bluuebunny/crossref_metadata_2025 huggingface dataset:
Are lymphocyte β-adrenoceptors altered in patients with cystic fibrosis?
Authors: Feldman Ross D. , Fick Robert B. , McArdle Wendy , Lai Cynthia C.-Y.
Published: August 2015

1. β-Adrenergic responsiveness may be decreased in cystic fibrosis. In order to determine whether this reflects an alteration in the human lymphocyte β-receptor complex, we studied 12 subjects with cystic fibrosis (six were stable and ambulatory and six were decompensated, hospitalized) as compared with 12 normal controls.

2. Lymphocyte β-receptor mediated adenylate cyclase activity (EC 4.6.1.1) was not decreased in the ambulatory cystic fibrosis patients as compared with controls. In contrast, decompensated hospitalized cystic fibrosis patients demonstrated a significant reduction in β-receptor mediated lymphocyte adenylate cyclase activity expressed as the relative increase over basal levels stimulated by the β-agonist isoprenaline compared with both normal controls and stable ambulatory cystic fibrosis patients (control 58 ± 4%; ambulatory cystic fibrosis patients 51 ± 7%; decompensated hospitalized cystic fibrosis patients 28 ± 5%; P < 0.05).

3. Our data suggest that defects in lymphocyte β-receptor properties in cystic fibrosis patients may be better correlated with clinical status than with presence or absence of the disease state.
Serum bile acid profile in thyroid dysfunction and effect of medical treatment
Authors: Kosuge Tomoo , Beppu Tomoe , Kodama Takao , Hidai Koh , Idezuki Yasuo
Published: August 2015

1. Serum non-esterified bile acid profile was examined in patients with thyroid dysfunction. Sixteen hyperthyroid patients, six hypothyroid patients, nine patients taking thyroid or antithyroid drugs and 26 healthy controls were studied. The medicated patients were euthyroid when serum samples were collected. Bile acid concentration was determined by the simplified microassay method involving mass fragmentation spectrometry.

2. The sum of the concentrations of the individual bile acids was not significantly different among the four groups. However, the composition of bile acid reflected the thyroid function. The most prominent bile acid was deoxycholic acid in the hypothyroid patients and chenodeoxycholic acid in the hyperthyroid patients. The serum bile acid profile of medically treated patients was similar to that of normal cpntrols. The ratio of the sum of deoxycholic and cholic acid to that of lithocholic and chenodeoxycholic acid was found to be a good indicator of thyroid function, while the ratio of cholic acid to chenodeoxycholic acid correlated poorly with it.

3. The characteristic effect of thyroid hormone on the serum bile acid composition in man was the shift from the ‘family’ of cholic acid to that of chenodeoxycholic acid. This is in agreement with experimental results in the rat, and suggests a specific action of thyroid hormone on the hydroxylating enzymes involved in the conversion of cholesterol into bile acids.
The effect of weight loss, operation and parenteral nutrition on fat clearance in patients with colorectal cancer
Authors: Wilson A. W. , Kirk C. J. C. , Goode A. W.
Published: August 2015

1. Fractional fat clearance rate (K2) in 21 patients with colorectal cancer was studied using the intravenous fat tolerance test.

2. K2 showed a negative correlation with weight change(r = −0.736, P < 0.001) with the tumour in situ.

3. Fourteen patients were retested 12 weeks after curative resection of their tumours. Eight of the fourteen patients had raised K2 values pre-operatively; in all these the K2 values were reduced post-operatively (pre-operative median 3.94%/min, range 2.63–7.20%/min, postoperative median 2.31%/min, range 1.57–5.36%/min, P < 0.01 by Wilcoxon's signed rank test). A high preoperative K2 value was associated with a large reduction in K2 post-operatively (r = − 0.844, P < 0.001).

4. Seven patients with relatively high K2 values received a pre-operative course of intravenous nutrition after which K2 values were significantly reduced (pre-feeding median 7.20%/min, range 4.72–12.12%/min, post-feeding median 4.44%/min, range 2.17–6.83%/min, P < 0.05).
Haemodialysis-associated amyloidosis: β2-microglobulin alone or associated with globin chains?
Authors: Argiles A. , Mourad G. , Axelrud-Cavadore Claude , Derancourt J. , Adell J. Jauregui , Mion C. , Cavadore J. C.
Published: August 2015

1. The protein constituents of amyloid fibrils were characterized in amyloid deposits extracted from surgical material obtained from a 66-year-old patient undergoing maintenance haemodialysis and operated for a carpal tunnel syndrome.

2. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis disclosed the presence of bands at 12 and 14 kDa. Two-dimensional electrophoresis and Western blotting confirmed that the proteins were β2-microglobulin (β2M) and globin chains.

3. When the effluent of high-performance gel filtration chromatography corresponding to molecular masses of 10–15 kDa was subjected to Edman degradation, only one amino acid residue was found at each step. The 18 residues determined corresponded to the N-terminal sequence of β2M.

4. Although globin chains were clearly present in the amyloid material, they were not accessible for sequence determination. The identification of the other protein constituents present in the amyloid material, along with β2M, should provide a better understanding of haemodialysis-associated amyloidosis, the mechanisms of formation of which have not yet been completely determined.
Evidence for γ-aminobutyric acid as the inhibitor of γ-aminobutyric acid binding in the plasma of humans with liver disease and hepatic encephalopathy
Authors: Levy L. J. , Leek J. , Losowsky M. S.
Published: August 2015

1. Gas–liquid chromatography and a radioreceptor assay were used to measure plasma γ-aminobutyric acid (GABA) in patients with liver disease and hepatic encephalopathy.

2. There was a significant correlation between the results obtained by the two methods, and compared with controls plasma GABA was elevated.

3. These findings suggest that the increased GABA binding inhibitory activity of plasma of these patients is probably due to GABA itself.
Endothelium-dependent relaxation in isolated human arteries and veins
Authors: Thom S. , Hughes A. , Martin G. , Sever P. S.
Published: August 2015

1. The role of the endothelium in mediating relaxation to acetylcholine, the calcium ionophore A23187, vasoactive intestinal peptide and peptide histidine methionine was studied using isolated human blood vessels.

2. Segments of renal, colic, pulmonary, uterine, transverse cervical, brachial, coronary and coeliac branch arteries, and saphenous veins, were obtained from surgical resection material for use in tissue bath studies.

3. Acetylcholine or A23187 produced endothelium-dependent relaxation in isolated vessels from all vascular beds studied. Coronary arteries, however, differed in their response to acetylcholine which produced predominantly a contractile response, either alone or after initial relaxation.

4. Vasoactive intestinal peptide and peptide histidine methionine produced endothelium-dependent relaxation in coeliac branch arteries. However, these peptides relaxed isolated pulmonary arteries independently of endothelium.

5. Endothelium-dependent relaxation in response to acetylcholine and A23187 was antagonized by nordihydroguaretic acid, a lipoxygenase inhibitor, and methylene blue and haemoglobin, inhibitors of soluble guanylate cyclase. In these respects the endothelium-dependent responses of human arteries to acetylcholine and A23187 resemble those described in other species.
The response of intracellular and surface ferritin after T-cell stimulation in vitro
Authors: Pattanapanyasat K. , Hoy T. G. , Jacobs A.
Published: August 2015

1. Measurements of T-lymphocyte surface ferritin using flow cytometry show that phytohaemagglutinin (PHA) stimulation causes a marked increase in the number of cells bearing spleen-type (S) and heart-type (H) ferritin on their membrane, whereas no such change occurs in non-stimulated cells. This coincides with increases in interleukin-2 receptors, transferrin receptors and HLA-DR antigen.

2. There is an increase in the intracellular concentration of both S- and H-ferritin in lymphocytes after PHA stimulation: H-ferritin increases five- to seven-fold, but S-ferritin only two- to three-fold. The maximum H/S ratio is about 15/1. However, these increases also occur in cells cultured in the absence of PHA.

3. Small amounts of both S- and H-ferritin are released into the medium, especially from stimulated cells, but the H/S ratios are lower than intracellular ratios.

4. The present findings suggest that lymphocyte stimulation followed by ferritin synthesis is accompanied by an increase in the amount of intracellular and cell surface ferritin and, possibly, the amount released from the cells.
Peripheral vascular responses during carotid baroreceptor stimulation in normotensive and hypertensive subjects
Authors: Duprez D. , De Pue N. , Clement D. L.
Published: August 2015

1. The carotid baroreceptors were stimulated for 2 min by neck suction at −30 and −60 mmHg in 19 normotensive subjects and 12 patients with moderate essential hypertension.

2. Blood pressure was measured with a mercury sphygmomanometer and heart rate was derived from beat-to-beat analysis of the electrocardiogram. Blood flow was measured simultaneously at calf and finger with venous occlusion plethysmography and the vascular resistance was calculated.

3. During neck suction at − 30 and − 60 mmHg there was a significant decrease in arterial blood pressure and heart rate. There was a transient vasodilatation of the calf blood vessels, while there was a sustained vasoconstriction of the finger blood vessels. These results were qualitatively similar in both groups; however, there were quantitative differences.

4. These experiments show that there is a selective autonomic control of the different peripheral vascular beds by the carotid baroreceptors in both normotension and mild essential hypertension.
Prostanoid synthesis by isolated rat glomeruli: Effect of oestrous cycle and pregnancy
Authors: Gregoire I. , Dupouy J. P. , Fievet P. , Sraer J. D. , Fournier A.
Published: August 2015

1. An increase in glomerular prostaglandin (PG) synthesis has been reported in two experimental models of increased glomerular filtration rate (GFR).

2. Because pregnancy, in women and rats, is also associated with an increased GFR, we studied PG biosynthesis by glomeruli isolated from pregnant rats in comparison with virgin rats at the different phases of the oestrous cycle.

3. PGE2 and PGF2α synthesis markedly increased during pregnancy (at day 21 of gestation a five- to sevenfold increase of PGE2 and PGF2α was seen; at day 15 of gestation a threefold increase of PGE2 and a sixfold increase of PGF2α was noted). However, thromboxane A2 (TXA2) synthesis was similar in all the groups studied.

4. Among the four phases of the oestrous cycle, dioestrus was characterized by a significant increase in glomerular synthesis of PGE2.

5. The fact that during pregnancy the increase in the vasodilator PGE2 is not counteracted by an increase in the constrictor TXA2 must be taken into account when explaining the glomerular hyperfiltration which characterizes the pregnant state.

6. The increase of PGE2 synthesis during dioestrus should be considered in studies of PG synthesis using virgin rats as controls.
Cardiovascular responses to upright tilting in healthy subjects
Authors: Hainsworth R. , Al-Shamma Y. M. H.
Published: August 2015

1. The cardiovascular responses to passive upright tilting were determined in healthy human subjects of various ages using entirely ‘non-invasive’ techniques. Cardiac output was determined by a single breath method and arterial blood pressure by an automatic sphygmomanometer.

2. Steady-state responses were achieved within 4–6 min from the onset of the tilt and were maintained for at least 15 min.

3. The reproducibilities of the responses to tilting by 60°, expressed as two standard deviations of the differences between responses on two occasions (mean responses in parentheses), were: cardiac output ±0.70 (−1.41) litre/min, heart rate ±7.6 (+ 14.7) beats/min, systolic blood pressure ± 15.5 (+ 1.0), and diastolic blood pressure μ13.1 (+ 13.6)mmHg.

4. Tilting by 20° resulted in no significant responses but between 20° and 60° responses were linearly related to the angle of tilt.

5. Supine values and responses to tilting by 60° were compared in subjects in four age groups between 20 and 80 years. With increasing age, the supine values of cardiac output declined and those of arterial blood pressures increased. Responses of heart rate, cardiac output and diastolic pressure declined by increasing age. These results, obtained from a healthy population, provide reference values for comparison with individuals who may have deficient postural responses.
Alveolar carbon monoxide: A comparison of methods of measurement and a study of the effect of change in body posture
Authors: Kirkham Andrew J. T. , Guyatt Andrew R. , Cumming Gordon
Published: August 2015

1. We have compared rebreathing, breath-hold and mean alveolar methods of measuring alveolar carbon monoxide (CO), at levels similar to those found in smokers, as a preliminary to using them as indirect measures of carboxyhaemoglobin levels. In the present study alveolar CO levels were raised by rebreathing a 2% CO mixture.

2. Breath-hold CO was measured after breath-hold times of 0–35 s in 5 s increments. Using generalized linear models, the maximum value for breath-hold CO was estimated to occur at 23 s. Breath-hold CO after a 20 and 25 s breath-hold were similar to and significantly greater than those of less than 20 s or greater than 25 s.

3. As expired CO increased, the difference between breath-hold and mean alveolar CO became proportionally larger. On average, breath-hold CO was 24% larger than mean alveolar CO.

4. Rebreathing, breath-hold and mean alveolar CO were compared at four different inspired oxygen concentrations. Expired CO increased significantly with increasing oxygen for all three methods. At end-tidal oxygen levels of less than 25%, breath-hold and rebreathing CO were similar, however, the overall mean difference between the three methods was significant.

5. While rebreathing CO was unaffected by changes in ventilation/perfusion of the lung, induced by change in body posture, both breath-hold and mean alveolar CO showed a significant fall with change from the supine to erect posture.

6. We conclude that under normoxic conditions, rebreathing and breath-hold CO (20 or 25 s breath-hold) were similar, whereas the mean alveolar method produced significantly lower values, presumably due to lack of equilibration. Altering ventilation/perfusion of the lung caused no mean change in the measurement of rebreathing CO but did affect the other methods.
A comparison of the renal actions of γ-l-glutamyl-l-dopa and γ-l-glutamyl-l-tyrosine in normal man
Authors: Jeffrey R. F. , MacDonald T. M. , Lee M. R.
Published: August 2015

1. The renal responses to the dipeptides γ-l-glutamyl-l-dopa (gludopa) and γ-l-glutamyl-l-tyrosine (glutyrosine) were compared when given intravenously in six normal male volunteers.

2. Gludopa is natriuretic and diuretic at a dose of 25 μg min−1 kg−1. At the same dose, glutyrosine had no effect on the volume or sodium content of the urine.

3. There was a 400-600-fold increase in urine dopamine output after gludopa; there was no conversion of glutyrosine to dopamine.

4. Gludopa significantly inhibited plasma renin activity, whereas with glutyrosine there was a non-significant increase.

5. Gludopa is a potent pro-drug for renal dopamine production and exerts natriuretic and hormonal effects. Glutyrosine appears to be inactive. The results support the contention that circulating l-dopa is the important physiological precursor for renal dopamine.
Effect of plasma from hypertensive subjects on Ca2+ transport in permeabilized human neutrophils
Authors: Zidek Walter , Sachinidis Agapios , Spieker Claus , Storkebaum Walter
Published: August 2015

1. The effects of plasma fractions from essential hypertensive subjects (n = 14) and normotensive subjects (n = 14) on Ca2+ transport in permeabilized human neutrophils was studied using an ion-selective electrode.

2. Plasma fractions were obtained by gel filtration and contained substances with a molecular mass in the range 1000–1500 daltons. This fraction isolated from essential hypertensive subjects has been shown to increase blood pressure after intravenous injection in the rat.

3. The rate of Ca2+ uptake by permeabilized neutrophils after addition of extracellular Ca2+ was significantly accelerated during incubation of the cells with the hypertensive fraction (1049.3 ±807.7% vs 242.5 ±320.9% of the control value, mean ± sd, P < 0.05).

4. It is concluded that the hypertensive plasma fraction increases Ca2+ accumulation in subcellular particles, so that under excitatory conditions Ca2+ release in arterial smooth muscle might be enhanced.
Abnormalities of sodium transport by sodium, potassium-activated adenosine triphosphatase in erythrocytes from obese children
Authors: Dianzani Irma , Boero Roberto , Guarena Cesare , Urbino Antonio , Corda Giuliana , Quarello Francesco , Cerutti Franco
Published: August 2015

1. Intracellular Na+ concentration [Na+]i and Na+ extrusion catalysed by sodium, potassium-activated adenosine triphosphatase (Na+, K+-pump) were evaluated in erythrocytes from 21 obese children and 20 normal weight- and age-matched controls.

2. Obese children showed a significantly decreased Vmax for Na+, K+-pump-mediated Na+ efflux (5638 ± 338 vs 7597 ±335 μmol h−1 litre−1 of cells mean±SEM, P = 0.01), while [Na+]i (9.3±0.3 vs 9.1 ± 0.5 mmol/litre of cells, mean±SEM, NS) and Na+ efflux in fresh cells (2380± 153 vs 2533 ± 180 μmol h−1 litre−1 of cells, mean ±sem, NS) were similar in both groups.

3. Mean diastolic blood pressure was significantly higher in obese children than in controls, although both groups were normotensive (73.8 ± 1.3 vs 66.2 ±1.9 mmHg, mean ± sem, P = 0.009).

4. Abnormal Na+, K+-pump activity is present in individuals with idiopathic obesity.

5. The possible link between obesity and blood pressure regulation may be mediated through modifications in Na+, K+-pump activity.
A study of the structure of the gene for lecithin: Cholesterol acyltransferase in four unrelated individuals with familial lecithin: Cholesterol acyltransferase deficiency
Authors: Humphries S. E. , Chaves M. E. , Tata F. , Lima V. L. M. , Owen J. S. , Borysiewicz L. K. , Catapano A. , Vergani C. , Gjone E. , Clemens M. R. , Williamson R. , McIntyre N.
Published: August 2015

1. We have used polyclonal antibodies and a complementary DNA clone for human lecithinxholesterol acyltransferase (LCAT) to study LCAT protein and the structure of the LCAT gene, respectively, in patients with familial LCAT deficiency from Norway, Ireland, Germany and Italy.

2. The patients had low levels of non-functional LCAT protein in their serum as measured by rocket Immunoelectrophoresis; its mol. wt. of approximately 68 000 was identical with that of LCAT in normal plasma, as judged by immunoblotting.

3. Enzymatic digestion of DNA samples from the patients produced LCAT gene fragments which were indistinguishable from those found in normal individuals.

4. We conclude that LCAT deficiency in these patients is not caused by a large deletion or rearrangement of the LCAT gene sequences.
Contrasting effects of intravenous and oral etidronate on vitamin D metabolism in man
Authors: Lawson-Matthew P. J. , Guilland-Cumming D. F. , Yates A. J. P. , Russell R. G. G. , Kanis J. A.
Published: August 2015

1. We have studied the early effects of intravenously and orally administered etidronate on vitamin D metabolism and indirect indices of calcium and skeletal metabolism in 17 patients with Paget's disease of bone.

2. Administration of etidronate by mouth (700–1400 mg daily for 1 month) or its intravenous infusion (300 mg daily for 5 days) decreased bone resorption as judged by urinary excretion of hydroxyproline and significantly increased renal tubular reabsorption of phosphate. No significant change in serum activity of alkaline phosphatase was noted with either regimen.

3. When etidronate was given by mouth there was a progressive decrease in fasting urinary calcium excretion and a rise in serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In contrast, intravenous etidronate decreased serum values of l,25-(OH)2D3 and was associated with a progressive increase in fasting calcium excretion, suggesting a decrease in the net influx of calcium from the extracellular compartment to bone. Significant inverse correlations were noted between the change induced in 1,25-(OH)2D3 values at 2 weeks and the changes in serum calcium, phosphate and fasting urinary excretion of calcium.

4. These observations suggest that the different effects of intravenous and oral etidronate on l,25-(OH)2D3 values are a consequence of different doses of etidronate used and the different effects of these regimens on the accretion of calcium into bone.
Skeletal muscle glutamine production in thermally injured rats
Authors: Ardawi M. Salleh M.
Published: August 2015

1. The effect of thermal injury (33–35% of body surface area) on the regulation of glutamine metabolism was studied in skeletal muscles of rats 7 days after injury.

2. Injury increased the rates of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb.

3. Injury produced decreases in the concentrations of skeletal muscle glutamine (36%, P < 0.001), glutamate (39%, P < 0.001), alanine (24%, P < 0.001), pyruvate (35%, P < 0.001), 2-oxoglutarate (51%, P < 0.001) and adenosine 5′-triphosphate (38%, P < 0.001). The concentrations of ammonia (42%, P < 0.001) and inosine 5′-phosphate (430%, P < 0.001) were increased.

4. The maximal activity of glutamine synthetase was increased (22–40%, P < 0.001) in muscles of injured rats, whereas that of glutaminase was unchanged.

5. Hindlimb blood flow decreased by approximately 15% in injured rats, which was accompanied by an enhanced net release of glutamine (80%, P < 0.001) and alanine (44%, P < 0.001).

6. It is concluded that there is an enhanced rate of release of both glutamine and alanine from skeletal muscle of thermally injured rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.
Lithium clearance measurements as an indication of cyclosporin a nephrotoxicity in the rat
Authors: Whiting P. H. , Simpson J. G.
Published: August 2015

1. Measurements of the rate of lithium clearance, which provides an estimate of proximal renal tubular iso-osmotic reabsorption (i.e. sodium and H2O), were used to study H2O and electrolyte reabsorption during the development of cyclosporin A (CsA) induced nephrotoxicity.

2. CsA, administered daily by gavage at 50 mg/kg body weight, produced a nephrotoxicity which was characterized by reductions in the clearance rates of creatinine, sodium and potassium, and increased glycosuria, enzymuria and urine flow rate.

3. Decreased lithium clearance rate and increased proximal iso-osmotic reabsorption accompanied significant reductions in creatinine clearance rate. Absolute proximal tubular reabsorption, however, was not affected by CsA administration.

4. Reductions in the absolute distal tubular reabsorption of sodium, potassium and H2O were also observed.

5. Alterations in renal tubular function occur early in the development of CsA nephrotoxicity as a result of both direct proximal tubulotoxicity and an effect on the afferent arteriole.

6. Measurements of the rate of lithium clearance may be a useful adjunct to the diagnosis of CsA nephrotoxicity.
Selective alteration of brush-border hydrolases in intestinal diseases in childhood
Authors: Phillips A. D. , Smith M. W. , Walker-Smith J. A.
Published: August 2015

1. Biochemical estimates of lactase, sucrase and maltase activities, carried out on intestinal biopsies appearing histologically normal, were compared with those obtained from children suffering from coeliac disease, cow's milk protein intolerance/postenteritis syndrome and the intractable diarrhoea syndrome of infancy. Lactase deficiency in these children was found to be more pronounced than sucrase or maltase deficiencies.

2. Quantitative cytochemical investigations showed characteristic disease-induced changes in the ability of enterocytes to express α- and β-glucosidases, but not alkaline phosphatase activities, during migration along stunted villi.

3. Separate estimates of the time course describing hydrolase development in normal and coeliac tissue showed the initial rate of lactase appearance to be halved in coeliac patients, while that for α-glucosidases remained constant and that for alkaline phosphatase increased by a factor of four. Enteroblastic replacement of mature enterocytes cannot provide a general explanation for hydrolase deficiency in diseased intestine.
Origins of endogenous noradrenaline overflow during reperfusion of the ischaemic rat heart
Authors: Dart A. M. , Riemersma R. A.
Published: August 2015

1. Reperfusion of the globally ischaemic isolated rat heart is associated with an enhanced overflow of endogenous noradrenaline (NA) after ischaemic periods of 20, 40 or 60 min but not of 10 min.

2. Reperfusion NA overflow, after 40 min of ischaemia, is suppressed by desipramine and increased when ischaemia follows a period of substrate deprivation.

3. Reperfusion after 40 min of ischaemia is associated with a significant rise in NA concentration despite a simultaneous 20-fold increase in flow. This increase in concentration is abolished by treatment with desipramine or if ischaemia follows a period of substrate deprivation.

4. Reperfusion NA overflow correlates with the reperfusion overflow of an extracellular space marker infused before the ischaemic episode.

5. These results suggest that ischaemia is heterogeneous and that NA is released into regions of particularly profound ischaemia from which it is subsequently eluted during reperfusion.
A ouabain-displacing factor in normal pregnancy, pregnancy-induced hypertension and pre-eclampsia
Authors: Gregoire I. , Roth D. , Siegenthaler G. , Fievet P. , Esper N. El , Favre H. , Fournier A.
Published: August 2015

1. A ouabain-displacing factor (ODF) was measured in the urine of non-pregnant, normotensive pregnant and hypertensive pregnant women by a receptor-binding assay with sodium, potassium-dependent adenosine triphosphatase.

2. Urinary ODF was significantly increased in normal pregnancy.

3. Greater increases were seen in pregnancy-induced hypertension and pre-eclampsia.
Effect of age and posture on human lymphocyte adenylate cyclase activity
Authors: Mader Scott L. , Robbins Alan S. , Rubenstein Laurence Z. , Tuck Michael L. , Scarpace Philip J.
Published: August 2015

1. A number of age-related changes have been reported in the catecholamine–adrenoceptor–adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses.

2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66–80 years) and seven healthy young subjects (age 27–34 years).

3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P < 0.025) and 73% in the young (P < 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal.

4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses.
Effects of pH and osmolarity on aerosol-induced cough in normal volunteers
Authors: Lowry R. H. , Wood A. M. , Higenbottam T. W.
Published: August 2015

1. The chemosensitivity of cough receptors stimulated by inhalation of aqueous aerosols was evaluated in 21 normal volunteers in three experiments.

2. The pH of isotonic saline was altered using small amounts of phosphate or glycine buffers to produce solutions with a pH range of 2.6–10.0. These solutions were nebulized ultrasonically and breathed for 1 min periods by seven subjects in random order and on separate days. Cough frequency during each 1 min inhalation was recorded. Only the two solutions of extreme pH (2.6 and 10.0) caused cough.

3. The effect of altering the osmolarity of the inhaled aerosol on cough was assessed using d-glucose over a range of 77–1232 mosmol/l. Saline solutions over the same range of osmolarity were also tested. The pH of d-glucose was raised to match that of saline by adding small amounts of sodium hydroxide. All solutions were nebulized and inhaled by seven subjects as described above for 1 min periods during which cough frequency was recorded. Forced expired volume in 1 s was recorded after each inhalation and did not alter in any subject by more than 10%. Subjects coughed when inhaling all the d-glucose solutions over the whole range of osmolarity. Cough occurred with saline solutions only at low chloride concentration and at the highest concentration.

4. In order to clarify whether the response to hypertonic saline was due to the high ionic content of the solutions or to its hypertonicity, two other solutions were tested. These were an isotonic and a hypertonic mixture of d-glucose and saline, containing ‘normal’ (150 mmol/l) ionic content. Cough occurred with the hypertonic solution but not with the isotonic solution, suggesting that hypertonicity does stimulate cough.

5. The mechanism of cough induction by citric acid was studied. An aerosol of 0.68% citric acid in saline was compared with sodium citrate, both with and without chloride, with d-glucose and with water in seven subjects. Cough occurred in response to all aerosols except sodium citrate in saline solvent. Additive effects of low pH and lack of chloride, and not the citrate ion, are responsible for the irritant properties of citric acid.

6. The chemosensitivity of the cough reflex induced by inhaled aerosols mirrors that already described in vivo for laryngeal rapidly adapting receptors.
Cyclosporin a prevents sensitization after blood transfusion in multiparous rats
Authors: Jones M. C. , Power D. A. , Stewart K. N. , Catto G. R. D.
Published: August 2015

1. Humoral immune responses to allogeneic blood transfusions and semi-allogeneic pregnancies were monitored by the indirect haemagglutination assay in strains of inbred rats.

2. Similar titres and ranges of cross-reactive allo-antibodies were induced by blood transfusions and pregnancy; the maternal alloantibody response to paternal antigens was not increased by an unrelated antigenic stimulus.

3. Immunosuppression with cyclosporin, A was effective in preventing the primary humoral immune response produced by blood transfusion but not in abrogating the established immune response to previous pregnancy.

4. These studies have established an animal model of sensitization that both stimulates, the clinical situation of many potential renal transplant recipients and permits analyses of the different antigenic stimuli involved.
Increased levels of platelet-activating factor (1-O-alkyl-2-acetylglycerophosphocholine) in blood after reversal of renal clip hypertension in the rat
Authors: McGowan H. M. , Vandongen R. , Kelly L. D. , Hill K. J.
Published: August 2015

1. This study analyses whole blood in acutely unclipped one-kidney, one-clip (1K,1C) hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the rapid blood pressure (BP) fall seen after unclipping.

2. Hypertensive 1K,1C rats were anaesthetized and a carotid and jugular cannula were inserted for BP measurement and anaesthetic infusion respectively. After a stable level of anaesthesia was attained, the constrictive clip was removed and BP was recorded for 30 min.

3. Blood was drawn from the aorta directly into ice-cold acetone. The extract was analysed for PAF by a bioassay using 5-hydroxy-[14C]tryptamine-labelled platelets.

4. Rats which showed a BP fall had elevated levels of PAF [55 ± 6 (sem) pg/ml] when compared with those with no fall in BP [26 ± 7 (sem) pg/ml] (P < 0.01).

5. This supports the hypothesis that activation of PAF biosynthesis may be a mechanism contributing to the fall in BP seen after unclipping the 1K,1C hypertensive rat.
Changes in jejunal permeability and passive permeation of sugars in intestinal biopsies in coeliac disease and Crohn's disease
Authors: Dawson D. J. , Lobley R. W. , Burrows P. C. , Notman J. A. , Mahon M. , Holmes R.
Published: August 2015

1. The relative effects of changes in mucosal surface area and mucosal permeability on the passive uptakes of mannitol and raffinose have been studied in vitro using jejunal biopsies from 48 controls, 32 patients with coeliac disease and 11 patients with Crohn's disease. Total mucosal permeation was corrected for surface area measured morphometrically to provide an index of mucosal permeability.

2. In untreated coeliac disease, permeation of mannitol was reduced by 35% (P = 0.006) and that of raffinose was increased by 66% (P = 0.0095) compared with controls, whereas mucosal permeability to mannitol was increased twofold (P = 0.009) and to raffinose fivefold (P = 0.0001). Mucosal permeability was similar for each sugar.

3. In treated coeliac disease, permeation and permeability for mannitol were normal, but remained elevated for raffinose by 23% (P = 0.036) and 41% (P = 0.024), respectively.

4. In Crohn's disease, permeation of mannitol was reduced by 21%, but that of raffinose and mucosal permeability to both sugars were normal.

5. These findings suggest that surface area is quantitatively more important than mucosal permeability in determining the total permeation of mannitol, while the converse is true for raffinose. The findings are compatible with paracellular uptake of raffinose, but with both paracellular and transcellular uptake of mannitol. Both pathways are affected in coeliac disease, whereas only transcellular uptake is affected in Crohn's disease.
31P nuclear magnetic resonance study of steady-state adenosine 5′-triphosphate levels during graded hypoxia in the isolated perfused rat kidney
Authors: Ratcliffe P. J. , Endre Z. H. , Scheinman S. J. , Tange J. D. , Ledingham J. G. G. , Radda G. K.
Published: August 2015

1. A model of controlled hypoxia in the isolated perfused rat kidney has been used to compare the extent of reduction in the steady-state level of adenosine 5′-triphosphate (ATP) from that initially observed with alterations in renal function and with the development of tubular cell injury.

2. ATP depletion was observed in response to decreased total oxygen delivery even when delivery greatly exceeded consumption and the venous oxygen tension remained in excess of 150 mmHg.

3. Increases in the fractional excretion of sodium occurred progressively below an apparent threshold value of whole kidney ATP of approximately 80% of the baseline.

4. With modestly decreased oxygen delivery, cellular injury was confined to deep proximal tubule and medullary thick ascending limb of Henle's loop. Severely decreased oxygen delivery rates were associated with cellular damage spreading throughout the cortex.

5. Even the smallest reductions in whole kidney ATP were associated with morphological damage to tubular cells. The extent of reduction in whole kidney ATP was closely correlated and approximately equivalent to the calculated volume of injured cells.

6. Our results indicate that reduction in whole kidney ATP during decreased oxygen delivery is a valid marker of the extent of injurious cellular hypoxia and are consistent with the view that cellular ATP concentrations in hypoxia are markedly inhomogeneous. They support the hypothesis that specific regions of the perfused kidney become critically hypoxic and develop cellular injury while overall oxygen delivery remains high. Areas at risk include deep proximal tubule as well as the medullary thick ascending limb of Henle's loop.
Dynamic measurement of human capillary blood pressure
Authors: Williams S. A. , Wasserman S. , Rawlinson D. W. , Kitney R. I. , Smaje L. H. , Tooke J. E.
Published: August 2015

1. Capillary blood pressure was measured in man using a dynamic servo-nulling system and direct micropuncture. This enabled assessments of the normal variations in pressure which influence fluid filtration and reabsorption.

2. Seventy-eight capillaries in 19 subjects were punctured in one of three positions around the capillary loop with the hand at the level of the sternal angle. Mean pressure around the loop fell from 37.7 ± 3.7 mmHg (arteriolar limb, mean ± sem, n = 12) to 19.4 ± 1.0 mmHg (apex, n = 25) to 14.6 ± 0.5 mmHg (venular limb, n = 41) at skin temperatures of 18.7–33.1°C. These values agree closely with Landis' original studies in 1930 [E. Landis (1930) Heart, 15, 209–228].

3. The mean filtration/reabsorption state of any particular capillary limb was not static because of cardiac, vasomotor and respiratory fluctuations in capillary pressure. From a total of 38 capillaries in which recordings were analysed for 30 s, the fluctuations in pressure were such that 27 capillaries probably had periods of both filtration and reabsorption.

4. Computerized superimposition and coherent averaging of trains of capillary pulses enabled an accurate description of the pulse waveform to be made in three capillaries. This was remarkably similar to waveforms from the radial artery, albeit at reduced amplitude (average 3.6 ± 3.4 mmHg, mean ± sd overall). The time for the pulse to travel between the radial artery and the finger capillary was approximately 10 ms, which implies a propagation velocity of several metres per second.

5. Fourteen long recordings of capillary pressure (mean 154 s) were subjected to computerized Fourier analysis and cross-correlation with other parameters. Low frequency fluctuations between 0.02 and 0.2 Hz (0.086 ± 0.05 Hz, mean ± sd) correlated closely with vasomotion in simultaneously recorded (laser-Doppler) skin blood flow (0.080 ± 0.5 Hz), although they were not synchronous. Higher frequencies between 0.2 and 0.6 Hz (0.28 ± 0.03 Hz) correlated well with respiration (0.29 ± 0.03 Hz), were synchronous and probably relate to respiratory fluctuations in venous pressure. The dynamic system has thus enabled us to describe the considerable variations in normal capillary pressure and to relate this variability to physiological influences.
Atrial natriuretic peptide and catecholamines in peripheral blood as indicators of cardiac dysfunction in the general population
Authors: Caidahl Kenneth , Hedner Jan , Hedner Thomas
Published: August 2015

1. From a screened cohort of 644 67-year-old men, drawn from the population of Gothenburg, 42 men with presumed cardiac dyspnoea were selected and compared with 45 random controls.

2. Cardiac function was evaluated by echocardiography and other non-invasive methods, and the potential of peripheral venous concentrations of immunoreactive atrial natriuretic peptide (IrANP), noradrenaline and adrenaline in revealing cardiac dysfunction was investigated.

3. Concentrations of venous IrANP and noradrenaline were both significantly, but weakly, related to the degree of dyspnoea and to pulmonary congestion.

4. IrANP, but not catecholamines, was also related to other indices of heart failure. The correlations were, however, due solely to increased immunoreactivity in men with severe dyspnoea; in most subjects with mild to moderate dyspnoea the level of IrANP was similar to that of the controls.

5. It is concluded that, in a population sample, the peripheral venous level of IrANP is more closely related to cardiac function than are catecholamines. Yet, the level of IrANP is not a very sensitive marker of cardiac dysfunction, suggesting that stimulation of α-human atrial natriuretic peptide release is a late phenomenon in the development of cardiac failure.
Diphosphonates and phosphate homoeostasis in man
Authors: McCloskey E. V. , Yates A. J. P. , Gray R. E. S. , Hamdy N. A. T. , Galloway J. , Kanis J. A.
Published: August 2015

1. The effects of three intravenous diphosphonates (etidronate, clodronate and aminohexane diphosphonate) on phosphate homoeostasis were studied in 30 patients with Paget's disease of bone and in three patients with hypoparathyroidism.

2. In Paget's disease, all three diphosphonates induced significant increases in serum phosphate and renal tubular reabsorption of phosphate. This effect was most marked and persistent after etidronate, whereas in the clodronate- and aminohexane diphosphonate-treated patients the increases were less, of shorter duration and followed thereafter by significant decreases in serum phosphate and renal tubular reabsorption of phosphate. Unlike etidronate, both clodronate and aminohexane diphosphonate caused a significant reduction in serum and urinary calcium, with appropriate homoeostatic increases in immunoassayable parathyroid hormone.

3. Phosphaturic responses to infused parathyroid hormone were observed in two patients with etidronate-induced hyperphosphataemia.

4. In three hypoparathyroid patients, clodronate induced a more marked increase in serum phosphate and renal tubular reabsorption of phosphate than in Paget‘s disease, which was of comparable degree but of shorter duration than that after etidronate in Paget's disease.

5. These findings suggest that all three diphosphonates increase renal tubular reabsorption of phosphate, but that this effect is attenuated with those diphosphonates which induce secondary hyperparathyroidism.
Plasma alkaline phosphodiesterase I in intrahepatic cholestasis induced by α-naphthylisothiocyanate in rats
Authors: Quayle Julie A. , Capstick Alison , Morris Anthony I. , Billington David
Published: August 2015

1. Administration of α-naphthylisothiocyanate (ANIT) to rats produced dose-dependent increases in plasma bile acid and bilirubin concentrations. Similar increases in plasma bile acid and bilirubin concentrations were evident in bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models.

2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S. R. Simpson, K. Rahman & D. Billington (1984) Clinical Science 67, 647–652] where, after bile duct ligation, serum alkaline phosphodiesterase I was elevated sixfold before any increase in alkaline phosphatase activity became apparent. Thus, plasma alkaline phosphodiesterase I does not offer as sensitive a marker of intrahepatic cholestasis (induced by ANIT) as it does of extrahepatic cholestasis (induced by bile duct ligation).

3. Hepatic alkaline phosphodiesterase I was unaffected by ANIT pretreatment while hepatic alkaline phosphatase was increased up to seven times. It is suggested that raised plasma alkaline phosphodiesterase I is due to regurgitation of the biliary enzyme rather than overspill of the enzyme from liver into blood.

4. Gel filtration showed that 24 h and 96 h after ANIT administration, rat serum contained a high molecular weight form of alkaline phosphodiesterase I, suggesting a different isoenzyme profile.
Interactions among stimulated human polymorphonuclear leucocytes, released elastase and bronchial antileucoprotease
Authors: Kramps J. A. , VanTwisk Ch. , Klasen E. C. , Dijkman J. H.
Published: August 2015

1. We investigated the effect of stimulated human polymorphonuclear leucocytes (PMN's) on both the antitrypsin and anti-elastase activity of bronchial antileucoprotease (ALP).

2. Incubation of ALP with stimulated human PMN's resulted in a rapid loss of anti-elastase activity which paralleled that of the antitrypsin activity, suggesting that both inhibitor activities are represented by the same active site.

3. The myeloperoxidase-oxidizing system was found to be responsible for the inactivation of ALP.

4. The oxidized inhibitor was unable to form stable complexes with PMN elastase but was resistant to breakdown by proteolytic enzymes from stimulated PMN's.

5. It was observed that stimulated cells are capable of releasing elastase which shows full activity in the presence of a large molar excess of ALP.

6. We conclude from this study that stimulated PMN‘s are able to inactivate ALP by which released elastase is able to express enzymatic activity in spite of the presence of this low-molecular-weight inhibitor. Thus, inactivation of ALP by triggered PMN's may contribute to destructive processes in which elastase is thought to be a mediator.
Intravenous morphine causes hypertension, hyperglycaemia and increases sympatho-adrenal outflow in conscious rabbits
Authors: May Clive N. , Ham Ian W. , Heslop Kirsten E. , Stone Frances A. , Mathias Christopher J.
Published: August 2015

1. In conscious rabbits, intravenous morphine (3 mg/kg) caused hypertension, bradycardia, hyperglycaemia and sedation. These changes were accompanied by large increases in plasma adrenaline and smaller increases in plasma noradrenaline.

2. These effects of morphine were prevented by intravenous naloxone, demonstrating their dependence on stimulation of opiate receptors.

3. Pretreatment with the antihistamines cimetidine and chlorpheniramine enhanced the morphine-induced rise in blood pressure, excluding a role for histamine release in the hypertensive action of morphine.

4. The centrally acting α2-adrenergic agonist clonidine prevented the morphine-induced hypertension and rise in plasma catecholamines, suggesting that these effects are exerted via central pathways. Clonidine alone reduced blood pressure and heart rate and produced hyperglycaemia.

5. α-Adrenergic blockade with phenoxybenzamine reduced the increase in blood pressure after morphine, although the increase in plasma catecholamines was augmented.

6. Pentobarbitone anaesthesia prevented the morphine-induced cardiovascular changes, the increase in plasma catecholamines and the hyperglycaemia.

7. These findings indicate, that in conscious rabbits, morphine induces hypertension by stimulation of opiate receptors leading to increased sympatho-adrenal activity. The hyperglycaemia appears to be in response to secretion of adrenaline. These effects probably result from a central action of morphine.