bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of Acute Gastric Erosions in the Cat by Individual Human Pepsins
Authors: Sacra P. , Roberts N.B. , Taylor W.H.
Published: August 2015

1. Differing amounts of human pepsins 1, 3 (pepsin A) and 5 (pepsin C or gastriscin) in aqueous HCl/NaCl at pH 1.3 were placed in Perspex rings on the exposed luminal surface of the perfused cat stomach to test for mucolytic and erosive activity in vivo, with the acid medium in control rings.

2. After incubation at 37°C for 60 or 120 min, the test and control solutions were replaced by the same volume of each test or control solution containing 18 mg of aspirin and incubated for a further 120 min.

3. The number of bleeding points or erosions was counted at 15 min intervals. None was observed with human pepsins 1, 3 and 5 or with pig pepsin A or in the control rings.

4. With aspirin, erosions developed in all ringed areas. Their rate of development with time for pepsin 1 and pig pepsin did not differ from controls. Significantly more erosions developed with human pepsins 3 (5 mg per ring, P < 0.001) and 5 (0.32 mg per ring, P < 0.05).

5. Human pepsins 3 and 5, applied at pH 1.3 to the mucosal surface of the perfused cat stomach, therefore cause erosions when administered with aspirin, but do not produce erosions when given alone. In man, pepsins secreted in increased amount or concentration may therefore be unlikely to cause significant mucosal erosion unless human gastric mucosa is less resistant to pepsins than cat mucosa. Pepsins may perhaps facilitate the action of a second factor, such as aspirin, or infection with Helicobacter pylori.
Spectral Analysis of Systolic Blood Pressure and Heart Rate after Heart Transplantation in Children
Authors: Constant Isabelle , Girard Arlette , Bidois Jérôme Le , Villain Elizabeth , Laude Dominique , Elghozi Jean-Luc
Published: August 2015

1. The aim of the study was to examine the short-term variability in blood pressure and heart rate in 19 children who had received heart transplants and in eight normal control children.

2. Blood pressure was determined by a finger arterial pressure device. We examined the power spectra for heart rate and systolic blood pressure in the supine and tilted positions. In addition, we studied the acute changes in blood pressure and heart rate during active standing.

3. In the transplanted children we could distinguish two groups (groups A and B) in whom heart rate variability differed, although in both it was greatly reduced compared with controls (group C). In group A there were no significant fluctuations in the mid-frequency range for heart rate. The gain of the relationship between systolic blood pressure and heart rate was very low and there were virtually no heart rate changes associated with passive tilting.

4. By contrast, in group B transplant patients the heart rate variability, as assessed by standard deviation, was about half that of normal controls. The power spectra attenuation was greater in the high-frequency than in the mid-frequency bands. On passive tilting the latter became enhanced, but not the high-frequency variability. On active standing the tachycardic response was about half that of controls. The findings suggest some reinnervation involving cardiac sympathetic fibres to a greater degree than the fast-responding vagal fibres.

5. In both groups A and B the drop in systolic blood pressure observed early in active standing was about 4–6 times as great as in controls. One possible mechanism could be the loss of cardiac afferents.

6. Time since operation was a critical factor for reinnervation, since all subjects from group B were transplanted more than 44 months prior to the recording.

7. We conclude that in a proportion of children who have received heart transplantation there is a delayed reinnervation of the heart, which probably involves sympathetic effectors rather than the vagus.
Nitric Oxide Synthase Activity is Increased in Patients with Sepsis Syndrome
Authors: Goode Helen F. , Howdle Peter D. , Walker Barry E. , Webster Nigel R.
Published: August 2015

1. We measured nitric oxide synthase activity in peripheral blood polymorphonuclear leucocytes from 10 patients with sepsis syndrome and 10 healthy subjects.

2. Synthase activity was significantly higher in patients with sepsis than in control subjects (1202 ± 579 compared with 595 ± 544 pmol of nitric oxide min−1 mg−1 of cell protein, P < 0.05).

3. Activity was greatest in those patients with the larger number of organ failures, although this failed to reach significance (1489 ± 560 in patients with three or more organ failures and 843 ± 404 pmol of nitric oxide min−1 mg−1 of cell protein in those with less than three, P = 0.11).

4. This study provides evidence for the role of overproduction of the vasodilator nitric oxide in sepsis syndrome.
Production of Eicosanoids and Cytokines by Kupffer Cells from Young and Old Rats Stimulated by Endotoxin
Authors: Brouwer A. , Parker S. G. , Hendriks H. F. J. , Gibbons L. , Horan M. A.
Published: August 2015

1. The clinicopathological features of endotoxaemia have been ascribed to cytotoxic mediators such as tumour necrosis factor, interleukins and eicosanoids. Macrophages, particularly Kupffer cells, are an important source of these mediators. Mortality from endotoxaemia is highly age related.

2. These studies focus on the role of hepatic Kupffer cells in the increased sensitivity of old rats to bacterial endotoxins. Possible age-related changes in the production of eicosanoids and induction of gene expression and secretion of interleukin 1, tumour necrosis factor and interleukin 6 were investigated in Kupffer cells derived from both young and old animals.

3. Basal production of biological response modifiers was low in cells of both young and old rats. Lipopolysaccharide stimulated production of the same types of monokines as described for other types of macrophages, although the pattern was specific for Kupffer cells.

4. Eicosanoids, predominantly prostaglandin D2 and prostaglandin F2α, were produced mainly during the first hour after exposure to lipopolysaccharide. Endotoxin stimulated synthesis of mRNAs of interleukin 1, interleukin 6 and tumour necrosis factor α resulting in increased secretion of these cytokines into the medium.

5. Kupffer cells from both young and aged animals appear to be exquisitely sensitive to endotoxin in respect of expression of mRNA for both interleukin 1α and interleukin 1β and less sensitive with respect to interleukin 6 and tumour necrosis factor α gene expression. At relatively high lipopolysaccharide concentrations interleukin 6 was secreted in particularly large amounts.

6. The effects of ageing on any of these responses of Kupffer cells were minimal.

7. It seems unlikely that age-related changes in the synthesis and secretion of eicosanoids and cytokines by Kupffer cells are an important factor in the increased susceptibility of old rats to LPS.
Increased Hepatic Secretion of Very-Low-Density Lipoprotein Apolipoprotein B-100 in Obesity: A Stable Isotope Study
Authors: Cummings Michael H. , Watts Gerald F. , Pal Cauvery , Umpleby Margot , Hennessy Thomas R. , Naoumova Rossitza , Sönksen Peter H.
Published: August 2015

1. We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography—mass spectrometry method in six obese subjects [three males, three females, age 41.5 ± 3.4 years (mean ± SEM), weight 105.0 ± 4.8 kg, plasma total cholesterol concentration 6.2 ± 0.4 mmol/l, triacylglycerol 2.8 ± 0.8 mmol/l, high-density lipoprotein cholesterol 1.0 ± 0.2 mmol/l] and six lean control subjects (three males, three females, age 41.8 ± 3.7 years, weight 68.2 ± 4.9 kg, total cholesterol concentration 4.5 ± 0.3 mmol/l, triacylglycerol 0.8 ± 0.2 mmol/l, high-density lipoprotein cholesterol 1.3 ± 0.1 mmol/l).

2. Plasma total cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the obese subjects than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB pool size and absolute secretion rate were significantly higher in the obese subjects than in control subjects (323.4 ± 99.8 mg versus 53.6 ± 17.1 mg, P = 0.004; and 42.3 ± 13.8 mg kg fat-free mass−1 day−1 versus 10.7 ± 0.4 mg kg fat-free mass−1 day−1, P = 0.01), but there was no significant difference in the fractional catabolic rate of VLDL apoB.

3. After pooling obese and control data, there was a significant positive association between VLDL apoB absolute secretion rate and (i) fat mass (r = 0.71, P = 0.009), (ii) plasma total cholesterol (r = 0.66, P = 0.019), (iii) triacylglycerol (r = 0.72, P = 0.008), (iv) total apolipoprotein B-100 (r = 0.77, P = 0.02), (v) mevalonic acid (r = 0.81, P < 0.001), (vi) fasting insulin (r = 0.61, P = 0.03) and (vii) fasting C-peptide (r = 0.70, P = 0.01) concentrations. There was also a significant positive association between plasma insulin and plasma mevalonic acid concentrations (r = 0.59, P = 0.04). The association between VLDL apoB absolute secretion rate and plasma mevalonic acid concentration remained significant after adjusting for plasma insulin concentration (r = 0.83, P = 0.01); however plasma insulin concentration was no longer associated with VLDL apoB absolute secretion rate (P = 0.40).

4. We conclude that increased hepatic secretion of VLDL apoB contributes to the elevated lipid concentrations observed in obesity. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion and may be partly mediated by increased cholesterol synthesis.
Acute Stimulation of Albumin Synthesis Rate with Oral Meal Feeding in Healthy Subjects Measured with [Ring-2H5]Phenylalanine
Authors: Hunter K. A. , Ballmer P. E. , Anderson S. E. , Broom J. , Garlick P. J. , McNurlan M. A.
Published: August 2015

1. The short-term effect of oral feeding on albumin synthesis rate was investigated in 12 healthy volunteers using two meal regimens. Albumin synthesis was measured over 90 min after injection of a ‘flooding’ amount (43 mg/kg body weight) of phenylalanine enriched to 7.5, 10 or 15 atoms% with the stable isotope [ring-2H5]phenylalanine.

2. In one set of subjects, consumption of five small hourly meals resulted in a consistent and significant increase (P < 0.05) in albumin fractional synthesis rate from a mean (± SEM) fasting value of 5.8 (± 0.4)%/day to 7.1 (± 0.4)%/day in the fed state.

3. A second study in which albumin synthesis was measured 30 min after consumption of a single larger meal was carried out in another set of volunteers. The fractional rate of albumin synthesis was again significantly elevated after feeding (P < 0.05), rising from 7.1 (± 0.4)%/day in the fasted state to 9.1 (± 0.6)%/day in the fed state. In both studies, similar responses were observed in the absolute rate of albumin synthesis (mg day−1 kg−1).

4. Albumin secretion time was significantly shorter (P < 0.05) after feeding in both studies, suggesting that the acute stimulation in albumin synthesis observed after feeding may in part be mediated via a post-transcriptional mechanism.

5. The response of total liver protein synthesis to oral feeding was investigated in an animal model employing adult rats studied with a flooding amount of [2,6-3H]phenylalanine.

6. The results indicated a stimulation of 20% with no difference in the proportion of albumin synthesis relative to total liver synthesis, determined from the immunoprecipitation of albumin from the liver.
Effects of Insulin-Like Growth Factor-1 and Growth Hormone on the Net Flux of Amino Acids across the Hind Limbs in the Surgically Traumatized Pig
Authors: Malmlöf Kjell , Cortova Zuzana , Saxerholt Henri , Karlsson Eivor , Arrhenius-Nyberg Vibeke , Skottner Anna
Published: August 2015

1. After surgery three groups of six female pigs weighing on average 52.2 kg (SD 3.5) received vehicle, recombinant insulin-like factor-1 (364.4 μg day−1 kg−1) or recombinant human growth hormone (467.7 m-i.u. day−1 kg−1) for two post-operative days. Vehicle and peptides were infused intravenously together with total parenteral nutrition providing 129 kJ day−1 kg−1 non-protein calories and 0.35 gN day−1 kg−1.

2. On both post-operative days the mean concentration of insulin-like growth factor-1 in arterial blood samples was clearly below presurgical levels in animals receiving vehicle or recombinant human growth hormone, whereas recombinant human insulin-like growth factor-1 infusions more than restored insulin-like growth factor-1 concentrations. These last samples, however, contained significantly (P<0.05) less insulin than those from other animals.

3. Infusion of recombinant human growth factor was often associated with higher circulating levels of amino acids compared with recombinant human insulin-like growth factor-1 infusions. Despite this, both hormones significantly (P < 0.05) increased the hind limb net balance of total amino acids on postoperative day 1. Net balances of −44.2, +69.5 and +100.9 μmol/min (pooled SE 35.3) were associated with infusion of vehicle, recombinant human insulinlike growth factor-1 and recombinant human growth hormone respectively. This response was also closely reflected in the group of non-essential amino acids.

4. The net efflux of alanine from the hind limbs was also significantly (P < 0.002) reduced, whereas glutamine was less affected.

5. On post-operative day 2, there was a general drop in cortisol and urea levels, implying a loss of catabolic tone. Concomitantly, most effects seen on amino acids flux after hormone administration on the previous day disappeared.

6. It is concluded that, in the acute catabolic state, both recombinant human insulin-like growth factor-1 and recombinant human growth hormone can prevent the erosion of body protein by increasing the peripheral net balance of amino acids and can thus increase the efficacy of total parenteral nutrition.
Effects of Low-dose Angiotensin II Infusion on Loop Segment Reabsorption: A Free-Flow Micropuncture Study in Rats
Authors: Fransen René , Boer Walther H. , De Roos Remmert , Boer Peter , Koomans Hein A.
Published: August 2015

1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule.

2. Endogenous angiotensin II was suppressed by pretreament with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 ± 0.05 to 1.10 ± 0.05 ml/min, Na+ excretion from 0.43 ± 0.09 to 0.13 ± 0.03 μmol/min, fractional delivery of water at the late proximal tubule from 50.1 ± 1.7 to 42.9 ± 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 ± 1.3 to 39.1 ± 3.5% and fractional delivery of water at the early distal tubule from 26.4 ± 1.4 to 21.9 ± 1.0% (P < 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly.

3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 ± 0.7 to 6.8 ± 0.9% (P < 0.05).

4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate.

5. The decrease in fractional excretion of Li+ followed the decrease in proximal reabsorption as measured directly by micropuncture. Angiotensin II infusion did not appear to affect Li+ reabsorption beyond the proximal tubule. Distal fractional Na+ reabsorption estimated by the Li+ clearance increased significantly during angiotensin II infusion.

6. In conclusion, our data indicate that a Na+-retaining dose of angiotensin II increases Na+ reabsorption in the proximal tubule, an effect correctly indicated by the change in the fractional excretion of Li+, does not influence Na+ reabsorption in the loop of Henle beyond the proximal tubule, but may increase Na+ reabsorption in more distal segments.
Is Allopurinol Beneficial in the Prevention of Renal Ischaemia—Reperfusion Injury in the Rat?: Evaluation by Near-Infrared Spectroscopy
Authors: Vaughan D. L. , Wickramasinghe Y. A. B. D. , Russell G. I. , Thorniley M. S. , Houston R. F. , Ruban E. , Rolfe P.
Published: August 2015

1. The role of allopurinol in the protection of kidney function following ischaemia—reperfusion injury has been investigated using the novel technique of near-infrared spectroscopy.

2. An in vivo model of rat kidney ischaemia was used, with the expected falls in blood and tissue oxygenation seen and confirmed by near-infrared spectroscopy.

3. Allopurinol infusion increased the rate of reperfusion of oxygenated blood seen in control rats (P < 0.05).

4. Allopurinol enhanced the rate of tissue oxygenation during early reperfusion (P < 0.01).

5. This study provides further evidence for the proposed benefits of allopurinol in ischaemia—reperfusion injury. Furthermore, the potential of near-infrared spectroscopy as a technique of value in interventional studies of this nature is confirmed.
Relation between Uroporphyrin Excretion, Acute Attacks of Hereditary Coproporphyria and Successful Treatment with Haem Arginate
Authors: Schoenfeld N. , Mamet R. , Dotan I. , Sztern M. , Levo Y. , Aderka D.
Published: August 2015

1. The increased urinary excretion of porphyrins as well as of their precursors was studied in a patient with hereditary coproporphyria during two acute attacks in which symptoms differed markedly in character and severity.

2. The increase in urinary coproporphyrin was similar in the ‘mild’ and in the ‘severe’ attack, indicating a lack of correlation between coproporphyrin level and clinical symptoms.

3. Aminolaevulinic acid, porphobilinogen and uroporphyrin exhibited significantly higher values during the ‘severe’ attack than during the ‘mild’ attack. During the severe attack these three compounds were increased 18-, 14- and 46-fold, respectively, compared with increases of 3-, 3- and 8-fold, respectively, during the mild attack.

4. The striking rise in the formation of uroporphyrin was reflected in the plasma porphyrin profile, which revealed predominance of uroporphyrin. In accordance with this finding, an increase in erythrocyte porphobilinogen deaminase of 130% was recorded.

5. The fluorescence emission spectra of saline-diluted plasma (excitation of 405 nm) showed a distinct peak at 618 nm during the ‘severe’ episode and a small peak during the ‘mild’ attack, pointing to the possibility of diagnosing an attack simply by following the fluorometric screen of plasma.

6. The ‘severe’ attack of coproporphyria was treated with daily infusions of haem arginate, 3 mg/kg, every day for 4 days, at the end of which period a dramatic clinical response was observed. The relief of symptoms was found to be clearly related to the moderate decrease in uroporphyrin excretion observed rather than to the steep decline in the precursors.
Selective Enhancement of α2-Adrenoceptor-Mediated Vasoconstriction in Insulin-Dependent Diabetic Patients with Microalbuminuria
Authors: Bodmer Charles W. , Schaper Nicolaas C. , Janssen Maureen , De Leeuw Peter W. , Williams Gareth
Published: August 2015

1. Microalbuminuria, the earliest clinical marker of microvascular disease, is an important predictor of early death in insulin-dependent diabetes, and abnormal vascular reactivity may contribute to microvascular disease. We have previously found that vasoconstrictive responses to noradrenaline are exaggerated in insulin-dependent diabetic patients with microalbuminuria as compared with both normoalbuminuric insulin-dependent diabetic patients and non-diabetic control subjects.

2. To determine whether this is due to increased sensitivity at α1- or α2-adrenergic receptors, we compared vascular responses to the α1-adrenergic agonist phenylephrine and the α2-adrenergic agonist clonidine.

3. We studied 15 insulin-dependent diabetic patients with microalbuminuria, 15 insulin-dependent diabetic patients with normal urinary albumin excretion and 14 non-diabetic subjects. Vascular constrictive responses were measured in dorsal hand veins.

4. No difference in vasoreactivity to phenylephrine was demonstrated between any of the three groups. However, enhanced vascular responsitivity to clonidine at infusion rates of 16–2048 ng/min (analysis of variance, P < 0.001) was found in insulin-dependent diabetic patients with microalbuminuria as compared with both non-diabetic control subjects and normoalbuminuric insulin-dependent diabetic patients. There were no significant differences between the dose—response curves of the diabetic group with normal urinary albumin excretion and the non-diabetic group.

5. Vasoconstriction mediated by α2-adrenergic receptors is therefore enhanced in normotensive insulin-dependent diabetic patients with microalbuminuria. If also present at the level of the peripheral resistance arterioles or the efferent glomerular arterioles, this could lead to systemic and intraglomerular hypertension, factors which may contribute to the development of diabetic nephropathy.
The SA Gene: Predisposition to Hypertension and Renal Function in Man
Authors: Harrap Stephen B. , Samani Nilesh J. , Lodwick David , Connor J. Michael , Fraser Robert , Davies David L. , Lever Anthony F. , Foy Chris J. W. , Watt Graham C. M.
Published: August 2015

1. The SA gene is expressed in the kidneys and is associated with hypertension in man and experimental animal models. Predisposition to hypertension is associated with renal haemodynamic abnormalities and increased renal SA gene expression.

2. We studied the distribution of the SA gene alleles (A1, A2), defined by the PstI polymorphism, in young adults with contrasting predisposition to hypertension to determine whether genetic variation at the SA gene locus is associated with variations in renal haemodynamics, electrolyte metabolism and the renin—angiotensin system.

3. The frequency of the A2 allele was not significantly different between subjects with high personal and parental blood pressures and subjects with low personal and parental blood pressures. We detected no overall relationship between blood pressures and SA genotype, even after taking sodium intake into account.

4. Glomerular filtration rate, renal blood flow, renal vascular resistance, plasma volume, exchangeable sodium and total body water did not differ according to SA genotypes. Moreover, we detected no significant effect of SA genotype on circulating components of the renin—angiotensin system or atrial natriuretic peptide.

5. In our population, genetic variation at the SA gene locus defined by PstI polymorphism does not influence the renal characteristics that contribute to the development of hypertension.
Comparative Effects of Recombinant Human Insulin-Like Growth Factor I and Insulin on Whole-Body and Forearm Palmitate Metabolism in Man
Authors: Laager Roland , Ninnis Ronald , Keller Ulrich
Published: August 2015

1. The effects of intravenous infusions of recombinant human insulin-like growth factor 1 and insulin on palmitate kinetics, lipolysis and on serum triacylglycerol were compared. Overnight-fasted normal subjects received high doses of insulin-like growth factor I (30 μgh−1 kg−1) and insulin (0.23 nmol h−1 kg−1; group 1), low doses of insulin-like growth factor I (5 μg h−1 kg−1) and insulin (0.04 nmol h−1 kg−1; group 2) or saline (control group). The doses of insulin-like growth factor I and insulin were equipotent with regard to increases in glucose uptake during 8 h euglycaemic clamping.

2. Whole-body palmitate flux (measured by continuous infusions of [2,2-D2]palmitate) was lowered dose-dependently by 68% ± 6% during insulin-like growth factor I and by 82% ± 2% during insulin after 8 h of infusions of high doses (insulin-like growth factor I versus insulin; not significant). Plasma palmitate, glycerol and triacylglycerol concentrations had decreased to a similar extent at the end of the infusions of both peptides at either dose.

3. The present results demonstrate that insulin-like growth factor I and insulin infused at doses which result in identical increases in glucose uptake during euglycaemic clamping are equipotent inhibitors of lipolysis.
Effect of Extracellular Potassium Concentration on the Sodium-Potassium Pump Rate in Human Lymphocytes
Authors: Webb George D. , Taylor Elizabeth A. , Vernon M. S. OH , Soh-Bee YEO , Leong L. NG
Published: August 2015

1. The purpose of this study was to determine whether physiological changes in extracellular free [K+] cause significant changes in the Na+-K+ pump rate and intracellular free [Na+].

2. The Na+-K+ pump rate was measured in human lymphocytes by determining ouabain-sensitive 86Rb+ influx at several concentrations of K+. The Na+-K+ pump rate increased within the physiological range of extracellular free [K+] (K1/2 = 1.5 mmol/l).

3. To test the hypothesis that elevation of extracellular free [K+] reduces intracellular free [Na+] rapidly, which in turn then slows the pump rate during experimental incubations, lymphocyte intracellular free [Na+] was measured using the fluorochrome sodium-binding benzofuran isophthalate. With larger elevations of extracellular free [K+], intracellular free [Na+] dropped more rapidly. Thus previous discrepancies among determinations of K1/2 may be the result of variations in incubation times, which can skew the pump rates measured during incubations in various extracellular free [K+] values. Steady-state intracellular free [Na+] varied inversely with extracellular free [K+].
Long-Term Fructose versus Corn Starch Feeding in the Spontaneously Hypertensive Rat
Authors: van der Schaaf Margriet R. , Joles Jaap A. , van Tol Arie , Koomans Hein A.
Published: August 2015

1. Fructose feeding, as opposed to vegetable starch feeding, has been shown to elevate blood pressure and to decrease insulin sensitivity in normotensive rats. The long-term relevance of this is unclear, and data in hypertensive strains are scarce.

2. We studied the effects of 27 weeks of a fructose-versus a corn-starch-enriched (69.5% w/w) diet in the spontaneously hypertensive rat.

3. In both dietary groups, blood pressure increased with ageing, with no apparent difference between the diets. The fructose-fed rats gained less weight. However, even selecting fructose-fed rats that matched the weight gain in the corn starch group, did not reveal a significant elevation of systolic blood pressure over time.

4. Extracellular fluid volume was comparable in fructose-fed and corn-starch-fed rats. No effects on creatinine clearance, proteinuria or renal histology were found. Fasting values of plasma triacylgycerols and cholesterol were increased mildly after 2 weeks on the fructose diet. However, fasting glucose and insulin measured after 2 weeks, and the response to an intraperitoneal glucose load, were no different. After 23 weeks of the diets, fasting values of plasma glucose, insulin, triacylglycerols and cholesterol did not differ. There were small differences in the response of plasma glucose levels to the intraperitoneal glucose load, but the area under the curve was not different. The baseline insulin resistance present in spontaneously hypertensive rats possibly blunts the metabolic response to dietary fructose.

5. After 27 weeks, the diets were switched in crossover design, and measurements were continued until 39 weeks. The fructose diet did not elevate systolic blood pressure in this follow-up experiment.

6. To summarize, long-term fructose versus corn starch feeding did not increase systolic blood pressure in spontaneously hypertensive rats. Metabolic variables were transiently affected and renal function was undisturbed. These findings suggest that long-term fructose feeding, compared with other dietary carbohydrates, is not specifically harmful in the spontaneously hypertensive rat.
High Water Intake Combined with Low Sodium Intake Abolishes the Antidiuretic Effect of Angiotensin II in Conscious Dogs
Authors: Kaczmarczyk Gabriele , Boemke Willehad , Zahrei-Fard Dawod , Braun Hermann
Published: August 2015

1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodium intake with and without concomitant post-prandial infusion of angiotensin II. Six trained dogs were exposed to diets containing either 0.5 or 14.5 mmol Na+ day−1 kg−1 body weight (low or high sodium respectively). They were studied from 20 min before to 4 h after food intake. In half of the experiments a physiological dose of angiotensin II (4 ng min−1 kg−1 body weight) was administered after food intake for four post-prandial hours. The water intake was high and equal on both diets (91 ml day−1 kg−1 body weight).

2. On a high-salt diet post-prandial sodium excretion and urine volume increased considerably above fasting values. This post-prandial increase was attenuated when angiotensin II was infused (post-prandial sodium excretion was 31% ± 3% of intake without versus 10% ± 1% with angiotensin II, post-prandial urine volume was 22% ± 2% without versus 8% ± 1% with angiotensin II, P < 0.05). Post-prandial increases in glomerular filtration rate and fractional sodium excretion were attenuated during angiotensin II infusion in dogs on a high-salt diet.

3. On a low-salt diet post-prandial sodium excretion remained low with or without angiotensin II infusion, whereas urine volume increased post-prandially, and this increase was greater when angiotensin II was administered (40% ± 3% versus 34% ± 2% of intake, P < 0.05).

4. Angiotensin II infusion increased mean arterial pressure by an average of 12 mmHg in dogs on a high-salt diet (P < 0.05) and by 7 mmHg in dogs on a low-salt diet. In dogs on a high-salt diet, right atrial pressure was on an average 3 cmH2O higher with than without angiotensin II (P < 0.05). In animals on a low salt intake post-prandial right atrial pressure decreased slightly, but remained in the range of fasting values, during angiotensin II infusion.

5. Neither plasma osmolality nor plasma sodium concentration changed in any of the four protocols.

6. We conclude that the post-prandial effects of angiotensin II in dogs on a high water intake depend on the amount of concomitant sodium intake. Angiotensin II reduces the post-prandial diuresis and natriuresis when given to sodium-loaded dogs, whereas angiotensin II does not reduce post-prandial urine flow and sodium excretion rates in dogs on a low sodium intake and may even augment water excretion in this condition.
Glomerular Expression of Smooth-Muscle Myosin Heavy-Chain Isoforms in Aminonucleoside Nephrosis in Rats
Authors: Nakamura Tsukasa , Kimura Kenjiro , Ebihara Isao , Takahashi Toshimasa , Tomino Yasuhiko , Aikawa Masanori , Yazaki Yoshio , Nagai Ryozo , Koide Hikaru
Published: August 2015

1. We investigated the glomerular expression of three types of myosin heavy-chain isoforms, including S-myosin heavy-chain 40 (SM1), S-myosin heavy-chain 29 (SM2) and FS-myosin heavy-chain 34 (SMemb) in puromycin aminonucleoside nephrosis.

2. There was little change in SM1 and SM2 mRNA levels throughout the experiment. In contrast, glomerular SMemb mRNA increased on days 2 and 4 (before and soon after the onset of proteinuria, respectively), but declined on day 8 (the peak of proteinuria).

3. Histological myosin heavy-chain expression was examined using three antibodies against SM1, SM2 and SMemb. Immunohistochemically, SM1 and SM2 were absent in the glomeruli associated with puromycin aminonucleoside nephrosis until day 20. The SMemb isoform was barely detectable in normal glomeruli, but substantial amounts of SMemb were demonstrated in the glomeruli of rats with puromycin aminonucleoside nephrosis. In the puromycin aminonucleoside-treated rats, the number of SMemb-positive glomerular cells increased on days 2 and 4.

4. We examined whether levels of α-smooth-muscle actin or proliferating cell nuclear antigen correlated with myosin heavy-chain levels in the glomeruli of rats with puromycin aminonucleoside nephrosis. None of the cellular components in the glomeruli was positive for either α-smooth-muscle actin or proliferating cell nuclear antigen in puromycin aminonucleoside nephrosis.

5. Administration of methylprednisolone to puromycin aminonucleoside-treated rats resulted in the rapid disappearance of proteinuria. However, methylprednisolone did not affect SMemb mRNA or immunostaining in the glomeruli of rats with puromycin aminonucleoside nephrosis.

6. These data suggest that SMemb may be a molecular marker for phenotypic change in early glomerular injury, and demonstrate that SMemb regulation differs from that of SM1, SM2, α-smooth-muscle actin and proliferating cell nuclear antigen in the glomeruli of rats with puromycin aminonucleoside nephrosis.
EMD 57033 Enhances Arrhythmias Associated with Increased Wall-Stress in the Working Rat Heart
Authors: Evans Stephen J. , Levi Allan J. , Lee John A. , Jones John V.
Published: August 2015

1. EMD 57033 produces a positive inotropic effect by increasing the sensitivity of cardiac muscle myofilaments to calcium. Since the elevation in intracellular calcium produced by conventional inotropic compounds is thought to be arrhythmogenic, it is hoped that compounds such as EMD 57033 may increase cardiac output without exacerbating arrhythmias in patients with cardiac failure. This is the first study to examine whether EMD 57033 influences the susceptibility of the heart to ventricular arrhythmias.

2. We used the isolated working rat heart to investigate the effect of EMD 57033 on wall-stress-induced ventricular arrhythmia. Arrhythmias were induced by increases in ventricular afterload, and the effect of 2 μmol/l EMD 57033 on ventricular arrhythmias was investigated. The effect of 2 μmol/l EMD 57033 on contractility and arrhythmias was also assessed in the presence of different levels of perfusate calcium.

3. EMD 57033 was positively inotropic in the working rat heart, but it also produced a reversible increase in wall-stress-induced ventricular arrhythmia. The incidence of both ventricular ectopics and complex arrhythmias such as ventricular tachycardia were significantly increased by EMD 57033. Arrhythmias increased progressively as the level of perfusate calcium was raised within the physiological range.

4. The mechanism by which EMD 57033 increases wall-stress-induced arrhythmia is unclear, but it seems unlikely to be directly due to elevation of intracellular calcium. Further studies of the arrhythmogenic profile of this novel compound are required in a variety of models to assess its suitability and safety as a potentially therapeutic compound in heart failure.
Luminal Epidermal Growth Factor is Trophic to the Small Intestine of Parenterally Fed Rats
Authors: Marchbank Tania , Goodlad Robert A. , Lee Chung Y. , Playford Raymond J.
Published: August 2015

1. Intestinal atrophy contributes to the clinical difficulties of patients on parenteral nutrition. Systemic administration of epidermal growth factor reverses this effect, but there is concern over the clinical safety of intravenous administration of growth factors. We therefore investigated whether administration of luminal epidermal growth factor could reverse the atrophy induced in a rat model of parenteral nutrition when epidermal growth factor was given alone or in combination with soya bean trypsin inhibitor to reduce proteolytic digestion of the epidermal growth factor.

2. Infusion of soya bean trypsin inhibitor alone decreased intraluminal tryptic activity by about 90% but did not result in increased proliferation. Intragastric infusion of epidermal growth factor (72 μg/day per rat) caused a 26% increase in proliferation (determined by 2-h metaphase arrest) in the duodenum (P < 0.01) when compared with animals receiving ‘control’ intragastric infusion. However, intragastric epidermal growth factor had no effect on more distal regions of the bowel, probably reflecting rapid proteolysis of the epidermal growth factor by luminal proteases. In contrast, a trophic effect of luminal epidermal growth factor was seen in the duodenum (28% increase, P < 0.01) and jejunum (24% increase, P < 0.05) of animals which had received epidermal growth factor with soya bean trypsin inhibitor. This was probably due to the soya bean trypsin inhibitor decreasing the rate of degradation of epidermal growth factor by intestinal proteases, allowing biologically active epidermal growth factor to reach more distal portions of the bowel.

3. We conclude that luminal administration of epidermal growth factor in combination with protease inhibitors could provide a novel approach to the treatment of intestinal atrophy induced by parenteral nutrition. This approach may also be useful for the treatment of ulceration of the small intestine in conditions such as necrotizing enterocolitis or Crohn's disease. Clinical studies are recommended.
Adverse Effects of Hypoxaemia on Diastolic Filling in Humans
Authors: Cargill Robert I. , Kiely David G. , Lipworth Brian J.
Published: August 2015

1. Abnormalities of myocardial relaxation may occur as a consequence of myocyte hypoxia. We have therefore examined the effects of hypoxaemia on right and left ventricular diastolic function in 10 healthy male subjects.

2. After resting to reach baseline haemodynamics, subjects were rendered hypoxaemic by breathing a variable nitrogen/oxygen mixture. Oxygen saturation (SaO2) was maintained at 85–90% for 20 min and then at 75–80% for a further 20 min. Haemodynamic and diastolic filling parameters were measured non-invasively at baseline and at the end of each period of hypoxaemia.

3. Diastolic filling of both ventricles was significantly impaired by hypoxaemia. In comparison with baseline, left ventricular isovolumic relaxation time and transmitral E-wave deceleration time corrected for heart rate were significantly prolonged at SaO2 75–80%: mean difference in corrected relaxation time, 9.8 ms (95% confidence interval 1–19); mean difference in corrected deceleration time, 34 ms (95% confidence interval 11–56). Similarly, right ventricular isovolumic relaxation time and transtricuspid E-wave deceleration time were significantly prolonged at SaO2 values of 75–80% compared with baseline: mean difference in relaxation time, 20.3 ms (95% confidence interval 3–38); mean difference in deceleration time, 33 ms (95% confidence interval 11–55).

4. During hypoxaemia there were dose-related increases in heart rate, cardiac output and mean pulmonary artery pressure, but no effects on mean arterial pressure.

5. Hypoxaemia significantly impairs relaxation of left and right ventricles in normal humans. These changes may reflect impairment of intracellular calcium transport secondary to the effects of myocyte hypoxia.
Vascular and Hormonal Responses to Arginine: Provision of Substrate for Nitric Oxide or Non-Specific Effect?
Authors: MacAllister R. J. , Calver A. L. , Collier J. , Edwards C. M. B. , Herreros B. , Nussey S. S. , Vallance P.
Published: August 2015

1. The vascular and hormonal effects of l- and d-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension.

2. Infusion of l- or d-arginine (40 μmol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n = 7) or essential hypertension (n = 7), or in age- and sex-matched control subjects (n = 7 in both groups).

3. Systemic infusion of 10 g of l-arginine (n = 5) or d-arginine (n = 3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics. Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system.

4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these non-stereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.
Aortic Distensibility in Patients with Cerebrovascular Disease
Authors: Lehmann E. D. , Hopkins K. D. , Jones R. L. , Rudd A. G. , Gosling R. G.
Published: August 2015

1. Non-invasive aortic compliance measurements have been used previously to assess the distensibility of the aorta in several pathological conditions associated with increased cardiovascular risk. We set out to establish whether aortic compliance is abnormal in patients with stroke.

2. Pulse wave velocity measurements of thoracoabdominal aortic compliance were made in 20 stroke patients and 25 age- and sex-matched hospitalized, non-stroke control subjects putatively free of cardiovascular disease. Since compliance varies with non-chronic changes in blood pressure, a blood pressure corrected index of aortic distensibility, Cp, was calculated.

3. Aortic compliance was significantly reduced in patients with stroke compared with non-stroke control subjects (0.46 ± 0.27 versus 0.86 ± 0.34%/10 mmHg, P < 0.0002), corresponding with higher values for pulse wave velocity. Stroke patients also had significantly higher systolic and diastolic blood pressures (P < 0.02 and P < 0.002 respectively) and total cholesterol levels (P < 0.004) than the control subjects. Calculation of Cp did not alter the observation of stiffer aortas in the stroke cohort (P < 0.0007).

4. In both stroke patient and control cohorts, as expected, inverse trends were observed between aortic compliance and blood pressure. Also as expected, in the control group Cp values did not show a relationship with blood pressure (r = 0.02, P = 0.092, not significant). However, in the stroke cohort a marked dependence of Cp on blood pressure was observed (r = −0.48, P = 0.03).

5. Transoesophageal echocardiographic studies have recently identified advanced atherosclerosis in the ascending aorta as a possible source of cerebral emboli and an independent risk factor for ischaemic stroke. Our observations of significantly stiffer thoracoabdominal aortas in patients with stroke lead us to hypothesize that a totally non-invasive assessment of aortic compliance may potentially prove a useful surrogate marker of such atherosclerotic risk.

6. Blood pressure-corrected indices of arterial elastic properties based on normotensive models are widely applied in the literature. Our observation that these indices exhibit a considerable blood pressure dependence leads us to urge caution in the use of such corrections, especially in hypertensive patients.
Circulating Angiotensin-Converting Enzyme, Von Willebrand Factor Antigen and Thrombomodulin in Exertional Heat Stroke
Authors: Shieh Shang-Der , Shiang Jeng-Chuan , Lin Yuh-Feng , Shiao Wen-Yen , Wang Jia-Yi
Published: August 2015

1. Military recruits frequently succumb to exertional heat stroke during intensive training. Since widespread endothelial injury is often associated with exertional heat stroke, the relationship between changes in three circulating endothelial cell markers (angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin) and exertional heat stroke was studied.

2. Twelve recruits who had succumbed to exertional heat stroke during basic physical training (5000 m running) were included in the study. Another 10 age-matched healthy subjects who had gone through the same physical training regimen were selected as controls.

3. Blood was withdrawn on admission and on discharge for analyses of angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin. Other physiological parameters and biochemical analyses reflecting renal and liver functions were also recorded.

4. Our results indicated that these subjects with exertional heat stroke exhibited impaired liver function as revealed by the significant elevation of both serum glutamic oxaloacetic transaminase (P < 0.05) and serum glutamic pyruvic transaminase (P < 0.05) as compared with normal healthy control subjects. Unfortunately, these values remained mostly somewhat elevated on discharge, although serum glutamic oxaloacetic transaminase was reduced dramatically. Indices of kidney functions, including creatinine clearance and uric acid and phosphorus secretion, were not significantly different from those observed in healthy controls.

5. Circulating angiotensin-converting enzyme activities in exertional heat stroke patients on admission were significantly lower than in normal subjects (10.68 ± 2.15 versus 21.21 ± 3.18 nmol hippuric acid min−1ml−1, P<0.05). In contrast, von Willebrand factor antigen, thrombomodulin and plasma renin activity were significantly elevated compared with corresponding values in healthy subjects (P < 0.001, 0.05 and 0.01 respectively). The values of these endothelial markers returned to normal on discharge.

6. These data suggest that the decrease in angiotensin-converting enzyme and increase in von Willebrand factor antigen and thrombomodulin associated with exertional heat stroke may reflect endothelial injuries. Since endothelial injuries may trigger haemostatic failure and/or disseminated intravascular coagulation, the monitoring of these values might be useful for the evaluation of endothelial status in patients suffering from exertional heat stroke.
Total Antioxidant Capacity and Lipid Peroxidation during Liver Transplantation
Authors: Galley Helen F. , Richardson Norma , Howdle Peter D. , Walker Barry E. , Webster Nigel R.
Published: August 2015

1. We assessed plasma total antioxidant capacity using enhanced chemiluminescence and plasma lipid peroxides in eight patients undergoing orthotopic liver transplantation and 26 healthy control subjects.

2. The antioxidant capacity of plasma decreased significantly on reperfusion of the donor liver (P < 0.05) during liver transplantation, although levels were not lower in patients than in control subjects.

3. Pre-reperfusion antioxidant capacity correlated negatively with the concentration of lipid peroxidation products appearing in the plasma by the end of the transplant (P < 0.02), but did not correlate with vitamin A or E concentrations.

4. This study provides evidence of oxidant stress during liver transplantation, as shown by antioxidant utilization associated with increased lipid peroxidation.