bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Pressure Response to Physical Exercise in Healthy Adolescents and Adolescents with Insulin-Dependent Diabetes Mellitus
Authors: Nordgren H. , Freyschuss U. , Persson B.
Published: August 2015

1. Reference values for systolic blood pressure during exercise are provided for 88 healthy adolescents (12–22 years of age) of both sexes. Data were related to oxygen uptake, heart rate, blood lactate concentration, rate of perceived exertion, age, sex, body size and physcial fitness.

2. The same variables were measured in 55 adolescents of both sexes with insulin-dependent diabetes mellitus of about 12 years duration and were analysed with respect to the healthy control group, to degree of metabolic control and to late diabetic complications.

3. In healthy adolescents the pressure response was not related to sex or age. When compared with control subjects diabetic patients had a higher diastolic blood pressure at rest and a more marked blood pressure increase, 23 versus 19 mmHg W−1 kg−1 body weight, during exercise with no sex difference. The blood pressure rise was not related to metabolic control, glomerular hyperfiltration or physical fitness.

4. Prolonged exercise tests were no more informative regarding the blood pressure response to exercise than the stepwise increased load test. Analysing the blood pressure increase versus relative work load (W/kg body weight) during exercise reveals blood pressure differences otherwise not noted. A diabetic patient with blood pressure above the 97.5% confidence limit during exercise seems to have a higher risk of developing incipient nephropathy 5 years later.
Sodium Status Affects Gc-B Natriuretic Peptide Receptor mRNA Levels, but Not Gc-A Or C Receptor Mrna Levels, in the Sheep Kidney
Authors: Fraenkel Margaret B. , Aldred G. Peter , McDougall John G.
Published: August 2015

1. In humans and experimental animals the natriuresis and diuresis resulting from infusion of atrial natriuretic peptide varies with the sodium status of the subject. Tissue binding studies have suggested that this may be related to changes in the renal receptors for the hormone.

2. In order to establish whether these changes are under transcriptional control, we examined the levels of mRNA for the three natriuretic peptide receptors [GC-A, GC-B and clearance (C) receptors] in renal cortex and medulla from six sodium-loaded, six sodium-depleted and four control sheep. cDNA probes specific to each receptor were generated using the polymerase chain reaction.

3. GC-B receptor mRNA levels were increased approximately two-fold in the renal cortex of sodium-depleted animals, whereas there was no influence on GC-B receptor mRNA levels in the renal medulla. There was no significant difference in mRNA levels for the GC-A and C receptors.

4. At present the role of the GC-B receptor and its natural ligand C-type natriuretic peptide in the control of renal function is unknown. The present experiments imply some intrarenal function for the GC-B receptor and its natural ligand, although the site of any such function, e.g. renal vasculature or tubules, remains unclear. In addition, we have shown that if GC-A and C receptor levels in the sheep are modulated by sodium, the regulation occurs beyond the level of gene transcription.
Post-Exercise Doppler-Echocardiographic Haemodynamics in Idiopathic Dilated Cardiomyopathy after Metoprolol Infusion
Authors: Perchet Hervé , Pouillart Frédéric , Duval-Moulin Anne Marie , Heintz Jean François , Hittinger LUC , Castaigne Alain , Dubois-Randé Jean Luc
Published: August 2015

1. The physiological effects of the acute administration of a β-adrenoceptor antagonist in patients with idiopathic dilated cardiomyopathy were assessed by performing post-exercise Doppler-echocardiography study. Eleven patients and six control subjects were studied. According to a double-blind randomized protocol, 5 mg of metoprolol or placebo was administered before cycloergometer exercise.

2. In patients, after metopolol, a significant decrease in heart rate and systolic blood pressure, as well as in peak aortic acceleration and cardiac output, was observed 2 min after exercise. Left ventricular end-diastolic diameter did not change from baseline values either after placebo or metoprolol. In normal subjects, as compared with placebo, a decrease in heart rate and peak aortic acceleration was observed after metoprolol, whereas systolic blood pressure did not change. A similar increase in cardiac output occurred after metoprolol, as compared with placebo, associated with an increase in left ventricular end-diastolic diameter and stroke volume.

3. Post-exercise Doppler echocardiography is a means of assessing haemodynamic changes occurring during exercise in patients with congestive heart failure. Although acute metoprolol administration does not provide beneficial haemodynamic effects, a decrease in the energy requirements of the heart and a faster recovery after exercise may participate in the long-term beneficial action of β-adrenoceptor antagonists.
Waveform Shape Analysis: Extraction of Physiologically Relevant Information from Doppler Recordings
Authors: Ramsay Margaret M. , Pipkin Fiona Broughton , Rubin Peter C. , Skidmore Robert
Published: August 2015

1. Doppler recordings were made from the brachial artery of healthy female subjects during a series of manoeuvres which altered the pressure—flow characteristics of the vessel.

2. Changes were induced in the peripheral circulation of the forearm by the application of heat or icepacks. A sphygmomanometer cuff was used to create graded occlusion of the vessel above and below the point of measurement. Recordings were also made whilst the subjects performed a standardized Valsalva manoeuvre.

3. The Doppler recordings were analysed both with the standard waveform indices (systolic/diastolic ratio, pulsatility index and resistance index) and by the method of Laplace transform analysis.

4. The waveform parameters obtained by Laplace transform analysis distinguished the different changes in flow conditions; they thus had direct physiological relevance, unlike the standard waveform indices.
Augmented Thermic Effect of Amino Acids under General Anaesthesia: A Mechanism Useful for Prevention of Anaesthesia-Induced Hypothermia
Authors: Selldén EVA , Brundin Tomas , Wahren John
Published: August 2015

1. Intravenous infusion of amino acids stimulates energy expenditure and heat accumulation in normal man. To find out whether such stimulation also occurs during general anaesthesia, thermogenesis was measured in 21 patients before, during and after anaesthesia and surgery.

2. Ten patients received a mixture of 19 amino acids (240 kJ/h) infused intravenously throughout the anaesthesia. The other 11 patients, serving as controls, received saline. Using catheters previously inserted into the pulmonary and a systemic artery, cardiac output, arteriovenous oxygen difference, pulmonary oxygen uptake and mixed blood temperature were measured.

3. During anaesthesia and surgery, the blood temperature fell by 0.67 ± 0.09 °C/h in the control patients and by 0.38 ± 0.06 C/h in the amino acid-treated patients. Anaesthesia during 34 ± 4 min before surgery reduced the pulmonary oxygen uptake by 145 ± 9 ml/min in the control patients and by 81 ± 10 ml/min in the amino acid-treated patients, corresponding to reductions in total energy expenditure of 47 W in the control group and 26 W in the amino acid-treated group. The difference, 21 W, illustrates the thermogenic action of the amino acids. This value may be compared with that of 4 W, observed in unanaesthetized individuals subjected to 30 min of identical amino acid infusions.

4. At awakening after the anaesthesia, the oxygen consumption rose to 71 ± 21% above the pre-anaesthesia level in the amino acid-treated patients, who, without shivering, rapidly returned to normothermia, whereas in the control patients the oxygen uptake remained slightly below the pre-anaesthesia level, despite sustained hypothermia and vigorous shivering.

5. It is concluded that general anaesthesia augments five-fold the thermic effect of amino acids and that peroperative infusion of amino acids effectively prevents anaesthesia-induced hypothermia.
Potential Role for Interleukin-1 in the Pathophysiology of Ulcerative Colitis
Authors: Wardle T. D. , Turnberg L. A.
Published: August 2015

1. Biopsies of colonic mucosa from patients with ulcerative colitis liberated more interleukin-1β, prostaglandin E2, leukotriene C4 and platelet-activating factor into the medium in which they were cultured than biopsies from patients with irritable bowel syndrome and histologically normal mucosa.

2. Addition of interleukin-1 stimulated release of greater quantities of all these inflammatory mediators, including interleukin-1 itself, from inflamed and normal mucosa.

3. Blockade of cyclo-oxygenase with indomethacin or of lipoxygenase with ICI 207968 or of phospholipase A2 with mepacrine inhibited release of prostaglandin E2 or leukotriene C4 or both of these plus platelet-activating factor, respectively.

4. Interleukin-1 stimulated the short-circuit current across isolated rat colonic mucosa mounted in flux chambers in a dose-dependent manner (Km 2 × 10−11 mol/l). This stimulation was markedly inhibited by the removal of chloride from the bathing media.

5. Indomethacin or ICI 207968 inhibited the short-circuit current response to interleukin-1 and a combination of these antagonists produced a greater inhibition. Mepacrine caused an even greater inhibition whereas tetrodotoxin plus mepacrine inhibited the current completely.

6. These data indicate that interleukin-1, released in excess from inflamed colonic mucosa, stimulates the release of a range of inflammatory mediators as well as of more interleukin-1. It probably acts by stimulating phospholipase A2 in inflammatory cells, probably lymphocytes, and can do so in normal and inflamed mucosa. Since, in rat colonic mucosa it stimulated an electrical response in very low concentrations, it is feasible that it is involved in the chloride secretion, and hence the diarrhoea, which may occur in inflammatory reactions. Hence treatment with mepacrine seems a prospect worth pursuing.
Short-Term Starvation Alters the Free Amino Acid Content of the Human Intestinal Mucosa
Authors: Ahlman BO , Andersson Kerstin , Leijonmarck Carl-Eric , Ljungqvist Olle , Hedenborg Lennart , Wernerman JAN
Published: August 2015

1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n = 6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon.

2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased.

3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon.

4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine.

5. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.
The Rat SA Gene Shows Genotype-Dependent Tissue-Specific Expression
Authors: Kaiser Michael A. , Lodwick David , Samani Nilesh J.
Published: August 2015

1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat.

2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes.

3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed.

4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus.

5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.
Serum Levels, Absorption Efficiency, Faecal Elimination and Synthesis of Cholesterol during Increasing Doses of Dietary Sitostanol Esters in Hypercholesterolaemic Subjects
Authors: Vanhanen H. T. , Kajander J. , Lehtovirta H. , Miettinen T. A.
Published: August 2015

1. Serum cholesterol reduction and changes in cholesterol metabolism were studied during rapeseed oil feeding without and with increasing amounts of sitostanol trans-esterified with rapeseed oil fatty acids and dissolved in rapeseed oil mayonnaise. Fifteen mildly hypercholesterolaemic subjects replaced 50 g of their usual dietary fat by 50 g of rapeseed oil fat mayonnaise for 6 weeks followed by randomization so that eight subjects continued on rapeseed oil mayonnaise alone (control group) for 15 weeks and seven on rapeseed oil mayonnaise with a small dose of sitostanol ester (800 mg/day of sitostanol) for 9 weeks followed by 6 weeks with higher dose of sitostanol ester (2000 mg/day of sitostanol).

2. During the rapeseed oil period the reduction in serum low-density lipoprotein cholesterol was 14% from the home diet. The control-adjusted reduction by the low sitostanol ester dose was 7.4% (not significant) and by the higher dose it was 15.7%.

3. The low dose of sitostanol ester had no consistent effect on cholesterol precursors or cholestanol in serum, reduced serum levels of campesterol and sitosterol by 28.2% and 23.6%, respectively, and reduced cholesterol absorption efficiency significantly from 28.7% to 23.4%. In accordance, faecal excretion of neutral and particularly endogenous neutral sterols increased (16.7% and 19.7%, respectively), but faecal cholesterol elimination and cholesterol synthesis were only insignificantly increased.

4. During the high dose of sitostanol ester the high-density lipoprotein- to low-density lipoprotein-cholesterol ratio increased. Serum levels of cholesterol precursor sterols, indicators of cholesterol synthesis, increased up to 12%, whereas those of cholestanol were slightly decreased and those of campesterol and sitosterol values were further reduced by 30% and 25.6%, respectively.

5. Associations of serum plant sterols and cholesterol precursors with cholesterol absorption efficiency and synthesis and the sitostanol-ester-induced changes in serum campesterol and lathosterol proportions with those in serum low-density lipoprotein-cholesterol suggest that reduced cholesterol absorption efficiency was the main reason for cholesterol reduction and that there was a compensatory increase in cholesterol synthesis.

6. The findings indicate that sitostanol ester dissolved in dietary fat is apparently unabsorbable and interferes with sterol absorption so that the serum levels of cholesterol and low-density lipoprotein-cholesterol are reduced to the extent that sitostanol ester-fat mixture in reasonable daily amounts can be recommended to replace dietary fat for lowering of serum cholesterol.
Platelet-Activating Factor Mediates Pancreatic Function Derangement in Caerulein-Induced Pancreatitis in Rats
Authors: Alonso Ricardo , Montero Angel , Arévalo Miguel , García Luis J. , Sánchez-Vicente Concepción , Rodríguez-Nodal Fernando , López-NOVOA José M , Calvo José J.
Published: August 2015

1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 μg/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis.

2. We have also observed the effect of the platelet-activating factor antagonist, BN-52021, on the hyper-amylasaemia and exocrine pancreatic secretion impairment associated with pancreatitis.

3. In rats with pancreatitis the basal pancreatic flow rate was increased (1.63 ± 0.41 versus 0.25 ± 0.03 μl/min). Total protein output was similar in both untreated (5.98 ± 1.93 μg/min) and caerulein-injected (6.5 ± 2.0 μg/min) animals. Amylase output was lower in rats with pancreatitis (19.6 ± 4.8 μ-units/min) than in controls (39.4 ± 16.6 μ-units/min).

4. Caerulein-treated animals had significantly higher serum amylase levels than untreated animals. BN-52021 significantly reduced the caerulein-induced hyperamylasaemia.

5. Portal blood platelet-activating factor levels increased in rats with pancreatitis and in rats infused with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood levels of platelet-activating factor that were lower than those with pancreatitis.

6. Morphological derangements associated with pancreatitis (inflammatory infiltration and cell vacuolization) were also markedly reduced in BN-52021-treated animals.

7. The results of this study suggest that platelet-activating factor is involved in the development of caerulein-induced acute pancreatitis in rats.
Comparison of Stable Isotopes and Radioisotopes in the Measurement of Iron Absorption in Healthy Women
Authors: Barrett Jon F. R. , Whittaker Paul G , Fenwick John D. , Williams John G. , Lind Tom
Published: August 2015

1. Stable isotope methods are being used to investigate the absorption of dietary iron. In order to be certain that this new methodology is accurate, we have compared results obtained using stable isotopes and inductively coupled plasma mass spectrometry with those determined using a radioisotope and whole body counting.

2. The stable isotope 54Fe (2.8 mg) was given to 10 healthy non-pregnant women. Six women received the isotope in aqueous form, and four took it with a meat meal. The 54Fe served as a carrier for 10 ng of the radioisotope 59Fe. An ampoule (200 μg) of the isotope 57Fe or 58Fe was then given intravenously, and in serum samples taken over the next 10 h the ratios of the stable iron isotopes were measured by inductively coupled plasma mass spectrometry and the oral iron absorption was calculated. This was then compared with the results obtained by using a whole body counter to measure (on day 0 and day 14) the γ-activity emitted by the radioisotope.

3. The mean iron absorption measured by both methods ranged from 8% to 45%. Measurement of the post-absorptive serum enrichment of the stable isotopes provided estimates of absorption from both aqueous and food iron which were similar to that yielded by whole body counting, the mean difference being −1.5% (95% confidence interval −5.2 to 2.1%). Absorption estimated by stable isotopes exhibited the same inverse relationship with the serum ferritin level (body iron stores) to that known to exist with whole body counting. Similar estimates of food iron absorption were obtained irrespective of the type of isotope used as an extrinsic label, implying that stable isotopes are as valid as radioisotopes in reflecting intrinsic food iron absorption.

4. This study validates the use of stable isotopes and post-absorption curves as a new and accurate technique in the measurement of iron absorption.
Signal Variance Electrocardiogram: A Test for Early Detection of Myocardial Involvement in Cystic Fibrosis?
Authors: Freyschuss Ulla , Hjelte Lena , Johannesson Marie , Nowak Jacek , Sylvén Christer
Published: August 2015

1. Variance electrocardiography is a new resting procedure for the detection of ischaemia-induced variability in the electrical expression of the depolarization phase. The analysis is performed on 220 cardiac cycles using high-fidelity ECG signals from 24 leads, and the electrical variability is expressed as an electrical variability index ranging from 1 to 150. In this study, variance electrocardiography was employed to detect cardiac involvement in 23 patients with cystic fibrosis.

2. Patients with cystic fibrosis presented a significantly higher mean electrical variability index than control subjects, and their index values correlated inversely with the arterial oxygen partial pressure and forced expiratory volume in 1.0 s. Patients with a high electrical variability index (> 75) displayed a lower clinical score (Shwachman score) and a longer duration of chronic colonization with Pseudomonas aeruginosa. Patients with conduction disturbances and patients with echocardiographic right ventricular pathology presented higher indices than those without.

3. Electrical variability index is increased in cystic fibrosis and correlates with other signs of cardiac and pulmonary derangement. Variance electrocardiography may therefore have the potential to be a sensitive and simple method for monitoring cardiac involvement in this disease.
Renal Effects of Local Infusion of Adenosine in Man
Authors: Edlund Anders , Ohlsén Hans , Sollevi Alf
Published: August 2015

1. The effects of local intra-arterial infusion of adenosine on renal blood flow, glomerular filtration and renin release in eight healthy awake subjects have been examined.

2. Renal blood flow and glomerular filtration rate were measured as the clearances of p-aminohippurate and inulin, respectively. After basal samplings, adenosine was infused intra-arterially at successive rates of 2 and 10 μg min−1 kg−1 for 40 min at each rate.

3. Apart from a small increase in heart rate (65 ± 4 to 71 ± 4 beats/min), there were no signs of sympathetic activation (unchanged blood pressure and catecholamine levels) during the infusion. Clearance of p-aminohippurate tended to increase, but not significantly, during adenosine infusion (518 ± 48 ml/min basal, 563 ± 52 ml/min during the highest dose of adenosine). The arterial plasma concentration of p-aminohippurate decreased by 9 ± 3% (P < 0.05), consistent with a small increase in renal blood flow in the infused kidney. Inulin clearance was reduced from 115 ± 3 to 97 ± 2 ml/min (P <0.001). The extraction of inulin, reflecting the filtration fraction, was 18% in both kidneys in the basal state. During infusion of adenosine the extraction in the infused kidney decreased to 12 ± 3% (P < 0.01 compared with the control kidney, 23 ± 3%).

4. The total excretion of Na+ was unchanged, but there was a minor decrease in K+ clearance. Thus, the K+/Na+ excretion ratio decreased from a basal value of 13 ± 2 to 10 ± 2 (P <0.01) at the highest dose of adenosine. The calculated renal uptake of oxygen was unchanged in the control kidney, but decreased in the adenosine-infused kidney from a basal value of 5.4 ± 0.5 ml/min to 3.8 ± 0.4 ml/min at the highest dose of adenosine (P < 0.01).

5. During continued intra-arterial adenosine infusion, nitroprusside was infused (0.3-2.5 μg min−1 kg−1) for 15 min to decrease blood pressure and stimulate renin production. Mean blood pressure decreased from 90 ± 2 to 63 ± 2 mmHg, whereas heart rate remained unaffected. There were increases in the arterial concentrations of adrenaline (0.3 ± 0.1 to 1.3 ± 0.3 nmol/l; P<0.01), aldosterone (136 ± 24 to 491 ± 144 pmol/l; P<0.001) and renin activity (0.8 ± 0.2 to 1.8 ± 0.5 pmol) of angiotensin I h−1 min−1; P < 0.05; values correspond to the basal state and 15 min of nitroprusside infusion, respectively). In the control kidney the arteriovenous concentration difference for renin activity increased from the basal state by 2.3 ± 0.8 pmol of angiotensin I h−1 ml−1, but remained unchanged in the adenosine-infused kidney (0.0 ± 0.3 pmol of angiotensin I h−1 ml−1, P < 0.02).

6. In conclusion, the direct renal effects of adenosine in healthy awake subjects include a local dilatation of postglomerular vessels, thereby decreasing glomerular filtration, and a reduction in renal oxygen consumption. Furthermore, adenosine prevents an increase in renin release during nitroprusside-induced hypotension.
Ventilatory and Heart Rate Responses after Exercise in Chronic Cardiac Failure
Authors: Riley M. , Stanford C. F. , Nicholls D. P.
Published: August 2015

1. To determine if the recovery period after exercise is abnormal in chronic cardiac failure, we studied 15 patients with stable chronic cardiac failure, and 14 normal subjects during and after symptom-limited maximal treadmill exercise.

2. In patients, O2 consumption fell exponentially from 16.8 (13.7-20.0) ml min−1 kg−1 at peak exercise to 6.0 (5.2-6.7) ml min−1 kg−1 at 3 min of recovery and in control subjects it fell from 30.2 (27.0-33.5) ml min−1 kg−1 to 6.7 (5.9-7.4) ml min−1 kg−1 (mean and 95% confidence intervals). The associated decay constants were slower in patients [0.70 (0.58-0.83) min−1 versus 0.93 (0.81-1.05) min−1 in control subjects (P < 0.01, t-test)].

3. CO2 consumption kinetics displayed similar abnormalities [(k: 0.55 (0.41-0.69) min−1 versus 0.71 (0.59-0.83) min−1, P < 0.05)] and heart rate kinetics showed a similar trend [(k: 0.53 (0.33-0.74) min−1 versus 0.76 (0.62-0.89) min−1, P = 0.08].

4. We conclude that patients with cardiac failure recover more slowly from exercise than normal subjects, and that this may further impair their ability to perform exercise, with consequent effect on quality of life.
Pressure-Diuresis-Natriuresis Response in Hyperthyroid and Hypothyroid Rats
Authors: Vargas Félix , Atucha Noemí M. , Sabio J. Mario , Quesada Tomás , García-Estañ Joaquín
Published: August 2015

1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 μg day−1 kg−1) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders.

2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired.

3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight.

4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.
Role for Endothelin in the Renal Responses to Radiocontrast Media in the Rat
Authors: Oldroyd S. , Slee S.-J. , Haylor J. , Morcos S. K. , Wilson C.
Published: August 2015

1. The involvement of endothelin in the renal responses to radiocontrast media was examined in the rat in vitro and in vivo using BQ123, a selective endothelin (ETA) receptor antagonist, and phosphoramidon, an endothelin-converting enzyme inhibitor.

2. For experiments in vitro, an isolated perfused rat kidney was employed perfusing in closed circuit with an albumin-based Krebs-Henseleit solution. The effects of BQ123 and phosphoramidon on the renal responses to iotrolan (iso-osmolar radiocontrast media) and diatrizoate (high-osmolar radiocontrast media) were examined. In vivo, renal conductance was measured using a Doppler flow probe in the anaesthetized rat pretreated with indomethacin, and the effects of BQ123 and phosphoramidon on the renal response to intravenous diatrizoate were examined.

3. In vitro, iotrolan and diatrizoate both produced a biphasic effect on the glomerular filtration rate, characterized by a transient increase followed by a sustained fall. Pretreatment with BQ123 (10 μmol/l), but not phosphoramidon (1 mmol/l), prevented both the increase and the sustained fall in glomerular filtration rate induced by radiocontrast media.

4. In vitro, iotrolan and diatrizoate both produced a sustained fall in renal perfusate flow. An initial increase in renal perfusate flow was only observed with diatrizoate. Pretreatment with BQ123 (10 μmol/l), but not with phosphoramidon (1 mmol/l), markedly inhibited the sustained fall in renal perfusate flow produced by both iotrolan and diatrizoate. BQ123 (10 μmol/l), however, markedly potentiated the renal vasodilatation produced by diatrizoate.

5. In vivo, in the anaesthetized rat treated with indomethacin, the sustained fall in renal conductance produced by diatrizoate (2.9 g of iodine/kg, intravenously) was markedly inhibited by pretreatment with BQ123 (1 mg/kg) but not with phosphoramidon (10 mg/kg).

6. A role for endothelin as a mediator of the renal responses of radiocontrast media is proposed.
A Comparison of Bone Mineral Density between Caucasian, Asian and Afro-Caribbean Women
Authors: Tobias J. H. , Cook D. G. , Chambers T. J. , Dalzell N.
Published: August 2015

1. We analysed the lumbar spine (L2-L4) and femoral neck bone mineral density results of Caucasian (n = 2232), Asian (Indian sub-continent) (n = 153) and Afro-Caribbean (n = 102) women referred for bone densitometry over a 30 month period. To assess the risk of osteoporosis, the results of Caucasian and Asian women were compared with those of a reference Caucasian population supplied by Lunar.

2. Subject characteristics were similar in all three groups, other than expected ethnic differences in stature and weight. We found that lumbar spine and femoral neck bone mineral density in Caucasians was lower than in Afro-Caribbeans, but higher than in Asians. Consistent with this, bone mineral density was also lower in Asians as compared with the reference Caucasian population, both at the lumbar spine and femoral neck. As a consequence, a higher proportion of Asian women were classified as being at increased risk of osteoporosis than Caucasian women.

3. Since ethnic differences in skeletal size might influence bone mineral density, we also obtained values for bone mineral content in Caucasian and Asian women that were corrected for projected skeletal area, and weight and years since menopause, using regression equations derived from the Caucasian study population. After this analysis, the difference in bone mineral content between Caucasians and Asians at the lumbar spine disappeared, while that at the femoral neck persisted.

4. We conclude that the assessment of risk of osteoporosis in Asian women by comparing bone mineral density with a reference Caucasian population may have limited validity because of the influence of skeletal size on such measurements.
Bone Density and Mineral Metabolism in Thyroidectomized Patients Treated with Long-Term l-Thyroxine
Authors: Giannini Sandro , Nobile Martino , Sartori Leonardo , Binotto Pierluigi , Ciuffreda Matteo , Gemo Giancarlo , Pelizzo Maria Rosa , D'Angelo Angela , Crepaldi Gaetano
Published: August 2015

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group.

2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, postmenopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients.

3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.

4. We conclude that long-term thyroid-stimulating hormone-suppressive treatment with L-thyroxine in thyroidectomized women is not associated with a decrease in spinal bone mass nor with calcitonin deficiency, and that L-thyroxine treatment may increase skeletal sensitivity to menopause-related bone loss.
Prolonged Changes in Protein and Amino Acid Metabolism after Zymosan Treatment in Rats
Authors: Rooyackers Olav E. , Saris Wim H. M. , Soeters Peter B. , Wagenmakers Anton J. M.
Published: August 2015

1. Intraperitoneal injections of zymosan were given to rats, according to a modified procedure, in order to create a pattern of illness with an acute critical phase for 36 h followed by a prolonged recovery phase lasting for at least 10 days. Changes in amino acid and protein metabolism were studied in both phases.

2. Differences between this modified and the original zymosan model are a lower mortality (16%), which is limited to the first 36 critical hours, and the absence of signs of severe illness during the prolonged recovery phase.

3. Wasting of muscle protein and decreased protein synthesis rates in muscle were observed during the acute phase of illness. Liver size and liver protein synthesis rates were increased during the same period. The decrease in the total amount of muscle protein and the increase in liver weight were still present 12 days after zymosan treatment, despite a normalization of protein synthesis rates. Large decreases were observed in the concentrations of the conditionally essential amino acids glutamine and arginine in muscle over 6 days. Decreases in plasma glutamine and arginine on day 12 after zymosan indicated that the rats were still not fully recovered on this day.

4. We conclude that injection of a single dose of zymosan in rats leads to metabolic derangements both during the acute phase of critical illness and during the prolonged recovery phase. The model seems suited for investigating the biochemical mechanisms behind these metabolic derangements and for studying therapeutic and nutritional interventions during recovery from critical illness.
An Angiotensin Converting Enzyme Inhibitor, Perindopril, Prevents Progression of Preformed Atherosclerotic Lesions in the Cholesterol-Fed Rabbit
Authors: Fennessy Paul A. , Campbell Julie H. , Campbell Gordon R.
Published: August 2015

1. The aim was to determine whether the angiotensin converting enzyme inhibitor perindopril, at a concentration approaching that used in human antihypertensive therapy, influences progression of preformed atherosclerotic plaques.

2. Rabbits had their right carotid artery de-endothelialized with a balloon catheter, which resulted in the formation of a myointimal thickening.

3. At 14 weeks post surgery groups I, II and III (n = 6 per group) were fed a 1% cholesterol-enriched diet for 6 weeks, then group I rabbits were sacrificed. Groups II and III were placed on a normolipidaemic diet for a further 6 weeks with group III rabbits also receiving 0.3 mg day−1 kg−1 perindopril. Groups IV and V were treated the same as groups II and III, respectively, except that they received a normal diet throughout.

4. Group I rabbits fed a 1% cholesterol-enriched diet for 6 weeks developed lipid-filled lesions covering 26.3 ± 14.3% of the surface area of the descending thoracic aorta. This was exacerbated in rabbits fed a 1% cholesterol diet for 6 weeks followed by 6 weeks on a normal diet (61.2 ± 27.3%). In rabbits fed a 1% cholesterol diet for 6 weeks then a normal diet for a further 6 weeks plus 0.3 mg day−1 kg−1 perindopril, the percentage surface area covered by lesions was 21.8 ± 15.8%. No lesions developed in the aortas of rabbits fed a normal diet. In the right coronary artery the resulting neointima in rabbits fed a 1% cholesterol diet for 6 weeks only was 42.4 ± 5.7% of the cross-sectional area of the vessel wall, 57.4 ± 8.0% in rabbits receiving 6 weeks' cholesterol diet then 6 weeks' normal diet, 36.0 ± 6.6% in rabbits fed a 6-week cholesterol diet then 6 weeks' normal diet with 0.3 mg day−1 kg−1 perindopril and 33.2 ± 4.9% and 31.8 ± 3.1% in rabbits on a normal diet throughout with 0 and 0.3 mg day−1 kg−1 perindopril respectively. The cellular composition of the lesions was also altered in perindopril-treated animals, with fewer and smaller fat-filled cells surrounded by more extracellular matrix.

5. Perindopril is effective in preventing progression of existing atherosclerotic lesions in the cholesterol-fed rabbit after 6 weeks on a normal diet.
Effects of Fasting on Fatty Acid Kinetics and on the Cardiovascular, Thermogenic and Metabolic Responses to the Glucose Clamp
Authors: Webber J. , Taylor J. , Greathead H. , Dawson J. , Buttery P. J. , Macdonald I. A.
Published: August 2015

1. The effects of fasting for 12, 36 and 72 h were examined in 19 normal subjects. Each subject was studied before and during a euglycaemic (4 mmol/l) hyperinsulinaemic (100 m-units min−1 m−2) clamp. Measurements were made of palmitate turnover and oxidation, glucose disposal, thermogenesis, intermediary metabolites and cardiovascular variables.

2. Basal respiratory exchange ratio fell from 0.78 ± 0.01 to 0.75 ± 0.01 to 0.72 ± 0.01 with fasting (P < 0.001). In response to the clamp it rose to 0.91 ± 0.02, 0.83 ± 0.01 and 0.77 ± 0.01 after 12, 36 and 72 h respectively. Metabolic rate rose during the clamp by 0.41 ± 0.06, 0.11 ± 0.03 and 0.14 ± 0.04 kJ/min respectively (P < 0.001 for 36- and 72-h values versus that at 12 h).

3. Fasting reduced total insulin-mediated glucose disposal rates from 42.6 ± 2.5, to 31.0 ± 1.8 to 21.3 ± 1.5 μmol min−1 kg−1 body weight after 12, 36 and 72h respectively (P < 0.001). Glucose oxidation fell from 16.9 ± 1.1 to 8.7 ± 1.7 to 0.2 ± 1.3 μmol min−1kg−1 body weight over the same period (P < 0.001). Non-oxidative glucose disposal rates did not change significantly.

4. Basal plasma palmitate turnover increased with duration of fasting, being 1.16 ± 0.08, 1.72 ± 0.17 and 2.30 ± 0.35 μmol min−1 kg−1 body weight. In response to the clamp, palmitate turnover fell to 0.42 ± 0.05, 0.69 ± 0.08 and 1.28 ± 0.45μmol min−1 kg−1 body weight. Plasma palmitate oxidation was 0.58 ± 0.04, 0.75 ± 0.06 and 1.13 ± 0.11 μmol min−1 kg−1 body weight basally, and fell to 0.16 ± 0.02, 0.28 ± 0.04 and 0.43 ± 0.13 μmol min−1 kg−1 body weight by the end of the clamp. The proportion of total lipid oxidation represented by plasma non-essential fatty acid oxidation was not affected by fasting, but fell in response to the clamp.

5. Fasting caused a progressive resistance to the effects of insulin and glucose on oxidative glucose disposal and on forearm glucose uptake. Insulin-mediated glucose storage was unaffected by fasting, but the apparent cost of this storage was reduced by fasting.
Modulation of Cytokine Production In Vivo by Dietary Essential Fatty Acids in Patients with Colorectal Cancer
Authors: Purasiri P. , Murray A. , Richardson S. , Heys S. D. , Horrobin D. , Eremin O.
Published: August 2015

1. The effects of essential fatty acids (γ-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer.

2. Total serum cytokines - interleukin (interleukin-1β, 2, 4 and 6), tumour necrosis factor-α and interferon-γ - were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation.

3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of γ-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: triacylglycerol, cholesterol and phospholipid.

4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation.

5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1β levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-α by 73% (P = 0.040) and interferon-γ by 67% (P = 0.050).

6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values.

7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.
Effects of a Low-Protein Diet on Glomerular Endothelin Family Gene Expression in Experimental Focal Glomerular Sclerosis
Authors: Nakamura Tsukasa , Fukui Mitsumine , Ebihara Isao , Osada Shiori , Takahashi Toshimasa , Tomino Yasuhiko , Koide Hikaru
Published: August 2015

1. The present study was designed to assess whether glomerular expression of mRNAs for endothelin-1 and endothelin-3, as well as endothelin receptors A and B is affected by a low-protein diet during the course of focal glomerular sclerosis.

2. Focal glomerular sclerosis was induced in rats by injection of puromycin aminonucleoside on days 0, 27, 34 and 41 in conjunction with unilateral nephrectomy on day 22. Control rats were subjected to nephrectomy or sham operation on day 22.

3. Animals were divided into six groups. In group 1, the puromycin aminonucleoside-injected rats were fed a standard diet containing 22% protein. In group 2, the puromycin aminonucleoside-injected rats were fed a low-protein diet containing 6% protein, which was initiated on the day of the first puromycin aminonucleoside injection. In group 3, the nephrectomized rats without puromycin aminonucleoside were fed a standard diet. In group 4, the nephrectomized rats without puromycin aminonucleoside were fed a low-protein diet. In group 5, the sham-operated rats were fed a standard diet. In group 6, the sham-operated rats were fed a low-protein diet.

4. The percentage of sclerotic glomeruli in group 1 rats increased markedly with time, reaching 77% on day 80.

5. The glomerular mRNA levels for endothelin-1 and endothelin receptors A and B increased significantly as glomerular sclerosis progressed, whereas no endothelin-3 mRNA was detected in the glomeruli of any group.

6. The endothelin-1 production in isolated glomeruli from group 1 increased significantly as glomerular sclerosis progressed.

7. In group 2, the low-protein diet reduced the prevalence of glomerular sclerosis, attenuated the rise in mRNA levels for endothelin-1 and endothelin receptors A and B and reduced endothelin-1 production in glomeruli from rats with focal glomerular sclerosis.

8. These data indicate that increases in glomerular endothelin-1 and endothelin receptor mRNA levels are associated with the development of puromycin aminonucleoside-induced glomerular sclerosis. These effects are blunted by administration of a low-protein diet.
Regional Matching of Ventilation and Perfusion during Lobar Bronchial Occlusion in Man
Authors: Morrell N. W. , Nijran K. S. , Biggs T. , Seed W. A.
Published: August 2015

1. Ventilation—perfusion balance in the presence of airway obstruction will depend on the efficiency of hypoxic pulmonary vasoconstriction beyond obstructed airways and the matching of redistributed blood flow and ventilation to the rest of the lung. This study investigated the relative importance of these mechanisms in man during experimental bronchial occlusion.

2. The bronchus to the left lower lobe was temporarily occluded with a balloon-tipped catheter during fibreoptic bronchoscopy in eight supine normal volunteers. Respiratory gas tensions were measured within the occluded lobe with a respiratory mass spectrometer. The distribution of ventilation and perfusion was assessed under control conditions and after 5 min of bronchial occlusion by computer analysis of the regional distribution of radioactivity during inhalation of 81mKr gas and following injection of 99mTc-labelled macroaggregated albumin respectively.

3. Respiratory gas partial pressures within the occluded lobes rapidly stabilized at mixed venous gas tensions: Po2 43.4 ± 2.2 (SEM) mmHg, Pco2 40.2 ± 1.8 mmHg. During occlusions the arterial oxygen saturation fell from a baseline of 96.3 ± 0.46% to a nadir of 92.1 ± 0.43%. Bronchial occlusion produced underventilation in the left lung relative to perfusion, both in the region of the occluded lower lobe and at the lung apex. Relative overventilation occurred in the right lung.

4. It is concluded that arterial hypoxaemia during lobal bronchial occlusion is caused primarily by shunting of mixed venous blood, though the shunt fraction is reduced by approximately 50% by hypoxic pulmonary vasoconstriction. In lung adjacent to obstructed regions reduced compliance may impair ventilation more than perfusion to contribute to hypoxaemia. It seems likely that redistribution of ventilation and perfusion to unobstructed regions during lobar bronchial occlusion is dependent on mechanical factors rather than O2- or CO2-dependent changes in bronchial or vascular tone.
Screening Tests for Microalbuminuria in Non-Diabetic Elderly Subjects and Their Relation to Blood Pressure
Authors: James M. A. , Fotherby M. D. , Potter J. F.
Published: August 2015

1. Microalbumuria in non-diabetic elderly subjects is predictive of vascular disease and mortality, and related to levels of blood pressure.

2. This study was designed to examine whether more restricted periods of urine collection retained the relation to the prevailing level of blood pressure and successfully identified subjects with microalbuminura.

3. Fifty elderly subjects (aged over 60 years) made two consecutive 24-h urine collections for measurement of urinary albumin excretion, divided between daytime and night-time periods. Thirty-three subjects also provided a random ‘spot’ urine sample. Clinic and 24-h ambulatory blood pressure were also recorded.

4. Median 24-h urinary albumin excretion was 15.75 mg; 17 subjects had microalbuminuria. The median 24-h albumin—creatinine ratio was 1.91 mg/mmol. A threshold albumin—creatinine ratio of ≧ 3.0 mg/mmol in a random urine sample predicted microalbuminura with 92% sensitivity and 90% specificity. Alternatively, threshold values of 2.5 mg/mmol for men and 4.5 mg/mmol for women in an overnight urine collection predicted microalbuminuria with 88% sensitivity and 100% specificity.

5. The closest relation between albumin—creatinine ratio and blood pressure was that between spot albumin—creatinine ratio and clinic systolic blood pressure (r = 0.64, P < 0.001). Albumin—creatinine ratio was generally related to clinic systolic blood pressure, diastolic blood pressure and ambulatory systolic blood pressure. Microalbuminuric subjects had significantly higher levels of clinic and ambulatory systolic blood pressure than non-microalbuminuric subjects.

6. Microalbuminuria in the elderly is most closely related to clinic systolic blood pressure. Screening for microalbuminuria in the elderly can usefully be performed by the measurement of albumin—creatinine ratio in a random urine sample, with a threshold of ≧ 3.0 mg/mmol.