bluuebunny/crossref_metadata_2025_split huggingface dataset:
The implication of bilitranslocase function in the impaired rifamycin SV metabolism in Gilbert's syndrome
Authors: Gentile Sandro , Persico Marcello , Baldini Giulia , Lunazzi Giancarlo , Tiribelli Claudio , Sottocasa Gian Luigi 
Published: August 2015

1. The plasma disappearance rate and the increment in plasma unconjugated bilirubin after intravenous administration of 5.9 μmol of rifamycin SV (RSV)/kg body wt. were investigated in 51 subjects with Gilbert's syndrome and 35 control subjects of both sexes.
2. Both the plasma disappearance rate and the unconjugated hyperbilirubinaemia after RSV administration were higher (P&lt;0.001) in Gilbert's syndrome. Females, both normal and with the syndrome, showed a significantly shorter t1/2 and a lower hyperbilirubinaemic response as compared with males. A linear correlation (P&lt;0.001) was present between RSV plasma half-life and the hyperbilirubinaemic response.
3. In vitro, RSV was shown to inhibit sulphobromophthalein (BSP) uptake in rat liver plasma-membrane vesicles with a Ki of 20 μmol/l. Evidence that this effect was due to competition for bilitranslocase was sought on preparations of the purified protein. Under these experimental conditions, RSV inhibited BSP binding with a Ki of 17 μmol/l.
4. Since RSV competes with BSP for binding to bilitranslocase in vitro, the data are interpreted as suggesting that reduced bilitranslocase function might underlie the delayed RSV plasma clearance and the exacerbated unconjugated hyperbilirubinaemia present in Gilbert's syndrome.
Dexamethasone effect on prostanoid formation in healthy man
Authors: Rosenkrantz Bernd , Náray-Fejes-Tóth Aniko , Fejes-Tóth Geza , Fischer Christine , Sawada Masafumi , Frölich Jürgen C. 
Published: August 2015

1. Dexamethasone was administered to six healthy female volunteers for 4 days, resulting in plasma levels of 4.8 ± 1.4 × 10−8 mol/l. Urinary excretions of six prostanoids as well as collagen-induced platelet thromboxane formation and aggregation were determined before, during and 1 month after administration of dexamethasone.
2. Dexamethasone had no effect on urinary thromboxane B2 (77 ± 22 ng/day vs 63 ± 16 ng/day during dexamethasone), dinor-thromboxane B2, the major urinary metabolite of thromboxane B2 (406 ± 84 ng/day vs 380 ± 90 ng/day), dinor-6-keto-prostaglandin F1α, the major urinary metabolite of prostacyclin (199 ± 41 ng/day vs 237 ± 53 ng/day), tetranor-5,1 l-diketo-7α-hydroxy-prostane-1,16-dioic acid, the major urinary metabolite of prostaglandins E1 and E2 (7712 ± 1677 ng/day vs 7886 ± 2565 ng/day) and tetranor-11-keto-5α, 7α-dihydroxy-prostane-1,16-dioic acid, the major urinary metabolite of prostaglandins F1α and F2α (14 394 ± 2053 ng/day vs 18288 ± 2251 ng/day). Prostaglandin E2 excretion slightly but significantly increased from 217 ± 48 ng/day to 294 ± 55 ng/day. Collagen-induced platelet thromboxane formation and aggregation were not altered.
3. These results suggest that glucocorticoids do not regulate renal, platelet or total body prostanoid formation in healthy man.
The biliary excretion of 25-hydroxy-[3H] vitamin D3 in the Gunn rat
Authors: Gascon-Barré Marielle 
Published: August 2015

1. The biliary excretion of 25-hydroxy-[3H]-vitamin D3 (25-(OH)-[3H]D3)-derived materials after the intravenous administration of 25-(OH)-[3H]D3 (1.25 nmol/100 g body weight) was studied during a period of 3 h in homozygous (icteric) and heterozygous (anicteric) Gunn rats.
2. The heterozygous rats excreted significantly more 25-(OH)-[3H]D3-derived materials than the homozygous Gunn rats (7.2 ± 1.5% vs 3.1 ± 0.5% of the administered dose, P&lt;0.025).
3. The lower biliary excretion of 25-(OH)-[3H]-D3-derived material in homozygous compared with heterozygous Gunn rats was not due to differences in the plasma 25-(OH)-[3H]D3 concentrations nor was it due to differences in the uptake of 25-(OH)-[3H]D3 by the liver since similar liver/plasma concentration ratios were observed in both groups of animals; it seemed, however, to be due to differences in the biliary transfer of 25-(OH)-[3H]-D3, as indicated by a lower bile/liver concentration ratio in homozygous than in heterozygous rats (1.39 ± 0.23 vs 0.49 ± 0.06, P&lt;0.05).
4. Moreover, samples of bile obtained from homozygous rats contained no β-glucuronidase-sensitive 25-(OH)-[3H]D3-derived materials but contained significantly more intact 25-(OH)-[3H]-D3 than samples obtained from heterozygous Gunn rats (P&lt;0.05). After hydrolysis of bile obtained from homozygous and heterozygous Gunn rats with the enzyme β-glucuronidase, the total amount of intact 25-(OH)-[3H]D3 recovered was found to be similar in the two groups of rats.
5. The results of the present experiments indicate that conjugation of 25-(OH)D3 with glucuronic acid is one of the metabolic pathways involved in its biliary transfer; they also illustrate that the homozygous Gunn rats constitute a good model to study the importance and biological significance of the glucuronidation pathway in the biliary excretion of vitamin D sterols.
Studies of α2-adrenoceptor antagonist potency in vitro: comparisons in tissues from rats, rabbits, dogs and humans
Authors: Waterfall J. F. , Rhodes K. F. , Lattimer N. 
Published: August 2015

1. The potencies of a number of selective α2-adrenoceptor antagonists have been measured in preparations from four species.
2. In the rat vas deferens, the newer synthetic antagonists Wy 25309, Wy 26392, Wy 26703 and RX 781094 were more potent than the alkaloid yohimbine in blocking a clonidine-induced inhibition of an electrically evoked twitch response.
3. In the rabbit vas deferens yohimbine was substantially more potent than the synthetic antagonists in reversing the action of clonidine.
4. Yohimbine was also more potent than the synthetic antagonists in blocking the B-HT 933-induced contractile responses of the dog saphenous vein and preventing adrenaline-induced aggregation of human platelets.
5. Together with previously published data derived from tritium overflow studies on rabbit pulmonary arteries and displacement of [3H]-rauwolscine binding from rat cerebral cortex and human platelets, the results suggest that the adrenoceptor currently labelled α2 may not be a single entity.
Inositol lipid breakdown as a step in α-adrenergic stimulus-response coupling
Authors: Michell Robert H. 
Published: August 2015

1. A widespread, and maybe universal, response to stimulation of α-adrenoceptors is inositol lipid hydrolysis: the receptor-coupled event is probably hydrolysis of phosphatidylinositol 4,5-bisphosphate. This reaction generates two second messenger molecules.
2. Inositol 1,4,5-trisphosphate may be responsible for the intracellular mobilization of Ca2+ that has long been recognized as a major mediator of the effects of α-receptor activation. In addition, the released 1,2-diacylglycerol probably contributes to control of cell function through activation of protein kinase C.
Vascular α2-adrenoceptors can mediate nerve stimulation-evoked contractions
Authors: Docherty James R. , Hyland Lisa 
Published: August 2015

1. It is now established that α2-adrenoceptors can be present on vascular smooth muscle as targets for exogenous agonists, but some controversy exists as to whether these vascular α2-receptors may also be the target for neurally released noradrenaline.
2. In human saphenous vein we have found evidence that the α2-antagonist yohimbine in low concentrations (0.01 μmol/l) can significantly inhibit stimulation-evoked contractions, whereas the α1-antagonist prazosin is more than ten times less potent.
3. It is concluded that, at least in some tissues, neuro-effector transmission can be mediated by vascular α2-adrenoceptors.
Human vascular smooth muscle responses mediated by α2 mechanisms in vivo and in vitro
Authors: Thom S. , Calvete J. , Hayes R. , Martin G. , Sever P. 
Published: August 2015

1. The effects of compounds with α2-agonist and α2-antagonist properties on human forearm blood flow and on isolated human arterial segments have been studied.
2. The findings from these studies in vivo and in vitro did not provide evidence in support of the hypothesis that postsynaptic α2-receptors mediate smooth muscle contraction in the tissues under investigation.
3. The constriction of the forearm vascular bed in response to low intra-arterial doses of idazoxan (RX 781094), an α2-antagonist, provides evidence for a physiological role for a presynaptic α2 autoregulatory mechanism.
4. The variability of the forearm vascular responses to higher doses of idazoxan highlights the pitfalls that may have misled previous authors in their interpretation of the results of similar studies. A U-shaped dose-response curve to compounds with mixed α2-and α1-antagonist properties may be constructed, which emphasizes the importance of the dose-dependent selectivity of these antagonists at α2- and α1-receptors.
5. The effect of idazoxan on the responses of arterial segments in vitro to exogenous catecholamines was dependent on the integrity of the endothelium, and provides evidence that α2-receptors may mediate release of the endothelium-derived relaxing factor.
The Distribution of Catecholamines between Platelets and Plasma in Normal Human Subjects
Authors: Smith C. C. T. , Curtis L. D. , Delamothe A. P. , Prichard B. N. C. , Betteridge D. J. 
Published: August 2015

1. We have used high-performance liquid chromatography with electrochemical detection to measure content of adrenaline and noradrenaline in platelets in 13 normal subjects at rest.
2. Subjects were exercised to raise plasma catecholamine levels and promote the platelet release reaction.
3. There was a significant positive correlation between plasma noradrenaline concentrations and platelet noradrenaline content.
4. Platelet/plasma concentration ratios were 1855 for noradrenaline and 268 for adrenaline at rest and 473 and 152 respectively after exercise.
5. Plasma noradrenaline levels positively correlated with age.
6. Determination of platelet factors released to the plasma showed increases of β-thromboglobulin and platelet factor 4 with exercise, whereas thromboxane B2 remained unchanged. No change in platelet catecholamine levels occurred with exercise and no correlations were observed between platelet catecholamines and released platelet factors.
7. These data suggest that plasma catecholamine levels influence platelet content and that noradrenaline and adrenaline are concentrated in platelets.
The Measurement of Breathlessness Induced in Normal Subjects: Validity of two Scaling Techniques
Authors: Adams L. , Chronos N. , Lane R. , Guz A. 
Published: August 2015

1. The intensity of breathlessness induced by ventilatory stimulation resulting from hypercapnia, hypoxia or exercise has been quantified in normals by using the two different sensory scaling techniques of linear visual analogue scaling and ratio magnitude estimation.
2. In naive individuals both techniques show good face validity.
3. When related to ventilation, quantification of breathlessness is moderately reproducible with both methods, even when subjects are kept in ignorance of the pattern of ventilatory stimulation.
4. There is a small within- and large between-subject variability with both scaling techniques; possible factors responsible are discussed.
5. The reproducibility of visual analogue scaling when related to ventilation is independent of the nature of the ventilatory stimulus and is maintained over intervals as long as 1 week when memory for the score given is unlikely to be an important factor.
6. The difficulties of interpreting subjective estimates of perceived breathlessness are discussed, together with the relative merits of the two scaling techniques.
Measurement of Blood Cortisol and Acid Output in Patients with Duodenal Ulceration and Normal Subjects During Insulin Hypoglycaemia
Authors: Athow Anna C. , Sewerniak Anna T. , Barton Tina P. , Clark C. G. , Lewin M. R. 
Published: August 2015

1. The blood cortisol and gastric acid responses to insulin hypoglycaemia were investigated in 18 healthy control subjects and 14 patients with endoscopically proven duodenal ulceration.
2. In both controls and patients, insulin hypoglycaemia caused blood cortisol and acid output to rise and peak simultaneously, the rises being significantly greater in patients with duodenal ulcer than in control subjects.
3. The peak acid output and the base to peak cortisol increments were also found to be significantly greater in patients with duodenal ulcer than in control subjects (P &lt; 0.001 and P &lt; 0.005 respectively).
4. We conclude that insulin hypoglycaemia causes stimulation of the sympathetic and parasympathetic nervous systems and of the hypothalamo-pituitary-adrenal axis, resulting in the simultaneous elevation of gastric juice acidity and blood cortisol levels. We have shown that synchronous rises in gastric acid and blood cortisol occur during insulin hypoglycaemia and that these rises are greater in patients with duodenal ulcer.
Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis
Authors: Gibson P. R. , Jewell D. P. 
Published: August 2015

1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin.
2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only.
3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l.
4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration.
5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.
γ-l-Glutamyl-l-Dopa is a Dopamine Pro-Drug, Relatively Specific for the Kidney in Normal Subjects
Authors: Worth D. P. , Harvey J. N. , Brown J. , Lee M. R. 
Published: August 2015

1. γ-l-Glutamyl-l-dopa was given by intravenous infusion to eight normal subjects at doses of 12.5 and 100 μg min−1 kg−1.
2. Both doses of the dipeptide resulted in an increase in mean urinary sodium excretion.
3. Mean effective renal plasma flow rose at both doses, but mean glomerular filtration rate increased only at the lower dose.
4. There was a fall in mean plasma renin activity after the infusion of both 12.5 and 100 μg min−1kg−1.
5. Mean urine free dopamine excretion increased by 280- and 2500-fold at infusion rates of 12.5 and 100 μg min−1 kg−1 respectively.
6. Mean plasma free dopamine rose at both doses but the increase at 12.5 μg min−1 kg−1 was not to a level previously associated with systemic effects of the catecholamine.
7. On administration of the dipeptide at 12.5 μg min−1 kg−1 there were no changes in blood pressure or heart rate, but at the higher dose there was a fall in diastolic blood pressure.
8. At a dose of 12.5 μg min−1 kg−1 in man, there is kidney specific conversion of gludopa to dopamine.
Cytosolic free Calcium and Intracellular Calcium Stores in Neutrophils from Hypertensive Subjects
Authors: Lew P. Daniel , Favre Laurent , Waldvogel Francis A. , Vallotton Michel B. 
Published: August 2015

1. Alterations in intracellular calcium have been implicated in the pathogenesis of essential hypertension. To see whether this is a generalized phenomenon we assessed cytosolic free calcium and intracellular calcium stores in neutrophils from normo- and hyper-tensive subjects, by trapping the fluorescent calcium indicator quin2 in intact cells.
2. Ten patients with untreated essential hypertension were compared with 10 age- and sex-matched normotensive subjects. The levels of cytosolic free calcium and intracellular calcium stores releasable by the calcium ionophore ionomycin did not differ. No significant relationship was found between blood pressure and the calcium parameters in all 20 subjects studied.
3. The results indicate that essential hypertension is not associated with a membrane defect in calcium handling of all human cell systems, leading to generalized increases in resting values of cytosolic free calcium.
4. Neutrophils do not appear to be a good model for intracellular calcium handling in vascular smooth muscle.
Influence of the parasympathetic and sympathetic nervous system on nocturnal bronchial obstruction
Authors: Postma D. S. , Keyzer J. J. , Koëuter G. H. , Sluiter H. J. , De Vries K. 
Published: August 2015

1. To determine whether an autonomic nervous system imbalance might underlie the nocturnal dyspnoea in patients with chronic airflow obstruction (CAO), we determined FEV1, sinus arrhythmia gap (SA gap), heart rate and urinary adrenaline and noradrenaline excretion every 4 h over 24 h. Measurements were performed in eight non-allergic patients with CAO and eight age- and sex-matched normal controls.
2. The amplitude of the circadian changes in FEV1 in patients and controls was 27 ± 2% and 7 ± 1% respectively (P &lt; 0.001).
3. Both an increased SA gap and a decreased heart rate are features of increased vagal activity. This vagal activity was significantly increased in patients, compared with normal controls (difference P &lt; 0.01), the difference being maximal at night. This increased activity might contribute to a bronchial obstruction in these patients.
4. Urinary adrenaline excretion was significantly higher by day than by night in both patients and normal controls (P &lt; 0.01). The urinary levels of adrenaline in the patients were significantly decreased at all hours of observation as compared with levels in normal controls (P &lt; 0.05).
5. Urinary noradrenaline levels were significantly lower in patients as compared with normal subjects (P &lt; 0.01), and lower by night than by day.
6. Urinary histamine and Nτ-methylhistamine excretion were in the normal range in each individual. Urinary levels, however, were significantly higher in patients at all hours of observation (P &lt; 0.05). No circadian rhythm was shown. Plasma cortisol levels showed a normal circadian variation, similar in patients and normal subjects.
7. Bronchial constriction in patients with CAO may be explained by an autonomic nervous system imbalance. Arguments favouring this hypothesis were the findings that CAO patients, in contrast with normal controls, showed lower urinary adrenaline and noradrenaline excretion throughout with a fall at night, and a higher vagal tone with an increase at night. Moreover, a higher histamine and Nτ-methylhistamine excretion both day and night existed in the patient group. A combination of these factors may lead to the nocturnal dyspnoea in patients with CAO.
Validation of a Doppler technique for beat-to-beat measurement of cardiac output
Authors: Mehta Nawzer , Iyawe Vincent I. , Cummin Andrew R. C. , Bayley Susan , Saunders Kenneth B. , Bennett E. David 
Published: August 2015

1. We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q).
2. We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method.
3. We obtained excellent overall correlation in a range of 0.5–10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min.
4. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity.
Tremor: an alternative approach for investigating adrenergic mechanisms in thyrotoxicosis?
Authors: Abila B. , Lazarus J. H. , Kingswood J. C. , Marshall R. W. , Wilson J. F. , Richens A. 
Published: August 2015

1. The effects of nadolol (or placebo) and carbimazole on thyrotoxic tremor were investigated in 18 thyrotoxic patients.
2. Both nadolol and carbimazole produced significant reductions in tremor power although nadolol did not cause any change in serum free tri-iodothyronine and free thyroxine concentrations.
3. The results are discussed in terms of the pathogenesis of thyrotoxic tremor and the potential usefulness of tremor in the investigation of adrenergic mechanisms in thyrotoxicosis.
Effects of age on body temperature and blood pressure in cold environments
Authors: Collins K. J. , Easton J. C. , Belfield-Smith Hazel , Exton-Smith A. N. , Pluck R. A. 
Published: August 2015

1. Mean deep body temperature fell by 0.4 ± 0.1 (sd) °C in five sedentary, clothed 63–70 year old men and by 0.1 ±0.1°C in four young adults after 2 h exposure in still air at 6°C (P &lt; 0.001).
2. The mean increase in systolic and diastolic pressure was significantly greater (P &lt; 0.002) in the older subjects (24 ± 4 mmHg systolic, 13 ± 4 mmHg diastolic) than in the young (14 ± 6 mmHg systolic, 7 ± 3 mmHg diastolic) after 2 h at 6°C. A small rise in blood pressure occurred in the older men at 12°C, but there was no increase in either group at 15°C.
3. The association of variables is particularly marked between systolic blood pressure and core temperature changes at 6°C.
4. There were no appreciable cold-adaptive changes in blood pressure or thermoregulatory responses after 7–10 days repeated exposure to 6°C for 4 h each day.
5. Blood pressure elevation in the cold was slower but more marked in the older men. These changes in blood pressure may provide a possible basis for delineating low domestic limiting temperature conditions.