bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in renal degradation of albumin in early experimental diabetes in the rat: a new factor in the mechanism of albuminuria
Authors: BURNE Melissa J. , PANAGIOTOPOULOS Sianna , JERUMS George , COMPER Wayne D. 
Published: August 2015

1.Albumin is normally excreted as a mixture of intact protein and fragments that are produced during renal passage. The purpose of this study was to investigate the ratio of intact versus degraded forms of excreted albumin to ascertain whether changes in this ratio could account for the apparent increase in albumin excretion seen in diabetes, as measured by standard radioimmunoassay techniques.
2.Four-week male Sprague–Dawley rats with streptozotocin-induced diabetes and age-matched control rats were intravenously injected with [3H]albumin. Urine collected over 2 h was analysed by size exclusion chromatography and radioimmunoassay. A standard radioimmunoassay found a 7-fold increase in albumin excretion rate in diabetic rats, whereas there was only a 2-fold increase in albumin excretion (intact plus fragments). Urine analysed by size exclusion chromatography showed severe degradation for control rats (% monomer = 4±2%); in diabetic rats there was a significant amount of monomer albumin excreted, along with moderately degraded and heavily degraded albumin (% monomer = 17±5%).
3.This study has shown that the radioimmunoassay, which specifically detects intact albumin, considerably underestimates the amount of total urinary albumin which consists of intact and degraded material. The increase in albumin excretion rate observed in diabetes as measured by radioimmunoassay is mainly due to a change in the amount of intact albumin excreted and this is specifically due to the inhibition of albumin degradation at a post-glomerular site and not due to the onset of any type of glomerular ‘shunt' pathway.
A novel method for the visualization of the in situ mucus layer in rat and man
Authors: JORDAN NICOLA , NEWTON JULIA , PEARSON JEFFREY , ALLEN ADRIAN 
Published: August 2015

1.The observed thickness of the gastric mucus barrier varies widely, even appearing discontinuous, depending on the methods used. Here we describe the development and application of a modified periodic acid Schiff/Alcian Blue staining technique for use on cryostat sections of gastric mucosa. This technique for the first time enables the preservation and visualization of the full thickness of the adherent gastric mucus layer and the underlying mucosa.
2.In designing this novel method we have selected those procedures which would result in the least alteration to the mucus layer. The methods used were snap freezing, cryostat sectioning of the whole stomach followed by brief ethanol pretreatment (10 min in 100% ethanol), a prolonged staining with periodic acid Schiff/Alcian Blue (15 min and 2.5 h respectively), a gentle post-fixation (45 min paraformaldehyde vapour at 37 °C) and the use of a water-soluble mountant.
3.A continuous, adherent mucus layer was observed over the surface of the rat gastric mucosa (periodic acid Schiff/Alcian Blue stained) and human gastric antral biopsies (periodic acid Schiff stained). In the rat the mean (S.D.) mucus thickness measurements along the antrum to oesophageal axis (which was divided histologically into four regions, A to D) were: A, 166 (47) μm; B, 179 (48) μm; C, 184 (50) μm; D (the non-glandular stratified epithelium at the top of the stomach), Absent. In human gastric antral biopsies the mean (S.D.) mucus thickness was 144 (52) μm.
4.This new technique has enabled the visualization and precise measurement of thickness of the gastric mucus layer in rat and man. The adherent gastric mucus layer was observed to be continuous in the rat glandular stomach and human antrum. In validation experiments in rat the mean mucus thickness measurements were found to be twice those measured by conventional histological techniques, in which the mucus layer appeared discontinuous and patchy. However, they were within the range of thickness values seen in unfixed tissues and in the rat in vivo preparation.
In utero programming of chronic disease
Authors: BARKER D. J. P. 
Published: August 2015

1.Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism.
2.These ‘programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension.
3.This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
Activation of myocardial and renal natriuretic peptides during acute intravascular volume overload in dogs: functional cardiorenal responses to receptor antagonism
Authors: BORGESON Daniel D. , STEVENS Tracy L. , HEUBLEIN Denise M. , MATSUDA Yuzuru , BURNETT John C. 
Published: August 2015

1.A family of structurally related but genetically distinct natriuretic peptides exist which include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of myocardial cell origin and C-type natriuretic peptide (CNP) of endothelial and renal epithelial cell origin. All three exert actions via cGMP, with ANP and BNP functioning via the natriuretic peptide A receptor and CNP via the natriuretic peptide B receptor.
2.Circulating and urinary natriuretic peptides were determined in response to acute intravascular volume overload (AVO). Additionally, their functional role in cardiorenal regulation during AVO was investigated by utilizing the natriuretic peptide receptor antagonist HS-142-1. Control (n = 5) and study dogs (HS-142-1, n = 9) underwent AVO with normal saline equal to 10% of body weight over 1 ;h. Both groups demonstrated similar significant increases in right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac output. Circulating ANP paralleled increases in right atrial pressure and pulmonary capillary wedge pressure, with no changes in plasma BNP or CNP. At peak AVO, urinary CNP excretion was increased compared with baseline (7.0±4.2 versus 62±8.0 ;pg/min, P< 0.05).
3.In the HS-142-1-treated group, plasma cGMP was decreased compared with the control group (9.6±1.1 to 5.0±1.2 ;pmol/ml, P< 0.05). A significant attenuation of natriuresis (566±91 versus 1241±198 ;μEq/min, P< 0.05) and diuresis (4.8±0.7 versus 10.1±2.0 ;ml/min, P< 0.05) was also observed at peak AVO in the HS-142-1 treated group.
4.These findings support differential and selective responses of the three natriuretic peptides to AVO, in which plasma ANP and urinary CNP are markers for AVO. Secondly, these studies confirm the role of ANP and CNP but not BNP in the natriuretic and diuretic response to acute volume overload.
Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics
Authors: NESTEL Paul J. , YAMASHITA Takeshi , SASAHARA Takayuki , CHIN-DUSTING Jaye P. F. , ESLER Murray D. , DART Anthony M. , JENNINGS Garry L. 
Published: August 2015

1.Obesity influences the responsiveness of the microcirculation; constriction is augmented probably reflecting heightened sympathetic nervous activity.
2.The responsiveness of the microcirculation in the forearm to constriction and dilation was therefore examined in 14 men and women with varying degrees of abdominal adiposity, to determine the potential effects of sympathetic nervous activity and adiposity on flow. Changes in basal blood flow were measured by venous occlusion plethysmography during intra-arterial infusions of noradrenaline, acetylcholine and sodium nitroprusside and after temporary ischaemia. Total body noradrenaline spillover was also measured, as an index of sympathetic neuronal activity.
3.Parameters of obesity were found to influence the responsiveness of the microcirculation. Changes in vascular resistance with noradrenaline (100 ;ng/min) were positively correlated with body weight, body mass index and waist circumference (r = 0.63, P = 0.02), whereas waist circumference was negatively correlated with post-ischaemia vasodilatation (r = -0.76, P = 0.002). Acetylcholine-induced vasodilatation was inversely related to body mass index (r = -0.53, P = 0.053).
4.Basal blood flow did not correlate with adiposity. Furthermore, vasodilatation with 800 ;ng/min sodium nitroprusside was inversely correlated with total body noradrenaline spillover (r = -0.77, P< 0.001); and changes in flows with noradrenaline (constriction) and post-ischaemia (dilation) were inversely related (r = -0.56, P = 0.035).
5.These findings, taken together, are consistent with increased local sympathetic neuronal responsiveness and diminished nitric-oxide-mediated dilation in the forearm vasculature with increasing body adiposity.
Prolonged stability of brain natriuretic peptide: importance for non-invasive assessment of cardiac function in clinical practice
Authors: BUCKLEY Martin G. , MARCUS Neil J. , YACOUB Magdi H. , Donald R. J. 
Published: August 2015

1.BNP and ANP are important research indices of severity of heart failure. However, uncertainty regarding the stability of these peptides at room temperature has limited their use to assess cardiac function in routine clinical practice.
2.We assessed the stability of BNP and ANP in blood samples left for 2 ;h or 2 days at room temperature compared with levels in blood processed immediately (initial). These times were chosen to reflect possible times for samples to be processed in a hospital outpatient clinic (2 ;h) or a blood sample posted to a laboratory from general practice (2 days). Samples were obtained from eight heart transplant recipients. Blood was separated and plasma stored immediately after collection (initial) and after 2 ;h or 2 days at room temperature respectively.
3.Initial plasma BNP and ANP values measured by radioimmunoassay after Sep-Pak extraction were 38.9±11.1(S.E.M.) pg/ml and 113.6±28.1 ;pg/ml, respectively. After 2 ;h at room temperature there was no significant fall in either peptide level (35.5±9.9 ;pg/ml, BNP; 104.9±30.6 ;pg/ml, ANP). However, after 2 days at room temperature there was a significant fall in ANP to 38.1±12.6 ;pg/ml (P< 0.005 versus initial level). In contrast, there was no significant fall in BNP after 2 days (32.0±8.4 ;pg/ml). After 2 days at room temperature only 30.4±4.3% of the ANP remained, but 86.0±5.0% of BNP compared with the initial ANP and BNP measurements.
4.Our study clearly showed that ANP is stable for 2 ;h and thus could be useful as a screening test for heart disease in hospital. In contrast, BNP remained stable for 2 days. Measuring BNP may thus be practical as a test of heart function both for routine use in hospital and by general practitioners in the community.
Factors determining cardiac hypertrophy in hypertensive patients with or without peripheral vascular disease
Authors: BRAHIMI M. , LEVY B. I. , SAFAR M. E. , DABIRÉ H. 
Published: August 2015

1.Coronary ischaemic disease and congestive heart failure are the principal causes of mortality in patients with peripheral vascular disease. Whether cardiac hypertrophy is present and even more pronounced in peripheral vascular disease than in other populations has never been explored.
2.Twenty-five hypertensive patients were investigated, 11 without and 14 with peripheral vascular disease, matched for age, sex, mean arterial pressure and antihypertensive drug treatment. Cardiac mass was determined using echocardiography together with measurement of systemic blood pressure, ratio between ankle systolic pressure (ASP) and brachial systolic pressure (BSP), and standard biochemical parameters including natriuresis per 24 ;h.
3.At the same mean arterial pressure, patients with peripheral vascular disease had a significantly higher cardiac mass (157±12 versus 116±6 ;g/m2; P< 0.01), pulse pressure (81±5 versus 55±4 ;mmHg; P< 0.01) and natriuresis (180±17 versus 144±6 ;mmol/24 h; P< 0.01) than controls. Using univariate correlations, cardiac mass was positively associated with pulse pressure, mean arterial pressure and natriuresis, and negatively with the ASP/BSP ratio. On the basis of multivariate regression analysis, only natriuresis was positively correlated to cardiac mass.
4.Patients with peripheral vascular disease develop a higher degree of cardiac hypertrophy in comparison with hypertensive subjects with the same level of mean arterial pressure. Sodium intake rather than mechanical factors seems to be the major modulating factor which influences the degree of cardiac hypertrophy.
Human cardiovascular variability, baroreflex and hormonal adaptations to a blood donation
Authors: FORTRAT Jacques-Olivier , NASR Olivier , DUVAREILLE Monique , GHARIB Claude 
Published: August 2015

1.We studied cardiovascular variability, baroreflex and blood volume regulating hormones to determine the relative roles of autonomic regulation and hormones during blood donation.
2.The sympathetic response was studied by measuring the R–R interval and systolic blood pressure variability using coarse graining spectral analysis in eight blood donors. Beat-by-beat R–R intervals and blood pressure were recorded for 20 ;min before and 5 ;min after a whole-blood donation of 480±10 ;ml (about 7 ;ml/kg of blood volume, over 4 ;min). Plasma catecholamines, vasopressin, atrial natriuretic peptide, endothelin, active renin, osmolality, Na+, K+, haemoglobin and haematocrit were measured just before and after blood withdrawal.
3.Blood donation led to increases in the plasma catecholamines (adrenaline, 21±2 versus 35±3 ;pg/ml; noradrenaline, 229±26 versus 323±37 ;pg/ml; dopamine, 34±3 versus 66±9 ;pg/ml) and in systolic blood pressure (130±6 versus 140±5 ;mmHg). These changes were independent of ionic or slow endocrine mechanisms. Heart rate, cardiovascular variability and the spontaneous baroreflex sensitivity did not change despite the increase in blood pressure and catecholamines. Thus the peripheral vascular control was probably involved.
4.We conclude that the absence of any change in heart rate usually observed during non-hypotensive hypovolaemic stress is probably due to the sympathetic activation being counterbalanced by the high supine vagal tone at the heart and not to the heterogeneous nature of the sympathetic neural response or to changes in sympathetic and parasympathetic activity without any change in autonomic balance.
Fractal dimension and approximate entropy of heart period and heart rate: awake versus sleep differences and methodological issues
Authors: YERAGANI Vikram K. , SOBOLEWSKI E. , JAMPALA V. C. , KAY Jerald , YERAGANI Suneetha , IGEL Gina 
Published: August 2015

1.Investigations that assess cardiac autonomic function include non-linear techniques such as fractal dimension and approximate entropy in addition to the common time and frequency domain measures of both heart period and heart rate. This article evaluates the differences in using heart rate versus heart period to estimate fractal dimensions and approximate entropies of these time series.
2.Twenty-four-hour ECG was recorded in 23 normal subjects using Holter records. Time series of heart rate and heart period were analysed using fractal dimensions, approximate entropies and spectral analysis for the quantification of absolute and relative heart period variability in bands of ultra low (< 0.0033 ;Hz), very low (0.0033–0.04 ;Hz), low (0.04–0.15 ;Hz) and high (0.15–0.5 ;Hz) frequency.
3.Linear detrending of the time series did not significantly change the fractal dimension or approximate entropy values. We found significant differences in the analyses using heart rate versus heart period between waking up and sleep conditions for fractal dimensions, approximate entropies and absolute spectral powers, especially for the power in the band of 0.0033–0.5 ;Hz. Log transformation of the data revealed identical fractal dimension values for both heart rate and heart period. Mean heart period correlated significantly better with fractal dimensions and approximate entropies of heart period than did corresponding heart rate measures.
4.Studies using heart period measures should take the effect of mean heart period into account even for the analyses of fractal dimension and approximate entropy. As the sleep–awake differences in fractal dimensions and approximate entropies are different between heart rate and heart period, the results should be interpreted accordingly.
Glycoxidation, and protein and DNA oxidation in patients with diabetes mellitus
Authors: KRAPFENBAUER K. , BIRNBACHER R. , VIERHAPPER H. , HERKNER K. , KAMPEL D. , LUBEC G. 
Published: August 2015

1.The role of oxidative stress in the pathogenesis of the diabetic state is being investigated extensively. Although oxidative stress has been reported in terms of glycoxidation, protein oxidation and DNA oxidation in diabetes mellitus, oxidation parameters have not been determined in parallel on the same study population.
2.We studied 24 patients with diabetes mellitus (14 patients with Type I diabetes with a mean age of 62.3±6.3 years and 10 patients with Type II diabetes aged 67.3±5.9 years) and compared them with age-matched non-diabetic controls. Urinary o-tyrosine, 8-hydroxy-2′-deoxyguanosine and pentosidine measurements by HPLC were made on two occasions (t1 and t2).
3.A clear statistical difference was found between diabetic patients and controls at t1 or t2 for 8-hydroxy-2′-deoxyguanosine and pentosidine, but not for o-tyrosine. No significant correlations were found between clinical and other laboratory parameters except high-density lipoprotein and uric acid. We revealed significantly increased glycoxidation and DNA oxidation in patients with Type I and Type II diabetes, but protein oxidation was not different from controls.
4.The finding of increased glycoxidation reflects increased oxidation of the carbohydrate moiety, whereas the increased levels of oxidized DNA may also be interpreted as due to increased DNA repair. The increased 8-hydroxy-2′-deoxyguanosine does not indicate the generation of an individual active oxygen species, but DNA could have been oxidized simply by alkenals from lipid peroxidation, as e.g. malondialdehyde. As no difference in protein oxidation (i.e. o-tyrosine) between diabetics and controls could be revealed, the oxidation of DNA by hydroxyl radical attack is unlikely, as o-tyrosine was proposed as a marker for hydroxyl radical attack. Therefore, the message is that increased glycoxidation can be confirmed, protein oxidation does not appear to take place and increased DNA oxidation is still not proven, as increased 8-hydroxy-2′-deoxyguanosine may simply reflect repair.
Protective agents used as additives in University of Wisconsin solution to promote protection against ischaemia–reperfusion injury in rat lung
Authors: CHIANG Chi-Huei , WU Kerry , YU Cheng-Ping , PERNG Wann-Cherng , YAN Horng-Chin , WU Chin-Pyng , CHANG Deh-Ming , HSU Kang 
Published: August 2015

1.An intervention to reduce ischaemia–reperfusion lung injury will be an important advance in transplant medicine. Although the mechanisms associated with producing ischaemia–reperfusion endothelial injury have not been completely elucidated, many of the injury mediators have been studied in detail. While no single pharmacological therapy is likely to be totally effective in eliminating this complex injury, we have developed a mixture of agents that are known to block pathways involved in producing ischaemia–reperfusion-associated lung vascular injury.
2.The present study modified University of Wisconsin solution (UW) by adding one of the protective agents prostaglandin E1 (PGE1), dexamethasone (Dex) or dibutyryl cAMP (Bt2-cAMP), or a combination of these, to the perfusate of rat lungs exposed to 4 ;h of cold ischaemia followed by 1 ;h of reperfusion. Nine modified UW solutions were studied: (1) UW+Dex, (2) UW+PGE1, (3) UW+Bt2-cAMP, (4) UW+Dex×3, (5) UW+PGE1×3, (6) UW+Bt2-cAMP×3, (7) UW+Dex+PGE1, (8) UW+Dex+Bt2-cAMP, (9) UW+PGE1+Bt2-cAMP. These solutions were utilized in individual experiments to assess haemodynamic changes, lung weight gain, the capillary filtration coefficient (Kfc) and pathology in all lungs.
3.The results indicate that lung weight gain and Kfc values were significantly lower than with UW alone in groups 1, 2 and 3, which contained only one additional protective agent. In groups 4, 5 and 6, which contain three times the concentration of each protective agent, both Kfc and lung weight gain were similar to those measured in groups 1, 2 and 3, i.e. lungs were protected but the protection was not dose dependent. In groups 7, 8 and 9, which contained two protective agents, lung weight gain and Kfc were greatly reduced compared with UW alone. Histopathological studies showed similar decreases in the injury profiles of lungs.
4.Although UW contains several antioxidant protective agents such as allopurinol and glutathione, it did not provide effective protection in our ischaemia–reperfusion lung injury model. UW modified with an additive of PGE1, Dex or Bt2-cAMP attenuated ischaemia–reperfusion injury. Furthermore, UW containing two of these protective agents augmented the protection. Among the modified solutions, it appears that UW+PGE1+Bt2-cAMP protects the lungs to a greater extent than all other solutions used in our study. We suggest that preservation solutions containing PGE1-Bt2-cAMP will provide additional protective effects to organs stored for transplantation.
Studies in vivo of ω-gliadins in gluten sensitivity (coeliac sprue disease)
Authors: ENSARI Arzu , MARSH Michael N. , MORIARTY Kieran J. , MOORE Carol. M. , FIDO Roger J. , TATHAM Arthur S. 
Published: August 2015

1.Highly purified ω-gliadins from wheat were used to challenge gluten-sensitized individuals. Characteristic responses by mucosal CD3+ and γδ+ lymphocytes were demonstrated. Each lymphocyte subset showed an increase within 8–12 ;h post-challenge, indicating a specific response by the rectal mucosa to this gliadin species.
2.Available sequence data for the ω-gliadins and homologous proteins from barley and rye indicate a common repeating octapeptide motif (consensus PQQPFPQQ). The results indicate, therefore, that the octapeptide repeat, or a contained sequence such as PQQP, plays an important role in the mucosal immunopathology of gluten sensitivity.
Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion
Authors: QUINLAN Gregory J. , MARGARSON Michael P. , MUMBY Sharon , EVANS Timothy W. , GUTTERIDGE John M. C. 
Published: August 2015

1.Albumin is often administered intravenously to critically ill patients as a volume expander, to combat hypoalbuminaemia, and to decrease hyperbilirubinaemia. There is, however, an ongoing debate concerning the therapeutic benefit of the former which is an expensive form of treatment.
2.Albumin has several biological functions, in particular as a ligand binder. It also acts as an extracellular transition metal ion-binding and radical-scavenging antioxidant. These functions are influenced by the presence of an exposed thiol group (cys 34) on the surface of the albumin molecule.
3.The ability of infused albumin to influence the plasma thiol pool, and hence antioxidant potential, was investigated in patients with sepsis syndrome.
4.Plasma thiol levels rose rapidly after albumin infusion and remained elevated even after plasma albumin levels had declined significantly, due to interstitial leakage. Data are suggestive of some form of thiol exchange in the plasma of these patients between albumin and molecules containing oxidized thiol groups.
5.Administration of albumin to patients with sepsis syndrome leads to a sustained increase in plasma thiols. Thiols have several important antioxidant functions, and thiol repletion in these patients, who are known to suffer from oxidative stress, may have beneficial antioxidant effects. Antioxidant repletion may represent an important facet of clinically administered albumin.