bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation between Pressor Sensitivity in Vivo and Contractile Reactivity in Vitro to Angiotensin II in Rats with Experimental Cirrhosis
Authors: Leehey David J. 
Published: August 2015

1. Decreased pressor sensitivity to angiotensin II occurs in cirrhosis, but the mechanism remains unclear.
2. Angiotensin II dose-response studies were performed in conscious, chronically instrumented cirrhotic and control rats, and angiotensin II concentration-response studies were performed in isolated blood vessels obtained from similar groups of animals.
3. Cirrhotic rats demonstrated a significantly decreased pressor response to angiotensin II (5-80 ng/kg intravenously). However, angiotensin II-generated tension in thoracic aortic rings isolated from cirrhotic rats and studied in vitro was not impaired. These findings are consistent with the concept that circulating vasodilator substances in cirrhosis rather than an abnormality intrinsic to vascular smooth muscle cells are responsible for the decreased pressor sensitivity to angiotensin II in vivo.
4. Pretreatment with the cyclo-oxygenase inhibitor indomethacin (3 mg/kg intravenously) restored pressor sensitivity to angiotensin II to normal, suggesting that cyclo-oxygenase products, possibily vasodilator prostaglandins, may be involved in mediating pressor resistance to this hormone in vivo.
Biochemical Correlates of Aortic Distensibility in vivo in Normal Subjects
Authors: Hopkins K. D. , Lehmann E. D. , Gosling R. G. , Parker J. R. , Sönksen P. H. 
Published: August 2015

1. Non-invasive aortic compliance measurements have been used previously to assess the distensibility of the aorta in several pathological conditions associated with increased cardiovascular risk. In adult patients with familial hypercholesterolaemia and those with growth hormone deficiency, aortic compliance has been found to correlate inversely with plasma cholesterol levels and age. We set out to establish if a relationship existed between the biophysical measurement of aortic compliance and biochemical variables in normal healthy adult subjects.
2. Blood pressure-corrected aortic distensibility, fasting insulin, insulin-like growth factor-I, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triacylgiycerol were measured in 38 (18 males, 20 females) normotensive healthy adults.
3. Blood pressure-corrected aortic distensibility was found to correlate inversely with age (r = −0.67, P &lt;0.001), low-density lipoprotein-cholesterol (r = −0.37, P &lt;0.02) and the low-density lipoprotein-/high density lipoprotein-cholesterol ratio (r = −0.33, P &lt;0.05) and positively with insulin-like growth factor-I (r = 0.47, P &lt;0.01). On separate analysis by sex, significant inverse correlations were observed in females between aortic distensbility and total cholesterol (r = −0.50, P &lt;0.02), low-density lipoprotein-cholesterol (r = −0.55, P &lt;0.01) and age (r = −0.74, P &lt;0.001). A positive correlation was found between aortic distensibility and insulin-like growth factor-I (r = 0.48, P &lt;0.05). On forced stepwise regression analysis, however, only age (P &lt;0.02) was found to be significant. In males, an inverse correlation was found between aortic distensibility and age (r = −0.57, P &lt;0.01), low-density lipoprotein-cholesterol (r = −0.51, P &lt;0.05) and the low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (r = −0.63, P &lt;0.01). Positive correlations were observed between aortic distensibility and high-density lipoprotein-cholesterol (r = 0.48, P &lt;0.05) and insulinlike growth factor-I (r = 0.48, P &lt;0.05). On forced stepwise regression analysis the low-density lipoprotein-/high-density lipoprotein-cholesterol ratio (P &lt;0.02) and age (P &lt;0.04) were found to be the only significant independent predictors of aortic distensibility in males.
4. In normal adult subjects insulin-like growth factor-I and high-density lipoprotein-cholesterol are associated with increased aortic distensibility, whereas low-density lipoprotein-cholesterol is associated with aortic stiffening. We suggest that the measurement of blood pressure-corrected aortic distensibility in normal, healthy subjects may potentially be a useful, non-invasive research tool for investigating the effect of biochemical factors on the biophysical properties of the aortic wall.
Neutrophil Platelet-Activating Factor in Normal and Hypertensive Pregnancy and in Pregnancy-Induced Hypertension
Authors: Beilin L. J. , Croft K. D. , Michael C. A. , Ritchie J. , Schmidt L. , Vandongen R. , Walters B. N. J. 
Published: August 2015

1. Platelet-activating factor is a phospholipid with potent vasodilator and platelet-activating properties. To test the hypothesis that a generalized change in cellular platelet-activating factor metabolism may be involved in the systemic vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied platelet-activating factor and eicosanoid synthesis in isolated leucocytes obtained from pregnant women before and after delivery compared with age-matched non-pregnant control subjects. Parallel observations were carried out in age- and gestation-matched women with uncomplicated hypertension in pregnancy and in women with pregnancy-induced hypertension and a further set of normotensive pregnant control subjects.
2. Leucocyte counts were higher in all pregnant groups compared with non-pregnant control subjects. Neutrophil production of platelet-activating factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in response to calcium ionophore stimulation were all lower in pregnant women compared with non-pregnant control subjects, but returned to similar levels 6 weeks post partum. There was no significant difference between essential hypertensive and normotensive groups. When women with pregnancy-induced hypertension were a priori subdivided into those with or without proteinuria, subjects with proteinuria showed significantly lower levels of neutrophil platelet-activating factor synthesis.
3. Plasma levels of the platelet-activating factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy, suggesting alterations in the activity of enzymes controlling synthesis or degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension the levels of plasma lyso-platelet-activating factor were higher than in normal pregnancy.
4. Thus this study demonstrates a reduction in the maximum capacity of neutrophils to synthesize platelet-activating factor and the three main classes of eicosanoids in vitro and a reduction in plasma lyso-platelet-activating factor levels in normotensive and essential hypertensive pregnancies. Contrary to expectation neutrophil prostacyclin metabolite generation was reduced in normal pregnancy. In pregnancy-induced hypertension with proteinuria the suppression of neutrophil platelet-activating factor synthesis was more pronounced. The results do not support the involvement of platelet-activating factor in the vasodilatation of pregnancy, but indicate profound changes in cellular phospholipid metabolism in normal pregnancy with further disturbances in pregnancy-induced hypertension by as yet unexplained mechanisms.
Is Receptor Cross-Regulation in Human Heart Caused by Alterations in Cardiac Guanine Nucleotide-Binding Proteins?
Authors: Ferro A. , Plumpton C. , Brown M. J. 
Published: August 2015

1. Guanine nucleotide-binding proteins (G-proteins) play a central role in signal transduction between a wide variety of cell-surface receptors and intracellular second messenger systems. Recently, we and others have demonstrated that cross-regulation can occur between a variety of G-protein-linked receptors in human heart. Chronic β1-adrenoceptor blockade gives rise to sensitization of β2-adrenoceptor and of 5HT4-receptor responses, both of which are mediated via stimulation of adenylate cyclase through stimulatory G-proteins (Gs), and also gives rise to desensit-ization of muscarinic M2-receptor responses, which inhibit adenylate cyclase through inhibitory G-proteins (Gi).
2. In order to investigate whether these effects are due to quantitative changes in cardiac G-protein isoforms, we measured their abundance in right atrial appendage from patients taking or not taking β1-adrenoceptor antagonists, by immunoblotting.
3. Samples of right atrial appendage homogenate were subjected to SDS/PAGE, and proteins were electroblotted on to nitrocellulose membranes. These were then probed with specific anti-G protein anti-sera, and binding was revealed by means of a secondary antibody labelled with alkaline phosphatase and using a chromogenic substrate. The resulting bands were quantified by laser densitometry.
4. No quantitative differences were detected, between these two groups of patients, in the amounts of α-subunit of ‘long’ or ‘short’ Gs isoforms (GsαL and GsαS), or in the amounts of Gi 1 + 2 α-subunit (Giα1 + 2). Nor was any difference found in the abundance of the β-subunit of G-proteins. No ‘other’ G-protein (Go) was detectable in these samples by immunoblotting.
5. We conclude that the phenomenon of receptor cross-regulation which we have previously observed in human right atrial appendage is unlikely to be explained by quantitative changes at the G-protein level.
Plasma Levels of Brain Natriuretic Peptide in Healthy Subjects and Patients with Essential Hypertension: Response to Posture
Authors: La Villa Giorgio , Vena Silvio , Conti Alberto , Fronzaroli Caterina , Brat Aldo , Lazzeri Chiara , Guerra Cristina Tosti , Madiai Stefania , Marra Nazzareno , Franchi Franco 
Published: August 2015

1. To examine whether posture-induced changes in central volume affect brain natriuretic peptide secretion, plasma levels of human brain natriuretic peptide-32-like immunoreactivity (hBNP-32-li) were measured by radioimmunoassay in 11 healthy subjects and 20 patients with essential hypertension after 15 min supine, 15 min sitting and 15 min with the legs raised at 60°, together with plasma atrial natriuretic peptide concentration, plasma renin activity and plasma aldosterone concentration.
2. In the supine position, the plasma hBNP-32-li level was 1.57 + 0.10 fmol/ml in healthy subjects and significantly higher in hypertensive patients (2.39 +0.13 fmol/ml, P &lt;0.001). In both groups, plasma hBNP-32-li level significantly (P &lt;0.001) decreased when sitting (normotensive, 1.22 +0.08 fmol/ml; hypertensive, 1.85 +0.15 fmol/ml, P &lt;0.001 versus normotensive) and increased again after leg raising (normotensive, 2.13+0.12 fmol/ml; P &lt;0.002 versus resting; hypertensive, 2.84 + 0.16 fmol/min, P &lt;0.001 versus resting, P &lt;0.025 versus normotensive).
3. The plasma atrial natriuretic peptide concentration showed similar behaviour to the plasma hBNP-32-li, whereas plasma renin activity and plasma aldosterone concentration increased during sitting and decreased during leg raising in both healthy subjects and hypertensive patients, who had significantly higher plasma aldosterone levels when supine and sitting.
4. The plasma hBNP-32-li level, measured in all postural positions, was directly correlated with plasma atrial natriuretic peptide concentration (normotensive: r = 0.55, P &lt;0.001; hypertensive: r = 0.69, P &lt;0.001) and inversely correlated with plasma renin activity (r = −0.56, P &lt;0.001 and r = −0.58, P &lt;0.001).
5. We have shown that two physiological procedures, assumption of the sitting position and raising the legs to 60°, significantly affect the plasma hBNP-32-li level in healthy subjects. The response of the plasma hBNP-32-li level to postural changes is maintained in patients with essential hypertension, who have increased plasma levels of this hormone. The relevance of the observed modifications in the plasma hBNP-32-li level to the homoeostatic response to posture remains to be established.
Insulin Resistance of Stress: Sites and Mechanisms
Authors: Brandi Luigi S. , Santoro Donatella , Natali Andrea , Altomonte Fiorella , Baldi Simona , Frascerra Silvia , Ferrannini Eleuterio 
Published: August 2015

1. Stress is associated with a severe, yet reversible, form of insulin resistance. The aim of this study was to quantify the kinetics of insulin action (sensitivity and responsiveness) on intermediary metabolism during post-surgical stress.
2. We studied nine patients 6–8 h after major uncomplicated surgery, and eight healthy subjects matched for age, weight, glucose tolerance and duration of fast. A three-step isoglycaemic insulin clamp was combined with indirect calorimetry, [6-3H]glucose infusion and the forearm technique.
3. The following significant (P &lt;0.05 or less) abnormalities were found in the patients. Hepatic glucose production was higher at baseline, and less suppressed by insulin. Whole-body glucose disposal was impaired at all insulin doses (by 33–60%). Glucose oxidation was depressed throughout the dose range but its increments in response to insulin were normal. In contrast, non-oxidative glucose disposal was essentially unresponsive. At all insulin levels, forearm glucose extraction was markedly depressed and forearm lactate release was in excess of concurrent glucose uptake, suggesting ongoing glycogenolysis despite insulin. Total lipolysis (plasma free fatty acid and glycerol levels) promptly responded to insulin but remained higher than in the control subjects throughout. In the forearm, even the highest insulin dose could not suppress net free fatty acid and glycerol release. Total lipid oxidation was increased throughout the insulin range, and calculated direct free fatty acid (as opposed to plasma free fatty acid) oxidation was virtually unaffected by insulin. Protein oxidation was slightly (35%) increased, but was suppressed normally in response to insulin. Energy expenditure was 20% higher at baseline, and tailed to rise with insulin. Arterial blood pH values were consistently (if slightly) lower, and net forearm proton release was higher, both at baseline and daring insulin infusion.
4. Post-surgical unsulin resistance is characterized by normal sensitivity but decreased responsiveness of glucose oxidation, lipolysis and plasma free fatty acid oxidation, whereas glycogen synthesis and direct free fatty acid oxidation are virtually unresponsive. For both glucose and lipid metabolism, the insulin resistance is particularly severe in forearm tissues, in which mild metabolic acidosis may play an additional role.
Free-Radical Activity after Reperfusion in Diabetic and non-diabetic Patients with Acute Myocardial Infarction
Authors: Gray Rosaire P. , Wickens David G. , Patterson David L. H. , Yudkin John S. 
Published: August 2015

1. Oxygen-derived free radicals have been implicated in reperfusion injury after thrombolytic therapy in acute myocardial infarction. To test the hypothesis that diabetic patients may have increased oxidative stress which may lead to increased reperfusion damage and thereby contribute to a poorer outcome in these patients, we measured two indices of free-radical activity, diene conjugate molar ratios as an index of lipid isomerization and thiobarbituric acid-reactive material as an index of lipid peroxidation, in 66 non-diabetic and 26 diabetic patients admitted with acute myocardial infarction who received thrombolytic therapy and in whom reperfusion was assessed using early time to peak creatine kinase-MB isoenzyme release.
2. Baseline diene conjugate molar ratios or thiobarbituric acid-reactivity did not differ significantly between diabetic and non-diabetic patients (1.97 + 0.98 versus 2.16 + 1.34; not significant and 2.10 + 0.60 versus 1.99 + 0.73 μmol/l; not significant). In patients with enzymic evidence of reperfusion (i.e. time to peak enzyme release ≦12h) diene conjugate molar ratios peaked at 6 h compared with 12 h in those with unsuccessful reperfusion (i.e. time to peak enzyme release &gt;12 h). In patients with unstable angina the maximum increase in the diene conjugate molar ratios was significantly less than in patients with acute myocardial infarction (6.80 + 12.3 versus 15.82 + 22.55%; P = 0.035). There was a significant fall in thiobarbituric acid-reactivity at 24 h in patients with enzymic evidence of reperfusion (P = 0.017). There were no major differences in these rises and falls between diabetic and non-diabetic patients.
3. These findings suggest the free-radical activity as assessed by diene conjugate molar ratios was increased after myocardial infarction, but the increase was not significantly different in diabetic and non-diabetic patients. Early peaking of free-radical activity was associated with enzymic evidence of reperfusion.
Change in Macro Molecular Composition of Interstitial Fluid from Swollen Arms after Breast Cancer Treatment, and Its Implications
Authors: Bates D. O. , Levick J. R. , Mortimer P. S. 
Published: August 2015

1. The pathophysiology of chronic arm oedema after treatment of breast cancer was investigated by collecting serum and subcutaneous interstitial fluid from the affected and contralateral arms by the wick method (both arms) and by aspiration (oedematous arm). The fluids were analysed for total protein, albumin, glycosaminoglycan and viscosity, and arm volume was measured.
2. Total protein concentration in the aspirated oedema fluid was 32.4 + 7.5 g/l (mean + SD throughout; n = 39). Protein concentration in wick fluid from the oedematous arm (35.8 + 7.3 g/l, n = 14) was not significantly different from that in aspirated fluid. The oedema protein concentrations were significantly lower than in wick fluid from the non-swollen arm (41.4 + 6.7 cmH2O, n = 13, P &lt;0.01, analysis of variance). This was surprising in view of the common assumption that, the condition being of lymphatic origin, the oedema protein concentration should be raised.
3. The ratio of aspirate protein concentration to serum protein concentration showed a weak but highly significant negative correlation with the percentage increase in arm volume (r = −0.47, n = 35, P &lt;0.005), again in contrast to conventional expectation. The demonstration of a reduced protein concentration in the swollen arm did not therefore depend solely on a comparison with the wick control results. The volume increased by on average 33% and the ratio of aspirate protein concentration to serum protein concentration averaged 0.52 + 0.11 on the swollen side and 0.64 + 0.13 on the unaffected side.
4. Serum protein concentration in the patients with arm swelling (61.2 + 4.9 g/l) was significantly lower than that in postmastectomy patients without this complication (65.0 + 6.2 g/l). Most of the decrease occurred in the albumin fraction (oedema patients, 383 + 5.1 g/l; control patients, 42.0 + 2.1 g/l). In oedema patients receiving the anti-oestrogen tamoxifen serum albumin concentration was on average 23 g/l lower than in oedema patients not under medication (P &lt;0.05, t-test).
5. Glycosaminoglycan concentration in oedema fluid was 0.8 +0.14 g/l (n = 21) and 75% was sulphated. Along with the plasma protein this raised the relative viscosity of the fluid to 1.34 + 0.16 (n = 11).
6. The reduction in interstitial protein concentration in the swollen arm, contrary to expectation in lymph-oedema, could be explained in several ways. One possible hypothesis in light of reported haemodynamic abnormalities in such arms is that capillary pressure rises, increasing capillary filtration rate. We conclude that the pathophysiology of postmastectomy oedema involves additional factors besides axillary node trauma, and we suggest that input (filtration) as well as output (lymph flow) requires evaluation.
Interactions of Hydrogen Peroxide with Interleukin-6 and Platelet-Derived Growth Factor in Determining Mesangial Cell Growth: Effect of Repeated Oxidant Stress
Authors: D'Souza R. J. , Phillips H. M. , Jones P. W. , Strange R. C. , Aber G. M. 
Published: August 2015

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10−8-10−4 mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts.
2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10−6 mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P &lt;0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, −6.7)% (P &lt;0.05) and 53.5 (107, 21.9)% (P &lt;0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10−6 mol/l H2O2 [49.9 (77.7, 12.3)%] (P &lt;0.01), whereas the addition of 10−6 mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P &lt;0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 103)% (P &lt;0.05).
3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.
Viral Infection of Bovine Bronchial Epithelial Cells Induces Increased Neutrophil Chemotactic Activity and Neutrophil Adhesion
Authors: Raz Meir , Robbins Richard A. , Kelling Clayton L. , Stine Lisa C. , Leikauf George D. , Rennard Stephen I. , Spurzem John R. 
Published: August 2015

1. Acute bronchitis secondary to viral infection is associated with an influx of neutrophils. We hypothesized that bronchial epithelial cells are capable of releasing neutrophil chemotactic activity in response to viral infection.
2. To test this hypothesis, primary cultures of bovine bronchial epithelial cells were inoculated with a bovine respiratory pathogen, bovine herpes virus-1.
3. Supernatants collected from inoculated cells, before signs of toxicity, demonstrated significant neutrophil chemotactic activity using a blind well chamber neutrophil chemotaxis assay. Lipoxygenase inhibitors markedly reduced the amount of neutrophil chemotactic activity released after bovine herpes virus-1 inoculation. Analysis of arachidonic acid metabolites in cell supernatants by reverse-phase h.p.l.c. confirmed that leukotriene B4, a potent neutrophil chemoattractant, was released.
4. We also confirmed that adhesion of neutrophils to bovine herpes virus-1-inoculated bronchial epithelial cells was increased and mediated in part by the neutrophil integrin, LFA-1.
5. Thus, virally infected airway epithelial cells release leucocyte chemoattractants and hence adhesive interactions, functions that are likely to be important in the inflammatory acute response to viral infection.