bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability of Near-Fainting Responses in Healthy 6–16-Year-old Subjects
Authors: Catherine C.E. , van Steenwijk de Jong-de Vos , Wieling Wouter , Harms Mark P. M. , Wesseling Karel H. 
Published: August 2015

1. Fainting is a common phenomenon in young subjects, but the final events before the actual faint are not well known. The aim of the present study was to study the inter-individual variability of haemodynamic events associated with near-fainting in children and teenagers.
2. Sixty-eight healthy subjects (aged 6–16 years) performed a 70° tilt-up test with intravascular instrumentation for 5 min. Responses in 29 near-fainting subjects were analysed and compared with 39 non-fainting subjects. Arterial pressure was measured by Finapres. Left ventricular stroke volume was computed from the pressure pulsation waveform.
3. Inability to maintain vasomotor tone was the mechanism underlying near-fainting in the vast majority of near-fainting subjects. The three classical haemodynamic responses (vasovagal, vasodepressor and vagal) could be recognized, but large individual differences were found. After tilt back, blood pressure in near-fainters showed a mirror response to the stage before tilt-back; blood pressure gradually increased and was normal at 1 min after tilt-back.
4. The variability in haemodynamic responses on approach of an orthostatic faint is wide in the young.
Hyperdynamic Circulation of Cirrhotic Rats with Ascites: Role of Endotoxin, Tumour Necrosis Factor-α and Nitric Oxide
Authors: Chu Chi-Jen , Lee Fa-Yauh , Wang Sun-Sang , Rei-Hwa LU , Tsai Yang-Te , Lin Han-Chieh , Hou Ming-Chih , Chan Che-Chang , Lee Shou-Dong 
Published: August 2015

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilatation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-α and NO in cirrhotic rats with ascites have never been specifically addressed.
2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-α and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances.
3. Plasma concentrations of endotoxin, TNF-α and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats.
4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-α and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/nitrite (r = 0.59, P &lt; 0.0001) and between plasma levels of endotoxin and TNF-α (r = 0.63, P &lt; 0.0001). No correlation was detected between plasma levels of TNF-α and nitrate/nitrite (r = 0.24, P &gt; 0.05).
5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.
Brown Adipose Tissue and Its Uncoupling Protein in Chronically Hypoxic Rats
Authors: Mortola Jacopo P. , Naso Lina 
Published: August 2015

1. Hypoxia is known to decrease thermogenesis. We set out to determine whether this is accompanied by alterations in the brown adipose tissue, which is a major source of non-shivering thermogenesis.
2. Measurements were performed on 25- and 64-day-old rats, after 4 days of hypoxia (10% inspired O2), and on ∼3.5-month-old rats in hypobaric hypoxia since birth, at an ambient temperature of 25°C.
3. All hypoxic rats had higher haematocrit and lower body mass than corresponding controls.
4. In the 25-day-old rats, hypoxia had minimal and non significant effects on brown adipose tissue mass, proteins and DNA concentration. The content of the mitochondrial uncoupling protein thermogenin, evaluated by immunoblot after electrophoretic separation, relative to the cytoskeleton actin (UCP/Act), was not significantly altered.
5. In 25-day-old rats exposed for 4 days to cold (ambient temperature = 7–9°C), brown adipose tissue was hyperplastic, with increased UCP/Act; hypoxia did not appreciably alter the response to cold.
6. In the 2-month-old rats, after 4 days of hypoxia UCP/Act was reduced to about 40% of control.
7. In the 3.5-month-old rats maintained in hypoxia since birth, brown adipose tissue mass was reduced in proportion to body mass, with little effect on total proteins and DNA; UCP/Act was decreased to about 50% of control.
8. We conclude that chronic hypoxia had a minimal effect on brown adipose tissue total proteins and DNA content. However, the uncoupling protein content can be greatly reduced, depending upon age and duration of hypoxia.
Relationship of Serum Leptin to Total and Truncal Body Fat
Authors: Solin Melina S. , Ball Madeleine J. , Robertson Iain , De Silva Andrea , Pasco Julie A. , Kotowicz Mark A. , Nicholson Geoff C. , Collier Greg R. 
Published: August 2015

1. In this study we investigated the relationship between serum leptin levels and body fat distribution in a random sample of women of widely ranging age and body mass index. Anthropometry and dual energy X-ray absorptiometry were used to measure body fat and its distribution.
2. Leptin levels (log transformed) were not significantly correlated with age, but were significantly positively correlated (P &lt; 0.001) with most anthropometric measures except waist-to-hip circumference ratio. The strongest correlations were with total grams of body fat and percentage body fat (r = 0.68 and 0.76 respectively, P &lt; 0.001). When corrected for percentage body fat the partial correlation coefficients for all other measures became non-significant. The correlation with truncal body fat fell significantly from 0.66 to −0.05 after correction, but the partial correlation with total body fat remained significant (P &lt; 0.005) when grams of truncal fat were controlled for (r = 0.21).
3. These results indicate that the relationship of serum leptin to percentage body fat is the strongest, and that truncal body fat, although the most metabolically active, does not appear to have an independent association with serum leptin.
Lipolysis and Lactate Production in Human Skeletal Muscle and Adipose Tissue following Glucose Ingestion
Authors: Kerckhoffs Daniëlle A. J. M. , Arner Peter , Bolinder Jan 
Published: August 2015

1. Using microdialysis, we compared lipolysis, as well as the production of lactate, in human adipose tissue and muscle after the ingestion of carbohydrate.
2. The absolute concentrations of glycerol and lactate were measured in subcutaneous adipose tissue, skeletal muscle and arterialized venous blood in eight normal subjects during basal conditions and 4 h after a 75 g oral glucose load. Nutritive blood flow in muscle and adipose tissue was monitored simultaneously with the microdialysis ethanol clearance technique.
3. At baseline, the concentrations of glycerol in adipose tissue and in muscle were about 7 times and about 2.5 times higher respectively than those in plasma. After glucose ingestion, the changes in glycerol concentrations differed significantly between the three compartments (P &lt; 0.0001). In plasma and adipose tissue, the concentrations decreased rapidly and markedly, but returned to baseline levels after 4 h. In muscle, the decrease in glycerol was less pronounced and more protracted.
4. At baseline, the concentrations of lactate in muscle and in adipose tissue were about 3 times and about 1.5 times higher respectively than those in plasma. After the ingestion of glucose, the levels increased transiently in similar ways in muscle, adipose tissue and plasma. The differences in absolute lactate concentrations between the three compartments were maintained after the glucose load (P &lt; 0.001).
5. Adipose tissue blood flow increased transiently after glucose ingestion, whereas muscle blood flow remained unchanged.
6. Both muscle and adipose tissue are a source of glycerol and lactate release during basal conditions and after glucose ingestion. The regulation of lactate production, but not of lipolysis, after carbohydrate ingestion is similar in the two tissues.
Glaxo/MRS Young Investigator Medal: Molecular Studies on Adenosine Deaminase Deficiency and Hereditary Haemorrhagic Telangiectasia
Authors: Shovlin Claire L. 
Published: August 2015

1. This manuscript describes two different strategies to progress from the clinical assessment of patients to the identification of disease-causing mutations. In the first disease, recognition of a metabolic abnormality allowed direct molecular analysis of the causal gene. In contrast, localization of the second disease gene by linkage analysis was critical to implicate a gene with a previously unsuspected disease role.
2. Two sisters with chronic respiratory disease and recurrent infections were identified as the first cases of adult onset immunodeficiency due to adenosine deaminase deficiency. Autosomal recessive inheritance of two mutations in the adenosine deaminase gene was demonstrated. Enzyme replacement therapy improved the patients' immunological and clinical status.
3. Individuals with pulmonary arteriovenous malformations were used to identify families with hereditary haemorrhagic telangiectasia (HHT, Rendu-Osler-Weber Syndrome). Linkage studies mapped the HHT disease gene in some families to chromosome 9, and demonstrated genetic heterogeneity. The chromosome 9 disease interval was refined, and several candidate genes were assessed. Following the first description of disease-segregating mutations, a complete analysis of the endoglin gene (which encodes an endothelial cell transforming growth factor-β receptor) identified seven novel mutations. Two mutations did not produce mutant mRNA, and disease severity was comparable between families, indicating that HHT results from stoichiometric insufficiency of endoglin.
4. Each study has implications extending beyond the relatively rare disease analysed. The adenosine-deaminase-deficient patients highlight a treatable cause of HIV-negative CD4+ lymphopenia in adults, perhaps accounting for further cases of ‘non-HIV AIDS’. The HHT studies have illuminated a novel area of vascular pathophysiology, with potential relevance to further disease states.
Influence of Mode of Contraction on the Mechanism of Acetylcholine-Mediated Relaxation of Coronary Arteries from Normotensive and Spontaneously Hypertensive Rats
Authors: Bund Stuart J. 
Published: August 2015

1. Endothelium-dependent acetylcholine-mediated relaxations of small coronary arteries (∼200 μm internal diameter) from 20 weeks old spontaneously hypertensive rats (SHR) and normotensive Wistar—Kyoto (WKY) controls were compared under pressurized no-flow conditions after the development of myogenic tone or constriction with the thromboxane A2 mimetic U46619.
2. Relaxations of WKY and SHR arteries following development of myogenic tone did not differ and were not significantly influenced by indomethacin alone (10 μmol/l) or in combination with Nω-nitro-l-arginine (l-NNA, 0.1 mmol/l). Maximum relaxations were significantly attenuated by 30 mmol/l K+ in the SHR, from 85 ± 7% (n = 11) to 20 ± 8% (n = 8), P &lt; 0.001, and in the WKY from 86 ± 5% (n = 9) to 39 ± 14% (n = 8), P &lt; 0.01.
3. Relaxations following constriction with U46619 were also similar in both rat strains. Maximum relaxations were 50 ± 11% (n = 8) in SHR and 60 ± 7% (n = 6) in WKY. Indomethacin did not influence these relaxations. The combination of indomethacin and l-NNA attenuated relaxations in WKY (P &lt; 0.01), but in the SHR the attenuation did not achieve statistical significance (P = 0.07) compared with controls; the maximum responses were reduced to 25 ± 7% (n = 8) and 14 ± 11% (n = 6) in the SHR and WKY respectively, but only in the WKY was this reduction significant (P &lt; 0.05).
4. These data demonstrate that, under control conditions, SHR and WKY coronary arteries relax equally effectively, regardless of mode of contraction, and also that the mechanism of acetylcholine-mediated relaxation differs according to the mode of contraction. Acetylcholine relaxes myogenic tone by a K+-sensitive mechanism in both WKY and SHR, consistent with a role for endothelium-derived hyperpolarizing factor; NO contributes substantially to the relaxation of U46619-induced tone by acetylcholine in the WKY, but to a diminished extent in the SHR.
5. These data indicate that the choice of vasoconstrictor agent is of critical concern when assessing mechanisms of endothelium-dependent relaxation and abnormalities thereof in hypertension.
Changes in Both the Membrane and the Enzyme Content of Individual Zymogen Granules are Associated with Sodium Taurocholate-Induced Pancreatitis in Rats
Authors: Manso Manuel A. , Orfao Alberto , Tabernero M. Dolores , Vicente Secundino , De Dios Isabel 
Published: August 2015

1. After monitoring the changes associated with necrotizing acute pancreatitis in rats from early stages to 24 h after infusion of 5% sodium taurocholate in the choledocus, we characterized by flow cytometry the zymogen granules that still remained in the pancreas 18 h after sodium taurocholate infusion in order to explore whether alterations in the enzyme content and/or in the composition of the granule membrane could be related to the intracellular mechanisms involved in the development of necrotizing acute pancreatitis.
2. Significant increases in the haematocrit, plasma and peritoneal exudate amylase levels and oedema were observed from the third hour after 5% sodium taurocholate infusion onwards. Additionally, cell alterations such as hypergranulation, dilatation of the endoplasmic reticulum and autophagic vacuoles were found 3 and 6 h after infusion. DNA decrease, degranulation and necrosis were observed from 12 h after sodium taurocholate infusion onwards.
3. Flow cytometric measurements of zymogen granules isolated from rat pancreas 18 h after 5% sodium taurocholate infusion revealed a significant decrease in their internal complexity without major changes in their size. Double staining of granules with Tetragonolobus purpureus lectin, which specifically binds l-fucose and specific anti-trypsinogen or anti-amylase antisera, showed that rats with induced pancreatitis have decreased amounts of l-fucose in the membrane glycoconjugates and lower enzyme content (70% and 30% less for trypsinogen and amylase respectively).
4. A decrease in l-fucose in the membrane together with membrane abnormalities observed by electron microscopy in zymogen granules isolated 18 h after sodium taurocholate infusion indicate an altered synthesis of new granules or lysis of preformed zymogen granules which would favour differential loss of granular enzymes, mainly tripsinogen, which in turn could increase the severity of disease.
Differential Regulation of Ventricular Adrenomedullin and Atrial Natriuretic Peptide Gene Expression in Pressure and Volume Overload in the Rat
Authors: Kaiser Michael , Kahr Ole , Shimada Yasuyuki , Smith Pamela , Kelly Martin , Mahadeva Harin , Adams Matthew , Lodwick David , Aalkjaer Christian , Avkiran Metin , Samani Nilesh J. 
Published: August 2015

1. Adrenomedullin is a recently discovered vasodilating and natriuretic peptide whose physiological and pathophysiological roles remain to be established. Like atrial natiuretic peptide adrenomedullin is expressed in the left ventricle. Ventricular expression of atrial natriuretic peptide is known to be markedly increased by volume or pressure overload. In this study we investigated whether ventricular expression of adrenomedullin is similarly stimulated under such conditions.
2. Ventricular adrenomedullin and atrial natriuretic peptide mRNA levels as well as those of a loading control mRNA (glyceraldehyde-3-phosphate dehydrogenase) were quantified by Northern blot analysis in (a) rats with severe post-infarction heart failure induced by left coronary ligation at 30 days post-surgery and (b) in rats with pressure-related cardiac hypertrophy induced by aortic banding at several time points (0.5, 1 and 4 h, and 1, 4, 7 and 28 days) after surgery. Levels were compared with those in matched sham-operated controls.
3. The mRNA level of atrial natriuretic peptide was markedly increased (8–10-fold) in the left ventricle of animals with post-infarction heart failure. In contrast, there was only a modest (40%) increase in the level of adrenomedullin mRNA. In rats with pressure-induced cardiac hypertrophy the ventricular level of atrial natriuretic peptide mRNA was again markedly increased (maximum 10-fold). The increase was first noticeable at 24 h post-banding and persisted until 28 days. In contrast, there was no change in adrenomedullin mRNA level compared with sham-operated rats at any time point.
4. Despite having similar systemic effects, the expression of adrenomedullin and atrial natriuretic peptide in the left ventricle is differently regulated. The findings imply distinct roles for the two peptides. The results do not support an important role for ventricular adrenomedullin expression in the remodelling process that occurs during the development of cardiac hypertrophy but suggest that ventricular adrenomedullin participates in the local and/or systemic response to heart failure
Neutrophil Cathepsin G Modulates Platelet P-Selectin Expression and Inhibits P-Selectin-Mediated Platelet-Neutrophil Adhesion
Authors: Ilton Marcus K. , Taylor Marcia L. , Misso Neil L. A. , Thompson Philip J. , Hung Joseph 
Published: August 2015

1. Close contact between platelets and neutrophils modulates their cellular interactions in thrombotic and inflammatory states, with stimulation of P-selectin expression on platelets by agonists such as thrombin and neutrophil-derived cathepsin G being critical in mediating platelet—neutrophil adhesion. This study compared the effects of thrombin and cathepsin G on platelet P-selectin expression and on P-selectin-mediated platelet—neutrophil adhesion.
2. Washed platelets and platelet—neutrophil mixed cell suspensions (platelet/neutrophil ratio, 10:1) were incubated with either the supernatant of activated neutrophils, purified cathepsin G or thrombin. Platelet P-selectin expression and platelet adhesion to neutrophils was quantified by flow fluorocytometric analysis.
3. The supernatant from activated neutrophils stimulated platelet P-selectin expression comparable to that produced by purified cathepsin G or thrombin. P-selectin expression induced by both activated neutrophil supernatant and purified cathepsin G was completely inhibited by α1-antichymotrypsin, a specific inhibitor of cathepsin G. Unlike thrombin, which induced maximum platelet P-selectin expression by 10 min, sustained to 120 min, cathepsin G induced an initial large increase in platelet P-selectin expression, followed by a progressive reduction over 30–60 min to baseline levels.
4. Co-incubation of neutrophils with thrombin-stimulated platelets resulted in a significant increase in P-selectin-mediated platelet—neutrophil adhesion, which was completely inhibited by preincubation of neutrophils with anti-sialyl Lewisx monoclonal antibody. Thrombin produced maximum platelet—neutrophil adhesion by 10 min which remained stable over 120 min. In contrast, cathepsin G-stimulated platelets did not adhere to neutrophils over 120 min of co-incubation. Addition of cathepsin G to thrombin-stimulated platelets caused a progressive reduction over 30–60 min to baseline levels of platelet—neutrophil adhesion.
5. Neutrophil-derived cathepsin G is a potent platelet activator, but unlike thrombin it causes a time-dependent loss of platelet P-selectin expression and inhibits P-selectin-mediated platelet—neutrophil adhesion. Therefore, cathepsin G may modulate thrombin-mediated platelet—neutrophil adhesive interactions in inflammation and thrombosis.
Aprotinin Reduces Nitric Oxide Production in Vitro and in Vivo in a Dose-Dependent Manner
Authors: Bruda N. L. , Hurlbert B. J. , Hill G. E. 
Published: August 2015

1. Cardiopulmonary bypass is associated with an increase in nitric oxide concentrations, and plasma levels of tumour necrosis factor and interleukin-1. Aprotinin, a serine protease inhibitor, commonly used during cardiopulmonary bypass to reduce blood loss, has been demonstrated to exhibit significant anti-inflammatory effects during and after cardiopulmonary bypass.
2. Airway nitric oxide was measured during cardiopulmonary bypass in 10 controls (Group 1), 10 subjects receiving half-dose aprotinin (Group 2) and 10 patients receiving full-dose aprotinin (Group 3). In vitro, a murine bronchial epithelial cell line (LA-4) was cultured with cytomix (a combination of tumour necrosis factor, interleukin-1, and (γ-interferon) with and without aprotinin in increasing concentrations. Nitrite concentrations, the stable and measureable end-product of nitric oxide oxidative metabolism, were measured in the culture supernatant by chemiluminescence.
3. Airway nitric oxide concentrations were increased after 50 min cardiopulmonary bypass compared with that measured at 5 min in controls (53 ± 5 versus 29 ± 3 ppb, P &lt; 0.05) but not in the aprotinin-treated groups (25 ± 4 versus 14 ± 5, Group 2; 21 ± 6 versus 15 ± 3 ppb, Group 3).
4. In a dose-dependent manner, nitrite levels (means ± S.E.M.) were significantly reduced by aprotinin at 500 and 1000 units/ml when compared with cells cultured in the presence of cytomix alone (P &lt; 0.05).
5. These data demonstrate that aprotinin, in a dose-responsive manner, reduces nitric oxide production in vivo and reduces cytokine-induced nitrite production by murine bronchial epithelial cells in vitro. Since increased airway nitric oxide is found in inflammatory lung diseases, like asthma, and anti-inflammatory therapy reduces the concentration of airway nitric oxide, these data support the concept that aprotinin is anti-inflammatory during cardiopulmonary bypass.
A Circadian Variation Exists for Soluble Levels of Intercellular Adhesion Molecule-I and E-Selectin in Healthy Volunteers
Authors: Maple C. , Kirk G. , McLaren M. , Veale D. , Belch J.J.F. 
Published: August 2015

1. We have previously shown a circadian variation in leucocyte activation and endothelial function which may explain why some inflammatory and vascular diseases show a circadian variation in disease activity/occurrence.
2. We have investigated the circadian variation of two soluble cell adhesion molecules, intercellular adhesion molecule-1 and E-selectin, in 10 healthy volunteers. Soluble intercellular adhesion molecule-1 is released from both activated leucocytes and endothelial cells while soluble E-selectin is released only from activated endothelium.
3. Results show a circadian variation exists for both soluble intercellular adhesion molecule-1 and E-selectin (both P &lt; 0.0001, analysis of variance) with a peak activity at 12:00 h for both measures and a minimum activity at 04:00 h for intercellular adhesion molecule-1 and 00:00 h for E-selectin.
4. These results demonstrate the existence of a diurnal variation in cell adhesion molecules, providing evidence in support of a diurnal pattern in endothelial and leucocyte activation. An alteration in this biological rhythm may help to explain the diurnal variation in disease activity in certain inflammatory and vascular disease states. Furthermore, it stresses the importance of sample time point standardization in clinical studies.