bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why does vasodilatation occur during syncope?
Authors: Robinson B. J. , Johnson R. H. 
Published: August 2015

1. Syncopal or near syncopal episodes have been observed in five subjects who stood or were tilted and in whom blood samples were being taken.
2. In all subjects bradycardia and hypotension developed before the onset of symptoms. Increases in plasma adrenaline concentrations occurred in all subjects, beginning before the faint. Changes in plasma noradrenaline concentrations were variable: in three subjects there was a marked fall and in the other two subjects an increase. Plasma vasopressin increased in all subjects.
3. Increases in plasma adrenaline may be contributing to the vasodilatation and arterial hypotension which occur during syncope.
Caffeine clearance and biotransformation in patients with chronic liver disease
Authors: Scott Nigel R. , Stambuk Drago , Chakraborty J. , Marks Vincent , Morgan Marsha Y. 
Published: August 2015

1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load.
2. In the control group, the mean (± sd) serum caffeine clearance was 1.3 ± 0.4 ml min−1 kg−1 and a mean of 56.4 ± 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 ± 1.4% of the administered caffeine was excreted unchanged.
3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 ± 1.2 ml min−1 kg−1 and a mean of 57.2 ± 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 ± 0.9% of the administered caffeine was excreted unchanged.
4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 ± 0.2 ml min−1 kg−1) was significantly impaired compared with controls (P &lt; 0.01) and a significant delay was observed in metabolite excretion in the urine. Thus the mean recovery of metabolites in the urine during the first 24 h (25.0 ± 11.2%) was significantly reduced compared with controls (44.1 ± 12.4%, P = 0.03), whereas the mean urinary metabolite recovery in the second 24 h (20.9 ± 10.5%) was insignificantly increased compared with controls (12.3 ± 7.8%). Overall, the mean recovery of metabolites in the urine in 48 h (45.9 ± 15.4%) was similar to that in the control group. The overall recovery of unchanged caffeine was significantly greater than in controls (5.0 ± 2.8% vs 2.0 ± 1.4%, P = 0.04), but the pattern of metabolite excretion was otherwise unchanged.
5. In the patients with liver disease there were significant linear correlations between the degree of hepatocellular dysfunction and the serum caffeine elimination half-life (r = 0.774; P &lt; 0.01) and the total recovery of methylxanthine metabolites in the urine, in the 0–24 h (r = 0.702; P = 0.002) and 0–48 h (r = 0.581; P = 0.018) periods.
6. Caffeine clearance is impaired in patients with decompensated cirrhosis either because of a reduction in hepatic caffeine uptake or else because of a reduction in ‘functioning hepatocyte mass’. However, the biotransformation of caffeine is unaltered in the presence of hepatic dysfunction.
Effects of the anabolic steroid stanozolol on cells derived from human bone
Authors: Vaishnav R. , Beresford J. N. , Gallagher J. A. , Russell R. G. G. 
Published: August 2015

1. In this study, cells derived from explants of human trabecular bone were treated with the anabolic steroid stanozolol in order to determine whether the potential therapeutic effect of this agent might be explained by direct effects on skeletal tissue.
2. Stanozolol at a concentration of 10−10 mol/l to 10−6 mol/l consistently stimulated the incorporation of [3H]thymidine into DNA of human bone cells and increased proliferation.
3. Stanozolol had variable effects on the expression of two other markers of the osteoblast phenotype, namely the bone-specific vitamin-K-dependent protein osteocalcin, and the enzyme alkaline phosphatase. Although stanozolol tended to increase the values, this was not seen in all experiments.
4. We conclude that human bone cells respond to stanozolol. The effects of this agent on cell proliferation may be important in understanding the mode of action of this drug in the treatment of osteopenic disorders.
α-Methyldopa selectively reduces alae nasi activity
Authors: Lahive K. C. , Weiss J. W. , Weinberger S. E. 
Published: August 2015

1. Sedatives such as the benzodiazepines and alcohol reduce upper airway muscle activity. We hypothesized that a sedating antihypertensive, α-methyldopa, might have similar effects. To investigate this hypothesis we studied the effect of α-methyldopa on alae nasi electromyographic (EMG) activity during hypercapnia.
2. We studied ten healthy subjects and three subjects with obstructive sleep apnoea during CO2-stimulated breathing. In a preliminary study four subjects demonstrated a fall in alae nasi EMG activity 4 h after the ingestion of 500 mg of α-methyldopa during CO2 rebreathing.
3. In six additional normal subjects and three subjects with obstructive sleep apnoea, we studied the alae nasi EMG activity during steady-state hypercapnia with PCO2 held constant 5 torr (0.7 kPa) above baseline. On 2 separate days we studied subjects before and 2 h after they had ingested 750 mg of α-methyldopa or placebo.
4. In the normal subjects the mean alae nasi EMG activity fell by 34% 2 h after ingestion of α-methyldopa (P &lt; 0.05) without a change in other ventilatory parameters.
5. In the sleep apnoea group the individual mean alae nasi EMG activity fell 16–49%, with ventilation and tidal volume falling in one patient.
6. We conclude that α-methyldopa selectively reduces upper airway motor activity.
Muscle fatigue and pain after eccentric contractions at long and short length
Authors: Newham D. J. , Jones D. A. , Ghosh G. , Aurora P. 
Published: August 2015

1. The effect of muscle length on the development of muscle pain and fatigue has been studied.
2. Eight normal young adults performed maximal eccentric contractions of the elbow flexors. The muscles of one arm were exercised at short length, and the contralateral muscle at long length. Each contraction lasted approximately 1 s, and was repeated once every 10 s for 30 min.
3. Muscle strength and frequency-force characteristics were measured from isometric contractions before, immediately after and at 24 h intervals for the next 4 days. Muscle tenderness was assessed daily.
4. The muscle strength was reduced by approximately 10% by exercise at short length, and by 30% by exercise at long length.
5. The 20:100 ratio (force generated by stimulation at 20 Hz/force generated at 100 Hz) fell by 30% after exercise at short length and had recovered after 24 h. Exercise at long length reduced this ratio by 65% and the muscles had not fully recovered 4 days later.
6. Muscle pain developed after both exercise regimens, but was slightly worse after that at long length.
7. It is concluded that there is a length-dependent component in the development of pain and fatigue after eccentric exercise, which had previously been thought to be caused solely by high force generation.
Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats
Authors: Luft F. C. , Steinberg H. , Ganten U. , Meyer D. , Gless K. H. , Lang R. E. , Fineberg N. S. , Rascher W. , Unger Th. , Ganten D. 
Published: August 2015

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar–Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks.
2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not.
3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin–angiotensin–aldosterone system and 18-hydroxy-deoxycorticosterone tended to decrease with NaCl, but not with mineral water.
4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower Pco2 and HCO−3 values and higher anion gap values than WKY rats. These values were not influence by the two regimens.
5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.
Magnesiuric and calciuric effects of terbutaline in man
Authors: Bos W. J. W. , Postma D. S. , van Doormaal J. J. 
Published: August 2015

1. The effect of terbutaline infusion over 4 h on serum levels of potassium, ionized calcium, phosphate and magnesium and urinary excretion of potassium, calcium, magnesium and adenosine 3′:5′-cyclic monophosphate was studied in six healthy volunteers.
2. Serum levels of potassium, calcium, phosphate and magnesium decreased. Urinary excretion of potassium decreased, whereas those of calcium, magnesium and adenosine 3′:5′-cyclic monophosphate increased.
3. These results indicate that the hypocalcaemic and hypomagnesaemic effects of terbutaline can, at least partly, be explained by enhanced urinary excretion of calcium and magnesium. This may have important implications for the short-term terbutaline treatment of patients with, for example, cardiac disease.
Transport and metabolism of 6-thioguanine and 6-mercaptopurine in mouse small intestine
Authors: Bronk J. R. , Lister Norma , Shaw M. I. 
Published: August 2015

1. The transport of 6-thioguanine and 6-mercaptopurine has been studied with isolated jejunal loops of mouse small intestine. H.p.l.c. was used to identify and quantify the thiopurines and their metabolites in the serosal secretions.
2. When the lumen of the intestinal loops contained either 6-thioguanine or 6-mercaptopurine at a concentration of 1 mmol/l, the concentration of unmetabolized drug in the serosal secretions reached a maximum of 0.13 ± 0.02 mmol/l (mean ± sem).
3. Analysis of the serosal secretions from the perfusions with either of the drugs revealed the appearance of an unknown compound which had the characteristics of a thiopurine and the same time course of appearance as the unmetabolized drug. Thus 6-thioguanine and 6-mercaptopurine are significantly metabolized during absorption in mouse intestine.
4. The unknown compound was identified as 6-thiouric acid, and with 1 mmol/l 6-thioguanine or 6-mercaptopurine in the lumen the concentration of this metabolite in the serosal secretions rose to a maximum of 0.13 ± 0.01 and 0.18 ± 0.03 mmol/l, respectively. At luminal drug concentrations of 0.1 mmol/l, the metabolite accounted for approximately 90% of the serosal thiopurine.
5. After an initial lag period of 20 min, linear rates of appearance in the serosal secretions were obtained for both the unmetabolized drugs and 6-thiouric acid.
6. Addition of the xanthine oxidase inhibitor oxypurinol at a luminal concentration of 0.3 mmol/l prevented the formation of 6-thiouric acid from 6-thioguanine. However, the inhibitor reduced the rate of 6-thioguanine appearance in the serosal secretions by 50%.
7. The conversion of 6-mercaptopurine to 6-thiouric acid was prevented when allopurinol or oxypurinol were added to the lumen. At a luminal drug concentration of 1 mmol/l, allopurinol increased the rate at which 6-mercaptopurine appeared in the serosal secretions by 90% compared with an increase of only 50% with oxypurinol.
8. The transport of water and glucose by the mouse intestinal loops was unaffected by 6-thioguanine or the xanthine oxidase inhibitors. However, 6-mercaptopurine caused significant reductions in the rate of water transport (30%) and glucose transport (39%). These effects were observed at a luminal drug concentration of 0.1 mmol/l and there was no further increase at a drug concentration of 1 mmol/l.
Sodium transport in the diseased human gallbladder and the effects of indomethacin
Authors: Jacyna M. R. , Ross P. E. , Hopwood D. , Bouchier I. A. D. 
Published: August 2015

1. Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of 22Na across isolated, inflamed human gallbladder mucosa maintained in a modified ‘Ussing’ flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis.
2. In 30 gallbladders studied, 57% had a net Na+ flux from mucosa to serosa (Na+ absorption), while 23% had a net Na+ flux from serosa to mucosa (Na+ secretion). The remaining 20% showed no overall net Na+ flux.
3. Indomethacin added to the serosal fluid reversed the direction of net Na+ flux in secreting gallbladders and caused an absorption of Na+. In Na+-absorbing gallbladders, indomethacin caused a slight reduction in Na+ absorption. No change in Na+ flux was induced in gallbladders with no initial net Na+ flux.
4. These results demonstrate that instead of absorbing Na+, some inflamed human gallbladders may secrete Na+. As this secretion can be reversed to the more usual absorption by indomethacin, it is likely that this secretion is mediated by prostaglandins.
Endocrine and renal response to water loading and water restriction in normal man
Authors: Shore Angela C. , Markandu Nirmala D. , Sagnella Giuseppe A. , Singer Donald R. J. , Forsling Mary L. , Buckley Martin G. , Sugden A. Louise , MacGregor Graham A. 
Published: August 2015

1. Nine normal subjects (eight male, one female) on a fixed daily intake of 150 mmol of sodium and 80 mnol of potassium, were randomized to receive either 3 days of 1.0 litre total water intake/24 h (food + fluid) or 4 days of 6.8 litres total water intake/24 h, and were then crossed over after a 3 day control period (2.7 litres water/24 h).
2. During water restriction, urine volume fell from 1.94 litres/24 h to less than 1 litre/24 h by the first day and was 0.77 litre/24 h on the final day. Plasma atrial natriuretic peptide levels were unchanged from baseline despite a large increase in plasma vasopressin and plasma and urine osmolality. Urinary sodium was unaltered throughout, while urinary potassium was increased on the final 2 days of water restriction.
3. During water loading, urine volume increased from 1.85 litres/24 h to 5.44 litres/24 h on the first day and remained at approximately 6 litres/24 h for the final 3 days. Plasma atrial natriuretic peptide showed no change. Plasma vasopressin and plasma and urine osmolality were reduced. Urinary sodium and potassium output were unchanged from baseline.
4. These results suggest that changes in plasma atrial natriuretic peptide are unlikely to be involved in the normal homoeostatic response to changes in water balance in man.
Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man
Authors: Mavichak Viroon , Coppin Christopher M. L. , Wong Norman L. M. , Dirks John H. , Walker Valerie , Sutton Roger A. L. 
Published: August 2015

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours.
2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P &lt; 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P &lt; 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria.
3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients.
4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.
Exercise and platelet intracellular free calcium concentration
Authors: Barr Susan M. , Lees Kennedy R. , McBryan Daniel D. , Reid James , Farish Elizabeth , Rubin Peter C. 
Published: August 2015

1. A positive correlation between blood pressure and platelet intracellular free calcium concentration ([Ca2+]i) has been reported. We examined the effect of acute changes in blood pressure associated with exercise on platelet [Ca2+]i.
2. Twenty-one subjects had blood pressure and heart rate readings taken after 60 min rest, and subjects were then exercised on a bicycle ergometer at 120 W for 30 min. Blood pressure and heart rate readings were repeated immediately after exercise, 30 min after exercise, and then after a further hour. Blood samples were taken after each set of blood pressure and heart rate readings for catecholamine, lactate and platelet [Ca2+]i estimations.
3. There were significant increases in systolic and diastolic blood pressure, heart rate, and plasma lactate and catecholamine levels during the course of the study. There were no significant changes in platelet [Ca2+]i.
4. These results suggest that the acute blood pressure changes related to exercise are not associated with a change in platelet [Ca2+]i.
Influence of amino acid administration on whole-body leucine kinetics and resting metabolic rate in postabsorptive normal subjects
Authors: Pacy P. J. , Garrow J. S. , Ford G. C. , Merritt H. , Halliday D. 
Published: August 2015

1. We have investigated the effect of an amino acid mixture (Varnin 14; 57.4 ±10.2 μmol h−1 kg−1) on whole-body leucine kinetics, calculated by a steady-state reciprocal pool model, and resting metabolic rate in eight postabsorptive normal subjects.
2. Vamin 14 infusion increased whole-body leucine flux (P &lt; 0.001), leucine employed for protein synthesis (P &lt; 0.001), leucine oxidation (P &lt; 0.001), metabolic clearance rate of α-ketoisocaproic acid (P &lt; 0.05) and levels of all three branched-chain amino acids (P &lt; 0.001) compared with the basal situation. In contrast, whole-body proteolysis was reduced (P &lt; 0.05).
3. Resting metabolic rate was increased during Vamin 14 infusion (P &lt; 0.05) and was positively correlated with whole-body protein synthesis (n = 16, r = 0.6342, P &lt; 0.01; y = 0.605x + 173.7), as was the change in metabolic rate with the change in protein synthesis (n = 8, r = 0.772, P &lt; 0.05; y = 0.493x − 10.85).
4. Overall, Vamin 14 infusion was associated with increased blood glucose (P &lt; 0.001), although the observed increase in plasma glucagon (t = 2.012) and plasma insulin (t = 1.683) failed to reach statistical significance.
5. These data lend a measure of support to the hypothesis that the apparent increase in whole-body protein synthesis in insulin-dependent diabetic (type I) subjects during insulin withdrawal may be substrate related.
Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit
Authors: Weinberg J. R. , Wright D. J. M. , Guz A. 
Published: August 2015

1. The cardiovascular effects of intravenous injections of interleukin-1 (IL-1) and tumour necrosis factor (TNF) have been investigated in the conscious rabbit. They have been compared with the effects of bacterial lipopolysaccharide (LPS) because both IL-1 and TNF are released from macrophages by LPS.
2. IL-1, TNF and Escherichia coli J5-LPS all caused hypotension when given intravenously in a dose with low mortality. The time course of the hypotension caused by IL-1 and LPS was similar, although the maximal fall in mean blood pressure occurred earlier after IL-1. TNF produced a more sustained fall in blood pressure. Hypotension was not accompanied by a compensatory tachycardia after any of the test substances. Hypotension was associated with a fever after TNF, hypothermia after LPS and no significant change in temperature after IL-1.
3. The packed cell volume did not change during hypotension in any of the study groups, implying that the hypotension was not due to fluid loss resulting from increased capillary permeability.
4. IL-1 and TNF are candidates for the role of effectors of LPS-induced hypotension.
Absence of a late-phase response or increase in histamine responsiveness after bronchial provocation with adenosine 5′-monophosphate in atopic and non-atopic asthma
Authors: Phillips G. D. , Holgate S. T. 
Published: August 2015

1. Adenosine 5′-monophosphate (AMP) causes bronchoconstriction in atopic and non-atopic asthma by a mechanism believed to involve histamine release from airway mast cells. To determine whether preformed mast cell mediators, principally histamine, can initiate a late-phase bronchoconstriction we have investigated the effect on the airways over a 24 h period of a single bronchial challenge with AMP.
2. Six atopic asthmatic subjects (all late responders to inhaled allergen) and six non-atopic asthmatic subjects were studied on two occasions for a 24 h period after inhalation of the provocation concentration of AMP required to produce a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (PC20) and 0.9% (w/v) sodium chloride placebo, respectively. The atopic asthmatic subjects were studied on a further occasion after challenge with the PC20 allergen.
3. Inhalation of the PC20 AMP resulted in an immediate fall in FEV1 to a mean maximum 25.5% below baseline without resulting in any late decrease in airway calibre. No significant increase in non-specific bronchial responsiveness as determined by measuring the PC20 histamine before, and at 3, 9 and 24 h after, AMP challenge, occurred. Inhalation of the PC20 allergen caused a reproducible late-phase bronchoconstriction and increase in non-specific bronchial responsiveness in all the atopic asthmatic subjects studied.
4. These results suggest that preformed mast cell mediators, principally histamine, play no role in the initiation of the late-phase reaction in allergen-provoked asthma, although they may contribute to the inflammatory changes involved.