bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the Occupancy Principle in Studies of the Metabolism of Vitamin B12 in Man
Authors: Bessent R. G. , Watson W. S. , MacDonald Caroline M. L. A. , Adams J. F.
Published: August 2015

1. The long-term clearance of radioactive vitamin B12 from serum and from whole body was measured in control subjects and patients with treated pernicious anaemia and the data were analysed by the occupancy principle to provide estimates of dietary intake, daily requirements and whole-body mass of vitamin B12.

2. In six cases the daily requirement for vitamin B12 ranged from 0·15 to 1·9 μg with an average of 1·0 μg. The whole-body vitamin B12 in four cases ranged from 780 to 1350 μg with an average of 1060 μg.

3. Estimates of the whole-body vitamin B12 on the assumption of single-pool equilibrium gave constantly changing results, which, together with discrepant half-lives for serum radioactivity and whole-body radioactivity, constitute evidence against the concept of single-pool equilibrium.
Erythrocyte Superoxide Dismutase Activity in Fanconi's Anaemia
Authors: Okahata Susumu , Kobayashi Yohnosuke , Usui Tomofusa
Published: August 2015

1. Erythrocyte superoxide dismutase activity was determined in 46 adults, 10 paediatric patients without anaemia and 11 paediatric patients with several types of anaemia. No difference was found in superoxide dismutase activity between adults and normal children.

2. The use of multiple parameters appeared to be important for the evaluation of erythrocyte superoxide dismutase activity.

3. Erythrocyte superoxide dismutase activity in three cases of typical Fanconi's anaemia was markedly depressed, when expressed either per mg of haemoglobin or per number of cells, and its aetiological significance is discussed.
Activities of Some Free-Radical Scavenging Enzymes and Glutathione Concentrations in Human and Rat Liver and their Relationship to the Pathogenesis of Tissue Damage in Iron Overload
Authors: Selden Clare , Seymour Carol A. , Peters T. J.
Published: August 2015

1. The activities and subcellular distribution of enzymes implicated in the protection of cells from free-radical mediated damage were determined in liver biopsy specimens from control and iron-overloaded patients.

2. There was a small but insignificant decrease in the activity of glutathione reductase in patients with secondary iron overload due to multiple transfusion therapy for thalassaemia major.

3. The activities of superoxide dismutase, catalase and glutathione peroxidase were similar in both patient groups.

4. Subcellular fractionation studies indicated a major cytosolic localization of these enzymes with a minor mitochondrial component. The relative proportions of the enzymes in the two locations was similar in both control and iron-overloaded patients.

5. Approximately 80% of the hepatic glutathione was present in the reduced form in both patient groups and it is concluded that although free-radical mediated damage might be implicated in the pathogenesis of tissue damage due to iron overload no significant defect in these protective mechanisms can be demonstrated.
Sialic Acid and the Microheterogeneity of Human Serum Ferritin
Authors: Cragg S. J. , Wagstaff M. , Worwood M.
Published: August 2015

1. Ferritin has been partially purified from the serum of patients with idiopathic haemochromatosis.

2. Incubation with neuraminidase of this partially purified serum ferritin eliminated much of the microheterogeneity of the protein so that only ferritin of isoelectric point approximately 5·8 was present.

3. There was no change in the total amount of ferritin present (measured immunologically) or in the percentage of ferritin binding to concanavalin A.

4. Incubation of liver, spleen or heart ferritin with neuraminidase did not change the isoelectric focusing patterns.
Urinary Conjugates of 4-Hydroxy-3-Methoxyphenylethylene Glycol Do Not Provide an Index of Brain Amine Turnover in Man
Authors: Boobis A. R. , Murray S. , Jones D. H. , Reid J. L. , Davies D. S.
Published: August 2015

1. The 24 h urinary excretion of free 4-hydroxy-3-methoxyphenylethylene glycol (HMPG), HMPG conjugated as glucuronide and HMPG conjugated as sulphate was determined in nine healthy volunteer subjects and six patients with phaeochromocytoma. In both groups of subjects most (97%) HMPG was in the conjugated form.

2. Although patients with phaeochromocytoma excreted five- to ten-fold the amounts of each of the forms of HMPG excreted by the control subjects the ratio of these different forms of HMPG to each other did not differ significantly between the groups.

3. In cerebrospinal fluid and brain about 80% of HMPG was free and of the conjugated HMPG in these two tissues most was in the glucuronide form.

4. It is concluded from these data that both HMPG sulphate and HMPG glucuronide have a substantial peripheral origin and that measurements of their urinary excretion cannot be used as an index of brain catecholamine turnover.
Rise in Plasma Alkaline Phosphatase at the Menopause
Authors: Crilly R. G. , Jones M. M. , Horsman A. , Nordin B. E. C.
Published: August 2015

1. Plasma alkaline phosphatase activity and urine hydroxyproline excretion were measured in age-matched premenopausal and postmenopausal women.

2. Both measurements were found to be significantly higher in postmenopausal women.

3. It is proposed that the rise in the plasma alkaline phosphatase, like that in the hydroxyproline excretion, may reflect the onset of bone loss that occurs after the menopause.
Renal Metabolism of Paracetamol: Studies in the Isolated Perfused Rat Kidney
Authors: Hart Sandra , Calder I. , Ross B. , Tange J.
Published: August 2015

1. The metabolism of [3H]paracetamol has been studied in the perfused rat kidney. Seventy-four per cent of filtered paracetamol was reabsorbed. Paracetamol appeared in the urine; 90%was unaltered but 10%appeared as metabolites: the glucuronide, sulphate, mercapturic acid and cysteine conjugates.

2. At concentrations of paracetamol of 1–3 mmol/l no impairment of renal physiological function was observed.

3. The presence of the mercapturic acid and cysteine conjugates in the urine demonstrates the capacity of the kidney for oxidative metabolism of paracetamol and hence the formation of potentially toxic intermediates.
Erythrocyte Catechol-O-Methyltransferase Activity and Indices of Sympathetic Activity in Man
Authors: Fitzgerald G. A. , Hamilton C. A. , Jones D. H. , Reid J. L.
Published: August 2015

1. Erythrocyte catechol-O-methyltransferase was studied in a population sample of 147 subjects.

2. There was a wide interindividual variability of catechol-O-methyltransferase activity, which was not unimodally distributed. Catechol-O-methyltransferase activity was not influenced by blood pressure, age or sex, nor was it related to plasma noradrenaline or urinary catecholamines or metanephrines.

3. It is not likely that inactivation of noradrenaline by O-methylation at least by erythrocytes is an important mechanism determining plasma noradrenaline, let alone arterial pressure.
Plasma α2 HS-glycoprotein Concentration in Paget's Disease of Bone: its Possible Significance
Authors: Ashton B. A. , Smith R.
Published: August 2015

1. The plasma concentration of the α2HS-glycoprotein has been measured in 58 normal adults and in patients with Paget's disease of bone before (24) and during treatment (16).

2. The average plasma α2HS-glycoprotein was lower in the patients with Paget's disease than in the normal adults and was inversely related to plasma alkaline phosphatase activity (r = −0.55, n = 24, P<0.001).

3. When the patients with Paget's disease were treated with either diphosphonate or calcitonin, the plasma α2HS-glycoprotein concentration increased towards normal. In those patients treated with calcitonin, this increase was too rapid to be entirely accounted for by a cessation of bone formation.
Urine Concentration of 3-ethyl-5-hydroxy-4,5-dimethyl-Δ3-pyrrolin-2-one (‘Mauve Factor’) is Not Causally Related to Schizophrenia or to Acute Intermittent Porphyria
Authors: Gorchein A.
Published: August 2015

1. 3-Ethyl-5-hydroxy-4,5-dimethyl-Δ3-pyrrolin-2-one (HPL, ‘mauve factor’) was determined quantitatively in the urine of schizophrenic, general medical and porphyric subjects by a sensitive gas/liquid-chromatographic method using a nitrogen-specific detector.

2. A comparative evaluation with previously used methods for HPL was made and some problems of specificity are discussed.

3. The concentration of HPL in early morning and spot samples of urine from 146 subjects with schizophrenia was not greater than that in 42 general medical patients, contrary to previous reports.

4. Of the three patients with acute intermittent porphyria, two excreted HPL. One subject, studied over a 2 year period, did so intermittently in a manner unrelated to her attacks of porphyria.

5. It is concluded that the urine content of HPL is unlikely to be causally related to schizophrenia or to the clinical manifestations of acute intermittent porphyria.
Absorption of Artificial Effusions from Synovial Joints: An Experimental Study in Rabbits
Authors: Levick J. R.
Published: August 2015

1. The absorption of fluid from the joint cavity was studied by measurement of the flow of Ringer solution or paraffin oil, from an infusion reservoir, into rabbit knee joints at constant pressures between 0 and 25 cm water.

2. Although no oil was absorbed across the synovium, oil flowed continuously into the joint cavity at constant intra-articular pressure. It was concluded that the joint capsule expanded with time (delayed compliance, viscous creep). Viscous creep of the capsule could explain, in part, the poor correlation observed clinically between effusion volume and pressure.

3. The rate of absorption of Ringer solution by the synovium was calculated by subtraction of the volumetric rate of creep from the volume inflow of Ringer solution. The absorption rate increased as a linear function of intra-articular pressure up to 9 cm water but as a much steeper (six-times) function of pressure above 9 cm water (the ‘breaking point’ phenomenon). Since pressure increases upon joint flexion, flexion may minimize synovial fluid volume by promoting fluid absorption.

4. The absorption rate was unaffected by ligation of the lymphatic drainage of the joint, but was reduced to between 79 and 85% by intermittent interruption of blood flow to the joint. Fluid accumulated in connective tissue outside the synovium.

5. It is concluded that these artificial effusions are absorbed partly into the synovial micro-circulation, in accordance with Starling's hypothesis of fluid exchange, and partly into compliant connective tissue outside the joint capsule. The increased sensitivity of flow to pressure above 9 cm water is explained by a progressive reduction in synovial resistance to flow, and implies facilitation of absorption of joint effusions of pressures over 9 cm water.
Interaction of Conventional and Antikaliuretic Diuretics with the Renal Prostaglandin System
Authors: Kramer H. J. , Düsing R. , Stinnesbeck B. , Prior W. , Bäcker Angela , Eden Jutta , Kipnowski J. , Glänzer K. , Krück F.
Published: August 2015

1. The effects of frusemide, hydrochlorothiazide and spironolactone on the renal prostaglandin system, and the interference with their diuretic and natriuretic effects by inhibition of prostaglandin synthase, were investigated in healthy human subjects.

2. Urinary excretion of prostaglandin E2 was increased by the administration of frusemide (P < 0.05), hydrochlorothiazide and particularly by spironolactone, the least potent natriuretic agent (P < 0.05). A qualitatively similar but statistically insignificant rise in excretion of prostaglandin F2α was observed with hydrochlorothiazide.

3. The rise in urinary excretion of sodium after frusemide and hydrochlorothiazide was significantly reduced by indomethacin, which also abolished the potassium-sparing effect of spironolactone and partially suppressed the diuretic-induced rise in plasma renin activity.

4. Indomethacin had no significant effect on urinary osmolality or free water absorption in the presence of frusemide or hydrochlorothiazide, but markedly enhanced urinary osmolality (P < 0.05) and free water absorption (P < 0.05) in the presence of spironolactone.

5. Increased renal prostaglandin activity after frusemide, hydrochlorothiazide and spironolactone may contribute to their natriuretic action which, in addition to the antikaliuretic effect of spironolactone, may be partially abolished by the presence of non-steroidal antiphlogistic agents.
Immunoreactive Substance P in Human Plasma: Response to Changes in Posture and Sodium Balance
Authors: Kramer H. J. , Düsing R. , Stelkens H. , Heinrich R. , Kipnowski J. , Glänzer K.
Published: August 2015

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake.

2. In 14 subjects plasma immunoreactive substance P was 168 ± 31 pmol/l when subjects were supine and 401 ± 51 pmol/l (P < 0.001) when they were ambulant.

3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 ± 39 pmol/l at 14.00 hours and a lowest value of 76 ± 9 pmol/l at 02.00 hours.

4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 ± 41 pmol/l, on a sodium intake ad lib., to 244 ± 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 ± 20 pmol/l (P < 0.001) by day 4 of high sodium intake (350 mmol/day).

5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.
Transvascular Albumin Flux and the Interstitial Water Volume in Experimental Pulmonary Oedema in Dogs
Authors: Prichard J. S. , Rajagopalan B. , Lee G. de J.
Published: August 2015

1. External counting of radioactivity over the lung has been used to measure the size of the interstitial compartment and transvascular albumin fluxes under normal and pathological conditions in the lungs of open-chested ventilated dogs.

2. When pulmonary hydrostatic pressure and plasma oncotic pressure were altered by transfusion of blood or sodium chloride solution (154 mmol/l), the transvascular transfer coefficient for serum albumin increased in relation to the increase in net intravascular force (hydrostatic pressure — oncotic pressure).

3. After alloxan, Pseudomonas bacteraemia or in the period after correction of experimentally induced haemorrhagic hypotension, the transvascular transfer coefficient for serum albumin increased to an extent greater than could be accounted for by any change in net intravascular force. This suggests that pulmonary capillary permeability to serum albumin alters with these procedures.

4. Alloxan administration caused a fulminant pulmonary oedema in which the size of the interstitial space, as measured by the external counting method, increased progressively.

5. Comparison of these results with direct studies carried out by others suggests that the external counting method provides a satisfactory technique for the study of pulmonary oedema; with simultaneous measurements of hydrostatic and oncotic pressure, it can be used to identify probable permeability changes in the pulmonary endothelium.
Failure to Demonstrate Renal Uptake of Labelled Platelets in Chronic Glomerulonephritis
Authors: Rigby R. J. , Driedger A. A. , Reid B. D. , Lindsay R. M. , Linton A. L. , Clark W. F.
Published: August 2015

1. Renal localization of autologous 111In-labelled platelets was studied in patients with chronic glomerulonephritis. External imaging was performed with a γ-camera fitted with a medium energy collimator and the images were collected by a computer.

2. Images of 111In-labelled platelet distribution showed that there was a marked contribution to the radioactivity within each renal silhouette from adjacent spleen or liver. It was not possible to demonstrate renal accumulation of 111In-labelled platelets.

3. The application of 111In-labelled platelets to the study of intrarenal platelet consumption in chronic glomerulonephritis is limited by the sensitivity of current techniques and the scatter from adjacent splenic and hepatic radioactivity.
Nitrous Oxide and the Cobalamins
Authors: Chanarin I.
Published: August 2015

Vitamin B12 is able to cleave the anaesthetic gas nitrous oxide and in the process is itself oxidized to an inactive form. This has provided an opportunity for exploring the effect of vitamin B12 deficiency in the experimental animal as well as in man, and hence for unravelling some of the tangled skeins of vitamin B12-folate interrelations.
Airway and Metabolic Resistance to Intravenous Salbutamol: A Study in Normal Man
Authors: Holgate S. T. , Stubbs W. A. , Wood P. J. , McCaughey E. S. , Alberti K. G. M. M. , Tattersfield A. E.
Published: August 2015

1. The airway and metabolic responses to an intravenous β2-agonist salbutamol have been investigated in normal subjects before and after chronic administration of inhaled salbutamol, 1600 μg daily for 2 weeks.

2. Before chronic inhalation of salbutamol there was a dose-dependent increase in specific airway conductance after intravenous salbutamol in cumulative doses from 25 to 300 μg.

3. Measurement of concentrations of blood glucose, lactate, pyruvate, glycerol, ketone bodies, non-esterified fatty acids, insulin, plasma cyclic AMP and cyclic GMP were made after each increment of salbutamol and all showed an increase apart from cyclic GMP.

4. After chronic inhalation of salbutamol there was a decrease in the airway, metabolic and insulin response to intravenous salbutamol. The cyclic AMP response showed little change.

5. This study confirms the development of adrenergic resistance in the airways of normal subjects after large doses of inhaled salbutamol and shows that this is associated with widespread metabolic adrenergic resistance.
The Effect of Methylprednisolone Sodium Succinate on Erythrocyte and Haemoglobin Function
Authors: Brada M. , Robinson L. A. , Bellingham A. J.
Published: August 2015

1. As it has been suggested that the beneficial effect of methylprednisolone in shock is due to its effect on erythrocyte oxygen affinity, we studied its effect on incubated erythrocytes and on haemoglobin solution.

2. Incubation of fresh whole blood anticoagulated with acid/citrate/dextrose with methylprednisolone (7 mmol/l) produced a significant decrease in oxygen affinity, which was not seen with lower concentrations of methylprednisolone. When either acid/citrate/dextrose blood stored for 10 days or fresh heparinized blood was used, no significant increase in the partial pressure of oxygen at 50% haemoglobin saturation (P50) was demonstrated even with methylprednisolone at 7 mmol/l. At the highest concentration achieved in plasma with standard therapeutic doses (56 μmol/l) there was no increase in P50 under all the conditions studied.

3. Methylprednisolone reduced the oxygen affinity of haemoglobin in solution. The reduction in oxygen affinity was less than that produced by 2,3-diphosphoglycerate and more than that of either sodium succinate or sodium chloride.

4. From the results of this study we conclude that the effect observed in whole cells is probably due to a direct effect of methylprednisolone on haemoglobin. To produce a significant decrease of oxygen affinity of whole blood in vitro requires a plasma concentration of methylprednisolone above that obtained in plasma in vivo, with the currently used therapeutic doses.
The Reproducibility of Double-Isotope Deconvolution Measurements of Intestinal Calcium Absorption
Authors: Tellez Marisol , Reeve J. , Royston J. P. , Veall N. , Wootton R.
Published: August 2015

1. Radiocalcium absorption was measured in duplicate in 10 subjects by the double-isotope method, with calcium as the oral carrier (2.5 mmol). Analysis of variance gave 95% confidence limits for a single measurement of fractional absorption and maximum absorption rate in a given individual of ±16.5% of administered dose and ±18.2% of dose/h respectively.

2. The size of these within individual variations suggests that alterations in the rate of calcium absorption-5-contribute to the week-to-week stabilization of some other controlled variable, such as plasma concentration of calcium.

3. In six of the subjects, calcium absorption was also measured with calcium loads at concentrations of 0.5, 5.0 and 20 mmol. Significant falls in fractional absorption, maximum absorption rate and mean transfer rate occurred as the load increased, together with a rise in mean transit time. Although between-individual differences at a given load were considerable, given a single-test result with a known carrier load, it is possible to predict quite accurately the results which would be obtained if a different carrier load were to be given.
N
τ-Methylhistidine Excretion and Myofibrillar Protein Breakdown in Patients Receiving Intravenous or Enteral Nutrition
Authors: Holbrook I. B. , Gross E. , Milewski P. J. , Shipley K. , Irving M. H.
Published: August 2015

1. Nτ-Methylhistidine, nitrogen and creatinine were measured in the urine of 10 volunteers on normal and meat-free diets and in 10 vegetarians, and compared with the results from the urine of eight patients with intestinal fistulae on intravenous or enteral nutrition containing no meat. The values obtained were used to calculate fractional breakdown rate of myofibrillar protein.

2. There was a significant fall in the excretion of Nτ-methylhistidine and creatinine and in apparent fractional breakdown rates after 2 days on a meat-free diet.

3. One of the patients had lower, and two of the patients had higher, fractional breakdown rates compared with the vegetarians.

4. Nτ-Methylhistidine and creatinine excretion-5-be a useful and non-invasive measurement of myofibrillar protein degradation in patients on meat-free diets. Firm conclusions cannot, however, be drawn without confirmatory, direct measurement of the breakdown rates of muscle protein in vivo.
Effect of Propranolol on Heart Rate, Blood Pressure and Plasma Noradrenaline during Coitus in the Rabbit
Authors: Gordon D. , Roddis S. A. , Sever P. S.
Published: August 2015

1. The effects of coitus on heart rate, blood pressure and plasma concentration of noradrenaline were studied in six male rabbits.

2. During coitus, heart rate rose from 228 ± 6 to 324 ± 8 beats/min (mean ± sem; n = 24). Mean blood pressure rose from 87 ± 3 to 165 ± 4 mmHg, and plasma concentration of noradrenaline from 2.07 ± 0.21 to 5.02 ± 0.26 nmol/l. The maximum heart rate did not occur until after the peak in blood pressure.

3. Propranolol had no effect on the power expended during coitus, but there was a dose dependent fall in the changes in heart rate, blood pressure and plasma concentration of noradrenaline.
Kinetics of Uptake of Lysine and Lysyl-Lysine by Hamster Jejunum in Vitro
Authors: Burston D. , Taylor E. , Matthews D. M.
Published: August 2015

1. The kinetics of 2-min uptake of l-lysine and l-lysyl-l-lysine have been studied by using rings of everted hamster intestine in vitro, and values for Kt and Vmax, established.

2. On a molar basis, mediated uptake was more rapid for the amino acid than for the peptide. Non-mediated uptake was more rapid for the peptide than for the amino acid.

3. Comparison of relative rates of uptake of lysine from equivalent solutions of lysine and lysyl-lysine showed that at low concentrations, uptake of lysine was less rapid from the peptide than from the amino acid, whereas at high concentrations, uptake of lysine was more rapid from the peptide than from the amino acid. This type of effect of concentration on relative rates of uptake from equivalent solutions of amino acid and peptide has not previously been described.
Effect of Conjugated and Unconjugated Hyperbilirubinaemia on the Plasma 25-Hydroxy-Vitamin D Response to Ultraviolet Radiation in the Rat
Authors: Long R. G. , Barragry J. M. , Mitchenere P. , Beer M. S. , Boucher B. J. , Cohen R. D.
Published: August 2015

1. Vitamin D deficiency was induced in anicteric Wistar rats, Wistar rats before common bile-duct ligation was performed and Gunn rats with unconjugated hyperbilirubinaemia.

2. The effect of ultraviolet radiation on plasma concentrations of 25-hydroxy-vitamin D was studied in a group of control anicteric Wistar rats (n = 11), Wistar rats 8 days after common bile-duct ligation (n = 7) with conjugated hyperbilirubinaemia and in Gunn rats (n = 11).

3. The plasma 25-hydroxy-vitamin D response to ultraviolet radiation was similar in the three groups.

4. It is suggested that neither conjugated nor unconjugated hyperbilirubinaemia prevent cutaneous vitamin D3 synthesis or 25-hydroxylation in the rat.
Speed of Onset of Adaptive Mucosal Hypoplasia and Hypofunction in the Intestine of Parenterally Fed Rats
Authors: Hughes C. A. , Dowling R. H.
Published: August 2015

1. To establish the speed of onset of jejunal and ileal mucosal hypoplasia and hypofunction in parenterally fed rats, we measured three indices of mucosal mass, three mucosal enzymes and quantitative histology after 3, 6, 10 and 15 days of total parenteral nutrition and compared the results with those in two orally fed control groups, one with and one without intravenous catheters and metabolic cage restraint. The kinetics of galactose absorption in vivo were also measured after 10 days of total parenteral nutrition and in both control groups.

2. The most striking decrease in both jejunal and ileal mucosal wet weight and protein and DNA content per 10 cm length of intestine, occurred after only 3 days of total parenteral nutrition; thereafter the mean values showed only a slight further decrease.

3. The results of the morphometric studies showed that the hypoplasia affected the villi slightly more than the crypts. Within 3 days of starting total parenteral nutrition, mean jejunal mucosal thickness decreased by 16% and after 15 days it had fallen by 28%. The ileum showed similar, although less marked, changes. In the jejunum (not the ileum) modest cellular hypotrophy accompanied the mucosal hypoplasia; there were more epithelial cells/unit length of mid-villus and there was more DNA per g of mucosa in the total parenteral nutrition group than in the control group of rats.

4. Jejunal galactose absorption from the 16, 32 and 64 mmol/l solutions was significantly less in the 10-day total parenteral nutrition rats than in the controls, the apparent Vmax being five times greater in the orally fed animals. The apparent Michaelis constant (Km) was also significantly less than normal in the jejunum of the parenterally fed rats, suggesting increased affinity of the hypothetical carrier for galactose, perhaps as a result of functionally hypermature cells.

5. Mucosal alkaline phosphatase and catalase activities per unit length of intestine decreased and α-d-glucosidase activity increased in the jejunum and ileum of the total parenteral nutrition rats.

6. These results show that during total parenteral nutrition, the ileum and particularly the jejunum show marked reductions in mucosal mass and function after only 3 days of total parenteral nutrition and that there is a more gradual and progressive loss of mucosal mass thereafter up to 15 days.
Zinc Transport in Normal Human Leucocytes: Dependence upon Media Composition
Authors: Jones R. B. , Hilton P. J. , Michael J. , Patrick J. , Johnson V. E.
Published: August 2015

1. The transport of zinc has been studied in normal human leucocytes incubated in both a tissue culture medium and Krebs buffer.

2. 65Zn influx is characterized by an initial rapid phase followed by a slower influx. 65Zn influx is directly dependent upon the extracellular zinc concentration.

3. Net zinc influx could only be demonstrated in Krebs buffer at zinc concentrations in excess of 4.3 μmol/l and in tissue culture fluid at zinc concentrations in excess of 43.1 μmol/l.

4. A 65Zn efflux rate constant of approximately 1.0 per h was observed in both 4.3 and 15.4 μmol of zinc/l of Krebs buffer or tissue culture fluid.

5. In a zero external zinc Krebs buffer the 65Zn efflux rate constant fell to 0.57 per h and was accompanied by a small net zinc efflux.
Active and Inactive Renin in Individual Juxtaglomerular Apparatuses
Authors: Gillies A. , Morgan T. , Fitzgibbon W.
Published: August 2015

1. Renin was measured in individual juxtaglomerular apparatuses before and after acidification in vitro..

2. Active renin increased with delivery of extra sodium by microperfusion to the macula densa and this increase was similar to that achieved with acidification.

3. In rats pretreated with an inhibitor of protein synthesis active renin increased when extra sodium was delivered to the macula densa.

4. Salt intake changed the amount of renin present in the juxtaglomerular apparatus. In rats on a high salt intake the total renin was low and was all in an active form.
Prostacyclin-Like Activity in the Female Rat Thoracic Aorta and the Inferior Vena Cava after Ethinyloestradiol and Norethisterone
Authors: Karpati L. , Chow F. P. R. , Woollard M. L. , Hutton R. A. , Dandona P.
Published: August 2015

1. Female rats were injected with ethinyloestradiol, norethisterone or both compounds for 30 days. Prostacyclin-like activity was measured in the thoracic aorta and inferior vena cava.

2. In the thoracic aorta of rats injected with ethinyloestradiol and ethinyloestradiol/norethisterone, prostacyclin-like activity was significantly increased. Norethisterone alone had no effect.

3. In the inferior vena cava of rats injected with ethinyloestradiol, norethisterone or both compounds, prostacyclin-like activity was not significantly altered. The amount of prostacyclin generated by the inferior vena cava was much lower than that by the aorta.

4. Experimentally induced changes in the vessel wall after the administration of contraceptive steroids must be due to factors other than diminished prostacyclin production.
Enzyme Inhibitors for Renin Assay in Rat Plasma
Authors: Tikkanen I. , Fyhrquist F. , Puutula-Räsänen L.
Published: August 2015

1. Degradation of 125I-labelled [Ile5]-angiotensin I and unlabelled angiotensin I was studied during incubation of rat plasma treated with disodium ethylenediaminetetra-acetate (disodium EDTA) at 37°C, pH 6.5, for 1 h with 8-hydroxyquinoline, phenylmethylsulphonyl fluoride or di-isopropyl fluorophosphate.

2. Isolelectric focusing showed approximately 100, 59–66 and 10–31% preservation of 125I-labelled angiotensin I during incubation with 8-hydroxyquinoline (5.0 mmol/l), phenylmethylsulphonyl fluoride (15 mmol/l) and di-isopropyl fluorophosphate (1.09 mmol/l) respectively. Mean recovery of unlabelled angiotensin I was 102, 77 and 32% with 8-hydroxyquinoline, phenylmethylsulphonyl fluoride and di-isopropyl fluorophosphate respectively.

3. 8-Hydroxyquinoline appears the preferable enzyme inhibitor for renin assay in rat plasma.
The Source of Serum Ferritin during Infection. Studies with Concanavalin A–Sepharose Absorption
Authors: Birgegård G.
Published: August 2015

1. Serum samples were collected from ten patients hospitalized for acute infections and from a control group of seven normal subjects. Tissue ferritin was obtained by purification of ferritin from normal human liver and from the ferritin standard of a commercially available assay kit.

2. The serum and tissue samples were incubated with concanavalin A-Sepharose, which has the ability to bind normal serum ferritin.

3. Concanavalin A, a plant lectin which binds to glucose, can be coupled to Sepharose particles and by incubation and centrifugation ferritin in normal serum can be absorbed to about 70%. The serum and tissue samples were incubated with concanavalin A-Sepharose and the ferritin content was measured before and after.

4. It was found that ferritin in the serum of patients with acute infections was absorbed to the same extent as in normal serum (about 80%), irrespective of the initial value. Only about 20% of the tissue ferritin was absorbed.

5. It is concluded that the ferritin in serum during infection is of the same glucosylated type as the ferritin normally present in serum, whereas intracellular ferritin is not glycosylated. This indicates that the elevation of serum ferritin during infection is caused by a release along the normal pathways, i.e. an augmented synthesis, not by leakage from damaged cells.
Deficit of Trabecular and Cortical Bone in Elderly Women with Fracture of the Femoral Neck
Authors: Elsasser U. , Hesp R. , Klenerman L. , Wootton R.
Published: August 2015

1. The mean attenuation coefficients of trabecular and cortical bone in the radius were measured in 32 female patients with fractured proximal femur, and in 28 age-matched female controls, with a special-purpose computed tomography-scanner.

2. The largest difference between the two groups was in the mean attenuation coefficients for trabecular bone in the distal radius. The mean value for fracture patients (0.53 cm−1) was significantly lower (P < 0.02) than the mean value for the controls (0.62 cm−1). These results are consistent with the view that a loss of trabecular bone predisposes to fractures of the proximal femur.
Indomethacin Increases Leucocyte β-Adrenoreceptors in Man
Authors: Güllner H.-G. , Kafka M. S. , Bartter F. C.
Published: August 2015

1. The effect of indomethacin, an inhibitor of prostaglandin synthesis, on number and sensitivity of α- and β-adrenoreceptors was studied in normal healthy volunteer subjects.

2. The subjects were studied under metabolic conditions. To achieve inhibition of prostaglandin synthesis indomethacin (2 mg day−1 kg−1) was given orally for 7 days. This dose decreased urinary excretion of prostaglandin E-like immunoreactivity by 70%.

3. The number of α-adrenoreceptors was measured by the specific binding of [3H]dihydroergocryptine to platelet membranes and that of β-adrenoreceptors by the binding of [3H]dihydroalprenolol to leucocyte membranes.

4. The number of α-adrenoreceptors did not change with indomethacin, nor did basal, prostaglandin E1- or noradrenaline-stimulated cyclic AMP production by platelet membranes. In contrast, the number of β-adrenoreceptors increased by 92%. Indomethacin did not affect, however, basal, 1-isoprenaline- or prostaglandin E1-stimulated cyclic AMP production in leucocyte membranes.

5. These results suggest that a reflex-mediated decrease in sympathetic discharge in response to an indomethacin-induced decrease in release of vasodilator prostaglandins may lead to an ‘up-regulation’ of β-adrenoreceptor sites.
The Intrarenal Regulation of Sodium Excretion in the Dog
Authors: Nizet A. , Deheneffe J. , Robin M.
Published: August 2015

1. The effect of sodium chloride-containing solution (saline) infusion on sodium excretion has been investigated in kidneys transplanted from donors into the neck vessels of other dogs (perfusors). The dogs (perfusors and donors) had been given sodium-enriched or sodium-poor diets (‘loaded’ and ‘deprived’ dogs).

2. Three series of experiments were performed: (A) loaded perfusor, loaded donor; (B) deprived perfusor, deprived donor; (C) deprived perfusor, loaded donor.

3. Kidneys from deprived dogs, transplanted into deprived perfusors, excreted less sodium after intravenous saline than kidneys from loaded dogs transplanted into loaded perfusors. However, the sodium excretion from the kidneys of loaded dogs transplanted into deprived perfusors was the same as that from the kidneys of loaded dogs transplanted into loaded perfusors. These differences suggest that intrarenal mechanisms are involved in the changes in sodium excretion which follow changes in dietary sodium balance.

4. The intrarenal mechanisms included changes in glomerular filtration rate and fractional sodium reabsorption, but not changes in filtration fraction or renin release.
Haemodynamic and Hormone Responses to Acute and Chronic Frusemide Therapy in Congestive Heart Failure
Authors: Ikram H. , Chan W. , Espiner E. A. , Nicholls M. G.
Published: August 2015

1. Since important interrelationships between haemodynamic and hormone indices are possible in cardiac failure, measurements of cardiac output, mean pulmonary artery pressure, plasma renin activity, angiotensin II and aldosterone were carried out before and during acute and chronic frusemide therapy in patients with oedematous heart failure who had been given digoxin.

2. Cardiac output fell significantly 90 min after acute frusemide injection, then returned to baseline. Mean pulmonary artery pressure declined steadily throughout the 4 h of observation.

3. These haemodynamic changes occurred in the absence of major hormonal fluctuations and related presumably to direct vascular and diuretic actions of frusemide.

4. With more chronic (8–10 days) oral frusemide therapy, reciprocal changes between haemodynamic and hormone indices were observed. As the diuretic response to frusemide diminished, cardiac output and pulmonary artery pressure declined whereas the renin-angiotensin system was activated. Statistically significant inverse correlations were observed between these haemodynamic and hormone indices.

5. In both acute and chronic phases of the study, fluctuations in aldosterone levels were regulated by the renin-angiotensin system whereas ACTH, plasma potassium and plasma sodium played, at best, supportive roles.
Long-term Regulation of Arterial Pressure, Glomerular Filtration and Renal Sodium Reabsorption by Angiotensin II in Dogs
Authors: Hall J. E. , Guyton A. C. , Smith M. J. , Coleman T. G.
Published: August 2015

1. This study was designed to quantify the role of angiotensin II in determining the chronic relationships between arterial pressure, renal haemodynamics and sodium excretion.

2. In six control dogs sodium balance was achieved during chronic increases in sodium intake from 5 to 495 mmol/day with small increases in arterial pressure (7mmHg), moderate increases in glomerular filtration rate (19%) and decreases in filtration fraction. Similar increases in sodium intake in dogs whose circulating levels of angiotensin II were fixed, due to a constant intravenous infusion of 4.85 pmol of angiotensin II min−1 kg−1, caused large increases in arterial pressure (42%), glomerular filtration rate (31%), filtration fraction and calculated renal sodium reabsorption above control. In six dogs whose angiotensin II formation was blocked by SQ 14 225, sodium balance at intakes of 5–80 mmol/day occurred at reduced arterial pressure, glomerular filtration rate, filtration fraction and sodium reabsorption although plasma aldosterone concentration was not substantially different from that in control dogs. At sodium intakes above 240 mmol/day arterial pressure was not altered by SQ 14 225.

3. These data indicate that during chronic variations in sodium intake angiotensin II plays a major role, independently of changes in plasma aldosterone concentration, in allowing sodium balance without large fluctuations in glomerular filtration rate or arterial pressure. The mechanism whereby angiotensin II conserves sodium chronically is through increased sodium reabsorption, since steady-state sodium reabsorption was increased by angiotensin II and decreased by SQ 14 225.
Evidence for the Participation of Sodium-Sensitive Pontine Catecholaminergic Neurons in the Maintenance of DOCA-Sodium Hypertension in Rats
Authors: De Champlain J. , Van Ameringen Marie-Reine
Published: August 2015

1. A reduced noradrenaline turnover rate has been previously demonstrated in the brain stem of deoxycorticosterone acetate (DOCA)-sodium hypertensive rats. In the present study, the turnover rate was measured in smaller brain regions and the effect of sodium depletion was studied on the turnover rate of these regions.

2. Catecholamine turnover rate was significantly reduced only in the pons, was slightly but not significantly reduced in the thoracic spinal cord and was normal in the upper and lower medulla oblongata, in the mesencephalon, in the hypothalamus and in the telencephalon.

3. The administration of a sodium-free diet for 3 weeks lowered significantly the blood pressure and concomitantly accelerated the turnover rate in the pons area of DOC A hypertensive rats.

4. It is concluded that pontine catecholaminergic fibres, sensitive to sodium balance, might be involved in the maintenance of DOCA-sodium hypertension in the rat.
Influence of the Sympathetic Nervous System on Aortic Compliance
Authors: Alicandri C. L. , Fariello R. , Agabiti-Rosei E. , Romanelli G. , Muiesan G.
Published: August 2015

1. Aortic compliance and plasma catecholamine levels were determined in 26 essential hypertensive patients: 14<45 years (group 1) and 12>45 years (group 2).

2. Aortic rigidity, the reciprocal of aortic compliance, was calculated by the ratio of pulse pressure to stroke volume. Pulse pressure was derived by arterial pressure measured in the ascending aorta. Stroke volume was obtained by dye dilution.

3. A significant correlation (r = 0.60) was found between aortic rigidity and plasma noradrenaline in group 2. In this group both aortic rigidity and plasma noradrenaline levels were consistently higher than in group 1.

4. In 15 patients (seven of group 1 and eight of group 2) aortic rigidity was again measured after acute phentolamine (five patients) and labetalol (ten patients) administration.

5. Aortic rigidity was reduced significantly after both α-adrenoreceptor blockade alone and combined α- and β-adrenoreceptor blockade. A highly significant correlation was found between aortic rigidity reduction and pretreatment noradrenaline levels (r = 0.77).

6. Aortic compliance is influenced, at least in part, by sympathetic nervous system activity. Drugs which block the peripheral effects of catecholamines may improve aortic compliance and consequently the control of systolic hypertension in selected cases.
Cardiac and Haemodynamic Measurements in Hypertensive Pregnancy
Authors: Larkin H. , Gallery Eileen D. M. , Hunyor S. N. , Gyory A. Z. , Boyce E. S.
Published: August 2015

1. Haemodynamic and left ventricular variables were determined by M-mode echocardiography in 21 normotensive and 36 hypertensive patients during the last trimester of pregnancy.

2. Blood pressure of hypertensive patients was lowered by bed rest only, or by oxprenolol or methyldopa, but remained elevated.

3. Cardiac output was raised in the last trimester of pregnancy in both normotensive and hypertensive patients.

4. Left ventricular mass was increased in normal pregnancy, but displayed an exaggerated increase in hypertensive patients.

5. Total peripheral resistance was inappropriately elevated in hypertensive pregnancy, except in the oxprenolol-treated group.

6. There was no reduction in heart rate or cardiac output in the group treated with β-adrenoreceptor blocking agents. These factors, in combination with normal peripheral resistance, may contribute to the improvement in foetal outcome described in maternal hypertension of pregnancy treated with oxprenolol.
Distensibility of the Left Atrial Wall in Spontaneously Hypertensive Rats Compared with That in Normotensive Wistar-Kyoto Rats
Authors: Ricksten S.-E. , Yao T. , Ljung B. , Thorean P.
Published: August 2015

1. The cardiac mechanoreceptors, which in rats are mainly located in the left atrial wall, are reset in spontaneously hypertensive rats. The atrial pressure has to be almost twice as high in spontaneously hypertensive rats as in normotensive controls to produce similar receptor activations, as is apparent from previous studies.

2. The present study was performed to investigate whether this resetting is due to decreased distensibility of left atrial walls in the spontaneously hypertensive rats.

3. Static load-length relationships were investigated in vitro on left atrial strips, and pressure-volume relationships were studied on isolated left atria from spontaneously hypertensive and normotensive Wistar-Kyoto rats.

4. The force per cross-sectional area exerted during a relative length increase of 80% was significantly greater in spontaneously hypertensive rats. The dynamic but not the static distensibility was significantly lower in these animals.

5. The decreased dynamic distensibility of left atrial walls in spontaneously hypertensive rats can at least partly explain the resetting of atrial receptor function.
Role of Haemodynamics, Catecholamines and Renin in Acute Hypercalcaemic Hypertension in Man
Authors: Marone C. , Beretta-Piccoli C. , Weidmann P.
Published: August 2015

1. The effect of acute hypercalcaemia on blood pressure, blood volume, haemodynamic indices, plasma catecholamines, renin and aldosterone levels was investigated in 10 patients.

2. Calcium infusion (15 mg/kg over 3 h) increased (P<0.05) plasma calcium and adrenaline levels, blood pressure, total peripheral resistance and packed cell volume. Plasma volume was decreased, and heart rate, cardiac output and plasma renin, aldosterone or dopamine levels were not significantly changed. Plasma noradrenaline was increased only minimally after 3 h of calcium infusion.

3. Mean blood pressure before and during calcium infusion correlated with concomitant serum calcium (r = 0.39; P<0.02) or adrenaline levels (r = 0.57; P<0.01); changes in blood pressure correlated with variations in plasma adrenaline (r = 0.68; P<0.001).

4. Acute hypercalcaemic hypertension is mediated by an increase in peripheral vascular resistance and may be induced by a direct effect of calcium on blood vessels. The calcium-mediated increase in adrenaline release may play a contributory, and plasma volume contraction an inhibitory, role.
Effect of Atenolol on Left Ventricular Function in Hypertensive Patients
Authors: Ibrahim M. Mohsen , Madkour M. Aziz , Mossallam Ragaa
Published: August 2015

1. Atenolol (100 mg/day) was given to 12 hypertensive patients for 8 weeks, and its effects on mean arterial pressure, cardiac index and ejection phase indices of myocardial performance were examined by echocardiography.

2. Echocardiographic studies were made before treatment after 4 weeks on placebo and repeated after 4 and 8 weeks of atenolol therapy. Mean arterial pressure fell by 14 and 21% after 4 and 8 weeks respectively. Cardiac index fell by 22 and 20%, and stroke index fell by 11 and 7%. Calculated peripheral resistance did not change significantly.

3. Ejection phase indices, namely fractional shortening, ejection fraction and normalized mean rate of circumferential fibre shortening, did not change. End-diastolic volume index did not change and there was no relationship between changes in heart rate and end-diastolic volume index.

4. The study shows that atenolol in the resting state has no effect on certain echocardiographic indices of left ventricular function when given orally to hypertensive patients with normal left ventricular size and function. The reduction in cardiac and stroke indices were presumably secondary to a decrease in cardiac venous filling.
Simple Method of Assessing Splenic Function in Coeliac Disease
Authors: Corazza G. R. , Bullen A. W. , Hall R. , Robinson P. J. , Losowsky M. S.
Published: August 2015

1. Erythrocytes with membrane abnormalities seen on interference contrast microscopy (‘pitted erythrocytes’) were counted in venous blood samples from patients with treated coeliac disease and dermatitis herpetiformis, and from control subjects and patients who had had an elective splenectomy.

2. The percentage of ‘pitted erythrocytes’ was compared with the 99mTc-labelled heat-damaged erythrocyte clearance, and with the splenic size computed from scintiscans.

3. There was a significant correlation between percentage ‘pitted erythrocytes’ and the above methods of measuring splenic function and size. Increase in the percentage of ‘pitted erythrocytes’ above the control range indicated splenic hypofunction.

4. The number of coeliac patients with percentage ‘pitted erythrocytes’ above the control range increased with increasing age at which they started a gluten-free diet.

5. Counting of ‘pitted erythrocytes’ is a simple and sensitive method of assessing splenic hypofunction in treated coeliac disease. It avoids radiation exposure, and is applicable to all ages and repeatable without risk.

6. The incidence of splenic hypofunction in coeliac patients may be related to the duration of untreated disease.