bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximal Renal Tubular Peptide Catabolism, Ammonia Excretion and Tubular Injury in Patients with Proteinuria: Before and after Lisinopril
Authors: Rustom Rana , Grime J. Steve , Costigan Michael , Maltby Paul , Hughes Anthony , Shenkin Alan , Critchley Mair , Bone J. Michael 
Published: August 2015

1. Progression to renal failure may be linked to the degree of proteinuria through tubulo-interstitial mechanisms. However, there are no data in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril. We developed a method to allow such studies, and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretion.
2. In this study, 10 patients with mild renal impairment (51Cr-EDTA clearance 63.7 ± 8.3 ml · min−1 · 1.73 m−2) and heavy proteinuria (8.2 ± 2.3 g/24 h) were given lisinopril (10–20 mg) for 6 weeks. Renal tubular catabolism of intravenous aprotinin was measured before and after lisinopril by renal imaging and urinary excretion of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Fresh timed urine collections were also analysed for ammonia excretion every fortnight from 6 weeks before treatment. Total urinary N-acetyl-β-d-glucosaminidase and the more tubulo-specific N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme were also measured.
3. After lisinopril proteinuria fell significantly as expected (from 9.5 ± 1.6 to 4.5 ± 1.0 g/24 h, P &lt; 0.01). This was associated with a reduction in metabolism over 26 h (from 1.7 ± 0.1 to 1.2 ± 0.1% dose/h, P &lt; 0.01) and in fractional degradation of aprotinin (from 0.08 ± 0.02 to 0.04 ± 0.007/h, P &lt; 0.04). Ammonia excretion also fell significantly (from 1.2 ± 0.1 to 0.6 ± 0.1 mmol/h, P &lt; 0.0001), as did both total urinary N-acetyl-β-d-glucosaminidase (P &lt; 0.0001) and the N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme (P &lt; 0.015). These observations after lisinopril treatment have not been described previously. There was no significant change in blood pressure nor in glomerular haemodynamics.
Genetics of Inflammatory Bowel Disease
Authors: Satsangi Jack , Parkes Miles , Jewell Derek P. , Bell John I. 
Published: August 2015

1. The aetiology of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided little insight into disease pathogenesis.
2. Concordance rates in twin pairs and siblings provide strong evidence that genetic factors are important in disease pathogenesis. In Oxford, information was obtained from 433 adult patients with Crohn's disease. Compared with the prevalence in the general population, the relative risks in siblings of patients with Crohn's disease calculated from these data were respectively 36.5 for Crohn's disease, 16.6 for ulcerative colitis and 24.7 for inflammatory bowel disease.
3. Clinical patterns of disease were compared in members of over 250 multiply affected families with inflammatory bowel disease. A high degree of concordance for many characteristics was noted (disease type, extent, extra-intestinal manifestations). However, in 77 affected parent—child pairs, the median age of onset in the parents was significantly higher than in offspring (P &lt; 0.0001). These data reflect the results from other studies throughout the world, and are consistent with the phenomenon of genetic anticipation.
4. A detailed study investigating the contribution of the major histocompatibility complex was undertaken. Eighty-three affected sibling pairs were involved in a linkage analysis study; 348 patients with inflammatory bowel disease and 472 controls were involved in a detailed allelic association study. These data provide evidence that the major histocompatibility complex is an important determinant in ulcerative colitis, but not in Crohn's disease.
5. Cytokine genes are important candidate genes in inflammatory bowel disease. Allelic association study was performed to investigate the contribution of the gene encoding the interleukin-1 receptor antagonist and tumour necrosis factor-α. These data do not suggest that these genes encode important determinants of disease susceptibility in inflammatory bowel disease.
6. A two-stage genome-wide search for susceptibility loci in inflammatory bowel disease was performed involving 186 affected sibling pairs. The data provide strong evidence for the model of Crohn's disease and ulcerative colitis as related polygenic disorders. Loci on chromosomes 3, 7 and 12 were linked to inflammatory bowel disease overall, whereas loci on chromosomes 2 and 6 were linked only in ulcerative colitis. Linkage with chromosome 16 was noted in Crohn's disease only. Fine mapping of these susceptibility loci is in progress, and may lead to gene identification with attendant clinical benefits.
Elevated Heart Rate Variability in Physically Active Young and Older Adult Women
Authors: Davy Kevin P. , Desouza Christopher A. , Jones Pamela P. , Seals Douglas R. 
Published: August 2015

1. Low heart rate variability is associated with an increased risk of cardiac sudden death, coronary heart disease and all-cause mortality. We have previously shown that physically active postmenopausal women demonstrate higher levels of heart rate variability and cardiac baroreflex sensitivity compared to their sedentary peers. The purpose of the present prospective study was to test the hypothesis that heart rate variability and cardiac baroreflex sensitivity would be reduced with age in sedentary but not physically active women. To accomplish this, we measured heart rate variability (both time and frequency domain) and spontaneous cardiac baroreflex sensitivity (SBRS, sequence method) in the sitting posture in 23 sedentary women [11 premenopausal and 12 postmenopausal (age, 28 ± 1 and 61 ± 2 years; Vo2max, 35.3 ± 1.4 and 21.7 ± 1.5 ml · min−1 · kg−1 respectively] and in 22 physically active women [12 premenopausal and 10 postmenopausal (age, 31 ± 1 and 59 ± 2 years; Vo2max, 52.5 ± 1.4 and 39.7 ± 1.8 ml · min−1 · kg−1)].
2. The S.D. of the R—R interval (time domain) was reduced (P &lt; 0.05) with age in both sedentary (52 ± 6 versus 33 ± 4 ms) and physically active women (72 ± 8 versus 49 ± 9 ms). The high-frequency power (3740 ± 1527 versus 915 ± 188 and 9516 ± 2849 versus 2803 ± 1083 ms2/Hz), total power of heart rate variability and SBRS (11 ± 2 versus 7 ± 2 and 19 ± 3 versus 13 ± 2 ms/mmHg) also demonstrated similar age-related reductions in sedentary and physically active women, respectively (all P &lt; 0.05). The S.D. of the R—R interval, high-frequency and total power of heart rate variability, and SBRS were higher (all P &lt; 0.05) in the physically active compared with the sedentary women at any age. There was no significant influence of age or physical activity status on the low-frequency power of heart rate variability. In addition, no significant differences in any of the time or frequency domain measures of heart rate variability or SBRS were observed in users compared with non-users of hormone replacement therapy.
3. The results of the present study suggest that heart rate variability and cardiac baroreflex sensitivity decline similarly with age in healthy sedentary and physically active women. However, physically active women demonstrate higher levels of heart rate variability and cardiac baroreflex sensitivity compared with their sedentary peers, regardless of age.
Increased Plasma Adrenomedullin Concentrations during Cardiac Surgery
Authors: Nishikimi Toshio , Hayashi Yukio , Iribu Gentaro , Takishita Shuichi , Kosakai Yoshio , Minamino Naoto , Miyata Atsuro , Matsuo Hisayuki , Kuro Masakazu , Kangawa Kenji 
Published: August 2015

1. Adrenomedullin (AM), a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Plasma AM concentrations are elevated in hypertension, heart failure and renal failure in proportion to the severity of the disease. This study was performed to investigate the pathophysiological significance of AM during cardiac surgery.
2. Serial blood samples were obtained from patients undergoing cardiac surgery and plasma AM concentrations were determined by specific radioimmunoassay.
3. Plasma AM concentrations did not increase with anaesthesia or surgery (n = 9). Plasma AM concentrations gradually increased during cardiopulmonary bypass and after pulmonary reperfusion. After pulmonary reperfusion, plasma AM concentrations increased further. In addition, we measured plasma AM concentrations in the pulmonary vein (n = 8) and coronary sinus (n = 8) to examine the contribution of the lungs and heart to the increase in circulating AM concentrations after cardiopulmonary bypass. However, no significant differences were seen in plasma AM concentrations of the pulmonary vein or the coronary sinus and the aorta. Peak AM concentrations during cardiac surgery correlated with duration of surgery. Elevated plasma AM levels during and after surgery began to decline next day after surgery and returned to normal levels 7 days after surgery.
4. These results demonstrate that plasma AM concentrations increase during cardiac surgery and that the duration of surgery may be related to the changes in AM concentrations. Taken together with recent findings that vascular endothelial cells and vascular smooth muscle cells actively produce AM, these results suggest that plasma AM during cardiac surgery may act as a vasodilatory hormone.
Serum Leptin Level: Possible Association with Haematopoiesis in Adolescents, Independent of Body Mass Index and Serum Insulin
Authors: Hirose Hiroshi , Saito Ikuo , Kawai Toshihide , Nakamura Keiko , Maruyama Hiroshi , Saruta Takao 
Published: August 2015

1. The obese gene product leptin, secreted exclusively from adipocytes, was discovered to serve as a satiety factor and to play an important role in regulating body weight. In adults, the serum leptin level reportedly increases with the degree of obesity. Leptin receptors are expressed in various tissues, and recent in vitro studies suggest a role for leptin in haematopoiesis.
2. The present study was designed to clarify the relationship between serum leptin and body mass index, peripheral blood cell counts, serum cholesterol, high-density lipoprotein-cholesterol, insulin and Cortisol levels in 299 Japanese male adolescents aged 15–16 years.
3. With simple linear correlation, log [serum leptin] showed a strong correlation with body mass index (r = 0.56), log [insulin] (r = 0.36) and leucocyte count (r = 0.22) (P &lt; 0.001 for all). There were also correlations with systolic blood pressure, erythrocyte count, haematocrit and high-density lipoprotein-cholesterol (P &lt; 0.01 for all). Even after adjustment for body mass index and log [insulin], log [leptin] correlated with leucocyte (P = 0.004) and erythrocyte (P = 0.057) counts. Stepwise multiple regression analyses revealed log [leptin] to correlate significantly with body mass index, log [insulin] and the leucocyte count (P &lt; 0.005 for all, r2 = 0.399).
4. To our knowledge, this is the first clinical study to show the possible association of serum leptin level with blood cell counts, independent of body mass index and serum insulin. We conclude that these data further support a role for leptin in haematopoiesis.
Bronchial reactivity and intracellular magnesium: a possible mechanism for the bronchodilating effects of magnesium in asthma
Authors: DOMINGUEZ Ligia J. , BARBAGALLO Mario , LORENZO Gabriele Di , DRAGO Agata , SCOLA Santi , MORICI Giuseppina , CARUSO Calogero 
Published: August 2015

1.Increased bronchial smooth muscle contractility with consequent bronchial hyperreactivity are characteristic physiopathological events of asthma. Since magnesium intervenes in calcium transport mechanisms and intracellular phosphorylation reactions, it constitutes an important determinant of the contraction/relaxation state of bronchial smooth muscle. In the present study we investigated the relationship between bronchial reactivity, assessed by methacholine-provocation test, and magnesium concentrations both at extracellular and intracellular levels measured by spectrophotometry. Twenty-two patients with mild-to-moderate asthma and 38 non-asthmatic subjects with allergic rhinitis (24 allergic to Parietaria pollen and 14 allergic to Grasspollen) were recruited to the study. Exclusion criteria included renal failure, hepatic diseases, heart failure and arterial hypertension.
2.The salient finding of our study is that there is a strong positive correlation between bronchial reactivity and the level of intracellular magnesium (r = 0.72, P< 0.0001), both when the groups are analysed separately or together. Intracellular magnesium concentrations in the group of patients with asthma were significantly lower (1.8±0.01 mmol/l; n = 22) when compared with levels in rhinitis subjects allergic to Parietaria(1.9±0.01 mmol/l; n = 24, P< 0.05), and with levels in rhinitis subjects allergic to Grass pollen (2.0±0.03;mmol/l; n = 14, P< 0.05). Serum levels of the ion were similar in all groups.
3.We conclude that the level of intracellular magnesium may be an important determinant of bronchial hyperreactivity, as supported by the significant positive correlation between these two parameters in allergic patients with known bronchial hyperresponsiveness. This finding, in addition to reports of the bronchodilating effects of magnesium administration in patients with asthma, confirms the proposed role of this ion in the pathogenesis and treatment of asthma.
Respiratory correlates of muscle sympathetic nerve activity in heart failure
Authors: NAUGHTON Matthew T. , FLORAS John S. , RAHMAN M. Atiar , JAMAL Munir , BRADLEY T. Douglas 
Published: August 2015

1.Sympathetic activation in congestive heart failure indicates a poor prognosis. Haemodynamic correlates of increased sympathetic nerve traffic to muscle (MSNA) and to the heart have been well characterized, but these account for only 50 to 60% of the variance in sympathetic activity between patients.
2.In healthy subjects, breathing pattern modulates MSNA and positive airway pressure consistently increases MSNA. However, in patients with heart failure, the influence of spontaneous breathing pattern and of short-term application of nasal continuous positive airway pressure on MSNA have not been described.
3.Spontaneous breathing frequency, tidal volume, end-expiratory lung volume, Pco2 and MSNA were recorded, along with blood pressure, heart rate and stroke volume in 14 men with congestive heart failure of idiopathic or ischaemic origin (left ventricular ejection fraction < 35%). Measurements were made during baseline rest, followed by 45 ;min of either nasal continuous positive airway pressure applied at 10 ;cmH2O (n = 9), or spontaneous breathing, in the absence of nasal continuous positive airway pressure (time control; n = 6).
4.At baseline, there was a significant positive correlation between MSNA burst frequency and breathing frequency (r = 0.758, P = 0.001), and an inverse correlation between MSNA burst incidence and tidal volume (r = -0.705, P = 0.005). These relationships were independent of left ventricular ejection fraction, stroke volume or cardiac output.
5.Nasal continuous positive airway pressure increased end-expiratory lung volume, but had no effect on breathing frequency, tidal volume or MSNA.
6.In patients with congestive heart failure, there is a significant independent and previously unrecognized correlation between spontaneous breathing pattern and MSNA; patients with rapid shallow breathing exhibit the highest degree of sympathetic activation. In distinct contrast to healthy subjects, the short-term application of nasal continuous positive airway pressure at 10 ;cmH2O does not increase MSNA in congestive heart failure.
Inhibition of renal 11β-hydroxysteroid dehydrogenase in vivo by carbenoxolone in the rat and its relationship to sodium excretion
Authors: SEWELL K. J. , SHIRLEY D. G. , MICHAEL A. E. , THOMPSON A. , NORGATE D. P. , UNWIN R. J. 
Published: August 2015

1.The type 2 isoform of 11β-hydroxysteroid dehydrogenase, an enzyme which converts cortisol or corticosterone to inactive 11-ketosteroid metabolites, is thought to be responsible for preventing access of endogenous glucocorticoids to mineralocorticoid receptors in the distal nephron; although direct in vivo evidence for this is still lacking. We have examined whether graded inhibition of renal 11β-hydroxysteroid dehydrogenase activities in vivo results in corresponding changes in urinary electrolyte excretion due to exposure of mineralocorticoid receptors to circulating endogenous glucocorticoids.
2.Anaesthetized rats were infused intravenously with vehicle alone or with one of three doses of carbenoxolone: 0.06, 0.6 or 6 ;mg/h. After measurement of renal electrolyte excretion, the kidneys were snap-frozen in liquid nitrogen and 11β-hydroxysteroid dehydrogenase activities were measured directly by enzyme assay in the presence of NAD+ or NADP+.
3.A dose-dependent inhibition of renal 11β-hydroxysteroid dehydrogenase activities was observed: the low, intermediate and high doses of carbenoxolone causing approximately 50%, 80% and > 90% inhibition respectively. Only with the high dose was an effect on renal function observed (decreased fractional Na+ excretion and urinary Na+/K+ ratio).
4.The poor correlation between the extent of inhibition of renal 11β-hydroxysteroid dehydrogenase and altered urinary Na+ excretion, apparent at the lower doses of carbenoxolone, suggests either that 11β-hydroxysteroid dehydrogenase has considerable functional reserve, or that it may not be the only mechanism determining mineralocorticoid receptor specificity in the distal nephron.
Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice
Authors: BUCKLEY Martin G. , MARCUS Neil J. , YACOUB Magdi H. 
Published: August 2015

Brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and N-terminal ANP are good research indices of the severity of heart failure. The stability of these peptides at room temperature has become an important factor in assessing their use as indicators of cardiac function in routine clinical practice. Inhibitors such as aprotinin are routinely added in the blood collection process, but may provide no benefit in sample collection and routine clinical practice. We assessed the stability of BNP, ANP and N-terminal ANP in blood samples collected in either the presence or the absence of the protease inhibitor aprotinin. Blood, either with or without aprotinin, was processed immediately (initial; 0 h) and after blood samples had been left for 3 h, 2 days or 3 days at room temperature. These times were chosen to reflect processing in a hospital outpatient clinic (2–3 h), or when posted from general practice (2–3 days). Initial plasma BNP, ANP and N-terminal ANP levels in the absence of aprotinin were 28.2±5.4, 44.2±7.9 and 1997±608 pg/ml respectively, and were not significantly different from initial values in the presence of aprotinin (29.0±5.9, 45.2±8.0 and 2009±579 pg/ml respectively). After 3 h at room temperature, there was a significant fall in ANP in the absence of aprotinin (36.7±7.9 pg/ml; P< 0.005), but not in the presence of aprotinin (41.2±7.6 pg/ml). Both BNP and N-terminal ANP were unchanged in either the absence (BNP, 27.6±5.5 pg/ml; N-terminal ANP, 2099±613 pg/ml) or the presence (BNP, 29.4±5.6 pg/ml; N-terminal ANP, 1988±600 pg/ml) of aprotinin. After 2 days at room temperature, ANP had fallen significantly in both the absence (16.9±3.4 pg/ml) and the presence (24.0±5.0 pg/ml) of aprotinin compared with initial values, and there was a significant difference in ANP levels in the absence and presence of aprotinin (P< 0.001). ANP levels had decreased further after 3 days at room temperature, to 11.9±3.4 pg/ml (no aprotinin) and 20.3±5.0 pg/ml (aprotinin added); these values were significantly different (P = 0.002). In contrast, there was no change in the levels of BNP or N-terminal ANP after 2 or 3 days at room temperature, in either the absence or the presence of aprotinin. These studies indicate that aprotinin adds little benefit to the stability of cardiac peptides at room temperature. Blood samples for BNP and N-terminal ANP measurement used as a test of heart function in hospital clinics and by general practitioners in the community could be taken into blood tubes containing only EDTA as anticoagulant and without the additional step of adding the routinely used inhibitor aprotinin.
Resveratrol induces vasorelaxation of mesenteric and uterine arteries from female guinea-pigs
Authors: NADERALI Ebrahim K. , DOYLE Patrick J. , WILLIAMS Gareth 
Published: August 2015

Naturally occurring hydroxystilbenes have been shown to induce vasorelaxation. Here, we studied the mechanism of resveratrol-induced vasorelaxation in different types of blood vessels, namely mesenteric (resistance) and main uterine (conductance) arteries, from female guinea-pigs on day 7 and day 15 of the oestrous cycle. Resveratrol (5–70 µmol/l) induced concentration-dependent relaxation of both mesenteric and uterine arteries preconstricted with either noradrenaline (NA; 10 µmol/l) or KCl (125 mmol/l). Resveratrol was 2-fold more potent in inducing relaxation of mesenteric arteries than of uterine arteries. Its effects on uterine arteries from both day-7 and day-15 guinea-pigs were similar, irrespective of the constrictor used, but it was significantly (P < 0.01) more potent in inducing relaxation of mesenteric arteries contracted with NA compared with those constricted with KCl. In day-7 arteries precontracted with NA, NG-nitro-l-arginine methyl ester (l-NAME; 10 µmol/l) had no effects on the time course of resveratrol-induced vasorelaxation in either mesenteric or uterine arteries. However, indomethacin (50 µmol/l) significantly (P < 0.05) potentiated resveratrol's effect on mesenteric, but not uterine, arteries. Indomethacin had no effect on resveratrol-induced vasorelaxation of arteries contracted with KCl, whereas l-NAME significantly (P < 0.05) reduced the effects of resveratrol on uterine, but not on mesenteric, arteries. In day-15 arteries, l-NAME significantly (P < 0.01) attenuated the effects of resveratrol on mesenteric arteries contracted with NA. Indomethacin had no effect on resveratrol activity. This study indicates that: (a) the effect of resveratrol on resistance arteries is greater than that on conductance arteries; (b) the effects of resveratrol are not mediated via prostanoids, but NO may play a role; and (c) the stage of the oestrous cycle has no influence on resveratrol-induced vasorelaxation.