bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnesium Sulphate Reverses the Carotid Vasoconstriction Caused by Endothelin-1, Angiotensin II and Neuropeptide-Y, but Not That Caused by NG-nitro-l-Arginine Methyl Ester, in Conscious Rats
Authors: Kemp P. A. , Gardiner S. M. , Bennett T. , Rubin P. C. 
Published: August 2015

1. Magnesium sulphate (MgSO4) has been used for many years in the prevention of eclamptic seizures, but its mechanism of action has never been elucidated. Recent studies suggest that cerebral vasospasm is an important feature of eclampsia and we have developed and tested the hypothesis that MgSO4 can reverse cerebral vasoconstriction.
2. Studies were performed in conscious, male Long Evans rats with pulsed Doppler probes sutured around both common carotid arteries after the external carotid artery had been ligated on the left, thus allowing simultaneous measurement of changes in common and internal carotid blood flow. Intravascular catheters were placed in the abdominal aorta for measurement of systemic blood pressure and in the right jugular vein for administration of drugs. Mean arterial blood pressure and mean Doppler shift signals were used to calculate percentage changes in common and internal carotid vascular conductance.
3. After a period of recovery the animals were infused with endothelin-1, angiotensin II, neuropeptide-Y or NG-nitro-l-arginine methyl ester alone or in combination, and MgSO4 in low or high dose was infused when the effects of the vasoconstrictors had become established.
4. MgSO4 itself, at the low dose, had no effect on carotid vascular conductance. Endothelin-1, angiotensin II and neuropeptide-Y all reduced common and internal carotid vascular conductance and this effect was significantly attenuated by low dose MgSO4. The carotid vasoconstrictor action of endothelin-1 was completely abolished by high dose MgSO4. Combinations of the peptides (endothelin-1/angiotensin II; endothelin-1/neuropeptide-Y; angiotensin II/neuropeptide-Y) also reduced common and internal carotid vascular conductance and these effects were substantially reversed, or completely abolished, by high dose MgSO4. The effect of NG-nitro-l-arginine methyl ester on common and internal carotid vascular conductance was significantly inhibited by human α-calcitonin gene-related peptide, but, in contrast, MgSO4 had no influence.
5. We have tested and confirmed our hypothesis that MgSO4 can reverse cerebral vasoconstriction. The failure of MgSO4 to influence the effects of NG-nitro-l-arginine methyl ester suggest that its vasodilator effect may involve the production of nitric oxide. These findings provide a basis for the action of MgSO4 in eclampsia, and suggest that it may be of value in other circumstances where cerebral vasoconstriction occurs.
Effect of Glucocorticosteroid Treatment on β-Adrenoceptor Subtype Function in Adipocytes from Patients with Asthma
Authors: Reynisdottir Signy , Wahrenberg Hans , Bylin Gunnar , Arner Peter 
Published: August 2015

1. Adrenoceptor subtype function was studied in isolated adipocytes obtained by subcutaneous fat biopsies from nine patients with mild asthma. The biopsies were taken before and after 7 days treatment with 25 mg of prednisolone given orally. Lipolytic activity after stimulation with various adrenergic agents was measured, using glycerol release as an index of lipolysis. The number of β1- and β2-adrenoceptor binding sites was determined in radioligand binding experiments and β1- and β2-adrenoceptor mRNA levels were measured with a solution hybridization assay.
2. Lipolytic sensitivity (ED50) to isoprenaline, a nonselective β-adrenoceptor agonist, increased 50-fold after treatment (P = 0.04). Sensitivity to terbutaline, a selective β2-adrenoceptor agonist, increased 25-fold (P =0.01), whereas the ED50 values for dobutamine, a selective β1-adrenoceptor agonist, did not change significantly. Likewise, the sensitivity to the α2-adrenoceptor agonist, clonidine, and to the drugs acting at post-receptor levels did not change significantly. Basal and maximum lipolytic rates on stimulation were not altered by the treatment.
3. The number of β2-adrenoceptor binding sites increased by 60% after treatment (P &lt;0.05), whereas the β1-adrenoceptor binding sites were not affected. The affinity of each receptor subtype for the displacing ligand, ICI 118.551, was not significantly altered by steroids. No significant changes were demonstrated in either β1- or β2-adrenoceptor mRNA levels.
4. Thus, glucocorticoids selectively increase β2-adrenoceptor density and function in patients with asthma, studied by using subcutaneous fat cells as an experimental model.
Bombesin Reduces Food Intake after a Preload in Man by a Cholecystokinin-Independent Mechanism
Authors: Lieverse R. J. , Jansen J. B. M. J. , Masclee A. A. M. , Lamers C. B. H. W. 
Published: August 2015

1. A double-blind study was undertaken to determine whether the infusion of bombesin inhibits the intake of a carbohydrate-rich meal, consumed 15 min after a 300 ml banana shake, in nine lean healthy subjects and whether the possible inhibition of food intake by bombesin is mediated by cholecystokinin.
2. The amount of food eaten during infusion of bombesin (267 ±60 g) and bombesin combined with the cholecystokinin-receptor antagonist loxiglumide (269±39g) was slightly (P = 0.09) less than during saline infusion (384 ± 40 g). In addition, preprandial feelings of hunger were significantly less during infusion of both bombesin and bombesin combined with loxiglumide.
3. In conclusion, infusion of bombesin tends to inhibit the intake of a carbohydrate-rich meal after a preload by a cholecystokinin-independent mechanism.
Gene Expression of Metalloproteinases and Their Inhibitor in Renal Tissue of New Zealand Black/White F1 Mice
Authors: Nakamura Tsukasa , Ebihara Isao , Osada Shiori , Takahashi Toshimasa , Yamamoto Masatoshi , Tomino Yasuhiko , Koide Hikaru 
Published: August 2015

1. The present study was carried out to determine how levels of the mRNA of metalloproteinases (metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and 92 kDa type IV collagenase) and tissue inhibitor of metalloproteinases are regulated in the renal tissues of New Zealand Black/White F1 mice.
2. mRNA levels for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased significantly with the progression of nephritis in New Zealand Black/White F1 mice.
3. At 48 weeks of age, the levels of mRNA for metalloproteinase-1, 72 kDa type IV collagenase, metalloproteinase-3 and tissue inhibitor of metalloproteinases increased by 8-, 4-, 8- and 15-fold, respectively, in the renal tissues of New Zealand Black/White F1 mice compared with New Zealand White mice.
4. In the kidneys of New Zealand White mice, however, the mRNA levels for these proteins changed little throughout the experimental period.
5. We could not detect expression of mRNA for 9 2 kDa type IV collagenase in the renal tissue of New Zealand Black/White F1 mice at 8 weeks of age or in New Zealand White mice at 8, 24 or 48 weeks of age, whereas we could detect expression of mRNA for this protein in New Zealand Black/White F1 mice at 24 and 48 weeks of age when mononuclear cells had infiltrated the interstitium and surrounding blood vessels.
6. At 24 weeks of age, New Zealand Black/White F1 mice were divided into two groups and received either methylprednisolone or saline injection for 24 weeks.
7. The development of histopathological lesions and increases in mRNA for metalloproteinases and tissue inhibitor of metalloproteinases were suppressed by treatment with methylprednisolone.
8. These data suggest that abnormal regulation of the genes for metalloproteinases and tissue inhibitor of metalloproteinases contribute to the accumulation of extracellular matrix components in lupus nephritis and that the beneficial effect of methylprednisolone is associated with its ability to suppress the expression of mRNA for metalloproteinases and tissue inhibitor of metalloproteinases.
Dissolved Urate Promotes Calcium Oxalate Crystallization: Epitaxy is Not the Cause
Authors: Grover Phulwinder K. , Ryall Rosemary L. , Marshall Villis R. 
Published: August 2015

1. Increasing the concentration of dissolved urate promotes the crystallization of calcium oxalate from urine. The possibility was investigated that this effect may be caused by heterogeneous nucleation of calcium oxalate by particles of crystalline urate.
2. Urine samples were collected from 10 healthy men, centrifuged and filtered, and a solution of sodium urate was added to increase the medium urate concentration from 2.2 to 5.6 mmol/l. Calcium oxalate crystallization was induced by the addition of oxalate, followed by incubation for 90 min in a shaking waterbath at 37°C. The crystalline material was filtered out and the urate concentration was determined in the filtrate.
3. No difference in the urate concentration before and after induction of calcium oxalate crystallization was observed. These findings were confirmed by infra-red spectroscopy, X-ray powder diffraction and ultraviolet wet chemical analysis with detection limits of 5-10, 1.0 and 0.055%, respectively; urate was not detected in the calcium oxalate crystals.
4. In addition, three urine samples were collected and passed through 10 kDa ultrafiltration membranes to remove any colloidal particles which might have been present. The urate concentration was increased and an oxalate load was added as before, prior to incubation at 37°C in a shaking water bath for 5 min, followed by passage through 10 kDa ultrafiltration membranes. Scanning electron microscopy revealed no particles on the membranes thereby indicating that colloidal or crystalline urate was not formed early in the crystallization experiments.
5. It was concluded that the promotion of calcium oxalate crystallization by urate, and thereby the formation of calcium oxalate renal stones, is not caused by heterogeneous nucleation and subsequent epitaxial growth of calcium oxalate upon particles of urate.
Effects of Oral and Intravenous Calcitriol on Serum Calcium Oxalate Saturation in Dialysis Patients
Authors: Marangella Martino , Vitale Corrado , Cosseddu Domenico , Petrarulo Michele , Linari Franco 
Published: August 2015

1. To determine whether the multiple changes in the blood chemistry profile induced by calcitriol may be conducive to secondary systemic oxalosis we have studied nine patients on regular dialysis treatment under three different regimens: (1) oral calcitriol, 0.25 μg/daily for at least 6 months. (2) off calcitriol, a 1-month withdrawal of the drug, taken as the baseline study period; (3) intravenous calcitriol, 1 μg three times weekly at the end of dialysis, with tests performed at 1 and 3 months from initiation.
2. Serum concentrations were measured pre- and post-dialysis at the end of each study period. The whole dialysate was used for the determination of the overall calcium and oxalate removal by dialysis. The degree of saturation with calcium oxalate mono-hydrate was estimated by a computer program. Serum calcitriol concentrations were also assessed.
3. Total and ionized serum calcium did not change on average, although mild hypercalcaemia developed in some patients on intravenous calcitriol. There was an increase in plasma level of oxalate during both oral and intravenous calcitriol treatment, but this was less pronounced during intravenous therapy. Removal of oxalate by dialysis was also greater in patients on oral calcitriol.
4. These increases were probably originated from intestinal absorption and secondary to hyper-absorption of dietary calcium. Consequently, the degree of saturation with calcium oxalate before dialysis rose during calcitriol treatment, irrespective of the route of administration.
5. These results emphasize that, in addition to soft tissue calcification due to calcium phosphates, ectopic calcium oxalate crystallization must also be viewed as a potential risk associated with long-term administration of calcitriol.
Potassium Channels in Hypokalaemic Periodic Paralysis: A Key to the Pathogenesis?
Authors: Links T. P. , Smit A. J. , Oosterhuis H. J. G. H. , Reitsma W. D. 
Published: August 2015

1. A possible role for the ATP-sensitive potassium channels in the pathogenesis of hypokalaemic periodic paralysis was investigated.
2. We assessed insulin release and muscle strength after intravenous glucose loading with and without the potassium channel opener pinacidil and the potassium channel blocker glibenclamide in three patients with hypokalaemic periodic paralysis and in a pair of matched control subjects for each patient.
3. A significantly higher initial insulin response (1.5-30 min) was found in the patients with hypokalaemic periodic paralysis in comparison with the control subjects. During potassium channel blocking with glibenclamide the insulin release was more enhanced in patients than in control subjects. On the other hand, the potassium channel opener pinacidil impaired the insulin release in healthy control subjects but not in patients. The serum glucose levels showed no differences between patients and control subjects. In one of the patients with hypokalaemic periodic paralysis glucose loading resulted in a fall in muscle strength, which did not occur during the administration of pinacidil.
4. These findings suggest a disturbance in the ATP-sensitive potassium channel in patients with hypokalaemic periodic paralysis, which is not limited to pancreatic β cells, but may be also involved in the abnormal behaviour of skeletal muscle.
A New Calcitonin-Receptor-like Sequence in Rat Pulmonary Blood Vessels
Authors: Njuki F. , Nicholl C. G. , Howard A. , Mak J. C. W. , Barnes P. J. , Girgis S. I. , Legon S. 
Published: August 2015

1. Two rat clones have been isolated which are similar to known calcitonin-receptor sequences. One of these does not have the distribution expected of a calcitonin receptor. It is widely distributed, with extremely high levels of expression in the lung, where it is associated with the blood vessels.
2. This rat sequence may represent the receptor for calcitonin-gene-related peptide or islet amyloid polypeptide. Both have binding activity in the lung and are potent vasodilators. The gene represented by this sequence may therefore play an important role in the maintenance of vascular tone.
Cardiovascular and Sympatho-Adrenal Responses to Mental Stress in Primary Hypertension
Authors: Lindqvist Madeleine , Kahan Thomas , Melcher Anders , Hjemdahl Paul 
Published: August 2015

1. Eleven untreated men with mild to moderate primary hypertension and 10 normotensive control subjects were studied at rest and during a mental stress test (Stroop colour word conflict test), which has previously been used in studies of hypertensive patients with regard to non-invasive cardiovascular variables and venous plasma catecholamine concentrations.
2. Heart rate, central cardiovascular pressures, cardiac output (thermodilution) and forearm blood flow (strain gauge plethysmography) were determined. Systemic and forearm vascular resistances were calculated. Arterial and venous plasma adrenaline and noradrenaline concentrations were measured by h.p.l.c., and arterial noradrenaline spillover and noradrenaline overflow from the forearm were assessed by isotope methodology ([3H]noradrenaline). Neuropeptide Y-like immunoreactivity was measured by radioimmunoassay.
3. In hypertensive patients heart rate, arterial blood pressure, cardiac output and forearm blood flow increased by 28%, 13%, 37% and 115%, respectively, and forearm and systemic vascular resistances decreased by 48% and 21%, respectively (P &lt;0.001 for all responses), during stress. These responses were not different from those of the control group.
4. Arterial noradrenaline spillover rose by 63% and noradrenaline overflow from the forearm rose by 150% in the hypertensive patients in response to mental stress (P &lt;0.001); no significant group differences could be demonstrated. However, the forearm noradrenaline overflow response to stress tended to be greater in the hypertensive group (P = 0.11). Arterial adrenaline concentrations doubled in both groups (P &lt;0.001).
5. Arterial neuropeptide Y-like immunoreactivity increased slightly and similarly in the two groups (+7% in hypertensive patients and +9% in control subjects, P &lt;0.05 for both) in response to mental stress. No net overflow of neuropeptide-Y-like immunoreactivity could be detected over the forearm.
6. It is concluded that the cardiovascular and sympatho-adrenal responses to mental stress evaluated in this study are similar in hypertensive patients and control subjects. Stress-induced vasodilatation occurs in the forearm despite signs of increased local sympathetic activity, indicating that powerful neurohormonal vasodilator mechanisms are activated by mental stress.
Effect of Noradrenaline on Renal Sodium and Water Handling in Euhydrated and Overhydrated Man
Authors: Lang Chim C. , Rahman Abdul R. , Balfour David J. K. , Struthers Allan D. 
Published: August 2015

1. The renal effects of incremental doses of intravenously infused noradrenaline were evaluated in normal subjects during two different water loads, 5 ml/kg (n = 6) and 20 ml/kg (n = 9), producing conditions of euhydration and overhydration, respectively.
2. Noradrenaline infusion rates ranged from 0.015 to 0.075 μg min−1 kg−1. In the euhydrated subjects, noradrenaline caused a dose-dependent fall in urinary sodium excretion and an increase in urinary flow rate. During overhydration similar doses of noradrenaline caused a fall in urinary sodium excretion but a decrease in urinary flow rate.
3. Although there was no detectable change in glomerular filtration rate, a dose-dependent fall in effective renal plasma flow was observed in both hydration states during noradrenaline infusion.
4. Noradrenaline infusion was associated with a dose-dependent increase in proximal tubular sodium reabsorption as assessed by the lithium clearance method. Fractional reabsorption of sodium by the distal nephron was, however, unchanged by noradrenaline in both hydration states.
5. Plasma vasopressin concentration was unchanged by noradrenaline in euhydrated subjects. The renin-angiotensin-aldosterone axis was stimulated by noradrenaline in both euhydrated and overhydrated subjects.
6. Thus we conclude that plasma circulating noradrenaline has a dose-dependent antinatriuretic effect in man. The antinatriuretic effect of noradrenaline is mediated mainly at the proximal tubule in man. We have also shown that during overhydration, noradrenaline decreased urinary flow rate. In contrast, in euhydrated subjects, noradrenaline increased urinary flow rate with no accompanying changes in plasma vasopressin concentration, which suggests a direct effect of noradrenaline on the renal tubular permeability to water.
Can Ultrafiltration Occur with a Hypo-Osmolar Solution in Peritoneal Dialysis?: The Role for ‘Colloid’ Osmosis
Authors: Mistry Chandra D. , Gokal Ram 
Published: August 2015

1. In peritoneal dialysis the removal of excess body water (ultrafiltration) is traditionally achieved by means of dialysis solution made hypertonic to plasma by the addition of an osmotic agent. In vitro, the osmotic flow may be directed against the osmolality gradient by using a hypo-osmolar solution, but this phenomenon has not previously been applied to clinical peritoneal dialysis.
2. The ultrafiltration performances of hypo-osmolar dialysis solutions containing a high-molecular-weight glucose polymer (weight average molecular weight 22 000), isolated by fractionation of hydrolysed corn starch, were compared with those of hypertonic glucose solutions over a 12 h exchange in 11 patients well established on continuous ambulatory peritoneal dialysis.
3. Five per cent (272 +1.1 mosmol/kg) and 7.5% (277 + 2.0 mosmol/kg) glucose polymer solutions produced net ultrafiltration of 243 +53 and 526 +59 ml that were significantly greater than the ultrafiltration of −48 +96 and 223 +84 ml associated with 1.36% (339 +1.9 mosmol/kg) and 2.27% (393 +3.2 mosmol/kg) glucose solutions, respectively. The net ultrafiltration with 10% glucose polymer (284 +2.0 mosmol/kg) and 3.86% glucose (482 + 1.6 mosmol/kg) solutions were similar (699 +48 versus 708 +82 ml).
4. The transperitoneal absorption of glucose polymer was substantially lower than that of glucose solutions as was the potential calorie load per millilitre of ultrafiltrate.
5. The addition of 0.35% glucose (molecular weight 180) to 7.5% glucose polymer solution raised the dialysate osmolality to an iso-osmolar level (299 +0.8 mosmol/kg) and produced ultrafiltration which was 29% greater than with 7.5% glucose polymer solution alone.
6. The demonstration of ultrafiltration with hypo-osmolar dialysate represents an important advance towards the formulation of a physiological iso-osmolar dialysis solution, which may have long-term benefits over the conventional hypertonic solutions. The iso-osmolar combination of ‘colloid’ and ‘crystalloid’ osmotic agents looks promising with a potential for a wide range of ultrafiltration capabilities as well as metabolic correction.
CD45RA+ T Cells: Not Simple Virgins
Authors: Lightstone Liz , Marvel Jacqueline 
Published: August 2015

1. The T cells which mediate immunological memory remain elusive. Identification of such cells would open the door to increasingly specific immunotherapy in areas such as transplantation and autoimmunity.
2. Over the last few years attempts have been made to identify phenotypic markers which can distinguish naive or virgin T cells from primed or memory ones. In humans, great hopes were raised when it was shown that the level of expression of the higher-molecular-mass isoforms (CD45RA) of the tyrosine phosphatase, CD45, correlated with previous exposure to antigen.
4. However, our studies in the mouse and more recent studies in rat and human suggest that expression of CD45RA more closely correlates with the state of responsiveness of the T cell.
5. Thus, with time, activated/memory T cells return to a state of quiescence or hypo-responsiveness and express high levels of CD45RA. Hence, not all CD45RA+ T cells are virgins.
A Novel Antiserum Specific to Apolipoprotein B-48: Application in the Investigation of Postprandial Lipidaemia in Humans
Authors: Peel Andrew S. , Zampelas Antonios , Williams Christine M. , Gould Barry J. 
Published: August 2015

1. Apolipoprotein B-48, the transport protein for chylomicrons, is identical with apolipoprotein B-100 for the first 48% of its sequence. No antiserum has yet been reported that can recognize apolipoprotein B-48, but not apolipoprotein B-100.
2. In the present study an antiserum was raised to the C-terminal sequence of apolipoprotein B-48, using specific chemical reactions to ensure that the charged carboxyl group of the C-terminal isoleucine residue was free. In a Western blot the antiserum was shown to bind to a protein band having the characteristics of apolipoprotein B-48, but not to apolipoprotein B-100.
3. In the early evening 11 subjects were given a test meal which contained 40 g of mixed oil and retinyl palmitate. Blood samples were collected over 9 h. Chylomicron-enriched fractions were prepared and analysed for triacylglycerol, retinyl palmitate and apolipoprotein B-48, the latter after separation using SDS/PAGE and visualization by chemiluminescence on a Western blot. Both triacylglycerol and apolipoprotein B-48 showed an early peak at 1 h, which was not seen with retinyl palmitate. All three substances gave a broader peak between 5 and 6 h post-prandially. Retinyl palmitate concentrations declined rapidly during the late (6-9 h) postprandial period, but apolipoprotein B-48 concentrations remained elevated.
4. This study has shown that an antiserum has been produced which is specific for apolipoprotein B-48. This has enabled measurement of postprandial concentrations of the protein that revealed features of chylomicron metabolism which have not been reported previously.