bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bicarbonate Therapy and Intracellular Acidosis
Authors: Goldsmith D. J. A. , Forni L. G. , Hilton P. J. 
Published: August 2015

1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and bicarbonate across cell membranes after alkali administration, leading to the phenomenon of ‘paradoxical’ intracellular acidosis, has been held responsible for some of these adverse effects.
2. Changes in intracellular pH in suspensions of leucocytes from healthy volunteers were monitored using a fluorescent intracellular dye. The effect in vitro of increasing extracellular pH with sodium bicarbonate was studied at different sodium bicarbonate concentrations. Lactic acid and propionic acid were added to the extracellular buffer to mimic conditions of metabolic acidosis.
3. The addition of a large bolus of sodium bicarbonate caused intracellular acidification as has been observed previously. The extent of the intracellular acidosis was dependent on several factors, being most evident at higher starting intracellular pH. When sodium bicarbonate was added as a series of small boluses the reduction in intracellular pH was small. Under conditions of initial acidosis this was rapidly followed by intracellular alkalinization.
4. Although intracellular acidification occurs after addition of sodium bicarbonate to a suspension of human leucocytes in vitro, the effect is minimal when the conditions approximate those seen in clinical practice. We suggest that the observed small and transient lowering of intracellular pH is insufficient grounds in itself to abandon the use of sodium bicarbonate in human acidosis.
Plasma Oxygen during Cardiopulmonary Bypass: A Comparison of Blood Oxygen Levels with Oxygen Present in Plasma Lipid
Authors: Petyaev I. M. , Vuylsteke A. , Bethune D. W. , Hunt J. V. 
Published: August 2015

1. Although not often appreciated, it is a fact that molecular oxygen is more soluble in lipids than in aqueous solution. We have recently developed a method to monitor oxygen within the lipid content of plasma. Monitoring plasma oxygen is one essential element during open heart surgery using a cardiopulmonary bypass pump and oxygenator. Currently oxygen is monitored electrochemically and is based upon monitoring the partial pressure of oxygen in a gas equilibrated with whole blood.
2. To determine the relative importance of lipid-associated oxygen in blood and assess the potential use of such a measurement we present comparisons of changes in oxygen associated with whole blood and lipid content of plasma before, during and after cardiac surgery.
3. In a limited number of patients studied (n = 28), aged between 34 and 86 years, oxygen in lipid increased with decreased extracorporeal blood temperature during cardiopulmonary bypass, increased in proportion to oxygen supplied and appeared to be a better monitor of oxygen than conventional electrochemical systems currently in use. Oxygen associated with whole blood and plasma lipid was markedly below normal on aortic declamping after cardiopulmonary bypass, suggesting an hypoxic episode at this point. Levels of oxygen in the lipid phase of plasma returned to normal presurgical values 6–8 h after surgery.
4. Calculation of the concentration of lipid-associated oxygen present in plasma suggests that plasma lipids contain up to 25% of that typically ascribed to haemoglobin. Thus, we suggest that monitoring lipid-associated oxygen may prove a better alternative to current methods of measuring oxygen status. Furthermore, we suggest that plasma lipid is a hitherto unsuspected pool of circulating oxygen which may play a significant role in tissue oxygen supply.
Plasma Levels of Adrenomedullin in Patients with Acute Myocardial Infarction
Authors: Yoshitomi Yuji , Nishikimi Toshio , Kojima Shunichi , Kuramochi Morio , Takishita Shuichi , Matsuoka Hiroaki , Miyata Atsuro , Matsuo Hisayuki , Kangawa Kenji 
Published: August 2015

1. Adrenomedullin, a newly identified vasorelaxant peptide, participates in the regulation of the cardiovascular system. To investigate the pathophysiological significance of adrenomedullin in patients with acute myocardial infarction, we measured plasma levels of adrenomedullin.
2. Cardiac catheterization was performed on admission, after 1 day, and after 4 weeks in 36 patients with acute myocardial infarction. We measured plasma levels of adrenomedullin, atrial natriuretic peptide and brain natriuretic peptide in the right atrium, pulmonary artery and aorta.
3. Plasma levels of adrenomedullin in the right atrium (mean ± SEM) were significantly increased on admission (4.2 ± 2.6 h) in patients with acute myocardial infarction (10.6 ± 1.0 pmol/l) compared with controls (5.2 ± 0.3 pmol/l, P &lt; 0.01). In addition, plasma levels of adrenomedullin were further elevated in patients with congestive heart failure (12.3 ± 1.4 pmol/l) compared with patients without congestive heart failure (7.8 ± 0.6 pmol/l, P &lt; 0.01). In patients with congestive heart failure, plasma adrenomedullin on admission significantly correlated with atrial natriuretic peptide and brain natriuretic peptide.
4. These results suggest that plasma adrenomedullin increases in the early phase of acute myocardial infarction and that volume expansion may be one of the additional stimuli for the release of adrenomedullin in patients with acute myocardial infarction complicated by congestive heart failure.
Nitric Oxide Modulation of Coronary Artery Myogenic Tone in Spontaneously Hypertensive and Wistar—Kyoto Rats
Authors: Garcia Susana R. , Bund Stuart J. 
Published: August 2015

1. The endothelium contributes substantially to the modulation of myogenic tone in coronary arteries from spontaneously hypertensive rats (SHR) and Wistar—Kyoto rats (WKY). This study has addressed the contributions of endothelium-derived nitric oxide and cyclo-oxygenase products to this modulation in small coronary arteries (approximately 200 μm internal diameter) from 20-week-old SHR and WKY under pressurized, no-flow conditions in an arteriograph.
2. Active pressure—diameter relationships were uninfluenced by the cyclo-oxygenase inhibitor indomethacin (10 μmol/l) in either rat strain. In the presence of indomethacin and the nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA, 0.1 mmol/l), coronary arteries from SHR and WKY generated significantly greater myogenic tone. This increase in tone was similar in both strains.
3. In endothelium-denuded arteries, indomethacin and l-NNA did not influence tone.
4. Therefore, these results demonstrate that endothelium-derived nitric oxide is basally released to attenuate SHR and WKY coronary artery myogenic tone, whereas endothelium-derived cyclo-oxygenase products have no net vasoactive influence. Additionally, these data suggest that basal nitric oxide-mediated relaxation is normal in SHR coronary arteries and is therefore unlikely to be a pathogenic mechanism in this animal model of hypertension.
Non-Invasive Investigation of Endothelium-Dependent Dilatation of the Brachial Artery in Women with Primary Raynaud's Phenomenon
Authors: Ringqvist Åsa , Jonason Tommy , Leppert Jerzy , Ringqvist Ivar 
Published: August 2015

1. Primary Raynaud's phenomenon is characterized by white fingers and toes with impaired perfusion in response to cold or emotional stress. The aetiology has not been clarified. In previous studies we have demonstrated a season-linked inability in women with primary Raynaud's phenomenon to raise their plasma cGMP levels in response to whole-body cooling, suggesting a dysfunction of the l-arginine—NO—cGMP pathway. To further elucidate the possibility of such a defect in patients with primary Raynaud's phenomenon, we determined flow-mediated dilatation of the brachial artery.
2. Twenty-two premenopausal, non-smoking women with primary Raynaud's phenomenon (mean age 39 ± 8 years) and 23 healthy controls (mean age 41 ± 7 years) were studied during two winter weeks. The diameter of the right arm brachial artery was measured by high resolution ultrasonography, at rest and during reactive hyperaemia. The investigation was conducted both with the participants at rest at room temperature and after 40 min of whole-body cooling.
3. Both study groups showed a marked attenuation of flow-mediated dilatation during whole-body cooling, which could partly but not solely be explained by a decreased shear rate. There was, however, no significant difference in flow-mediated diameter (D) increase (% flow-mediated dilatation; ΔD/D × 100) between primary Raynaud's phenomenon and controls, either at room temperature (7.8 ± 0.8 and 9.0 ± 0.8) or in response to whole-body cooling (3.8 ± 1.2 and 4.4 ± 0.7).
4. Thus, whole-body cooling markedly impairs flow-mediated dilatation in women. Flow-mediated dilatation is, however, not decreased in women with primary Raynaud's phenomenon at room temperature or during whole-body cooling, indicating that this particular aspect of endothelial function is not impaired in this setting.
Mild Metabolic Alkalosis Impairs the Natriuretic Response to Bumetanide in Normal Human Subjects
Authors: Loon Nicholas R. , Wilcox Christopher S. 
Published: August 2015

1. This study was designed to test the hypothesis that acid—base status affects the response to a loop diuretic in human subjects. The renal responses to bumetanide (1 mg intravenously) were studied in eight normal subjects consuming a constant diet supplemented for 3 days on three separate occasions with equivalent quantities of NaCl, NaHCO3 (metabolic alkalosis) or NH4Cl (metabolic acidosis).
2. A significant (P &lt; 0.025) reduction in bumetanide-induced diuresis (−40%), natriuresis (−21%), and chloruresis (−25%) was observed during NaHCO3 compared with NaCl. The renal response was unaltered during NH4Cl.
3. The creatinine and para-aminohippurate clearances were unchanged during NaHCO3, as were the blood pressure and plasma levels of renin activity, aldosterone and noradrenaline, and the plasma volume.
4. Bumetanide excretion was increased during NaHCO3 compared with NaCl (2.13 ± 0.18 versus 1.76 ± 0.17 μg/min, P &lt; 0.025) but was not changed during NH4Cl (1.68 ± 0.26 μg/min; not significant).
5. Plasma aldosterone concentration was increased 3-fold during acidosis and the kaliuretic response to bumetanide was enhanced significantly.
6. In conclusion, compared with NaCl, NaHCO3 reduces the diuretic, natriuretic and chloruretic response to bumetanide without significant changes in renal haemodynamics, plasma volume, the renin—angiotensin—aldosterone axis or the sympathetic nervous system, and despite increasing renal bumetanide excretion. NH4Cl enhances aldosterone secretion and diuretic-induced kaliuresis.
Sustained Modifications of Protein Metabolism in Various Tissues in a Rat Model of Long-Lasting Sepsis
Authors: Breuillé Denis , Arnal Maurice , Rambourdin Fabienne , Bayle Gérard , Levieux Didier , Obled Christiane 
Published: August 2015

1. Sepsis was induced in rats by an intravenous injection of live bacteria. Infected and pair-fed animals were studied before the infection, in an acute septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a late septic phase (day 10). Protein synthesis rates were measured in vivo after administration of a flooding dose of l[1-13C]valine.
2. During the acute phase, muscle protein loss associated with infection resulted from both a decrease in protein synthesis and an increase in proteolysis. During the chronic phase and the late phase, the increase of proteolysis in infected rats as compared with pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis rates were not significantly modified by infection. However, skin protein content decreased 6 and 10 days after infection, suggesting an increased proteolysis in response to sepsis.
3. Protein synthesis in liver of infected rats was twice that of pair-fed animals. Liver protein synthesis remained elevated in infected rats compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma concentrations of fibrinogen were evident at all periods studied. α2-Macroglobulin and α1-acid glycoprotein reached peak concentrations during the acute phase (concentrations increased 50 times in infected rats). On day 10, the levels of these proteins were still about 12-fold higher.
4. Protein synthesis rates were significantly increased in the digestive tract and lung of infected rats compared with pair-fed groups on days 2 and 6, but were similar in the two groups on day 10 postinfection. The fractional protein synthesis rate was increased 3-fold over the entire experimental period in the spleen.
5. The results show that sepsis stimulates protein synthesis in various tissues over a long time, and that skin, like muscle, can provide amino acids to the rest of the body.
Effect of Oxidative Stress on Lymphocytes from Elderly Subjects
Authors: García-Arumí E. , Andreu A. L. , López-Hellín J. , Schwartz S. 
Published: August 2015

1. Oxidative damage has been associated with ageing, but there is no agreement as to whether or not it is produced by a decrease in antioxidant defences with the ageing process. In purified lymphocytes from 47 healthy elderly (75.27 ± 0.91 years) and 47 healthy young (29.87 ± 0.53 years) volunteers, we studied the levels of antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), protein oxidative damage (as protein carbonyl content) and lysosomal proteolytic activity (cathepsins B, H and L), with and without exposure to oxidative stress produced by 25 μmol/l H2O2.
2. There were no differences in antioxidant enzyme activities in the stressed and non-stressed samples between the young and elderly subjects, indicating that there was no relationship between age and antioxidant enzyme activity even in oxidative stress. However, a dissimilar response to oxidative stress was observed in protein oxidative damage and cathepsin B and L activities, depending on the age of the donor.
3. With these results we conclude that oxidative stress produces greater protein oxidative damage and increased protein degradation in elderly subjects than in young ones; this effect cannot be attributed to dissimilar antioxidant enzyme responses to oxidative stress, since these did not differ between the two age groups.
Neutrophil Priming: Pathophysiological Consequences and Underlying Mechanisms
Authors: Condliffe A. M. , Kitchen E. , Chilvers E. R. 
Published: August 2015

1. Neutrophil priming by agents such as tumour necrosis factor-α, granulocyte/macrophage colony-stimulating factor and lipopolysaccharide causes a dramatic increase in the response of these cells to an activating agent; this process has been shown to be critical for neutrophil-mediated tissue injury both in vitro and in vivo.
2. The principle consequence of priming, aside from a direct effect on cell polarization, deformability and integrin/selectin expression, is to permit secretagogue-induced superoxide anion generation, degranulation and lipid mediator (e.g. leukotriene B4 and arachidonic acid) release. It is now recognized that most priming agents also serve an additional function of delaying apoptosis and hence increasing the functional longevity of these cells at the inflamed site.
3. The potential mechanisms underlying priming are discussed; current data suggest a dissociation between priming and changes in receptor number and/or affinity, G-protein expression, phospholipase C and phospholipase A2 activation and changes in intracellular Ca2+ concentration. However, more recent studies support a key role for protein tyrosine phosphorylation and enhanced phospholipase D and phosphoinositide 3-kinase activity in neutrophil priming.
4. Recent work has also revealed the potential for neutrophils to spontaneously and fully ‘de-prime’ after an initial challenge with platelet-activating factor. This ability of neutrophils to undergo a complete cycle of priming—de-priming (and re-priming) reveals a previously unrecognized flexibility in the control of neutrophil behaviour at an inflamed site.
CYFRA 21-1, a Cytokeratin Subunit 19 Fragment, in Bronchoalveolar Lavage Fluid from Patients with Interstitial Lung Disease
Authors: Kanazawa Hiroshi , Yoshikawa Takahiro , Yamada Masashi , Shoji Seiichi , Fujii Tatsuo , Kudoh Shinzoh , Hirata Kazuto , Yoshikawa Junichi 
Published: August 2015

1. It has been suggested that CYFRA21-1, a cytokeratin subunit 19 fragment, is potentially useful for diagnosis and monitoring of lung carcinoma. However, serum levels of CYFRA21-1 are also increased in a high proportion of patients with interstitial lung disease. In this study we measured CYFRA21-1 levels in bronchoalveolar lavage fluid from 10 normal subjects, 18 patients with idiopathic pulmonary fibrosis and 14 patients with sarcoidosis, and determined whether any relationship exists between CYFRA21-1 levels in bronchoalveolar lavage fluid and clinical parameters.
2. CYFRA21-1 levels in bronchoalveolar lavage fluid were significantly higher in patients with sarcoidosis (mean value 8.3 ng/ml, P &lt; 0.01) and idiopathic pulmonary fibrosis (42.5 ng/ml, P &lt; 0.005) than in normal controls (1.0 ng/ml). Moreover, higher CYFRA21-1 levels in bronchoalveolar lavage fluid were found in sarcoidosis patients in radiological stage 2 or 3 than in those in stage 1. In patients with idiopathic pulmonary fibrosis, there was a significant correlation between CYFRA21-1 levels, and percentage of inflammatory cells in bronchoalveolar lavage fluid (r = 0.56, P &lt; 0.05) and the magnitude of the alveolar — arterial oxygen pressure difference [P(a — a)o2] gradient (r = 0.66, P &lt; 0.01).
3. Serial bronchoalveolar lavage samples were obtained from six patients with clinically active pneumonitis after they had undergone systemic corticosteroid therapy. CYFRA21-1 levels were significantly lower after these patients exhibited clinical improvement (P &lt; 0.05).
4. These findings suggest that the level of CYFRA21-1 in bronchoalveolar lavage fluid is a useful marker for the clinical diagnosis of pneumonitis, and is also adequate for the evaluation of disease activity, especially over the course of treatment.
Effects of β-blockers on the Concentration and Oxidizability of Plasma Lipids
Authors: Dimmitt Simon B. , Williams Peta D. , Croft Kevin D. , Beilin Lawrence J. 
Published: August 2015

1. β-blockers improve morbidity and mortality after myocardial infarction, probably by several mechanisms. We investigated potentially relevant effects of β-blockers in vivo and in vitro on plasma lipid oxidizability. Forty-two healthy men were randomized to receive placebo (13), metoprolol (14) or propranolol (15).
2. At 4 weeks, the effects on heart rate, blood pressure and lipids appeared similar and subjects taking a β-blocker were combined. Compared with placebo, those on a β-blocker gained 0.5 kg in weight (P = 0.04), heart rate fell from 63 to 52 beats/min (P &lt; 0.0001) and blood pressure fell from 116/74 to 113/69 mmHg (P &lt; 0.005); high-density lipoprotein (HDL)-cholesterol fell from 1.26 to 1.11 mmol/l (P = 0.005), there being no change in the ratio of free to esterified cholesterol in HDL, and there was an apparent rise in serum triacylglycerols from 1.18 to 1.43 mmol/l (P = 0.15 when adjusted for weight gain). Low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) did not change. In this study, the oxidizability of LDL was unaffected by β-blocker therapy. β-blockade was not associated with any change in LDL fatty acid profile, or β-carotene or α-tocopherol content which might account for the reduced LDL oxidizability previously reported in patients treated with β-blockers. Furthermore, neither atenolol nor propranolol, at concentrations up to 100 μmol/l, had any effect on in vitro oxidizability of LDL obtained from healthy volunteers.
3. In contrast to the favourable haemodynamic effects conferred by β-blockers, the effects on weight and serum triacylglycerols and HDL-cholesterol appear to be adverse and we did not demonstrate any changes in lipid oxidizability which might be relevant to the protective effects of β-blockers in patients with coronary disease.
Increased Nitric Oxide Synthesis and Inducible Nitric Oxide Synthase Expression in Patients with Alcoholic and Non-Alcoholic Liver Cirrhosis
Authors: Sánchez-Rodríguez A. , Criado M. , Rodríguez-López A. M. , Esteller A. , De Arriba A. Martín , López-Novoa J. M. 
Published: August 2015

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis.
2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients.
3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. Nω-Nitro-l-arginine methyl ester (l-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease.
4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lympho-mononuclear cells from non-alcoholic cirrhotic patients.
5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters.
6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.