bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Protein Kinase C Inhibitors and 2,3-Butanedione Monoxime on the Long-Term Hypothermic Preservation of Isolated Rat Hearts
Authors: Fagbemi Oluwole S. , Northover Basil J. 
Published: August 2015

1. This study examines the protective effect of staurosporine, chelerythrine, Ro 31-8220 and 2,3-butanedione monoxime in rat hearts during hypothermic storage.
2. Hearts were microperfused at 4°C for 24 or 48 h with a storage buffer that in some cases contained one of these protein kinase C inhibitors either alone or in combination with 2,3-butanedione monoxime. After hypothermic storage, hearts were rewarmed to 37°C with Krebs—Henseleit buffer. Cardiac function was then assessed in either Langendorff mode or working heart mode.
3. Compared with values from fresh non-stored hearts, hypothermic stored hearts showed a significant decrease in both coronary flow and left ventricular developed pressure when the stored hearts were reperfused in Langendorff mode. The decrease in coronary flow and left ventricular developed pressure was more pronounced in hearts stored for 48 h than in those stored for 24 h.
4. Hearts stored for 24 or 48 h, with or without the protein kinase C inhibitors, and then perfused in working mode generated less aortic flow and less cardiac output than fresh unstored hearts.
5. Hearts preserved in solutions containing staurosporine, chelerythrine, Ro 31-8220 or 2,3-butanedione monoxime had significantly higher left ventricular developed pressure values on reperfusion than hearts stored without any such drug.
6. Addition of 2,3-butanedione monoxime to a storage buffer containing either staurosporine, chelerythrine or Ro 31-8220 further improved left ventricular developed pressure, aortic flow and cardiac output values in these stored hearts. The group of hearts stored in a buffer containing 2,3-butanedione monoxime and chelerythrine gave the highest left ventricular developed pressure value seen during reperfusion.
7. The ATP and creatine phosphate concentrations of hearts stored in buffer alone were significantly lower than those of fresh unstored hearts, irrespective of the duration of storage. ATP concentrations were better preserved in hearts stored in a buffer containing 2,3-butanedione monoxime or/and one of the protein kinase C antagonists than those stored without such antagonists. A positive correlation was found between peak cardiac output values and the concentrations of combined high-energy phosphates in various groups of stored and reperfused hearts.
8. The present study showed that inhibition of protein kinase C during long-term hypothermic storage significantly increased high-energy phosphate concentrations and also improved contractile function during reperfusion.
Neutrophil CD11B Expression and Neutrophil Activation in Pre-Eclampsia
Authors: Barden A. , Graham D. , Beilin L. J. , Ritchie J. , Baker R. , Walters B. N. , Michael C. A. 
Published: August 2015

1. Neutrophil activation was examined in 22 women with pre-eclampsia and 22 age- and gestation-matched control subjects using whole-blood flow cytometry to assess basal and platelet-activating factor stimulated CD11b and CD18.
2. Basal neutrophil CD11b expression was significantly increased in women with pre-eclampsia compared with normal pregnancy before delivery. A similar non-significant trend for CD18 was also observed.
3. Before delivery, neutrophil CD11b expression increased in a dose-dependent fashion after platelet-activating factor stimulation, with the differences between the groups maintained. A similar dose-dependent increase in CD18 expression was observed after platelet-activating factor.
4. There were no between-group differences in expression of either CD11b or CD18 at either 6 weeks or 6 months post partum, either before or after platelet-activating factor stimulation.
5. Neutrophil CD11b was positively correlated with plasma uric acid (r = 0.44, P = 0.04) in women with pre-eclampsia, suggesting that the extent of neutrophil activation correlates with disease severity.
6. An increase in basal neutrophil CD11b expression in women with pre-eclampsia is likely to be an index of neutrophil activation in vivo. Neutrophil release of free radicals and proteases may then help perpetuate a vicious cycle of endothelial and vascular dysfunction in the placental and systemic circulations. The cause of this activation is not known but could involve platelet activation, increased production of endothelin-1 or release of cytokines. Further studies will be required to elucidate the consequences of neutrophil activation in pre-eclampsia.
Renal Handling of Urate and Sodium during Acute Physiological Hyperinsulinaemia in Healthy Subjects
Authors: Maaten J. C. Ter , Voorburg A. , Heine R. J. , Wee P. M. Ter , Donker A. J. M. , Gans R. O. B. 
Published: August 2015

1. The renal effects of insulin may play a central role in the association between insulin resistance, hypertension and hyperuricaemia. After a 2-h baseline period, we investigated the effects of exogenous insulin for 4 h (50 m-units h−1 kg−1) on fractional renal sodium and urate excretion in 13 healthy subjects, using the euglycaemic clamp and lithium clearance technique, and performed a control experiment in eight of the subjects.
2. Insulin caused a decline in both fractional renal sodium excretion, from 1.13 ± 0.41% to 0.88 ± 0.58% (control study: 0.81 ± 0.35 to 1.35 ± 0.49%; P &lt; 0.001, insulin versus control), and fractional renal urate excretion, from 6.72 ± 1.87% to 5.71 ± 2.02% (control study: 7.03 ± 2.06 to 7.05 ± 1.94%; P = 0.085, insulin versus control). The changes in fractional renal sodium and urate excretion were positively correlated (r = 0.71, P &lt; 0.01). Estimated fractional distal sodium reabsorption increased during insulin infusion from 93.7 ± 2.8% to 96.7 ± 1.9% (control study: 95.7 ± 1.5% to 93.6 ± 1.1%; P &lt; 0.001, insulin versus control). Estimated fractional proximal tubular sodium reabsorption fell from 81.0 ± 0.5% to 73.7 ± 4.7% during insulin infusion, but less in the control study (81.5 ± 4.3% to 79.3 ± 4.8%; P = 0.056, insulin versus control). The changes in fractional proximal tubular sodium reabsorption and fractional distal sodium reabsorption during insulin infusion were inversely correlated (r = −0.59, P = 0.03).
3. During the course of the insulin infusion experiment an inverse correlation between the changes in fractional sodium and urate excretion, and the insulin-mediated glucose disposal, became gradually evident (r = −0.73, P &lt; 0.01, and r = −0.71, P &lt; 0.01, respectively; fourth hour of the insulin infusion period).
4. We conclude that exogenous insulin acutely decreases renal sodium and urate excretion, and that this effect is probably exerted at a site beyond the proximal tubule.
Effect of Seed Crystals of Uric Acid and Monosodium Urate on the Crystallization of Calcium Oxalate in Undiluted Human Urine in Vitro
Authors: Grover Phulwinder K. , Ryall Rosemary L. 
Published: August 2015

1. The aim of this study was to determine whether seed crystals of uric acid or monosodium urate promote the epitaxial deposition of calcium oxalate in undiluted human urine. The effects of seed crystals of uric acid, monosodium urate or calcium oxalate on calcium oxalate crystallization induced in pooled 24-h urine samples collected from six healthy men were determined by [14C]oxalate deposition and Coulter counter particle analysis. The precipitated crystals were examined by scanning electron microscopy.
2. Seed crystals of uric acid, monosodium urate and calcium oxalate increased the precipitated particle volume in comparison with the control containing no seeds by 13.6%, 56.8% and 206.5% respectively, whereas the deposition of [14C]oxalate in these samples relative to the control was 1.4% (P &lt; 0.05), 5.2% (P &lt; 0.01) and 54% (P &lt; 0.001) respectively. The crystalline particles deposited in the presence of monosodium urate seeds were smaller than those in the control samples. Scanning electron microscopy showed that large aggregates of calcium oxalate were formed in the presence of calcium oxalate seeds, which themselves were not visible. In contrast, monosodium urate and, to a lesser extent, uric acid seeds were scattered free on the membrane surfaces and attached like barnacles upon the surface of the calcium oxalate crystals.
3. It was concluded that seed crystals of monosodium urate and uric acid do not promote calcium oxalate deposition to a physiologically significant degree in urine. Howsever, binding of monosodium urate and uric acid crystals and their subsequent enclosure within actively growing calcium oxalate crystals might occur in vivo, thereby explaining the occurrence of mixed urate/oxalate stones.
Fetal Growth and Insulin Resistance in Adult Life: Role of Skeletal Muscle Morphology
Authors: Thompson C. H. , Sanderson A. L. , Sandeman D. , Stein C. , Borthwick A. , Radda G. K. , Phillips D. I. W. 
Published: August 2015

1. Thinness at birth is associated with insulin resistance in adult life and an apparent delay in activation of glycolysis/glycogenolysis in exercising skeletal muscle. As developmental abnormalities of skeletal muscle histology or metabolism may explain this association we examined muscle histology, biochemistry and blood flow in a group of 27 adult women whose birth details were known.
2. Subjects were examined by near-infrared spectroscopy to determine forearm muscle oxygen supply, and by muscle biopsy and forearm plethysmography. Those with a ponderal index at birth &lt; 23 kg/m3 were insulin resistant (assessed by the short insulin-tolerance test — mean rate constants for glucose disappearance = 4.14 compared with 4.83%/min, P = 0.045) and had significantly more rapid muscle reoxygenation than the remainder of the subjects (13 compared with 22 s, P = 0.004).
3. Thinness at birth did not influence muscle capillary density, muscle glycogen content, glycogen synthase activity, citrate synthase activity or resting forearm blood flow.
4. Insulin resistance seen after fetal malnutrition was not associated with abnormal muscle histology, resting muscle blood flow, mitochondrial volume or glycogen content.
5. The increase in muscle reoxygenation rate in adult subjects who were thin at birth could occur to promote oxidative ATP synthesis in compensation for the delay in activation of glycolysis/glycogenolysis. It suggests altered regulation rather than structure of the muscle microcirculation. These changes appear to antedate the structural and biochemical changes seen in muscle from patients with established diabetes.
Heart Rate Variability in Patients with Daytime Sleepiness Suspected of Having Sleep Apnoea Syndrome: A Receiver-Operating Characteristic Analysis
Authors: Keyl Cornelius , Lemberger Peter , Pfeifer Michael , Hochmuth Karin , Geisler Peter 
Published: August 2015

1. Periodic breathing is known to be associated with cyclic fluctuations in heart rate. The purpose of this study was to evaluate the capability of spectral analysis of heart rate variability to identify episodes with periodic breathing in patients suspected of having sleep apnoea syndrome.
2. Forty-eight subjects complaining of chronic daytime sleepiness were studied using polysomnography and additional monitoring of Holter-ECG and synchronized pulse oximetry. The recordings were divided into 20 min episodes which were identified as recordings registered during normal breathing, periodic breathing, and periods of both normal and abnormal breathing. Power spectral analysis was performed on episodes which met the criteria of stationarity of data (313 episodes with normal breathing, 264 episodes with continuous periodic breathing, 80 episodes with both normal and periodic breathing pattens).
3. The ability of parameters, derived from analysis of heart rate variability, to discriminate between episodes with normal and periodic breathing was assessed by receiver-operating characteristic analysis.
4. The spectral power component in the frequency range 0.01–0.07 Hz revealed the greatest accuracy for discriminating between normal and periodic breathing (area under the receiver-operating characteristic curve = 0.929; standard error = 0.009). The analysis of the episodes classified as false-positive at a given test sensitivity of 90% and a corresponding specificity of 77% revealed that half of these episodes had been recorded during transient central nervous arousal reactions related to periodic leg movements or heavy snoring.
5. We concluded that power spectral analysis of heart rate variability offers a possible means of identifying episodes of sleep-related breathing disorders or periodic leg movements. Therefore, analysis of heart rate variability may be a valuable additional diagnostic tool in patients undergoing Holter-ECG recording.
Effect of Urodilatin Infusion on Renal Haemodynamics, Tubular Function and Vasoactive Hormones
Authors: Carstens JAN , Jensen Kaare T. , Pedersen Erling B. 
Published: August 2015

1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron.
2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a crossover design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min−1 kg−1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance.
3. The 20 ng min−1 kg−1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min−1 kg−1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect.
4. We conclude, that the urodilatin dose of 20 ng min−1 kg−1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.
Mild Endotoxaemia and the Inflammatory Response Induced by a Marathon Race
Authors: Camus G. , Poortmans J. , Nys M. , Deby-Dupont G. , Duchateau J. , Deby C. , Lamy M. 
Published: August 2015

1. To address the question of whether endotoxaemia could be involved in the inflammatory response induced by long-term strenuous exercise, 18 male marathon runners [mean age 41±2 (SEM) years] were studied. Their performance in the marathon ranged from 2 h 46 min to 4 h 42 min.
2. Four venous blood samples were drawn: at rest, just before the race (baseline); within 15 min following the completion of the marathon; after 1 h of recovery; and the morning after the race.
3. The following humoral markers of the inflammatory response to exercise were measured: polymorphonuclear myeloperoxidase (MPO), anaphylatoxin C5a (C5a), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Plasma endotoxin was measured by a sensitive and rapid chromogenic Limulus assay. All inflammatory markers were significantly increased (P &lt; 0.001) after the race, reaching in most cases peak values in the first blood sample drawn following the completion of the marathon [MPO, 298±19 ng/ml (SEM); C5a, 1.45±0.32 ng/ml; TNF-α, 20±3 pg/ml; IL-6, 88 + 13 pg/ml] when compared with baseline [MPO, 146 ±16 ng/ml (SEM); C5a, 0.27±0.2 ng/ml; TNF-α, 12 ± 1.5 pg/ml: IL-6, 1.0±0.5 pg/ml]. Traces of plasma endotoxin (ranging from 5 to 13 pg/ml, with one exceptionally high value of 72 pg/ml measured in one runner) were detected in seven subjects within the first hour of recovery. An ELISA method was used to determine the endogenous IgG antibodies toward a range of Gram-negative bacterial lipopolysaccharides (LPSs) of different sizes and structures. A transient decrease in certain anti-LPS activities, mainly against rough LPS, occurred in most cases in the first blood sample drawn after the race. There was no correlation between the magnitude of the inflammatory response to exercise, as assessed by the increase in blood levels of humoral markers of inflammation, and the changes in circulating endotoxin levels of anti-LPS IgG activity following the race.
4. From these results, we conclude that the mild, transient endotoxaemia detected in some of our subjects does not play a major role in the observed inflammatory response to a marathon competition.
Signalling Pathways Involved in the Mitogenic Effects of cAMP
Authors: Withers D. J. 
Published: August 2015

1. Elevation of intracellular cyclic AMP (cAMP) is a potent mitogenic signal for a number of cell types, including Swiss 3T3 cells, thyroid epithelial cells and the somatotroph cells of the anterior pituitary.
2. Activation of the mitogen-activated protein kinase (MAPK) cascade has been shown to underlie the mitogenic effects of many growth factors. However, the precise relationship between the mitogenic effects of cAMP and the MAPK cascade is not fully defined.
3. In Swiss 3T3 cells, elevation of cAMP did not stimulate kinases at all three levels of the MAPK cascade. Additionally, blockade of the MAPK pathway failed to inhibit cAMP-stimulated DNA synthesis.
4. Mitogenic combinations of cAMP strongly stimulated the phosphorylation and activation of the serine/threonine kinase p70 S6 kinase, p70S6K, an effect that was inhibited by rapamycin. This agent markedly inhibited cAMP-stimulated DNA synthesis, suggesting a critical role for p70S6K in cAMP mitogenic signalling.
5. Thus, multiple parallel but distinct signalling pathways may be involved in the action of mitogens. This redundancy has important implications for the pathogenesis and treatment of conditions characterized by inappropriate activation of growth factor signalling pathways.
Adrenomedullin: A Hypotensive Hormone in Man
Authors: Lainchbury John G. , Cooper Garth J. S. , Coy David H. , Jiang Ning-Yi , Lewis Lynley K. , Yandle Timothy G. , Richards A. Mark , Nicholls M. Gary 
Published: August 2015

1. Adrenomedullin, a recently discovered 52-amino-acid peptide hormone, circulates in plasma at low picomolar levels in man. Animal studies and studies in vitro indicate that it has diverse biological actions, including vasodilatation, natriuresis and diuresis, and positive inotropism as well as antiproliferative effects. We investigated the bioactivity of two doses of adrenomedullin in healthy human subjects.
2. Human adrenomedullin was given intravenously to eight male subjects at 2 and 8 ng min−1 kg−1, and haemodynamic, hormonal, renal and biochemical responses were recorded in a placebo (vehicle)-controlled, randomized study.
3. Compared with vehicle, adrenomedullin reduced mean arterial pressure (P = 0.05 for duration of infusion, mean difference at end of infusion 7.7 mmHg), systolic arterial pressure (P = 0.04 for duration of infusion, mean difference at end of infusion 10.7 mmHg) and at the lower dose reduced diastolic arterial pressure (P = 0.05 for lower dose, mean difference at end of infusion 6.3 mmHg) in the absence of compensatory responses in sympathetic activity or renin release. Urine volume and electrolyte excretion were unaffected.
4. The threshold for biological activity of adrenomedullin in man is lower for arterial pressure than for renal or hormonal responses, and is evident at plasma concentrations seen in disorders of the circulation. Adrenomedullin may be an important hormone under pathophysiological circumstances.
Serum Leptin and Short-Term Regulation of Eating in Obese Women
Authors: Karhunen Leila , Haffner Steven , Lappalainen Raimo , Turpeinen ANU , Miettinen Heikki , Uusitupa Matti 
Published: August 2015

1. Leptin is generally thought to play a key role in the regulation of eating. However, its real role in human eating behaviour is still poorly known. Therefore, the role of leptin in the regulation of eating was examined in obese binge- and non-binge-eating women during exposure to food and food-related stimuli.
2. Eleven binge- and ten non-binge-eating obese women took part in the study. In addition to serum leptin, serum insulin, non-esterified fatty acids, plasma glucose, salivation, the feeling of hunger and the desire to eat were repeatedly measured during the experiment.
3. Serum leptin levels did not differ between the binge- and non-binge-eating women. Neither were leptin levels associated with the feeling of hunger or the desire to eat food, nor with the amount or composition of food eaten. During food exposure leptin levels did not change, whereas at the same time serum insulin levels increased and serum non-esterified fatty acid levels decreased. The change in salivation during food exposure was inversely associated with the fasting leptin level.
4. This study indicates that serum leptin does not play a role in the regulation of eating in obese women, at least not in the short term. Furthermore, leptin levels are not different in obese binge-eating women as compared with obese non-binge-eating women. Interestingly, high fasting leptin levels may be associated with a decreased salivation response in the presence of food and food-related stimuli.