bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal of nerve damage in streptozotocin-diabetic rats by acute application of insulin in vitro
Authors: Burnstock Geoffrey , Mirsky Rhona , Belai Abebech
Published: August 2015

1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro.

2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum.

3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves.

4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes. If so, this could influence the use of insulin in the treatment of diabetes, particularly in view of the recent report that short-term continuous subcutaneous insulin infusion restores the function of the autonomic and peripheral nerves in type I diabetic patients [Krönert, K., Hülsen, J., Luft, D., Stetter, T. & Eggstein, M. (1987) Journal of Clinical Endocrinology and Metabolism, 64, 1219–1223].
Inter-relationship between urinary kallikrein-kinins and arginine vasopressin in man
Authors: Yamada K. , Hasunuma K. , Shiina T. , Ito K. , Tamura Y. , Yoshida S.
Published: August 2015

1. Physiological saline solution was infused in nine normal subjects and six patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected intramuscularly. Urine was collected in 30 min fractions before and after AVP administration.

2. The urinary excretions of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) and immunoreactive kinins (i-kinins) were significantly lower in patients with DI than in normal subjects before AVP administration, while there were no differences in plasma renin activity, plasma aldosterone concentration, creatinine clearance and blood pressure between the two groups, except for a marked water diuresis in patients with DI. The urinary excretion of KAL-A and i-kinins correlated positively with the urinary excretion of AVP.

3. AVP administration increased both plasma AVP and urinary excretion of AVP to similar levels in both groups. As a result, urine volume decreased to a greater degree in patients with DI than in normal subjects. In contrast, the urinary excretions of KAL-A and i-kinins were increased by AVP administration, with a greater response in normal subjects than in the patients with DI.

4. After overnight fasting, acute water loading was carried out orally for 15 min in six normal subjects. At 30 min plasma AVP was suppressed by water loading to almost the basal level found in patients with DI. Urinary excretions of KAL-A and i-kinins in the first 30 min fraction after loading were also suppressed to the basal level in patients with DI. Later, the urinary excretion of KAL-A increased together with the increase in urine flow. Urine volume and free water clearance markedly increased except in the first 30 min fraction, compared with the control period.

5. Thus it is suggested that AVP is one of the factors regulating the renal kallikrein-kinin system in man, although it seems likely that urine flow is still a major factor in urinary kallikrein-kinin excretion.
Transamination of methionine in humans
Authors: Blom Henk J. , Boers Godfried H. J. , van den Elzen Jacintha P. A. M. , Gahl William A. , Tangerman Albert
Published: August 2015

1. This study was designed to investigate the transamination pathway of methionine in humans.

2. Evidence is provided that methanethiol and its metabolites are formed via transamination of methionine.

3. Gas-liquid chromatography was used to measure serum and urinary transamination metabolites of methionine: 2-keto-4-methylthiobutyrate, 3-methylthiopropionate and methanethiol, and the metabolites of methanethiol, dimethylsulphide, protein—S—S—CH3 (a mixed disulphide of blood proteins and methanethiol) and X—S—S—CH3 (a mixed disulphide of methanethiol and another thiol with an unknown component X).

4. Methionine and the transamination intermediates were measured in 10 normal subjects, in six normal subjects after L-methionine loading (0.1 g/kg body weight) and in a male patient with hepatic methionine adenosyltransferase (EC 2.5.1.6) deficiency.

5. In the patient with methionine adenosyltransferase deficiency, at least 20% of methionine was degraded via transamination. In normal subjects transamination of methionine did exist but was quantitatively not important in methionine catabolism, not even after methionine loading.

6. The results of this study might be of importance for future studies on the role of methanethiol in hepatic encephalopathy.
The renin gene in patients with malignant hypertension and raised plasma renin activity
Authors: Samani N. J. , Ruprai A. K. , Brammar W. J. , Swales J. D.
Published: August 2015

1. We have examined the hypothesis that the raised plasma renin activity in patients with malignant hypertension without an underlying cause is the consequence of expression of a duplicate renin gene.

2. DNA extracted from leucocytes of patients with malignant hypertension and of normotensive controls was digested with the restriction endonuclease PstI and hybridized with a radioactively labelled human renin complementary DNA probe. As an internal control the DNA was concurrently hybridized with a human c-myc protooncogene probe.

3. The signals for each subject from the two probes were quantitatively compared by densitometry.

4. There was no evidence of duplication of the renin gene in the patients with malignant hypertension.
Relationship between leucocyte sodium content and high blood pressure during development and resolution of pre-eclampsia
Authors: Seon R. , Forrester T.
Published: August 2015

1. One hundred and five primigravidae were followed sequentially at 4-weekly intervals starting at gestational week 31. They were seen again at 6 weeks post partum.

2. At each visit measurements were made of blood pressure as well as of leucocyte and erythrocyte sodium and potassium content.

3. Eighty-five subjects completed the study. Seven developed pre-eclampsia.

4. In both controls and patients who developed preeclampsia, leucocyte and erythrocyte sodium content increased with gestational age and fell post partum. These changes were of greater magnitude in the patients with pre-eclampsia. Cell potassium fell in both groups, but to a greater extent in patients with pre-eclampsia.

5. These changes in cell sodium paralleled those in blood pressure in both groups.

6. These data suggest that the excessive blood pressure changes in pre-eclampsia might be related to similar changes in cell sodium content.
Local pathological responses to slow-release recombinant interleukin-1, interleukin-2 and γ-interferon in the mouse and their relevance to chronic inflammatory disease
Authors: Dunn C. J. , Hardee M. M. , Gibbons A. J. , Staite N. D. , Richard K. A.
Published: August 2015

1. The present study describes the pathological responses to local administration of recombinant cytokines in subcutaneously implanted slow-release ethylene vinyl acetate (EVA) co-polymer in mice.

2. EVA-recombinant human interleukin-1β (104 units) implants induced the formation of chronic granulomatous inflammatory tissue between 4 and 7 days after implantation, characterized by predominant macrophage infiltration, neovascularization and fibrosis which persisted up to 21 days after-implantation. EVA-recombinant human interleukin-1α (104–105 units) implants induced a qualitatively similar but less intense response.

3. In contrast, recombinant human interleukin-2 (102–104 units) implants resulted in early lymphocytic vasculitis (4 days) and the development of a predominantly lymphoid lesion comprised of lymphoblasts and significant mononuclear cell proliferation by 7 days.

4. EVA-recombinant γ-interferon (103–104 units) implants failed to elicit a significant tissue response; with the exception of multinucleate giant cell formation the characteristics of these lesions closely resembled the mild fibrotic responses observed for EVA-bovine serum albumin (0.5–12.5 mg) implants.

5. These observations suggest that continuous endogenous local release of interleukin-1 or interleukin-2 in vivo is sufficient for the development of specific pathological features characterizing chronic immuno-inflammatory diseases.
Changes in forearm blood flow at elevated ambient temperature and their role in the apparent impairment of glucose tolerance
Authors: Frayn K. N. , Whyte P. L. , Benson H. A. , Earl D. J. , Smith H. A.
Published: August 2015

1. Antecubital venous plasma glucose and insulin concentrations after ingestion of 75 g of glucose were higher in six normal subjects when studied at an ambient temperature of 33°C than at an ambient temperature of 23°C; the mean area under the glucose-time curve increased from 833 at 23°C to 990 mmol min 1−1 at 33°C, that for insulin from 5300 to 7900 m-units min 1−1.

2. Core temperature was elevated by 0.5°C at 33°C ambient, although there was no marked stress response as judged by plasma levels of catecholamines, cortisol and growth hormone; at 2 h after glucose ingestion, mean noradrenaline levels were lower at 33°C than at 23°C (1.1 at 33°C vs 1.8 nmol/l at 23°C), adrenaline slightly higher (0.18 at 33°C vs 0.09 nmol/l at 23°C), cortisol and growth hormone unchanged.

3. Forearm blood flow was markedly elevated at 33°C ambient (mean total flow 9.1 at 33°C vs 1.8 ml min−1 100 ml−1 at 23°C), as were antecubital venous partial pressure of oxygen (mean 10.1 at 33°C vs 5.6 kPa at 23°C) and oxygen saturation (mean 92% at 33°C vs 70% at 23°C). There was a positive correlation between oxygen saturation and area under the glucose tolerance curve.

4. In separate experiments, arterialized glucose concentrations were measured after glucose ingestion at 23°C ambient. Antecubital venous glucose concentrations at 33°C ambient were intermediate between venous and arterialized concentrations at 23°C ambient.

5. It is concluded that the apparent impairment of glucose tolerance at elevated ambient temperature is caused at least in part by increased arterialization of the antecubital venous blood. This potential variable must be considered in research or diagnostic procedures based on the use of venous blood.
Different cation transport inhibitor in malignant renal hypertension and in uraemia
Authors: Simon Geza
Published: August 2015

1. We investigated whether the previously reported circulating frusemide-like factor in rats with malignant renal hypertension was specific to this syndrome, or was also present in rats with chronic uraemia. 86Rb uptake (K+ transport) of monolayers of vascular smooth muscle cells was measured in the plasma of rats with malignant one-kidney, one-clip hypertension and of uraemic rats (60–70% nephrectomy).

2. Compared with control plasma, ouabain-insensitive 86Rb uptake of cells was reduced and ouabain-sensitive 86Rb uptake was unchanged in the plasma of rats with malignant hypertension. The reverse was found in the plasma of uraemic rats.

3. Inhibition of ouabain-sensitive 86Rb uptake of cells occurred in the plasma of rats with malignant hypertension when an angiotensin II antagonist was added to the reaction mixture.

4. The findings confirm the presence of a frusemide-like plasma factor in malignant hypertension and a ouabain-like plasma factor in uraemia. The presence of a ouabain-like plasma factor in malignant hypertension is camouflaged by an elevated circulating angiotensin II level, which stimulates K+ transport.
Abnormal sodium handling occurs in the isolated perfused kidney of the nephrotic rat
Authors: Firth John D. , Raine Anthony E. G. , Ledingham John G. G.
Published: August 2015

1. In order to examine the handling of sodium by the nephrotic kidney when separated from the immediate influences of renal nerves and humoral factors, kidneys were taken from nephrotic rats (puromycin aminonucleo-side) and studied over a range of perfusion pressures using the isolated perfused kidney technique.

2. When perfused with medium containing 6.7 g/dl albumin, the nephrotic kidneys performed differently from controls with a reduction in sodium excretion at all pressures [(mean ± sem) 1.14 ± 0.43 vs 4.20 ± 0.69 μmol/min at 105 mmHg (14 kPa); 6.32 ± 1.56 vs 44.60 ± 5.30 μmol/min at 150 mmHg (20 kPa)]. Renal vascular resistance, inulin clearance, fractional sodium excretion and fractional lithium excretion were also reduced.

3. When kidneys were perfused without oncotic agent these differences between nephrotic and control kidneys remained. Perfusion with medium containing 10 g/dl albumin, designed to prevent glomerular filtration, abolished the difference in vascular resistance between the two groups. Captopril had no effect on the sodium retention or vascular resistance of nephrotic kidneys.

4. It was concluded that (a) the isolated nephrotic kidney demonstrates increased avidity for sodium, (b) the abnormality of sodium handling is not dependent on the presence of altered oncotic forces, and (c) the alteration in vascular resistance is conditional upon glomerular filtration.
Evidence that intravenous morphine stimulates central opiate receptors to increase sympatho-adrenal outflow and cause hypertension in conscious rabbits
Authors: May Clive N. , Whitehead Catherine J. , Heslop Kirsten E. , Mathias Christopher J.
Published: August 2015

1. In conscious rabbits, intravenous morphine caused hypertension, bradycardia, hyperglycaemia and increased plasma adrenaline and noradrenaline. These effects were prevented by ganglionic blockade with pentolinium.

2. The cardiovascular responses to morphine were not altered by pretreatment with a vasopressin V1-receptor antagonist.

3. After bilateral adrenalectomy morphine caused a similar rise in noradrenaline but no increase in adrenaline. The rise in blood pressure was attenuated and the hyperglycaemia was abolished.

4. Adrenaline infused intravenously to mimic the levels that occurred after morphine caused a similar degree of hyperglycaemia but only a small increase in blood pressure.

5. Pretreatment with intracerebroventricular naloxone prevented the morphine-induced hypertension, hyperglycaemia, increase in plasma catecholamines, respiratory depression and sedation.

6. These results demonstrate that, in conscious rabbits, intravenous morphine causes hypertension by increasing sympathetic vasoconstrictor nerve activity and elevating plasma adrenaline levels; the latter alone produces the hyperglycaemia. Vasopressin release is not involved in the hypertensive response to morphine. The effects of morphine appear to result from stimulation of central opiate receptors leading to enhanced sympathoadrenal outflow.
Effects of sodium depletion on renal prostanoid synthesis in rats: influence of the converting enzyme inhibitor captopril
Authors: Rathaus M. , Podjarny E. , Pomeranz A. , Shapira J. , Kariv N. , Bernheim J.
Published: August 2015

1. The synthesis of prostaglandin (PG) E2, PGF2α, 6-keto-PGF1α and thromboxane (TX) B2 by isolated glomeruli, cortical tubules, inner medullary slices and outer medullary slices was measured in salt-depleted (LNa) rats and in salt-depleted rats receiving captopril (LNa-CEI). Animals were studied before and after 4, 9 and 15 days of Na+ depletion.

2. Na+ balance was reached in LNa rats after 4 days. Blood pressure and creatinine clearance remained stable. Serum Na+ decreased from 140 ± 1 to 126 ± 1 mmol/l (mean ± sem, P < 0.01). In contrast, LNa-CEI rats were unable to conserve Na+ adequately: fractional excretion of Na+ and natriuresis were constantly greater than in LNa animals. As a consequence, LNa-CEI rats developed severe hyponatremia, lost weight and their creatinine clearance decreased.

3. The glomerular synthesis of PGE2, PGF2α and 6-keto-PGF1α, but not of TXB2, was significantly increased in LNa rats. In LNa-CEI rats, the synthesis of PGE2 and 6-keto-PGF1α was similar to control values, but PGF2α and TXB2 synthesis was elevated at day 9. In cortical tubules, PGE2 and PGF2α were unaffected by Na+ depletion, but 6-keto-PGF1α and TXB2 were increased and a similar trend was observed in LNa-CEI rats. In outer medulla of LNa rats, a decrease in all the eicosanoids measured was observed at day 4. In LNa-CEI animals, the synthesis of PGE2 and PGF2α, but not of 6-keto-PGF1α and TXB2, was significantly depressed. In inner medulla, Na+ depletion only tended to decrease PGF2α and 6-keto-PGF1α, but in the presence of captopril, the synthesis of all prostanoids was significantly decreased.
Regional and time-dependent effects of inflammatory mediators on airway microvascular permeability in the guinea pig
Authors: Evans T. W. , Rogers D. F. , Aursudkij B. , Chung K. F. , Barnes P. J.
Published: August 2015

1. Airway oedema resulting from increased microvascular permeability is a characteristic pathological finding of asthma. The regional effects of putative mediators involved in asthma on airway microvascular permeability have been studied.

2. The effects of histamine, leukotriene (LT) D4 and platelet-activating factor (PAF) on microvascular permeability in the nasal mucosa, larynx, trachea, main bronchi and intrapulmonary airways of the guinea pig were assessed by measuring the extravasation of intravenously administered Evans Blue dye.

3. PAF and LTD4 caused increased microvascular leakage throughout the respiratory tract, although their effects were maximal in different regions. Histamine had no significant effect on intrapulmonary airways. PAF was more potent than LTD4 and histamine at all airway levels. For example, in the trachea the doses required to cause leakage of 50% of maximal (ED50) were 10.4 nmol/kg, 138 nmol/kg and 11.2 μmol/kg, respectively, for PAF, LTD4 and histamine.

4. The effect of the three mediators was maximal 5 min after intravenous administration. Histamine, but neither LTD4 nor PAF, still caused significant leakage 30 min after administration.

5. The increased microvascular leakage induced by the mediators was inhibited by their respective specific receptor antagonists, suggesting that the effect was mediated via specific receptors.

6. Histamine, LTD4 and PAF have varying potencies in increasing microvascular permeability in the guinea-pig respiratory tract, exert their maximal effect in different regions and have varying durations of action.
Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans
Authors: Goldstein David S. , Stull Robin , Eisenhofer Graeme , Gill John R.
Published: August 2015

1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown.

2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week.

3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation.

4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.
Interleukin-1 potentiates the development of collagen-induced arthritis in mice
Authors: Killar L. M. , Dunn C. J.
Published: August 2015

1. The subcutaneous administration of recombinant human interleukin-1β (rhIL-1β) was found to induce an increased incidence and earlier onset of collagen-induced arthritis in mice.

2. The rhIL-1β had different effects, depending on when it was administered after collagen-immunization.

3. The effect of rhIL-1β may be due, in part, to augmentation of the immune response to type II collagen.

4. Interleukin-1-accelerated, collagen-induced arthritis will provide a useful model for investigating the role of interleukin-1 in the regulation of arthritic diseases, and the development of anti-arthritic therapeutics.
Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man
Authors: Albers S. , Wernerman J. , Stehle P. , Vinnars E. , Fürst P.
Published: August 2015

1. A commercial amino acid solution supplemented with two synthetic dipeptides, l-alanyl-l-glutamine (Ala-Gln) and glycyl-l-tyrosine (Gly-Tyr), or alternatively with isonitrogenous amounts of free alanine and glycine has been continuously infused over 4 h in six apparently healthy volunteers.

2. The infusion of the solutions was not accompanied by any side effects and the volunteers reported no complaints.

3. Infusion of the alanine- and glycine-supplemented control solution resulted in an increase of the concentration of these amino acids, while no appreciable change in free glutamine concentration was observed and free tyrosine revealed a steady decrease throughout the infusion.

4. Infusion of the peptide-supplemented solution resulted in a prompt equimolar liberation of the constituent free amino acids (glutamine, alanine, tyrosine and glycine), approaching steady state after about 30 min infusion, while only trace but stable concentrations of the two dipeptides were measured throughout the infusion. No peptides were detectable in urine. The findings suggest a nearly quantitative extracellular hydrolysis of the infused dipeptides and indicate a subsequent utilization of the liberated free amino acids.

5. The estimated metabolic clearance rates and total body plasma clearances were very similar for the two dipeptides (Ala-Gln 35.9 ± 9.5 ml min−1 kg−1 and 2.9 ± 0.9 1/min, respectively; Gly-Tyr 33.7 ± 9.5 ml min−1 kg−1 and 2.7 ± 0.9 1/min, respectively); thus there is little difference in the metabolic handling of these dipeptides.

6. The study provides firm evidence that the synthetic dipeptides Ala-Gln and Gly-Tyr are quantitatively hydrolysed and that these peptides can be used as a safe and efficient source of free glutamine and tyrosine as part of a commercial solution.
Effect of parenteral nutrition on protein turnover in endotoxaemic rats
Authors: Ash S. A. , Griffin G. E.
Published: August 2015

1. Intravenous infusion of endotoxin into rats over 18 h caused a reduction in food intake to 20% of normal levels, weight loss, hypoalbuminaemia and a fall in rates of protein synthesis in vivo in heart and skeletal muscle.

2. Measurements of protein turnover in vitro in skeletal muscle of endotoxaemic animals, showed a 50% fall in protein synthesis rates and a 200% increase in rates of protein degradation.

3. Total parenteral nutrition was only partially able to reverse endotoxin-induced weight loss. Total parenteral nutrition did not reverse endotoxin-induced catabolism in cardiac or skeletal muscle, but was able to reverse the catabolism of protein in skeletal muscle produced by starvation.

4. Endotoxin treatment elevated rates of protein synthesis in vivo in liver. The combination of parenteral nutrition and endotoxaemia further increased the rate of protein synthesis in the liver. Parenteral nutrition did not influence endotoxin-induced hypoalbuminaemia.
Doppler Characterization of the Immediate Blood Flow Velocity Pattern after Release of Prolonged Venous Occlusion of the Forearm
Authors: West J. N. W. , Salih M. S. , Littler W. A.
Published: August 2015

1. There is a biphasic flow response measured plethysmographically after release of prolonged venous occlusion of the forearm.

2. The response consists of an early, vasodilatory, increase in flow and is followed by a decrease in flow relative to control, thought to be mediated by myogenic contraction of resistance vessels.

3. Methodological constraints with the technique of forearm plethysmography have to date precluded an individual beat-by-beat examination of this response, in particular for resolving the question of the immediate flow pattern after release of venous occlusion. It has been suggested by Caro, Foley & Sudlow [Journal of Physiology (London) (1970), 207, 257–269] that there is a delay of up to five systolic beats before vasodilatation takes place, leading to their suggestion that the vasodilatation is passive and secondary to an increased flow through emptied capacitance vessels.

4. The introduction of peripheral Doppler techniques has led us to re-examine this response in an attempt to define short-term resistance vessel behaviour on a beat-by-beat basis.

5. Our data confirmed the hypothesis of Caro, Foley & Sudlow [Journal of Physiology (London) (1970), 207, 257–269] that there is a constant and definite latency preceding the onset of vasodilatory flow, as reflected by changes in Doppler velocities.
Effect of the Cyclo-Oxygenase Inhibitor Fenbufen on Muscle and Liver Protein Metabolism, Muscle Glutamine and Plasma Insulin in Endotoxaemic Rats
Authors: Jepson M. M. , Millward D. J.
Published: August 2015

1. The effect of fenbufen (γ-oxo-[1,1′-biphenyl]-4-butanoic acid), a known cyclo-oxygenase inhibitor, on the changes in muscle and liver protein metabolism in response to Escherichia coli endotoxin has been investigated in the rat.

2. Young male rats were fed a purified diet [18% (w/w) casein], with or without fenbufen (1.2 g/kg of diet). Groups of animals were injected with either endotoxin (LPS; Escherichia coli lipopolysaccharide 0.127 B8; 3 mg/kg body weight) or saline. Rectal temperature and food intake were measured over the following 24 h period, after which time measurements were made of muscle and liver protein content and synthesis in vivo, muscle protein degradation as the difference between protein synthesis and growth rates, muscle glutamine concentration and plasma insulin.

3. Fenbufen treatment alone tended to lower rectal temperature. It also reduced plasma insulin, slightly reduced food intake and slowed growth and muscle protein turnover, although muscle glutamine concentrations were unchanged. The slower protein synthesis mainly reflected reduced translational activity, which was consistent with the reduced insulin concentration.

4. LPS treatment increased rectal temperature by 1.6°C, and this was abolished by fenbufen, indicating that the dose of the drug was sufficient to block prostaglandin production in the hypothalamus.

5. LPS treatment induced similar losses in body weight and muscle protein in both control and fenbufen groups, despite a 50% lower food intake in the LPS plus fenbufen group compared with the LPS-only group. The loss of muscle protein in both groups reflected reduced protein synthesis and increased protein degradation. LPS treatment alone induced elevated plasma insulin, but fenbufen blocked this response and the insulin levels remained depressed. Muscle glutamine concentration fell in both LPS-treated groups, suggesting that the depression of protein synthesis and the development of the insulin resistance might be linked to the loss of intracellular glutamine.

6. LPS induced a relative increase in hepatic protein content, and total protein synthesis (by approximately 40%); fenbufen had no influence on these responses.

7. It is concluded that whereas treatment with fenbufen has marked effects on plasma insulin concentration, it has no influence on muscle and liver protein metabolism during endotoxaemia. Alternative mechanisms to those involving prostaglandins as mediators of the catabolic response of muscle are discussed, including those involving the glutamine transporter.
Effects of the Baroreceptor Reflex System on Atrial Natriuretic Factor Secretion during Volume Expansion in Dogs
Authors: Kohara K. , Otsuka A. , Mikami H. , Katahira K. , Tsunetoshi T. , Ogihara T.
Published: August 2015

1. The purpose of this study was to determine whether the baroreceptor reflex system affects the secretion of atrial natriuretic factor directly or indirectly during acute volume expansion.

2. Lactated Ringer's solution containing low mol. wt. dextran was infused at 20 ml/kg for 1 h into dogs in which baroreceptors had been denervated surgically (Vx), dogs in which the autonomic system had been blocked with hexamethonium (Hx) and control dogs.

3. The plasma noradrenaline level was significantly higher in the Vx group and lower in the Hx group than in the control group throughout the experiment. The plasma levels of arginine vasopressin in the Vx and Hx groups were significantly higher than in the control group.

4. The plasma atrial natriuretic factor levels in the three groups showed similar increases during and after volume expansion.

5. The plasma atrial natriuretic factor level was significantly correlated with the right atrial pressure during volume expansion.

6. From these results, it seems unlikely that changes in the plasma level of atrial natriuretic factor during volume expansion are regulated by the baroreceptor reflex directly or indirectly by systemic changes in the sympathetic nervous system or arginine vasopressin secretion.
Atrial Natriuretic Peptide-Induced Decreases in Renal Blood Flow in Man: Implications for the Natriuretic Mechanism
Authors: Janssen Wilbert M. T. , de Zeeuw Dick , van der Hem Gjalt K. , de Jong Paul E.
Published: August 2015

1. We studied the effect of a low-dose infusion of atrial natriuretic peptide (ANP) on renal blood flow in healthy volunteers. We additionally investigated the effect of ANP on renal haemodynamic function and on urinary sodium excretion.

2. ANP induced a rise in packed cell volume and a slight increase (but no decrease) in the renal extraction of hippuran. These changes did not offset the observed fall in effective renal plasma flow. Renal blood flow thus truly decreased and renal vascular resistance increased.

3. ANP induced an increase in glomerular filtration rate and a decrease in urinary osmolality in the first hour of ANP infusion, whereas absolute and fractional sodium excretion increased significantly only in the second hour of ANP infusion. The decrease in urinary osmolality in the first hour of ANP infusion correlated with the induced natriuresis. The changes in urinary osmolality and sodium excretion both correlated with the changes in plasma ANP levels.

4. These data indicate that ANP may cause a decrease in renal blood flow and an increase of renal vascular resistance in man. Our results suggest a role for ANP-induced (intra)renal haemodynamic changes in ANP-induced natriuresis, possibly through an increase in the filtered load of sodium into a washed-out medullary interstitium.
Circadian Rhythm of Glomerular Filtration Rate in Normal Individuals
Authors: Koopman M. G. , Koomen G. C. M. , Krediet R. T. , de Moor E. A. M. , Hoek F. J. , Arisz L.
Published: August 2015

1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles.

2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (sd 22) in the daytime, a minimum of 86 ml/min (sd 12) at night and with a relative amplitude of 33% (sd 15).

3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well.

4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion.

5. Urinary albumin and β2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm.

6. The highest quantity of sodium, water and β2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.
Binding Sites for 125I-Labelled Endothelin-1 in the Kidneys: Differential Distribution in Rat, Pig and Man Demonstrated by Using Quantitative Autoradiography
Authors: Davenport Anthony P. , Nunez Derek J. , Brown Morris J.
Published: August 2015

1. Quantitative receptor autoradiography in vitro has been used to determine the distribution and density of specific binding sites for 125I-labelled endothelin-1 in human, porcine and rat kidneys. Immunocytochemistry was used to visualize von Willebrand factor-positive endothelial cells in adjacent sections to those used for autoradiography.

2. High levels of specific binding were detected in the vasa recta and papilla of all three species with lower levels in the medulla and cortex.

3. A major difference between the species was observed within the glomeruli, where high levels of binding were found in the rat but no detectable binding sites in pig or man.
Diet-Induced Thermogenesis in Patients with Gastrointestinal Cancer Cachexia
Authors: Weston P. M. T. , King R. F. G. J. , Goode A. W. , Williams N. S.
Published: August 2015

1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease.

2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake.

3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg).

4. Diet-induced thermogenesis was reduced in weight-losing cancer patients.

5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia.
An Investigation of the Role of Possible Neural Mechanisms in Cholera Toxin-Induced Secretion in Rabbit Ileal Mucosa in Vitro
Authors: Moriarty K. J. , Higgs N. B. , Woodford M. , Turnberg L. A.
Published: August 2015

1. Cholera toxin stimulates intestinal secretion in vitro by activation of mucosal adenylate cyclase. However, it has been proposed that cholera toxin promotes secretion in vivo mainly through an indirect mechanism involving enteric neural reflexes.

2. We examined this hypothesis further by studying the influence of neuronal blockade on cholera toxin-induced changes in fluid transport across rabbit ileum in vitro. Mucosa, stripped of muscle layers, was mounted in flux chambers and luminal application of crude cholera toxin (2 μg/ml) caused a delayed but sustained rise in the short-circuit current, electrical potential difference and Cl− secretion. Pretreatment with the nerve-blocking drug, tetrodotoxin (5 × 10−6 mol/l serosal side), failed to influence the secretory response to cholera toxin, and addition of tetrodotoxin at the peak response to cholera toxin also had no effect.

3. That tetrodotoxin could block neurally mediated secretagogues was confirmed by the demonstration that the electrical responses to neurotensin (10−7 mol/l and 10−8 mol/l) were blocked by tetrodotoxin (5 × 10−6 mol/l). Furthermore, the response to cholera toxin of segments of ileum, which included the myenteric, submucosal and mucosal nerve plexuses, was not inhibited by tetrodotoxin.

4. We conclude that cholera toxin-induced secretion in rabbit ileum in vitro is not mediated via a neurological mechanism.
Increased Plasma Atrial Natriuretic Factor and Reduced Plasma Renin in Patients with Poorly Controlled Diabetes Mellitus
Authors: Bell Gordon M. , Bernstein Richard K. , Laragh John H. , Atlas Steven A. , James Gary D. , Pecker Mark S. , Sealey Jean E.
Published: August 2015

1. To investigate atrial natriuretic factor (ANF) and its relationship to the renin system in diabetes, we measured plasma immunoreactive ANF and plasma renin activity (PRA) in 27 non-ketotic diabetic patients without evidence of cardiac or overt renal disease, and compared them with 26 age- and sex-matched normal subjects.

2. Diabetic patients were divided prospectively into poor (PGC, n = 14) or moderate (MGC, n = 13) glycaemic control depending on their concurrent plasma glycohaemoglobin (HbA1) levels (> 9% or < 9%, respectively). Plasma ANF was elevated in PGC diabetic patients (15.7 ± 1.8 fmol/ml, mean ± sem) compared with MGC diabetics (9.9 ± 0.8 fmol/ml, P < 0.001) and normal subjects (10.1 ± 1.3 fmol/ml, P < 0.05).

3. In contrast, PRA was lower in the PGC diabetic patients (1.3 ± 0.3 pmol of angiotensin I h−1 ml−1) compared with the other groups (2.5 ± 0.5 and 2.1 ± 0.2 pmol of angiotensin I h−1 ml−1, P < 0.05). Diabetic groups had proportionally more patients with high prorenin values (over 30 ng h−1 ml−1) than the normal group, but there was no difference between the diabetic groups.

4. Among the diabetic patients, ANF was directly related to HbA1 (r = 0.49, P < 0.005) and urinary albumin excretion (r = 0.40, P < 0.02), and was inversely related to PRA (r = −0.36, P < 0.04) and plasma creatinine (r = −0.42, P < 0.02).

5. Systolic blood pressure was greater in PGC diabetic patients [133 ± 5 mmHg (17.7 ± 0.7 kPa)] than in MGC diabetic patients [117 ± 4 (15.6 ± 0.5 kPa), P < 0.05] and normal subjects [121 ± 3 (16.1 ± 0.4 kPa), P < 0.05]. Diastolic pressure was not significantly different among the groups.

6. The directionally opposite changes in plasma ANF and plasma renin in PGC diabetic patients may reflect a normal response to expansion of intravascular volume. It remains to be established whether these changes are factors in the early renal dysfunction of diabetes mellitus.
Serum Digoxin-Like Substances in Pregnancy-Induced Hypertension
Authors: Poston L. , Morris J. F. , Wolfe C. D. , Hilton P. J.
Published: August 2015

1. Endogenous digoxin-like immunoreactivity (EDLI) was measured in the serum of 85 normotensive pregnant (NTP) women and 77 women with pregnancy-induced hypertension (PIH) by a radioimmunoassay (New England Nuclear). All women were in the third trimester.

2. EDLI, which was undetectable in serum from nonpregnant women, was present in NTP and PIH and was significantly higher in PIH. EDLI correlated with gestational age in NTP, but not in PIH.

3. Ouabain-sensitive Na+ transport was estimated in normal peripheral blood leucocytes after incubation with sera from 50 NTP and 42 PIH women. Significant inhibition of active Na+ transport occurred only with the serum of hypertensive patients without proteinuria.

4. EDLI did not correlate with the effect of the sera on active Na+ transport. The radioimmunoassay therefore provides a poor index of Na+ transport inhibitory activity in PIH.
Altered Erythrocyte Cation Permeability in Familial Pseudohyperkalaemia
Authors: Dagher G. , Vantyghem M. C. , Doise B. , Lallau G. , Racadot A. , Lefebvre J.
Published: August 2015

1. Erythrocyte cation transport pathways have been investigated in a family with pseudohyperkalaemia.

2. Ouabain- and bumetanide-resistant Na+ and K+ effluxes in three pseudohyperkalaemic patients were not different from those of control subjects when assessed at 37°C.

3. When the temperature was decreased to 20°C and 9°C, K+ passive permeability markedly increased and Na+ permeability remained unchanged in these patients. In contrast, in control subjects a reduction in temperature caused a marked reduction in Na+ and K+ passive permeability.

4. These findings could account for the marked increase in plasma K+ concentration observed at sub-physiological temperatures.

5. The Na+−K+ co-transport pathway was reduced in all members of the family, but the Na+−K+ pump was reduced in only two of them. These alterations were independent from the pseudohyperkalaemic state.
A Modified Method of Quantifying the Carotid Baroreceptor-Heart Rate Reflex in Man: The Effect of Age and Blood Pressure
Authors: Cowie M. R. , Rawles J. M.
Published: August 2015

1. Carotid baroreceptor-heart rate sensitivity has been measured non-invasively by a modified neck-chamber method that utilizes all cardiac intervals recorded in 6 min during 84 respiratory cycles.

2. In a replication study in 10 subjects the mean baroreflex sensitivity was 5.52 ms/mmHg and the mean (sd) difference between determinations was 0.70 (0.74) ms/mmHg.

3. Baroreflex sensitivity was measured in 48 untreated subjects of mean age 43 (range 20–71) years with blood pressures ranging from 104 to 202 mmHg (13.9 to 26.9 kPa) systolic and 52 to 120 mmHg (6.9 to 16.0 kPa) diastolic [average 142/87 mmHg (18.9/11.6 kPa)]. Both systolic and diastolic pressures correlated with age (r = 0.53, P < 0.001 and r = 0.44, P < 0.01).

4. Baroreflex sensitivity determined throughout respiration was log-normally distributed with a median value of 2.24 ms/mmHg, which declined with age (r = −0.63, P < 0.001).

5. After allowing for the effects of age, baroreflex sensitivity throughout respiration was not independently related to either systolic or diastolic blood pressure.
Carbidopa Does Not Affect the Renal Response to Atrial Natriuretic Factor in Man
Authors: Lewis Helen M. , Wilkins M. R. , Kendall M. J. , Lee M. R.
Published: August 2015

1. The dependence of atrial natriuretic factor on renal dopamine for its renal effects in man was examined in 10 healthy volunteers using the dopa decarboxylase inhibitor carbidopa.

2. Each volunteer attended on two occasions, and received an infusion of atrial natriuretic factor (4 pmol min−1 kg−1) for 60 min after pretreatment with either placebo or carbidopa orally. These were administered in random, double-blind fashion.

3. A similar increase in plasma atrial natriuretic factor concentration was seen after atrial natriuretic factor infusion on both visits.

4. Infusion of atrial natriuretic factor produced a small unsustained rise in urinary dopamine excretion. This increase in urinary dopamine excretion was blocked by carbidopa with no effect on the natriuresis.

5. Urinary guanosine 3′:5′-cyclic monophosphate excretion increased in response to the atrial natriuretic factor infusion whether placebo or carbidopa was given. Guanosine 3′:5′-cyclic monophosphate, but not dopamine, may be a mediator of the renal response to atrial natriuretic factor in man.
Lithium Clearance in Chronic Nephropathy
Authors: Kamper A.-L. , Holstein-Rathlou N.-H. , Leyssac P. P. , Strandgaard S.
Published: August 2015

1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function.

2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of lithium or influence of osmotic diuresis.

3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min.

4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min.

5. Lithium clearance data were independent of whether renal disease was of primarily glomerular or tubular origin and, further, were not influenced by long-term conventional antihypertensive treatment.

6. It is concluded that, even with a reduced kidney function, the data are compatible with the suggestion that lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct). With more severe impairment the proximal tubule also becomes involved in the adjustment.
Relation between Plasma β-Endorphin and the Ventilatory Response to Hypercapnia in Humans
Authors: Levick M. P. , Lovelock M. , Smith R. , Saunders N. A.
Published: August 2015

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear.

2. We studied the relationship between circulating immunoreactive β-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma β-endorphin and Cortisol levels.

3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma β-endorphin levels was observed (r = −0.35, P < 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma β-endorphin levels (r = −0.36, P < 0.01).

4. Repetitive hypercapnia prevented the fall in plasma Cortisol that occurred under control conditions (P < 0.02) but had no effect on plasma β-endorphin.

5. We conclude that plasma β-endorphin may play a role in the central chemical control of breathing in man.