bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep
Authors: Polla Barbara S. , Clerc Josiane , Pittet Jean-François , Morel Denis R. 
Published: August 2015

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2−) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min−1 kg−1).
2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy.
3. O2− generation by isolated monocytes was measured by the O2− dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2− production was significantly (P = 0.008) higher for non-survivors (31.3 ± 8.8 nmol 30 min−1 10−6 cells; n = 4) than for survivors (6.2 ± 2.3 nmol 30 min−1 10−6 cells; n = 7).
4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2− production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2− production with opsonized zymosan.
5. These results suggest that (1) increased O−2 production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2− production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.
Damage to erythrocytes from long-term heat stress
Authors: Utoh Junichi , Harasaki Hiroaki 
Published: August 2015

1. Erythrocytes are known to haemolyse in vitro at 48–50°C. We hypothesized that erythrocytes might be damaged at much lower temperatures if they are incubated for prolonged periods. Erythrocytes from healthy human donors (n = 7) were incubated at 37, 40, 42, 44, 46 or 48°C for 4–48 h. The haemolytic percentage and osmotic fragility were then measured by a modification of the method of Parpart et al. [9].
2. Significant haemolysis and increased fragility were not observed at any temperatures after incubation for 4 h. However, the haemolytic percentage increased after incubation for 24 h at 44°C (9.1 ± 4.9%, P&lt;0.01), 46°C (52.4 ± 14.1%, P&lt;0.01) and 48°C (98.0 ± 2.6%, P&gt; 0.01) and after incubation for 48 h at 42°C (9.8 ± 4.5%, P&lt;0.01) when compared with the values before heating (1.1 ± 0.9%). The osmotic fragility also increased after incubation for 24 h at and above 42°C.
3. Although heat-induced haemolysis and an increase in fragility have not been known to occur below 48°C, these were quite apparent after incubation for 24–48 h at only 42°C. This suggests that with regard to thermal effects, it is important to consider not only the temperature but also the duration of heating.
Membrane incorporation of non-esterified fatty acids and effects on the sodium pump of human erythrocytes
Authors: Dwight J. F. St. J. , Ribeiro A. C. Mendes , Hendry B. M. 
Published: August 2015

1. Sodium pump function has been assessed by measurement of ouabain-sensitive 86Rb uptake in human erythrocytes after incorporation of palmitic, stearic, oleic and linoleic acids into the erythrocyte membrane. 14C-labelled fatty acids were used to measure membrane uptake of these substances.
2. For palmitic, oleic and linoleic acids, up to 1000 nmol of the fatty acid/ml of packed cells can be incorporated without causing significant haemolysis. For stearic acid, 270 nmol/ml of packed cells was incorporated in similar conditions. More than 88% of the fatty acid incorporated could be extracted with a 50 μmol/l fatty-acid-free albumin solution and was, therefore, in a non-esterified form in the erythrocyte membrane. The concentrations of palmitic, stearic, oleic and linoleic acids incorporated in these experiments represent a five- to ten-fold increase above the normal concentrations of these fatty acids in the membrane.
3. Up to 1000 nmol of palmitic, oleic and linoleic acids/ ml of packed cells and up to 270 nmol of stearic acid/ml of packed cells could be incorporated without a significant change in mean ouabain-sensitive 86Rb uptake with respect to control cells. Mean percentage changes in ouabain-sensitive 86Rb uptake for all these experiments were: palmitic acid, 3.7% (sd 11.4, n = 15); stearic acid, 4.0% (sd 5.7, n = 7); oleic acid, −4.8% (sd 19, n = 17); linoleic acid, 2.2% (sd 15.6, n = 19).
4. The demonstration of near-normal sodium pump activity in the presence of greatly elevated membrane levels of these fatty acids makes it extremely unlikely that they act as modulators of sodium pump function in vivo.
Isolation and purification of human biliary vesicles with potent cholesterol-nucleation-promoting activity
Authors: Miquel Juan Francisco , Rigotti Attilio , Rojas Eduardo , Brandan Enrique , Nervi Flavio 
Published: August 2015

1. Cholesterol nucleation is a critical step in the formation of cholesterol gallstones. This nucleation takes place after aggregation and fusion of cholesterol-rich biliary vesicles, a process probably modulated by biliary proteins. The present study was conducted to identify specific proteins associated with native cholesterol-rich biliary vesicles and to explore their effect on the cholesterol-nucleation time of supersaturated artificial bile.
2. Hepatic bile was obtained from six patients with cholesterol gallstone disease. Biliary vesicles were isolated by ultracentrifugation and were purified by gel filtration chromatography. A small amount of protein (less than 1% by weight) remained associated with the purified cholesterol-rich biliary vesicles. The electrophoretic profile of these proteins was remarkably similar in all six patients, showing the presence of at least six polypeptides (of molecular mass from 52 to 200 kDa), five of them having carbohydrate residues (except the 52 kDa one). The effect of reconstituted biliary vesicle solutions, containing their specific vesicular proteins, on cholesterol-nucleation time was studied by mixing the vesicle solution with artificial supersaturated bile. A potent cholesterol-pronucleating activity, reflected in a 20–70% reduction in nucleation time, was present in the biliary vesicle solutions compared with control solutions having a similar lipid composition. The pronucleating activity disappeared on heating and was not detected in the micellar fraction containing the major proportion of biliary proteins.
3. These results indicate that cholesterol-rich biliary vesicles containing a unique and defined glycoprotein profile can be isolated and purified from human hepatic bile. The potent cholesterol-pronucleating activity of the biliary vesicles from patients with gallstones was unrelated to their lipid composition or cholesterol content. This activity was probably associated with their glycoprotein component, supporting the view that vesicular proteins may have a central role in the pathogenesis of cholesterol gallstone disease.
Acute administration of tumour necrosis factor-α or interleukin-1-α does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat
Authors: Evans Rhys D. , Ilic Vera , Williamson Dermot H. 
Published: August 2015

1. Administration of tumour necrosis factor (cachectin) and of interleukin-1-α increased the plasma level of non-esterified fatty acids in fed rats, and in the case of interleukin-1-α the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations.
2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-α. Parallel changes occurred in hepatic ketone bodies.
3. It is concluded that tumour necrosis factor-α and interleukin-1-α are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.
Danazol induces resistance to both insulin and glucagon in young women
Authors: Bruce Raymond , Godsland Ian , Stevenson John , Devenport Maxeen , Borth Fiona , Crook David , Ghatei Mohammed , Whitehead Malcolm , Wynn Victor 
Published: August 2015

1. Danazol elevates plasma insulin, plasma glucagon and serum low-density lipoprotein concentrations and reduces the serum high-density lipoprotein concentration.
2. Associations between these disturbances were studied in 17 women receiving danazol therapy for endometriosis. Eleven women underwent intravenous glucose tolerance tests with measurement of plasma glucose, insulin, C-peptide and glucagon concentrations and modelling analysis of intravenous glucose tolerance test concentration profiles. Six women underwent glucagon sensitivity tests. Serum concentrations of lipids and lipoproteins were measured in all cases.
3. Danazol reduced the fasting plasma glucose and insulin concentrations, but markedly raised the fasting plasma glucagon concentration. The insulin and C-peptide responses to the intravenous glucose tolerance test were increased twofold and the net decrement in glucagon concentration was increased tenfold. The glucose response to the intravenous glucose tolerance test was unaffected. Insulin sensitivity was reduced by 55%. Both first-phase plasma insulin responsiveness and net first-phase pancreatic insulin secretion were increased; insulin half-life was prolonged. The glucose response to the glucagon sensitivity test was reduced on treatment. The calculated low-density lipoprotein cholesterol level rose by 20%, whereas high-density lipoprotein cholesterol level fell by 47%. None of these changes in serum lipoprotein levels correlated with changes in insulin metabolism. In general, metabolic changes normalized after 3 months.
4. Danazol increases the sensitivity of pancreatic insulin and glucagon secretion to glucose. Danazol-induced insulin and glucagon resistance could be due to receptor down-regulation resulting from hypersecretion of insulin and glucagon.
Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: Evidence against a role for platelet-activating factor
Authors: McCormack David G. , Crawley David E. , Barnes Peter J. , Evans Timothy W. 
Published: August 2015

1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation.
2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor anatagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed.
3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 μg of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2α was also measured. To quantify lung injury, the wet/ dry ratio of lung weight was determined.
4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin.
5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic ‘sensor’ within the respiratory tract.
Enhanced synthesis of neutrophil-activating peptide-I/interleukin-8 in active ulcerative colitis
Authors: Mahida Y. R. , Ceska M. , Effenberger F. , Kurlak L. , Lindley I. , Hawkey C. J. 
Published: August 2015

1. We studied neutrophil-activating peptide-1/interleukin-8 in inflammatory bowel disease.
2. Mucosal levels of neutrophil-activating peptide-1/ interleukin-8 were significantly higher in patients with active ulcerative colitis [median 74.5 (range 17.7–450.8) pg/mg] than in patients with active Crohn's disease [10.4 (4–46.9) pg/mg; P&lt;0.002] or in normal control subjects [10.4(4–16.6) pg/mg; P &lt;0.002].
3. Circulating neutrophil-activating peptide-1/interleukin-8 was generally undetectable but there were higher levels of anti-neutrophil-activating peptide-1/interleukin-8 antibodies in patients with active ulcerative colitis [62.9 (3.4–239) ng/ml] than in patients with active Crohn's disease [5.9 (2.1–18.10) ng/ml; P &lt;0.001] or in control subjects [6.1 (3.2–15.8) ng/ml; P &lt;0.001].
4. Neutrophil-activating peptide-1/interleukin-8 may be of specific functional importance in mediating inflammation in ulcerative colitis.
Nitrogen absorption from isonitrogenous solutions of l-leucyl-l-leucine and l-leucine: A study in the isolated perfused rat small intestine
Authors: Plauth Mathias , Kremer Ingrid , Raible Armin , Stehle Peter , Fürst Peter , Hartmann Franz 
Published: August 2015

1. We assessed the efficacy of nitrogen absorption from luminal L-leucine (1.2 and 12 mmol/l) and from isonitrogenous l-leucyl-l-leucine (0.6 and 6.0 mmol/l) in a preparation of vascularly and luminally perfused rat small intestine by measuring luminal leucyl-leucine disappearance and venous leucine appearance.
2. No intact dipeptide was found in the vascular perfusate. Leucine-nitrogen absorption, as judged by venous leucine appearance, was as efficient from free leucine (29 ± 3 and 245 ± 19 ng-atom min−1 g−1) as from leucyl-leucine (27 ± 4 and 211 ± 58 ng-atom min−1 g−1). It was not reduced in the presence of glycyl-l-proline or of the brush-border dipeptidase inhibitors alanine-β-naphthylamide and cilastatin.
3. After one passage of the whole small intestine, only trace amounts of dipeptide, but large amounts of free leucine, were detected in the luminal effluent. Peptidase activity in the luminal effluent was demonstrated in 100000 g supernatant and was inhibited by p-hydroxymercuribenzoate, but not by brush-border dipeptidase inhibitors.
4. We propose that nitrogen absorption from luminal leucyl-leucine may proceed predominantly via intraluminal peptide hydrolysis and subsequent transport of free leucine. Nevertheless, our findings and conclusions are at variance with previous observations and current opinion on intestinal handling of dipeptides, which may be due, in part, to the different methodological approach.
Ferrous ions detected in cerebrospinal fluid by using bleomycin and DNA damage
Authors: Gutteridge John M. C. 
Published: August 2015

1. During pathological states of iron-overload or oxidant stress, low-molecular-mass iron can become available within extracellular fluids.
2. This iron would be converted to the ferrous state were it not for the protective anti-oxidant protein caeruloplasmin.
3. The ferrous-ion-oxidizing activity of caeruloplasmin rapidly converts ferrous ions back to the less reactive ferric state so that they can bind to available binding sites on transferrin.
4. Cerebrospinal fluids, however, often appear to contain low-molecular-mass iron, high levels of ascorbate and low levels of ferroxidase activity with little or no iron-binding capacity.
5. When iron ions are present in cerebrospinal fluid they are therefore likely to be in the ferrous state.
6. The development and application of an assay to speciate and measure ferrous ions in simple aqueous solution and their redox cycling activity in biological fluids is described.
Hysteresis of the venous pressure-volume relationship in the forearm of borderline hypertensive subjects
Authors: Journo H. J. , Chanudet X. A. , Pannier B. M. , Laroque P. L. , London G. M. , Safar M. E. 
Published: August 2015

1. The forearm venous pressure-volume relationship was studied in 14 young men with borderline hypertension and in 16 control subjects of the same age and sex. Strain-gauge plethysmography was used to evaluate volume changes after slow increases and decreases in distention, in order to estimate the amplitude of the hysteresis curve.
2. Compared with normotensive control subjects, subjects with borderline hypertension had significantly higher values of blood pressure, heart rate and forearm blood flow.
3. Baseline forearm venous tone was slightly, but not significantly, increased in borderline hypertensive subjects (21.35 ± 6.53 versus 18.75 ± 5.95 mmHg ml−1 100 ml−1) and was significantly enhanced after a cold pressor test. The increase was no higher in the borderline hypertensive subjects than in the normotensive control subjects.
4. The area of the hysteresis curve was significantly decreased (7.58 ± 3.58 versus 10.34 ± 5.67 arbitrary units; P = 0.0092) as was the extent of isotonic relaxation (creep) (0.28 ± 0.11 versus 0.39 ± 0.22 ml/100 ml; P = 0.0098) in borderline hypertensive subjects compared with control subjects. Both parameters were unaffected by the cold pressor test.
5. The study suggests that the viscous component of the venous wall is altered in young patients with borderline hypertension, indicating intrinsic changes in vascular segments which are not exposed to increased intraluminal pressure.
Vascular responses and ion exchange in diabetes: Authors' reply
Authors: Ritter J. M. , Viberti G. C. 
Published: August 2015

1. Na+/Li+ countertransport is not a gold standard, or indeed any other kind of standard. It is a measure of the activity of one particular cation exchanger.
2. There is a large body of literature regarding the effects of oxidized low-density lipoprotein (LDL) in experimental animals and in vitro. Whether abnormal oxidized LDL or one of many other possible mechanisms underlies the inverse relationship that we observed between vascular sensitivity in vivo to nitroprusside or carbachol with erythrocyte Na+/Li+ countertransport in diabetic patients remains to be seen.
3. We caution against post hoc subgroup analysis (smokers versus non-smokers, low versus high plasma lipid levels, etc.) in studies of this size.
Variations in the glycoforms of serum α1-antichymotrypsin in liver diseases and after liver transplantation
Authors: Hachulla E. , Laine A. , Hedouin V. , Fournier C. , Maury F. , Mathieu C. , Pruvot F. R. , Declerck N. , Paris J. C. , Degand P. 
Published: August 2015

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the microheterogeneity of α1-antichymotrypsin due to various glycoforms in sera from patients with various liver diseases and after liver transplantation.
2. Studies by isoelectric focusing and immunoblotting and by crossed immunoelectrophoresis without concanavalin A in the first dimension allowed us to show that there is no dramatic variation in electrophoretic heterogeneity of α1-antichymotrypsin in the serum of patients with liver diseases or after liver transplantation when compared with that of normal subjects. Therefore the heterogeneity observed in crossed immunoaffinity electrophoresis is due to various interactions with concanavalin A.
3. The results were expressed as the ratio of concanavalin A non-reactive glycoforms plus concanavalin A weakly reactive glycoforms to concanavalin A reactive glycoforms, called Rα1-ACT. Rα1-ACT was significantly higher in patients with cirrhosis (n = 53) when compared with normal subjects (n = 30). The median Rα1-ACT was 1 (range 0.72–1.25) in normal subjects. It was 1.6 (range 1.18–3.02), 1.45 (range 0.65–4.12) and 2.24 (range 1.03–19) in cirrhosis of Child's grade A, B and C, respectively. There was a dramatic decrease in glycoforms with mostly biantennary glycans in some patients with Child's grade C cirrhosis. Serum levels of α1-antichymotrypsin were lower than normal only in some patients with Child's grade C cirrhosis.
4. Among the patients with acute viral hepatitis studied (n=17), five were studied longitudinally. Rα1-ACT increased after the peak level of serum transaminases and remained high while the level of serum transaminases decreased and liver regeneration occurred. In these patients there was no alteration in glycoforms with mostly biantennary glycans.
5. Four patients were studied after liver transplantation. During the first days after transplantation Rα1-ACT was low because of an increase in glycoforms with mostly biantennary glycans. After the first week, Rα1-ACT rose above the normal range because of an increase in glycoforms with pluriantennary glycans and it returned to normal within 3 post-operative weeks. Rα1-ACT remained high in a patient who presented with liver rejection.
6. The present study suggests that Rα1-ACT is a helpful additional marker for the evaluation of hepatocyte function.
Central bradykininergic system in normotensive and hypertensive rats
Authors: Alvarez Azucena L. , Delorenzi Alejandro , Santajuliana Daniel , Finkielman Samuel , Nahmod Victor E. , Pirola Carlos J. 
Published: August 2015

1. The kinin antagonist des-Arg9−[Leu8]bradykinin, injected into the lateral ventricle, caused a long-lasting, dose-dependent reduction in arterial blood pressure and heart rate in spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats; the antagonist also blocked the pressor response to ventricularly infused bradykinin in both strains.
2. Bradykinin content was increased in the hypothalamus and septum and decreased in the dorsal medulla of spontaneously hypertensive rats when compared with those of normotensive Wistar-Kyoto rats, whereas similar bradykinin contents were observed in the pineal gland, hypophysis and rostroventrolateral medulla of both rat strains.
3. Increased concentrations of bradykinin and its precursor kininogen were found in the cerebrospinal fluid of spontaneously hypertensive rats.
4. Bradykinin receptor numbers, measured as the binding of [125I-Tyr1]bradykinin to nervous tissue, were found to be increased in the dorsal medulla and hypophysis, and to be decreased in the pineal gland, of spontaneously hypertensive rats.
5. Therefore, the central kinin system may participate, by both pre- and post-synaptic mechanisms, in the maintenance of hypertension in spontaneously hypertensive rats.