bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 &lt; 0.05).
4. Allopurinol enhanced the rate of tissue oxygenation during early reperfusion (P &lt; 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 &lt; 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 &lt; 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 &lt; 0.05).
4. Angiotensin II infusion increased mean arterial pressure by an average of 12 mmHg in dogs on a high-salt diet (P &lt; 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 &lt; 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 &lt; 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 &lt; 0.01) and jejunum (24% increase, P &lt; 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.