bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deglycosylation of α1-proteinase inhibitor is impaired in the faeces of patients with active inflammatory bowel disease (Crohn's disease)
Authors: Mizon Charlotte , Yamani Jamal El , Colombel Jean-Frédéric , Maes Pierrette , Balduyck Malika , Laine Anne , Cortot Antoine , Tartar André , Mizon Jacques 
Published: August 2015

1. α1-Proteinase inhibitor (α1-antitrypsin) was excreted in the faeces of patients with inflammatory bowel disease in different molecular forms: Mr-51 000 and Mr-45 000 forms were widely found in the stools of patients with active disease, whereas a Mr-38 000 species was frequently recovered from healthy subjects and patients with quiescent disease (Mizon, Becuwe, Balduyck et al. Clin. Chem. 1988; 34, 2268–70).
2. N-Terminal sequencing of the Mr-38000 form of α1-proteinase inhibitor, after SDS/PAGE and electro-transfer on polyvinyl difluoride membranes, showed that it differed from plasma α1-proteinase inhibitor by the loss of 17 N-terminal amino acids.
3. Carbohydrate analysis of the isolated Mr-38 000 form revealed a total lack of neutral sugars.
4. In contrast, the Mr-51000 form of α1-proteinase inhibitor is glycosylated and thus could be differentiated by virtue of its reactivity with concanavalin A. The analysis of 25 faecal extracts from patients with Crohn's disease allowed us to confirm that the presence of the glycosylated form of α1-proteinase inhibitor was closely related to the degree of inflammation.
5. From these data, it may be hypothesized that the hydrolytic activity of some glycosidases is greatly reduced in active Crohn's disease.
Hypotension induced by intravascular administration of nerve growth factor in the rat
Authors: Yan Q. , Settle S. L. , Wilkins M. R. 
Published: August 2015

1. The observation that the area postrema expresses a high level of nerve-growth-factor-receptor immunoreactivity prompted an investigation of the effects of nerve growth factor on autonomic function in the rat.
2. Bolus injection of pharmacological doses of the peptide via the femoral vein led to reproducible, dose-dependent falls in blood pressure.
3. Administration via the vertebral artery, a more direct route to the brainstem, did not appear to lower the threshold dose required to induce hypotension. Furthermore, pretreatment with hexamethonium did not inhibit the hypotensive response to nerve growth factor.
4. Administration of a second dose of nerve growth factor after recovery from the first injection produced little or no fall in blood pressure. Similarly, pretreatment with the mast cell degranulating agent, compound 48/80, rendered the animal refractory to nerve growth factor.
5. The fall in blood pressure induced by nerve growth factor was markedly attenuated by pretreatment with chlorpheniramine.
6. It is concluded that the fall in blood pressure induced by intravenous administration of pharmacological doses of nerve growth factor is mediated by vasoactive substances, particularly histamine, released from mast cells.
Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger N-acetylcysteine
Authors: Knight Kenneth R. , MacPhadyen Karen , Lepore Diana A. , Kuwata Noriyuki , Eadie Patricia A. , O'Brien Bernard McC. 
Published: August 2015

1. The burst of damaging oxygen free-radicals at the time of reperfusion is one of the crucial factors affecting skin flap survival after an ischaemic interval. In these experiments the efficacy of the antioxidant and free-radical scavenger N-acetylcysteine in improving the survival of ischaemic rabbit epigastric skin flaps was tested.
2. At the time of reperfusion flaps were given: (1) balanced salt solution by intravenous whole-body administration, (2) N-acetylcysteine (200 mg/kg) by intravenous whole-body administration, (3) balanced salt solution by intra-arterial infusion into the flap, (4) N-acetylcysteine (20 mg/kg) by intra-arterial infusion into the flap, or (5) N-acetylcysteine (200 mg/kg) by intra-arterial infusion into the flap. Flap survival at 1 week, and tissue levels of parameters related to free-radical production, blood levels of thromboxane B2 and peripheral resistance during reperfusion were determined.
3. Compared with controls (groups 1 and 3) which had flap survival rates (expressed as percentage surface area surviving) of 27.1% and 31.6%, respectively, N-acetylcysteine treatment in group 2 (55.2%) and group 4 (51.9%) resulted in significant (P &lt; 0.05) improvements in flap survival. The survival rate in group 5 (37.7%) was not significantly better than that of the controls.
4. N-Acetylcysteine significantly reduced parameters related to free-radical production in the skin flap after 30 min of reperfusion, determined as tissue levels of malonyldialdehyde and protein oxidation products. There was also a significant decrease in peripheral resistance when low-dose N-acetylcysteine (group 4) was infused intra-arterially into the flap. The systemic levels of thromboxane B2, a prostanoid promoting thrombosis, were not significantly altered by administration of N-acetylcysteine.
5. N-Acetylcysteine proved to be a successful therapeutic agent for the salvage of experimental ischaemic rabbit skin flaps, when used as a low-dose intra-arterial or high-dose intravenous treatment. The possible clinical benefits in humans have yet to be demonstrated.
Effect of a single test dose of lithium carbonate on sodium and potassium excretion in man
Authors: Shirley D. G. , Singer D. R. J. , Sagnella G. A. , Buckley M. G. , Miller M. A. , Markandu N. D. , MacGregor G. A. 
Published: August 2015

1. The possible natriuretic and kaliuretic effects of a single dose of lithium, as used in lithium clearance studies, were investigated in 15 healthy subjects on fixed sodium (100 mmol/24 h) and potassium (70 mmol/24 h) intakes. Lithium carbonate (300 mg or 600 mg) or placebo tablets were administered, double-blind and in random order, midway through a 48 h urine collection (divided into six 8 h periods), at 23.00 hours.
2. During the three 24 h periods which preceded the administration of lithium or placebo (control days), rates of sodium and potassium excretion followed normal circadian patterns, but no differences in excretion rates between the 3 control days were observed. Placebo tablets did not affect excretion rates.
3. After the 300 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 17 mmol (P &lt; 0.05); almost all of the natriuretic effect occurred during the first two 8 h periods. No effect on potassium excretion was observed.
4. After the 600 mg dose of lithium carbonate, 24 h sodium excretion increased by approximately 48 mmol (P &lt; 0.001) and 24 h potassium excretion increased by approximately 19 mmol (P &lt; 0.01). These effects were confined to the first two 8 h periods and thus occurred before and during the usual lithium clearance period.
5. Plasma renin activity, measured in 10 subjects, increased after the 600 mg dose of lithium carbonate (P &lt; 0.005), but plasma concentrations of aldosterone and atrial natriuretic peptide were not significantly affected. Neither the 300 mg dose of lithium carbonate nor the placebo tablets affected hormone levels.
6. It is recommended that the test dose of lithium carbonate for use in lithium clearance studies should not exceed 300 mg.
Responses of glucose and glucoregulatory hormones to exercise in thyrotoxic and myxoedematous patients before and after 3 months of treatment
Authors: Sestoft Leif , Christensen Niels Juel , Saltin Bengt 
Published: August 2015

1. The effect of moderate endurance exercise on blood glucose concentration and on glucoregulatory hormones was studied in nine thyrotoxic and five myxoedematous humans before and 3 months after anti-thyroid and substitution therapy, respectively.
2. At rest, the fasting concentrations of insulin and pro-insulin correlated positively with the prevailing total tri-iodothyronine concentration, whereas the concentrations of noradrenaline and cortisol correlated inversely with the tri-iodothyronine concentration.
3. During exercise the plasma insulin, pro-insulin and C-peptide concentrations decreased. The plasma glucagon concentration increased slightly in thyrotoxic patients before and after treatment and was largely unchanged in myxoedematous patients in either state.
4. The plasma noradrenaline concentration increased before and after treatment in both groups, with concentrations two times higher in the myxoedematous than in the thyrotoxic patients. Treatment for 3 months did not change this pattern. The plasma adrenaline concentration increased in both groups, but in the untreated thyrotoxic patients the increase was two to three times greater than that after treatment or that in the myxoedematous group.
5. The blood glucose concentration decreased in eight of nine untreated thyrotoxic patients, but was largely unchanged after treatment or in the myxoedematous patients. A strong negative correlation was found between the decline in blood glucose concentration and the increase in plasma adrenaline concentration in the thyrotoxic group.
6. Thus, during exercise untreated thyrotoxic patients are prone to hypoglycaemia, show an inadequate glucagon response, and exhibit a large counter-regulatory increase in plasma adrenaline concentration.
Albumin metabolism in fasted subjects during late pregnancy
Authors: Olufemi O. Samson , Whittaker Paul G. , Halliday Dave , Lind Tom 
Published: August 2015

1. Albumin fractional synthetic rate was determined in five non-pregnant subjects and five normal pregnant subjects in late gestation after an overnight fast by simultaneous prime and intravenous infusion of two precursor amino acids, [15N]glycine and l-[1-13C]leucine, with additional priming of the large but, slowly turning over, urea pool with [15N2]urea.
2. The two tracers yielded similar values of albumin fractional synthetic rate: 6.1 and 6.0%/day in nonpregnant subjects and 7.3 and 7.6%/day in pregnant subjects, for glycine and leucine, respectively. While plasma volume was greater and serum albumin concentration was significantly reduced during pregnancy, the calculated intravascular albumin mass was significantly increased in pregnant subjects.
3. The amount of albumin synthesized in the intravascular compartment was significantly greater at 8.8 and 9.5 g/day in pregnant subjects compared with 6.4 and 6.3 g/day in non-pregnant control subjects (glycine and leucine methods, respectively). Calculated whole-body protein turnover using glycine was not different between the two subject groups, but leucine flux was higher in pregnant subjects. Partitioning of nitrogenous products in urine revealed that pregnant subjects excreted less urea, less ammonia and less creatinine than the non-pregnant control subjects.
4. These findings suggest that whereas the serum albumin concentration decreases during pregnancy secondary to the large increase in plasma volume, there is an increase in albumin synthesis such that total intravascular albumin mass is increased in late pregnancy.
Evidence for two distinct and functionally important sites of enhanced thromboxane production after bilateral ureteral obstruction in the rat
Authors: Harris K. P. G. , Yanagisawa H. , Schreiner G. F. , Klahr S. 
Published: August 2015

1. After bilateral ureteral obstruction there is an enhanced production of thromboxane A2 by the kidney which contributes to a decline in renal function. An acute interstitial macrophage infiltrate also occurs.
2. The relative contribution of infiltrating cells and intrinsic renal cells to the enhanced production of thromboxane A2 by the hydronephrotic kidney were determined. The effects of both irradiation and subsequent administration of the thromboxane synthesis inhibitor OKY-046 on both thromboxane B2 excretion and renal function were examined in rats with 24 h bilateral ureteral obstruction.
3. Irradiation effectively prevented the leucocyte infiltrate after bilateral ureteral obstruction (1.2 ± 0.8 × 105 versus 27.1 ± 0.1 × 105 cells/g of cortex, n = A in each group), resulted in a significantly higher inulin clearance (2.78 ± 0.27 versus 1.49 ± 0.17 ml min−1 kg−1 body weight, n = 7 and n = 8, respectively, P &lt; 0.001) and reduced thromboxane B2 excretion to 39% of non-irradiated values. Subsequent administration of OKY-046 to previously irradiated animals further reduced thromboxane B2 excretion to 20% of the value in non-irradiated rats with bilateral obstruction and further increased inulin clearance to 3.34 ± 0.26 ml min−1 kg−1 body weight.
4. Glomerular macrophage numbers were decreased after bilateral ureteral obstruction (in contrast to the interstitium). However, glomeruli isolated from rats with 24 h bilateral ureteral obstruction exhibited enhanced production of thromboxane B2 compared with sham-operated control rats (855.6 ± 31.1 versus 392.2 ± 25.5 pg 60 min−1 mg−1 of protein, P &lt; 0.001).
5. These data suggest that the increased renal production of thromboxane A2 after bilateral ureteral obstruction results from both renal infiltration by metabolically active macrophages and enhanced prostanoid production by the glomeruli. Both sources of thromboxane A2 contribute to altered renal function after bilateral ureteral obstruction.
Haemostatic responses and vasopressin release during colonoscopy in man
Authors: Hampton K. K. , Grant P. J. , Primrose J. , Dean H. G. , Davies J. A. , Prentice C. R. M. 
Published: August 2015

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis.
2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination.
3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition.
4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VIII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml.
5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group.
6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.
Angiotensin II augments sympathetically mediated arteriolar constriction in man
Authors: Seidelin Peter H. , Collier Joseph G. , Struthers Allan D. , Webb David J. 
Published: August 2015

1. In animal studies, angiotensin II facilitates adrenergic neurotransmission by both pre- and postsynaptic mechanisms. We have investigated whether this interaction occurs in forearm resistance vessels in man.
2. The effect of arterial infusion of angiotensin II (320 fmol/min) on sympathetic vasoconstriction produced by lower-body negative pressure (15 mmHg) was studied in six subjects, and that on the response to exogenous noradrenaline (37.5–150 pmol/min) was studied in a further eight subjects. Forearm blood flow was measured by strain-gauge plethysmography.
3. The dose of angiotensin II was chosen to produce no alteration in resting blood flow, and those of noradrenaline were selected to provide a reduction in blood flow equivalent to that produced by lower-body negative pressure.
4. Lower-body negative pressure produced no change in heart rate or diastolic blood pressure, but caused an initial 5 mmHg fall in systolic blood pressure (P &lt; 0.01). Blood flow was reduced by 21 ± 6% in both forearms by lower-body negative pressure during saline infusion. During angiotensin II infusion, there was a marked difference in the response to lower-body negative pressure, with blood flow being reduced by 40 ± 7% in the infused arm, but only by 21 ± 4% in the control arm (P &lt; 0.05). Angiotensin II infusion had no effect on resting blood flow or the responses to noradrenaline.
5. We conclude that angiotensin II augments sympathetic vasoconstriction in forearm resistance vessels in man at a concentration that has no direct effect on blood flow. The absence of an effect of angiotensin II on the response to noradrenaline suggests that augmentation of sympathetic vasoconstriction occurs pre-synaptically through facilitation of noradrenaline release.
Effect of age on hypothalamic prostaglandin E2 production and fever in response to tumour necrosis factor (cachectin) and endotoxin in rats
Authors: Bibby D. C. , Grimble R. F. 
Published: August 2015

1. Decreased febrile responses to interleukin-1 and endotoxin have been noted in a number of species with ageing.
2. The present study extends these observations by examining the pyrogenic response to intravenous recombinant human tumour necrosis factor-α (50 μg/kg) using conscious rats aged 7,20 and 80 weeks.
3. The febrile response decreased in magnitude and duration with age. Fevers of 0.9 °C and of 5 h duration were observed in the youngest rats, whereas those aged 80 weeks were afebrile. The depression in serum zinc level and the elevation in liver zinc level, which occurred 7 h after injection, were unaffected by age.
4. The mechanism of the reduced pyrogenic response was examined by assessing prostaglandin E2 production in vitro from hypothalami of rats, aged 10 and 24 weeks, in response to Escherichia coli endotoxin and tumour necrosis factor.
5. Whereas the production of prostaglandin E2 increased by 47% and 52%, respectively, in hypothalami from 10-week-old rats, no response to either pyrogen was obtained in tissue from rats aged 24 weeks.
6. Maturity brings about a decreased responsiveness of hypothalamic prostaglandin E2 production to pyrogens, which may explain the decreased febrile responses observed.
Role of plasma non-esterified fatty acids during and after exercise
Authors: Walker M. , Cooper B. G. , Elliott C. , Reed J. W. , Orskov H. , Alberti K. G. M. M. 
Published: August 2015

1. The importance of circulating non-esterified fatty acids as a substrate during and after low-grade exercise has been examined by using a nicotinic acid analogue to inhibit lipolysis. Seven healthy men received acipimox or placebo on separate occasions. After 90 min, bicycle exercise was performed for 45 min (40% of pre-determined maximum oxygen uptake), followed by a 60 min recovery period.
2. The plasma concentration of non-esterified fatty acids increased during exercise after placebo (320 ± 80 to 630 ± 110 μmol/l) and remained elevated in the post-exercise period. Basal concentrations were lower after acipimox (100 ± 10 μmol/l; P &lt; 0.05); they declined to 60 ± 10 μmol/l during exercise and remained at this level for the rest of the study.
3. Lipid oxidation increased from 0.8 ± 0.1 to 4.2 ± 0.5 mg min−1 kg−1 during exercise after placebo (P&lt; 0.001) and remained elevated in the post-exercise period (1.2 ± 0.1 mg min−1 kg−1). It was lower after acipimox, but still increased from 0.3 ± 0.1 to 2.3 ± 0.2 mg min−1 kg−1 with exercise. Carbohydrate oxidation was increased after acipimox compared with after placebo, but only reached significance during the post-exercise period (P &lt; 0.05).
4. Although acipimox abolished the rise in the plasma concentration of non-esterified fatty acids during exercise, there was only a 50% decrease in the rate of lipid oxidation. This suggests that an alternative source of non-esterified fatty acids makes an important contribution to the supply of lipid for oxidation during exercise. The elevated plasma concentration of non-esterified fatty acids and lipid oxidation after exercise serve to limit the further oxidation of carbohydrate.
Kidney renin gene expression after renin inhibition in the marmoset
Authors: Kitami Yutaka , Hiwada Kunio , Murakami Eiki , Iwata Takeru , Muneta Shinjiro , Kokubu Tatsuo 
Published: August 2015

1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day−1 kg−1) for 1 week.
2. The mean blood pressure was significantly decreased (P&lt; 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration.
3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P &lt; 0.05 for each, n = 5).
4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 ± 3.5 versus 12.8 ± 5.5 pg/μg of total RNA, means ± sd, P &lt; 0.05, n = 5).
5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.
Stimulating effects of atenolol on vasodepressor prostaglandin generation in spontaneously hypertensive rats
Authors: Hirawa Nobuhito , Uehara Yoshio , Numabe Atsushi , Takada Satoru , Matsuoka Hiroaki , Ikeda Toshio , Sugimoto Tsuneaki , Yagi Shigeru , Ishii Masao 
Published: August 2015

1. To assess the role of the vasodepressor prostaglandin system in the antihypertensive properties of β-adrenoceptor antagonist, we investigated the alterations of prostaglandin generation in the kidney and in the aorta when spontaneously hypertensive rats were treated with atenolol for 2 weeks.
2. The blood pressure reduction was associated with an increase in urinary sodium excretion and urinary prostaglandin E2 excretion. The sodium excretion was positively related to the prostaglandin E2 excretion.
3. Basal release of prostaglandin E2 from the sliced renal cortex was enhanced by the atenolol treatment. Prostacyclin-generating capacity in the aortic wall was also significantly increased.
4. Atenolol treatment stimulated prostaglandin synthesis in the kidney and vascular wall in a dose-dependent manner. However, atenolol per se did not directly stimulate prostaglandin synthesis in the vascular wall.
5. Inhibition of prostaglandin generation by a cyclo-oxygenase inhibitor, indomethacin, was associated with attenuation of the antihypertensive effects of atenolol.
6. Thus these data indicate that sub-chronic atenolol treatment stimulates vasodepressor prostaglandin generation in the kidney and in the aortic vessels, and this shares the antihypertensive effects of this drug with the mechanism of β-adrenergic antagonism probably mediated through vasorelaxation and natriuresis.