. , Miller N. E. , Lewis B.
Published: August 2015

1. Measurements were made of the maximal low-density lipoprotein (LDL) receptor activities of blood lymphocytes from 81 healthy men with a wide range of plasma LDL cholesterol concentrations (1.45-7.55 mmol/l).

2. Receptor activity was quantified by measuring the degradation of 125I-labelled LDL (10 μg of protein/ml) to trichloroacetic acid-soluble material during a 6 h incubation, after derepression of the lymphocytes for 72 h in lipoprotein-deficient medium.

3. No significant correlation existed between LDL receptor activity in vitro and plasma LDL cholesterol concentration in vivo (r = −0.08).
Uptake of l-Leucyl-l-Leucine and Glycylsarcosine by Hamster Jejunum in Vitro
Authors: Matthews D. M. , Burston D.
Published: August 2015

1. Preliminary observations of the effects on intestinal transport of the lipophilic properties of the amino acid side chains of a series of neutral dipeptides showed that, contrary to expectation, l-valyl-l-valine and not l-leucyl-l-leucine was the most powerful inhibitor of uptake of the hydrolysis-resistant dipeptide glycylsarcosine by hamster jejunum in vitro.

2. Investigation of the kinetic characteristics of uptake of l-leucyl-l-leucine showed that Kt and Vmax. were lower than the corresponding values for l-valyl-l-valine, suggesting a higher apparent affinity for transport and a lower maximal velocity of transport. Ki for the inhibitory effect of l-leucyl-l-leucine on uptake of glycylsarcosine was less than one-half of the Kt for l-leucyl-l-leucine, so that inhibition was stronger than that expected from the apparent affinity for transport obtained from the kinetics of uptake of the inhibitor. In spite of this, l-leucyl-l-leucine was a much less powerful inhibitor of uptake of glycylsarcosine than was l-valyl-l-valine.

3. The results suggest that total uptake of l-leucyl-l-leucine at pH 5 is the result of at least two processes: uptake of intact peptide by one or more mechanisms, and also hydrolysis followed by uptake of free amino acid. At most concentrations, more than half the mediated uptake of l-leucyl-l-leucine was in the form of intact peptide.

4. The results of experiments on competition for uptake between dipeptides were unexpected. l-leucyl-l-leucine could inhibit mediated uptake of intact glycylsarcosine completely, but glycylsarcosine could not cause complete inhibition of mediated uptake of intact l-leucyl-l-leucine. Glycylsarcosine could, however, cause complete inhibition of mediated uptake of intact l-valyl-l-valine, which in turn could cause complete inhibition of mediated uptake of intact l-leucyl-l-leucine. The existence of more than one dipeptide uptake system in the small intestine seems probable.
Splenic Function in Sickle-Cell Diseases
Authors: Zago M. A. , Bottura C.
Published: August 2015

1. Studies of splenic function were carried out on patients with sickle-cell diseases by the measurement of the clearance of autologous heat-damaged 99mTc-labelled erythrocytes from circulation and into the spleen, the spleen area by a scintillation scanning, the enumeration of pitted erythrocytes by direct-interference microscopy, and the percentage of irreversibly sickled cells (ISC) and of cells with Howell-Jolly bodies. All measurements were performed in seven HbS homozygotes, 10 patients with sickle cell β°-thalassaemia (S/β°-thalassaemia), three patients with sickle-cell disease (SC), four AS heterozygotes and 17 controls.

2. Three different patterns of splenic function were observed among the 20 patients with symptomatic sickle-cell diseases: six patients had enlarged hyperactive spleens, four had enlarged hypoactive spleens, and in 10 patients no splenic activity was detected.

3. The percentage of ISC was higher in sickle-cell anaemia than in S/β°-thalassaemia and very low in SC patients.

4. These results would suggest that the spleen goes through similar successive functional stages in the sickle-cell diseases, namely enlargement in the early years of life, which is followed by hypo-activity and finally atrophy. This evolution seems to be faster in sickle-cell anaemia than in S/β°-thalassaemia and SC disease.
The Effect of the Mammalian Neuropeptide, Gastrin-Releasing Peptide (GRP), on Gastrointestinal and Pancreatic Hormone Secretion in Man
Authors: Wood Susan M. , Jung Roland T. , Webster Joan D. , Ghatei Mohammed A. , Adrian Thomas E. , Yanaihara Noburu , Yanaihara Chizuko , Bloom Stephen R.
Published: August 2015

1. Gastrin-releasing peptide, a newly isolated mammalian peptide similar in its structure and actions to the amphibian peptide, bombesin, has recently been localized to nerves in the brain, gut and pancreas. The present study investigates its effects on gut and pancreatic peptides in man.

2. Intravenous infusion of 0.7 and 2.9 pmol min−1 kg−1 produced significant elevation of plasma gastrin, cholecystokinin-like immuno- reactivity and neurotensin. It was found also to potentiate glucose-dependent insulin secretion.

3. Its specific location in nerve fibres in the proximal gut and pancreas and its selective effect on gastroenteropancreatic peptides may favour its role as a physiological regulatory neuropeptide.
The Immunological Assessment of α1-Antitrypsin with Reference to Its Function in Bronchial Secretions
Authors: Stockley R. A. , Afford S. C.
Published: August 2015

1. The quantification of α1-antitrypsin (α1AT) by standard immunological techniques is altered by interaction of the protein with leucocyte elastase.

2. The results obtained for α1-antitrypsinleucocyte elastase mixtures in the presence of a functional excess of the inhibitor were relatively accurate for the first 6 h. However, continued incubation for more than 24 h led to a major over-estimation of the α1AT as the result of breakdown of the enzyme-inhibitor complex releasing a partially proteolysed form of the inhibitor.

3. In the presence of excess enzyme up to a twofold overestimation of α1AT occurred within 1 h and the degree of overestimation increased with time (up to threefold at 24 h). This was eventually associated with the presence of only a partially proteolysed form of α1AT (mol wt. ⋍ 50000).

4. Different results for each sample were obtained when different polyclonal antisera were used to quantify the α1AT.

5. Complete inactivation of α1AT by oxidation resulted in little change in the immunological quantification of the protein. However, further addition of H2O2 led to a progressive underestimation of the α1AT.

6. The effect of physicochemical alteration on the immunological quantification of α1AT by different antisera should be borne in mind for all studies assessing this protein in lung secretions.
Carbohydrate and Lipid Metabolism during Continuous Ambulatory Peritoneal Dialysis (CAPD): The Effect of a Single Dialysis Cycle
Authors: Heaton A. , Johnston D. G. , Burrin J. M. , Orskov H. , Ward M. K. , Alberti K. G. M. M. , Kerr D. N. S.
Published: August 2015

1. The effect on hormonal status and intermediary metabolism of a single 6 h dialysis cycle at two different concentrations of dialysate glucose was investigated in six patients on continuous ambulatory peritoneal dialysis.

2. The basal blood glucose level was elevated by 0.5 mmol/l, associated with a threefold increase in basal serum insulin compared with seven normal controls. Blood glucose and serum insulin rose further during dialysis, particularly with hypertonic (215 mmol of glucose/l) dialysis fluid and levels remained high for 6 h after the onset.

3. Plasma glucagon concentrations were 2.7-fold increased and did not decrease to normal during dialysis.

4. Concentrations of the gluconeogenic precursors lactate and alanine were consistently raised, and levels of circulating non-esterified fatty acids and ketone bodies were lowered, particularly with hypertonic dialysis fluid.

5. The long-term effects of sustained hyper-insulinaemia, including suppression of lipolysis and ketogenesis, require further investigation.
Blood Pressure and Immunoglobulins
Authors: De Bruijn A. M. , Geers F. C. A. , Hylkema R. S. A. J. , Vermeeren R. , Hofman A.
Published: August 2015

1. Serum concentrations of IgG and IgM were measured in 87 hypertensive and 87 normotensive subjects, matched for age and gender, and selected from the same general population.

2. No significant differences between these two groups were found, in contrast to some previous reports.

3. The reasons for this discrepancy are discussed.
The Effect of Local Temperature on the Response of An Extremity to Indirect Heating in Man
Authors: Allen J. A. , Finlay R. J. , Roddie I. C.
Published: August 2015

1. Venous occlusion plethysmography was used to measure blood flow through the extremities of five normal subjects before and during exposure to a standard heat load with one extremity maintained at a cold (15°C) and the other at a neutral (35°C) temperature.

2. In the foot, local cold (15°C) delayed the onset and reduced by about 92% the vasodilatation during release of sympathetic vasoconstrictor tone caused by body heating.

3. Similar results were obtained in the hand exposed to cold (15°C) but the suppression of the reflex vasodilatation in response to body heating was about 66%.

4. This difference between the hand and foot did not appear to be related to the greater length of the foot since the distal half of the foot reacted like the total foot: local cooling suppressed the reflex vasodilatation by 88%.

5. The results suggest that sympathetic release tests should not be carried out in a laboratory with an environmental temperature as low as 15°C, especially when the circulation to the foot is under investigation.
Effect of Treatment on Skeletal Muscle Dysfunction in Hypothyroidism
Authors: Khaleeli A. A. , Edwards R. H. T.
Published: August 2015

1. Abnormalities in skeletal muscle function were characterized in 19 hypothyroid subjects and the extent and time course of recovery in these abnormalities after treatment determined.

2. Slow muscle relaxation was observed on examination in 11 patients and 12 out of 16 patients had a reduced quadriceps maximum relaxation rate (MRR) and 11 out of 15 had a prolonged ankle jerk relaxation time (AJRT).

3. Measurements of quadriceps force revealed significant muscle weakness when comparison with 15 age matched healthy subjects was made (P<0.001). This weakness was often not evident on clinical examination.

4. A raised plasma creatine kinase (CK) activity was characteristic.

5. With treatment the plasma CK activity and the AJRT rapidly became normal often long before the serum thyroid-stimulating hormone (TSH) was normal, but the quadriceps MRR was slower to recover. It was rarely normal before the serum TSH became normal. Weakness was slow to recover and seven patients remained weak at the end of the study despite being euthyroid for a mean period of 1 year, but strength increased modestly overall (P < 0.01). The urinary creatinine/height index was unchanged, indicating that total muscle mass does not alter with therapy.
The Stability of Gastric Acid Secretion during Prolonged Pentagastrin Stimulation in Man
Authors: Petersen B. , Christiansen J. , Kirkegaard P. , Olsen P. Skov
Published: August 2015

1. Prolonged stimulation with pentagastrin in doses of 100 and 500 ng h−1 kg−1 was performed in nine healthy subjects.

2. A plateau in gastric secretion was reached after 90 min with 100 ng h−1 kg−1 and 500 ng h−1 kg−1 resulted in a secretory plateau after 60 min.

3. When the plateau was reached the acid secretion rate was constant for the rest of the study, that is 4 h after beginning the pentagastrin infusion. Medians and interquartile ranges of acid output were 4.9 (3.7–5.2) and 8.1 (5.8–9.5) mmol of H+/30 min.

4. We conclude that no ‘fade’ of gastric acid secretion occurs during 4 h of submaximal pentagastrin stimulation in normal subjects, and that the time required for reaching a secretory plateau is dependent on the dose of pentagastrin.
Content of Hepatic Reduced Glutathione in Chronic Alcoholic Patients: Influence of the Length of Abstinence and Liver Necrosis
Authors: Videla Luis A. , Iturriaga Hernán , Pino María E. , Bunout Daniel , Valenzuela Alfonso , Ugarte Guillermo
Published: August 2015

1. The relationship between the content of hepatic reduced glutathione (GSH) and the length of abstinence was investigated in 45 chronic alcoholic patients.

2. Hepatic GSH levels were significantly correlated (r = 0.58; P<0.001) with the length of alcohol withdrawal in the whole group. According to liver histology patients were divided into two groups, with and without hepatic necrosis. Subjects without necrosis showed a significant positive correlation (r = 0.71; P<0.001) between GSH values and the length of abstinence; no correlation (r = −0.22; P<0.40) was observed in the group with necrosis.

3. According to the period of abstinence patients were separated into two groups, with a short (≪ 5 days) and a prolonged (> 5 days) alcohol withdrawal. Patients with and without necrosis exhibited comparable mean levels of liver GSH (2.04 ± sem 0.21 and 1.74 ± 0.23 μmol/g respectively; P<0.30) when studied after short periods of abstinence. Alcoholics without liver necrosis showed significantly higher hepatic GSH levels than those with necrosis (3.23 ± 0.30 and 1.60 ± 0.33 respectively; P < 0.01) after prolonged periods of alcohol withdrawal. Similar results were obtained when liver GSH levels were expressed as a function of the mean surface area of hepatocytes, which was not significantly different between patients with and without hepatic necrosis.

4. Parameters assessing the nutritional status of patients with and without necrosis were not significantly different. Steatosis, histologically scored and irrespective of the period of abstinence, was higher in patients with liver necrosis and it did not correlate with hepatic GSH (r = −0.17; not significant). Fibrosis was observed in 20 cases and it did not modify the positive correlation between liver GSH content and the period of abstinence (with fibrosis: r = 0.57; P < 0.01; without fibrosis: r = 0.58;P < 0.01).

5. The changes observed in liver GSH content might be of pathogenic importance in alcoholic liver disease through alterations in lipoperoxidative processes in the hepatocyte.
Circadian Variation in Number and Affinity of β2-Adrenoceptors in Lymphocytes of Asthmatic Patients
Authors: Titinchi S. , Al Shamma M. , Patel K. R. , Kerr J. W. , Clark B.
Published: August 2015

1. To determine whether circadian variation in adrenoceptor function might underlie the ‘morning dip’ in peak expiratory flow (PEF) rate and its abolition by salbutamol we measured indices of β-adrenoceptor function (Bmax. and Kd), the ratio FEV1/FVC, and plasma cortisol at 08.00 and 18.00 hours on and off salbutamol (4 mg given orally every 4 h) in five extrinsic asthmatic patients and five normal volunteers.

2. There was a significant circadian variation in receptor numbers (Bmax.) in both the control and asthmatic groups which was not abolished on treatment with salbutamol.

3. Both groups appeared to compensate for loss of receptor number induced by salbutamol administration by increasing receptor affinity.

4. For comparable combinations of drug/time, there was no significant difference between the control and asthmatic groups.

5. We conclude that the ‘morning dip’ observed in asthmatic patients cannot simply be explained by changes in cell receptor number or affinity, as our results suggest that both groups have intact β-adrenoceptor function. Nevertheless, our observations of the normal circadian rhythm has important implications for future studies of β-adrenoceptors in asthmatic patients.
The Effect of Histamine on the Human Fingertip Circulation
Authors: Coffman Jay D. , Cohen Richard A. , Rasmussen Helen M.
Published: August 2015

1. The effect of intra-arterial histamine on fingertip blood flow (FBF) and vascular resistance (FVR) was studied in normal subjects during reflex sympathetic vascoconstriction induced by body cooling and vasoconstriction caused by intra-arterial noradrenaline.

2. In a room at 20°C, FBF increased from 15.3 ± 35.5 (sd) to 28.3 ± 55.9 ml min−1 100 ml−1 of tissue and FVR decreased from 23.7 ± 17.7 to 11.9 ± 9.9 mmHg·min−1 100 ml−1 (P < 0.01) during infusions of histamine (0.5–4 μg/min) in 14 subjects. In nine of these subjects, the disappearance half times of local injections of Na131I were measured and decreased from 19.8 ± 10.9 to 12.9 ± 7.3 min during histamine infusions, indicating an increase in nutritional flow. Arteriovenous shunt flow was also probably affected, for increases in FBF were sometimes large and FBF increased without a change in the radioisotope half time in two subjects.

3. Neither cimetidine nor pyrilamine (mepyramine) consistently prevented the FBF responses to histamine. Administration of both antihistamines together attenuated the response.

4. During noradrenaline infusions in four subjects, a large increase in FBF (8.9 ± 10.9 to 39.0 ± 8.2 ml, P<0.005) occurred at the smallest dose (0.5 μg/min) of histamine.

5. It is concluded that histamine can vasodilate fingertips and increase nutritional blood flow during reflex sympathetic vasoconstriction. This vasodilatation may be mediated via both histamine H1 and H2 receptors.
Clinical Testing of Gliadin Fractions in Coeliac Patients
Authors: Ciclitira P. J. , Evans D. J. , Fagg N. L. K. , Lennox E. S. , Dowling R. H.
Published: August 2015

1. Since the toxic fraction of cereal flour which damages the small bowel mucosa of patients with coeliac disease has not been fully defined in vivo, we studied the effect of intraduodenal infusions of different doses of unfractionated gliadin and of α-, β-, γ- and ω-gliadin subfractions on the morphology of multiple jejunal biopsies taken from two patients with treated coeliac disease.

2. A dose-response study with increasing quantities of unfractionated gliadin in one coeliac patient showed that 1000 mg produced marked damaged in serial jejunal biopsies taken 2–3 h after commencing the infusion and that the changes had almost completely disappeared 72 h later.

3. α-, β-, γ- and ω-gliadin were prepared, checked for purity and investigated for toxicity in two coeliac patients. After an intraduodenal challenge with 1000 mg of the four gliadin sub-fractions these were shown to have induced damage in the mucosa of jejunal biopsies taken 6 h later.

4. These observations confirm the results of studies in vitro, which suggest that not only α- but β-, γ- and ω-gliadin are enterotoxic in coeliac disease.