bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Measurement of Hepatic Extraction of Chenodeoxycholic Acid and Ursodeoxycholic Acid in Man
Authors: Marigold J. H. , Bull H. J. , Gilmore I. T. , Coltart D. J. , Thompson R. P. H.
Published: August 2015

1. The hepatic extraction ratios of chenodeoxycholic acid and ursodeoxycholic acid have been measured in 12 patients without, and 20 patients with, liver disease.

2. Ten of the patients without liver disease were studied during cardiac catheterization, with a continuous infusion technique. Two of the patients without liver disease and all those with liver disease received an intravenous bolus of [14C]chenodeoxycholic acid or [14C]ursodeoxycholic acid, during transvenous liver biopsy.

3. The extraction ratio of chenodeoxycholic acid was 0·63 ± 0·03 (mean ± sem) and of ursodeoxycholic acid 0·53 ± 0·01, in the patients without liver disease. In those with mild liver disease, extraction was slightly impaired (chenodeoxycholic acid: 0·49 ± 0·03; ursodeoxycholic acid: 0·43 ± 0·05), whereas in those with more severe liver disease it was greatly reduced (chenodeoxycholic acid: 0·16 ± 0·08; ursodeoxycholic acid: 0·07 ± 0·01).

4. The results suggest that (a) direct measurements confirm the accuracy of indirect estimates of hepatic extraction of chenodeoxycholic acid, (b) hepatic extraction of chenodeoxycholic acid is lower than that of cholic acid and glycocholic acid, but higher than that of ursodeoxycholic acid, (c) progressive impairment of the extraction ratios of these two bile acids occurs as the severity of liver disease increases, and (d) the ratios are correlated with indocyanine green extraction ratios.
Aspirin, Dipyridamole and Platelet Survival in Patients with Diabetes Mellitus
Authors: Tindall Hilary , Paton R. Colin , McNicol George P.
Published: August 2015

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day).

2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods.

3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P < 0·001) prolongation of platelet survival from 7·3 ± 0·2 (mean ± sem) days to 8·4 ± 0·1 days.

4. In group II patients, when compared with the mean placebo result of 7·2 ± 0·2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P < 0·01) longer only after high-dose-aspirin/dipyridamole (9·8 ± 0·5 days) but not after low-dose-aspirin/dipyridamole (8·3 ± 0·5 days) or aspirin alone (7·3 ± 0·3 days).

5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.
Effect of Benoxaprofen on Release of Slow-Reacting Substances from Human Lung Tissue In Vitro
Authors: Lee V. Y. , Hughes J. Margaret , Seale J. P. , Temple Diana M.
Published: August 2015

1. Macroscopically normal human lung tissue was obtained from operative specimens removed for lung cancer and challenged with antigen or calcium ionophore. The release of histamine and slow-reacting substances was measured by fluorimetric and bioassay techniques respectively.

2. Benoxaprofen, a drug with inhibitory effects on the lipoxygenase and cyclo-oxygenase pathways, caused a dose-related reduction of release of slow-reacting substances without affecting histamine release.

3. These results with human lung tissue in vitro suggest that benoxaprofen may be used to investigate the role of slow-reacting substances in experimental and clinical asthma.
Effects of Serum from Patients with Fulminant Hepatic Failure on Leucocyte Sodium Transport
Authors: Sewell R. B. , Hughes R. D. , Poston Lucilla , Williams Roger
Published: August 2015

1. Serum from patients with fulminant hepatic failure inhibits the ouabain-sensitive sodium efflux in leucocytes. A 1:100 dilution of the serum was necessary before the inhibition became undetectable.

2. Dialysates of the serum through cuprophane in vitro and polyacrylonitrile haemodialysis in vivo were inhibitory in small amounts.

3. Ultrafiltrates (<10 000 daltons) of serum were chromatographed on Sephadex G-25 and the elution profile obtained from patients with fulminant hepatic failure was both qualitatively and quantitatively different from that of normal controls. Material from peaks 3, 4, 5 and 7 in patients with fulminant hepatic failure inhibited leucocyte sodium transport.

4. The dialysate from haemodialysis with the polyacrylonitrile membrane contained most peaks, particularly peaks 4 and 5. Adsorption of serum with polymer coated charcoal in vitro largely removed peaks 5−8.
Altered Jejunal Surface pH in Coeliac Disease: Its Effect on Propranolol and Folic Acid Absorption
Authors: Kitis G. , Lucas M. L. , Bishop H. , Sargent A. , Schneider R. E. , Blair J. A. , Allan R. N.
Published: August 2015

1. Propranolol and folic acid absorption were studied separately in healthy subjects, non-coeliac patients and patients with treated and untreated coeliac disease.

2. The surface pH of jejunal biopsy samples was measured with a pH electrode.

3. When compared with values found in healthy subjects, plasma propranolol levels were elevated in coeliac disease and, in contrast, serum folic acid levels were depressed after oral administration of the drug. Jejunal surface pH was more alkaline in the coeliac groups than in the healthy and non-coeliac subjects.

4. Pharmacokinetic analysis of the plasma drug levels allowed evaluation of the rate constants associated with absorption and elimination. The absorption rate constant was decreased for folic acid in the coeliac group, but increased for propranolol. These changes correlated with variation in surface pH.

5. Although the changes in drug disposition in treated and untreated coeliac disease are the result of several factors, it is suggested that jejunal surface pH may affect the rate of absorption and therefore the plasma concentration-time profile of drugs which undergo dissociation.
Ciliary Inhibitory Effects of Asthma Patients' Sputum
Authors: Dulfano M. J. , Luk C. K. , Beckage M. , Wooten O.
Published: August 2015

1. Sputum sols, obtained from patients with chronic obstructive pulmonary diseases, were applied to frogs' isolated palates and the effect on ciliary beat frequency was examined.

2. During clinical exacerbations, a significant number of asthmatic patients produced a distinct, slurry type of sputum, which induced ciliostasis. This ciliary inhibition largely disappeared with clinical improvement, at which time there was also a change of the type of sputum from slurry to mucoid.

3. Samples obtained from normal volunteers and from the great majority of the patients, excluding those with asthma, had no effect on ciliary beating.
Vitamin D from Skin: Contribution to Vitamin D Status Compared with Oral Vitamin D in Normal and Anticonvulsant-Treated Subjects
Authors: Davie M. W. J. , Lawson D. E. M. , Emberson C. , Barnes J. L. C. , Roberts G. E. , Barnes N. D.
Published: August 2015

1. The plasma 25-hydroxycholecalciferol [25-(OH)D3] response to measured u.v. irradiation applied thrice weekly for 10 weeks was investigated in normal and in anticonvulsant-treated subjects.

2. Levels of plasma 25-(OH)D3 achieved after u.v. irradiation were similar in both normal and anticonvulsant-treated subjects, suggesting that hepatic microsomal enzyme induction does not lead to low plasma 25-(OH)D3 concentrations.

3. Cholecalciferol was present in plasma of normal subjects in a very low concentrations (< 5·0 nmol/l) and did not increase until plasma 25-(OH)D3 levels exceeded 62·5 nmol/1.

4. Cholecalciferol occurred in significant concentrations in plasma during whole body u.v. irradiation or during oral dosage of 62·5 nmol (1000 i.u) or more daily.

5. Plasma 25-(OH)D3 concentrations reached a steady state after 5–6 weeks of u.v. irradiation or of oral intake within the usual intake range.

6. Cholecalciferol synthesis in skin calculated from the steady-state equation was 0·0015 ± 0·0008 nmol/mJ.

7. Cholecalciferol synthesis in skin was also calculated from the oral dosage required to yield the same plasma 25-(OH)D3 concentration as u.v. irradiation and was 0.0024 ± 0.0018 nmol/mJ.

8. Rates of cholecalciferol synthesis calculated from these data suggest that many of the population of England receive insufficient u.v. irradiation to maintain vitamin D status throughout the year.
Muscle Protein Synthesis Measured by Stable Isotope Techniques in Man: The Effects of Feeding and Fasting
Authors: Rennie M. J. , Edwards R. H. T. , Halliday D. , Matthews D. E. , Wolman S. L. , Millward D. J.
Published: August 2015

1. Measurements have been made of whole-body and skeletal muscle protein synthesis in fed and fasted adults with l-[1-13C]leucine.

2. The marked increase in whole-body synthesis on feeding largely reflects the changes in protein synthesis in muscle, which doubles on feeding, compared with a 40% increase in that of the rest of the body.

3. Skeletal muscle in fed man contributes more than half to total protein synthesis occurring in the whole body.
The Antidiuretic Effect of Chronic Hydrochlorothiazide Treatment in Rats with Diabetes Insipidus: Renal Mechanisms
Authors: Shirley D. G. , Walter S. J. , Laycock J. F.
Published: August 2015

1. Brattleboro rats with hereditary diabetes insipidus were maintained in metabolism cages for 12–14 days. During the final 5–7 days hydrochlorothiazide was added to the food of half the animals, resulting in a sustained antidiuresis. At the end of this time all rats were anaesthetized and their renal function was investigated.

2. Water, sodium and potassium excretion rates during anaesthesia were similar to their respective values during the final period in metabolism cages.

3. Total glomerular filtration rate and superficial nephron filtration rate were similar in untreated and thiazide-treated animals. Fractional fluid reabsorption in proximal convoluted tubules, as measured by tubular fluid/plasma inulin concentration ratios in late surface convolutions, was moderately increased in the thiazide-treated rats, and was associated with a small reduction in the volume of fluid delivered to more distal nephron segments.

4. The osmolality of renal papillary interstitial fluid from thiazide-treated rats was considerably greater than that from untreated animals. There was also a small increase in papillary fluid sodium concentration.

5. It is concluded that the mechanism of the sustained antidiuresis during chronic hydrochlorothiazide administration in diabetes insipidus differs from that of the acute response. The changes in proximal tubular function during chronic thiazide treatment only partially account for the reduction in urine volume; it seems probable that the raised papillary osmolality, by enhancing water reabsorption at sites beyond the proximal tubule, makes a greater contribution to the antidiuresis.
Beneficial Effect of Low Phosphorus Diet in Uraemic Rats: A Reappraisal
Authors: Laouari Denise , Kleinknecht Claire , Cournot-Witmer Giulia , Habib Renée , Mounier Françoise , Broyer Michel
Published: August 2015

1. Diets deficient in phosphorus have been shown to preserve the renal function of uraemic rats, but the role of concomitant alterations in the intake of other nutrients caused by such diets was not elucidated.

2. Five groups of uraemic rats were compared. Three (A, B, C) received (ad libitum) diets deficient (0·03%), low (0·2%) or normal (0·5%) in P. Two groups (D, E) received restricted amounts of 0·2% and 0·5% P diets by pair-feeding with group A rats.

3. Phosphorus deficient diet resulted in marked anorexia, growth arrest, low P and high calcium plasma levels and severe rickets, but renal function became stabilized. Groups B and C had both higher total food intake and weight gain but a significantly higher mortality rate. After 36 weeks, mortality was 90% in these groups, and was 19%, 28% and 44% in groups A, D and E rats respectively, despite a higher P consumption in group E than in group B rats.

4. Normal P diet was associated with severe renal calcium deposits and high calcium heart content, which were related to the degree of hyperparathyroidism evaluated by bone histology.

5. Preservation of renal function was mainly mediated by reduction in some other components of the diet and not by P restriction itself. Normal P diet with restricted dietary allotments had little adverse effect on survival, and its influence on renal histology is not easy to explain.

6. Restriction in P sufficient to cause moderate hypophosphataemia, disappearance of phosphaturia and to prevent hyperparathyroidism without causing anorexia and other severe side effects, had little or no beneficial effect on renal deterioration.
The Responses to Water Deprivation in Lithium-Treated Patients with and without Polyuria
Authors: Morgan D. B. , Penney M. D. , Hullin R. P. , Thomas T. H. , Srinivasan D. P.
Published: August 2015

1. Urine osmolality and plasma and urine arginine vasopressin (AVP) were measured before, during and at the end of 23 h of water deprivation in four groups of subjects. There were eight non-polyuric manic-depressive patients taking lithium (the lithium group), seven manic-depressive patients taking other psychotropic drugs but not lithium (the other drug group), seven healthy subjects (the control group) and three lithium-treated patients with polyuria (the polyuric lithium group).

2. The lithium group had a resistance to the effect of AVP on the renal tubule with a fivefold increase in AVP excretion at a given urine osmolality. However, their water homoeostasis was intact as they lost no more weight during water deprivation than did the control group.

3. The relationship beween urine osmolality and AVP excretion has been defined from these results and the effect of lithium treatment on it has been characterized. The results suggest that lithium competitively inhibits the effect of AVP on the renal concentrating mechanism but does not decrease the ‘theoretical’ maximum urine osmolality.

4. The other drug group had a high basal urine flow which was due to a primary increase in water intake. The responsiveness of the renal concentrating mechanism to AVP was the same in this group as in the control group.

5. The polyuric lithium group had the highest basal urine flow and lost the greatest amount of weight during water deprivation. Neither urine osmolality nor AVP excretion was at a maximum in the basal state, as both increased during water deprivation. These relationships between urine osmolality and AVP excretion indicated a much greater resistance to AVP than in the other lithium-treated patients.

6. We suggest that these patients are polyuric as they become thirsty and drink before their AVP secretion increases to levels high enough to overcome the resistance to AVP. The results suggest, however, that in the basal state their water intake may be more than the minimum determined by the resistance to AVP.
Characterization of Renal Prostaglandin E Responsiveness in Decompensated Cirrhosis: Implications for Renal Sodium Handling
Authors: Epstein Murray , Lifschitz Meyer , Ramachandran M. , Rappaport Kenneth
Published: August 2015

1. It has been suggested that endogenous renal prostaglandin E (PGE) constitutes a determinant of renal haemodynamics and renal sodium handling in patients with cirrhosis. We have accordingly assessed the effects of augmenting endogenous prostaglandins on renal function. We utilized water immersion to the neck since previous studies demonstrated that the redistribution of blood volume and concomitant central hypervolaemia thus induced produces a prompt and marked augmentation of PGE excretion in normal man.

2. Thirteen cirrhotic patients were studied twice while in balance on a daily 10 mmol of sodium/100 mmol of potassium diet during control and during water immersion. Urinary PGE was determined hourly for 6 h.

3. Cirrhotic patients manifested a wide continuum of responses characterized by either a sluggish or barely discernible natriuretic response (n = 5) or an appropriate natriuretic response (n = 8).

4. Water immersion to the neck resulted in a highly significant increase in mean UPGEV, which was threefold that manifested by normal subjects studied under identical conditions. Furthermore, cumulative sodium excretion during immersion correlated with PGE excretion (P < 0·05).

5. These findings, together with the results of studies utilizing prostaglandin synthase inhibitors, are consistent with the postulate that renal PGE may play a role in the alterations of renal function in decompensated cirrhosis.
Role of Enhanced Sympathetic Nervous System Activity and Reduced Na+,K+-Dependent Adenosine Triphosphatase Activity in Maintenance of Elevated Blood Pressure in Obesity: Effects of Weight Loss
Authors: Sowers J. R. , Whitfield L. A. , Beck F. W. J. , Catania R. A. , Tuck M. L. , Dornfeld L. , Maxwell M.
Published: August 2015

1. To investigate factors regulating blood pressure in obesity we have compared Na+ transport mechanisms and plasma noradrenaline (NA) responses to upright posture and isometric hand grip exercise in obese patients with transport mechanisms and NA responses in age, sex and race matched non-obese subjects. In the obese subjects we examined the effects of caloric restriction and weight reduction over a 12 week period on intracellular erythrocyte cation concentrations, Na+,K+-dependent ATPase activity and 86Rb uptake as well as responses of NA, plasma renin activity (PRA), aldosterone and mean arterial pressure to posture and isometric exercise.

2. Obese patients had greater (P < 0.05) basal supine plasma NA as well as enhanced NA responses to upright posture and exercise. Supine plasma NA as well as NA responses were reduced (P < 0.05) after 4 weeks caloric restriction and PRA and aldosterone responses were decreased (P < 0.05) after 8 weeks caloric restriction. Plasma NA at the onset of the diet correlated (r = 0.68, P < 0.01) with blood pressure, and decrements in NA and blood pressure were also related (r = 0.60, P < 0.01). Reductions in supine PRA and supine plasma NA during wieght loss were correlated (r = 0.55, P < 0.05) and the reduction in PRA may therefore be secondary to a decrease in sympathetic nervous system activity.

3. The intracellular Na+/K+ ratio in erythrocytes was greater in the obese patients than in non-obese controls whereas erythrocyte Na+,K+-ATPase activity and 86Rb uptake in obese patients was reduced (P < 0.01). There were significant negative correlations between Na+,K+-ATPase activity and 86Rb uptake and the degree of obesity. Although Na+,K+-ATPase and 86Rb increased and intracellular Na+ decreased during the 12 weeks of weight loss, they remained altered compared with values in non-obese subjects.
Riboflavin Analogues: A Novel Class of Antihypertensive Drugs
Authors: Trachewsky D. , Kem D. C.
Published: August 2015

1. Riboflavin analogues were tested in three hypertensive rat models: the DOCA-salt hypertensive rat, spontaneously hypertensive rats (SHR) and Dahl S rats.

2. When 1.6 mg of 7,8-dimethyl-10-formyl-methylisoalloxazine (FMI) or 7,8-dimethyl-10-(2′-hydroxyethyl)isoalloxazine (HEI) was administered with 3.0 mg of DOCA twice weekly for 9 weeks, the systolic blood pressure (SBP) of the unanaesthetized rats rose to only 136 ± 5 mmHg compared with 165 ± 5 mmHg during DOCA treatment alone. The analogues blunted the retention of iliopsoas muscle Na+ and water due to DOCA.

3. In subsequent studies, the more potent riboflavin analogue 7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine (CBI) was employed. Administration of 0.5 mg of CBI/100 g body wt. twice weekly for 7 weeks lowered the SBP of the unanaesthetized SHR from 188 ± 7 mmHg to 148 ± 2 mmHg. The rats tolerated the medication well. CBI was more effective than hydrochlorothiazide, which at 2.2 mg/100 g body wt. daily only lowered the SBP to 167 ± 5 mmHg. The combined administration of CBI and hydrochlorothiazide produced an additive effect in that the SBP was reduced to 126 ± 4 mmHg.

4. CBI treatment resulted in a 36% and 11% decrease in the iliopsoas muscle Na+ concentration and water content respectively, suggesting that the untreated SHR is retaining Na+. The hydrochlorothiazide-treated SHR exhibited elevated levels of serum aldosterone. There was a profound suppressive effect of CBI on the secondary hyperaldosteronism generated by hydrochlorothiazide which was also reflected in the iliopsoas muscle K+ concentration.

5. In contrast to the SHR, the administration to the Dahl S rats of CBI for 8 weeks at 0.5 mg/100 g body wt. twice weekly reduced neither their SBP nor their iliopsoas muscle Na+ and water contents.

6. These results are consistent with our hypothesis that the antihypertensive actions of the riboflavin analogues are closely associated with their ability to modify the effects of mineralocorticoids on Na+ balance. These data suggest that riboflavin analogues also decrease aldosterone production and may function as dual-mechanism diuretic agents with K+ sparing properties and thus act as a novel class of antihypertensive drugs.
Acute Reduction in Inactive Renin after Stimulation of Active Renin by Converting Enzyme Inhibition (CEI) in Man
Authors: Hsueh W. A. , Goldstone R. , Carlson E. J. , Horton R.
Published: August 2015

1. Administration of a single dose of captopril, 50 mg, to normal man (n = 7) on a low salt intake induced a 12.5 ± 0.9-fold rise in active renin. The rise in active renin was associated with a reciprocal decrease in circulating inactive renin to 10% or less of control levels.

2. Repeated administration of captopril (50 mg p.o. q 6 h × 3 days) to normal man resulted in increases in both active and inactive renin concentration in plasma.

3. When a single dose of captopril was administered to three patients with hyporeninaemic hypoaldosteronism, no changes in their circulating levels of active or inactive renin occurred.

4. These observations suggest that renal conversion of inactive to active renin may be important in active renin production.
Reversible Renal Nerve Denervation in the Cat: Effects on Haemodynamic and Excretory Functions of the Ipsilateral and Contralateral Kidneys
Authors: Golin R. , Stella A. , Zanchetti A.
Published: August 2015

1. In anaesthetized cats, reversible nenal nerve denervation (cooling of the renal nerves on one side at 4°C for 16 min) was performed and its effects on haemodynamic and excretory functions of the ipsilateral and the contralateral kidneys were studied.

2. Renal nerve cooling did not cause any change in arterial pressure. Slight increase in blood flow, no change in glomerular filtration rate and a large increase in water and sodium excretion occurred in the ipsilateral kidney; simultaneously, no change in blood flow, a slight and transient decrease in glomerular filtration rate, and a significant decrease in diuresis and natriuresis were observed in the contralateral kidney.

3. Ipsilateral and contralateral renal changes were equally evident in the early (minutes 0 to 8) and late phases (minutes 8 to 16) of the cooling period.

4. When renal nerve cooling was repeated after surgical denervation of the contralateral kidney all contralateral effects were abolished.
Interaction of the Sympathetic Nervous System with Vasopressin and Renin in the Maintenance of Blood Pressure in Rats
Authors: Hatzinikolaou Peter , Gavras Irene , North William G. , Brunner Hans R. , Gavras Haralambos
Published: August 2015

1. Anephric and intact rats were submitted sequentially to catecholamine depletion (‘chemical sympathectomy’) vasopressin inhibition and angiotensin blockade whilst blood pressure and plasma levels of each hormone were monitored.

2. Depletion of catecholamines to 15–25% of baseline levels was associated with significant fall of blood pressure. A close correlation existed between these variables.

3. Chemical sympathectomy caused stimulation of plasma vasopressin, which reached excessively high levels in anephric animals. These were inversely correlated with the levels of depleted catecholamines.

4. Vasopressin inhibition after chemical sympathectomy caused profound and lasting hypotension in anephric rats but only a transient small fall in blood pressure in intact rats. Angiotensin blockade after chemical sympathectomy in intact rats caused a transient small fall in blood pressure; subsequent vasopressin inhibition in these rats caused profound lasting hypotension.

5. It is concluded that resting blood pressure is mainly sustained by the sympathetic nervous system, whereas renin and vasopressin are important back-up mechanisms to maintain compromised blood pressure.
Changes in Blood Pressure, Body Fluids, Circulating Angiotensin II and Aldosterone, with Improved Diabetic Control
Authors: O'hare J. A. , Ferriss J. B. , Twomey B. M. , Gonggrijp H. , O'sullivan D. J.
Published: August 2015

1. We studied 12 normotensive non-ketotic diabetic patients during poor metabolic control, with sustained hyperglycaemia, and again, after an interval of 3 weeks, when metabolic control was improved. On each occasion we measured blood pressure, total exchangeable sodium, plasma volume, transcapillary escape rate of albumin, and plasma concentrations of angiotensin II and aldosterone.

2. With improved diabetic control there was a small but significant fall in arterial pressure. Total exchangeable sodium was normal when control was poor but rose significantly to above normal with improved control.

3. Plasma volume also rose significantly with improved control, and the transcapillary escape rate of albumin fell and the intravascular mass of albumin rose.

4. Plasma angiotensin II and aldosterone concentrations were significantly above normal during poor metabolic control, but fell to normal with improved control.

5. These findings indicate a resetting of the relationship between blood pressure and exchangeable sodium when diabetic control improves. The association between exchangeable sodium and concentrations of angiotensin II and aldosterone also appears altered in diabetic patients. These changes associated with varying metabolic control must be considered when studying cardiovascular disease in diabetic patients.
Pain and Fatigue after Concentric and Eccentric Muscle Contractions
Authors: Newham D. J. , Mills K. R. , Quigley B. M. , Edwards R. H. T.
Published: August 2015

1. Normal subjects performed a step test in which the quadriceps of one leg contracted concentrically while the contralateral muscle contracted eccentrically.

2. Maximal voluntary force and the force:frequency relationship were altered bilaterally as a result of the exercise, the changes being greater in the muscle which had contracted eccentrically. Recovery occurred over 24 h.

3. Electromyographic studies using three sites on each muscle showed an increase in electrical activation during the exercise only in the muscle which was contracting eccentrically. Recovery followed a time course similar to that of the contractile properties.

4. Pain and tenderness developed only in the muscle which had contracted eccentrically. Pain was first noted approximately 8 h after exercise and was maximal at approximately 48 h after exercise, at which time force generation and electrical activation had returned to pre-exercise values.

5. Eccentric contractions cause more profound changes in some aspects of muscle function than concentric contractions. These changes cannot be explained in simple metabolic terms, and it is suggested that they are the result of mechanical trauma caused by the high tension generated in relatively few active fibres during eccentric contractions.
Release of a 6-Oxoprostaglandin E1-like Substance from Human Platelets
Authors: Lofts F. J. , Moore P. K.
Published: August 2015

1. Human platelet-rich plasma incubated at 37°C generates an antiaggregatory prostaglandin which is spasmogenic on gastrointestinal smooth muscle.

2. Platelet-rich plasma from female donors generated more biological activity and was more sensitive to the anti-aggregatory activity of added prostaglandin I2 (PGI2) compared with that from age-matched male controls.

3. After thin-layer chromatography of extracted platelet-rich plasma, biological activity was detected in a zone which co-chromatographed with 6-oxoprostaglandin E1.

4. Neither extracted platelet-rich plasma nor authentic 6-oxoprostaglandin E1 were inactivated following incubation with purified 15-hydroxyprostaglandin dehydrogenase.

5. The relevance of these findings for regulating platelet reactivity is discussed.
The Influence of Different Types of ω3 Polyunsaturated Fatty Acids on Blood Lipids and Platelet Function in Healthy Volunteers
Authors: Sanders T. A. B. , Roshanai Farah
Published: August 2015

1. Five healthy subjects took a daily supplement of 20 ml of linseed oil for 2 weeks. After a break of at least 6 weeks, the same subjects took a similar amount of MaxEPA (a fish oil fraction) for 2 weeks. The linseed oil supplement provided 9.38 g of linolenic acid (18:3 ω3) and the MaxEPA supplement provided 3.03 g of eicosapentaenoic acid (20:5 ω3) and 2.93 g of docosahexaenoic acid (22:6 ω3). The effects of the supplements on plasma lipid concentrations and on the fatty acid composition of platelet phosphoglycerides were studied.

2. In a second experiment, five male subjects took 5, 10 and 20 g of MaxEPA/day in random order for 3 week periods; each experimental period was separated by a break of at least 6 weeks. These doses of MaxEPA provided 0.83, 1.67 and 3.33 g of 20:5 ω3 and 0.80, 1.61 and 3.22 g 22:6 ω3 respectively. The effects of these supplements on plasma lipid concentrations, the fatty acid composition of platelet phosphoglycerides, template bleeding time and platelet aggregation induced by collagen and the prostaglandin analogue compound U46619 were studied.

3. In the platelet lipids, the proportion of 20:5 ω3 was increased by the 20 ml linseed oil supplement but the increase was small compared with the increase brought about by even 5 g of MaxEPA/day. The proportion of arachidonic acid (20:4 ω3) was substantially decreased by the MaxEPA supplement but not by the linseed oil supplement. The ratio of 20:4 ω6/20:5 ω3 fell from 32:1 in the control periods to 11:1 with 5 g, 7:1 with 10 g and 5:1 with 20 g of MaxEPA/day. The MaxEPA supplement also led to increases in the proportions of 22:5 ω3 and 22:6 ω3 and decreases in those of 20:3 ω6 and 22:4 ω6.

4. Bleeding times tended to be prolonged with the MaxEPA supplement but did not follow any dose-dependent trend. Platelet aggregation induced by both collagen and compound U46619 was not inhibited in vitro.

5. Plasma triglyceride concentrations were lowered by the MaxEPA supplement but not by the linseed oil supplement. Plasma triglyceride concentrations were substantially lowered by 10 g and 20 g of MaxEPA/day. Total plasma cholesterol concentrations were slightly lowered and HDL cholesterol concentrations were slightly increased by 20 g of MaxEPA/day. No other significant differences were noted.
Development of Hypertension in Renal Disease
Authors: Brod J. , Bahlmann J. , Cachovan M. , Pretschner P.
Published: August 2015

1. Central and peripheral haemodynamics, circulating blood volume and plasma renin activity (PRA) were investigated under resting conditions in 97 patients with chronic nonuraemic renal parenchymatous disease and without anaemia. For comparison a group of 17 healthy subjects was used.

2. An initial abnormality appeared in 12 out of 32 normotensive renal patients. It consisted of a markedly increased circulating blood volume, raised cardiac output, low total peripheral and forearm vascular resistance, hyperfusion of the forearm and increased venous distensibility. PRA was slightly (but insignificantly) higher in these hyperkinetic subjects with relaxed peripheral vessels than in the other 20 normotensive renal patients who did not differ haemodynamically from the control subjects.

3. Fifteen out of 47 renal patients with a mild or moderate hypertension (stage I–II WHO) were hyperkinetic. However, in these there was no compensatory vasodilatation in response to the high cardiac output: forearm blood flow was normal and venous distensibility below that of the control subjects. Blood volume was normal. Plasma renin activity (PRA) was the same as in the normotensive renal patients.

4. The difference between stage I–II and stage III was due entirely to a rise in total peripheral vascular resistance.

5. A re-examination of these patients 2-8 years after they had been first studied revealed that 11 out of the 12 originally hyperkinetic normotensive renal patients were now hypertensive compared with only one-half of the originally normokinetic normotensive renal subjects.

6. It is concluded that an inability of the diseased kidney to control volume homoeostasis leads to hypervolaemia, which raises cardiac output in the renal patients whilst still normotensive. As long as the arterioles adjust to the high output and the capacitance system to the high volume, blood pressure remains normal. When this adaptation of the periphery ceases, blood pressure rises, normalizing (possibly through a pressure diuresis) blood volume. PRA does not correlate with any of these changes and only in advanced renal hypertension may its rise partly contribute to the maintenance of high blood pressure without being its cause.
Nocturnal Hypoxaemia in Chronic Obstructive Pulmonary Disease
Authors: Stradling J. R. , Lane D. J.
Published: August 2015

1. Day and night arterial oxygen saturation (Sao2) has been measured in forty-one patients with chronic obstructive pulmonary disease (COPD), mean FEV1 0.84 (range 0.4-1.4) litres, and with a range of daytime Sao2 values of 67-95%.

2. The mean and biggest falls in Sao2 at night were much greater in the patients with lower daytime saturations. However, when falls in arterial oxygen tension (Pao2) were estimated from the decreases in Sao2, there was no correlation between the estimated biggest fall in Pao2 and daytime Sao2 and only a weak correlation between estimated mean fall in Pao2 and daytime Sao2.

3. Measurement of ventilation in four hypoxaemic patients with COPD (range 60-90% Sao2) by respiratory inductance plethysmography showed that nocturnal hypoxaemic dips were accompanied by diminished ventilation, which was not always shown by nasal thermistors.

4. Because nocturnal hypoxaemic dips are transient the ideal alveolar-arterial oxygen difference, which assumes a constant respiratory exchange ratio, cannot be used to assess the mechanism of hypoxaemia.

5. Erythrocyte mass was strongly correlated with daytime Sao2 but this correlation was not significantly improved by including nocturnal hypoxaemia in the regression.

6. The results suggest that greater falls in Sao2 at night are related to lower initial Sao2 values and that the cause-5-be a reduction in ventilation.
Adenosine Diphosphate-Degrading Activity in Placenta
Authors: Barradas M. , Khokher M. , Hutton R. , Craft I. L. , Dandona P.
Published: August 2015

1. The degradation of ADP by the placenta and umbilical artery was investigated.

2. Supernatants from incubations of finely chopped placental and umbilical arterial tissue were incubated with [14C]ADP for various durations from 0 to 30 min.

3. Products of ADP degradation were separated by thin-layer chromatography and radioactivity incorporated into each product was measured.

4. Placental supernatants induced a more rapid degradation of ADP than the umbilical artery supernatants. The main product of ADP degradation by placental supernatants at 30 min was adenosine, whereas that of umbilical artery was AMP.

5. This conversion by placenta of ADP, a potent platelet aggregator and vasoconstrictor, into adenosine, a potent platelet anti-aggregator and vasodilator,-5-be important in the maintenance of perfusion of the foetoplacental unit.
Biochemical Mechanisms of Hepatic Encephalopathy
Authors: Crossley I. R. , Wardle E. N. , Williams Roger
Published: August 2015

Although there are similarities between the encephalopathy of acute hepatic failure and that due to cirrhosis, it is clear that some of the biochemical abnormalities arise in different ways and the relative roles of the various factors contributing to the production of encephalopathy may differ. in addition, in fulminant hepatic failure, changes in the permeability of the blood—brain barrier may enhance the effects of biochemical abnormalities and this may also be important in the genesis of cerebral oedema, which commonly complicates this form of encephalopathy. When considering encephalopathy complicating cirrhosis, it is important to recognize that the latter can be precipitated by a variety of insults each of which may lead to encephalopathy. Most research has concentrated on the accumulation in the blood of ‘toxic’ substances normally metabolized by the liver. Although no single toxin has yet been identified which alone can be responsible for hepatic encephalopathy, excess ammonia, mercaptans, fatty acids and an abnormal plasma amino acid profile have been incriminated in its pathogenesis. Irrespective of the ‘toxin’, three main pathogenetic mechanisms have been proposed to account for its action: (a) disturbed brain energy metabolism, (b) deranged neurotransmitter balance, (c) direct effects on neuronal membranes. These mechanisms are not regarded as mutually exclusive but have their final common effect of interrupting normal neurotransmission.
The Epidemiology of Plasma Renin
Authors: Meade T. W. , Imeson J. D. , Gordon D. , Peart W. S.
Published: August 2015

1. The epidemiological characteristics of plasma renin activity (PRA) were established in 1999 members of occupational groups in North and West London.

2. The main finding was that PRA was inversely associated with systolic blood pressure in men, the percentage fall in PRA (on a log scale) being 8.4% for each increase of one standard deviation in systolic blood pressure. There was a less obvious inverse relationship in women.

3. However, blood pressure accounted for less than 1% of the variance in PRA.

4. Mean PRA in both smokers and ex-smokers was about 20% higher than in non-smokers.

5. PRA fell with increasing age, was lower in women than in men and considerably lower in blacks (of either sex) than whites.

6. PRA was lower in the first quarter of the menstrual cycle than in the rest of the cycle.

7. Haemoglobin, blood cholesterol, leucocyte count and Factor VIII were positively correlated with PRA.

8. PRA was lower in men with diagnosed hypertension than in those without; there was no significant difference in the women.

9. PRA was lower in those who had had myocardial infarcts in the past than in those who had not.

10. The data as a whole suggest that it may be low, not high, levels of PRA which are associated with increased risks of cardiovascular disease in which hypertension is a predisposing factor.

11. The explanation may be a homoeostatic fall in PRA in response to a rise in blood pressure rather than a major causal role for PRA in the pathogenesis of essential hypertension and target-organ damage.
Purine Transport and Metabolism in Man: The Effect of Exercise on Concentrations of Purine Bases, Nucleosides and Nucleotides in Plasma, Urine, Leucocytes and Erythrocytes
Authors: Harkness R. A. , Simmonds R. J. , Coade S. B.
Published: August 2015

1. After decreasing muscle ATP by a 2 min period of intense exercise, we have studied purine metabolism by using high-pressure liquid chromatography.

2. A major increase in hypoxanthine concentration in plasma and urine was found with increases in xanthine and, in plasma, inosine. Erythrocyte hypoxanthine rose with the level in plasma, but there was no corresponding rise in IMP, the first intracellular metabolite of hypoxanthine. No rises in uridine or urate were found in plasma.

3. Plasma adenosine did not rise and fall significantly after exercise, but a small rise and fall in adenine nucleotide concentrations in plasma was found.

4. Running, swimming and games, which tended to be at the weekend, were associated with a rise in hypoxanthine and xanthine excretion; exercise was probably the cause of the higher excretion during the day than at night. Such activities do not produce changes in concentrations of ATP in muscle, although turnover must rise.

5. The results are consistent with widespread purine exchange between tissues and a ‘circulating hypoxanthine pool’.
Mucosal Enzyme Activities, with Special Reference to Enzymes Implicated in Bicarbonate Secretion, in the Duodenum of Rats with Cysteamine-Induced Ulcers
Authors: Stiel Danny , Murray Denver J. , Peters Timothy J.
Published: August 2015

1. Duodenal mucosa was collected from control rats and from animals which had received cysteamine, cysteamine plus cimetidine or pentagastrin. Animals which received cysteamine with or without cimetidine developed acute duodenal ulcers. Cysteamine treatment resulted in gastric acid hypersecretion, which was largely abolished by concurrent cimetidine administration.

2. Activities of enzymes implicated in bicarbonate secretion, HCO−3-activated ATPase, carbonic anhydrase and Na+ + K+-activated ATPase, were measured in the duodenal mucosa of control rats and animals 24 h after subcutaneous administration of cysteamine. Assays of these enzymes in duodenal mucosal homogenates from animals with cysteamine-induced ulcers showed significant decreases in HCO−3-activated ATPase and carbonic anhydrase activities compared with controls.

3. Alkaline phosphatase activity also fell significantly in the cysteamine-treated animals, and possibly reflects the HCO−3-activated ATPase activity in the brush-border membrane. in contrast, activities of other marker enzymes from the brush-border membrane and from several intracellular organelles were unchanged, indicating an absence of gross organelle pathology in this experimental model.

4. Similar changes in enzyme activity were not caused by treatment with pentagastrin. Administration of cimetidine with the cysteamine did not protect the animals against ulceration, and the activity of HCO−3-activated ATPase was persistently decreased. However, the carbonic anhydrase activity was unaltered in this latter group, compared with controls.

5. These findings suggest that in cysteamine-induced duodenal ulceration both gastric acid hypersecretion and impaired duodenal resistance occurs. It is suggested that decreased activities of key enzymes implicated in HCO−3 secretion may reflect the biochemical basis for the decreased mucosal resistance.
The Influence of a High Dietary Intake of Purine-Rich Animal Protein on Urinary Urate Excretion and Supersaturation in Renal Stone Disease
Authors: Fellström B. , Danielson B. G. , Karlström B. , Lithell H. , Ljunghall S. , Vessby B.
Published: August 2015

1. Eight recurrent renal stone-forming patients were housed in a metabolic ward and fed on a low (LPD) and a high (HPD) animal protein diet, which were isoenergetic. Metabolic studies were made after 2 weeks on each diet.

2. There was a 90% increase in urinary urate on HPD compared with LPD, whereas serum urate did not change consistently.

3. The urinary acid excretion increased by 200%, including a 100% increase in ammonium ion excretion. A fall in urine pH by 0.9 unit was also seen.

4. The calculated ion activities of the urines revealed a profound increase in the uric acid supersaturation, from undersaturation to supersaturation, and in some cases even surpassing the formation product ratio. The ammonium urate supersaturation also increased. The sodium urate supersaturation was unchanged, despite an induced natriuresis.

5. The risk of forming uric acid or ammonium urate crystals or stones in the urine was increased on a high protein diet, whereas the risk of forming sodium urate crystals was no greater than on a low protein diet.

6. As uric acid and ammonium urate crystals under certain conditions may adsorb a macromolecular fraction of the human urine, which inhibits calcium oxalate crystal growth, it is proposed that this mechanism, along with a decrease in urine pH, may also interfere with the inhibitory activity of calcium oxalate crystal growth and aggregation.
Changes in the Number and Activity of Sodium Pumps in Erythrocytes from Patients with Hyperthyroidism
Authors: Rubython E. Jill , Cumberbatch M. , Morgan D. B.
Published: August 2015

1. The sodium content, the rate and rate constant of ouabain-sensitive sodium efflux and the number of sodium pumps (indicated by the ouabain-binding capacity) were measured in erythrocytes from patients with hyperthyroidism and compared with values obtained in euthyroid patients and healthy control subjects. Erythrocyte zinc content was measured as a simple estimate of the content of carbonic anhydrase.

2. In the hyperthyroid patients, erythrocyte sodium content was increased, whereas the rate and rate constant of ouabain-sensitive sodium efflux, the ouabain-binding capacity and erythrocyte zinc content were all decreased.

3. The sodium pumps in hyperthyroidism had the same affinity for ouabain and the same rate constant per pump as those in healthy controls.

4. The decrease in the efflux rate constant could be entirely accounted for by the decrease in the number of sodium pumps.

5. Although the sodium efflux was decreased in the hyperthyroid patients, the change was less than expected for the decrease in the efflux rate constant. This suggests that there is an increase in the ground permeability of the erythrocyte membrane in hyperthyroidism.

6. In the hyperthyroid patients the number of sodium pumps and erythrocyte zinc content were inversely related to the plasma levels of thyroxine and tri-iodothyronine, but more closely to the latter.

7. These results suggest that the thyroid hormones may influence the erythrocyte's content of a range of proteins which happens to include the sodium pump.
α1-Antitrypsin and Reactive Systemic Amyloidosis
Authors: Maury C. P. J. , Teppo A.M. , Fröseth B. , Wegelius O.
Published: August 2015

1. Serum contains amyloid A-degrading activity. This activity is markedly reduced in patients with rheumatoid arthritis (RA) complicated by amyloidosis. α1-Antitrypsin inhibits the degradative activity. To test the hypothesis that the activity of this enzyme is regulated by α1-antitrypsin, we determined the concentrations, elastase-inhibitory activity and phenotypes of α1-antitrypsin in 24 RA patients with and in 26 RA patients without amyloidosis.

2. α1-Antitrypsin concentrations and biological activity were significantly increased in both patient groups compared with control subjects, but there was no difference between the two patient groups.

3. All patients who had developed amyloidosis were of the normal protease inhibitor (Pi) MM-phenotype.

4. We conclude that the difference in the amyloid A-degrading activity between RA patients with or without amyloidosis cannot be accounted for by differences in concentration, activity or Pi type of α1-antitrypsin.