bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of cyclosporin A preparation and Cremophor-EL in rabbit mesenteric artery and thoracic aorta in vitro
Authors: Yaris Ersin , Tuncer Meral , Ilhan Mustafa 
Published: August 2015

1. We studied the in vitro and direct effects of intravenous cyclosporin A preparation (Sandimmun) and its solvent (Cremophor-EL) on acetylcholine-induced endothelium-dependent relaxation, phenylephrine-induced contraction and drug-induced contraction of rabbit thoracic aorta and superior mesenteric artery segments.
2. At the lower concentration (5 μg/ml), cyclosporin A preparation inhibited endothelium-dependent relaxation of the superior mesenteric artery but not of the thoracic aorta. At this concentration cyclosporin A preparation augmented phenylephrine-induced contraction in both segments but by more in the superior mesenteric artery, and induced a slow increase in the tone of isolated superior mesenteric artery and thoracic aortic rings, which was greater in magnitude in the superior mesenteric artery than in the thoracic aorta.
3. Acetylcholine-induced endothelium-dependent relaxation was inhibited by cyclosporin A preparation (50 μg/ml) in both arteries but to a greater extent in the superior mesenteric artery.
4. The solvent of the intravenous cyclosporin A preparation (Cremophor-EL) in concentrations corresponding to those of the drug caused less inhibitory effects than cyclosporin A preparation on acetylcholine-induced endothelium-dependent relaxation, had comparable effects on phenylephrine-induced contraction, and produced similar contractions of both arteries.
5. The results indicate that Cremophor-EL may contribute to the inhibitory action of cyclosporin A preparation on acetylcholine-induced endothelium-dependent relaxation in the superior mesenteric artery, but is fully responsible for the smooth-muscle-contracting effect and the potentiation of phenylephrine-induced contraction in both arteries.
Neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma
Authors: Mouri Toraichi , Sone Masahiko , Takahashi Kazuhiro , Itoi Keiichi , Totsune Kazuhito , Hayashi Yutaka , Hasegawa Sumio , Ohneda Makoto , Murakami Osamu , Miura Yukio , Katakura Ryuichi , Tachibana Shinro , Maebashi Masaru 
Published: August 2015

1. We investigated the usefulness of neuropeptide Y as a plasma marker for phaeochromocytoma, ganglioneuroblastoma and neuroblastoma using a simple and highly sensitive r.i.a. for human neuropeptide Y.
2. Plasma immunoreactive neuropeptide Y concentrations were measured without extraction in plasma samples (100 μl) from patients with various diseases.
3. The plasma immunoreactive neuropeptide Y concentration in patients with phaeochromocytoma (172.3 ± 132.4 pmol/l, mean ± sd, n = 23) was significantly higher than that in healthy adult subjects (40.1 ± 10.1 pmol/l, n = 40, P&lt;0.0001). The plasma immunoreactive neuropeptide Y concentrations in patients with ganglioneuroblastoma (590.7 ± 563.6 pmol/l, n = 6) and patients with neuroblastoma (566.9 ± 524.4 pmol/l, n = 15) were significantly higher than those in control children (1–9 years old, 82.2 ± 39.9 pmol/l, n = 72, P&lt;0.0001).
4. The plasma immunoreactive neuropeptide Y concentration in patients with essential hypertension (34.0 ± 3.7 pmol/l, n = 18) was within the normal range, but in patients with chronic renal failure undergoing maintenance haemodialysis (192.1 ± 68.0 pmol/l, n = 25) and in non-dialysed patients with chronic renal failure (85.1 ± 23.1 pmol/l, n = 7) it was significantly higher than that in healthy adult subjects (P&lt;0.0001).
5. Eighty-seven per cent of the patients with phaeochromocytoma, 67% of the patients with ganglioneuroblastoma and 80% of the patients with neuroblastoma showed plasma immunoreactive neuropeptide Y concentrations higher than the upper limits in the control subjects [62 pmol/l (adult) and 160 pmol/l (children)].
6. These results suggest that neuropeptide Y is a useful plasma marker for these tumours in addition to other factors unless the patients have renal failure.
Circulating histamine and eosinophil cationic protein levels in nocturnal asthma
Authors: Fitzpatrick Michael F. , MacKay Thomas , Walters Carol , Tai Po-Chun , Church Martin K. , Holgate Stephen T. , Douglas Neil J. 
Published: August 2015

1. To investigate the role of mast cells and eosinophils in the pathogenesis of nocturnal asthma, the plasma methylhistamine concentration, serum eosinophil cationic protein level and peak expiratory flow rate were measured 2-hourly for 24 h in 10 patients with nocturnal asthma and in 10 healthy control subjects. Nocturnal asthma was defined as at least one nocturnal awakening per week due to cough, wheeze or breathlessness with an average overnight fall in peak expiratory flow rate of at least 15% during a 2-week run-in period.
2. The lowest peak expiratory flow rate occurred at 02.00–04.00 hours in the group with nocturnal asthma, whose overnight fall in peak expiratory flow rate was 29 ± 5% in comparison with 5 ± 1% (means ± sem) in the normal subjects.
3. Plasma methylhistamine levels at night (0.200–04.00 hours) were lower than during the day (10.00–20.00 hours) in both asthmatic patients and normal subjects (asthmatic patients: day, median 0.22 ng/ml, 95% confidence intervals 0.18–0.34 ng/ml; night, 0.17 ng/ml, 0.13–0.24 ng/ml; P&lt;0.01; normal subjects: day, 0.31 ng/ml, 0.24–0.41 ng/ml; night, 0.24 ng/ml, 0.21–0.33 ng/ml; P&lt;0.01).
4. The serum eosinophil cationic protein level was higher by day (30 ng/ml, 8–47 ng/ml) than by night (21 ng/ml, 5–34 ng/ml; P&lt;0.04) in the group with nocturnal asthma, but did not change significantly with the time of day in the normal subjects (day: 8 ng/ml, 4–14 ng/ml; night: 8 ng/ml, 5–21 ng/ml).
5. Peripheral blood eosinophil counts fell in the early morning in the patients with nocturnal asthma (day: 0.52 × 109/l, 0.14–0.76 × 109/l; night: 0.29 × 109/l, 0.13–0.57 × 109/l; P= 0.03), but did not change significantly in the normal subjects.
6. This study indicates that a rise in plasma histamine concentration is not a prerequisite for nocturnal asthma.
Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus
Authors: Chan J. C. N. , Critchley J. A. J. H. , Ho C. S. , Nicholls M. G. , Cockram C. S. , Swaminathan R. 
Published: August 2015

1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24 h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion ≤ 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion ≥ 300 mg/day).
2. The supine systolic blood pressure (mean ± sd) was higher in patients with abnormal albuminuria (group 1: 140.9 ± 27.4 mmHg; group 2: 158.1 ± 26.4 mmHg; group 3: 166.7 ± 23.9 mmHg; F = 13.1, P&lt;0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9–37.1) pg/ml; group 2: 39.1 (34.2–44.6) pg/ml; group 3: 50 (38.6–54.7) pg/ml; F = 4.24, P&lt;0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2–1437.0) nmol/day; group 2: 1142.3 (975.9–1337.2) nmol/day; group 3: 982.7 (775.7–1245) nmol/day; F = 3.10, P&lt;0.05, analysis of variance]. Using stepwise multiple regression analysis, plasma atrial natriuretic peptide concentration (r2 = 0.31, F = 56.2, P&lt;0.001) was associated with supine systolic blood pressure (β = 0.56, P&lt;0.001), which was (r2 = 0.38, P&lt;0.001) related to urinary albumin excretion (β = 0.23, P&lt;0.001). In patients with urinary albumin excretion &gt; 30 mg/day, plasma atrial natriuretic peptide concentration was negatively correlated with urinary dopamine output (r = −0.25, P&lt;0.02).
3. Based on these observations, we hypothesize that, in patients with non-insulin-dependent diabetes mellitus, defective dopamine mobilization in the renal tubules may cause impaired natriuresis with increased blood pressure. A compensatory rise in the plasma atrial natriuretic peptide concentration may then contribute to the development of abnormal albuminuria.
Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in man
Authors: Rustom R. , Maltby P. , Grime J. S. , Stockdale H. R. , Critchley M. , Bone J. M. 
Published: August 2015

1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for the renal tubular turnover of small filtered proteins in man. Lysine potently inhibits tubular peptide uptake, and may thus depress the uptake and metabolism of aprotinin. This was investigated in 14 glomerulonephritic patients with normal renal function and variable proteinuria and in one healthy subject.
2. 99mTc-labelled aprotinin was given intravenously alone, and again 3 days later, immediately after the intravenous administration of 3–6 g of lysine, followed by an infusion over 1 h of 0.3–1.9 g of lysine/kg in individual patients. Activity over kidneys and in urine was measured over 24 h and chromatography was used to separate the undegraded peptide from free isotope.
3. At the low dosage of lysine (&lt; 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake) was unchanged, but early urine samples contained some undegraded aprotinin. Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6 ± 0.2% of dose/h with no lysine to 0.9 ± 0.1% of dose/h in the 24 h after lysine, suggesting suppression of tubular aprotinin degradation. Corrected fractional degradation was calculated from the mean urinary excretion of free isotope over a given interval, determined by chromatography, divided by the mean cumulative kidney counts over this same interval, and this also fell after lysine from 0.06 ± 0.006 to 0.03 ± 0.006 h−1 (P&lt;0.005) between 3.75 and 24 h.
4. By contrast, in nine subjects given more lysine (&gt; 0.8 g/kg) tubular uptake fell and urine contained more undegraded aprotinin at all times. However, the corrected urinary excretion of free isotope (determined by chromatography) was unchanged and, paradoxically, fractional degradation rose from 0.06 + 0.01 to 0.10 ± 0.01% of dose/h (P&lt;0.025) between 3.75 and 24 h.
5. Thus, lysine seemed to have a biphasic effect, inhibiting tubular peptide degradation at the low dosage, but depressing uptake into the tubular cell at the high dosage. This, in turn, might relieve intra cellular proteolytic enzymes from autoinhibition by aprotinin and result in a paradoxical restoration of tubular metabolism.
Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis
Authors: Scherzer Pnina , Wald Hanna , Rubinger Dvora , Popovtzer Mordecai M. 
Published: August 2015

1. To further explore the Na+-retaining effect of indomethacin along the whole length of the nephron, the Na+-K+-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2.
2. Indomethacin increased Na+-K+-ATPase activity in the proximal convoluted tubule (+24%, P&lt;0.001 versus control), proximal straight tubule (+75%, P&lt;0.001 versus control), medullary thick ascending limb (+68%, P&lt;0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P&lt;0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na+-K+-ATPase activity by −42% (P&lt;0.001 versus control).
3. Indomethacin also strongly increased Na+-K+-ATPase activity in the cortical collecting duct of adrenalectomized rats.
4. In isolated tubules from control rats, prostaglandin E2 reduced Na+-K+-ATPase activity in the proximal convoluted tubule (−33%, P&lt;0.05), proximal straight tubule (−60%, P&lt;0.001), medullary thick ascending limb (−43%, P&lt;0.001), cortical thick ascending limb (−25%, P&lt;0.001) and cortical collecting duct (−45%, P&lt;0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na+-K+-ATPase activity (+32%, P&lt;0.05).
5. That these changes in Na+-K+-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.
Plasma, platelet and erythrocyte glutathione peroxidases as risk factors in ischaemic heart disease in man
Authors: Porter M. , Pearson D. J. , Suarez-Mendez V. J. , Blann A. D. 
Published: August 2015

1. Plasma, platelet and erythrocyte glutathione peroxidase activities and serum lipid concentrations were measured in patients with ischaemic heart disease and matched control subjects.
2. Mean plasma and platelet glutathione peroxidase activities were significantly lower in the patients with ischaemic heart disease. Erythrocyte glutathione peroxidase activities and serum lipid concentrations were similar in patients with ischaemic heart disease and control subjects.
3. No correlations between plasma, platelet and erythrocyte glutathione peroxidase activities were observed.
4. The combination of plasma and platelet glutathione peroxidase activities provided an 86% discrimination between patients with ischaemic heart disease and matched control subjects.
5. Our data suggest that plasma and platelet glutathione peroxidases may be significant risk factors for ischaemic heart disease. Plasma glutathione peroxidase is a previously unrecognized risk factor.
Decreased faecal exoglycosidase activities identify a subset of patients with active Crohn's disease
Authors: Yamani Jamal El , Mizon Charlotte , Capon Calliope , Colombel Jean-Frederic , Fournet Bernard , Cortot Antoine , Mizon Jacques 
Published: August 2015

1. α1-Proteinase inhibitor (α1-antitrypsin) is excreted in a deglycosylated form (Mr 38000) in the faeces of healthy subjects and in patients with quiescent Crohn's disease. By contrast, in most patients with active Crohn's disease, α1-proteinase inhibitor is excreted in a glycosylated form (Mr 51000).
2. Faecal extracts containing deglycosylated α1-proteinase inhibitor are able to deglycosylate α1-proteinase inhibitor by an exoglycosidic process. Conversely, we demonstrate that in faecal extracts from patients excreting glycosylated α1-proteinase inhibitor, glycosidase activities, such as N-acetyl-β-glucosaminidase (EC 3.2.1.30), α1-mannosidase (EC 3.2.1.24) and particularly β-galactosidase (EC 3.2.1.23), are strongly decreased.
3. Degradation of glycosidases by proteases could not explain the decreased glycosidase activity in these faecal extracts.
4. Our data suggest that a modification of the bacterial colonic flora (or of its metabolic activity) occurs in most patients with active Crohn's disease and could be responsible for an impaired colonic salvage of carbohydrates.
Effects of spermine on water absorption, polyethylene glycol 4000 permeability and collagenase activity in rat descending colon in vivo
Authors: Mendizabal M. V. , Naftalin R. J. 
Published: August 2015

1. The effects of spermine in the concentration range 0–10 mmol/l on (a) the fluid absorption, (b) the polyethylene glycol permeability, (c) the release of collagenase activity activity into the lumen and (d) the histological appearance of rat descending colon were examined.
2. Spermine (5 mmol/l) decreased fluid absorption from 48.83 ± 2.98 (n = 7) to 23.98 ± 2.32 (n = 6) μl h−1 cm−2 (P&lt;0.01); polyethylene glycol 4000 permeability was increased from 0.030 ± 0.001 (n = 7) to 0.047 ± 0.003 (n = 6) cm/h (P&lt;0.01) and luminal collagenase activity increased from a negligible control value to 250 ± 39 (n = 6) units/ml (P&lt;0.001). Spermine also caused oedema formation within the mucosal interstitial fluid, without inducing an overt breakdown of the mucosa at the luminal surface.
3. Polyamine-free dialysed seminal plasma had no effect on polyethylene glycol 4000 permeability, although it still caused a significant decrease in colonic fluid absorption from 48.83 ± 2.98 (n = 7) (control) to 31.41 ± 2.08 (n = 5) μl h−1 cm−2 (P&lt;0.01).
4. Low-molecular-mass heparin (600 units/ml) prevented the spermine (5 mmol/l)- and whole-semen-induced increase in colonic polyethylene glycol 4000 permeability and reduced the effect of semen on fluid absorption by 63% (P&lt;0.001) and that of spermine by 56% (P&lt;0.01).
5. The Zn2+ chelator and collagenase inhibitor o-phenanthroline reduced the effect of spermine on fluid absorption and polyethylene glycol 4000 permeability by 100% (P&lt;0.001) and on interstitial oedema formation. o-Phenanthroline also reduced the effects of whole semen on fluid absorption (by 70%, P&lt;0.01) and on polyethylene glycol 4000 permeability by 95%, P&lt;0.01).
6. A synthetic peptide inhibitor of mammalian collagenase activity with high affinity reduced the effects of whole semen on polyethylene glycol 4000 permeability (P&lt;0.01) and on fluid absorption (P&lt;0.01) in a dose-dependent manner. The inhibitor (2 mmol/l) also reduced the effects of spermine (5 mmol/l) on fluid absorption and polyethylene glycol 4000 permeability.
7. These results indicate that polyamines that are present within semen in the concentration range 5–15 mmol/l act co-operatively with seminal collagenases to disrupt the colonic barrier. Cationic polyamines may activate collagenases by binding to and neutralizing the anionic charge of heparins within the interstitial matrix.
Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control
Authors: Pedersen M. Mau , Christiansen J. Sandahl , Pedersen E. B. , Mogensen C. E. 
Published: August 2015

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intra-individual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 ± 8 years, duration of diabetes 9 ± 5 years, mean arterial blood pressure 90 ± 5 mmHg (means ± sd), urinary albumin excretion rate 5.4 × / ÷ 1.6 μg/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [125I]-iothalamate and 131I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control.
2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (σ = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002].
3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R2 = 0.36, analysis of variance: P = 0.009).
4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin.
5. When compared with eight healthy control subjects, atrial natriuretic peptide was moderately increased in the diabetic patients [4.7(4.2–6.2) versus 3.9 (3.4–4.6) pmol/l, median (first and third quartile), 2P&lt;0.05].
6. In conclusion, the study identified individual changes in atrial natriuretic peptide, arginine vasopressin and long-term glycaemic control as factors associated with intra-individual variation in glomerular filtration rate. It is suggested that atrial natriuretic peptide is involved in the regulation of glomerular filtration rate and possibly specifically in diabetic hyperfiltration.
Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs
Authors: Deutz N. E. P. , Reijven P. L. M. , Athanasas G. , Soeters P. B. 
Published: August 2015

1. After operation, changes in nitrogen metabolism occur. Although increased flux of amino acids from peripheral to splanchnic organs after operation has been described, substrate utilization by the individual organs in the splanchnic area is less well characterized. We were specifically interested in substrate flux across the spleen as it is an organ with important immunological functions.
2. Therefore, hindquarter, gut, spleen and liver fluxes of amino acids, ammonia, glucose, lactate and blood gases were measured for 4 days after a standard operation in pigs. In a separate control group, fluxes were measured 2–3 weeks after this operation and these values were assumed to represent the normal situation.
3. One day after operation, the hindquarter effluxes of glutamine, alanine and several essential amino acids were increased (P&lt;0.001), but these normalized at the end of the observation period. In the same period, liver glutamine uptake increased (P&lt;0.01), concomitantly with increased HCO-3, glucose and urea production, which also normalized. Portal drained viscera ammonia production decreased, concomitant with decreased glutamine uptake (P&lt;0.001). After operation, the splenic release of ammonia increased sevenfold (P&lt;0.05) and that of lactate increased from −158 ± 544 to 3294 ± 642 nmol min−1 kg−1 body weight (P&lt;0.001). Glucose uptake increased from −964 ± 632 to −3933 ± 1524 nmol min−1 kg−1 body weight and glutamine efflux (391 ± 143) reversed to uptake (−752 ± 169 nmol min−1 kg−1 body weight) (P&lt;0.001).
4. The experiments show that after operation in the pig, amino acid flow is from peripheral tissue to liver, probably for gluconeogenesis. The increased postoperative splenic metabolism possibly represents an indication of increased substrate utilization by the immune system.