bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of changes in inspiratory flow rate on cough responses to inhaled capsaicin
Authors: Barros M. J. , Zammattio S. L. , Rees P. J.
Published: August 2015

1. Twelve non-smoking subjects inhaled capsaicin at three different inspiratory flow rates: 50, 100 and 150 litres/min. Capsaicin was delivered by a breath-actuated dosimeter; inhalations consisted of 0.21–13.6 nmol of capsaicin in doubling amounts given in random order.

2. The mean number of coughs per challenge decreased with increasing inspiratory flow rate. The difference in cough numbers were significant: 7.7 (95% confidence interval 2.5–12.8) for 50 versus 100 litres/min and 10.9 (95% confidence interval 5.0–16.9) for 100 versus 150 litres/min.

3. On a separate day, a cough threshold was measured by giving increasing doses of citric acid that were inhaled at 50 litres/min. There was a positive correlation between the sensitivity to capsaicin and the cough threshold to citric acid (r = 0.69, P = 0.01), and also between the cough latencies (r = 0.67, P = 0.02).

4. The negative relationship between the cough response and the inspiratory flow rate may be caused by increased laryngeal deposition at lower inspiratory flow rates.

5. These results are compatible with a similar anatomical distribution of cough receptors for capsaicin and citric acid.

6. These results suggest that changes in inspiratory flow rate may affect the results of cough challenges.
Effects of the Fab fragment of digoxin antibody on the natriuresis and increase in blood pressure induced by intracerebroventricular infusion of hypertonic saline solution in rats
Authors: YAMADA Kaoru , GOTO Atsuo , HUI Chen , YAGI Noriko , SUGIMOTO Tsuneaki
Published: August 2015

1. The effects of intravenous injection of Fab fragments of anti-digoxin IgG (Digibind) on the changes in blood pressure, urine volume and urinary sodium excretion after intracerebroventricular infusion of artificial cerebrospinal fluid with normal or high sodium concentration were examined in anaesthetized rats.

2. The biological efficacy of Digibind was confirmed by experiments in vitro and in vivo, which showed that pre-treatment with Digibind completely abolished or significantly attenuated the aortic contractile response or pressor response to digoxin in guinea-pigs.

3. Infusion of high-sodium cerebrospinal fluid, but not normal-sodium cerebrospinal fluid, into the lateral brain ventricle of rats caused marked increases in blood pressure, urine volume and urinary sodium excretion.

4. Digibind did not significantly affect the increases in blood pressure, urine volume and urinary sodium excretion caused by intracerebroventricular infusion of high-sodium cerebrospinal fluid.

5. Digoxin-like immunoreactive factor may play a minor role, if any, in central nervous system-induced natriuresis in rats.
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation
Authors: Harris Roger C. , Söderlund Karin , Hultman Eric
Published: August 2015

1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.

2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.

3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.

4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.

5. No side effects of creatine supplementation were noted.

6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
Glucose-6-phosphatase in normal adult human intestinal mucosa
Authors: Pears John , Jung Roland T. , Jankowski John , Waddell Ian D. , Burchell Ann
Published: August 2015

1. The existence of specific glucose-6-phosphatase activity in human intestinal mucosa has been somewhat controversial.

2. We have demonstrated the presence of low levels of specific glucose-6-phosphatase activity in normal human adult intestinal mucosa. Activity was found in oesophagus, stomach, duodenum and colon.

3. Immunoblot analysis using antibodies monospecific for the 36.5 kDa liver glucose-6-phosphatase catalytic subunit demonstrated that intestinal mucosa contains low levels of the glucose-6-phosphatase enzyme protein.

4. The low levels of activity together with problems of proteolysis make human intestinal biopsies unsuitable for use in the diagnosis of type 1 glycogen-storage disease.
Dopamine and the Kidney: Ten Years on
Authors: Lee M. R.
Published: August 2015

Ten years ago the Editorial Board of Clinical Science invited me to write an Editorial Review on dopamine and the kidney. The result was published in 1982 in Volume 62 [1]. It was my hope that it would serve to stimulate other investigators to take up this area of renal physiology and pharmacology and to help to solve some of the problems left unanswered at that time. Since 1982 much has happened: there have been major successes, such as the delineation of the renal and adrenal dopamine receptors, and some relative failures, such as the lack of development of clinically useful peripheral dopamine agonists for use in hypertension and congestive cardiac failure. Nevertheless, continuous progress has been made and it is my task in this Review to try to describe this general advance while not omitting remaining areas of uncertainty.

The areas which I will undertake to describe are:

1. The renal receptors for dopamine. 2. The source of dopamine in the urine and its formation in the kidney. 3. The actions of dopamine upon the kidney. 4. The interaction of renal dopamine with other substances. 5. Dopamine formation in hypertensive and oedematous states. 6. The search for specific peripheral dopaminergic agonists of therapeutic utility. 7. Final conclusions and unanswered questions.
Effects of Oral Alcohol on Superior Mesenteric Artery Blood Flow in Normal Man, Horizontal and Tilted
Authors: Maule S. , Chaudhuri K. Ray , Thomaides T. , Pavitt D. , McCleery J. , Mathias C. J.
Published: August 2015

1. The cardiovascular effects of oral alcohol (0.5 g/kg body weight diluted to 300 ml in sugar-free orange juice) were compared with those of placebo in 10 normal subjects. Measurements were made while the subjects were supine and horizontal for 45 min and after 10 min of 45° head-up tilt.

2. After alcohol, plasma alcohol levels rose from 1.9 ± 1.3 to 61.6 ± 6.5 mg/100 ml. After placebo, plasma alcohol levels did not increase. After alcohol and placebo, supine blood pressure was unchanged; heart rate, both supine and during tilt, rose after alcohol only.

3. After alcohol, superior mesenteric artery and digital skin blood flow increased and calculated vascular resistances fell. There was no change after placebo.

4. Forearm blood flow, forearm vascular resistance and cardiac index did not change in either phase, except for a fall in cardiac index during tilt but only after alcohol.

5. In conclusion, the acute ingestion of 0.5 g of alcohol/kg body weight in normal subjects raised heart rate and actively dilated the superior mesenteric artery and digital skin vessels. There was no effect on blood pressure, cardiac output and skeletal muscle vascular tone. During head-up tilt after alcohol, there was a tendency for blood pressure to fall with a compensatory rise in heart rate.
Increased Whole Body Protein Breakdown Predominates over Increased Whole Body Protein Synthesis in Multiple Organ Failure
Authors: Arnold J. , Campbell I. T. , Samuels Therese A. , Devlin J. C. , Green Ceri J. , Hipkin L. J. , MacDonald I. A. , Scrimgeour C. M. , Smith K. , Rennie M.J.
Published: August 2015

1. Whole body protein turnover was measured using a primed-constant infusion of L-[1−13C]leucine with measurement of breath 13CO2 production and plasma 13C α-ketoisocaproate enrichment. Ten fasting patients, requiring mechanical ventilation and suffering from multiple organ failure, and six healthy control subjects were studied.

2. Protein breakdown and leucine removal from the plasma for protein synthesis were significantly higher in the patients than in the control subjects (P <0.01). In addition, leucine oxidation was almost 75% higher in the patients than in the healthy control subjects (P <0.05).

3. Plasma concentrations of glucose, insulin and growth hormone were not different between the two groups, but those of glucagon (not significant), noradrenaline (P <0.05) and cortisol (P <0.01) were almost two- and three-fold higher in the patients than in the control subjects.

4. Mean energy expenditure, measured by indirect calorimetry, was 30% higher in the patients than in the healthy control subjects (P <0.01).

5. Combining the data from both groups of subjects and using multiple regression analysis, cortisol was found to be the most significant predictor of (i) protein breakdown (48% of variance explained), (ii) leucine oxidation (69%) and (iii) hourly energy expenditure (54%).

6. The present investigation using [13C]leucine tracer methods demonstrated, in patients with multiple organ failure, that whole body protein breakdown and synthesis increased concomitantly and were twice as high as rates measured in healthy control subjects. Of the hormones measured in the present study, Cortisol appears to have the most significant effect on whole body protein turnover.
Estimation of the Hepatic Extraction Ratio of Indocyanine Green in Swine
Authors: Kisor David F. , Frye Reginald F. , Kudsk Kenneth A.
Published: August 2015

1. The hepatic extraction ratio of Indocyanine Green was measured directly by trans-hepatic catheterization in 14 outbred swine (eight well-fed, six malnourished). A specific two-compartment pharmacokinetic model was fitted to the arterial Indocyanine Green concentration-time data and used to estimate the hepatic extraction ratio of Indocyanine Green.

2. The specific two-compartment pharmacokinetic model was modified to represent more accurately the physiological process of Indocyanine Green removal. Simulations were performed using this new model to estimate the hepatic extraction ratio of Indocyanine Green in the swine.

3. Similarly to previous findings, our data showed that the original model consistently overestimated the hepatic extraction ratio of Indocyanine Green (i.e. the model estimate was compared with the true, directly measured value).

4. The comparison of the modified model and the original model clearly indicates the reason for the overprediction of the hepatic extraction ratio of Indocyanine Green by the latter. The simulations using the new model indicate that the percentage of binding of Indocyanine Green to its transport protein (glutathione S-transferase) for removal in the bile will affect the estimation of the hepatic extraction ratio of Indocyanine Green. Thus, the amount of Indocyanine Green available for removal is less than that assumed by the original model.
Pulmonary Vascular Reactivity and Ischaemia-Reperfusion Injury in the Rat
Authors: Messent M. , Griffiths M. J. D. , Evans T. W.
Published: August 2015

1. The endothelium has been shown to modulate the pulmonary vascular response to hypoxia in the rat. Acute lung injury is associated with loss of hypoxic pulmonary vasoconstriction and increased pulmonary vascular permeability. Similar loss of the vascular response to hypoxia is seen after ischaemia-reperfusion injury of the myocardium.

2. The effects of reperfusion injury on pulmonary endothelial integrity, as shown by the albumin escape index and hypoxic pulmonary vasoconstriction, were investigated in isolated, blood-perfused rat lungs.

3. Ischaemia for 0.5 h, which itself caused no increase in the albumin escape index, was followed by reperfusion for 0.25 h, 0.5 h and 1 h. Controls were subjected to 2 h of perfusion only (n = 5 in all groups). The pulmonary pressor response to hypoxia (fractional inspired oxygen concentration, 3%) was measured before and after ischaemia-reperfusion, and the dilator response to acetylcholine was measured after ischaemia-reperfusion in all cases.

4. Ischaemia-reperfusion significantly increased the albumin escape index after 0.5 h (mean ± SEM, 1.40 ± 0.27) and 1 h (2.0 ± 0.30) compared with controls (0.54 ± 0.30, P <0.05 in both cases). The pulmonary pressor response to hypoxia was augmented significantly after reperfusion when compared with baseline hypoxic pulmonary vasoconstriction (change from baseline: 13.2 ± 4.63 and 22.2 ± 7.1% after 0.5 and 1.0 h of reperfusion, respectively, P <0.05). Vasorelaxation of sustained hypoxic vasoconstriction using acetylcholine was similar in both control lungs and those subjected to ischaemia-reperfusion.

5. These results suggest that the pressor response to hypoxia is augmented after damage to the pulmonary vascular endothelium induced by ischaemia-reperfusion. Although this may be due to diminished release of endothelium-derived relaxing factors, the normal vasodilator response to acetylcholine suggests the phenomenon is not due to a reduction in the release of endothelium-derived relaxing factor/nitric oxide.
Human Pyruvate Dehydrogenase Complex as An Autoantigen in Primary Biliary Cirrhosis
Authors: Palmer Jeremy M. , Bassendine Margaret F. , James Oliver F. W. , Yeaman Stephen J.
Published: August 2015

1. The sera of more than 90% of patients with primary biliary cirrhosis contain antimitochondrial antibodies which react with the E2 component of the pyruvate dehydrogenase complex, identified as the major autoantigen in primary biliary cirrhosis. All previous studies in this area have utilized protein derived from animal tissue or have used recombinant human pyruvate dehydrogenase complex E2 expressed in Escherichia coli.

2. We report the preparation and characterization of native pyruvate dehydrogenase complex and pyruvate dehydrogenase complex E2 from human heart tissue and its application in studies of immune reactivity with the sera of patients with primary biliary cirrhosis.

3. The immune reactivity of sera from patients with primary biliary cirrhosis versus the bovine and human E2/X components of pyruvate dehydrogenase complex was indistinguishable in both immunoblotting and the more sensitive e.l.i.s.a.

4. These findings suggest that the reactivity of sera from patients with primary biliary cirrhosis against the major autoantigen of the disease is a property of that antigen, independent of its human or bovine origin. Furthermore, this justifies the use of bovine pyruvate dehydrogenase complex in past and future work on primary biliary cirrhosis antibody reactivity.
Relationship between Insulin Release, Antinatriuresis and Hypokalaemia after Glucose Ingestion in Normal and Hypertensive Man
Authors: Natali Andrea , Galvan Alfredo Quiñones , Santoro Donatella , Pecori Neda , Taddei Stefano , Salvetti Antonio , Ferrannini Eleuterio
Published: August 2015

1. Insulin simultaneously causes hypokalaemia and antinatriuresis, and it has been suggested that the two effects are tightly coupled. Whether these actions are preserved in patients with essential hypertension is not known.

2. Eight hypertensive patients and eight normotensive control subjects were studied before and after the ingestion of 75 g of glucose. Despite similar glycaemic profiles, the patients showed a hyperinsulinaemic response incremental area 49 ±8 versus 27 ± 6 nmoll−1 3h, P <0.04) but a blunted hypokalemic response (−7±1 versus −16±1%, P <0.001). Both absolute and fractional urinary excretion of sodium and potassium were significantly decreased during glucose-induced hyperinsulinaemia in hypertensive patients as well as in normotensive subjects (P <0.05 for all changes).

3. To test whether hypokalaemia is required for insulin-induced antinatriuresis, each hypertensive patient received another oral glucose load during which enough potassium chloride was given to clamp the plasma potassium concentration at baseline. Under these conditions, significant insulin-induced antinatriuresis still occurred. In addition, whereas the glycaemic profile was superimposable, the response of the plasma insulin concentration was significantly greater with than without maintenance of the plasma potassium concentration (total area 79 ± 14 versus 63 ± 8 nmoll−1 3h, P <0.04).

4. We conclude that (a) insulin causes antinatriuresis, antikaliuresis and hypokalaemia under physiological conditions; (b) in hyperinsulinaemic (insulin-resistant) patients with essential hypertension, the anti-natriuretic action of insulin is quantitatively preserved; and (c) clamping plasma potassium levels prevents insulin-induced antikaliuresis but not anti-natriuresis, and potentiates the insulin secretory response to glucose.
Effect of Inhalation of 30% Nitrous Oxide on Spectral Components of Heart Rate Variability in Conscious man
Authors: Galletly D. C. , Tobin P. D. , Robinson B.J. , Corfiatis T.
Published: August 2015

1. Periodicities in cardiac interbeat interval may be resolved into discrete frequency components by applying Fourier analysis to heart rate time series. Low-frequency components (<0.15 Hz) are believed to be under parasympathetic and sympathetic control, whereas a higher frequency component in phase with respiration is believed to be entirely parasympathetic. The ratio of the power in the low-/high-frequency spectrum gives an estimate of sympathetic/para-sympathetic balance.

2. This study examined, using heart rate variability spectral analysis, the cardiac autonomic effects of breathing 30% N2O in normal subjects. While supine, the inhalation of N2O caused a significant fall in high-frequency power and a rise in the low-/high-frequency spectrum. During air breathing, tilting caused a significant rise in the mean blood pressure, heart rate, low-frequency power and low-/high-frequency spectrum. During N2O breathing, tilting caused a rise in the heart rate and the mean blood pressure, but no significant alteration in the power of individual spectral components. During tilting, the heart rate, the low-frequency and low-/high-frequency spectrum were less when breathing N2O than when breathing air.

3. These observations are consistent with the effect of N2O being an enhanced sympathetic balance of sinoatrial control, with the primary effect being through reduced parasympathetic tone. Enhanced sympathetic dominance of heart rate variability was seen on standing while subjects breathed air, but this effect was blunted with N2O.
Effects of Decreased Glutamine Supply on Gut and Liver Metabolism in vivo in Rats
Authors: Heeneman Sylvia , Deutz Nicolaas E. P.
Published: August 2015

1. It has recently been suggested that glutamine may be a conditionally essential nutrient rather than a non-essential amino acid. Therefore, administration of methionine sulphoximine was used to create a model of decreased arterial glutamine concentrations for 4 days. Glutamine consumption in portal-drained viscera and liver was measured after an overnight fast by determining fluxes and intracellular concentrations in normal rats, methionine sulphoximine-treated rats and pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids and ammonia and production of urea by the liver were determined concomitantly.

2. Methionine sulphoximine treatment for 4 days resulted in a 50% decrease in arterial glutamine concentration. Although the glutamine consumption and the intracellular glutamine concentration of the intestine were reduced by 50% at day 4, no changes in intestinal amino acid and ammonia metabolism were observed.

3. In the liver, glutamine consumption was reduced and ammonia uptake was increased, but urea synthesis was not changed. The decreased intracellular glutamine, glutamate, aspartate and ammonia concentrations coincided with a substantial reduction in liver branched-chain amino acid production.

4. These results suggest that reduced intestinal glutamine uptake does not induce marked changes in intestinal amino acid metabolism. The decreased liver branched-chain amino acid production suggests a reduction in the net liver protein degradation rate during methionine sulphoximine treatment.
Muscle Blood Flow during Intermittent Exercise: Comparison of the Microdialysis Ethanol Technique and 133Xe Clearance
Authors: Hickner R. C. , Bone D. , Ungerstedt U. , Jorfeldt L. , Henriksson J.
Published: August 2015

1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol technique and 133Xe clearance during intermittent isometric contractions (5 s on/10 s off) of the thigh at 0–60% of the maximal voluntary isometric contraction force.

2. A linear increase in blood flow over a 25-fold range was detected using both l33Xe clearance and the microdialysis ethanol technique.

3. The median correlation coefficient between percentage maximal voluntary isometric contraction force and the ethanol outflow/inflow ratio, a marker of blood flow, was r = −0.98 (−0.94 to −0.99) (median and range, n = 6). The corresponding correlation coefficient for 133Xe clearance was r = 0.97 (0.92–0.98), the correlation coefficient between the ethanol outflow/inflow ratio and 133Xe clearance being r = −0.92 (−0.89 to −0.94).

4. Dialysate glucose concentration, although affected by blood flow, was not always significantly correlated with blood flow changes (r = 0.70; 0.51-0.95).

5. It may be concluded that the ethanol technique provides a valid measure of changes in local skeletal muscle blood flow. The data furthermore show that a linear increase in thigh skeletal muscle blood flow exists during the studied protocol of intermittent isometric contractions.
Effects of Nitric Oxide Donors in Vitro on the Arachidonic Acid-Induced Platelet Release Reaction and Platelet Cyclic GMP Concentration in Pre-Eclampsia
Authors: Hardy E. , Rubin P. C. , Horn E. H.
Published: August 2015

1. Platelet activation in vivo occurs in healthy pregnancy and is more pronounced in pre-eclampsia.

2. This study has investigated: (i) the inhibitory potency of the nitric oxide donors 3-morpholinosydnonimine and sodium nitroprusside, on the platelet release reaction in vitro in non-pregnant, healthy pregnant and pre-eclamptic women; (ii) the concentration of cyclic GMP during incubation of washed platelets with sodium nitroprusside in a separate group of non-pregnant, healthy pregnant and pre-eclamptic women.

3. The half-maximal inhibitory concentration of sodium nitroprusside, in the presence of a phosphodiesterase inhibitor, for inhibition of the platelet release reaction was lower in the pre-eclamptic subjects than in the non-pregnant subjects (P < 0.05).

4. Several of the pre-eclamptic women were studied again postnatally. The half-maximal inhibitory concentrations of sodium nitroprusside and 3-morpholinosydnonimine were higher in the postnatal than in the antenatal sample (P < 0.02).

5. Peak platelet cyclic GMP responses to sodium nitroprusside were significantly higher in the pre-eclamptic women than in the healthy pregnant and non-pregnant women.

6. These results suggest that platelets are more sensitive to the inhibitory effects of nitric oxide donors in pre-eclampsia.
Increased Systolic Blood Pressure in Adult Rats Induced by Fetal Exposure to Maternal Low Protein Diets
Authors: Langley Simon C. , Jackson Alan A.
Published: August 2015

1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein).

2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets.

3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period.

4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15–22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups.

5. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly impair aspects of physiological and biochemical function in the fetus. This has potential adverse consequences for the later health of the offspring.
Evaluation of Multi-Frequency Bio-Impedance Analysis for the Assessment of Extracellular and Total Body Water in Surgical Patients
Authors: Hannan W. J. , Cowen S. J. , Fearon K. C. H. , Plester C. E. , Falconer J. S. , Richardson R. A.
Published: August 2015

1. Multi-frequency bio-impedance analysis has been used to estimate extracellular and total body water in a heterogeneous group of 43 surgical patients (23 males, 20 females).

2. Radioisotope-dilution methods were used for the measurement of extracellular and total body water.

3. Resistance and reactance were measured between wrist and ankle at frequencies from 5 kHz to 1 MHz.

4. Extracellular and total body water were estimated by multiple stepwise regression using the radioisotope values as the dependent variables. The parameters included in the regression were: resistance and reactance at each frequency, body habitus parameters, plasma albumin and plasma sodium.

5. The standard errors of the estimates between the measured and esitmated values were 1.73 litres (coefficient of variation 9.6%) and 2.17 litres (coefficient of variation 6.0%) for extracellular and total body water, respectively.

6. These errors represent a useful improvement relative to those obtained from anthropometric estimates. However, the improvements relative to the use of a single frequency (50 kHz) are not clinically significant.
Amino Acid Profile and Aromatic Amino Acid Concentration in Total Parenteral Nutrition: Effect on Growth, Protein Metabolism and Aromatic Amino Acid Metabolism in the Neonatal Piglet
Authors: Wykes Linda J. , House James D. , Ball Ronald O. , Pencharz Paul B.
Published: August 2015

1. The protein and amino acid utilization of two commercially available amino acid solutions, one egg-patterned (Vamin), the other human-milk-patterned (Vaminolact), were studied in piglets receiving total parenteral nutrition. It was hypothesized that Vaminolact was deficient in total aromatic amino acids, so a third group received a human-milk-patterned amino acid solution with added phenylalanine.

2. The piglets were on total parenteral nutrition for 8 days from day 2 or 3 of life. They all received a total energy intake of 1040 kJ day−1 kg−1 with macro-nutrient intakes of 14.6g of amino acid, 27.4 g of glucose and 9.4 g of fat day−1 kg−1.

3. Nitrogen balances were performed on days 3-8 of total parenteral nutrition. On day 8 a primed constant infusion of (1-14C]-phenylalanine was given to measure phenylalanine flux and fractional conversion to tyrosine. Transamination catabolites of phenylalanine and tyrosine were measured in urine on day 7.

4. The piglets receiving Vaminolact gained significantly less weight (0.86 kg compared with 1.18 kg for Vamin and 1.20 kg for phenylalanine-supplemented Vaminolact; P < 0.02) and nitrogen (1435 mg day−1 kg−1 compared with 1601 mg and 1836 mg day−1 kg−1 for the other groups; P < 0.0001).

5. The piglets receiving Vamin had high plasma phenylalanine levels (2234 μmol/l compared with 156 μmol/l for Vaminolact and 399 μmol for phenylalanine-supplemented Vaminolact; P < 0.0001). Those receiving Vamin also had an elevated excretion of phenylalanine transamination metabolites and low plasma lysine levels. Phenylalanine flux was highest in the Vamin group, intermediate in the phenylalanine-supplemented Vaminolact group and lowest in the Vaminolact group.

6. We conclude that Vaminolact is limiting in aromatic amino acids and that the addition of phenylalanine to the level in Vamin significantly improves growth and nitrogen retention; however, increasing the phenylalanine content of total parenteral nutrition is not the most metabolically suitable way to provide aromatic amino acids in neonatal total parenteral nutrition.
Studies with Radiolabelled Serum Amyloid P Component Provide Evidence for Turnover and Regression of Amyloid Deposits In Vivo
Authors: Hawkins Philip N.
Published: August 2015

1. Quantitative scintigraphic and turnover studies, utilizing the specific binding affinity of serum amyloid P component for amyloid fibrils, have been developed as a tool for evaluating amyloid deposits in vivo.

2. Serial studies in over 300 patients have shown characteristic, diagnostic tissue distributions of amyloid in different types of amyloidosis. There is generally a poor correlation between quantity of amyloid and associated organ dysfunction.

3. Contrary to previous expectations, regression of amyloid has been demonstrated systematically for the first time: AA, AL and variant transthyretin-associated amyloid deposits often regress rapidly, and sometimes completely, if the supply of fibril protein precursors is substantially reduced.
Physiology and Pathophysiology of Heart Rate and Blood Pressure Variability in Humans: Is Power Spectral Analysis Largely An Index of Baroreflex Gain?
Authors: Sleight Peter , La Rovere Maria Teresa , Mortara Andrea , Pinna Gianni , Maestri Roberto , Leuzzi Stefano , Bianchini Beatrice , Tavazzi Luigi , Bernardi Luciano
Published: August 2015

1. It is often assumed that the power in the low-(around 0.10 Hz) and high-frequency (around 0.25 Hz) bands obtained by power spectral analysis of cardiovascular variables reflects vagal and sympathetic tone respectively. An alternative model attributes the low-frequency band to a resonance in the control system that is produced by the inefficiently slow time constant of the reflex response to beat-to-beat changes in blood pressure effected by the sympathetic (with or without the parasympathetic) arm(s) of the baroreflex (De Boer model).

2. We have applied the De Boer model of circulatory variability to patients with varying baroreflex sensitivity and one normal subject, and have shown that the main differences in spectral power (for both low and high frequency) between and within subjects are caused by changes in the arterial baroreflex gain, particularly for vagal control of heart rate (R—R interval) and left ventricular stroke output. We have computed the power spectrum at rest and during neck suction (to stimulate carotid baroreceptors). We stimulated the baroreceptors at two frequencies (0.1 and 0.2 Hz), which were both distinct from the controlled respiration rate (0.25 Hz), in both normal subjects and heart failure patients with either sensitive or poor baroreflex control.

3. The data broadly confirm the De Boer model. The low-frequency (0.1 Hz) peak in either R—R or blood pressure variability) was spontaneously generated only if the baroreflex control of the autonomic outflow was relatively intact. With a large stimulus to the carotid baroreceptor it was possible to influence the low-frequency R—R but not low-frequency blood pressure variability. This implies that it is too simplistic to use power spectral analysis as a simple measure of autonomic balance

its underlying modulation is more complex than generally believed.

4. It may be that power spectral analysis is more a sensitive indicator of baroreflex control, particularly of vagal control, than direct evidence of autonomic balance. of course, there is often a correlation between the gain of the reflex and the autonomic balance of vagus and sympathetic. These considerations may help our understanding of some conditions, such as exercise or heart failure, when the power spectral analysis method fails to identify increased sympathetic discharge; this failure may partly be explained by the decrease in baroreflex sensitivity which occurs in these two conditions.
Brain Natriuretic Peptide: Effect on Left Ventricular Filling Patterns in Healthy Subjects
Authors: Clarkson Peter B. M. , Wheeldon Nigel M. , MacLeod Catherine , Coutie Wendy , MacDonald Thomas M.
Published: August 2015

1. Elevated plasma concentrations of brain natriuretic peptide are found in conditions associated with impaired left ventricular diastolic function. The purpose of this study was to determine whether this peptide actually plays a physiological role in improving myocardial performance in diastole.

2. Nine normal subjects received infusions of brain natriuretic peptide or placebo in a randomized, double-blind, crossover study. Brain natriuretic peptide infusion produced a significant reduction in isovolumic relaxation time (means and 95% confidence interval for difference−10.8 ms, −14.5 to −7.0 ms) (P < 0.01) and significantly increased both the peak E/A velocity (0.54, 0.14–0.94) (P < 0.05) and the E/A time velocity integral (1.09, 0.20–1.98) (P < 0.05).

3. These responses were evident at concentrations of brain natriuretic peptide that produced no associated effects on blood pressure, heart rate or stroke distance.

4. Brain natriuretic peptide infusion in normal subjects significantly reduces isovolumic relaxation time and improves transmitral Doppler flow profiles, suggesting that this peptide may be important in the control of left ventricular diastolic relaxation in man.
Glucose-Induced Thermogenesis in Splanchnic and Leg Tissues in Man
Authors: Simonsen Lene , Ryge Camilla , Bülow Jens
Published: August 2015

1. Fourteen healthy subjects were investigated before and for 4 hours after oral intake of 75 g of glucose (n = 8) or tap water (n = 6). Whole-body energy expenditure was measured by an open-circuit ventilated hood system. Blood samples for determination of oxygen, carbon dioxide, glucose and lactate were taken from an artery, a hepatic vein and a femoral vein. Blood flow in the splanchnic region was measured by constant infusion of Indocyanine Green. Leg blood flow was measured by venous occlusion strain-gauge plethysmography. Oxygen uptake and carbon dioxide output in the splanchnic and leg tissues were calculated as the product of blood flow and arteriovenous differences in oxygen or carbon dioxide concentrations. Net exchanges of glucose and lactate across the splanchnic and leg tissues were calculated as the product of blood flow and arteriovenous differences in whole-blood glucose or lactate concentrations.

2. Splanchnic oxygen uptake had a biphasic course with an initial increase from 2.35 ± 0.88 (SD) mmol/min to 2.85 ± 1.20 mmol/min 30 min after the glucose intake (P < 0.005) and a later decrease below the basal value to around 2.02 mmol/min 90–180 min after the glucose intake (P < 0.05). The integrated increase in the splanchnic oxygen uptake during the 4 h after the glucose intake was −32.6 ± 49.7 mmol/240 min. Leg oxygen uptake increased from 4.3 ± 1.4 μmol min−1 100 g−1 to 7.0 ± 3.2 μmol min−1 100 g−1 90 min after the glucose intake (P < 0.01). The integrated increase in leg oxygen uptake was 305.1 ± 394.3 μmol 240 min−1 100 g−1. Assuming leg oxygen uptake mainly represents average skeletal muscle, the skeletal muscle mass can explain around 45% of the whole-body glucose-induced thermogenesis.

3. It is concluded that the splanchnic tissues do not contribute to the integrated glucose-induced thermogenesis owing to a biphasic response in oxygen uptake, with an initial increase and a later decrease. Measurements across a leg give the same information as measurements across a forearm with respect to estimation of glucose-induced thermogenesis in skeletal muscle.
Microalbuminuria Reflects a Generalized Transvascular Albumin Leakiness in Clinically Healthy Subjects
Authors: Jensen Jan Skov , Borch-Johnsen Knut , Jensen Gorm , Feldt-Rasmussen BO
Published: August 2015

1. In epidemiological studies microalbuminuria, i.e. slightly elevated urinary albumin excretion rate, predicts increased atherosclerotic vascular morbidity and mortality. This study aimed to test the hypothesis that microalbuminuria in clinically healthy subjects is associated with a systemic transvascular albumin leakiness. In animal experiments the outflux of albumin and lipids to the arterial wall are highly correlated, and both are elevated in atherosclerosis.

2. All participants were recruited at random from a population-based epidemiological study, where the upper decile of urinary albumin excretion rate was 6.6 μg/min. Twenty-seven patients with persistent microalbuminuria (urinary albumin excretion rate 6.6–150 μg/min), and 56 age- and sex-matched control subjects with persistent normoalbuminuria (UAER ≤ 6.6 μg/min) were studied.

3. The systemic transvascular albumin leakage was measured as the fractional disappearance rate of 125I-labelled albumin from the total plasma compartment in 1 h after intravenous injection.

4. The fractional disappearance rate of albumin from the plasma compartment was higher in the microalbuminuric than in the normoalbuminuric group [5.8 (95% confidence interval 5.3–6.2; n = 27) versus 5.0 (4.6–5.5; n = 56)%/h, P < 0.05]. The positive correlation between urinary albumin excretion rate on continuous scale (logarithmically transformed) and the fractional disappearance rate of albumin from the plasma compartment [slope 0.4 (95% confidence interval 0.1–0.7; n = 83), r = 0.29, P < 0.005] was independent of age, sex, smoking status, blood pressure, body size, plasma volume, plasma albumin concentration and concentrations of blood glucose, serum insulin and serum lipids.

5. In conclusion, microalbuminuria is an independent marker of systemic transvascular albumin leakiness in clinically healthy subjects. This finding may partly explain the increased atherosclerotic vascular morbidity and mortality in microalbuminuric subjects. It is suggested that the observed transvascular leakiness, in addition, may cause increased lipid insudation to the arterial walls.
Plasma-Mediated Neutrophil Activation during Acute Myocardial Infarction: Role of Platelet-Activating Factor
Authors: Siminiak Tomasz , Egdell Robin M. , O'Gorman Daniel J. , Dye Julian F. , Sheridan Desmond J.
Published: August 2015

1. Polymorphonuclear neutrophils are involved in the development of myocardial injury during ischaemia through the release of free oxygen radicals and by adhesion of activated polymorphonuclear neutrophils to endothelium, resulting in plugging of coronary capillaries. Polymorphonuclear neutrophil activation may be a result of contact with ligands expressed by endothelial cells and/or a response to soluble stimuli released from ischaemic tissue to the plasma.

2. To investigate this we studied plasma-mediated polymorphonuclear neutrophil activation in vitro using plasma samples collected from 14 patients with acute myocardial infarction at time of admission and 6 h and 1, 2, 5 and 7 days later. Plasma samples were incubated with washed polymorphonuclear neutrophils isolated from healthy donors. Expression of adhesion molecules CD18/CD11b integrin and L-selectin (Leu-8) were measured by flow cytometry and superoxide anion production in polymorphonuclear neutrophils was measured by chemiluminescence.

3. Plasma samples obtained 6 h and 1 day after admission were capable of inducing CD18/CD11b antigen expression, superoxide anion production and L-selectin shedding in the washed polymorphonuclear neutrophils, and this effect was significant when compared with plasma taken at 5 and 7 days after admission.

4. The plasma-mediated polymorphonuclear neutrophil stimulation was prevented when the PMN were pretreated with platelet-activating factor receptor antagonists BN52021 or BN50739. The platelet-activating factor concentrations detected in the plasma samples were not higher than those detected in plasma from healthy subjects.

5. These findings suggest that during acute myocardial infarction peripheral plasma contains soluble stimuli capable of inducing polymorphonuclear neutrophil integrin expression, L-selectin shedding and oxygen free radical production and that platelet-activating factor appears to act as an autocrine polymorphonuclear neutrophil stimulus.
Comparison of Bio-Impedance Spectroscopy and Multi-Frequency Bio-Impedance Analysis for the Assessment of Extracellular and Total Body Water in Surgical Patients
Authors: Hannan W. J. , Cowen S. J. , Plester C. E. , Fearon K. C. H. , Debeau A.
Published: August 2015

1. Measurements of extracellular and total body water provide useful information on the nutritional status of surgical patients and may be estimated from whole-body bio-impedance measurements at different frequencies.

2. Resistance and reactance were measured at 50 frequencies from 5 kHz to 1 MHz in 29 surgical patients (17 males, 12 females) with a wide range of extracellular to total body water ratios.

3. A fit to the spectrum of reactance versus resistance data gave predicted resistances at frequencies zero and infinity. Values of extracellular and total body water determined by this bio-impedance spectroscopy technique were regressed against values obtained from radioisotope dilution. The standard errors of the estimate were 1.893l and 3.259l respectively.

4. Resistance indices (height2/resistance) at selected frequencies gave the highest correlations with extracellular and total body water at 5 kHz and 200 kHz respectively, and prediction equations derived from multiple stepwise regressions also showed these to be the optimum frequencies. The standard errors of the estimate for this multi-frequency bio-impedance analysis method were 1.937l and 2.606l for extracellular and total body water respectively.

5. To assess the ability of the two methods to measure changes in extracellular and total body water, reproducibility was assessed from repeat measurements 10 min apart in a subgroup of 15 patients. Bio-impedance spectroscopy gave mean coefficients of variation for extracellular and total body water of 0.9% and 3.0% respectively. For multi-frequency bio-impedance analysis the corresponding coefficients of variation were 0.9% and 0.6%.

6. It is concluded that a simple impedance analyser operating at only two frequencies compares favourably with the more complex spectroscopy technique for the determination of extracellular and total body water in surgical patients.
Effects of Intermittent Pressure-Induced Strain on the Electrophysiology of Cultured Human Chondrocytes: Evidence for the Presence of Stretch-Activated Membrane Ion Channels
Authors: Wright Malcolm , Jobanputra Paresh , Bavington Charles , Salter Donald M. , Nuki George
Published: August 2015

1. Cyclical pressurization of cultured chondrocytes results in increases in cyclic AMP and in the rate of proteoglycan synthesis. Intermittent increases in hydrostatic pressure are also associated with hyperpolarization of chondrocyte cell membranes and activation of Ca2+-dependent K+-ion channels but the physiological basis for this response to mechanical stimulation is unclear.

2. Experiments have been undertaken to better define the types of ion channels involved and to explore the possibility that the hyperpolarization response associated with cyclical pressurization of chondrocytes follows activation of stretch-activated ion channels.

3. The mean membrane potential of chondrocytes in non-confluent monolayer cell culture rose from −15.3 ± 0.24 mV to −21.1 ± 0.28 mV (n = 60, P < 0.0001) after intermittent pressurization (0.33 Hz, 16 kPa, 20 min).

4. Strain gauge measurements showed that cyclical pressurization was associated with strain on the base of the culture plate. The amplitude of the hyperpolarization response was proportional to the microstrain to which cells were subjected.

5. Membrane hyperpolarization did not occur when chondrocytes were subjected to cyclical pressurization in rigid glass culture dishes or plastic dishes positioned in the pressurization chamber so as to avoid bending of the base of the culture dish.

6. Indirect evidence that the hyperpolarization response after intermittent pressure-induced strain was associated with stimulation of stretch-activated ion channels was obtained from experiments with gadolinium, amiloride and hexamethylene amiloride, each of which abolished hyperpolarization.

7. Experiments with apamin, charybdotoxin and iberiotoxin showed that the Ca2+-activated K+ channels involved in the hyperpolarization response are apamin-sensitive, charybdotoxin- and iberiotoxin-resistant, low-conductance channels.

8. Somatostatin and cadmium chloride, which block L-type calcium channels, abolished strain-induced chondrocyte hyperpolarization. EGTA, which chelates extracellular Ca2+, reduced the response to 48% of control values, and thapsigargin, which raises intracellular Ca2+ by inhibition of Ca2+—ATPase in endoplasmic reticulum, caused hyperpolarization independently with further hyperpolarization after pressure-induced strain. These data indicate that chondrocyte hyperpolarization was dependent on intracellular Ca2+ concentrations.

9. Further work is required to determine whether stretch-activated ion channels shown to be associated with chondrocyte hyperpolarization after cyclical pressure-induced strain are also involved in the signal transduction process that leads to increases in proteoglycan synthesis.