bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanism of Amphotericin-Induced Distal Acidification Defect in Rats
Authors: Julka Naresh K. , Arruda Jose A. L. , Kurtzman N. A.
Published: August 2015

1. The effect of chronic and acute administration of amphotericin B on renal function, especially urinary acidification, was studied in rats. Chronic intraperitoneal administration of amphotericin B resulted in blood concentrations similar to or higher than those seen in patients treated with the antibiotic, but failed to produce hyperchloraemic acidosis. The minimum urine pH achieved during NH4Cl-induced acidosis was significantly higher in amphotericin-treated rats than in controls; net acid excretion, however, was not significantly different from that of controls. These data were interpreted as indicating the presence of an incomplete distal acidification defect.

2. The ability to raise urine-blood (U-B)Pco2 during alkalinization of the urine was examined in another group of amphotericin-treated rats. The data on amphotericin-treated rats could be artificially divided into two groups. One group had a normal glomerular filtration rate (GFR) and was able to raise the (U-B)Pco2 gradient during administration of the HCO−3 to the same as that seen in control rats infused with the vehicle for amphotericin, sodium deoxycholate. The second group, which comprised only 15% of the total, had a decreased glomerular filtration rate and an abnormally low (U-B)Pco2. The normal (U-B)Pco2 was interpreted as the result of normal H+ secretion during alkalinization of the urine. The low (U-B)Pco2 in the second group was attributed to the low urinary HCO−3 concentration.

3. In order to investigate the effect of large concentrations of amphotericin on distal H+ secretion, amphotericin was administered acutely to HCO−3-loaded rats. Acute intravenous administration of amphotericin resulted in a significant decrease in (U-B)Pco2 and urine HCO−3 concentration; the decrease in urinary Pco2 was of greater magnitude than the decrease in urine HCO−3 concentration, leading to a rise in urine pH. The maximum urine pH achieved during HCO−3 loading (maximal urine HCO−3 was the same in both groups) was significantly higher in the animals infused acutely with amphotericin than in controls, thus indicating that amphotericin-treated animals have a distal acidification defect. These data are compatible with the hypothesis that amphotericin induces an acidification defect by increasing H+ back-diffusion in the form of carbonic acid or dissolved CO2 when the urine is highly alkaline and in the form of weak acid or proton when the urine is acid.
Post- and Pre-Natal Assessment of α-l-Iduronidase Deficiency with a Radiolabelled Natural Substrate
Authors: Hopwood J. J. , Muller Vivienne , Pollard A. C.
Published: August 2015

1. α-l-Iduronidase activity was assayed by incubation of iduronosyl anhydro[1-3H]mannitol 6-sulphate with homogenates of cultured skin fibroblasts, amniotic cells and leucocytes derived from normal individuals, patients affected with α-l-iduronidase deficiency disorder (mucopolysaccharidosis type I: Hurler, Scheie and Hurler-Scheie compound) and parents of such patients.

2. The assay for α-l-iduronidase, described for use with these cell types, clearly distinguished affected homozygotes from heterozygotes and normal controls.

3. The mean specific activity of α-l-iduronidase in homogenates prepared from cultured skin fibroblasts and leucocytes from more than seven obligate heterozygotes for mucopolysaccharidosis type I was found to be about one-half of the mean of more than 40 normal controls. A number of heterozygotes had α-l-iduronidase activity that identified them as carriers; others had values clearly within the normal range. Thus heterozygote detection of mucopolysaccharidosis type I is not certain.

4. With iduronosyl anhydro[1-3H]mannitol 6-sulphate used as substrate, cell types from five pregnancies at risk for α-l-iduronidase deficiency were examined; each foetus was predicted to be unaffected. For one foetus it was not possible from measurements of total enzyme activity alone to distinguish between the heterozygous carrier state and affected homozygote. The difficulty was resolved by comparing Michaelis-Menten kinetics of this enzyme in fibroblasts derived from the propositus, mother and normal controls with the kinetics of the enzyme in amniotic cells isolated from the foetus at risk and from normal controls.
Plasma Renin Activity and Sodium, Potassium and Water Excretion during Reversal of Hypertension in the One-Clip, Two-Kidney Hypertensive Rat
Authors: Ten Berg R. G. M. , Leenen F. H. H. , De Jong W.
Published: August 2015

1. The effect of removal of the clip on blood pressure, plasma renin activity and the excretion of water, sodium and potassium was studied in renal hypertensive rats. Hypertension was induced by application of a clip with an internal diameter of 0·20 mm, which was removed after 1, 2 or 3 weeks, and by using a clip with an internal diameter of 0·25 mm, which was removed after 2 weeks. The contralateral kidney remained undisturbed.

2. Blood pressure was almost normal 24 h after the removal of the clip; 70–90% of the total decrease in blood pressure occurred within 2–5 h.

3. The increased plasma renin activity, which was observed 2 and 3 weeks after application of a 0·20 mm clip, had returned to control values 24 h after removal of the clip. One week after application of a 0·20 mm clip, and 2 weeks after a 0·25 mm clip, plasma renin activity did not differ significantly from control values, before as well as after unclipping.

4. No significant differences were found between unclipped and sham-operated renal hypertensive rats, nor between the latter and the sham-operated normotensive control rats for water, sodium and potassium excretion, and for change in body weight, during the 24 h after the removal of the clip.

5. It is concluded that urinary loss of water and/or sodium does not play an important role in the acute decrease of blood pressure which occurs after the removal of a renal artery clip in one-clip, two-kidney hypertensive rats. A decrease in peripheral plasma renin activity can only partly explain the reversal of the hypertension.
Vitamin D and Magnesium Absorption in Man
Authors: Hodgkinson A. , Marshall D. H. , Nordin B. E. C.
Published: August 2015

1. The effects of vitamin D and its hydroxylated derivatives on calcium and magnesium absorption have been examined in 47 balance studies on patients with various disorders of calcium or bone metabolism.

2. Vitamin D significantly increased the mean net absorption of calcium and also the calcium balance. The mean net absorption of magnesium was also significantly increased although the rise was much less than that of calcium and the mean magnesium balance was unaffected.

3. It is suggested that the slight effect of vitamin D on magnesium absorption may be incidental to its stimulation of active calcium transport, since the latter system has weak affinities for other alkaline earth ions including strontium, barium and magnesium.
Heparin-Released Plasma Lipases in Chronic Renal Failure and after Renal Transplantation
Authors: Crawford G. A. , Savdie E. , Stewart J. H.
Published: August 2015

1. Post-heparin plasma from normal subjects, patients with chronic renal failure and recipients of renal allografts were subjected to affinity chromatography on heparin—agarose (Sepharose 4B) columns to separate two fractions representing hepatic lipase and lipoprotein lipase respectively.

2. The optimum conditions for assay of each fraction were determined for both normal and uraemic plasma.

3. Normal males had activities of hepatic lipase which were higher, and activities of lipoprotein lipase which were lower, than normal females. There was no consistent relationship to age for either enzyme.

4. Thirty patients with chronic renal failure untreated by dialysis had significantly elevated serum triacylglycerol concentrations, and significantly lowered lipoprotein lipase activities when compared with control groups with similar ages for each sex. However, only in uraemic males was hepatic lipase activity significantly reduced.

5. In a study of female patients with chronic renal failure, there were no significant differences in activities of hepatic lipase or lipoprotein lipase or concentrations of serum triacylglycerols between eight patients receiving dialysis treatment and eight untreated by dialysis.

6. Although serum triacylglycerol concentrations were raised in the group of 15 renal transplant recipients, lipase activities were not diminished. The only significant change was elevation of hepatic lipase activity in female graft recipients.

7. No relationship was found between the enzyme activities and fasting serum triacylglycerol concentrations in any group. However, there was a weak inverse correlation between serum creatinine and hepatic lipase in female patients from both renal failure and transplant groups.

8. Similar results were obtained when the enzymes were assayed with, as substrate, a laboratory-prepared emulsion of 14C-labelled triolein in water with soya-bean lecithin as emulsifier, or commercially prepared soya-bean oil in water, emulsified with egg-yolk lecithin and containing glycerol (Intralipid).
Parathyroid Function in Primary Osteoporosis
Authors: Bouillon R. , Geusens P. , Dequeker J. , De Moor P.
Published: August 2015

1. Parathyroid hormone and 25-hydroxy-vitamin D concentrations were measured in patients with severe primary osteoporosis and the results were compared with those found in normal subjects and in patients with primary hyperparathyroidism of vitamin D deficiency.

2. The parathyroid hormone concentrations in 19 patients with primary osteoporosis were within the normal range, both in the basal state (215 ± 85 ng/l, mean ± sd) and during a maximal stimulation (460 ±154 ng/l) induced by the infusion of disodium EDTA (70 mg/kg body weight). Increased serum concentrations of parathyroid hormone were found in patients with primary hyperparathyroidism (821 ± 323 ng/l, n = 33) and nutritional vitamin D deficiency (565 ± 144 ng/l, n = 11).

3. Serum 25-hydroxy-vitamin D concentrations (16·8 ± 7·7 μg/l) were found to be normal in patients with primary osteoporosis. Slightly (9·1 ± 2·1 μg/l) or markedly lower (2·2 ± 1·1 μg/l) 25-hydroxy-vitamin D concentrations were found respectively in patients with primary hyperparathyroidism and secondary hyperparathyroidism due to vitamin D deficiency. The serum concentration of the vitamin D-binding protein was normal in all groups.

4. A clearcut separation was therefore obtained between osteoporotic subjects (normal parathyroid hormone and normal 25-hydroxy-vitamin D concentrations) and patients with either primary hyperparathyroidism (increased parathyroid hormone and normal 25-hydroxy-vitamin D) or vitamin D deficiency (high parathyroid hormone and very low 25-hydroxy-vitamin D).
Urine Reinfusion Diuresis and Natriuresis in Rats: Role of Water, Electrolytes and Urea
Authors: Norman R. A. , Coleman T. G. , Kastner P. R.
Published: August 2015

1. The purpose of this study was to determine the role of reinfused water, electrolytes and urea in the diuresis and natriuresis of urine reinfusion.

2. Three groups of rats underwent 5 h of urine reinfusion. The first group served as a control, and during urine reinfusion the urinary volume and sodium excretion increased to 10 or 12 times control values.

3. In a second group, urine reinfusion was followed by 2 h of infusion of Ringer solution at a rate equal to the urine flow rate; 71% of the diuresis and 75% of the natriuresis resulting from urine reinfusion were maintained.

4. In a third group, urine reinfusion was followed by infusion of Ringer solution with urea added. The infusion rate was equal to urine flow rate and the concentration of urea was equal to that in the urine; 98% of the diuresis and 102% of the natriuresis were maintained.

5. These results indicate that the majority of urine-reinfusion diuresis and natriuresis is due to reinfused volume and electrolytes, and the remainder, in these experiments at least, could be explained by the reinfused urea. Therefore there was no need to postulate additional urinary natriuretic factors to explain the results of urine reinfusion.
Mucosal Enzymes in Human Inflammatory Bowel Disease with Reference to Neutrophil Granulocytes as Mediators of Tissue Injury
Authors: Kane S. P. , Vincenti A. C.
Published: August 2015

1. Biopsies of rectal mucosa were obtained for histology and enzyme analysis from 32 patients with inflammatory and functional bowel disorders, and the biopsies were classified morphologically as active colitis, quiescent colitis or normal.

2. Supernatant fractions of biopsy homogenates were assayed for their content of the proteolytic enzymes α-chymotrypsin, elastase and cathepsin D, and of protein, unsaturated vitamin B12-binding capacity, lysozyme, myeloperoxidase and N-acetyl-β-glucosaminidase.

3. Mean unsaturated vitamin B12-binding capacity was significantly raised above normal in the active colitic mucosa, and mean lysozyme activity was raised above normal in both active and quiescent mucosae.

4. In active colitic mucosa there was no rise above normal in mean activities of any of the proteolytic enzymes, though a significant fall below normal occurred in mean N-acetyl-β-glucosaminidase activity in the active colitic group.
Characteristics of a Renin-Binding Substance for the Conversion of Renin into a Higher-Molecular-Weight Form in the Dog
Authors: Kawamura Minoru , Ikemoto Fumihiko , Funakawa Susumu , Yamamoto Kenjiro
Published: August 2015

1. Renal cortical homogenates of the dog were subjected to sieve separation, a Nucleopore Filter being used to separate the renin granules.

2. The molecular weight of renin in the granules was estimated to be about 40 000 by gel filtration. Renin was converted into a higher-molecular-weight form (60 000) by mixing with cytosol in the presence of sodium tetrathionate, a thiol inhibitor.

3. When cytosol was pretreated with acid (pH 30) or heating (100°C), the molecular-weight conversion did not occur.

4. Cytosol was separated into three parts by gel filtration. Fraction A included substances with a molecular weight of over 47 000, fraction B from 47 000 to 32 000, and fraction C from 32 000 to 15 000. The mixture of renin in the granules with fraction A and sodium tetrathionate resulted in the formation of a higher-molecular-weight form of the enzyme, but no change in molecular weight was detected when renin was mixed with fractions B or C and sodium tetrathionate.
Effect of Phlorhizin on Renal Glucose and Phosphate Transport in the Dog
Authors: Wen Sung-Feng
Published: August 2015

1. Clearance and micropuncture studies were performed in 19 thyroparathyroidectomized dogs to examine the inter-relationship between the renal transport of sodium, glucose and phosphate.

2. All experiments were carried out before and after the intravenous administration of phlorhizin [7 mg (15 μmol)/kg] with a sustaining infusion of the same dose/h. Thirteen dogs were studied during hydropenia (group I) and six dogs in the volume-expanded state (group II).

3. In the proximal tubule, phlorhizin significantly reduced sodium reabsorption in hydropenic dogs, but had no effect in volume-expanded dogs. Proximal tubular glucose reabsorption was completely inhibited by phlorhizin in both groups, but no significant change in phosphate reabsorption was observed.

4. Fractional glucose excretion in the urine reached 83–89% after phlorhizin, values significantly less than 100%, suggesting a residual reabsorption of glucose in a more distal segment or in deep nephrons. The changes in fractional excretion of sodium and phosphate were significantly correlated.

5. The effect of phlorhizin on both sodium and glucose reabsorption in the proximal tubule in hydropenic dogs suggests the existence of a co-transport mechanism, whereas the absence of an effect on sodium transport in volume-expanded dogs despite complete inhibition of glucose reabsorption indicates the existence of a sodium-independent component of net proximal tubular glucose transport.

6. Absence of the effect of phlorhizin on proximal tubular phosphate transport in the face of a significant reduction in sodium reabsorption implies that the reciprocal relationship between glucose and phosphate transport could be masked by the changes in sodium transport. Thus the sodium-phosphate transport relationship may prevail over that of glucose-phosphate in the proximal tubule.
Clonidine and Sympathetic Activity during Sleep
Authors: Maling T. J. B. , Dollery C. T. , Hamilton C. A.
Published: August 2015

1. Blood pressure, heart rate, plasma noradrenaline and electroencephalographic variables were measured simultaneously during sleep in five healthy males before and after slow-release clonidine (300 μg orally) or placebo.

2. The blood pressure fall during sleep correlated significantly with the depth of sleep.

3. Clonidine significantly reduced systolic blood pressure during sleep and profoundly reduced total paradoxical sleep duration.

4. Plasma noradrenaline declined progressively during the sleep period and concentrations were significantly lower after clonidine compared with placebo.
Isolation of a Renal Thiol Protease that Activates Inactive Plasma Renin
Authors: Slater Eve E. , Gounaris Anne D. , Haber E.
Published: August 2015

1. A thiol protease with properties similar to those of cathepsin B (EC 3.4.22.1) has been isolated and purified from human renal cortex.

2. This enzyme can generate renin activity from renin-suppressed and anephric human plasma at pH 5·5.

3. The renin activity thus generated is inhibited completely by antibody to purified human renal renin. This activation therefore represents the release of inactive renin.
Plasma Noradrenaline Correlates with α-Adrenoreceptor-Mediated Vasoconstriction and Blood Pressure in Patients with Essential Hypertension
Authors: Kiowski W. , Van Brummelen P. , Bühler F. R.
Published: August 2015

1. The relationships between plasma noradrenaline concentration at rest and blood pressure, as well as increase in forearm blood flow in response to a brachial artery infusion of the α-adrenoreceptor-blocking agent phentolamine, were investigated in hypertensive and normotensive subjects of similar age.

2. In 44 hypertensive patients plasma noradrenaline correlated with systolic, diastolic and mean blood pressures, but no difference in the mean plasma noradrenaline concentration was found.

3. In 11 patients and 14 normotensive subjects α-adrenoreceptor blockade resulted in a similar increase in forearm blood flow. Only in the patients, however, was this increase related to plasma noradrenaline and blood pressure.

4. In patients with established essential hypertension plasma noradrenaline can be considered to be a marker of α-adrenoreceptor-mediated vasoconstriction, which, in part, determines the height of the blood pressure.
Sympatho—Adrenal and Cardiovascular Response to Mental Stress and Orthostatic Provocation in Latent Hypertension
Authors: Hjemdahl P. , Eliasson K.
Published: August 2015

1. Seven latent hypertensive patients and seven matched controls were subjected to standardized mental stress and orthostatic provocation.

2. Mental stress increased blood pressure by approximately 25%, heart rate by 25 beats/min, plasma glycerol by 50% and plasma cyclic AMP by 25% in both groups. Plasma glucose and renin activity were unchanged. Plasma noradrenaline and adrenaline were essentially unchanged during stress.

3. There was an insignificant tendency towards higher noradrenaline levels in latent hypertensive subjects and two of these subjects displayed an exaggerated noradrenaline response to standing.

4. Our results indicate that the physiological responses to mental stress are caused by selective neuronal activation, rather than by generalized sympatho-adrenal activation. Latent hypertension does not seem to be associated with adrenergic hyperactivity or receptor supersensitivity, except possibly in individual cases.
Sodium Excretion and Blood Pressure in Essential Hypertensive Patients during the Early Phase of Hospital Admission
Authors: De Leeuw P. W. , Wester A. , Van Soest G. A. W. , Vaarties-Steeman J. E. M. , Birkenhäger W. H.
Published: August 2015

1. In 91 essential hypertensive patients cumulative sodium balance was studied during the first week after they were taken into hospital. Sodium intake was fixed at 55 mmol/day.

2. After the first week, when sodium equilibrium was achieved, haemodynamic and endocrinological studies were carried out (cardiac output, renal plasma flow, plasma volume, measurements of plasma concentrations of total and active renin, aldosterone and noradrenaline).

3. On the basis of cumulative sodium balance a discrimination could be made between three groups. Group I (23 patients) accumulated sodium (52 mmol) before attaining equilibrium; group II (35 patients) were in balance from the beginning; group III (33 patients) exhibited a negative balance and lost on the average 125 mmol before equilibrium was attained.

4. On admission blood pressure and other characteristics were similar in the three groups. The decrease in blood pressure over the first 24 h period was equal. After that, the group characterized by a negative cumulative sodium balance (III) continued to exhibit a fall in blood pressure whereas groups I and II did not.

5. After sodium equilibrium had been attained, the haemodynamic profiles were somewhat different between groups. Group I (with a positive balance) showed greater systemic and renal vascular resistances than the other groups.

6. It is concluded that sodium loss contributes to the decrease in blood pressure on the second day of hospital admission and after. The blood pressure reduction during the first day is due to an independent mechanism, e.g. a decrease in sympathetic nervous tone.

7. It is also apparent that the attainment of sodium equilibrium during clinical investigations constitutes no guarantee that subjects are physiologically comparable; the preceding sodium balance has to be taken into account.
Antihypertensive Effects of Clonidine in Tetraplegic Subjects Devoid of Central Sympathetic Control
Authors: Mathias C. J. , Reid J. L. , Wing L. M. H. , Frankel H. L. , Christensen N. J.
Published: August 2015

1. The effects of 300 μg of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections.

2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower.

3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2–4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the rise in intravesical pressure caused by bladder stimulation was unchanged by clonidine.

4. The pressor response to intravenous noradrenaline in two tetraplegic subjects and to intravenous phenylephrine in a further two tetraplegic subjects was unchanged by clonidine.

5. Clonidine may have additional antihypertensive effects which occur independently of actions in the brain. These effects may be exerted by an action either on sympathetic neurones in the spinal cord or on presynaptic α-adrenoreceptors in the periphery.
The Evidence that Salt is an Important Aetiological Agent, If Not the Cause, of Hypertension
Authors: Morgan T. , Myers J. , Carney S.
Published: August 2015

1. Salt intake and the incidence of hypertension correlate between populations.

2. Salt intake within a population may correlate with the incidence of hypertension.

3. Disorders that lead to retention of salt cause hypertension.

4. Modest salt restriction reduces blood pressure in many patients.

5. Reducing salt balance and preventing the compensatory rise in angiotensin II controls blood pressure in most patients.

6. Salt is the probable cause of the epidemic of hypertension in the Western world; this could be prevented by salt restriction.
Baroreflex Sensitivity in Renal Failure
Authors: Tomiyama Osamu , Shiigai Tatsuo , Ideura Terukuni , Tomita Kimio , Mito Yasuyoshi , Shinohara Shinsuke , Takeuchi Jugoro
Published: August 2015

1. Baroreflex sensitivity was evaluated in 22 non-dialysed patients with chronic renal failure secondary to chronic glomerulonephritis. Baroreflex sensitivity was judged by the slope of the linear regression of the pulse interval on the rise in systolic blood pressure with injection of phenylephrine or reduction by amyl nitrite inhalation.

2. Baroreflex sensitivity was reduced in these patients as compared with normal controls. Reduction of baroreflex sensitivity was significantly greater in nine hypertensive than 13 normotensive patients with chronic renal failure.

3. A significant positive correlation was found between baroreflex sensitivity and motor nerve conduction velocity measured on ulnar nerve in 13 patients examined.

4. Saline was given with high dietary salt intake to seven normotensive patients with chronic renal failure for 2 or 5 days in order to determine whether the severe depression of baroreflex sensitivity can be an initiating factor for hypertension. Blood pressure was raised to hypertensive levels within 5 days in two patients in whom baroreflex sensitivity was nearly as low as that of hypertensive patients, but not in five cases whose baroreflex sensitivity was normal or only mildly depressed. Plasma volume increased to the same degree in both groups. Baroreflex sensitivity did not change in the former two cases despite blood pressure elevation.

5. It is concluded that reduced baroreflex sensitivity in chronic renal failure correlated with the presence of hypertension, as well as uraemic neuropathy, and may be one of the pathogenetic mechanisms of hypertension in end-stage chronic glomerulonephritis.
Sieving Studies in ‘Urea-Induced Nephropathy’ in the Dog
Authors: Vanrenterghem Y. , Vanholder R. , Lammens-Verslijpe M. , Lambert P. P.
Published: August 2015

1. The intrarenal infusion of concentrated urea after clamping of the renal artery produced immediate proteinuria in the dog. The predominant lesion on ultramicroscopy was destruction of the epithelial layer. Colloidal iron staining showed decreased fixed anionic charges in the capillary wall.

2. Sieving studies with neutral macromolecules such as 125I-labelled polyvinylpyrrolidone and [3H]-dextran or an electronegatively charged polymer, [3H]dextran sulphate, showed a moderate increase in permeability to the neutral tracers and a much more severe alteration of the electrostatic barrier to the anionic polymer. The fractional clearance of dextran sulphate molecules increased to a greater extent than clearance of neutral dextrans of comparable size.

3. The shape of the curve relating the fractional clearance of dextran sulphate to molecular size is also modified in the contralateral kidney. This may be due to elevated plasma angiotensin II concentrations.
The Relationship between Plasma Biotin Concentration and Circulating Leucocyte β-Methylcrotonyl-CoA Carboxylase and Propionyl-CoA Carboxylase
Authors: Bartlett K. , Horsburgh T. , Gompertz D.
Published: August 2015

1. A newly developed biotin assay was used to monitor plasma and urinary biotin concentration after the oral administration of biotin.

2. In two normal subjects, leucocyte propionyl-CoA carboxylase and β-methylcrotonyl-CoA carboxylase were markedly stimulated after the administration of biotin.
An Association between Plasma Progesterone and Erythrocyte Carbonic Anhydrase I Concentration in Women
Authors: Paciorek J. , Spencer N.
Published: August 2015

1. Erythrocyte carbonic anhydrase I was measured by immunoelectrophoresis in blood samples taken at intervals during the menstrual cycle of 26 normal women. Plasma progesterone concentrations were also measured in 18 of these subjects. In every case, the erythrocyte carbonic anhydrase I concentration reached a maximum at that point in the cycle when there was maximum secretion of progesterone. Statistical analysis indicated that the observed changes in erythrocyte carbonic anhydrase I concentration are highly significant and that erythrocyte carbonic anhydrase I and plasma progesterone concentrations are significantly correlated.

2. In three pregnant subjects the erythrocyte carbonic anhydrase I concentration showed a steady increase up to term.

3. Women taking progestogens in contraceptive pills, in doses of 1 mg/day or greater, had significantly higher concentrations of erythrocyte carbonic anhydrase I compared with females receiving no medication.

4. These observations strongly suggest that there may be a causal connection between plasma progesterone concentration and erythrocyte carbonic anhydrase I concentration in women.
Influx of Glycylsarcosine and l-Lysyl-l-Lysine into Hamster Jejunum in Vitro
Authors: Taylor E. , Burston D. , Matthews D. M.
Published: August 2015

1. This paper reports an investigation of whether the dipeptides glycylsarcosine and l-lysyl-l-lysine share a single mediated transport mechanism into hamster jejunum, or whether one of these peptides is taken up in part by a mediated mechanism unavailable to the other. The investigation, using rings of everted jejunum in vitro, was carried out at pH 5 in order to reduce brush border and/or intramedium hydrolysis of lysyl-lysine.

2. The kinetics of uptake of each peptide was studied over a wide range of concentrations. Estimates of the simple diffusion component in uptake of each peptide were made by the method of self-inhibition of transport as previously described. After correction for simple diffusion, uptake of each peptide conformed to Michaelis-Menten kinetics, and values for Kt and Vmax. were obtained.

3. It was found that each peptide was capable, at infinitely high concentration, of complete inhibition of mediated uptake of the other. The inhibitory effect was competitive. We concluded that glycylsarcosine and lysyl-lysine were taken up by a common mediated mechanism (or possibly mechanisms), neither peptide being taken up by a mediated mechanism unavailable to the other.

4. A previous paper showed that l-glutamyl-l-glutamic acid and glycylsarcosine were taken up by a common mediated mechanism, and this paper shows that l-lysyl-l-lysine and glycylsarcosine are taken up by a common mediated mechanism. It is therefore postulated that the neutral dipeptide glycylsarcosine, the acidic dipeptide glutamyl-glutamic acid and the basic dipeptide lysyl-lysine all share a common mediated mechanism for uptake. This suggests that peptide uptake differs from amino acid uptake in that it is indifferent to the net charge on the amino acid side chain(s).
Estimation of Cardiac Output from the Rate of Change of Alveolar Carbon Dioxide Pressure during Rebreathing
Authors: Winsborough Mary , Miller J. N. , Burgess D. W. , Laszlo G.
Published: August 2015

1. A new CO2-rebreathing method for estimating cardiac output is described, and compared with a method employing N2O performed at the same time.

2. The subject inhales from a reservoir of 30% O2 in N2 and rebreathes into and out of an empty bag for 10s.

3. Oxygenated mixed venous Pco2 is then determined by rebreathing 7–15% CO2 in O2, the mixture being selected to obtain a plateau of CO2 concentration.

4. Pco2 rises exponentially towards the plateau value during the rebreathing of 30% O2. Cardiac output is calculated from the rate of change of the alveolar—mixed venous Pco2 difference by a differential version of the Fick equation employing published CO2 dissociation curves for whole blood in vitro.

5. The slope of the regression of cardiac output on V̇o2 is similar to that obtained in other studies employing direct Fick measurements. The slope is some 15% greater than obtained with N2O but the difference is significant only when Oz consumption is greater than 2 litres/min.

6. The CO2 dissociation slope of blood does not differ during pulmonary gas exchange in vivo from that determined at equilibrium in vitro.

7. The volume of pulmonary blood available for CO2 exchange may rise to about 1 litre in heavy exercise, with a transit time of 1–2 s in the lungs.

8. The method can be employed for estimating pulmonary blood flow during physiological studies in subjects with normal lungs.
The Role of Prostaglandins in Glucagon-Induced Natriuresis
Authors: Kirschenbaum M. A. , Zawada E. T.
Published: August 2015

1. Three groups of anaesthetized dogs were studied to determine the role of renal prostaglandins in glucagon-induced natriuresis.

2. Urine flow, sodium and prostaglandin E excretion rates increased significantly in the experimental kidney with glucagon infusion (0.20 μg/min) into the renal artery. These changes were completely reversed after the administration of either of two inhibitors of prostaglandin synthesis.

3. Infusion of glucagon (0.20 μg/min) after the administration of either of the prostaglandin synthetase inhibitors failed to increase either urine flow rate or sodium excretion above control values and failed to elevate urine prostaglandin E excretion rates.

4. Infusion of glucagon (0.75–1.25 μg/min) resulted in significant elevations in urine flow rate, glomerular filtration rate, renal plasma flow, urine sodium and prostaglandin E excretion rates.

5. The data presented indicate that the diuresis and natriuresis seen with the infusion of glucagon (0.20 μg/min) are accompanied by an increase in urine prostaglandin E excretion and are reversed by the administration of inhibitors of prostaglandin synthesis, suggesting that the increased urine flow and sodium excretion rates are dependent on prostaglandin-mediated mechanisms. The administration of glucagon in higher doses appears to be associated with alterations in electrolyte excretion and glomerular filtration rate, which presumably is related to factors other than prostaglandin synthesis and release.
Insulin-Induced Renin Release: Blockade by Indomethacin in the Rat
Authors: Campbell W. B. , Zimmer Judith A.
Published: August 2015

1. Since prostaglandins appear to mediate adrenergically stimulated renin release, the effect of indomethacin was examined on insulin-induced renin and catecholamine release in conscious rats. Insulin (10 units/kg subcutaneously) increased plasma renin activity from 2.8 ± 0.5 to 9.0 ± 1.1 pmol h−1 ml−1 (P<0.001) while also increasing plasma adrenaline, noradrenaline and the urinary excretion of prostaglandin E2 and F2α. Plasma potassium and glucose were reduced by 16 and 54%respectively.

2. Indomethacin (14 μmol/kg subcutaneously) reduced the urinary excretion of prostaglandin E2 and F2α by 67 and 54%respectively, without altering the other parameters.

3. Indomethacin inhibited insulin-induced renin release by 67%(P<0.01) and blocked the insulin-induced increases in urinary postaglandin E2 and F2α. The insulin-induced changes in plasma catecholamines, potassium and glucose were unaltered by indomethacin.

4. These findings suggest that renal prostaglandins mediate this form of adrenergically stimulated renin release by acting at a site distal to the β-adrenoreceptor.
Identification of Two Types of Porphyria Cutanea Tarda by Measurement of Erythrocyte Uroporphyrinogen Decarboxylase
Authors: Elder G. H. , Sheppard Diane M. , De Salamanca R. E. , Olmos A.
Published: August 2015

1. Erythrocyte uroporphyrinogen decarboxylase activity has been measured in 27 patients with porphyria cutanea tarda, of whom 11 had a family history of overt porphyria cutanea tarda.

2. Eight patients from six families had erythrocyte uroporphyrinogen decarboxylase activities that were decreased to about half of control values. This decrease was shown by family studies to be inherited as an autosomal dominant characteristic. Two of these patients had no family history of overt porphyria cutanea tarda.

3. Nineteen patients had uroporphyrinogen decarboxylase activities close to or within the range found in 18 control subjects. Of these, five patients had a family history of porphyria cutanea tarda.

4. Inheritance of an autosomal dominant gene which decreases uroporphyrinogen decarboxylase activity in erythrocytes and liver is an uncommon cause of porphyria cutanea tarda and may not explain all cases of familial porphyria cutanea tarda. The hepatic enzyme defect in the common type of porphyria cutanea tarda, in which erythrocyte uroporphyrinogen decarboxylase activity is normal, may be caused either by inheritance of a gene whose effect is restricted to the liver or by chemicals that selectively inhibit the hepatic enzyme.
Metabolic Effects of the Use of Protein-Sparing Infusions in Postoperative Patients
Authors: Foster K. J. , Alberti K. G. M. M. , Binder C. , Hinks Leslie , Karran S. , Smythe Patricia , Talbot S. , Turnell D. , Ørskov H.
Published: August 2015

1. The mechanism of the purported protein-sparing effects of different postoperative intravenous regimens still remains controversial. We have therefore measured circulating concentrations of metabolites and hormones in blood and urine nitrogen excretion in patients receiving (a) sodium chloride solution (saline), (b) 1.5 g of glucose day−1 kg−1 body weight, (c) 1.5 g of glucose day−1 kg−1 with insulin (0.56 unit day−1 kg−1) or (d) mixed amino acids (1.5 g day−1 kg−1) after abdominal operation.

2. Compared with results for saline-treated patients, glucose infusion resulted in raised glucose and insulin concentrations and lowered ketone body and non-esterified fatty acid concentrations but did not influence protein catabolism.

3. Addition of insulin lowered blood glucose by approximately 1 mmol/l. Total nitrogen excretion during glucose/insulin infusion was significantly less than during saline infusion.

4. Infusion of amino acids, compared with saline infusion, resulted in raised blood glucose, alanine, serum insulin and plasma glucagon concentrations but lower concentrations of plasma non-esterified fatty acids and blood ketone bodies. Insulin concentrations, however, were similar in both amino acid- and glucose-treated groups.

5. Amino acid infusion increased urea and total nitrogen excretion but net nitrogen loss was only 1.9 mmol of nitrogen day−1 kg−1 compared with 12.7 mmol day−1 kg−1 in the saline-treated group and 11.0 mmol day−1 kg−1 in the glucose-treated group.

6. Glucose (and insulin) infusion appeared to inhibit gluconeogenesis, and amino acids to enhance it. The nitrogen-sparing effect of amino acids appears largely related to their mass and is apparently unrelated to changes in ketone bodies and insulin.
Subcellular Fractionation Studies on Hepatic Tissue from a Patient with Pompe's Disease (Type II Glycogen-Storage Disease)
Authors: Peters T. J. , Jenkins W. , Dubowitz V.
Published: August 2015

1. An homogenate of liver biopsy taken from a patient with Pompe's disease (type II glycogen-storage disease) was analysed by enzyme microassay and subcellular fractionation by sucrose-density-gradient centrifugation.

2. A strikingly low activity of lysosomal acid α-d-glucosidase was noted but there was also increased activity of neutral α-d-glucosidase (found in endoplasmic reticulum).

3. Activities of the acid hydrolases, acid phosphatase and β-N-acetyl-d-glucosaminidase, were elevated compared with those of controls. Measurement of latent β-N-acetyl-d-glucosaminidase activity and results of subcellular fractionation experiments, indicated a marked fragility of certain populations of lysosomes. Lysosomes containing predominantly acid phosphatase and β-d-glucuronidase activities appeared to have normal integrity.

4. Assessment of organelle pathology by enzyme microassay indicated low mitochondrial and peroxisomal enzyme activities. In addition there was evidence of mitochondrial damage as reflected by increased sucrose permeability and by ultrastructural studies.
Prostaglandin Synthesis and Inactivation in Kidneys and Lungs of Rats with Experimental Diabetes
Authors: Hoult J. R. S. , Moore P. K.
Published: August 2015

1. Microsomal prostaglandin synthesis and tissue prostaglandin concentrations in the kidneys of rats made diabetic by pretreatment with alloxan or streptozotocin were significantly decreased but were unchanged in lungs.

2. Prostaglandin inactivation was increased in kidneys of alloxan-diabetic rats but not changed in streptozotocin-diabetic kidneys or in the lungs of either group.

3. These changes in prostaglandin metabolism may cause a renal prostaglandin deficit and could contribute to certain pathological sequelae observed in diabetes mellitus.
The Effects of Treatment with Insulin on Serum High-Density-Lipoprotein Cholesterol in Rats with Streptozotocin-Induced Diabetes
Authors: Durrington P. N. , Stephens W. P.
Published: August 2015

1. No significant difference in serum high-density-lipoprotein (HDL) cholesterol was observed when control rats were compared with rats with streptozotocin-induced diabetes of 14 days duration. Blood glucose and serum cholesterol and triglyceride concentrations were significantly higher in the diabetic group.

2. In a second experiment rats with streptozotocin-induced diabetes of 8 days duration were given long-acting porcine insulin (1 unit/day or 3 units/day subcutaneously for 14 days) and were compared with a control group. Blood glucose and serum cholesterol and triglyceride concentrations did not differ significantly with the two doses of insulin and there was no significant difference between serum high-density-lipoprotein cholesterol in control rats and either of the two groups of rats given insulin.

3. When the rats given insulin were grouped according to their blood glucose concentrations, those with blood glucose in the range 20–30 mmol/l were found to have significantly higher serum high-density-lipoprotein cholesterol concentrations than those with higher or lower blood glucose levels or than controls. There was thus a statistically significant curvilinear relationship between blood glucose and serum high-density-lipoprotein cholesterol concentrations.
Ventilatory Pattern and Drive after Acute Myocardial Infarction
Authors: Clarke H. , Dhingra S. , Anthonisen N. R.
Published: August 2015

1. In 18 patients with acute myocardial infarction, we measured ventilation, frequency, inspiratory duration and the pressure at the mouth 0.1 s after the onset of inspiration against an occluded airway; mean inspiratory flow and the fraction of the breathing cycle devoted to inspiration were calculated. Measurements were made on 2–3 consecutive days soon after admission and repeated 4–10 days after admission.

2. Eight patients showed no clinical evidence of left heart failure at any time; in these patients no changes in breathing pattern, ventilation or occlusion pressure were observed.

3. Ten patients were in heart failure, as judged by the presence of râles and/or hypoxaemia on day 1 of the study, and all had recovered on the last day. When in failure these patients demonstrated increased minute ventilation, occlusion pressure was increased more than was mean inspiratory flow and their breathing pattern was altered. Tidal volume was similar to that in patients without failure and did not change with time, but frequency was initially high and fell as recovery from failure occurred. The duration of inspiration was decreased during failure, so mean inspiratory flow was increased. The fraction of the breathing cycle devoted to inspiration was constant and similar to that in patients without failure.

4. While in failure no patients were acidotic and not all patients were hypoxaemic; administration of oxygen did not influence results in two patients during failure.

5. These results indicate that clinically detectable pulmonary oedema is associated with increased ventilatory drive, which cannot be explained on the basis of hypoxaemia or hypercapnia. The observed changes in breathing pattern were probably due at least in part to vagal reflexes, and these may have contributed to the increase in drive.
Renin Release during Head-up Tilt Occurs Independently of Sympathetic Nervous Activity in Tetraplegic Man
Authors: Mathias C. J. , Christensen N. J. , Frankel H. L. , Peart W. S.
Published: August 2015

1. The role of the sympathetic nervous system in the release of renin during head-up tilt has been studied in five normal subjects and in four tetraplegic patients with cervical spinal-cord transection above the sympathetic outflow. Blood pressure, heart rate and concentrations of plasma noradrenaline, plasma adrenaline and plasma renin activity were measured during head-up tilt to 45° before and after acute β-adrenoreceptor blockade with intravenous propranolol.

2. In the normal subjects there were minimal changes in blood pressure during head-up tilt and there was a rise in both plasma noradrenaline concentration and plasma renin activity. After propranolol values of plasma renin activity at rest fell with little change occurring during head-up tilt.

3. In the tetraplegic patients there was a substantial fall in blood pressure during head-up tilt. Concentrations of plasma noradrenaline and adrenaline did not change but there was a marked increase in plasma renin activity. Values of plasma renin activity both at rest and during head-up tilt were unaffected by propranolol.

4. We conclude that in tetraplegic patients renin release during head-up tilt may occur independently of sympathetic nervous activity and is probably largely dependent on activation of renal vascular receptors.
Propionate Enhancement of Acetoacetate Oxidation in Perfused Rat Hearts
Authors: Revsin-Lanier Betty , Lebowitz Joyce , Morrow Grant
Published: August 2015

1. In isolated perfused rat hearts, acetoacetate oxidation was significantly enhanced by propionate.

2. No enhancement of acetoacetate oxidation could be observed in vitamin B12-deficient rat hearts when propionate was present.

3. Although the mechanisms of enhancement are not clear, ketone clearance is enhanced by propionate and may provide an insight into the therapy of certain diseases characterized by ketosis.
Renin Precursor from Mouse Kidney Identified by Cell-Free Translation of Messenger RNA
Authors: Poulsen K. , Vuust J. , Lund T.
Published: August 2015

1. The biosynthetic precursor of renin (pre-prorenin) from mouse kidney is a single chain polypeptide with a molecular weight of 50 000.

2. This is the same value as previously found for mouse submaxillary gland pre-prorenin.

3. Mouse kidney pre-prorenin (mol. wt. 50 000) is larger than the enzymatically active renin (mol. wt. 40 000).
Regional Lung Function in Bilateral Diaphragmatic Paralysis
Authors: Amis T. C. , Ciofetta G. , Hughes J. M. B. , Loh L.
Published: August 2015

1. The distribution of regional function in the lungs of six patients with bilateral diaphragmatic paralysis was investigated by continuous inhalation and infusion of the radioactive gases 81mKr and 85mKr during tidal breathing.

2. In the supine and right lateral decubitus postures the vertical distribution of ventilation per unit alveolar volume was less in the dependent zones, the reverse of that found in normal subjects. In the upright posture ventilation was slightly decreased at the lung base. Perfusion per unit alveolar volume was more uniformly distributed than normally in the upright posture, and decreased from superior to inferior in the supine posture. In the lateral decubitus posture, perfusion of the lower lung was greater than that of the upper. Ventilation/perfusion ratios were more uniformly distributed in the patients than in normal subjects, except in the right lateral decubitus posture.

3. Alterations in the distribution of ventilation may be explained in terms of the altered mechanical interaction of chest wall, mediastinal and abdominal contents, with selective use of intercostal and accessory muscles. The effects on the distribution of blood flow are probably related to the low end-expiratory lung volume.