bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical specificity of coughing in man
Authors: Godden D. J. , Borland C. , Lowry R. , Higenbottam T. W.
Published: August 2015

1. The purpose of this study was to test whether cough response to inhaled ultrasonically nebulized fluid is dependent on the ionic content of the fluid.

2. Coughing was recorded in human volunteers during inhalation of aqueous solutions in a series of double blind randomized experiments.

3. The occurrence of cough was found to be dependent on the concentration of chloride ions in the inhaled fluid, cough frequency progressively increasing as chloride ion concentration was reduced.

4. It is proposed that the ion composition of the surface lining fluid of the airway may moderate the cough response by means of a chemoreceptor, although tonicity may also be important.
Effect of noradrenaline, vasopressin and angiotensin II on renal prostaglandins in man
Authors: Loup Richard , Favre Laurent , Vallotton Michael B.
Published: August 2015

1. To examine the response of renal prostaglandins (PG) to systemic and renal vasoconstriction noradrenaline (NA), arginine vasopressin (AVP) and angiotensin II (ANG II) were each infused into eight healthy female subjects for 3 h on different days. Urinary excretion of PGE2, PGF2α and 6-keto-PGF1α was determined hourly.

2. NA and ANG II stimulated excretion of PGF2α significantly, but not of PGE2 or 6-keto-PGF1α AVP stimulated renal PGF2α and 6-keto-PGF1α significantly, but not PGE2.

3. A weak correlation was found between urinary PGF2α and diastolic blood pressure during NA and ANG II infusions, but not during AVP infusion.

4. The release of renal PG does not appear to constitute an obligatory and concomitant response to the blood pressure rise induced by the pressor agonists. The greater response of PGF2α than of PGE2 may result from a preferential direct effect on PGF2α secretion or from an increased conversion of PGE2 into F2α.
The effect of chronic hydrochlorothiazide administration on renal function in the rat
Authors: Walter S. J. , Shirley D. G.
Published: August 2015

1. Hydrochlorothiazide was administered at two doses to Long-Evans rats for 7–10 days. Both doses resulted in an initial natriuresis and diuresis. After 1 day of treatment the natriuresis abated, but the diuresis persisted.

2. The mechanisms responsible for these chronic effects were investigated by performing clearance and micropuncture studies on all animals; collections were made from late proximal tubules and from early and late regions of distal tubules.

3. Values for total glomerular filtration rate and single-nephron filtration rate in thiazide-treated rats were not significantly different from those in control animals.

4. The delivery of sodium to the end of the proximal convoluted tubule was considerably reduced in each group of thiazide-treated rats. Although sodium delivery to the early distal tubule was also significantly lower than in control animals, the difference had disappeared by the late distal tubule.

5. It is concluded that the return of sodium excretion to control levels during chronic hyrochlorothiazide administration is a consequence of increased fractional reabsorption by the proximal tubules, secondary to a thiazide-induced sodium depletion. This results in less sodium being delivered to the nephron site at which thiazides exert their major inhibitory effect.

6. Fluid delivery to the end of the proximal convoluted tubule and to the early distal tubule was significantly reduced in thiazide-treated rats; in animals given the higher dose of diuretic it was also significantly reduced at the end of the distal tubule. Nevertheless, in both thiazide-treated groups urine flow rate was elevated, suggesting that reabsorption of water from the collecting ducts is reduced during chronic thiazide administration.
Nicotine does not cause ‘bronchitis’ in the rat
Authors: Rogers D. F. , Williams Deborah A. , Jeffery P. K.
Published: August 2015

1. Nicotine is of interest as a major constituent of cigarette smoke and as an additive to chewing gum used to help patients to stop smoking.

2. Specific pathogen-free rats were given an aerosol or injections of nicotine hydrogen (+) tartrate (l-isomer) for 2 or 3 weeks at three doses and the number of secretory cells in the surface epithelium of airways was determined.

3. By aerosol, a dose giving 10 ng of nicotine/ml of plasma had no effect on secretory cell number.

4. By injection, nicotine had a ‘bi-phasic’ effect depending on dose: it reduced secretory cell number at plasma concentrations of 650 ng/ml of plasma or increased it at 2360 ng/ml of plasma.

5. Thus nicotine alone, given to rats at doses similar to those found in cigarette smokers and those who chew nicotine gum, does not cause secretory cell hyperplasia in the conducting airways of the rat.
A comparison of the relative effectiveness of three transplant preservation fluids upon the integrity and function of rabbit proximal convoluted tubules perfused in vitro
Authors: Pirie Susan C. , Potts D. J.
Published: August 2015

1. Rabbits were anaesthetized and kidneys removed directly with no flush (group NF), or alternatively kidneys were flushed (group F) with sodium phosphate buffered 140 mmol/1 sucrose (PBsuc 140), Collins C2 (C2) or Euro-Collins (EC) transplant preservation solutions and stored at 4°C for 0–4, 24 or 48 h. Mid-cortical proximal convoluted tubule (PCT) segments were dissected from all groups and set up for microperfusion in vitro. Observations were made of tubule morphology, fluid reabsorption rate (Jv), bath leak of the glomerular marker iothalamate and transmural potential difference (p.d.), both at 37°C and at 15–20°C, in order to compare the relative effectiveness of the solutions in the preservation of tubule integrity and immediate function.

2. Tubules from kidneys flushed with EC and C2 contained luminal debris and frequently had high bath leaks of iothalamate, both indicative of poor preservation of tubule integrity. In contrast, tubules from NF kidneys and PBsuc140-flushed kidneys were free of luminal debris with a lower incidence of high iothalamate leaks.

3. Tubules from PBsuc140-flushed and EC-flushed kidneys after 0–4 and 24 h storage had Jv that were similar to those of NF kidneys. Tubules from all groups of flushed kidneys after 48 h cold storage and all tubules from C2-flushed kidneys showed reduced Jv values. In all cases Jv was reduced to approximately zero when the temperature was lowered to 15–20°C.

4. Transmural p.d. was similar in all groups except for particularly low p.d. values observed in tubules from C2-flushed kidneys after 48 h storage.

5. These observations suggest that PBsuc140 is more effective in the preservation of tubule function during prolonged cold storage than the glucose-based Collins solutions. The marked difference in the effectiveness of C2 and EC contra-indicates the inclusion of magnesium (present in C2) for preservation of kidneys, as judged by experiments on the rabbit.
Effect of angiotensin II on prostanoid synthesis in isolated rat glomeruli
Authors: Podjarny E. , Shapira J. , Rathaus M. , Kariv N. , Bernheim J.
Published: August 2015

1. The influence of angiotensin II (ANG II) on the synthesis of glomerular prostanoids is controversial, possibly because of the different methodologies employed. In order to assess this inter-relationship isolated rat glomeruli were incubated with and without shaking. The use of shaking during incubation significantly increased the amounts of prostanoid synthesized, most probably because of continuous non-specific activation of phospholipase (PLA2) activity.

2. After preincubation in a non-shaking bath, ANG II was added for a second incubation period. A marked increase of prostaglandin (PG) E2 and, to lesser degree, of thromboxane (TX) B2 was noted, with no change on PGF2α synthesis.

3. These results show (a) that preincubation without shaking, by lowering the non-specific activation of the PLA2 activity, may unmask, in vitro, specific peptide stimulation, and (b) that ANG II, stimulating principally PGE2 synthesis, may modify the vasoactive status of the glomerular vasculature.
Influence of alveolar hypoxia on pulmonary vasomotor responses to almitrine in the dog
Authors: Hughes J. M. B. , Allison D. J. , Goatcher A. , Tripathi A.
Published: August 2015

1. Almitrine bismesylate (5–10 μg/kg) was given as an intravenous bolus to anaesthetized, paralysed dogs (a) with closed-chest (n = 5) and (b) with open-chest (n = 7) in whom the retrocardiac lobe was separately ventilated. Pulmonary, lobar and systemic haemodynamics were measured under hypoxic, normoxic and hyperoxic conditions. Total pulmonary blood flow was measured by thermodilution and lobar flow by electromagnetic flow meter.

2. In the closed-chest preparations, almitrine caused an increase in pulmonary vascular resistance (PVR) at all levels of inspired oxygen, the increments being 82% (30% O2), 91% (air) and 9% (13% O2). The control PVR varied inversely with arterial Po2 but there was no significant interaction between the almitrine and hypoxia induced vasoconstriction with multiple linear regression analysis.

3. In the open-chest preparations, PVR and lobar vascular resistance (LVR) increased after almitrine by 48% and 41% respectively when both lung and lobe inspired 30% O2. When the lobe was switched to 12.5% O2 or nitrogen (lung inspiring 30%) PVR again increased (+ 52%) after almitrine but LVR decreased in five of seven lobes (lobar flow increasing despite constant cardiac output), the overall change being − 4%. Analysis of covariance showed that the lobar response to almitrine was significantly different under hypoxic conditions compared with hyperoxic (P < 0.05).

4. With ventilation maintained constant, there was no significant change in arterial Po2 after almitrine in any experimental condition.

5. In conclusion, almitrine is generally a pulmonary vasoconstrictor but can dilate vessels when they are constricted by local hypoxia. Almitrine does not enhance local hypoxic vasoconstriction in the dog.
Effects of chronic uraemia on the formation of glucose and urea plus ammonia from l-alanine, l-glutamine and l-serine in isolated rat hepatocytes
Authors: Klim Rita A. , Albajar Marta , Hems Reginald , Williamson Dermot H.
Published: August 2015

1. The effects of chronic uraemia on glucose production and nitrogen release (urea plus ammonia formation) from alanine, glutamine or serine in isolated rat hepatocytes were studied.

2. Uraemia increased the rate of formation of urea plus ammonia from all three amino acids by 38-93% when they were present at a final concentration of 10 mmol/l. At lower concentrations (2 mmol/l) the rate of nitrogen release was not significantly increased.

3. Hepatocytes from normal rats whose food intake had been restricted to the level of that of uraemic rats did not show the increased rates of nitrogen release.

4. The increased rates of nitrogen release with hepatocytes from uraemic rats were not accompanied by increased rates of glucose synthesis. Instead, accumulation of metabolic intermediates occurred: lactate and pyruvate (alanine or serine as substrates) and glutamate (glutamine as substrate).

5. Livers of uraemic rats had increased activities of glutarninase (30%) and serine dehydratase (100%).

6. Hepatocytes from normal rats treated with phlorhizin to increase the plasma glucagon/insulin ratio behaved in a similar manner to hepatocytes from uraemic rats. They had increased serine dehydratase activity, and increased rates of utilization of serine or glutamine.

7. The possible implications of these findings for human uraemia are discussed.
Ventilatory sensitivity to inhaled carbon dioxide around the control point during exercise
Authors: Cummin Andrew R. C. , Alison Jennifer , Jacobi Margaret S. , Iyawe Vincent I. , Saunders Kenneth B.
Published: August 2015

1. Rapid steady-state CO2 responses were determined in five normal adults at rest and at up to six levels of exercise by injecting pure CO2 at a constant flow into the inspiratory limb of a breathing circuit.

2. Ventilation (V) was measured with a dry gas meter and Pco2 at the mouth was recorded by a mass spectrometer. Mean alveolar Pco2 (Paco2) was taken as equal to end-tidal Pco2 at rest, and during exercise was derived graphically from the sloping alveolar plateaus. The accuracy of the latter method was checked in separate experiments against arterial Pco2 (Paco2).

3. The mean results showed a linear relationship between change in Paco2 and change in V for work loads ranging from rest to 75 W (r = 0.94–0.98). Above 75 W the response became concave down with an initial essentially isocapnic phase.

4. This suggests that during exercise there is a large increase in CO2 sensitivity about the control point.
Evidence for adaptive diet-induced thermogenesis in man during intravenous nutrition with hypertonic glucose
Authors: King R. F. G. J. , McMahon M. J. , Almond D. J.
Published: August 2015

1. This study was designed to investigate the thermogenic effect of intravenously administered nutrition with glucose (given with a fixed nitrogen intake of 12.5 g daily as amino acids) as the principal source of energy. The protocol was designed so that each patient received their energy intake in five consecutive periods of 3 days with intakes ranging from 6650 to 17100 kJ/day with increments or decrements of 2600 kJ.

2. Thermogenesis from administered glucose was evident between levels of energy supply of 6650 kJ/day and 17100 kJ/day. The progressive rise in oxygen consumption and carbon dioxide production accounted for a total of 31% of the additional glucose which was administered. The net rate of fat synthesis from glucose reached a maximum 147 g/day at an energy supply of 14 500 kJ/day.

3. This study suggests that both fat synthesis and the associated obligatory thermogenesis is the main component of diet-induced thermogenesis in response to glucose intakes in excess of 150 kJ day−1 kg−1. If the energy cost of fat synthesis (fat associated obligatory thermogenesis) is taken to be 22% of the total energy of the increase in glucose supplied, then only 9% (31–22%) of the glucose can be accounted for by adaptive thermogenesis.
Binding of glycosaminoglycans to sodium urate and uric acid crystals
Authors: Fellström Bengt , Lindsjö Monica , Danielson Bo G. , Ljunghall Sverker , Wikström Björn
Published: August 2015

1. The binding of heparin, chondroitin sulphate and the low molecular weight heparin analogue pentosan polysulphate to sodium urate and uric acid crystals was studied by the use of competitive binding technique. Trace amounts of radioactively labelled glycosaminoglycans were used in the binding step, and varying amounts of unlabelled glycosaminoglycans for the competition experiments.

2. The experiments were carried out in 140 mmol/l NaCl at pH 6, with or without 5 mmol/l CaCl2 in the solution.

3. A reversible and almost complete binding of heparin and chondroitin sulphate to sodium urate crystals did occur in the presence of calcium, whereas pentosan polysulphate bound incompletely. The binding was much less pronounced in the calcium-free conditions.

4. Uric acid crystals did not bind any of the three inhibitors, not even with calcium present.

5. The clinical relevance depends on whether sodium urate microcrystals are present in the urine of calcium stone patients, to cause a binding and thereby a masking or inactivation of these inhibitors in the urine, which seems to be possible in the presence of calcium. However, the potential of pentosan polysulphate for the treatment of calcium stone patients does not seem to be at risk from this effect.
Renal water excretion before and after remission of nephrotic syndrome: Relationship between free water clearance and kidney function, arginine vasopressin, angiotensin II and aldosterone in plasma before and after oral water loading
Authors: Pedersen E. B. , Danielsen H. , Sørensen S. S. , Jespersen B.
Published: August 2015

1. An oral water load of 20 ml/kg body wt. was given to eight patients with nephrotic syndrome before and after remission of the syndrome, and to 13 healthy control subjects. Urine volume (D), free water clearance (Cwater), plasma concentrations of arginine vasopressin (AVP), angiotensin II (ANG II) and aldosterone (Aldo), were determined before and three times during the first 4 h after loading.

2. D and Cwater increased to a significantly lower level (P < 0.01) after water loading in patients with nephrotic syndrome than in control subjects, but D and Cwater were normal after remission of the syndrome. The maximum increase in Cwater (ΔCwater max.) was 1.07 ml/min (median) before remission and 7.93 ml/min after, compared with 8.01 ml/min in the control group.

3. Creatinine clearance (Ccr) increased significantly after remission (63 ml/min to 88 ml/min, P < 0.01), and the fractional excretion of sodium was enhanced. AVP was higher in the nephrotic syndrome both before (2.9 pmol/l) and after remission (2.9 pmol/l) compared with the control group (1.8 pmol/l). ANG II and Aldo did not change after remission and remained at the same level as in the control group.

4. The elevation in ΔCwatermax after remission was accompanied by an increase in Ccr in all patients and ΔCwatermax. and Ccr were significantly correlated (ρ = 0.600, n = 16, P < 0.05). No relationship was found between the change in ΔCwater max. and ANG II and Aldo.

5. AVP was significantly suppressed in patients with nephrotic syndrome before remission, but not after remission nor in control subjects, so that although AVP did not differ in nephrotic patients before and after remission, AVP cannot be excluded as a contributory factor to the reduction in Cwater in the nephrotic syndrome.

6. It is concluded that patients with nephrotic syndrome excrete an oral water load slower than control subjects and that the excretion rate is normal after remission of the syndrome. It is suggested that the normalization of Cwater may be attributed to an increase in glomerular filtration rate or a decrease in proximal tubular sodium reabsorption, although a possible role for AVP has not been excluded.
Circulating hyaluronate: Concentration in different vascular beds in man
Authors: Bentsen Kirsten D. , Henriksen Jens H. , Laurent Torvard C.
Published: August 2015

1. The plasma concentration of hyaluronate (hyaluronic acid; HA) was measured in different vascular beds in order to determine regional kinetics of endogenous HA in fasting, supine subjects with normal (n = 6) or moderately decreased kidney function (n = 9).

2. In both groups hepatic venous HA was significantly below the value obtained in plasma from pulmonary artery, inferior vena cava, and renal veins (P < 0.001), giving a net hepato-splanchnic extraction ratio of HA about 33%.

3. The concentration of HA in renal veins was significantly below that of the pulmonary artery and inferior vena cava (P < 0.05). Average net renal extraction ratio of HA in normal kidneys was approximately 20%. Unilateral kidney function was assessed by 131I-hippuran renography, and the kidney with better function had a significantly higher extraction ratio when compared with the kidney with the lower function (P < 0.025). HA was inversely correlated to glomerular filtration rate (r = − 0.59, P < 0.02).

4. Assuming a plasma flow of 800 and 600 ml/min in normal liver and kidneys, respectively, the average normal plasma clearances of HA in these organs in the resting subject may be estimated to be 250 and 120 ml/min, respectively.

5. The results indicate that the hepato-splanchnic region normally plays a major role in the bio-degradation of endogenous circulating HA. The kidneys also eliminate the compound, presumably the low-molecular-weight fraction of the material. The results may explain abnormally high values of circulating HA in patients with diseases in these organs.
The effect of tobacco smoke upon airway secretion in the cat
Authors: Peatfield A. C. , Davies Julia R. , Richardson P. S.
Published: August 2015

1. We have collected secretions from a segment of trachea in the neck of cats anaesthetized with chloralose. At the start of experiments sodium [35S]sulphate and [3H]glucose were given into the segment to radiolabel secretions by biosynthesis. Subsequently, changes in output of radiolabelled macromolecules were used to indicate changes in mucin secretion rate.

2. Cigarette smoke, diluted to 10% by volume, was passed through the larynx or through the tracheal segment, or given into the lower airway. Control insufflations of air were given by the same routes.

3. When cigarette smoke was passed through the larynx, it did not change the secretion rate of radio-labelled mucins into the tracheal segment.

4. Cigarette smoke, given directly into the tracheal segment, stimulated the output of 35S-labelled mucins. Cutting the autonomic nerves to the segment failed to alter the response to cigarette smoke, but ganglion blockade with pentolinium abolished it.

5. Cigarette smoke given into the lower airways and lungs stimulated the output of radiolabelled mucins into the segment. Denervation of the segment failed to prevent this, but ganglion blockade abolished the response.

6. Measurements of plasma nicotine concentrations in some experiments showed that nicotine was absorbed from smoke in the lower airway and also suggested some absorption of nicotine from the tracheal segment.

7. We conclude that nicotine, absorbed either directly into the tracheal wall or via the blood, can stimulate the autonomic ganglia which innervate airway submucosal mucous glands. This mechanism outweighed the effect of airway irritant reflexes in these experiments.
Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes
Authors: Connell J. M. C. , Ding Yu-An , Fisher B. M. , Frier B. M. , Semple P. F.
Published: August 2015

1. Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects.

2. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 ± 0.8 sd sites/platelet in diabetic patients and 6.4 ± 0.8 in normals, P < 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 ± 1.5 × 10−10 mol/l in diabetic patients and 5.4 ± 1.4 × 10−10 mol/l in normals).

3. Plasma concentrations of renin and angiotensin II were similar in both groups.

4. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.
Ribonucleic acid turnover in man: RNA catabolites in urine as measure for the metabolism of each of the three major species of RNA
Authors: Sander Gernot , Topp Heinrich , Heller-Schöch Gesa , Wieland Jan , Schöch Gerhard
Published: August 2015

1. Urinary excretion of the non-reusable modified RNA catabolites pseudouridine (ψ), 7-methylguanine (m7Gua) and N2,N2-dimethylguanosine (m22Guo) was measured in preterm infants and in adults. The values (in μmol/mmol of creatinine) were: for preterm and ‘small for gestational age’ infants (n = 26; number of samples = 38) ψ = 164 (sd 32), m7Gua = 39.1 (sd 9.0), m22Guo = 10.6 (sd 2.1); for adults (n = 32) ψ = 25.3 (sd 3.1), m7Gua = 4.8 (sd 0.89), m22Guo = 1.53 (sd 0.42).

2. Our measurements were compared with an expectation derived from the average cellular distribution of ψ, m7Gua and m22Guo between rRNA, tRNA and mRNA. m22Guo occurs exclusively in iRNA, ψ in both rRNA and tRNA, and m7Gua in all three RNA classes, in proportions which can be estimated for the steady state. Urinary excretion of ψ and m22Guo should reflect their steady-state distribution, since rRNA and tRNA have been shown to have similar turnover rates in mammalian tissues.

3. We conclude that we can use the excretion of m22Guo to assess whole-body tRNA turnover. Since tRNA contains ψ constant proportion to m22Guo, the proportion of urinary ψ stemming from tRNA can be estimated, and the remainder (~ 60–65%) is an indicator of rRNA turnover. Finally, the excretion of m7Gua far exceeds the proportion predicted to come from rRNA and tRNA. We ascribe this excess (~ 60–70% of the total) to the turnover of the mRNA ‘cap’-structure, which is typical for all higher organisms. mRNA turnover is known to be much higher than that of rRNA or tRNA.

4. Calculated average RNA turnover rates (in μmol day−1 kg−1 body weight) were: for preterm infants 0.1 rRNA, 1.93 tRNA, 2.44 mRNA-‘cap’; for adults 0.037 rRNA, 0.63 tRNA, 0.62 mRNA-‘cap’.

5. Estimation of RNA turnover rates may supplement the hitherto more widely used 15N tracer studies in assessing whole-body metabolic state. Results obtained up to now closely agree with the findings from 15N tracer studies (approximately threefold higher turnover rates in preterm infants than in adults). This is probably correlated with the fact that RNA is intimately involved in all steps of protein synthesis.
The effect of polyethylene glycol by gavage on electrolyte and water excretion in the rat
Authors: Sonkodi S. , Tichy B. , Brown W. B. , Robertson J. I. S.
Published: August 2015

1. The effects of polyethylene glycol (PEG) 200 administered by gavage on electrolyte and water excretion were investigated in the rat.

2. PEG 200 led, in intact rats, to dose-related increased drinking and to diuresis.

3. In the first 2 h after PEG 200 administration, water consumption in intact rats exceeded urine output.

4. PEG 200 enhanced the excretion of both sodium and potassium, but the sodium excretion was proportionately greater, resulting in an elevation of the urinary sodium/potassium ratio.

5. Bilateral nephrectomy was not accompanied by increased drinking in PEG 200-treated rats, although raised serum osmolality was seen.

6. Thus, given by gavage, PEG 200 is not an inert vehicle for drug administration.
Urinary kallikrein response to repeated frusemide injections in rats: Effect of adrenalectomy and deoxycorticosterone acetate treatment
Authors: Obika L. F. O. , Marin-Grez M.
Published: August 2015

1. The effect of repeated intravenous injections of frusemide (0.17 mg/kg) on the urinary kallikrein excretion of normal, adrenalectomized and deoxycorticosterone acetate (D0CA)-treated adrenalectomized rats was studied.

2. Adrenalectomy decreased baseline urinary kallikrein excretion, while DOCA treatment restored it to normal.

3. Frusemide injections repeatedly increased urinary kallikrein excretion in the three groups of rats studied. Compared with control and DOCA-treated animals, adrenalectomized rats were less responsive.

4. The excretion of urinary kallikrein was positively correlated with urine volume and with the excretion of sodium and potassium in all groups. The regression lines were shifted to the left in DOCA-treated adrenalectomized rats showing that mineralocorticoids enhance the effect of frusemide on urinary kallikrein excretion. The regression lines between urinary kallikrein excretion and the measured variables in adrenalectomized rats did not differ from those of control animals.

5. We conclude that the response of urinary kallikrein to frusemide is influenced by the level of mineralocorticoid activity. The effect of frusemide on urinary kallikrein excretion does not appear to be a ‘wash-out’ of the enzyme since its influence did not subside after repeated injections.
The contribution of PGI2 to the effects of captopril in conscious dogs in differing states of sodium balance
Authors: Watson Michael L. , Jones Robert L.
Published: August 2015

1. There is some evidence that increased prostaglandin synthesis may mediate some of the effects of the angiotensin converting enzyme inhibitor captopril.

2. The potential role of prostaglandin (PG)I2 in this process was assessed by measurement of changes in urinary 6-keto-PGF1α excretion after captopril in eight sodium replete and depleted conscious dogs.

3. In sodium replete animals captopril induced a small decrease in blood pressure, transient increases in effective renal plasma flow and urinary 6-keto-PGF1α excretion, and progressive increases in plasma renin activity (PRA) and urinary sodium excretion.

4. By contrast, during sodium depletion captopril induced a large decrease in blood pressure, a transient increase in effective renal plasma flow and urinary 6-keto-PGF1α excretion, an early large but transient increase in PRA and small progressive increase in sodium excretion.

5. The time course of changes after captopril suggested that increased PGI2 synthesis may contribute to the transient decrease in renal vascular resistance.

6. The increase in PRA during sodium depletion was not associated with any change in urinary 6-keto-PGF1α excretion.
Inherited variations in glomerular handling of antigen between Lewis and DA rats
Authors: Jones J. M. Boulton , Chandrachud Lata , Mosely Hannah
Published: August 2015

1. Inherited differences in the quantity and site of renal deposition of antigen were studied in two inbred strains of healthy rats, one of which, Lewis, is susceptible to Heymann's nephritis and the other (DA) is resistant.

2. Deposition of human cationic immunoglobulin G (IgG) was significantly less in the liver, spleen and kidneys of Lewis rats compared with DA rats, which suggests that the density of the negatively charged molecules in the capillary walls of Lewis rats is less than in DA rats. Immunofluorescent studies of the kidneys 15 min after administration of cationic IgG showed that it could be detected only on the glomerular basement membrane (GBM) and that the intensity of the deposits was less in Lewis rats.

3. The mesangial uptake of aggregated IgG was greater in DA rats at all times studied. There was remarkable similarity in the glomerular processing of cationic IgG and aggregated IgG in both strains.

4. These differences in glomerular properties, capillary charge and mesangial uptake may lead to differences in the deposition of antigen within the glomerulus and in the response to the subsequent inflammatory reactions. This provides a new hypothesis for genetic predisposition of individuals to particular glomerulopathies.
Compensatory spleen growth and protective function in rats
Authors: Van Wyck David B. , Witte Marlys H. , Witte Charles L.
Published: August 2015

1. To quantify compensatory spleen growth after reduction in splenic mass and to determine the effect of age and vascular supply on remnant growth, we examined adult and weanling rats for remnant regeneration and adult rats for host protection against bloodstream pneumococcal challenge at intervals up to 180 days after partial resection or autograft implantation.

2. In adults, subtotally resected spleens with remnant blood flow and segmental anatomy otherwise intact (eutopic remnants) displayed prompt but relatively limited gains in remnant weight and nucleated cell number, and growth after 60 days was minimal; survival after pneumococcal challenge was directly related to initial remnant weight and unrelated to length of postoperative interval. Splenic autografts (ectopic remnants), by comparison, underwent necrosis early after devascularization, recovered initial remnant weight slowly, fell far short of restoring original cellularity, and even 6 months after implantation barely attained initial size; moreover, host protection against pneumococcaemia was no different in rats with autografts than in those with no residual spleen. Remnants in situ (both partial resection and whole spleens) grew more vigorously in weanling than adult rats.

3. The results suggest that splenic regeneration after either partial resection or implantation is much more limited than previously suggested, at least in disease-free rats, and is regulated by size and integrity of the initial remnant spleen, adequacy of vascular inflow, and age of the host. Whereas eutopic remnants provide protection against blood-borne pneumococcal challenge in proportion to initial residual size, ectopic remnants even with prolonged maturation fail to display immunoprotective function.
Development and application of a superfusion technique for the study of renin secretion in rat renal cortical cells
Authors: Drury P. L. , Williams B. C. , Edwards C. R. W. , Oddie C. J. , Horne B.
Published: August 2015

1. A dynamic column superfusion system has been developed for the study of renin secretion in rat renal cortical cells.

2. Cells were isolated by collagenase digestion and mechanical dispersion, before suspension with polyacrylamide beads and superfusion with oxygenated physiological medium.

3. Renin was detected in the superfusate by incubation of fractions with excess nephrectomized sheep substrate in the presence of angiotensinase inhibitors followed by radioimmunoassay of the angiotensin I generated.

4. Optimized methodology included a purposebuilt polytetrafluorethylene flow cell, a 1 h equilibration to achieve a steady state, 5 min eluate collections, a 15 min stimulatory and a 30 min recovery period, and duration of perfusion of up to 270 min.

5. Significant increments above baseline renin release were seen with the stimuli of adrenaline, noradrenaline and isoprenaline. These could be demonstrated with concentrations of 10−9 mol/l (adrenaline), 5 × 1O−10 mol/l (noradrenaline) and 1O−9 mol/l (isoprenaline).

6. This technique has significant advantages over previous methods for the study of renin secretion in vitro at the cellular level. It is reproducible and sensitive, and avoids many of the limitations of static cell suspension and kidney slice methods.
Fatty acid synthesis in vitro by liver tissue from control subjects and patients with alcoholic liver disease
Authors: Venkatesan S. , Leung Nancy W. Y. , Peters Timothy J.
Published: August 2015

1. Percutaneous liver biopsy specimens were obtained from 11 control subjects, 24 alcoholic patients and six diabetic patients with mild to severe fatty liver and incubated in Krebs–Henseleit buffer containing 3H2O. The incorporation of 3H into fatty acid was measured and the absolute rate of fatty acid synthesis calculated.

2. Fatty acid synthesis rates were significantly lower in alcoholic fatty liver than in controls.

3. Fatty acid synthesis rates were similar in controls and patients with diabetic fatty livers.

4. Addition of 50 mmol/l ethanol did not alter the fatty acid synthesis rates in vitro. It is concluded that enhanced lipogenesis is not the major cause of fatty liver in patients with alcoholic fatty liver.
Exaggerated responsiveness of immunoreactive atrial natriuretic peptide to saline infusion in chronic renal failure
Authors: Walker Robert G. , Swainson Charles P. , Yandle Tim G. , Nicholls M. Gary , Espiner Eric A.
Published: August 2015

1. Plasma levels of immunoreactive alpha human atrial natriuretic peptide (IR-ANP) were measured in nine patients with chronic renal failure before and after removal of 1.3–3.7 litres of fluid by ultrafiltration and again during volume repletion with intravenous sodium chloride solution (150 mmol/l: saline).

2. Baseline levels of IR-ANP were elevated but fell by 22% during ultrafiltration.

3. Saline infusion induced a rapid and steep rise in IR-ANP levels which were 150% of baseline while body weight was still 2% below baseline.

4. Changes in plasma renin, angiotensin II, aldosterone and vasopressin during the study were slight compared with the change in IR-ANP, but noradrenaline levels rose threefold during ultrafiltration.

5. There was a significant positive relationship between arterial pressure and IR-ANP levels before and after ultrafiltration.

6. These results lend support to the suggestion that atrial peptides are of physiological importance, especially in states of chronic fluid overload such as chronic renal failure.
Atrial natriuretic peptide inhibits the effect of endogenous angiotensin II on plasma aldosterone in conscious sodium-depleted rats
Authors: Chartier Lynn , Schiffrin Ernesto L.
Published: August 2015

1. Previous studies have shown that atrial natriuretic peptide (ANP) inhibits the secretion of aldosterone by isolated adrenal glomerulosa cells stimulated by angiotensin II, adrenocorticotropic hormone and potassium in vitro. We have also demonstrated that this inhibitory effect of ANP on plasma aldosterone induced by angiotensin II and adrenocorticotropic hormone can be reproduced in vivo in conscious unrestrained rats. In this study, we have investigated the effect of an intravenous infusion of ANP on plasma aldosterone in conscious unrestrained sodium-depleted rats.

2. During sodium depletion, the rise in plasma renin activity which determines an increment in the circulating concentration of angiotensin II was accompanied by a rise in aldosterone secretion as expected. ANP infused intravenously at a dose which increased the plasma concentration of the peptide three- to five-fold, produced a significant decrement in the concentration of aldosterone in plasma after an infusion period of 120 min. There was no significant effect of ANP on plasma renin activity and plasma corticosterone concentration.

3. Since the increase in plasma aldosterone levels in sodium-depleted rats is mainly dependent on the activation of the renin–angiotensin system, we conclude that ANP may modulate the effect of endogenous as well as exogenous angiotensin II on plasma aldosterone secretion.
Vasoactive intestinal peptide: A direct renal natriuretic substance
Authors: Duggan K. A. , MacDonald G. J.
Published: August 2015

1. To establish whether or not vasoactive intestinal peptide (VIP) acts directly on the kidney and also to define the renal responses to it, we compared the natriuretic and haemodynamic responses to VIP (10−4–100 pmol min−1 kg−1) infused intravenously with those obtained by direct infusion into the renal artery in seven conscious male rabbits.

2. VIP had significant effects on the renal circulation without changing systemic arterial pressure or pulse rate. There was a significant fall from control in effective renal plasma flow (P < 0.05 renal infusion, P < 0.01 intravenous infusion) and glomerular filtration rate (P < 0.01 renal, P < 0.05 intravenous). The derived renal vascular resistance rose significantly from control (P < 0.01 renal, P < 0.01 intravenous).

3. Despite the significant decline in filtered sodium load (P < 0.01 renal, P < 0.001 intravenous), there was a significant log dose-related increase in fractional sodium excretion (P < 0.005) with intrarenal infusion of VIP.

4. We conclude that the actions of VIP on intrarenal blood vessels and renal tubules are direct, leading to increases in renal vascular resistance and fractional sodium excretion.
The relationship between intestinal crypt cell production and intestinal water absorption measured in vitro in the rat
Authors: Goodlad R. A. , Plumb J. A. , Wright N. A.
Published: August 2015

1. In studies on intestinal adaptation it is often important to obtain contemporaneous data on the rate of cell production and the functional status of the intestine.

2. The measure of the rate of accumulation of vincristine arrested metaphases in microdissected intestinal crypts to determine the crypt cell production rate (CCPR), is one of the most effective methods of estimating intestinal epithelial cell proliferation which is robust enough to withstand scrutiny. However, studies in the field of intestinal adaptation could be much more informative if a valid measure of intestinal function could also be included. One such method is the water absorption capacity in vitro.

3. The intraperitoneal injection of vincristine sulphate (1 mg/kg) had no significant effect on the water absorption capacity of the small intestine, as measured by the segmented flow single pass perfusion method; thus the CCPR of the jejunum and intestinal water absorption were both measured in 19 groups of hypo- and hyper-proliferative rats which should have been in a relatively ‘steady state’ of cell production and turnover.

4. The minimum values were obtained after hypophysectomy and the maximum values were observed in lactation. CCPR and absorption were significantly correlated (P < 0.001) with each other. There was a significant (P < 0.001) correlation between both CCPR and absorption and dry weight of the intestinal segment studies with food intake. Body weight was a poor predictor of either CCPR or absorption.

5. The combined study of CCPR and water absorption is a practical and convenient approach to the study of intestinal cell proliferation and intestinal adaptation, and shows that in ‘steady state’ models of hypoplasia and hyperplasia, cell production is closely linked to functional capacity and both of these are also related to the food intake.
The effect of muscle paralysis on the radial growth of collagen fibrils in developing tendon
Authors: Scott Pr J. E. , Haigh Marion , Neo Geok-Eng , Gibson Sarah
Published: August 2015

1. Voluntary muscle activity in chick embryos was paralysed by administration in ovo of tubocurarine hydrochloride, administered in single or multiple doses, from day 9 to day 13 after fertilization. Control eggs were given saline instead of tubocurarine or were simply incubated without operative interference. Embryos were killed at 9, 13, 14, 16 and 19 days after fertilization. Flexor digitorum tendons were removed, fixed in glutaraldehyde, embedded in plastic, sectioned, and stained with phosphotungstic acid for electron microscopy. The diameters of the tendon collagen fibrils were measured, on electron micrographs, using a Magiscan Mk II programme.

2. Tendon collagen fibril expansion was not inhibited by tubocurarine treatment. It is concluded that the rapid increase of collagen fibril diameters, which coincides in the normal embryo with the first onset of use of the associated muscle, is not dependent on muscle activity. There remains a possibility that other ways of producing tension in the tendon could provide sufficient stimulus to fibril expansion.
Lack of angiotensin I accumulation after converting enzyme blockade by enalapril or lisinopril in man
Authors: Nussberger J. , Brunner D. B. , Waeber B. , Biollaz J. , Brunner Hans R.
Published: August 2015

1. In nine normal volunteers, a series of five venous blood samples was obtained before and up to 24 h after converting enzyme inhibition by a single oral dose of enalapril or lisinopril. Plasma renin activity and blood angiotensin I were measured.

2. A close linear relationship was found between the increase in plasma renin activity and the increase in blood angiotensin I.

3. The linear correlation between plasma renin activity and blood angiotensin I remained after converting enzyme inhibition.

4. Thus, the rise in angiotensin I after inhibition of the conversion of angiotensin I to angiotensin II is due to an enhanced release of renin rather than to accumulation of angiotensin I.
AMP deaminase deficiency: Study of the human skeletal muscle purine metabolism during ischaemic isometric exercise
Authors: Sinkeler S. P. T. , Binkhorst R. A. , Joosten E. M. G. , Wevers R. A. , Coerwinkel M. M. , Oei T. L.
Published: August 2015

1. Muscle biopsies were taken from 10 control subjects and five AMP deaminase (AMPD) deficient individuals before and after an ischaemic isometric exercise test and analysed for purine nucleotide, NAD+, creatine phosphate (CP) and lactate content.

2. The decrease of ATP induced by the exercise test was significantly lower in the AMPD deficient patients than in the controls, but the decrease of creatine phosphate and the increase of lactate did not differ. There were no significant differences in the exertional performance level between patients and controls and no evidence was obtained of an increased energy expenditure per unit of performance in AMPD deficiency.

3. The AMPD deficient individuals were equally capable of maintaining a high adenylate energy charge (EC) as the control subjects, which indicates a normal regulation of the balance between ATP consumption and ATP regeneration.

4. ATP, ADP and total adenine nucleotide (TAN) but not AMP, were significantly elevated in the AMPD deficient patients as compared with the controls before as well as after the exercise test. This underlines the role of AMPD activity in the adenine nucleotide catabolism of skeletal muscle.
Effects of variation of the tri-iodothyronine/reverse triiodothyronine ratio in vivo on the metabolic characteristics of subsequently isolated hepatocytes
Authors: Al-Saadi A. , Sprague D. , Sugden M. , Goode A. , Orr S.
Published: August 2015

1. Reverse tri-iodothyronine (3,3′,5′-tri-iodothyronine, rT3), a major product of the peripheral monodeiodination of thyroxine, was administered subcutaneously to fed rats at a dose of 100 μg/100 g body weight for 2 consecutive days.

2. This dose induced a 17-fold increase in plasma rT3 (from 0.05±sem 0.01 to 0.85±0.11 ng/ml, P > 0.001) whilst the plasma T3 concentration was decreased to half of the control value (0.40 ± 0.03 to 0.20 ± 0.02 ng/ml, P > 0.01).

3. As a result of these changes the T3/rT3 ratio was therefore decreased from 8.0 ±1.6 to 0.23 ± 0.03 (P > 0.001).

4. Hepatocytes prepared from control or rT3treated rats were incubated with [l-14C]oleate and the rates of 14CO2 release and glucose production were estimated. Despite the changes in ratio of T3 to rT3 observed in vivo, rates of 14CO2 release and glucose production rate from hepatocytes subsequently isolated were unchanged.
Influence of age on deterioration of the remnant kidney in uninephrectomized rats
Authors: Okuda Seiya , Motomura Kenichi , Sanai Tohru , Tsuruda Hiroshi , Oh Yukinori , Onoyama Kaoru , Fujishima Masatoshi
Published: August 2015

1. To investigate the influence of age on the remnant kidney, unilateral nephrectomy was performed in rats at 1 day (group N-0), 2 weeks (group N-2), 4 weeks (group N-4) or 8 weeks (group N-8) of age. Serial changes in urinary protein during 48 weeks after the uninephrectomy and blood chemistries and renal histology at week 48 were compared between the groups.

2. The increase in proteinuria was significantly greater in groups N-0, N-2 and N-4 than in group N-8 from week 32 to week 48 after the uninephrectomy. There was no significant difference in urinary protein between groups N-0, N-2 and N-4. Hypoproteinaemia and hypoalbuminaemia were also more severe in groups N-0, N-2 and N-4 than in group N-8 at week 48.

3. A compensatory renal growth in groups N-0 and N-4 was significantly greater than that in group N-8 at week 48 after the uninephrectomy.

4. Focal and segmental glomerular sclerosis, a characteristic finding in the uninephrectomy groups, was significantly more marked in groups N-0, N-2 and N-4 than in group N-8 at week 48.

5. We conclude that uninephrectomy at young ages leads to increased incidence of glomerular sclerosis in rats compared with uninephrectomy in the adult.
Exercise-induced changes in renal function and their relation to plasma noradrenaline in insulin-dependent diabetic children and adolescents
Authors: Johansson B.-L. , Berg U. , Bohlin A.-B. , Lefvert A.-K. , Freyschuss U.
Published: August 2015

1. Exercise-induced changes in renal haemodynamics, water homoeostasis, urinary albumin excretion and their possible relation to plasma noradrenaline were studied in seven insulin-dependent diabetic children and adolescents without signs of autonomic or somatic neuropathy. Six age-matched clinically healthy patients in remission from the minimal change nephrotic syndrome served as controls.

2. The diabetic patients had a higher glomerular filtration rate and effective renal plasma flow and a lower venous plasma noradrenaline level in the basal state. They also had a higher systolic blood pressure compared with the controls. During exercise the diabetic patients showed a less marked reduction in glomerular filtration rate and urinary flow and a greater increase in filtration fraction. Their heart rate increase during exercise was lower. An inverse correlation between the percentage changes in noradrenaline and glomerular filtration rate during exercise was noted solely in the diabetic patients. They also showed a less marked increase in the ratio between potassium and sodium clearances during and 20 min after exercise. Albumin excretion did not differ between the two groups.

3. We suggest that the sympatho-adrenergic effects of exercise on heart rate, renal haemodynamics and water homoeostasis are blunted in our diabetic patients. Hence, signs of impaired sympathetic activity might be disclosed in young diabetic patients with a disease of fairly short duration.